Computing & Medicine / Biology Timeline

The anonymous author of the sensational evolutionary treatise Vestiges of the Natural History of Creation (Robert Chambers) included a lengthy quote from Babbage’s discussion of programming the Difference Engine from the Ninth Bridgewater Treatise to explain how evolutionary change might occur through time.

This was one of the earliest references to computing within the context of biology.

Long after refusing to fund the completