4406 entries. 94 themes. Last updated December 26, 2016.

Biology / Evolution Timeline


2,800,000 BCE – 8,000 BCE

The Oldest Hominin Fossils Found Outside of Africa Circa 1,800,000 BCE

Fossil skull of D2700. (Click on image to view larger.)

Fossil skull of D2700. (Click on image to view larger.)

In 1991 Georgian anthropologist and paleontologist David O. Lordkipanidze discovered at Dmanisi, in the Kvemo kartli region of Georgia, hominin remains first classified as a new species, Homo georgicus, but later classified within H. erectus, sometimes called Homo erectus georgicus. Since then additional fossil remains dating roughly from this period were excavated from the site.

"The conventional view of human evolution and how early man colonised the world has been thrown into doubt by a series of stunning palaeontological discoveries suggesting that Africa was not the sole cradle of humankind. Scientists have found a handful of ancient human skulls at an archaeological site two hours from the Georgian capital, Tbilisi, that suggest a Eurasian chapter in the long evolutionary story of man. The skulls, jawbones and fragments of limb bones suggest that our ancient human ancestors migrated out of Africa far earlier than previously thought and spent a long evolutionary interlude in Eurasia – before moving back into Africa to complete the story of man.  

"Experts believe fossilised bones unearthed at the medieval village of Dmanisi in the foothills of the Caucuses, and dated to about 1.8 million years ago, are the oldest indisputable remains of humans discovered outside of Africa. But what has really excited the researchers is the discovery that these early humans (or "hominins") are far more primitive-looking than the Homo erectus humans that were, until now, believed to be the first people to migrate out of Africa about 1 million years ago.  

"The Dmanisi people had brains that were about 40 per cent smaller than those of Homo erectus and they were much shorter in stature than classical H. erectus skeletons, according to Professor David Lordkipanidze, general director of the Georgia National Museum. 'Before our findings, the prevailing view was that humans came out of Africa almost 1 million years ago, that they already had sophisticated stone tools, and that their body anatomy was quite advanced in terms of brain capacity and limb proportions. But what we are finding is quite different," Professor Lordkipanidze said.  

" 'The Dmanisi hominins are the earliest representatives of our own genus – Homo – outside Africa, and they represent the most primitive population of the species Homo erectus to date. They might be ancestral to all later Homo erectus populations, which would suggest a Eurasian origin of Homo erectus.'

"Speaking at the British Science Festival in Guildford, where he gave the British Council lecture, Professor Lordkipanidze raised the prospect that Homo erectus may have evolved in Eurasia from the more primitive-looking Dmanisi population and then migrated back to Africa to eventually give rise to our own species, Homo sapiens – modern man.  

" 'The question is whether Homo erectus originated in Africa or Eurasia, and if in Eurasia, did we have vice-versa migration? This idea looked very stupid a few years ago, but today it seems not so stupid,' he told the festival.  

The scientists have discovered a total of five skulls and a solitary jawbone. It is clear that they had relatively small brains, almost a third of the size of modern humans. 'They are quite small. Their lower limbs are very human and their upper limbs are still quite archaic and they had very primitive stone tools,' Professor Lordkipanidze said. 'Their brain capacity is about 600 cubic centimetres. The prevailing view before this discovery was that the humans who first left Africa had a brain size of about 1,000 cubic centimetres.'

"The only human fossil to predate the Dmanisi specimens are of an archaic species Homo habilis, or 'handy man', found only in Africa, which used simple stone tools and lived between about 2.5 million and 1.6 million years ago.  

" 'I'd have to say, if we'd found the Dmanisi fossils 40 years ago, they would have been classified as Homo habilis because of the small brain size. Their brow ridges are not as thick as classical Homo erectus, but their teeth are more H. erectus like,' Professor Lordkipanidze said. 'All these finds show that the ancestors of these people were much more primitive than we thought. I don't think that we were so lucky as to have found the first travellers out of Africa. Georgia is the cradle of the first Europeans, I would say,' he told the meeting.  

" 'What we learnt from the Dmanisi fossils is that they are quite small – between 1.44 metres to 1.5 metres tall. What is interesting is that their lower limbs, their tibia bones, are very human-like so it seems they were very good runners,' he said.  

"He added: 'In regards to the question of which came first, enlarged brain size or bipedalism, maybe indirectly this information calls us to think that body anatomy was more important than brain size. While the Dmanisi people were almost modern in their body proportions, and were highly efficient walkers and runners, their arms moved in a different way, and their brains were tiny compared to ours.

'Nevertheless, they were sophisticated tool makers with high social and cognitive skills,' he told the science festival, which is run by the British Science Association.  

"One of the five skulls is of a person who lost all his or her teeth during their lifetime but had still survived for many years despite being completely toothless. This suggests some kind of social organisation based on mutual care, Professor Lordkipanidze said" (http://www.independent.co.uk/news/science/a-skull-that-rewrites-the-history-of-man-1783861.html [09 September 2009], accessed 08-08-2013).


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Pithecanthropus erectus, the First Known Specimen of Homo erectus Circa 1,800,000 BCE – 141,000 BCE

Original fossil bones of Pithecanthropus erectus (now Homo erectus) found in Java in 1891. (Click on image to view larger.)

Illustration of Java Man scull. (Click on image to view larger.)

In 1891 Dutch physician, paleoanthropologist and geologist Eugène Dubois discovered a fossil skullcap, femur and a few teeth at Trinil - Ngawi Regency on the banks of the Solo River in East Java, Indonesia. Dubois characterized this specimen as a species "between humans and apes," naming it Pithecanthropus erectus (ape-human that stands upright). Prior to Dubois human fossils such as Neanderthal 1 and Cro-Magnon had been discovered by accident; Dubois was the first scientist to set out to discover prehistoric human fossils, and for his controversial discovery of Pithecanthropus erectus he received great fame and notoriety. 

In 1936 a more complete specimen of Pithecanthropus erectus was discovered by German-born paleontologist and geologist G. H. R. von Koenigswald in the village of Sangiran, Central Java, 18 km to the north of Solo. 

"Until older human remains were discovered in the Great Rift Valley in Kenya, Dubois' and Koenigswald's discoveries were the oldest hominid remains ever found. Some scientists of the day suggested Dubois' Java Man as a potential intermediate form between modern humans and the common ancestor we share with the other great apes. The current consensus of anthropologists is that the direct ancestors of modern humans were African populations of Homo erectus (possibly Homo ergaster), rather than the Asian populations exemplified by Java Man and Peking Man. Dubois' specimen was later classified as Homo erectus, a species that lived throught most of the Pleistocene epoch, originating in Africa and spreading as far as England, Georgia, India, Sri Lanka, China and Java" (Wikipedia article on Java Man, accessed 08-21-2013).

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The Oldest Almost Complete Mitochondrial Genome Sequence of a Hominin Circa 400,000 BCE

The "Homo Heidelbergensis Cranium 5" from Sima de los Huesos in Spain.

The exterior of the Denivosa Cave

Molar found in Denisova Cave of the Altay Mountains in Southern Siberia.

On December 4, 2013 Matthias Meyer, Eduald Carbonell and Svante Pääbo and colleagues reported that the almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos in Spain, dating back roughly 400,000 years, shows that it is closely related to the lineage leading to mitochonrial genomes of Denisovans, an eastern Eurasian sister group to Neanderthals.

"The fossil, a thigh bone found in Spain, had previously seemed to many experts to belong to a forerunner of Neanderthals. But its DNA tells a very different story. It most closely resembles DNA from an enigmatic lineage of humans known as Denisovans. Until now, Denisovans were known only from DNA retrieved from 80,000-year-old remains in Siberia, 4,000 miles east of where the new DNA was found.

"The mismatch between the anatomical and genetic evidence surprised the scientists, who are now rethinking human evolution over the past few hundred thousand years. It is possible, for example, that there are many extinct human populations that scientists have yet to discover. They might have interbred, swapping DNA. Scientists hope that further studies of extremely ancient human DNA will clarify the mystery" (http://www.nytimes.com/2013/12/05/science/at-400000-years-oldest-human-dna-yet-found-raises-new-mysteries.html?hp&_r=0, accessed 12-04-2013).

Meyer et al, "A mitochondrial genome sequence of a hominin from Sima de ls Huesos", Nature (2013) doi:10.1038/nature12788.

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The Oldest Fossil Remains of Anatomically Modern Humans Circa 195,000 BCE

Scull from the River Omo. (Click on image to view larger.)

The bones of an early member of our species, Homo sapiens, known as Omo I, excavated from Ethiopia's Kibish rock formation. The bones are kept in the National Museum of Ethiopia. When the first bones from Omo I were found in 1967, they were thought to be 130,000 years old. Later, 160,000-year-old bones of our species were found elsewhere. Now, a new study by scientists from the University of Utah and elsewhere determined that Omo I lived about 195,000 years ago -- the oldest known bones of the human species. (Credit: John Fleagle, Stony Brook University) (Click on image to view larger.)

Location of Omo Valley in Ethiopia, Africa. (Click on image to view larger.)

Between 1967 and 1974 a scientific team from the Kenya National Museums directed by Richard Leakey and others discovered a collection of hominid bones at the Omo Kibish sites near the Omo River, in Omo National Park in south-western Eithiopia.  These fossil bones, which include two partial skulls as well as arm, leg, foot and pelvis bones, are known as the Omo remains. In 2013, when I wrote this entry, these were the oldest fossil remains of anatomically modern humans, or anatomically modern Homo sapiens—individuals with the range of phenotypes of modern humans.

"In 2004, the geologic layers around the fossils were dated, and the authors of the dating study concluded that the 'preferred estimate of the age of the Kibish hominids is 195 ± 5 ka [thousand years ago]", which would make the fossils the oldest known Homo sapiens remains. In a 2005 article on the Omo remains, Nature magazine said that, because of the fossils' age, Ethiopia is the current choice for the 'cradle of Homo sapiens' " (Wikipedia article on Omo remains, accessed 08-21-2013).

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The First Complete Neanderthal Genome Sequence Circa 128,000 BCE

Svante Pääbo.

A map of the Altai Mountain range.

On December 18, 2013 Svante Pääbo and colleagues from the Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology in Leipzig, together with scientists from research centers in America, China, Russia and other countries, announced that they sequenced the complete genome of a 130,000 year old Neanderthal woman from a single toe found in a Siberian cave in the Altai Mountains. There DNA evidence has been unusually well preserved because of very low average temperature. Comparison of this complete Neanderthal genome with those of 25 modern humans enabled the authors to compile a list of mutations that evolved in modern humans after their ancestors branched off from Neanderthals some 600,000 years ago. "The list of modern human things is quite short," said John Hawks, a paleoanthropologist at the University of Wisconsin who was not involved in the study. The paper, published in the journal Nature, was entitled "The complete genome sequence of a Neanderthal from the Altai Mountains"  doi:10.1038/nature12886.

The abstract read as follows:

"We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans."

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Scientists Sequence Woolly Mammoth Genome--the First of an Extinct Animal Circa 100,000 BCE

The largest European specimen of a Wooly Mammoth.

A Steppe Mammoth skull in Sibera.

A male Asian Elephant in India.

A chart from the Mammoth Genome Project depicting gene-encoding bases on chromosomes of both a human and a mammoth. 

On November 19, 2008 scientists from the Mammoth Genome Project at Pennsylvania State University, University Park, reported the genome-wide sequence of the woolly mammoth, an extinct species of elephant that was adapted to living in the cold environment of the northern hemisphere.  The woolly mammoth, Mammuthus primigenius, was a species of mammoth, the common name for the extinct elephant genus Mammuthus. One of the last in a line of mammoth species, it diverged from the steppe mammothM. trogontherii, about 200,000 years ago in eastern Asia. Its closest extant relative is the Asian elephant.

The genome sequence of the woolly mammoth was the first sequence of the genome of an extinct animal, and it opened up the possibility of reconstructing species from the last Ice Age.

"They sequenced four billion DNA bases using next-generation DNA-sequencing instruments and a novel approach that reads ancient DNA highly efficiently."

'Previous studies on extinct organisms have generated only small amounts of data," said Stephan C. Schuster, Penn State professor of biochemistry and molecular biology and the project's other leader. "Our dataset is 100 times more extensive than any other published dataset for an extinct species, demonstrating that ancient DNA studies can be brought up to the same level as modern genome projects' (quoted from Genetic Engineering and Biotechnology News accessed 11-21-2008).

" 'By deciphering this genome we could, in theory, generate data that one day may help other researchers to bring the woolly mammoth back to life by inserting the uniquely mammoth DNA sequences into the genome of the modern-day elephant,' Stephan Schuster of Pennsylvania State University, who helped lead the research, said in a statement." (quoted from Reuters 11-19-2008, accessed 11-21-2008).

"The appearance and behaviour of this species are among the best studied of any prehistoric animal due to the discovery of frozen carcasses in Siberia and Alaska, as well as skeletons, teeth, stomach contents, dung, and depiction from life in prehistoric cave paintings. Mammoth remains had long been known in Asia before they became known to Europeans in the 17th century. The origin of these remains was long a matter of debate, and often explained as being remains oflegendary creatures. The animal was only identified as an extinct species of elephant by Georges Cuvier in 1796." (Wikipedia article on Woolly Mammoth, accessed 10-31-2013).

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Computational Micro-Biomechanical Analysis of Neanderthal's Fossilized Hyoid Bone Suggests that Neanderthals Could Speak Circa 60,000 BCE

A computational micro-biomechanical analysis of a Neanderthal hyoid bone found in Kebara Cave, Israel, suggests that Neanderthals could speak. This was suspected since discovery in 1989 of a Neanderthal hyoid that looked like that of humans. A study published in December 2013 suggests that not only did the bone resemble that of humans but it was also used in a similar way.

"Stephen Wroe, from the University of New England, Armidale, NSW, Australia, said: 'We would argue that this is a very significant step forward. It shows that the Kebara 2 hyoid doesn't just look like those of modern humans - it was used in a very similar way.'

"He told BBC News that it not only changed our understanding of Neanderthals, but also of ourselves.

"' Many would argue that our capacity for speech and language is among the most fundamental of characteristics that make us human. If Neanderthals also had language then they were truly human, too.' "

Ruggero D'Anastasio, Stephen Wroe et al, "Micro-Biomechanics of the Kebara 2 Hyoid and Its Implications for Speech in Neanderthals," Plos One, December 18, 2013, DOI: 10.1371/journal.pone.008226. The Abstract of the article:

"The description of a Neanderthal hyoid from Kebara Cave (Israel) in 1989 fuelled scientific debate on the evolution of speech and complex language. Gross anatomy of the Kebara 2 hyoid differs little from that of modern humans. However, whether Homo neanderthalensis could use speech or complex language remains controversial. Similarity in overall shape does not necessarily demonstrate that the Kebara 2 hyoid was used in the same way as that of Homo sapiens. The mechanical performance of whole bones is partly controlled by internal trabecular geometries, regulated by bone-remodelling in response to the forces applied. Here we show that the Neanderthal and modern human hyoids also present very similar internal architectures and micro-biomechanical behaviours. Our study incorporates detailed analysis of histology, meticulous reconstruction of musculature, and computational biomechanical analysis with models incorporating internal micro-geometry. Because internal architecture reflects the loadings to which a bone is routinely subjected, our findings are consistent with a capacity for speech in the Neanderthals." 

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Discovery of the Cro-Magnons, the First European Early Modern Humans Circa 41,000 BCE

Cro Magnon skull. (Click on image to view larger.)

Abri de Cro-Magnon - rock shelter of Cro Magnon. (Click on image to view larger.)

After workmen stumbled across extinct animal bones, flint tools and a human skull in a rock shelter near the French village of Les Eyzies, French geologist and prehistorian Louis Lartet was asked to conduct excavations. In March 1868 Lartet discovered the first five skeletons of early modern humans at the Abri de Cro-Magnon (rock shelter of Cro-Magnon), near the commune of Les Eyzies-de-Tayac-Sireuil in southwestern France. He discovered the partial skeletons of four prehistoric adults and one infant along with perforated shells used as ornaments, an object made from ivory, and worked reindeer antler. These Cro-magnon humans were soon identified as a new prehistoric human race distinct from the Neanderthal fossils discovered in Germany in 1856.

Lartet, L. “Mémoire sur une sepulture des anciens troglodytes du Périgord.” Annales des sciences naturelles: Zoologie et paléontologie ser 5, 10 (1868) 133-45.

Lartet, L. “Une sépulture des troglodytes du Périgord,” Bulletins de la Société d’Anthropologie de Paris 3 (1868) 335-349.

(This entry was last revised on April 16, 2014.)

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The First Specimen to be Recognized as an Early Human Fossil Circa 40,000 BCE

Fossilized scullcap of Neanderthal 1. (Click on image to view larger.

Drawing of fossilized scullcap of Neanderthal 1. (Click on image to view larger.)

Map showing range of Neanderthals. From Science Magazine. (Click on image to view larger.)

Map showing location of Neander Valley in Germany. (Click on image to view larger.)

In August 1856, laborers in a mining operation discovered human bones in the Kleine Feldhofer Grotte in the Neandertal (Neanderthal), a small limestone valley in northern Germany. This finding, consisting of a partial skull, pelvis and assorted long bones, which later became known as Neanderthal 1, became the first specimen to be recognized as an early human fossil. The oval shaped skull with a low, receding forehead and distinct browridges, the thick, strong bones were distinctly different from modern humans.

The bones were sent to Johann Carl Fuhlrott, a science teacher in Elberfeld, who immediately recognized that the bones were a previously unknown type of human. This conclusion was borne out by Hermann Schaaffhausen, a physician and anthropologist in Bonn to whom Fuhlrott sent a cast of the cranium. Over the winter of 1856–57 Schaaffhausen examined the Neanderthal bones in detail, and in 1857 he and Fuhlrott published preliminary announcements of the discovery in the Verhandlungen. des naturhistorischen Vereines des preussischen Rheinlande und Westphalens.XIV (1857) xxxviii-xlii, l-lii.  Fuhlrott’s account appears on page l (Roman numeral pagination).

In 1864, Neanderthal 1 became the first fossil hominin species to be named. Geologist William King suggested the name Homo neanderthalensis (Neanderthal Man). Several years after Neanderthal 1 was discovered, scientists realized that prior fossil discoveries, by Philippe-Charles Schmerling in 1829 at Engis, Belgium, and in 1848 at Forbes Quarry, Gibraltar (Gibralter 1)—were also Neanderthals. Even though they weren’t recognized at the time, these earlier discoveries, and that of the so-called "Red Lady of Paviland" by William Buckland at Paviland Cave (Goat's Hole) South Wales in 1823, were among the first early human fossils ever found.

♦ As recently as March 1999 archaeologists Ralf Schmitz and Jurgen Thissen pinpointed the site where Neanderthal 1 was discovered in 1856, and dug up missing parts of the original skeleton that had been passed over in the original excavation. They found 20 bone fragments— a molar, a vertebra, ribs, a toe, and a bit of pelvis; one of the fragments exactly fit the left knee joint of the specimen found in 1856. Continuation of the excavation in 2000 recovered thousands of artefacts. Mitochondrial DNA of two samples fresh from the ground were fully sequenced, and completed in 2009, finally allowing an objective biological means of comparison between Neanderthals and modern humans.


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The Denisova Hominin, a Third Kind of Human Circa 39,000 BCE

Molar found in Denisova Cave of the Altay Mountains in Southern Siberia. (Click on image to view larger.)

The Family Tree - Neanderthals and Denisovans were closely related. DNA comparisons suggest that our ancestors diverged from theirs some 500,000 years ago. (Click on image to view larger.)


 A Tale of Three Humans

A third kind of human, called Denisovans, seems to have coexisted in Asia with Neanderthals and early modern humans. The latter two are known from abundant fossils and artifacts. Denisovans are defined so far only by the DNA from one bone chip and two teeth—but it reveals a new twist to the human story.

Chip Clark, Smithsonian Institution.

On March 24, 2010 scientists announced the discovery of a finger bone fragment of an eight year old girl who lived about 41,000 years ago, found in the remote Denisova Cave in the Altai Mountains in Siberia, a cave which was also inhabited by Neanderthals and modern humans. Discovery of two teeth and a toe bone belonging to different members of the same population were later reported.These three objects are the only specimens from which the Denisova hominins are known. The average annual temperature of Denisova Cave remains at 0°C (32°F), a factor which contributed to the preservation of archaic DNA among the diverse prehistoric remains discovered, in addition to the Denisova hominin remains. 

Using a new technique for sequencing ancient DNA from bone, in August 2012 scientists from the Max Planck Institute reconstructed the genome of the Denisova hominins and announced that they were a new species, that they interbred with our species, and that the DNA results suggest that they had dark hari, eyes, and skin.  

"Analysis of the mtDNA of the finger bone showed it to be genetically distinct from the mtDNAs of Neanderthals and modern humans [Katsnelson 2010]. However, subsequent study of the genome from this specimen suggests this group shares a common origin with Neanderthals. They ranged from Siberia to Southeast Asia, and they lived among and interbred with the ancestors of some present-day modern humans, with up to 6% of the DNA of Melanesians and Australian Aboriginies deriving from Denisovans.

"It was in 2008 when Russian archaeologists discovered the finger bone fragment, and nick-named it 'X Woman'. Artifacts, including a bracelet, excavated in the cave at the same level were carbon dated to approximately 40,000 BP.

"A team of scientists led by Johannes Krause and Svante Paabo from the Max Planck Institute in Germany sequenced mtDNA from the fragment. The analysis indicated that modern humans, Neanderthals and the Denisova hominin last shared a common ancestor around 1 million years ago [Katsnelson 2004].

"The mtDNA analysis further suggested this new hominin species was the result of an early migration out of Africa, distinct from the later out-of-Africa migrations associated with Neanderthals and modern humans. Some argue it may be a relic of the earlier African exodus of Homo erectus, because of the tooth size, although this has not been proved. The conclusions of both the excavations and the sequencing are still debatable because the evidence shows that the Denisova Cave has been occupied by all three human forms" (http://www.bradshawfoundation.com/origins/denisova_hominin.php, accessed 07-07-2013).

For images and a very readable account of these discoveries see "The Case of the Missing Ancestor," nationalgeographic.com, July, 2013.


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Neanderthal Genome Reveals Interbreeding with Humans Circa 36,000 BCE

Svante Pääbo

In May 2010 paleogeneticist Svante Pääbo and colleagues at the Max Planck Institute for Evolutionary Anthropology in Leipzig published a draft genome sequence of DNA obtained from Neanderthal bones recovered from Vindija Cave that were around 38,000 years old. Neanderthal fossils found in this cave near the city of VaraždinCroatia, are among the best preserved in the world.

In their preliminary draft of the Neanderthal genome announced in February 2009 the scientists indicated that

"Previous mitochondrial analysis of Neanderthal DNA has uncovered no sign that Neanderthals and humans interbred sufficiently to leave a trace. A preliminary analysis across the new genome seems to confirm this conclusion, but more sequence data could overturn this conclusion" (http://www.newscientist.com/article/dn16587-first-draft-of-neanderthal-genome-is-unveiled.html#.UnKcfFCsim4. accessed 10-31-2013). 

However, comparison in 2010 of the full Neanderthal sequence with that of modern humans suggested that there was some interbreeding between Homo neanderthalensis and Homo sapiens.

"Bone contains DNA that survives long after an animal dies. Over time, though, strands of DNA break up, and microbes with their own DNA invade the bone. Pääbo's team found ways around both problems with 38,000 and 44,000-year-old bones recovered in Croatia: they used a DNA sequencing machine that rapidly decodes short strands and came up with ways to get rid of the microbial contamination.

"They ended up with short stretches of DNA code that computers stitched into a more complete sequence. This process isn't perfect: Pääbo's team decoded about 5.3 billion letters of Neanderthal DNA, but much of this is duplicates, because – assuming it's the same size as the human genome – the actual Neanderthal genome is only about 3 billion letters long. More than a third of the genome remains unsequenced. . . .

"Any human whose ancestral group developed outside Africa has a little Neanderthal in them – between 1 and 4 per cent of their genome, Pääbo's team estimates. In other words, humans and Neanderthals had sex and had hybrid offspring. A small amount of that genetic mingling survives in "non-Africans" today: Neanderthals didn't live in Africa, which is why sub-Saharan African populations have no trace of Neanderthal DNA" (http://www.newscientist.com/article/dn18869-neanderthal-genome-reveals-interbreeding-with-humans.html#.UnKfSFCsim4, accessed 10-31-2013).

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1,000 BCE – 300 BCE

The First Description of Book Scorpions, by Aristotle Circa 350 BCE

Among the many original descriptions in Aristotle's  De historia animalium, the founding work of descriptive zoology, was the first to description of pseudoscorpions. These Aristotle probably found among book rolls in a library where they would have been feeding on booklice. Pseudoscorpions are generally beneficial to humans since they prey on clothes moth larvae, carpet beetle larvae, booklice, ants, mites, and small flies. They are tiny and inoffensive, and are rarely seen due to their size. Aristotle wrote in Book V, Chapter 26 of his De historia animalium:

"1. There are also other minute animals, as I observed before, some of which occur in wool, and in woollen goods; as the moths, which are produced in the greatest abundance when the wool is dusty, as especially if a spider is enclosed with them, for this creature is thirsty, and dries up any fluid which may be present. This worm also occurs in garments. There is one which occurs in old honeycombs, like the creature which inhabits dry wood; this appears to be the least of all creatures, it is called acari, it is white and small. Others also are found in books, some of which are like those which occur in garments; others are like scorpions; they have no tails, and are very small. And on the whole, they occur in everything, so to say, which from being dry, becomes moist, or being moist, becomes dry, if it has any life in it" (Aristotle's History of Animals, In Ten Books, Translated by Richard Cresswell [London, 1862] 135). 

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800 – 900

The Earliest Surviving Copy of Aristotle's Biological Works Circa 850

A Greek manuscript of Aristotle's Biological Works, written in Constantinople in the mid-9th century, and preserved at Corpus Christi College, Oxford(Corpus Christi College, MS. 108) is probably the oldest surviving manuscript of the texts that founded the science of biology. It contains annotations in Greek hands of the 12th and 13th centuries.

"A list of contents has been added on the last page (fol. 183v) in an English hand of the mid-13th century, which may be that of Robert Grosseteste, one of the earliest Englishmen to study Greek. Two titles and a few words of the 13th-cent. Latin translation by William of Moerbeke were added. . . in an English humanistic hand possibly identifiable as that of John Farley (d. 1464), fellow of New College and registrar of Oxford University, whose study of Greek is known from other manuscripts" (Hunt, R.W., The Survival of the Classics, Oxford: Bodleian Library [1975] No. 54.).

The manuscript was given to Corpus Christi College, Oxford by Henry Parry in 1623.

"The surviving corpus of Aristotle derives from medieval manuscripts based on a 1st century BC edition. There were no commentaries on the biological works written until they were collectively translated into Arabic. The first appearance of Aristotle's biological writings in the West are Latin translations of an Arabic edition by Michael Scot, which forms the basis of Albertus Magnus's De animalibus. In the 13th century William of Moerbeke produced a Latin translation directly from the Greek. The first printed editions and translations date to the late 15th century, the most widely circulated being that of Theodorus Gaza. In addition to the three works traditionally referred to as History of Animals, Parts of Animals and Generation of Animals, there are a number of briefer ‘essays’ on more specialized topics: On animal motion, On animal locomotion, On respiration, On life and death, On youth and old age, On length and shortness of life, On sleeping and waking, On the senses and their objects (the last six being included in the so-called Parva naturalia). Whether one should consider De Anima (On the soul) part of this project or not is a difficult question. What is certainly clear, however, is that there are important connections between the theoretical approach to the relationship between body and soul defended in that work and the distinctive way that Aristotle approaches the investigation of animals" (http://plato.stanford.edu/entries/aristotle-biology/).

(This entry was last revised on 04-30-2014.)

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1450 – 1500

Aristotle's "De animalibus", the First Printed Compilation of Works on Biology 1476

In 1476 printers Johann de Colonia and Johannes Manthen of Venice issued Aristotle's De animalibus, translated from the Greek by Greek humanist Theodorus Gaza (Greek: Θεόδωρος Γαζής, Theodoros Gazis), and edited by Ludovicus Podocatharus, perhaps with expenses born by Podocatharus. Aristotle was the first scientist to gather empirical evidence about the biological world through observation. The printed edition, which contained his De historia animalium (descriptive zoology), De partibus animalium (animal physiology), and De generatione animalium (embryology), was the first printed compilation of works relating to biology. The Historia's "comprehensiveness and acumen made it the outstanding descriptive zoology of ancient times. . . . It outlasted the work of such later encyclopedic compilers as Pliny, and combined with Aristotle's other zoological works it became-- through the Arabic version translated into Latin by Michael Scot-- the major ingredient in Albertus Magnus' De animalibus, which dominated the field until the sixteenth century" (Dictionary of Scientific Biography). Joseph Needham (p. 39) called De generatione animalium "the first great compendium of embryology ever written"; it contained Aristotle's studies of the chick in embryo, and introduced his hypothesis that embryos were produced by the working of the male dynamic element (semen) upon the female plastic element (menstrual blood), to which the semen gave form. Book II presented Aristotle's embryological classification of animals and a discussion of the question of epigenesis versus preformation-- an antithesis that Aristotle was the first to perceive, and which was to define the subsequent history of embryology.

On June 8, 2016 Bonham's in New York auctioned a remarkable copy of this work printed on vellum. Rebecca Rego Barry published an excellent account of it in TheGardian.com on May 11, 2016, from which I quote:

"The rediscovery of a 15th-century illuminated edition of Aristotle’s De animalibus (On Animals) in Tennessee late last year was 'pretty incredible', said Christina Geiger, director of fine books and manuscripts at Bonhams auction house in New York. Not only is the book an 'incunable' – printed before 1501, when the ink was still wet on moveable type – but this deluxe copy was printed on vellum, or animal skin. Only one other copy [printed on vellum] exists and it belongs to the Bibliothèque Nationale in Paris....

"An invitation from Pope Nicholas V prompted a new Latin translation of the book by Greek scholar and refugee Theodore Gaza, printed in Venice by John of Cologne and John Manthen in 1476. The auctioneers believe that Gaspare da Padova is the artist responsible for the volume’s decorative initials and borders painted in gold and various colors. A handful of special vellum copies were probably produced for sponsors. Only one was thought to have survived before this recent finding.

"Bonhams will offer the Renaissance-era rarity at auction in New York on 8 June. It is estimated to fetch $300,000 to $500,000. 

"The book last surfaced at auction on 5 March 1891, when American publisher and book collector William Evarts Benjamin purchased it for $850. 'We don’t know if he sold it or kept it,' said Geiger. 'We checked all of his catalogues over at the Grolier Club and we checked his archives at Columbia and couldn’t find a reference to it. But he’s listed as the buyer in 1891, and then it just fell off the map completely.'

"No proof of the volume’s existence appears in the Census of 15th Century Books Owned in America published in 1919. The consignors’ grandmother acquired the book before 1964. The family retains letters between her and a librarian she contacted to make inquiries. 'Those intervening years are a big question mark,' said Geiger.

“ 'Part of what’s interesting for me is that if that sale in 1891 had been just a few years later, [De animalibus] probably would have been bought by Huntington or Morgan or one of the great collectors of incunables in America, but it was just a little bit too early.'

"Geiger’s research turned up a long line of distinguished ownership before that 1891 sale, beginning with Luigi Serra, fourth Duke of Cassano (1747-1825). It then moved through the hands of bookseller James Edwards to Sir Mark Masterman-Sykes, the famed nineteenth-century book collector, who had it re-bound in red morocco gilt. His coat of arms still embellishes the binding.

"It was while De animalibus was in Sir Mark’s collection that the well-known English bibliophile TF Dibdin had the opportunity to see it. He recorded his impression in his Bibliographical Decameron (1817): 'Yet how can I omit to mention, with the distinction which it merits, the very beautiful, if not matchless, copy of Theodore Gaza’s Latin version of Aristotle upon Animals, of the date of 1476, in folio, UPON VELLUM, from the press of John of Cologne – of which my friend Sir MM Sykes is the fortunate possessor?! If my memory be not treacherous, this is the most exquisite specimen of an early Venetian vellum book that I have ever seen.'

"Geiger said: 'This is that very copy, almost exactly 200 years later.You could probably go back and find out when he was at Sykes’ home. I haven’t gone back that deep, but [Dibdin’s] book was published in 1817, so here we are in 2016 and [De animalibus] is in the same condition. That’s the other thing. For a book that fell through the cracks, it didn’t get run over. It’s just in beautiful condition.'

"Other 19th-century owners of the volume include English publisher and bookseller William Pickering, Sir John Hayford Thorold, bookseller and collector Bernard Quaritch, and American railway tycoon and banker Brayton Ives."

J. Norman (ed.), HistoryofMedicine.com Nos. 274; 275; 462. Needham, History of Embryology 37-43. Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) No. 69. ISTC No.: ia00973000. In November 2013 a digital facsimile was available from the Bayerische Staatsbibliothek at this link.

(This entry was last revised on 05-13-2016.)

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The Aldine Aristotle, One of the Most Significant Publishing Ventures of the Fifteenth Century 1495 – 1498

Between November 1495 and June 1498 scholar printer Aldus Manutius (Teobaldo Mannucci) of Venice issued the first edition in the original Greek of Aristotle's Opera omnia. The set appeared in five thick quarto or small folio volumes, often bound in six. Assembling all of the texts was a major challenge for Aldus and his associates, requiring the help of scholars in different countries, and yet during the publication process Greek texts of both the Poetics and On Rhetoric, remained elusive. The editio princeps of Aristotle appeared at the close of a century that had witnessed a strong revival in Greek and humanistic studies; it was the first major Greek prose text, or collection of texts, to be reintroduced to the Western world in its original language by means of the printing press, and its success launched Aldus's efforts to produce further editiones principes of other Greek authors. In addition to the Aristotelian works, the five volumes contained works by Aristotle's successor Theophrastus, the commentator on Aristotle, Alexander of Aphrodisias, the neo-Platonic philosopher Porphyrius, and Philo of Alexandria (Philo Judaeus) along with the spurious De historia philosophia attributed to Galen.

" 'The Aldine Aristotle' remains, in terms of the labour involved and the magnificence of the result, the greatest publishing venture of the fifteenth century. The centrality of Aristotle in intellectual life of the time can hardly be overstressed. In Latin dress he lay at the heart of any university course in philosophy, as dominant at the end of the Quattrocento as in the preceding three hundred years. The humanist return ad fontes, to the original unobscured by imprecise translation and the encrustations of scholastic commentary, was the indispenable background to the edition. . . .

"Certain important Aristotelian works were as yet unfindable, notably the Rhetoric and the Poetics—Aldus was later to print the first Greek editions of both. The second volume is largely taken up with the works of Theophrastus, the successor of Aristotle in the Athenian Lyceum. . . . (Davies, Aldus Manutius, Printer and Publisher of Renaissance Venice (1999) 20-22).

ISTC No.: ia00959000. In March 2014 digital facsimiles of all five volumes were available from the Bayerische Staatsbibliothek. Volume 1 was available at this link.

Dibner, Heralds of Science, no. 73.  Carter & Muir, Printing and the Mind of Man (1967) no. 38. Renouard, Aldus Manutius, pp. 7-9. Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 70. 

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1650 – 1700

Precursor of Malthus 1677

In The Primitive Organization of Mankind Considered and Examined According to the Light of Nature (1677) English jurist Matthew Hale  "seems to have been the first to use the expression 'Geometrical Proportion' for the growth of a population from a single family" (Hutchinson). In this he anticipated Malthus. Hale believed that in animals, especially insects, various natural calamities reduce the numbers to low levels intermittently, so maintaining a balance of nature.

J. Norman (ed.) Morton's Medical Bibliography, 5th ed (1991) No. 215.

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The Structural Relationships between the Body of Man and the Anthropoid Ape 1699

In 1699 English Physician and comparative anatomist Edward Tyson published in London Orang-Outang, sive Homo Sylvestris; or, the Anatomy of a Pygmie Compared with that of a Monkey, an Ape and a Man, including 8 folding plates engraved by Michael Vandergucht after drawings by the artist and anatomist, William Cowper.

Tyson's anatomy of the "orang-outang" (in Tyson's case a chimpanzee rather than an orangutan) was the first work to demonstrate the structural relationships between the anatomy of man and the anthropoid ape. For Tyson the term Orang-Outang meant "man of the woods."

In 1641 the Dutch surgeon and anatomist Nicholas (or Nicolaes) Tulp had used the same words to describe a chimpanzee, which he illustrated in his Observationum medicarumThis book included the first, limited description by a scientist of an African anthropoid ape. Regarding Tulp's description Tyson said that "I confess that I do mistrust the whole representation."

The ape which Tulp described seems to have come from Angola, and Tulp had the opportunity to observe it in the private menagerie of the Prince of Orange. Tulp seems to have learned the name orang-outang from Samuel Blomartio, a friend who had lived in Borneo and was familiar with the Javanese word for "man of the woods." Tulp seems to have been under the impression that orangutans were widely distributed throughout the tropics rather than limited to Asia, and thus confused the two species. The classification of the orangutan in the the Ponginae (Pongo) subfamily of the family hominidae, outside of the subfamily homininae from which humans descend, and to which the chimpanzee belongs, had not yet occurred.

Perhaps with some humor, but also to confirm the anatomical similarities, Tyson had Cowper draw the standing dissected figures of chimpanzees in the style of the famous Vesalian musclemen. A believer in the "Great Chain of Being" or scala naturae, Tyson identified the chimpanzee as the link directly below mankind, stating in his "Epistle Dedicatory" that it "seems the Nexus of the Animal and Rational."

Tyson's anatomical study— the first conducted of a great ape— had a powerful influence on all subsequent thought on man's place in nature. Thomas Huxley referred to it extensively in his 1863 book with that title. Tyson's last section of Orang-Outang is devoted to "A Philological Essay Concerning the Pygmies of the Ancients," an early contribution to the study of primate-oriented folklore.

Cole, History of Comparative anatomy, 198-221. Montague, Edward Tyson (1943) ch. 8. Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 2120.  Spencer, Ecce Homo. An Annotated Bbiliographic History of Physical Anthropology (1986) no. 1.92.

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1700 – 1750

Pierre-Louis Moreau de Maupertuis' Pioneer Theory of Epigenesis and Biparental Heredity 1744 – 1745

Pierre Louis Maupertuis

Venus Physique by Maupertuis

Dissertation physique a l'occasion du negre blanc by Maupertuis

In 1744 French mathematician, philosopher and man of letters Pierre-Louis Moreau de Maupertuis issued anonymously Dissertation physique a l'occasion du negre blanc in Leiden through an unidentified publisher. This small book on human heredity was inspired by the appearance in Paris of a young albino negro. The case prompted Maupertuis to search for other cases of abnormal traits being passed down in a family from one generation to the next.  The following year he explored the issue of human heredity more fully in his Venus physique which incorporated a reprint of the 1744 Dissertation.

Issued anonymously in 1745, and without publishing location or the name of its printer, Venus physique refuted the preformationist theories of embryonic development held by most of his contemporaries in favor of the then-discredited epigenetic hypothesis, which Maupertuis had adopted after considering the obvious facts of biparental heredity.  Maupertuis rejected all vitalist or spiritual interpretations of the hereditary mechanism, arguing that biparental heredity required corporeal contributions from each parent. This argument was based on research that Maupertuis performed shortly after his arrival in Berlin in 1740, when he began collecting the pedigrees of the polydactylous Ruhe family. These pedigrees showed that the abnormal trait could be passed either by the male or female parent and that the trait tended to weaken and disappear over time as polydactylous individuals continued to marry normal spouses.  According to Glass, Maupertuis's theories of biparental heredity and epigenesis substantially anticipated those of Darwin, Mendel and de Vries nearly a century and a half later.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 215.1.

Glass, "Maupertuis, pioneer of genetics and evolution," Forerunners of Darwin 1745-1859, ed. Glass, Temkin & Straus (1968) 51-83.

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1750 – 1800

Zimmerman Issues the First Textbook on Zoogeography 1777

The first textbook of zoogeography, containing the first world map showing the distribution of mammals, was Specimen zoologiae geographicae, quadrupedem domicilia et migrationes sistens by German Geographer and Zoologist Eberhard August Wilhelm von Zimmerman  published in Leiden in 1777.

Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 2280.

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Johann Gottfried von Herder, Enlightenment Precursor of Evolution by Natural Selection 1784 – 1791

From 1784 to 1791 German philosopher, poet and literary critic Johann Gottfried von Herder published in Leipzig Ideen zur Philosophie der Geschichte der Menschheit in 4 volumes. Herder's history has long been regarded as a very strong statement of the theory of evolution before Darwin; many passages come close to general statements on evolution by natural selection. Among the passages most often regarded as anticipatory are those on the temporal sequence of forms from simpler to more highly organized, and on the overabundance of nature with the ensuing struggle for existence between species and individuals. 

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 215.3.

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Christian Konrad Sprengel Issues the Founding Work of Floral Ecology 1793

In 1793 German theologist and naturalist Christian Konrad Sprengel issued Das entdeckte Geheimniss der Natur im Bau und in der Befruchtung der Blumen from Berlin through Friedrich Viewig dem aeltern, publishers. Sprengel's work, with its 25 plates engraved after drawings by the author, made a fundamental contribution to our understanding of the role insects play in plant fertilization, and is recognized as one of the founding works of what is now known as pollination or floral ecology. 

Although J. G. Kölreuter had established the role of insects in the pollination of flowering plants in the 1760s, this phenomenon aroused little interest until nearly three decades later, when Sprengel, an amateur botanist, began observing the pollination of geraniums. After spending six years examining the relationship between flowers and their pollinating insects, Sprengel concluded that floral structure in entire orders of flowering plants can be interpreted only by analyzing the role of each part in relation to insect visits. He realized, as Kölreuter had not, that the entire structure of the flower was geared to this method of fertilization, and was the first to describe and illustrate, in nearly 500 species, the principal adaptive floral mechanisms concerned in pollination. In an important corollary, Sprengel noted the great frequency of dichogamy (the maturation at different rates of male and female organs in the same flower), and concluded that Nature did not intend any flower to be fertilized by its own pollen. Darwin recognized the importance of Sprengel’s work, which he read in 1841, and elaborated upon Sprengel’s observations in the Origin of Species (1859), Orchids (1862) and Cross and Self Fertilization (1876).

In December 2013 a digital facsimile of Darwin's extensive manuscript notes preserved in his copy of Sprengel at Down House was available from the Internet Archive at this link.

Dibner, Heralds of Science 30. Norman 1990. Nissen (botany) 1883. Morton, History of Botanical Science, pp. 326-328. 42702

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Malthus on Population 1798

In 1798 economist and demographer Thomas Malthus published in London An Essay on the Principle of Population, as it Affects the Future Improvement of Society. In this rebuttal of the utopian views of William Godwin, Malthus reasoned that populations inscrease by geometrical proportion but food supply only increases arithmetically. He argued that if both food and "the passion between the sexes" are necessary to man's existence, but populations have a much greater tendency to increase than does the food supply, then a "strong and constantly operating check"—such as famine, disease, or sexual deprivation—must be imposed to keep the population level consistent with the level of subsistence. 

Malthus's suppositions, though reasonable, were largely intuitive. Though the Essay contained no supporting numerical data, it was extremely influential on passage of the Census Act or Population Act of 1800, which led in 1801 to the first Census of England, Scotland and Wales. Using some of the information gathered in the first census, Malthus supplied factual documentation to support his theories in the greatly expanded second edition of his Essay published in 1803.

Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 1431.

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1800 – 1850

Lamarck Issues the First Published Statement of Lamarckism 1801

A portrait of Jean Baptiste Pierre Antoine de Monet, Chevalier de Lamarck

Systême des animaux sans vertèbres

In 1801 French soldier, biologist, and naturalist Jean Baptiste Pierre Antoine de Monet, Chevalier de Lamarck published Systême des animaux sans vertèbres. The "Discours d'overture" occupying the first forty-eight pages of this work contained Lamarck's first published statement of his evolutionary theory of species development, including his idea of the continuous progressive perfection of species from the simplest to the most complex, and his famous theory of the inheritance of acquired characteristics, generally called "Lamarckism."  The Systême was also the first zoological work to employ the term "invertebrates" to describe what had previously been lumped under the imprecise category of "insects and worms."

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) No. 215.5.

Hook & Norman, The Haskell F. Norman Library of Science & Medicine (1991) no. 1261.

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Humboldt & Bonpland Describe Geographical-Ecological Plant Associations 1805

In 1805 naturalist, explorer and polymath Friedrich Wilhelm Heinrich Alexander von Humboldt and botanist and explorer Aimé J. A. Bonpland published in Paris Essai sur la géographie des plantes; accompagné d'un tableau physique des régions équinoxales [Vol. I of Voyage aux régions êquinoxales du nouveau continent]. In this contribution to ecology Humboldt and Bonpland founded the study of the geographical distribution of plants. In 1799 Humboldt and Bonpland embarked on a six-year tour of research through South America and Mexico, a trip which would afterwards be called, justifiably, "the scientific discovery of America."  The two amassed exhaustive data in a wide array of fields from meteorology to ethnography, and gathered 60,000 plant specimens, 6,300 of which had been hitherto unknown in Europe.  Their American travel journals— issued under the general title Voyage aux régions équinoxiales du nouveau continent, fait en 1700, 1800, 1801, 1802, 1803 et 1804— were published in thirty-four volumes between 1807 and 1834; the sheets of the present work were reissued as Vol. I of the Voyage, with an extra half-title and general title and the plate colored. [We have also seen a copy with the plate uncolored.] Humboldt classified these volumes into six subject groups, of which this volume on plant geography constituted the whole of the fifth.  It contains some very interesting ideas on the relation between natural classification of plants and their geographical distribution, as well as one of the earliest attempts to describe the distribution of plants by characterizing geographical-ecological plant associations.

Hook & Norman , The Haskell F. Norman Library of Science and Medicine (1991) no. 1111.

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Lamarck's Most Extensive Exposition of his Theory of the Inheritance of Acquired Characteristics 1809

A portrait of Jean-Baptiste Lamarck by Charles Thévenin

Philosophie Zoologique by Lamarck

In 1809 French naturalist and biologist Jean-Baptiste Pierre Antoine de Monet, Chevalier de Lamarck published Philosophie zoologique. This 2-volume work was Lamarck's most extensive presentation of his evolutionary theory of species development. The work was divided into three parts, the first two of which contained a more elaborate analysis of the evidence for increasing levels of complexity, and a more detailed discussion of Lamarck's two-factor theory than his original brief exposition of 1801. The third part provided a very detailed extension of these earlier theories: the problem of a physical explanation (as opposed to a philosophical or religious one) for the emergence of the higher mental faculties. Lamarck's explanation linked mind's progressive development to an increasing structural complexity of the nervous system— a necessary and crucial argument for including man among the products of evolutionary processes.  For Lamarck, the development of the nervous system was one of the most important events in the evolutionary process, as it was at that point, according to his theory, that animals began to conceive ideas and control their movements, thus enabling them voluntarily to form the habits (such as stretching the neck up to feed on high branches) that would eventually result in the development of new organs.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) No. 216. 

Hook & Norman, The Haskell F. Norman Library of Science & Medicine (1991) No. 1267.

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William Charles Wells Publishes the First Recognizable Statement of the Theory of Natural Selection 1818

In 1818, a year after the death of Scottish American physician and scientist, William Charles Wells, his Two Essays: One upon Single Vision with Two Eyes; the Other on Dew. A Letter to the Right Hon. Lloyd, Lord Kenyon and an Account of a Female of the White Race of Mankind, Part of whose Skin Resembles that of a Negro was published in London. Wells’s “Account of a female of the white race. . . ." was read before the Royal Society in 1813, but first appeared in print posthumously. It contained the first recognizable statement of the principle of natural selection. In his study of an albino negro woman, Wells assumed a biological evolution of the human species, drawing an analogy between man’s selective breeding of domestic animal varieties and nature’s selection of varieties of men best suited to various climates.  He wrote,

"[What was done for animals artificially] seems to be done with equal efficiency, though more slowly, by nature, in the formation of varieties of mankind, fitted for the country which they inhabit. Of the accidental varieties of man, which would occur among the first scattered inhabitants, some one would be better fitted than the others to bear the diseases of the country. This race would multiply while the others would decrease, and as the darkest would be the best fitted for the [African] climate, at length [they would] become the most prevalent, if not the only race."

Neither Charles Darwin nor Alfred Russel Wallace was familiar with Wells’s paper when they formulated the theory of natural selection, but after Darwin published the Origin in 1859 Wells' paper was called to his attention, and Darwin paid tribute to Wells’s pioneering statement in the historical introduction to the third edition of the Origin. Wells’s paper was contained in the first collected edition of his essays on binocular vision and on dew formation, both of which represented advances in the knowledge of these subjects.

Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 2200.

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William Lawrence Describes the Natural History of Man 1819

William Lawrence

The Court of Chancery during the reign of George I by Benjamin Ferrers

Surgeon and scientist William Lawrence published Lectures on Physiology, Zoology and the Natural History of Man in 1819. This work set out Lawrence’s radical—and to our eyes, remarkably advanced—ideas concerning evolution and heredity. Arguing that theology and metaphysics had no place in science, Lawrence relied instead on empirical evidence in his examination of variation in animals and man, and the dissemination of variation through inheritance. On the question of cause, Lawrence disagreed with those who ascribed variation to external factors such as climate, and rejected the Lamarckian notion of the inheritance of acquired characteristics. His understanding of the mechanics of heredity was well ahead of his time: he stated that “offspring inherit only [their parents’] connate qualities and not any of the acquired qualities,” and that the “signal diversities which constitute differences of race in animals . . . can only be explained by two principles . . . namely, the occasional production of an offspring with different characters from those of the parents, as a native or congenital variety; and the propagation of such varieties by generation” (p. 510).

While Lawrence did not grasp the role that natural selection plays in the origination of new species, he recognized that “selections and exclusions,” including geographical separation, were the means of change and adaptation in all animals, including humans. He noted that men as well as animals can be improved by selective breeding, and pointed out that sexual selection was responsible for enhancing the beauty of the aristocracy: “The great and noble have generally had it more in their power than others to select the beauty of nations in marriage; and thus . . . they have distinguished their order, as much by elegant proportions of person, as by its prerogatives in society” (p. 454). He investigated the human races in detail, and insisted that the proper approach to this study was a zoological one, since the question of variation in mankind “cannot be settled from the Jewish Scriptures; nor from other historical records” (p. 243).

The Natural History of Man came under fire from conservatives and clergy for its materialist approach to human life, and Lawrence was accused of atheism for having dared to challenge the relevance of Scripture to science. In 1822 the Court of Chancery ruled the Natural History blasphemous, thus revoking the work’s copyright. Lawrence was forced to withdraw the book, a fact reflected in the comparative rarity of the first edition. However, the book’s notoriety was such that several publishers issued their own pirated editions, keeping the work in print for several decades. A list of the London editions of Lawrence’s work, taken from OCLC, follows:

1819 J. Callow (authorized)

1819 s.n. (?)

1822 W. Benbow

1822 J. Smith

1822 Kaygill & Price (unillustrated)

1823 R. Carlile

1823 J. Smith

1834 J. T. Cox

1838 J. Taylor

1840 J. Taylor

1844 J. Taylor

1848 H. G. Bohn

1866 Bell & Daldy

Editions were also published in Edinburgh and America. Darwin owned one of the unauthorized editions listed above, the one issued by “the notorious shoemaker-turned-publisher William Benbow, who financed his flaming politics by selling pornographic prints” (Desmond & Moore, Darwin, p. 253). Darwin was obviously impressed with Lawrence’s work, citing it five times in The Descent of Man (1871). 

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The First Ecological Experiment; Source of Darwin's Principle of Divergence 1826

In 1826 horticulturalist George Sinclair, head gardener for the Duke of Bedford at Woburn Abbey, published the third edition of Hortus gramineus woburnensis; Or, an account of the results of experiments on the produce and nutritive qualities of different grasses and other plants used as the food of the more valuable domestic animals. . . . This work, published in London, contained 60 lithographed plates by Charles Joseph Hullmandel and was available with plates either black & white or hand-colored.  

In his experiment Sinclair compared the performance of different species and mixtures of grasses and herbs growing on different types of soil. Sinclair first mentioned the experiment in the first edition of Hortus gramineus woburnensis (1816). However, the results, which were so significant for Darwin’s theory of evolution by natural selection, were not published until the third edition of 1826. They showed that a greater diversity of grasses planted resulted in greater production of plant matter.  

Sinclair’s experiment provided the foundation of Darwin’s “principle of divergence,” a building block of his theory of evolution by natural selection, by illuminating a central question in ecology and evolution: How is diversity of species in the natural world maintained? Darwin referred to Sinclair’s experiment in On the Origin of Species (1859), but did not mention Sinclair’s name or cite his work, and it was only recently discovered that Sinclair’s Hortus gramineus worburnensis was the source of Darwin’s knowledge (see Andy Hector and Rowan Hooper, “Darwin and the first ecological experiment,” Science Magazine 295, no. 5555 [25 Jan. 2002]: 639-40).

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Identified on his Calling Cards as "The Discoverer of Natural Selection" 1831

In 1831 Scottish landowner and fruit farmer Patrick Matthew published from Edinburgh On Naval Timber and Arboriculture with Critical Notes on Authors Who Have Recently Treated the Subject of Planting. From statements made in this book Matthew is considered the first to clearly and completely anticipate the Darwin-Wallace theory of evolution by natural selection. Matthew used the expression “natural process of selection” and was acknowledged by Darwin in the third and subsequent editions of his Origin: “Mr. Patrick Matthew . . . gives precisely the same view on the origin of species as that . . . propounded by Mr. Wallace and myself.” Matthew’s anticipation of Darwin is found in the appendix to his little-read book on arboriculture; however, he gives no scientific evidence for his view. Even so, Matthew had cards printed up identifying himself as “the discoverer of natural selection.”

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 216.3.

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Foundation of the Cell Theory 1838

In 1838 German botanist Matthias Jakob Schleiden published "Beiträge zur Phytogenesis" in Müller's Archiv für Anatomie, Physiologie und wissenschaftliche Medicin (1838) 137-76, which was issued from Berlin. Schleiden’s work represented key step in the evolution of the search for the elementary unit common to the animal and plant kingdoms. Acting upon his belief that plants represented aggregates of individual cells, Schleiden published a study of the vegetable cell, beginning with the cell nucleus (discovered by botanist Robert Brown in 1832), and proceeding to a discussion of its role in the formation of cells. Schleiden’s “watch-glass” theory of cell formation was wrong—he believed that they crystallized in a formative liquid containing sugar, gum and mucous—but it focused attention on the problem of cell reproduction and provided a testable hypothesis. More significant was Schleiden’s insistence that plants consisted entirely of cells and cell products. Tradition has it that the cell-theory was conceived in a conversation between Schleiden and Schwann on phytogenesis. In 1839 Theodor Schwann published from Berlin Mikroskopische Untersuchungen, in which he demonstrated that Schleiden’s conclusion also applies to animals, thus establishing the cell as the elementary unit common to both plant and animal kingdoms.

Norman (ed) Morton's Medical Bibliography (1991) no. 112. Carter & Muir, Printing and the Mind of Man (1967) no. 307a.  Hook & Norman, The Haskell F. Norman Library of Science & Medicine (1991) no. 1907. Hughes, History of Cytology, 37ff.

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Steenstrup's Theory of Alternation of Generations or Metagenesis 1842

A portrait of Japetus Steenstrup 

In 1842 Danish zoologist and biologist in København Johannes Japetus Smith Steenstrup published Om Fortplantning og Udvikling gjennem vexlende Generations-raekker. In this work Steenstrup expounded the the theory of the alternation of generations, or alternation of phases or metagenesis. He showed that certain animals produce offspring which never resemble them but which, on the other hand, bring forth progeny which return in form and nature to their grandparents or more distant ancestors. 

J. Norman (ed) Morton's Medical Bibliography (1991) no. 217.

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The First Full-Length Exposition in English of an Evolutionary Theory of Biology is Published Anonymously 1844

In 1844 the anonymous author of Vestiges of the Natural History of Creation provided the first full-length exposition in English of an evolutionary theory of biology; it was the most sensational book on its subject to appear prior to Darwin’s On the Origin of Species. By stating the case for evolution in a manner comprehensible to the general public, if not acceptable to the scientific community, the book absorbed the worst of the general public opposition to the concept, thus helping to prepare the way for the Origin. Vestiges was one of the greatest scientific best-sellers of the Victorian age, going through at least twelve large editions in England, numerous American editions, and several foreign-language translations. Remarkably, the identity of its author, the Scottish publisher, writer, and geologist Robert Chambers, was kept secret throughout his lifetime, and only divulged after Chambers's death in 1871. Secrecy of authorship undoubtedly contributed to the sensationalism surrounding the work.

Vestiges also played a significant role in transmitting some of Charles Babbage’s pioneering ideas on programming and coding mathematical operations. Babbage, in his Ninth Bridgewater Treatise (1837), had likened the Creator to a kind of master computer programmer (although this term did not exist in Babbage’s time), and the operations of the universe to a gigantic program whose myriad changes over time had been set up from the very beginning. Babbage’s ideas were alien to most of the Victorian public, since virtually no one in Babbage’s time was accustomed to thinking in terms of a programmed series of mathematical operations. However, Babbage’s ideas about natural laws resembling “programs” received a much wider audience through the Vestiges. The thirteenth chapter of Vestiges, entitled “Hypothesis of the development of the vegetable and animal kingdoms,” is devoted to the question of how the earth’s most complex organisms could have evolved from its simplest, given the observed fact that “like begets like.” On pages 206-211 of the 1844 edition, Chambers showed that evolutionary change occurring over long periods of time could be seen as similar to the workings of Babbage’s Difference Engine, programmed from the beginning of its operation to produce in sequence several different series of numbers according to a succession of mathematical rules. This is one of the very earliest references to computing within the context of biology.

"During the whole time which we call the historical era, the limits of species have been, to ordinary observation, rigidly adhered to. But the historical era is, as we know, only a small portion of the entire age of our globe. We do not know what may have happened during the ages which preceded its commencement, as we do not know what may happen in ages yet in the distant future. All, therefore, that we can properly infer from the apparently inevitable production of like by like is, that such is the ordinary procedure of nature in the time immediately passing before our eyes. Mr. Babbage’s illustration powerfully suggests that this ordinary procedure may be subordinate to a higher law which only permits it for a time, and in proper seasons interrupts and changes it" (Chambers 1844, 211).

Hook & Norman, Origins of Cyberspace (2002) no. 55.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 218.

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1850 – 1875

Darwin & Wallace Issue the First Printed Exposition of the Theory of Evolution by Natural Selection August 20, 1858

Charles Darwin

Alfred Russel Wallace

A diagram of natural selection

Living barnacles

On August 20, 1858 Charles Darwin and Alfred Russel Wallace published "On the tendency of species to form varieties; and on the perpetuation of varieties and species by natural selection" in the Journal of the Proceedings of the Linnean Society. This was the first printed formal exposition of the theory of evolution by natural selection. Darwin had developed the essential elements of his theory by 1838 and set them on paper in 1844; however, he chose to keep his work on evolution unpublished for the time, instead concentrating his energies first on the preparation for publication of his geological work on the Beagle voyage , and then on an exhaustive eight-year study of the barnacle genus Cirripedia.

In 1856, at the urging of Charles Lyell, Darwin began writing a vast encyclopedic work on natural selection; however, it is possible that the extremely cautious Darwin might never have published his evolutionary theories during his lifetime had not Alfred Russel Wallace, a naturalist born in New Zealand, independently discovered the theory of natural selection. Wallace conceived the theory of natural selection during an attack of malarial fever in Ternate in the Mollucas, Indonesia (Febuary, 1858) and sent a manuscript summary to Darwin, who feared that his discovery would be pre-empted.

In the interest of justice Joseph Dalton Hooker and Charles Lyell suggested joint publication of Wallace's paper prefaced by a section of a manuscript of a work on species written by Darwin in 1844, when it was read by Hooker, plus an abstract of a letter by Darwin to Asa Gray, dated 1857, to show that Darwin's views on the subject had not changed between 1844 and 1857. The papers by Darwin and Wallace were read by Lyell before the Linnean Society on July 1, 1858 and published on August 20.

"There are five different forms in which the original edition can be found, but they are all from the same setting of type. Four of these are the results of the publishing customs of the Linnean Society of London and the fifth is the authors' offprints. The Journal came out in parts and was available to Fellows of the Society with Zoology and Botany together in each part, Zoology alone, or Botany alone. Later it appeared in volume form made up from reserved stock of the parts with new title pages, dated in the year of completion of the volume, and indexes. This again was available complete or as Zoology or Botany alone. The Zoology was signed with numbers and the Botany with letters. The Darwin-Wallace paper occurs in the complete part in blue wrappers, or in the Zoology part in pink wrappers; the Botany parts were in green. The Linnean Society has all the forms in its reference files, although it does not hold the offprint.

"The authors' offprints were issued in buff printed wrappers with the original pagination retained. They have 'From the Journal of the Proceedings of the Linnean Society for August 1858.' on page [45]. They were printed from the standing type but, presumably, after the copies of the number had been run off. The only copies which I have seen have been inscribed personally by Darwin, but Life and letters, Vol. II, p. 138, notes that Darwin had sent eight copies to Wallace, still in the far-east, and had kept others for him" (http://darwin-online.org.uk/EditorialIntroductions/Freeman_TendencyofVarieties.html, accessed 11-25-2014).

On November 24, 2014, as a result of an international collaboration with the Darwin Manuscript Project based at the American Museum of Natural History, New York, Cambridge University's Cambridge Digital Library published online more than 12,000 hi-resolution images of manuscripts by Darwin, with transcriptions and detailed notes. These papers chart the evolution of Darwin’s intellectual journey, from early theoretical reflections while on board HMS Beagle, to the publication of On the Origin of Species 155 years earlier, on November 24, 1859. The papers document the origins of Darwin’s theory of evolution – including the pages where he first coined and committed to paper the term "natural selection." 

J. Norman (ed.), Morton's Medical Bibliography[1991] no. 119.  Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 591.

(This entry was last updated on 11-25-2014)

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Charles Darwin's "On the Origin of Species by Means of Natural Selection" November 24, 1859

The title page of On the Origin of Species by Charles Darwin

Charles Darwin

On November 24, 1859 Charles Darwin issued through the London publisher, John Murray, his book entitled On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. From its original publication, through the early years of the twenty-first century, this work remained one of the most widely appreciated, or disputed, classics in the history of science.

The idea of species evolution can be traced as far back as the ancient Greek belief in the "great chain of being". Darwin's great achievement was to make this centuries-old "underground" concept acceptable to the scientific community and educated readers by cogently arguing for the existence of a viable mechanism— natural selection— by which new species evolve over vast periods of time.  Darwin's work contained only a single illustration- a branching evolutionary tree, the first known presketch of which appears in Darwin's notebooks in 1839.

Though Darwin stated his case for evolution by natural selection persuasively and in the most diplomatic of tones, the work evoked a storm of controversy, causing Darwin to revise it through six editions during his lifetime. Since its publication the scientific evidence supporting evolution by natural selection has reached a massive—even overwhelming— preponderance, yet the controversy over evolution has never abated.

There is only one issue of the first edition of On the Origin of Species, and although three cloth binding and advertisement variants have been identified, no priority has been established. 1250 copies were printed, of which about 1,170 were available for sale; the remainder consisted of 12 author's copies, 41 review copies, 5 copyright copies, and "Darwin required ninety copies to be sent as presentations to friends, family, and scientists [Correspondence, 8: 554-6]" (Kohler & Kohler, see below, 333). Following Darwin's instructions, these presentation copies were sent out by the publisher, usually inscribed "From the Author" by the publisher's clerk.  The book was offered to booksellers two days earlier on November 22, and oversubscribed by 250 copies causing John Murray to propose a new edition immediately.

On the Origin of Species is undoubtedly the most famous book in the history of the life sciences, and one of the world's most famous books on any subject. It is also perhaps the most published book in the history of science and the most translated book originally published in English. As a result of this fame, a great deal of historical research has been concentrated on this work. Early in 2009 Cambridge University Press published The Cambridge Companion to the "Origin of Species," edited by Michael Ruse and Robert J. Richards. Most pertinent to book collecting and book history is the excellent chapter on "The Origin of Species as a Book" by Michèle Kohler and Chris Kohler.

Among the many very informative details the Kohlers include, of particular interest to the history of collecting rare books in the history of science is their observation that the first edition may have first been offered as collectable "rare book" by Bernard Quaritch Ltd in 1903 for £2-10-0, "a premium on the price of a new copy, not a discount." (p. 345). They also observe that the price of the first edition remained essentially static in the rare book trade until it began to rise in the 1920s, after which it very gradually moved upward. When I first opened my shop at the beginning of 1971 the price of a fine copy of the first edition in the original cloth was $1000. At this time the work was relatively common, and there were usually several copies of the first edition on the market at one time. In 2014 a fine copy of the first edition was worth approximately $150,000. This represented an appreciation rate far higher than most other science classics.

♦ In 2014 darwin-onlin.org.uk made available Darwin's complete publications, his private papers and manuscripts, and so-called "supplementary works." When I visited the site its index page advertised,"over 400 million hits since 2006."  Another site, the Darwin Manuscripts Project at the American Museum of Natural History in New York, provided DARBASE, a union catalogue of Darwin manuscripts in institutions and private collections.  An intriguing brief manuscript in Darwin's hand reproduced there showed that Darwin apparently considered writing a chapter "On the Geological Antiquity of Man And on the Descent (origin) of Species by variation." This was a topic of interest to me in 2014 as we prepared our book on The Discovery of Human Origins. My research till 2014 indicated that Darwin avoided publishing on the topic of human origins, leaving it to Huxley, Lyell and others. 

According to their children's accounts, Charles and Emma Darwin and their children had a happy family life, and Darwin was known not to be protective of his manuscripts after they were published. As a result, the Darwin children were allowed to doodle on the versos of some of his manuscripts, including the original manuscript of On the Origin of Species. In February 2014 reproductions of some of the more elaborate of those doodles were reproduced at this link.

Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) No. 593.

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Henry Walter Bates Describes "Batesian Mimicry" 1862

In "Contributions to an Insect Fauna of the Amazon Valley: Lepidoptera: Heliconidae," Transactions of the Linnean Society of London 25 (1862) 495-566 English naturalist and explorer Henry Walter Bates first stated and solved the problem of mimicry, known today as "Batesian mimicry." In this adaptation for survival the palatable species mimics a unpalatable model in a form of protective coloration that evolved through natural selection.

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Charles Lyell Issues "The Geological Evidences of the Antiquity of Man" January 1863

English geologist Charles Lyell published in London The Geological Evidences of the Antiquity of Man with Remarks on Theories of the Origin of Species by Variation. The publisher's advertisements inserted at the back of the first edition were dated January 1863.

Though he had been slow to accept evolutionary theory, and long remained skeptical about the question of human origins, Lyell became convinced in the late 1850s of the antiquity of man by the increasing number of discoveries of man-made flint tools found alongside the fossil remains of extinct animals. After collecting and analyzing the evidence for several years, Lyell made the case for human antiquity in his Geological Evidences of the Antiquity of Man, a work in which he also announced his acceptance of Darwin’s theory of evolution as “the best explanation yet offered of the connection between man and those animals which have flourished successively on the earth.” Lyell’s decision to include in this work the argument for evolution by natural selection, as well as information concerning the relationship between man and the primates, raised the level of scientific controversy concerning the whole issue of human antiquity, which had previously been developing mainly on the basis of geological, paleontological, and archaeological evidence without direct reference to the larger issues of evolution. The book also took the topics out of the confines of scientific journals and brought them to a much larger audience through Lyell’s superb powers of exposition.

Through the many reviews of this book published in popular magazines and newspapers, the public was treated to even more information on the topic. It is probably because of the success of Lyell’s work, along with those of Huxley, John Lubbock, that Darwin chose to bypass the subject of human antiquity in the Descent of Man (1871), writing:

“The high antiquity of man has recently been demonstrated by the labours of a host of eminent men, beginning with M. Boucher de Perthes; and this is the indispensable basis for understanding his origin. I shall, therefore, take this conclusion for granted, and may refer my readers to the admirable treatises of Sir Charles Lyell, Sir John Lubbock, and others.”

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Thomas Huxley Issues "Man's Place in Nature" February 1863

In 1863 English biologist, paleontologist  and evolutionist Thomas Henry Huxley published Evidence as to Man’s Place in Nature in London. The first issue of the edition contained publisher’s advertisements dated February 1863.

On February 18, 1863, Darwin wrote to Huxley, “Hurrah the monkey book has come!” (quoted in Desmond, Huxley, The Devils’ Disciple [1994] 312). Man’s Place in Nature was the first book to directly address the evidence for human evolution from primates. Together with Lyell’s Geological Evidences of the Antiquity of Man, which was published a few weeks earlier, Man’s Place in Nature was also the first book to consider the role of prehistoric human remains as evidence for human evolution. While Lyell approached the topics primarily from the geological point of view, Huxley approached the subjects mainly from the point of view of comparative anatomy.

Concerning Huxley’s work, Darwin wrote in The Descent of Man: “Prof. Huxley, in the opinion of most competent judges, has conclusively shewn that in every visible character man differs less from the higher apes, than these do from the lower members of the same order of primates.” (p.3).

Sometimes called “Darwin’s bulldog”, Huxley enjoyed involvement in scientific controversy that more cautious scientists such as Darwin preferred to avoid. Like Lyell’s Antiquity of Man, Huxley’s book took topics which had previously been confined mostly to scientific journals and brought them to the attention of the reading public. Because Huxley’s and Lyell’s books were often reviewed together in popular magazines, this tended to generate even further controversy.

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Hemoglobin is Named 1864

In 1864 German physiologist and chemist in Tübingen Felix Hoppe-Seyler named the protein crystallized from blood haematoglobulin or haemoglobin (hemoglobin).

Hoppe-Seyler, “Ueber die chemischen und optischen Eigenschaftern des Blutsfarbstoffs,Arch. f. path. Anat. u. Physiol. (Virchow’s Archiv) 29 (1864) 233-35.

Judson, Eighth Day of Creation, 490.

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John Lubbock's "Pre-Historic Times" is Published 1865

In 1864 English banker, politician, naturalist and archaeologist John Lubbock publised Pre-Historic Times, as Illustrated by Ancient Remains, and the Manners and Customs of Modern Savages. After delivering a series of lectures at the Royal Institution on “The Antiquity of Man” in the summer of 1864, Lubbock organized his material into a book that addressed not only the topic of human antiquity but the larger issues of the lives and cultures of people in the Stone Age. A masterpiece of scientific exposition, Pre-historic Times became his best-known work, in which he coined the terms “Paleolithic” and “Neolithic” to distinguish between the earlier and later Stone Age periods. He wrote:

"From the careful study of the remains which have come down to us, it would appear that Pre-historical Archaeology may be divided into four great epochs.

"First, that of the Drift; when man shared the possession of Europe with the Mammoth, the Cave bear, the Wooly-haired rhinoceros, and other extinct animals. This we may call the ‘Paleolithic’ period.

"Secondly, The later or polished Stone age; a period characterized by beautiful weapons and instruments made of flint and other kinds of stone, in which, however we find no trace of the knowledge of any metal, excepting gold, which seems to have been sometimes used for ornaments. This we may call the ‘Neolithic ‘period.

"Thirdly The Bronze age, in which bronze was used for arms and cutting instruments of all kinds.

"Fourthly, The Iron age, in which that metal had superseded bronze for arms, axes, knives, etc; bronze, however still being in common use for ornaments, and frequently also for the handles of swords and other othersm, but never for the blades. Stone weapons, however, of many kinds were still in use during the age of Bronze, and even during that of Iron. So that the mere presence of a few stone implements in not in itself sufficient evidence, that any given ‘find’ belongs to the Stone age" (p. 3).

In contrast to some of the other early researchers in these fields who focused on the geology of the prehistoric sites, in finding the artifacts, and in studying the artifacts themselves, Lubbock studied the artifacts of Stone Age cultures in order shed light on the function of ancient implements as part of an overall attempt to reconstruct what life might have been like in the Stone Age. In order to gain further insight into life in prehistoric times he also studied the lives of a wide variety of non-western peoples, some of whose lives and cultures appeared to him to provide strong analogs to life during the Stone Age.

His book incorporates five earlier published papers, all of which appeared in The Natural History Review: “On the Kjökkenmöddings: Recent geological-archaeological researches in Denmark” (October 1861); “On the evidence of the antiquity of man, afforded by the physical structures of the Somme Valley” (January 1862); “On the ancient lake habitations of Switzerland” (July 1862); “North American archaeology” (January 1863); and “Cave-men” (July 1864). To these previously published papers Lubbock added three chapters devoted to the customs and beliefs of primitive races. In a final chapter he summed up his conclusions on the origins of man and of civilization.

Pre-Historic Times may be the most influential work on archaeology of the nineteenth century. It remained a standard work for over 50 years, with the seventh and final edition appearing just after Lubbock’s death in 1913.

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Mendel's Discovery of the Mendelian Ratios 1866

Augustinian Abbey of St. Thomas in Brno

Gregor Mendel

In 1866 Austrian scientist and friar of the Augustinian Abbey of St Thomas in Brno (now Czech Republic) Gregor Mendel published "Versuche ber Pflanzen-Hybriden," Verhandlungen des naturforscheden Vereines in Brünn 4 1865, [3]-47 (1866). Reporting Mendel's eight years of experimental work on artificial plant hybridization, this paper recorded the discovery of the Mendelian ratios, the most significant single achievement in the history of genetics. Working with clearly identifiable traits in the pea plant, (seed color and shape, stem length, position of the flowers) Gregor Mendel discovered a generalized set of rules concerning heredity. He postulated that there are discrete units of heredity (what we call genes) that are transmitted from generation to generation even though some of these are not expressed as an observable trait in every generation. He discovered dominant and recessive traits— what we call segregation and what we call alleles

"In comparison with his predecessors, Mendel was original in his approach, and in his interpretation of experimental results. He reduced the hitherto extremely complex problem of crossing and heredity to an elementary level appropriate to exact analysis. He left nothing to chance. . . . Altogether new was his use of large populations of experimental plants, which allowed him to express his experimental results in numbers and subject them to mathematical treatment. By the statistical analysis of large numbers Mendel succeeded in extracting "laws" from seemingly random phenomena. This method, quite common today, was then entirely novel. Mendel, inspired by physical sciences, was the first to apply it to the solution of a basic biological problem and to explain the significance of a numerical ratio" (D.S.B.).

Published in the obscure journal of a provincial natural science society, Mendel's work went virtually unnoticed, and remained so until 1900 when the Mendelian ratios were independently rediscovered by Hugo de Vries, Carl Correns and Erich von Tschermak.

♦ In February 2012 Mendel's original manuscript of his famous paper was returned to the Mendel Museum at the Augustinian Abbey of St. Thomas in Brno. The monastery had been closed down in 1953 at which time the manuscript was hidden by the Augustinian monks. In the 1980s the manuscript was sent for safekeeping to Vienna, and then to Germany.  After much negotiation between the Czech Republic and Germany the manuscript was returned to the place of its origin.

Dibner, Heralds of Science no. 35. Norman, Morton's Medical Bibliography (1991) no. 222. Horblit, One Hundred Books Famous in Science no. 73a.  Carter & Muir, Printing and the Mind of Man (1967) no. 356.  Hook & Norman, The Haskell F. Norman Library of Science and Medicine (1991) no. 1490.

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Alfred R. Wallace's "The Malay Archipelago" Describes the Wallace Line 1869

In 1869 British naturalist, explorer, and evolutionist Alfred Russel Wallace published The Malay Archipelago.

"The preface summarizes Wallace’s travels, the thousands of specimens he collected, and some of the results from their analysis after his return to England. The first chapter describes the physical geography and geology of the islands with particular attention to the role of volcanoes and earthquakes. It also discusses the overall pattern of the flora and fauna including the fact that the islands can be divided, by what would eventually become known as the Wallace line, into 2 parts, those whose animals are more closely related to those of Asia and those whose fauna is closer to that of Australia. The following chapters then describe in detail the places Wallace visited. Wallace includes numerous observations on the people, their languages, ways of living, and social organization, as well as on the plants and animals found in each location. He talks about the biogeographic patterns he observes and their implications for natural history, both in terms of biology (evolution ) and the geologic history of the region. He also narrates some of his personal experiences during his travels. The final chapter is an overview of the ethnic, linguistic, and cultural divisions among the people who live in the region and speculation about what such divisions might indicate about their history. The book is dedicated to Charles Darwin" (Wikipedia article on The Malay Archipelago, accessed 05-08-2009).

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Johannes Friedrich Miescher Discovers DNA 1869 – 1871

Felix Hoppe Seyler

University of Tübingen

Friedrich Miescher

In 1869, while working at Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany, Swiss physician and biologist Johannes Friedrich Miescher  isolated a new class of compounds rich in organic phosphorous from the nuclei of white blood cells. These he called nuclein (nuclear protein). In 1871 Miescher published this discovery in "Ueber die chemische Zusammensetzung der Eiterzellen,"  Hoppe-Seyler, Felix, ed., Med.-chem. Untersuchungen , IV (1866-71) 441-60. Miescher concluded correctly that these "nucleins," were as important a center of metabolic activity as the proteins.

Miescher’s “nuclein” was later demonstrated to be the hereditary genetic material (DNA). He also was the first to suggest the existence of a genetic code.

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Darwin Predicts that Human Origins Will be Found in Africa 1871

Charles Darwin published a 2-volume work entitled The Descent of Man, and Selection in Relation to Sex. Twelve years after the publication of On the Origin of Species, Darwin made good his promise to “throw light on the origin of man and his history” by publishing The Descent of Man in which he compared man’s physical and psychological traits to similar ones in apes and other animals, and showed how even man’s mind and moral sense could have evolved through processes of natural selection.

In discussing man’s ancestry, Darwin did not claim that man was directly descended from apes as we know them today, but stated that the extinct ancestors of Homo sapiens would have to be classed among the primates. This statement was widely misinterpreted by the popular press, and caused a furor second only to that raised by the Origin. Darwin also added an essay on sexual selection, i.e. the preferential chances of mating that some individuals of one sex have over their rivals because of special characteristics, leading to the accentuation and transmission of those characteristics.

Darwin originated of the single-origin hypothesis in paleoanthropology.

"In paleoanthropology, the recent African origin of modern humans is the mainstream model describing the origin and early dispersal of anatomically modern humans. The theory is called the (Recent) Out-of-Africa model in the popular press, and academically the recent single-origin hypothesis (RSOH), Replacement Hypothesis, and Recent African Origin (RAO) model. The hypothesis that humans have a single origin (monogenesis) was published in Charles Darwin's Descent of Man (1871). The concept was speculative until the 1980s, when it was corroborated by a study of present-day mitochondrial DNA, combined with evidence based on physical anthropology of archaic specimens" (Wikipedia article on Recent African origin of modern humans, accessed 05-15-2010).

Darwin wrote in a section of The Descent of Man entitled "On the Birthplace and Antiquity of Man":

"In each great region of the world the living mammals are closely related to the extinct species of the same region. It is, therefore, probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man's nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere. But it is useless to speculate on this subject, for an ape nearly as large as a man, namely the Dryopithecus of Lartet, which was closely allied to the anthropomorphous Hylobates, existed in Europe during the Upper Miocene period; and since so remote a period the earth has certainly undergone many great revolutions, and there has been ample time for migration on the largest scale."

In spite of Darwin's suggestion, few if any 19th century researchers on human origins searched in Africa for evidence. It was not until Raymond Dart's highly controversial discovery of the first African hominin (hominid), Australopithecus africanus, in 1925 that serious attention began to paid to the African origins of mankind.

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Darwin Founds Ethology, Studies the Conveyance of Information, and Contributes to Psychology 1872

In 1872 Charles Darwin issued The Expression of the Emotions in Man and Animals through his publisher, John Murray. This book, which contained numerous wood-engraved text illustrations, was also illustrated with seven heliotype plates of photographs by pioneering art photogapher Oscar Gustave Rejlander, and was the only book by Darwin illustrated with photographs.

“With this book Darwin founded the study of ethology (animal behavior) and conveyance of information (communication theory) and made a major contribution to psychology” (DSB). Written as a rebuttal to the idea that the facial muscles of expression in humans were a special endowment, the work contained studies of facial and other types of expression (sounds, erection of hair, etc.) in man and mammals, and their correlation with various emotions such as grief, love, anger, fear and shame. The results of Darwin’s investigations showed that in many cases expression is not learned but innate, and enabled Darwin to formulate three principles governing the expression of emotions—relief of sensation or desire, antithesis, and reflex action.

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1875 – 1900

The First Comprehensive Global Study of Zoogeography, Including the first Global Biodiversity Map 1876 – December 2012

In 1876 British naturalist, explorer, and evolutionist Alfred Russel Wallace published The Geographical Distribution of Animals through Macmillan publishers in London. Wallace studied the fauna of the Malay archipelago and was struck both with its resemblances to and differences from that of South America, where he did extensive research in the Amazon rainforest. His research expanded into this extensive 2-volume work—the first comprehensive world-wide study of zoogeography, illustrated with numerous thematic maps, including the first global biodiversity map, a map of zoogeographic regions of the world.

Wallace's biodiversity map was not formally updated until December 2012: Holt, Lessard et al "An Update of Wallace's Zoogeographic Regions of the World," Science DOI: 10.1126/science.1228282.

"Wallace recognized that the world is divided into so-called biogeographic regions, which today we know reflect the breakup of the continental plates roughly 200 million years ago. As the former mega-continent of Pangaea split apart, the evolutionary branches of those species cleaved off from one another. Millenniums of isolation following this divergence led to Australia’s wildly unique marsupials, for example, and Madagascar’s beloved lemurs. Wallace recognized these differences and produced a map identifying six major global biodiversity regions. Other maps have been produced since, but for this new effort, the researchers decided to take into account not only the current distribution of vertebrates, but also how they relate genetically.  

“ 'Genetic sequencing allowed us to do things that weren’t possible before,' Dr. Lessard said. 'Looking at these evolutionary links allows us to know which parts of the world are more closely related to other parts of the world.' With a team of 14 international colleagues, Dr. Lessard helped compile and analyze the phylogenetic relationships of 21,037 species of amphibians, birds and mammals. Whereas Wallace highlighted six major animal realms, the team identified 11, and within those realms made 20 regional distinctions. The results were published online today by the journal Science.  

"A few surprises turned up in their analyses. For example, new realms in Central America, East Asia and Oceana emerged. The northernmost stretches of the Canadian tundra make more sense grouped with the Palearctic realm, which encompasses Siberia, Europe and North Asia, than with North America’s Nearctic realm. 'Apparently, plant people kind of informally recognized that grouping in the past,' Dr. Lessard said. 'But for animals, I’ve never seen a map of biogeographic regions showing that connection.'

"The dividing lines will soon be uploaded and freely accessible on Google Earth, and the researchers hope to add information detailing which big animal families are found in each realm and region for curious citizens or researchers to explore" (http://green.blogs.nytimes.com/2012/12/21/a-biodiversity-map-version-2-0/?src=rechp, accessed 12-23-2012).

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Pioneering Study of Community Ecology 1877

In 1877 German zoologist and environmentalist Karl August Möbius published from Berlin Die Auster und de Austernwirschaft.

In this study of oyster culture precipitated by the impoverishment of natural oyster beds, Mobius provided the earliest description of a marine animal community maintained in a state of equilibrium by limitations of resources.  He was the

"first to describe in detail the interactions between the different organisms in the ecosystem of the oyster bank, coining the term 'biocenose'. This remains a key term in synecology (community ecology)" (Wikipedia article on Karl Möbius, accessed 01-13-2009).

J. Norman (ed.) Morton's Medical Bibliography, 5th ed. (1991) No. 145.61.

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"Mullerian Mimicry" is Described 1878

German physician and biologist Johann Friedrich Theodor Müller (better known as Fritz Müller) emigrated with his family to the German community of Blumenau, Santa Catarina, in southern Brazil. In 1878 he published "Ueber die Vortheile der Mimicry bei Schmetterlingen," Zool. Anz. 1 (1878) 54-55. In this paper Müller described what came to be known as "Müllerian mimicry." Batesian mimicry explained why an edible species would mimic an inedible one, but did not account for the superficial resemblances between two or more unpalatable species. Muller explained that a predator must learn which species are unpalatable, and the coloration of an unpalatable species serves as a warning coloration to predators. The selective advantage of Müllerian mimicry is that when two unpalatable species share similar warning colors fewer of both populations are lost because the warning colors are more quickly recognized by predators.  

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Discovery of Mitosis 1878 – 1882

In 1878 German biologist and founder of cytogenetics Walther Flemming at the University of Kiel published the results of his investigations of the process of cell division and the distribution of chromosomes to the daughter nuclei, a process he called mitosis from the Greek word for thread. His researches were first published in "Zur Kenntniss der Zelle und ihrer Theilungs-Erscheinungen," Schriften des Naturwissenschaftlichen Vereins für Schleswig-Holstein 3 (1878) 23–27. Continuing his researches, he published further results in 1882 Zellsubstanz, Kern und Zelltheilung (Cell Substance, Nucleus and Cell Division), a work which contained over 100 drawings. On the basis of his discoveries, Flemming surmised for the first time that all cell nuclei came from another predecessor nucleus; he coined the phrase omnis nucleus e nucleo, after Rudolph  Virchow's phrase omnis cellula e cellula.

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Richard Owen Calls Darwin the "Copernicus of Biology" November 5, 1882

Following the death on April 19, 1882 of Charles Darwin, English Paleontologist Richard Owen wrote to Spencer Walpole, Home Secretary in several governments and a trustee of the Natural History Museum in London, which had been built largely as a result of Owen's efforts. The purpose of the letter was to recommend that a statue of Darwin be placed in Westminster Abbey. This was the highest honor that England could bestow.

In the 1970s I acquired this letter as part of the Paul Victorius collection on Darwin and evolution. I sold it at auction in 1992 when I dispersed my Darwin's Century collection. It was described as lot 311 in the auction catalogue. I had always thought of the letter as a remarkable tribute to Darwin's achievements by his greatest opponent, and had viewed the letter as a kind of reversal of Owen's opposition to Darwin's ideas in Owen's old age. In the letter Owen acknowledges the general acceptance by scientists of Darwin's theory of natural selection and points out the progress that has occurred in science by its acceptance. He compares Darwin to Copernicus in the sense that Darwin caused caused rejection of the origin of species by "primary law' or creation, replacing it with the "secondary law" of natural selection, while Copernicus caused rejection of the geocentric theory of the solar system, replacing it by the heliocentric.

In February 2011 at the San Francisco Antiquarian Book Fair David Archibald pointed out the criticisms of Darwin's work which were cached, so-to-speak, in Owen's letter, and sent me a copy of the article by Kevin Padian "Owen's Parthian Shot," Nature, 412, July 12, 2001, 123-124. In this paper Padian pointed out various subtle criticisms of Darwin expressed in the letter, for details of which see his paper.

Where Owen expresses ambivalence seems primarily to be in the continuation of his comparison of Darwin with Copernicus. To me, just comparing the two is a reflection of Owen's appreciation of Darwin's place in history. However, Owen points out that Copernicus did not understand how the planets rotated around the sun and it took Galileo, Kepler, and Newton to answer these questions. Similarly Darwin did not understand the specific nature of the biological processes that caused natural selection to work, and Owen expresses the expectation that biology will eventually have its own Galileo, Kepler, and Newton. But, while Copernicus wrote a theoretical work, Darwin did understand the phenomenon accurately enough in terms of species populations. The hereditary mechanisms did not become understood in any detail until Watson and Crick's discovery of the "double helix," which had an impact on biology similar to Darwin's On the Origin of Species. Owen also points out that the "adoption of Darwin's hypothesis of the evolutional way of work is not general. . . ." Clearly, as Padian points out, Owen remained ambivalent about Darwin's contributions to science even as he acknowledged Darwin's place in history. 

Here is the text of Owen's letter:

"Sheen Lodge, Richmond Par, E. Sheen, S.W.

"5th November 1882

"Dear Mr. Walpole,

"In compliance with your request I have the pleasure to send the following on the subject we last discussed. Charles Darwin had peculiar claims to fitting posthumous recognition of his services to natural science. Of independent means, he devoted himself to the successful termination of his University career to the advancement of natural history. His desi re to accompany as naturalist the circumnavigatory expedition of H.M.S. Beagle under Captain Fitzroy was granted. The results to his favorite science were equal to, if they did not surpass, those of the naturalist Banks and Solander in the circumnavigatory voayge of Captain Cook. Darwin brough home rich collections in zoology, botany and palaeontology, and liberally made them over to national museums, on the condition of their being described by the competent officers.

"The results are the richly illustrated quartos, published by the Government, forming with Darwin's own Notes on the Voyage, in the well-known 8vo work, the most instructive and exemplary record of the natural-history gains of the circumnavigation. Perhaps the most important and novel researches made during the voyage are those in the nature and growth of coral-formations classified by him as 'atolls', barrier-reefs' and 'fringing-reefs', the description and explanation of which Darwin gives in his classical work on The Structure and Distribution of Coral Reefs (8vo, 1842).

"Since that date he has enriched his favorite science from time to time by monographs throwing most acceptable light on structures and vital actions of plants and animals; they are classical and perennial acquisitions to biology. The guiding principle underlying these works is that advocated in the Philosophie Zoologique of Lamarck, on the origin, viz., of species by secondary law, or evolution. But Lamarck's notion of the way of operation of that 'law', viz., by conditions affecting the exercise or disuse of parts of the body, is but partially accepted by Darwin; he substitutes another, a wider, and as he deems, a truer way of the operation of such 'secondary law', which he sums up under the term 'Natural Selection'.

"The great value of Darwin's series of works, summarizing all the evidences of embryology, physiology, paleontology then accessible, with experiments on the variation of species, is exemplified in the general acceptance by biologists of the 'secondary law by evolution' of the 'origin of species.' As a result, summaries and monographs now published in natural history are penned under the influence or in acceptance of that 'law'. In this respect Charles Darwin stands to biology in the relation in which Copernicus stood to astronomy. The rejection of the origin of species by primary law, or direct creation, is equivalent to the rejection of the fixity, centrality, and supreme magnitude of the Earth; it parallels the substitution of the heliocentric for the geocentric hypothesis. The accelerated progress of natural history under the guidance of 'evolution' resembles that of astronomy under the guidance of 'heliocentricity.'

"But the adoption of Darwin's hypothesis of the evolutional way of work is not general: Lamarck's hypothesis is found in some cases to be more applicable. And so it seems that Darwin parallels Coperncicus; save that the latter no only knew not, nor feigned to know, how the planets revolved round the sun.

"For that knowledge were requisite the subsequent labours of a Galileo, a Kepler, a Newton. Analogy raises the cheerful hope, if not condident expectation, that the science of living things will also be helped by its Galileo, its Kepler, finally its Newton; and that the way of operation of the 'secondary law originating species' will be as firmly established as the 'law of gravitation'. Meanwhile our British 'Copernicus of Biology' merits the mainfestation of gratitude and the honour which the Empire confers by a Statue in Westminster Abbey. In the British Museum sculptural memorials have been accorded to meritorious offers;—to Panizzi in relation to the Department of Printed Books; to John Edward Gray, in relation to the Department of Zoology. Whether the estimate of scientists at home or abroad of Charles Darwin's claims to posthumous honour be met, or their expectations fulfilled, by placing a statue in the Museum of Natural History may be a question for 'Administration.'

"Believe me,

   "Faithfully yours,

      "Richard Owen

"Rt. Hon. Spencer Horatio Walpole, M.P.

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Suggesting that the Nucleus Contains the Material Basis of Heredity 1883

Wilhelm Roux

A diagram of mitosis

In Über die Bedeutung der Kerntheilungsfiguren (Leipzig, 1883) German zoologist and embryologist Wilhelm Roux presented the report of his investigation why the nucleus undergoes the precise division of mitosis while the rest of the cell undergoes a rather crude division when one cell splits into two. He argued that mitosis ensures a precise halving of the nucleus, suggesting that the nucleus contains the material basis of heredity.

J. Norman (ed) Morton's Medical Bibliography (1991) no. 229.

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Decisive Proof of Chromosomal Individuality 1888

Theodor Boveri

Human chromosomes

Diagram of a centrosome

In "Zellen-Studien", Jena Z. Naturw., 22 (1888) 685-882, German biologist Theodor Boveri presented decisive proof of the maintenance of chromosomal individuality. Boveri's work with sea urchins showed that it was necessary to have all chromosomes present in order for proper embryonic development to take place. This discovery was an important part of the Boveri–Sutton chromosome theory. His other significant discovery was the centrosome, which he first described and named in this paper.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) 231.1.

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Postulating that Inheritance of Specific Traits is Controlled by Particles Called Pangenes 1889 – 1909

Hugo de Vries

Wilhelm Johannsen

In 1889 Dutch botanist and geneticist Hugo de Vries published Intracellulare Pangenesis in Jena at the press of Gustav Fischer. In this brief book he postulated that inheritance of specific discrete traits was transmitted during cell division by particles which he called pangens (English: pangenes). These he described as the smallest particle representing one hereditary characteristic. 

♦ Twenty years later Danish botanist and geneticist Wilhelm Johannsen abbreviated de Vries's term to gen to describe the fundamental physical and functional units of heredity. "Gen" in Danish and German word was translated into English as "gene."

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The Weissmann Barrier 1892

August Weismann

In 1892 German physician, zoologist and evolutionary biologist August Weismann, of Freiburg im Breisgau, published two books providing experimental evidence that acquired characteristics were not inherited. Aufsätze über Vererbung und verwandte biologische fragen and Das Keimplasma. Eine Theorie der Verebung.

According to Weissman's germ plasm theory, in a multicellular organism inheritance only takes place by means of the germ cellsgametes such as egg cells and sperm cells. Other cells of the body, somatic cells, do not function as agents of heredity. The effect is one-way: germ cells produce somatic cells and are not affected by anything the somatic cells learn, or any ability the body acquires during its life. Therefore genetic information cannot pass from soma to germ plasm and on to the next generation. This is referred to as the Weismann barrier.

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Discontinuous Variation as a Source of Evolutionary Change 1894

William Bateson

In 1894 English geneticist and Fellow of St. John's College, Cambridge, William Bateson published Materials for the Study of Variation Treated with Especial Regard to Discontinuity. This was Bateson's major work before his rediscovery of Mendel's laws of heredity. Like many other scientists during the last decades of the 19th century, Bateson rejected the orthodox Darwinian doctrine of natural selection, which taught that evolutionary change was the result of gradual and continuous accretion of seemingly insignificant variations. Bateson emphasized the importance of major or discontinuous variation as the source of evolutionary change, studying plant hybrids in an effort to determine how discontinuous variations are inherited, and summarizing his discoveries in the Materials.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 237.

Hook & Norman, The Haskell F. Norman Library of Science & Medicine (1991) no. 134. 

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Galton's "Law of Ancestral Heredity" 1897

Francis Galton

In his paper "The average contribution of each several ancestor to the total heritage of the offspring," published in the Proceedings of the Royal Society 61 (1897) 401-413, English polymath Francis Galton published his “Law of Ancestral Heredity,” based on both human and basset hound pedigrees. Galton first proposed the law in 1876, and revised it several times over the next two decades. His basic conception was that on average, parents provide offspring with half of inherited traits, grandparents contribute one quarter, great grandparents one eighth, and so on.

"The "law of ancestral heredity," as it turned out, was mistaken. Although he was interested in individual variations, Galton's mathematical methods treated them as "errors." In Gregor Mendel's more carefully conceived experiments with culinary peas, variations represented the expression of discrete alternative factors or (as we would say today) genes. Galton, in his personal correspondence with Darwin, came close to this conception, but never proceeded to a testable formulation." (http://www.genomenewsnetwork.org/resources/timeline/1876_Galton.php,)

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 239.

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1900 – 1910

Rediscovery and Confirmation of Mendel's Laws Simultaneously by Three Scientists 1900

Hugo de Vries

Carl Correns

Erich Tschermak, Elder von Seysenegg

In 1900 three scientists independently rediscovered Mendel's laws or ratios, which had remained unnoticed by the scientific community since Mendel had originally published them in 1866. Both de Vries and Correns rediscovered the laws before reading Mendel's paper.

Dutch botanist and geneticist Hugo de Vries published his account of the rediscovery in two papers: 

"Sur la loi de disjonction des hybrides," Comptes rendus Academie des Sciences (Paris) 130 (1900) 845-47.

His more detailed paper was "Das Spaltungsgestetz der Bastarde," Berichte der Deutsche Botanischen
Gesellschaft 18 (1900) 83-90.

Reading de Vries's paper in German led German botanist and geneticist Carl Correns of the University of Tübingen to write his own paper, although Correns claimed he had previously and independently arrived at the same conclusions. Correns's paper was:

"G. Mendel's Regel über das Verhalten der Nachkommenschaft der Rassenbastarde," Berichte der Deutsche Botanischen
Gesellschaft 18 (1900) 158-67.

The third scientist to "rediscover" Mendel's laws was the Austrian agronomist Erich Tschermak, Edler von Seysenegg (Erich von Tschermak).  Tschermak's first paper on the subject was:

"Über künstsliche Kreuzung bei Pisum sativum," Berichte der Deutsche Botanischen Gessellschaft 18 (1900) 232-39. 

His more detailed paper was "Über künstliche Kreuzung von Pisum sativum," Z. landwirsch. Versuchsw. in Osterreich," 3 (1900) 465-555.

Along with de Vries and Correns, Tschermak brought Mendel's work into prominence and confirmed it, though it is thought that Tschermak may not have fully understood the Mendelian laws before he read Mendel's work.

♦ Rediscovery of Mendel's laws clarified inheritance, but Mendel worked with traits of whole organisms (plants).  How characteristics are sorted and combined on a cellular level where reproduction takes place became the research projects of 20th century scientists.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) nos. 239.01, 239.1, 239.2.

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Coining the Term "Genetics" 1900 – 1902

William Bateson

Wilhelm Johannsen

A cover of The Journal of Genetics

Reginald Punnett

In 1900, very soon after Mendel's laws were rediscovered by De Vries, Correns, and Tschermak, the Royal Horticultural Society of England published an English translation of Mendel's 1866 paper as "Experiments in Plant-Hybridisation" in the Journal of the Royal Horticultural Society. Two years later, in 1902, English geneticist and Fellow of St. John's College, Cambridge, William Bateson issued Mendel's Principles of Heredity: a Defense as a small book in a small edition from Cambridge University Press, reprinting 1900 translation together with the first English translation of Mendel's second paper on Hieracium (1869). Bateson's book was the first English textbook on genetics, though the word did not yet exist; Bateson named the science "genetics: in 1905-6. 

Bateson became the chief popularizer of the ideas of Mendel following their rediscovery. In 1909 he published a much-expanded version of his 1902 textbook entitled Mendel's Principles of Heredity. This book, which underwent several printings, was the primary means by which Mendel's work became widely known to readers of English.

"Bateson first suggested using the word "genetics" (from the Greek gennō, γεννώ; "to give birth") to describe the study of inheritance and the science of variation in a personal letter to Alan Sedgwick... dated April 18, 1905. Bateson first used the term genetics publicly at the Third International Conference on Plant Hybridization in London in 1906. This was three years before Wilhelm Johannsen used the word "gene" to describe the units of hereditary information. De Vries had introduced the word "pangene" for the same concept already in 1889, and etymologically the word genetics has parallels with Darwin's concept of pangenesis.

"Bateson co-discovered genetic linkage with Reginald Punnett, and he and Punnett founded the Journal of Genetics in 1910. Bateson also coined the term "epistasis" to describe the genetic interaction of two independent traits" (Wikipedia article William Bateson, accessed 12-16-2013).

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Mutation Theory is Expounded 1901 – 1903

A painting of Hugo de Vries in his retirement, by Thérèse Schwartze


In 1886 Dutch botanist and geneticist Hugo de Vries began studying and experimenting with Oenothera lamarckiana, a species of evening primrose, after discovering a number of variants of this species growing wild in a meadow. Taking seeds from these, and growing them in his experimental gardens, he found that over the years several new forms appeared, most of which bred true.  De Vries called these new forms “mutations” and formulated a series of theses—the Laws of Mutation—in which he postulated that new elementary species arose through a process of discrete steps (“mutations” or “saltations”), and usually remained constant from their moment of origin. The results of his more than ten years of experimentation and study he published in Die Mutationstheorie. Versuche un Beobachtungen über die Entsehung von Arten im Pflanzenreich (2 vols., Leipzig, 1901-1903), in which he described in detail his work on the segregation laws, on phenomena of variation, and on plant mutations as the basis of evolution. 

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 240.   

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Proof that Different Chromosomes Perform Different Functions in Development 1902

Theodor Boveri

In his paper "Über mehrpolige Mitosen als Mittel zur Analyse des Zelkerns," Verhandlungen der physicalisch-medizinischen Gesselschaft zu Würzburg. Neu Folge 35, 67-90 (1902) 67-90, German biologist Theodor Boveri described experiments involving multipolar mitoses in sea urchin eggs feritized by two sperm. The experiments showed that different chromosomes perform different functions in development, and a full complement of chromosomes is necessary for reproduction.

"In culture, fertilized sea-urchin eggs undergo a complex cell division to form four cells without passing through the normal two-cell stage. This cell division involves four distinct spindle poles and the resulting cells, if gently separated, all have the potential to develop into normal adults. Occasionally, eggs will be fertilized simultaneously by two sperm, and in this case cell division also produces four cells or, more rarely, three. By comparing two populations of fertilized eggs, one exposed to a high concentration of sperm and the other to a low concentration, Boveri saw a direct correlation between the number of resulting deformed embryos and the amount of dispermic eggs.

"Boveri then looked at the development of the individual cells from dispermic eggs when separated at the four-cell stage. Unlike the conventionally fertilized eggs, the individual 'quarter embryos' very rarely developed normally. He also observed that the four separated cells tended to develop differently from each other. Boveri quantified these observations and found that the chance of one of a dispermic egg's quarter embryos developing normally was much greater than that of a dispermic egg as a whole: "certain quarters achieve more separately than all four quarters together".

"The nuclear material of each quarter embryo from dispermic eggs was different, because the chromosomes separated randomly towards the four poles. Boveri hypothesized that each cell needed a full set of chromosomes for normal development. If any chromosomes were missing, the cell would lack 'developmental potential', but duplication of chromosomes would have relatively minor effects, in keeping with Mendel's dominant characters" (http://www.nature.com/celldivision/milestones/full/milestone01.html, accessed 12-16-2013).

J. Norman (ed.) Morton's Medical Bibliography 5th ed (1991) no. 241.1

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The First Proof of Mendelian Heredity in Humans 1902 – 1908

In 1908 English physician Archibald Garrod delivered the Croonian Lectures at the Royal College of Physicians in London on inborn errors of metabolism. In his studies of the rare disease alkaptonuria, which affects about one in one million people, Garrod noted that over twenty-five percent of the recorded cases were the offspring of first cousins. In 1902 he consulted the pioneer English geneticist William Bateson about whether the disease might be hereditary. In a footnote to the first of his "Reports to the Evolution Committee of the Royal Society" (1902), Bateson noted Garrod's work and suggested that since first cousins are often similar genetically, Garrod's data might be best understood if one assumed alkaptonuria to be caused by a recessive gene:

"In illustration of such a phenomenon we way perhaps venture to refer to the extraordinarily interesting evidence lately collected by Garrod regarding the rare condition known as "Alkaptonuria." In such persons the substance, alkapton, forms a regular constituent of the urine, giving it a deep brown colour which becomes black on exposure. The condition is exceedingly rare, and, though met with in several members of the same families, has only once been known to be directly transmitted front parent to offspring. Recently, however, Garrod has a noticed that no fewer than five families containing alkaptonuric members, more than a quarter of the recorded cases, are the offspring of unions of first cousins. In only two other families is the parentage known, one of these being the case in which the father was alkaptonuric. In the other case the parents were not related. Now there may be other accounts possible, but we note that the mating of first cousins gives exactly the conditions most likely to enable a rare and usually recessive character to show itself. If the bearer of such a gamete mates with individuals not bearing it, the character would hardly ever be seen; but first cousins will frequently be bearers of similar gametes, which may in such unions meet each other, and thus lead to the manifestation of the peculiar recessive characters in the zygote. See A. E. Garrod, 'Trans. Med. Chir. Soc.,' 1899, p. 367, and 'Lancet,' November 30, 1901."

This was the first proof of Mendelian heredity in humans, and the foundation of human biochemical genetics. Garrod recognized alkaptonuria to be a genetic disease and, in his Croonian lectures of 1908, hypothesized that each such biochemical defect, or "inborn error of metabolism," was caused by an interruption or block in a metabolic sequence due to the congenital lack of a particular enzyme. Little notice was taken of Garrod's work at the time, in part because his hypothesis regarding the "one gene-one enzyme" link could not be tested until the late 1930s-early 1940s, notably in the work of Beadle and Tatum (1941).

Garrod's lectures were first published as "The Croonian Lectures on Inborn Errors of Metabolism," Lancet 2 (1908) 1-7, 142-8. 173-9, 214-20. They were published in book form as Inborn Errors of Metabolism (London, 1909). Garrod's first paper on the subject dealt with alkaptonuria (Lancet 2, 1901, 1484-6.)

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) nos. 244.1, 3921.

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Genetic Variability, Phenotype and Genotype 1903

In 1903 the Danish geneticist Wilhelm Johannsen issued Ueber Erblichkeit in Populationen und in reinem LinienThis work, published in Jena by Georg Fischer, provided more support for the Mendelian laws of inheritance by showing that in certain self-fertilizing plants a pure line of descendants can be maintained indefinitely, in which case natural selection is not effective; selection depends upon genetic variability.

In "Om arvelighed i samfund og i rene linier," Oversigt over det Kongelige Danske Videnskabernes Selskabs Forhandlinger, 3 (1903) 247-270, Johannsen coined the terms phenotype and genotype. Johannsen pubished a German translation of this paper in Ueber Erblichkeit....

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Theorizing that Chromosomes Carry the Hereditary Material 1903

In "The Chromosomes in Heredity," Biological Bulletin 4 (1903) 231-51 American geneticist and physician Walter Stanborough Sutton advanced the theory that Mendel's factors were hereditary particles borne by the chromosomes, and that Mendel's laws for his factors were the direct result of the behavior of chromosomes in meiosis. 

Independently of Sutton, German biologist Theodor Boveri proposed a similar view in Ergebnisse über die Konstitution der chromatischen Substanz des Zelkerns (1904), causing the theory to be known as the "Sutton-Boveri theory or the Boveri-Sutton chromosome theory."

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) nos. 242.1, 242.2.

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DNA is Distinguished from RNA 1903

In his paper “Darstellung und Analyse einiger Nucleinsäuren,” Hoppe-Seyl. Z. physiol. Chem. 39 (1903) 4-8, 133-35, 479-83 Lithuanian American biochemist Phoebus Aaron Theodore Levene, working in New York, distinguished between DNA and RNA.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 725.1.

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The Hardy-Weinberg Equilibrium 1908

In 1908 mathematician G. H. Hardy of Cambridge University and general practitioner and obstetrician Wilhelm Weinberg of Stuttgart independently discovered what came to be known as the "Hardy-Weinberg equilibrium (Hardy–Weinberg principle). This 

"states that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences. These influences include non-random matingmutationselectiongenetic driftgene flow and meiotic drive. Because one or more of these influences are typically present in real populations, the Hardy–Weinberg principle describes an ideal condition against which the effects of these influences can be analyzed."

"Mendelian genetics were rediscovered in 1900. However, it remained somewhat controversial for several years as it was not then known how it could cause continuous characteristics. Udny Yule (1902) argued against Mendelism because he thought that dominant alleles would increase in the population. The American William E. Castle (1903) showed that without selection, the genotype frequencies would remain stable. Karl Pearson (1903) found one equilibrium position with values of p = q = 0.5. Reginald Punnett, unable to counter Yule's point, introduced the problem to G. H. Hardy, a British mathematician, with whom he played cricket. Hardy was a pure mathematician and held applied mathematics in some contempt; his view of biologists' use of mathematics comes across in his 1908 paper where he describes this as "very simple".

To the Editor of Science: I am reluctant to intrude in a discussion concerning matters of which I have no expert knowledge, and I should have expected the very simple point which I wish to make to have been familiar to biologists. However, some remarks of Mr. Udny Yule, to which Mr. R. C. Punnett has called my attention, suggest that it may still be worth making...
Suppose that Aa is a pair of Mendelian characters, A being dominant, and that in any given generation the number of pure dominants (AA), heterozygotes (Aa), and pure recessives (aa) are as p:2q:r. Finally, suppose that the numbers are fairly large, so that mating may be regarded as random, that the sexes are evenly distributed among the three varieties, and that all are equally fertile. A little mathematics of the multiplication-table type is enough to show that in the next generation the numbers will be as (p+q)2:2(p+q)(q+r):(q+r)2, or as p1:2q1:r1, say.
The interesting question is — in what circumstances will this distribution be the same as that in the generation before? It is easy to see that the condition for this is q2 = pr. And since q12 = p1r1, whatever the values of p, q, and r may be, the distribution will in any case continue unchanged after the second generation

"The principle was thus known as Hardy's law in the English-speaking world until 1943, when Curt Stern pointed out that it had first been formulated independently in 1908 by the German physician Wilhelm WeinbergWilliam Castle in 1903 also derived the ratios for the special case of equal allele frequencies, and it is sometimes (but rarely) called the Hardy–Weinberg–Castle Law" (Wikipedia article on Hardy-Weinberg principle, accessed 12-16-2013).

Hardy, "Mendelian Proportions in a Mixed Population," Science 28 (1908) 49-50.

Weinberg, "Über den Nachweis der Vererbung beim Menschen," Jahr. Ver.f. Vaterland Nat. Würz. 64 (1908) 369-82.

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The Theory of Polygenic Inheritance 1909 – 1911

In 1909 Swedish botanist Nils Herman Nillson-Ehle, a professor at Lund University, advanced the "multiple factor" theory, or theory of polygenic inheritance, in which a trait is produced from the cumulative effects of more than one gene. Traits that display a continuous distribution, such as height, hair or skin color, are polygenic. The inheritance of polygenic traits does not show the phenotypic ratios characteristic of Mendelian inheritance, though each of the genes contributing to the trait are inherited as described by Mendel. Einvironmental factors may affect polygenic inheritance, thus adding still other contributing factors to the "multiple factor" theory.

Nilsson-Ehle, "Kreuzungsuntersuchungen an Hafer und Weizen," Lunds Univiversitets Årsskrift. N.F. Atd 2, 5, Nr. 2 (1909) 1-122, N.F. Afd. 2, 7 (1911) Nr. 6, 1-84.

♦ Independently of Nilsson-Ehle, in 1910 American plant geneticist Edward Murray East of Harvard University published an essentially identical theory in "A Mendelian Interpretation of Variation that is Apparently Continuous," American Naturalist 44 (1910) 65-82. 

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) nos. 245, 245.1.

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1910 – 1920

Sex-Linked Inheritance; Demonstration that Genes are Carried on Chromosomes 1910

Around 1908 American geneticist Thomas Hunt Morgan of Columbia University started working on the fruit fly Drosophila melanogaster, and with his students mutated Drosophila through physical, chemical, and radiational means. In his "Fly Room" he began cross-breeding experiments to find inherited mutations, but with no significant success for two years. Finally in 1909, a series of heritable mutants appeared, some of which displayed Mendelian inheritance patterns, and in 1910 Morgan noticed a white-eyed mutant male among the red-eyed wild types. When white-eyed flies were bred with a red-eyed female their progeny were all red-eyed. A second generation cross produced white-eyed males—a sex-linked recessive trait, the gene for which Morgan named white. In discovering sex-linked inheritance Morgan was the first to link the inheritance of a specific trait definitively with a particular chromosome, demonstrating that genes are carried on chromosomes.

Morgan, "Sex-Limited Inheritance in Drosophila," Science 32 (1910) 120-22.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 245.2.

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Genetic Recombination is Proposed September 10, 1911

While studying the chromosome theory of heredity in 1911, American geneticist Thomas Hunt Morgan occasionally noticed that "linked" traits would separate. Meanwhile, other traits on the same chromosome showed little detectable linkage. To explain his results Morgan proposed a process of crossing over, or recombination. Specifically, he proposed that the two paired chromosomes could "cross over" to exchange information. Morgan also proposed that Mendelian factors (genes) are arranged in a linear series on chromosomes, "similar to pearls on a string." He hypothetized that the interchange of genetic information broke the linkage between genes. The closer two genes were to one another on a chromosome, he theorized, the greater their chance of being inherited together. Conversely, genes located farther away from one another on the same chromosome were more likely to be separated during recombination. Therefore, Morgan correctly proposed that the strength of linkage between two genes depends upon the distance between the genes on the chromosome

Morgan, "Random segregation versus coupling in Mendelian inheritance," Science 34 (1911) 384.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 245.3.

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Using Cross-Over Data to Construct the First Genetic Map 1913

Soon after American geneticist Thomas Hunt Morgan of Columbia University presented his hypothesis that the strength of linkage between two genes depends upon the distance between the genes on the chromosome, his student Alfred Henry Sturtevant, then a 19-year-old undergraduate, working in Morgan's Fly Room, realized that if frequency of crossing over was related to distance, one could map out the genes on a chromosome. If the farther apart two genes were on a chromosome, the more likely it was that these genes would separate during recombination, Sturtevant recognized that the "proportion of crossovers could be used as an index of the distance between any two factors" (Sturtevant, 1913). Collecting a stack of laboratory data, Sturtevant went home and spent most of the night drawing the first chromosomal linkage map for the genes located on the X chromosome of fruit flies. He showed that the gene for any specific trait was in a fixed location (locus), and in his 1913 paper Sturtevant included the first genetic map with all its genes in the correct position, and also laid out the logic for genetic mapping. His maps proved that genes are arranged in a linear sequence along chromosomes and paved the way for genetic maps of other species besides Drosophila.

Sturtevant, "The Linear Arrangement of Six Sex-Linked Factors in Drosophila, as shown by their mode of Association," Journal of Experimental Zoology 14 (1913) 43-59. 

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 245.4. 

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Discovery of Nondisjunction 1913

In 1913 Calvin Bridges, a genetics student of Thomas Hunt Morgan at Columbia University, discovered nondisjunction (non-disjunction)— the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2.

Bridges, "Non-Disjunction of the Sex Chromosomes of Drosophila," Journal of Experimental Zoology 15 (1913) 587-606.

Bridges expanded his research into "a masterful Ph.D. thesis"  entitled on "Non-disjunction as Proof of the Chromosome Theory of Heredity," Genetics 1, no. 2 (March 1916) 107-163.

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Mendelian Laws are Demonstrated by Observable Events Occurring in Cells 1915

In 1915 American zoologist and geneticist Thomas Hunt Morgan, and his students and co-workers in the Fly Room at Columbia University: Alfred H. Sturtevant, Hermann J. Muller and Calvin B. Bridges published The Mechanism of Mendelian Heredity. Summarizing the research the team had done since 1910, this widely read textbook presented evidence that genes are arranged linearly on chromosomes, and that Mendelian laws are demonstrated by observable events occurring in cells.

"By 1915 Morgan and his co-workers were able to present the locations on a genetic map for 30 distinct genes of the four Drosophila chromosomes" (Brock pp. 14-15)

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Foundation of Biometrical Genetics 1918

In 1918 English statistician, evolutionary biologist, geneticist and eugenicist Ronald A. Fisher, then of Bradfield College, published "The Correlation Between Relatives on the Supposition of Mendelian Inheritance," Transactions of the Royal Society of Edinburgh 52 (1918) 399-433. This paper reconciled Mendelian genetics with the biometric observations of Karl Pearson and Francis Galton. It laid the foundation for what came to be known as biometrical genetics, introducing the analysis of variance— a considerable advance over the earlier correlation methods, and included the first use of "variance" in statistics. The paper showed that the inheritance of traits measurable by real values (i.e., continuous or dimensional traits) is consistent with Mendelian principles. It formed the basis of the genetics of complex trait inheritance, and mitigated debates between biometricians and Mendelians on the compatibility of particulate inheritance with natural selection

"Fisher had originally submitted his paper (then entitled "The correlation to be expected between relatives on the supposition of Mendelian inheritance") to the Royal Society, to be published in the [Philosophical] Transactions of the Royal Society of London. The two referees, the biologist R. C. Punnett and the statistician Karl Pearson, believed that the paper contained areas they were unable to judge, due to lack of expertise, and expressed some reservations. Though the paper was not rejected, Fisher carried a feud with Pearson from 1917 on, and instead sent the paper via J. Arthur Thomson to the Royal Society of Edinburgh, which published it in its Transactions" (Wikipedia article on The Correlation between Relatives...., accessed 12-21-2013).

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 248. 

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First Use of the Word Gene 1919

In 1919 American geneticist Thomas Hunt Morgan of Columbia University published The Physical Basis of Heredity. In this book he first used the word gene. Previously he had used the term "Mendelian unit"or "factor". 

"On the basis of genetic analysis, Morgan could present a number of characteristics of genes.

1. A gene could have more than one effect. For instance, insects that had the white-eye gene not only had white eyes, but also grew slower and had a lower viability.

2. The effects of the gene could be modified by external conditions, but these modifications were not transmitted to future generations. The gene itself was stable; only the character that the gene controlled varied.

3. Characters that were indistinguishable phenotypically could be the product of different genes.

4. At the same time, each character was the product of many genes. For instance, 50 different genes were known to afect eye color, 15 affected body color, and 10 affected length of wing.

5, Heredity was therefore not some property of the 'organism as a whole', but rather of the genes.

6. Genes of the pair did not ump out of one chromosome into another, but changed when the chromosome thread broke as a piece in front of or else behind them. Thus, crossing-over affected linked genes as groups and was a product of the behavior of the chromosome as an entity.

"Morgan's studies were based, to a great extent, on the availabity of a large number of mutants, bu the nature of the mutation process itself remained a mystery...." (Brock p. 15).

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1920 – 1930

"Mathematical Theory of Natural and Artificial Selection" 1924

With R. A. Fisher and Sewall Wright, British-born geneticist and evolutionary biologist John Burdon Sanderson Haldane (J.B.S. Haldane) developed the mathematical theory of population genetics. In 1924 Haldane began publication of his "Mathematical Theory of Natural and Artificial Selection." The first part appeared in the Transactions of the Cambridge Philosophical Society 23 (1924) 19-41. Parts II through IX appeared in the Proceedings of the Cambridge Philosophical Society from 1924 to 1932. The tenth and final part, "Some Theorems on Natural Selection," appeared in Genetics 19 (1934) 412-429.

In "A Mathematical Theory of Natural and Artificial Selection" Haldane showed the direction and rates of change of gene frequencies. He also pioneered investigation of the interaction of natural selection with mutation and with migration.

In 1932 Haldane issued a book, The Causes of Evolution, summarizing these results for a wider audience, and including the majority of his mathematical treatment of the subject in an extensive appendix. This body of work was a component of what came to be known as the "modern evolutionary synthesis", re-establishing natural selection as the premier mechanism of evolution by explaining it in terms of the mathematical consequences of Mendelian genetics.

In December 2013 when I wrote this entry parts 1 and 10 of Haldane's "Mathematical Theory...." were available at the links provided above, along with part V, which was available at this link. The remaining parts were available to subscribers from the Cambridge Journals website.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 254. 

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Proof that X-Rays Can Induce Mutations 1927

In 1927 American geneticist and educator Herman J. Muller, of the University of Texas at Austin, showed that radiation causes mutations that are passed on from one generation to the next. This was the first suggestion that inherited traits might be altered or controlled, and it created a sensation. “Man’s most precious substance, the hereditary material which he could pass on to his offspring, was now potentially in his control. X rays could  ‘speed up evolution,’ if not in practice at least in the headlines. Like the discoveries of Einstein and Rutherford, Muller’s tampering with a fundamental aspect of nature provoked the public awe “(Carlson, "An unacknowledged founding of molecular biology: H. J. Muller’s Contribution to Gene Theory, 1910-36," Journal of the History of Biology 4 (1971) 149-70). 

A student of Thomas Hunt Morgan, Muller studied mutations and sought to map genes to specific chromosomes, but unlike most other early geneticists, Muller was particularly interested in the physical and chemical nature and operations of genes. Beginning in November 1926 Muller subjected male fruit flies to relatively high doses of radiation, then mated them to virgin female fruit flies. In a few weeks' time he was able to induce more than 100 mutations in the resulting progeny—about half the number of all mutations discovered in Drosophila over the previous fifteen years.

From Muller's work a clear, quantitative connection between radiation and lethal mutations quickly emerged. Some mutations were deadly; the effects of other mutations in offspring were visible but not lethal. As Muller interpreted his results, radioactive particles passing through the chromosomes randomly affected the molecular structure of individual genes, rendering them either inoperative or altering their chemical functions. Muller's discovery created a media sensation after he delivered a paper entitled "The Problem of Genetic Modification" at the Fifth International Congress of Genetics in Berlin. This was published in Verhandlungen des V. Internationalen Kongress fur Veresbungswissenschaft 1927 (1928) 234-260. 

Muller, "Artificial Transmutation of the Gene," Science 66 (1927) 84-87. 

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Demonstration that Bacteria Can Transfer Genetic Information Through an Unidentified Transforming Factor 1928

At the English Ministry of Health's Pathological Laboratory bacteriologist Frederick Griffith was sent pneumococci samples taken from patients throughout the country. He amassed a large number, and would type—in other words classify—each pneumococci sample to research patterns of pneumonia epidemiology. In 1928 he published "The Significance of Pneumococcal Types," Journal of Hygiene (Cambridge) 27 (1928) 113-59. In this paper he showed that Streptococcus pneumoniae, implicated in many cases of lobar pneumonia, could transform from one strain into a different strain. This phenomenon he attributed to an unidentified transforming principle or transforming factor.

Griffith's research was one of the first experiments that suggested that bacteria are capable of transferring genetic information through a process known as transformation. Research by Avery, MacLeod, and McCarty reported in 1944 isolated DNA as the material that communicated this genetic information.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1992) no. 251.2.

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1930 – 1940

R. A. Fisher's "The Genetical Theory of Natural Selection" 1930

The Genetical Theory of Natural Selection published at Oxford in 1930 by English statistician, evolutionary biologist, geneticist, and eugenicist Ronald A. Fisher, developed ideas on sexual selection, mimicry and the evolution of dominance.

"He famously showed that the probability of a mutation increasing the fitness of an organism decreases proportionately with the magnitude of the mutation. He also proved that larger populations carry more variation so that they have a larger chance of survival. It was in this book that he set forth the foundations of what was to become known as population genetics. Fisher's book also had a major influence on the evolutionary biologist W. D. Hamilton and the development of his later theories on the genetic basis for the existence of kin selection.

"Fisher had a long and successful collaboration with E.B. Ford in the field of ecological genetics. The outcome of this work was the general recognition that the force of natural selection was often much stronger than had been appreciated before, and that many ecogenetic situations (such as polymorphism) were not selectively neutral, but were maintained by the force of selection. Fisher was the original author of the idea of heterozygote advantage, which was later found to play a frequent role in genetic polymorphism. The discovery of indisputable cases of natural selection in nature was one of the main strands in the modern evolutionary synthesis" (Wikipedia article on Ronald Fisher, accessed 12-21-2013).

Fisher issued a second, slightly revised edition of the work in 1958. In 1999 The Genetical Theory of Natural Selection. A Complete Variorum Edition edited by Henry Bennett was published by Oxford University Press, reprinting the original 1930 text with footnotes added showing where changes were made in 1958, and with editorial notes and an annotated bibliography of papers by Fisher on topics related to The Genetical Theory of Natural Selection. 

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Wright's Quantitative Theory of the Effects of Natural Selection on Populations 1931

In 1931 American geneticist Sewall Wright at the University of Chicago published "Evolution in Mendelian Populations," Genetics 16 (1931) 97-159. This was the first detailed presentation of Wright's quantitative theory of the effects of mutation, migration, selection, and population size on changes in gene frequencies in populations. Together with R. A. Fisher and J.B.S. Haldane, Wright blended the science of population genetics with Darwin's theory of natural selection to create what was known as the modern evolutionary synthesis.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 253.1.

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"The Inborn Factors in Disease" 1931

In 1931 English physician Archibald Garrod, Regius Professor of Medicine at Oxford, issued The Inborn Factors in Disease from Oxford at the Clarendon Press. The result of his continuing researches on what he previously designated as Inborn Errors of MetabolismGarrod argued that chemical individuality could result in individuals having a predisposition to certain diseases. This concept, which Garrod initially called diathesis, he regarded an an inherited predisposition expressed as chemical individuality in forms more subtle than those so obvious in the inborn errors of metabolism. This view was later much appreciated with the development of recominbant DNA methods to identify inherited genetic defects.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 253.2.

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Niels Bohr Asks if Living Processes Could be Described in Terms of Pure Physics and Chemistry 1933

In 1933 Danish physicist Niels Bohr delivered a lecture on Light and Life before an international congress of light therapists in Copenhagen. His lecture marks his first detailed attempt to apply concepts arising from quantum mechanics (particularly complementarity) to areas outside physics.

“Here, for the first time, Bohr raised a question that was to preoccupy him, off and on, until his death: Would it ever be possible to push the analysis of living processes to the limit where they can be described in terms of pure physics and chemistry?” (Pais, Niels Bohr's Times, 411, 441-42, quote from 442).

Bohr’s lecture may be viewed as one of the foundation stones of molecular biology, in that it inspired the young physicist Max Delbrück (who was in the audience when Bohr delivered it) to switch from physics to biology “to find out whether indeed there was anything to this point of view” (quoted in Pais, p. 442). In 1935, two years after hearing Bohr’s lecture, Delbrück and two other scientists published a paper on genetic mutations caused by x-ray irradiation, in which they concluded that the gene must be a molecule. The ideas expressed in that paper inspired Schrödinger to write his famous What is Life?, a work which in turn motivated Watson, Crick, Wilkins and other scientists to devote their careers to unraveling “the secret of the gene” (quoted in Moore, Schrödinger, p. 403). Delbrück himself became a leader of what was known as the “phage group” of bacterial geneticists; in 1969, he received a share of the Nobel Prize for physiology / medicine for describing the means by which living cells are infected with viruses. “It is fair to say that with Max [Delbrück], Bohr found his most influential philosophical disciple outside the domain of physics, in that through Max, Bohr provided one of the intellectual fountainheads for the development of 20th century biology” (quoted in Pais, p. 442).

Bohr's lecture was published in Danish as "Lys og liv," Naturens Verden 17 (1933) 49-59. It was published in English as "Light and Life," Nature 131 (March 25, 1933) 421-423, and it was also published in German.  

Judson, The Eighth Day of Creation, 32-35.

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Timofeeff-Ressovsky Publishes One of the Key Conceptual Papers in the Early History of Molecular Biology 1935

In 1935 Soviet biologist and geneticist Nikolai Vladimirovich Timofeeff-Ressovsky (Nikolaj Vladimirovich Timofeev-ResovskijНиколай Владимирович Тимофеев-Ресовский), working in Berlin, in collaboration with German physicist and radiation biologist Karl Zimmer and German-American biophysicist Max Delbrück, published "Ueber die Natur der Genmutation und der Genstruktur," Nachrichten von der Gesellschaft der Wissenschaften zu Göttingen, mathematisch-physikalische Klasse, Fachgruppe VI, 1, (1935), [189]-245. 

One of the key conceptual papers in the early history of molecular biology, this work represented the debut in genetics of the physicist Max Delbrück, a student and lifelong friend of Danish physicist Niels Bohr. Delbruck turned from quantum physics to biology after being inspired by speculations in Bohr's 1932 lecture "Light and life," about the application of quantum mechanics to problems in biology. 

"Über die Natur der Genmutation und der Genstruktur" (often referred to as "the green paper" after the color of its printed wrappers, or the "Dreimanner" paper after the number of its authors) was divided into four sections. The first, by Timofeeff-Ressovsky, described the mutagenic effects of x-rays and gamma rays on Drosophila melanogaster; the second part, by Zimmer, analyzed Timofeeff-Ressovsky's results theoretically. The third and most remarkable section, by Delbrück, put forth a model of genetic mutation based on atomic physics that "shows the maturity, judgment and breadth of knowledge of someone who had been in the field for years . . . its carefully worded predictions have stood the test of time" (Perutz, p. 557).

The three authors of the paper "concluded that a mutation is a molecular rearrangement within a particular molecule, and the gene a union of atoms with which a mutation, in the sense of a molecular rearrangement or dissociation of bonds, can occur. The actual calculations of the size of the gene, deduced from calculations on the assumption of a spherical target, were not cogent, as Delbrück [later] wryly admitted in his Nobel Prize lecture, but the entire approach to the problem of mutation and the gene adopted by the three collaborators was highly stimulating to other investigators" (DSB [suppl.]).

The Timofeeff-Zimmer-Delbrück paper provided much of the material for Erwin Schrodinger's book What is Life? (1944), a work that takes a "naive physicist's" approach to the problems of heredity and variation; it is often cited as having inspired Watson, Crick, Wilkins and others to focus their careers on the problems of molecular biology. In his 1987 paper, "Physics and the Riddle of Life," Max Perutz examined the relationship between Schrodinger's book and the Timofeeff-Zimmer-Delbrück paper, pointing out, among other things, that the two most important chapters in Schrodinger's book were paraphrased from "Ueber die Natur der Genmutation und der Genstruktur."

"In retrospect, the chief merit of What is Life? is its popularization of the Timofeeff, Zimmer and Delbrück paper that would otherwise have remained unknown outside the circles of geneticists and radiation biologists" (Perutz, p. 558). Perutz, "Physics and the riddle of life," Nature 326 (1987) 555-559.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 254.1

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Warren Weaver Coins the Term "Molecular Biology" 1938

Perhaps the only mathematician to name a new biological discipline, in 1938, as Director of the Natural Sciences Division of the Rockefeller Foundation, Warren Weaver coined the term molecular biology to describe the use of techniques from the physical sciences (X-rays, radioisotopes, ultracentrifuges, mathematics, etc. ) to study living matter. In the same year the Rockefeller Foundation awarded research grants to Linus Pauling for research on the structure of hemoglobin. Under Weaver's direction the Rockefeller Foundation became a primary funder of early research in molecular biology.

Warren Weaver, "Molecular biology: origin of the term", Science 170 (1970) 591-2. 

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1940 – 1950

The "One Gene- One Enzyme" Hypothesis November 1941

In November 1941 American geneticists at Stanford University George W. Beadle and Edward L. Tatum published the results of their experiments with the bread mold Neurospora crassa. They concluded that ultraviolet light treatment somehow caused a mutation in a gene that controls the synthesis of an enzyme involved in the synthesis of the essential nutrient. They also showed that the defect is inherited in typical Mendelian fashion. 

"...Beadle and Tatum first irradiated a large number of Neurospora, and thereby produced some organisms with mutant genes. They then crossed these potential mutants with non-irradiated Neurospora.

"Normal products of this sexual recombination could multiply in a simple growth medium. However, Beadle and Tatum showed that some of the mutant spores would not replicate without addition of a specific amino acid—arginine. They developed four strains of arginine-dependent Neurospora—each of which, they showed, had lost use of a specific gene that ordinarily facilitates one particular enzyme necessary to the production of arginine" (http://www.genomenewsnetwork.org/resources/timeline/1941_Beadle_Tatum.php, accessed 12-22-2013).

Beadle and Tatum's experiments are often considered the first significant result in what came to be called molecular biology. In 1948 their collaborator at Caltech, Norman Horowitz, characterized their results as the "one gene- one enzyme hypothesis." Although the concept was extremely influential, the hypothesis was recognized as an oversimplification soon after its proposal. More accurately, it was later understood that each gene specifies the production of a single polypeptide— a protein or protein component. Two or more genes may contribute to the synthesis of a particular enzyme, and some products of genes are not enzymes per se, but structural proteins.

Beadle & Tatum, "Genetic Control of Biochemical Reactions in Neurospora," Proceedings National Academy of Sciences 27 (1941) 499-506.

J. Norman, Morton's Medical Bibliography 5th ed (1991) no. 254.3.

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Schrödinger's "What is Life?" "The Program has to Build the Machinery to Execute Itself" March 1943 – 1944

In March 1943 quantum physicist and theoretical biologist Erwin Schrödinger delivered a series of lectures at Trinity College Dublin entitled What is Life? The Physical Aspect of the Living Cell. These lectures popularized ideas about the physical basis of biological phenomena developed by Max Delbrück and N. V. Timofeev-Ressovsky in a paper they published in 1935. Even during wartime in England Schrödinger's lectures gained enough publicity to be reported on in the April 5, 1943 issue of Time magazine. The lectures were published  as a small book in 1944 by Cambridge University Press.  In this form they profoundly influenced James D. Watson and others, such as Francis Crick, whose background was in physics.

Watson wrote: "From the moment I read Schrödinger's What is Life I became polarized toward finding out the secret of the gene" (Watson in Cairns, Phage and the Origins of Molecular Biology, 239).

In his autobiography molecular biologist Sydney Brenner pointed out a fundamental mistake in Schrödinger’s understanding of how genes would operate:

“Anyway, the key point is that Schrödinger says that the chromosomes contain the information to specify the future organism and the means to execute it. I have come to call this ‘Schrödinger’s fundamental error.’ In describing the structure of the chromosome fibre as a code script he states that. ‘The chromosome structures are at the same time instrumental in bringing about the development they foreshadow. They are code law and executive power, or to use another simile, they are the architect’s plan and the builder’s craft in one.’ [Schrödinger, p. 20,]. What Schrödinger is saying here is that the chromosomes not only contain a description of the future organism, but also the means to implement the description, or program, as we might call it. And that is wrong! The chromosomes contain the information to specify the future organism and a description of the means to implement this, but not the means themselves. This logical difference was made crystal clear to me when I read the von Neumann article [Hixon Symposium, 1948] because he very clearly distinguishes between the things that read the program and the program itself. In other words, the program has to build the machinery to execute itself” (Brenner, My Life in Science [2001] 33-34).

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Demonstration that DNA is Responsible for Bacterial Transformation 1944

In 1944 Canadian-born American physician and researcher Oswald T. Avery, Canadian-American geneticist Colin M. McLeod, and American geneticist Maclyn McCarty, at the Rockefeller Institute in New york, published "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types. Induction of Transformation by a Desoxyribonucleic [sic] Acid Fraction Isolated from Pneumococcus Type III," Journal of Experimental Medicine 79 (1944) 137-58. The results reported in this paper demonstrated that DNA is the material responsible for bacterial  transformation.

In 1928 English bacteriologist Frederick Griffith demonstrated that Streptococcus pneumoniae, implicated in many cases of lobar pneumonia, could transform from one strain into a different strain. This phenomenon he attributed to an unidentified transforming principle or transforming factor.  In the years that followed a series of Rockefeller researchers, including Oswald Avery, continued to study transformation.

"Though interrupted, sometimes for years at a time, these studies were from 1928 onwards the centerpiece of Avery's lab agenda. Around 1940, they were activated by Colin MacLeod's efforts to purify the chemical agent responsible for changes of serotype — whether proteinnucleic acid, or some other class of molecule — and demonstrate that it was necessary and sufficient to cause the Griffith phenomenon. Studies on pneumococcal transformation were grossly burdened by a wide variety of variables, which needed to be controlled to allow quantitative estimation of transforming activity in extracts undergoing various stages of purification. MacLeod, over a number of years of research, had resolved several thorny technical issues to render the experimental system somewhat more reliable as an assay for biological activity. By the time McCarty arrived at the Rockefeller University, Avery's team had just about decided that the active reagent was not a protein. But what was it then? Could it be a soluble saccharide, RNA, or, least likely, DNA? The progress of this research over the next three years is beautifully described in McCarty's memoirThe Transforming Principle, written in the early 1980s.

"As purification progressed, exposure of extracts to crystalline RNase and to proteinase preparations helped Avery's team determine that the biological activity of extracts was not dependent on RNA or protein. Crystalline DNase was not available until 1948, but biological activity was rapidly reduced by tissue extracts rich in DNase. McCarty's arrival at Rockefeller University was also marked by another milestone, namely, the development of a diphenylamine reagent assay to positively correlate DNA with biological activity. It gradually became evident that the active material in purified extracts had astonishingly high potency in micrograms of DNA that could consummate the pneumococcal transformation in vitro.

"McCarty, MacLeod, and Avery wrestled with the standard of proof required to claim that they had accomplished pneumococcal transformation with highly purified DNA from extracts. After much self-inquiry, in 1944, they published in the Journal of Experimental Medicine that the active material was, indeed, DNA, bereft of protein or any other known polymer" (Wikipedia article on MacLyn McCarty, accessed 12-22-2013).

J. Norman (ed) Morton's Medical Bibliograhy 5th ed (1991) no. 255.3.

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Avery, McLeod & McCarty Discover that Bacteria Share Genetic Information Through Bacterial Conjugation 1946

Inspired by the 1944 Avery, McLeod and McCarty demonstration that that DNA is the material responsible for bacterial  transformation, medical student Joshua Lederberg began to investigate his hypothesis that, contrary to prevailing opinion, bacteria did not simply pass down exact copies of genetic information, making all cells in a lineage essentially clones. After making little progress at Columbia, Lederberg wrote to geneticist Edward Tatum, his post-doctoral mentor, proposing a collaboration. In 1946 Lederberg took a leave of absence to study under Tatum at Yale University. Later that year Lederberg and Tatum showed that the bacterium Escherichia coli entered a sexual phase during which it could share genetic information through bacterial conjugation. In their very brief paper (less than one page) the authors reported the discovery of sexual processes in the reproduction of bacteria: "Gene Recombination in Escherichia coli," Nature 158 (1946) 558. 

J. Norman (ed) Morton's Medical Bibliography (1991) no. 255.4.

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The First Speculation that Amino Acids are Determined by Nucleic Acids July 1946

In July 1946 The Society for Experimental Biology held its first symposium on the topic of Nucleic Acids at Cambridge. At this meeting William Astbury "pointed out "the relationship between the step size of nucleic acid—3.3 angstrom units—and the step size of amino acids—3.5 angstrom units. Astbury discussed the notion of the amino acids being determined by the nucleic acid" (Sydney Brenner, My Life in Science, 30).

Astbury, "X-ray Studies of Nucleic Acids," Symposium Society Experimental Biology 1 (1947) 67-76.

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Discovery of the Sex Chromatin: Beginning of Cytogenetics 1949

In 1949 Canadian physician and medical researcher Murray L. Barr and his graduate student Edwart G. Bertram, working at the University of Western Ontario, showed that it is possible to determine the genetic sex of an individual according to whether there is a chromatin mass present on the inner surface of the nuclear membraine of cells with resting or intermittent nuclei (sex chromatin). In Barr's words:

"After several years spent on several research projects, all of which were in the field of neurocytology, i.e. the cells of the nervous system, I decided in 1948 to start a project that was designed to learn whether heightened nerve cell activity produced any structural changes in these cells. The experiment required stimulation of a nerve in cats, during which they were anaesthetized. The animals were anaesthetized again when the portion of the brain containing the stimulated cells was removed for microscopic examination. The cats were therefore subjected to no discomfort or pain.

Just after the details of the experiment had been worked out, Ewart G. Bertram applied for a position as a graduate student leading to the Master of Science degree and we worked together on the project.... Examination of the sections showed that the nerve cell nuclei contained an especially prominent mass of chromatin, i.e. the particulate matter derived from the chromosomes, these being the nuclear components that bear the genes. However, it was soon found that the special mass of chromatin was present in the cell nuclei of some animals and not of others. Checking the experimental records showed that the mass was present in the nuclei of female cats and absent from those of male cats. It was therefore named the sex chromatin because of the sex difference and this discovery was the beginning of the new science of human cytogenetics, i.e. the relation of chromosome abnormalities to developmental defects. Methods of testing suitable for use in humans were devised and before long, it was shown that numerical or structural abnormalities of the chromosome were responsible for a number of developmental defects. The best known are Turner's syndrome in females, Klinefelter's syndrome in males and Down's syndrome in persons of both sexes. The use of testing for chromosomal abnormalities is of particular interest to paediatricians, endocrinologists and psychiatrists, especially those who are involved with the mentally retarded."

Barr & Bertram, "A Morphological Distinction between Neurones of the Male and Female, and the Behaviour of the Nucleolar Satellite during Accelerated Nucleoprotein Synthesis," Nature 163 (4148) (1949) 676-7. doi:10.1038/163676a0.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 255.5

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"The Key to the Whole Double Helix Story" Before Watson & Crick June 1949 – 1952

In June 1949 Norwegian chemist, biologist and crystallographer Sven Furberg, who was first to propose a helical structure for DNA, distributed only about five or six copies of his typed PhD dissertation at Birkbeck College London, entitled An X-ray Study of Some Nucleosides and Nucleotides.

"Furberg, reasoning with marked brilliance and luck from data that were meager but included his own x-ray studies, got right the absolute three-dimensional configuration of the individual nucleotide: where Astbury had set sugar parallel to base, Furberg, in what he called the standard configuration, set them at right angles. As a structural element, that standard configuration was a powerful help. 'Furberg's nucleotide—correcting Astbury's error—was absolutely essential to us,' Crick told me. Furberg went on to draw a couple of models of DNA, one of which was a single chain in helical form with the bases sticking out flat and parallel to each other, rising 3.4 angstroms from one to the next, eight nucleotides making one complete turn of the screw in about 27 angstroms. Plausible physically, this helix had too little in it; it failed to account for the density of DNA. Furberg stopped building models and publishe his results in June of 1949—in his doctoral dissertation. . . .

"Over the next three years, Furberg's results appeared piecemeal in a series of papers. From his thesis, his models were well known to Randall's group at King's College. . . . Otherwise, Furberg's models remained almost unnoticed—even by Bernal, who wrote, in 1968, that they had contained 'the key to the whole double helix story' and blamed himself for 'letting the opportunity slip'; Furberg at last got his helical model into print in Acta Chemica Scandinavica late in 1952, in time for Watson and Crick to cite it in the notes to their announcement of the successful solution the next spring" (Judson, The Eighth Day of Creation, 94).

Furberg, "On the Structure of Nucleic Acids," Acta Chemica Scandinavica (1952) 634-40.

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The Beginning of the Molecular Approach to Disease November 1949

In "Sickle Cell Anemia, a Molecular Disease," Science 110 (1949) 543-48 Linus PaulingHarvey A. ItanoSeymour J. Singer and Ibert C. Wells established sickle-cell anemia as a genetic disease in which affected individuals have a different form of the metalloprotein hemoglobin in their blood. The paper introduced the concept of a "molecular disease," and represents the beginning of molecular medicine.

"The paper helped establish that genes control not just the presence or absence of enzymes (as genetics had shown in the early 1940s) but also the specific structure of protein molecules. It was also an important triumph in the efforts of Pauling and others to apply the instruments and methods of the physical sciences to biology, and Pauling used it promote such research and attract funding" (Wikipedia article on Sickle Cell Anemia, a Molecular Disease, accessed 01-17-2014).

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 3154.1.

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1950 – 1960

"Chargaff's Rules" 1950

In 1950 Austrian-American biochemist Erwin Chargaff of Columbia University reported his observation from analyses of different DNAs that DNA from any cell of all organisms should have a 1:1 ratio of pyrimidine and purine bases and, more specifically, that the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine (base pair equality). Watson and Crick's model of the structure of DNA confirmed Chargaff's Rules.

Chargaff, "Chemical Specifity of Nucleic Acids and the Mechanism of their Enzymatic Degradation," Experimenta (Basel) 6 (1950) 201-9.

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Linus Pauling Reports the First Discovery of a Helical Structure for a Protein February 28, 1951

On his fiftieth birthday, February 28, 1951, American physical chemist Linus Pauling reported with his co-workers at Caltech, the American biochemist Robert Corey and the African-American physicist and chemist Herman Branson, the discovery of the alpha helix (α-helix). This was the first discovery of a helical structure for a protein. Their discovery built upon and confirmed the research of William Astbury reported in 1931.

"Although incorrect in their details, Astbury's models of these forms were correct in essence and correspond to modern elements of secondary structure, the α-helix and the β-strand (Astbury's nomenclature was kept), which were developed by Linus Pauling, Robert Corey and Herman Branson in 1951; that paper showed both right- and left-handed helixes, although in 1960 the crystal structure of myoglobin showed that the right-handed form is the common one. . . .

"Two key developments in the modeling of the modern α-helix were (1) the correct bond geometry, thanks to the crystal structure determinations of amino acids and peptides and Pauling's prediction of planar peptide bonds; and (2) his relinquishing of the assumption of an integral number of residues per turn of the helix. The pivotal moment came in the early spring of 1948, when Pauling caught a cold and went to bed. Being bored, he drew a polypeptide chain of roughly correct dimensions on a strip of paper and folded it into a helix, being careful to maintain the planar peptide bonds. After a few attempts, he produced a model with physically plausible hydrogen bonds. Pauling then worked with Corey and Branson to confirm his model before publication. In 1954 Pauling was awarded his first Nobel Prize "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances" (such as proteins), prominently including the structure of the α-helix" (Wikipedia article on Alpha helix, accessed 01-17-2014).

Pauling, Corey, and Branson, “The Structure of Proteins: Two Hydrogen-Bonded Configurations of the Polypeptide Chain," Proceedings National Academy of Sciences 37 (1951) 205-11.

Judson, The Eighth Day of Creation, 88-89.

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The Hershey-Chase "Waring Blender Experiment" 1952

In the early twentieth century biologists thought that proteins carried genetic information. This was based on the belief that proteins were more complex than DNA. In 1928 Frederick Griffith's research suggested that bacteria are capable of transferring genetic information through a process known as transformation. Research by Avery, MacLeod, and McCarty communicated in 1944 isolated DNA as the material that communicated this genetic information

The Hershey–Chase experiment, often called the "Waring Blender experiment," was conducted in 1952 by American bacteriologist and geneticist Alfred D. Hershey and his research partner American geneticist Martha Chase at Cold Spring Harbor Laboratory, New York. The experiment showed that when bacteriophages, which are composed of DNA and protein, infect bacteria, their DNA enters the host bacterial cell, but most of their protein does not, confirming that DNA is the hereditary material.

Hershey & Chase, "Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage," J. Gen. Physiol. 36 (1952) 39-56.

Judson, The Eighth Day of Creation, 108. J. Norman (ed) Morton's Medical Bibliography 5th edition (1991) no. 256.

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Rosalind Franklin's Photo #51 of Crystalline DNA May 2 – May 6, 1952

Between May 2 and May 6, 1952 English molecular biologist Rosalind Franklin, working at King's College, Cambridge took photograph No. 51 of the B-form of crystalline DNA. This was her finest photograph of the substance,  showing the characteristic X-shaped "Maltese cross" clearer than before. 

About eight months later, on January 26, 1953, Franklin showed this photograph to physicist and molecular biologist Maurice Wilkins. Four days later, on January 30, 1953 Wilkins showed the photograph to James Watson. 

The following day Watson asked laboratory director Lawrence Bragg if he could order model components from the Cavendish Laboratory machine shop. Bragg agreed. Watson's account of Franklin's photo 51 to Francis Crick confirmed that they had the vital statistics to build a B-form model: the photo confirmed the 20Å diameter, with a 3.4Å distance between bases. This, plus the repeat distance of 34Å, helix slope about 40°, and the likehood of 2 chains, not 3, seemed to be sufficient to build a model.

Franklin's file copy of Photograph 51, labeled in her handwriting, is preserved at the J. Craig Venter Institute.

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The Idea of a Genetic Code 1953 – 1954

In 1953 and 1954 Russian-American theoretical physicist, cosmologist and science writer George Gamow, while at George Washington University, came up with the idea of a genetic code in his paper “Possible Mathematical Relation between Deoxyribonucleic Acids and Proteins” (Det. Kongelige Danske Videnskabernes Selskab: Biologiske Meddeleiser 22, no. 3 [1954] 1-13).

In the fall of 1953 Gamov gave Crick an earlier draft of this paper entitled “Protein synthesis by DNA molecules.”

“Gamov’s scheme was decisive, Crick has often said since, because it forced him, and soon others, to begin to think hard and from a particular slant—that of the coding problem—about the next stage, now that the structure of DNA was known” (Judson,The Eighth Day of Creation, 236).

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Discovery of The Double Helix April 25, 1953

At the Cavendish Laboratory, University of Cambridge, in 1953 James D. Watson and Francis Crick discovered the self-complimentary double-helical structure of the DNA molecule. In their paper, “Molecular Structure of Nucleic Acids. A Structure for Deoxyribose Nucleic Acid,” Nature 171 (1953) 737-38, they stated that, “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

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Proposal of a Method of DNA's Method of Replication May 30, 1953

On May 30, 1953 James D. Watson and Francis Crick published “Genetical Implications of the Structure of Deoxyribonucleic Acid, ” Nature 171 (1953) 964-7. In this paper Watson and Crick proposed the the method of replication of DNA. This discovery has been called as significant, or possibly even more significant, than their discovery of the double-helical structure of DNA published in April 1953.

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Crick's "On Protein Synthesis" September 1957

In September 1957 molecular Biologist Francis Crick delivered his paper “On Protein Synthesis,” published in Symp. Soc. Exp. Biol. 12 (1958): 138-63. In it Crick proposed two general principles:

1) The Sequence Hypothesis:

“The order of bases in a portion of DNA represents a code for the amino acid sequence of a specific protein. Each ‘word’ in the code would name a specific amino acid. From the two-dimensional genetic text, written in DNA, are forged the whole diversity of uniquely shaped three-dimensional proteins

"In this context, Crick discussed the 'coding problem'—how the ordered sequence of the four bases in DNA might constitute genes that encode and disburse information directing the manufacture of proteins. Crick hypothesized that, with four bases to DNA and twenty amino acids, the simplest code would involve "triplets"—in which sequences of three bases coded for a single amino acid" (Genome News Network, Genetics and Genomics Timeline 1957).

2) The Central Dogma:

“Information is transmitted from DNA and RNA to proteins but information cannot be transmitted from a protein to DNA.” This paper “permanently altered the logic of biology.” (Judson)

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First Proof of the Semiconservative Replication of DNA 1958

The deciphering of the structure of DNA by James Watson and Francis Crick in 1953 suggested that each strand of the double helix would serve as a template for synthesis of a new strand. However, there was no way of knowing how the newly synthesized strands might combine with the template strands to form two double helical DNA molecules. The Meselson–Stahl experiment by American geneticists and molecular biologists Matthew Meselson and Franklin Stahl at Caltech in 1958 supported the hypothesis that DNA replication was semiconservative. In semiconservative replication, each of the two new double-stranded DNA helices consist of one strand from the original helix and one newly synthesized.

Meselson & Stahl, "The Replication of DNA in Escherichia coli," Proceedings National Academy of Sciences 44 (1958) 671-82. 

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 256.6.

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1960 – 1970

Crick & Brenner Propose The Genetic Code 1961

At Cambridge in 1961 Francis Crick, Sydney Brenner and colleagues proposed that DNA code is written in “words” called codons formed of three DNA bases. DNA sequence is built from four different bases, so a total of 64 (4 x 4 x 4) possible codons can be produced. They also proposed that a particular set of RNA molecules subsequently called transfer RNAs (tRNAs) act to “decode” the DNA.

“There was an unfortunate thing at the Cold Spring Harbor Symposium that year. I said, ‘We call this messenger RNA’ Because Mercury was the messenger of the gods, you know. And Erwin Chargaff very quickly stood up in the audience and said he wished to point out that Mercury may have been the messenger of the gods, but he was also the god of thieves. Which said a lot for Chargaff at the time! But I don’t think that we stole anything from anybody— except from nature. I think it’s right to steal from nature, however” (Brenner, My Life, 85).

Francis Crick, L. Barnett, Sydney Brenner and R. J. Watts-Tobin, “General Nature of the Genetic code for Proteins,” Nature 192 (1961): 1227-32.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 256.8.

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Brenner, Jacob & Meselson Demonstrate the Existence of Messenger RNA 1961

In 1961 South African molecular biologist Sydney Brenner working at the Cavendish Laboratory in Cambridge, French molecular biologist François Jacob at the Institut Pasteur in Paris, and American molecular biologist Matthew Meselson at Caltech in Pasadena showed that short-lived RNA molecules that they called messenger RNA (mRNA) carry the genetic instructions from DNA to structures in the cell called ribosomes. They also demonstrated that ribosomes are the site of protein synthesis.

Brenner, Jacob & Meselson, "An Unstable Intermediate Carrying Information from Genes to Ribosomes for Protein Synthesis," Nature 190 (1961) 576-80.

J. Norman (ed) Morton's Medical Bibliography 5th ed (1991) no. 256.10.

In January 2014 images of Sydney Brenner's original autograph manuscript for this paper, and typed drafts were available from the Cold Spring Harbor Laboratories CSHL Archives Repository at this link.

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Jacob & Monod Explain the Basic Process of Regulating Gene Expression in Bacteria 1961

In 1961 French biologists François Jacob and Jacques Monod explained the basic process of regulating gene expression in bacteria, showing that enzyme expression levels in cells is a result of regulation of transcription of DNA sequences. Their experiments and ideas gave impetus to the emerging field of molecular developmental biology, and of transcriptional regulation in particular.

Jacob & Monod, "Genetic Regulatory Mechanisms in the Synthesis of Proteins," Journal of Molecular Biology 3 (1961) 318-56.

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Robert MacArthur & E.O. Wilson Issue "The Theory of "Island" Biogeography" 1967

In 1967 ecologist Robert MacArthur of Princeton and biologist E. O. Wilson of Harvard published The Theory of Island Biogeography through Princeton University Press. In this work they showed that the species richness of an area could be predicted in terms of such factors as habitat area, immigration rate and extinction rate.

"Island biogeography is a field within biogeography that attempts to establish and explain the factors that affect the species richness of natural communities. The theory was developed to explain species richness of actual islands. It has since been extended to mountains surrounded by deserts, lakes surrounded by dry land, forest fragments surrounded by human-altered landscapes. Now it is used in reference to any ecosystem surrounded by unlike ecosystems. The field was started in the 1960s by the ecologists Robert MacArthur and E.O. Wilson, who coined the term theory of island biogeography, as this theory attempted to predict the number of species that would exist on a newly created island.

"For biogeographical purposes, an 'island' is any area of suitable habitat surrounded by an expanse of unsuitable habitat. While this may be a traditional island—a mass of land surrounded by water—the term may also be applied to many untraditional 'islands', such as the peaks of mountains, isolated springs in the desert, or expanses of grassland surrounded by highways or housing tracts. Additionally, what is an island for one organism may not be an island for another: some organisms located on mountaintops may also be found in the valleys, while others may be restricted to the peaks" (Wikipedia article on Island biogeography, accessed 05-08-2009).

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Max Perutz Solves the Molecular Structure of Hemoglobin at High Resolution 1968

Thirty years after beginning his research on hemoglobin Austrian-born British molecular biologist Max Perutz at Cambridge solved the Fourier synthesis of hemoglobin at 2.8Å, and built an atomic model of the molecule.

Perutz el al, "Three-dimensional Fourier Synthesis of Horse Oxyhaemoglobin at 2.8Å Resolution: The Atomic Model," Nature 219 (1968) 131-39.

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1970 – 1980

Cohen & Boyer Demonstrate the First Practical Method for Cloning a Gene 1973

In 1973 Stanley Cohen, Annie Chang, Robert Helling, and Herbert Boyer demonstrated that if DNA is fragmented with restriction endonucleases and combined with similarly restricted plasmid DNA, the resulting recombinant DNA molecules are biologically active and can replicate in host bacterial cells. Plasmids can thus act as vectors for the propagation of foreign cloned genes.

This was the first practical method of cloning a gene, and a breakthrough in the development of recombinant DNA technologies and genetic engineering.

Cohen, Chang, Boyer and Helling, “Construction of Biologically Functional Bacterial Plasmids in Vitro,” Proc. Nat. Acad. Sci. 70 (1973): 3240-3244

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The First of the Three Cohen-Boyer Recombinant DNA Cloning Patents is Granted 1974

In 1974 the first of the three Cohen-Boyer recombinant DNA cloning patents was granted, leading to the foundation of the biotechnology industry.

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The Asilomar Conference on Recombinant DNA February 1975

In February 1975 the Asilomar Conference on Recombinant DNA Molecules, organized by Paul Berg, Maxine Singer, and Richard Roblin occurred in Asilomar, California.

"In addition to an international group of 150 scientists, the participants included lawyers (including Daniel Singer, Maxine Singer's husband) to help consider legal and ethical issues, and 16 journalists to cover the four-day event. A primary aim of the group was to consider whether to lift the voluntary moratorium [on recombinant DNA (rDNA) research] and if so, under what conditions research could proceed safely. The participants concluded (though not unanimously) that rDNA research should proceed but under strict guidelines. Their recommendations went to a National Institutes of Health committee chaired by NIH director Donald Fredrickson and charged with formulating those guidelines, which were issued in July 1976" (http://profiles.nlm.nih.gov/CD/Views/Exhibit/narrative/dna.html, accessed 07-25-2009).

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Genentech is Founded April 7, 1976

On April 7, 1976 venture capitalist Robert A. Swanson and biochemist Herbert W. Boyer founded the first genetic engineering company, Genentech, to use recombinant DNA methods to make medically important drugs.

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The Sanger Method of Rapid DNA Sequencing 1977

In 1977 English biochemist Frederick Sanger and colleagues at the University of Cambridge independently developed a method for the rapid sequencing of long sections of DNA molecules. Sanger’s method, and that developed by Gilbert and Maxam, made it possible to read the nucleotide sequence for entire genes that run from 1000 to 30,000 bases long. Sanger sequencing was the most widely used sequencing method for approximately 25 years. 

In 1980 Sanger shared the 1980 Nobel Prize in Chemistry with Walter Gilbert and Paul Berg. Paul Berg received half of the price "for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA". The other half was split between Walter Gilbert and Frederick Sanger "for their contributions concerning the determination of base sequences in nucleic acids".  This was Sanger's second Nobel prize.

Sanger, F., Nicklen, S., and Coulson, A.R. "DNA Sequencing with Chain-Terminating Inhibitors," Proc. Nat. Acad. Sci. (USA) 74 (1977) 546-67.

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1980 – 1990

The First Whole Genome Shotgun Sequence 1982

In 1982 British biochemist Frederick Sanger and colleagues sequenced the entire genome of bacteriophage lambda using a random shotgun technique. This was the first whole genome shotgun (WGS) sequence.

Sanger, et alNucleotide Sequence of Bacteriophage Lambda,” J. Mol. Biol. 162 (1982) 729-73.

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The First Study of Ancient DNA (aDNA) November 15, 1984

On November 15, 1984 Russell Higuchi, Barbara Bowman, and Mary Freiberger from the Department of Biochemistry at the University of California, Berkeley and Oliver A. Ryder & Allan C. Wilson, of the Research Department, San Diego Zoo, published "DNA sequences from the quagga, an extinct member of the horse family," Nature 312, 282-284; doi:10.1038/312282a0.  This was probably the first study of DNA isolated from ancient specimens, or ancient DNA (aDNA).

"To determine whether DNA survives and can be recovered from the remains of extinct creatures, we have examined dried muscle from a museum specimen of the quagga, a zebra-like species (Equus quagga) that became extinct in 1883. We report that DNA was extracted from this tissue in amounts approaching 1% of that expected from fresh muscle, and that the DNA was of relatively low molecular weight. Among the many clones obtained from the quagga DNA, two containing pieces of mitochondrial DNA (mtDNA) were sequenced. These sequences, comprising 229 nucleotide pairs, differ by 12 base substitutions from the corresponding sequences of mtDNA from a mountain zebra, an extant member of the genus Equus. The number, nature and locations of the substitutions imply that there has been little or no postmortem modification of the quagga DNA sequences, and that the two species had a common ancestor 3–4 Myr ago, consistent with fossil evidence concerning the age of the genus Equus."

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Origins of the Human Genome Project December 1984 – April 1987

In 1985, as Director of the U.S. Department of Energy’s (DOE) Health and Environmental Research Programs, Charles DeLisi and his advisors proposed, planned and defended before the White House Office of Management and Budget and the Congress, the Human Genome Project. The proposal created a storm of controversy, but was included in President Ronald Reagan’s Fiscal Year 1987 budget submission to the Congress, and subsequently passed both the House and the Senate.

The beginning of the project may have occurred in a workshop known as the Alta Summit held in Alta, Utah, December 1984.

"Robert Sinsheimer, then Chancellor of the University of California, Santa Cruz (UCSC), thought about sequencing the human genome as the core of a fund-raising opportunity in late 1984. He and others convened a group of eminent scientists to discuss the idea in May 1985. This workshop planted the idea, although it did not succeed in attracting money for a genome research institute on the campus of UCSC. Without knowing about the Santa Cruz workshop, Renato Dulbecco of the Salk Institute conceived of sequencing the genome as a tool to understand the genetic origins of cancer. Dulbecco, a Nobel Prize winning molecular biologist, laid out his ideas on Columbus Day, 1985, and subsequently in other public lectures and in a commentary for Science. The commentary, published in March 1986, was the first widely public exposure of the idea and gave impetus to the idea's third independent origin, by then already gathering steam.

"Charles DeLisi, who did not initially know about either the Santa Cruz workshop or Dulbecco's public lectures, conceived of a concerted effort to sequence the human genome under the aegis of the Department of Energy (DOE). DeLisi had worked on mathematical biology at the National Cancer Institute, the largest component of the National Institutes of Health (NIH). How to interpret DNA sequences was one of the problems he had studied, working with the T-10 group at Los Alamos National Laboratory in New Mexico (a group of mathematicians and others interested in applying mathematics and computational techniques to biological questions). In 1985, DeLisi took the reins of DOE's Office of Health and Environmental Research, the program that supported most biology in the Department. The origins of DOE's biology program traced to the Manhattan Project, the World War II program that produced the first atomic bombs with its concern about how radiation caused genetic damage.

"In the fall of 1985, DeLisi was reading a draft government report on technologies to detect inherited mutations, a nagging problem in the study of children to those exposed to the Hiroshima and Nagasaki bombs, when he came up with the idea of a concerted program to sequence the human genome.9 DeLisi was positioned to translate his idea into money and staff. While his was the third public airing of the idea, it was DeLisi's conception and his station in government science administration that launched the genome project" (Robert Mullan Cook-Deegan, Origins of the Human Genome Project, accessed 05-24-2009).

In March 1986 the Department of Energy, Office of Health and Environmental Research, sponsored a workshop at Los Alamos. This was edited by M. Bitensky and published as Sequencing the Human Genome. Summary Report of the  Santa Fe Workshop, March 3-4, 1986

The initial report on the Human Genome Project appeared in April 1987 as:

Report on the Human Genome Initiative for the Office of Health and Environmental Research, Prepared by the Subcommittee on Human Genome of the Health and Environmental Research Advisory Committee for the U.S. Department of Energy Office of Energy Research Office of Health and Environmental Research.

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The First Semi-Automatic DNA Sequencer 1986

In 1986 Leroy Hood and Lloyd Smith from the California Institute of Technology developed the first semi-automatic DNA sequencer, working with a laser that recognized fluorescing DNA markers.

"A biologist at the California Institute of Technology and a founder of API [Applied Biosystems, Inc.], Hood improved the existing Sanger method of enzymatic sequencing, which was becoming the laboratory standard. In this method, DNA to be sequenced is cut apart, and a single strand serves as a template for the synthesis of complementary strands. The nucleotides used to build these strands are randomly mixed with a radioactively labeled and modified nucleotide that terminates the synthesis. Fragments of all different lengths result. The resulting array, sent through a separation gel, reveals the order of the bases. Transferred to film, an "autoradiograph" provides a readable sequence from raw data. This data could be transferred to a computer by a human reader.

"In automating the process, Hood modified both the chemistry and the data-gathering processes. In the sequencing reaction itself, he sought to replace the use of radioactive labels, which were unstable, posed a health hazard, and required separate gels for each of the four DNA bases.

" • In place of radioisotopes, Hood developed chemistry that used fluorescent dyes of different colors—one for each of the four DNA bases. This system of "color-coding" eliminated the need to run several reactions in overlapping gels.

"The fluorescent labels were also aspects of the larger system that revolutionized the end stage of the process—the way in which sequence data was gathered. Hood integrated laser and computer technology, eliminating the tedious process of information-gathering by hand.

" • As the fragments of DNA percolated through the gel, a laser beam stimulated the fluorescent labels, causing them to glow. The light they emitted was picked up by a lens and photomultiplier, and transmitted as digital information directly into a computer" (Genome News Network, Genetics and Genomics Timeline 1989, accessed 05-25-2009).

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1990 – 2000

Expressed Sequence Tags 1991

In 1991 J. Craig Venter and colleagues at the National Institute of Health described a fast new approach to gene discovery using Expressed Sequence Tags (ESTs). Although controversial when first introduced, ESTs were soon widely employed both in public and private sector research. They proved economical and versatile, used not only for rapid identification of new genes, but also for analyzing gene expression, gene families, and possible disease-causing mutations.

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Venter Founds Celera Genomics May 1998

In May 1998 Craig Venter founded Celera Genomics, with Applera Corporation (Applied Biosystems) in Rockville, Maryland, to sequence and assemble the human genome.

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2000 – 2005

The Most Extensive Computation Undertaken in Biology to Date June 26, 2000

The Celera logo

The Human Genome Project logo

On June 26, 2000 "Celera Genomics [Rockville, Maryland] announced the first complete assembly of the human genome. Using whole genome shotgun sequencing, Celera began sequencing in September 1999 and finished in December. Assembly of the 3.12 billion base pairs of DNA, over the next six months, required some 500 million trillion sequence comparisons, and represented the most extensive computation ever undertaken in biology.

The Human Genome Project reported it had finished a “working draft” of the genome, stating that the project had fully sequenced 85 percent of the genome. Five major institutions in the United States and Great Britain performed the bulk of sequencing, together with contributions from institutes in China, France, and Germany” (Genome News Network, Genetics and Genomics Timeline 2000, accessed 05-24-2009).

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Publication of the Human Genome Sequence February 15 – February 16, 2001

Sequencing machine screen shot

"Seven months after the ceremony at the White House marking the completion of the human genome sequence, highlights from two draft sequences and analyses of the data were published in Science and Nature. Scientists at Celera Genomics and the publicly funded Human Genome Project independently found that humans have approximately 30,000 genes that carry within them the instructions for making the body's diverse collection of proteins.

"The findings cast new doubt on the old paradigm that one gene makes one protein. Rather, it appears that one gene can direct the synthesis of many proteins through mechanisms that include 'alternative splicing.' "It seems to be a matter of five or six proteins, on average, from one gene," said Victor A. McKusick of the Johns Hopkins University School of Medicine, who was a co-author of the Science paper.

"The finding that one gene makes many proteins suggests that biomedical research in the future will rely heavily on an integration of genomics and proteomics, the word coined to describe the study of proteins and their biological interactions. Proteins are markers of the early onset of disease, and are vital to prognosis and treatment; most drugs and other therapeutic agents target proteins. A detailed understanding of proteins and the genes from which they come is the next frontier.

"One of the questions raised by the sequencing of the human genome is this: Whose genome is it anyway? The answer turns out to be that it doesn't really matter. As scientists have long suspected, human beings are all very much alike when it comes to our genes. The paper in Science reported that the DNA of human beings is 99.9 percent alike—a powerful statement about the relatedness of all humankind" (Genome News Network, Genetics and Genomics Timeline 2001, accessed 05-24-2009)


Venter, J.C. et al. "The sequence of the human genome," Science 291, 1304-1351 (February 16, 2001).

Lander, E.S. et al. The Genome International Sequencing Consortium. "Initial sequencing and analysis of the human genome," Nature 409, 860-921 (February 15, 2001).

"An initial rough draft of the human genome was available in June 2000 and by February 2001 a working draft had been completed and published followed by the final sequencing mapping of the human genome on April 14, 2003. Although this was reported to be 99% of the human genome with 99.99% accuracy a major quality assessment of the human genome sequence was published in May 27, 2004 indicating over 92% of sampling exceeded 99.99% accuracy which is within the intended goal. Further analyses and papers on the HGP continue to occur. An initial rough draft of the human genome was available in June 2000 and by February 2001 a working draft had been completed and published followed by the final sequencing mapping of the human genome on April 14, 2003. Although this was reported to be 99% of the human genome with 99.99% accuracy a major quality assessment of the human genome sequence was published in May 27, 2004 indicating over 92% of sampling exceeded 99.99% accuracy which is within the intended goal. Further analyses and papers on the HGP continue to occur" (Wikipedia article on Human Genome Project, accessed 01-09-2013).

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2005 – 2010

The Genetic Code of Avian Flu Virus H5N1 is Deciphered October 5, 2005

The Armed Forces Institute of Pathology logo

Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green)

On October 5,2005 scientists at the Armed Forces Institute of Pathology announced that they deciphered the genetic code of the 1918 avian flu virus H5N1, which killed as many as 50,000,000 people worldwide, from a victim exhumed in 1997 from the Alaskan permafrost. The scientists reconstructed the virus in the laboratory and published the genetic sequence.

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Watson's Genome is Sequenced May 31, 2007

James D. Watson

An example of DNA sequencing

On May 31, 2007 the genome of James D. Watson, co-discoverer of the double-helical structure of DNA, was sequenced and presented to Watson. It was the second individual human genome to be sequenced; the first was that of J. Craig Venter, which was sequenced in the Human Genome Project, the first working draft of which was completed and published in February 2001

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2012 – 2016

The Human Genome is Packed with At Least 4,000,000 Gene Switches September 6, 2012

On September 6, 2012 ENCODE, the Encyclopedia Of DNA Elements, a project of The National Human Genome Research Institute (NHGRI) of the National Institutes of Health, involving 442 scientists from 32 laboratories around the world, published  six papers in the journal Nature and in 24 papers in Genome Research and Genome Biology.

Among the overall results of the project to date was the monumental conclusion that:

"The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches" (http://www.nytimes.com/2012/09/06/science/far-from-junk-dna-dark-matter-proves-crucial-to-health.html?pagewanted=all, accessed 09-09-2012).

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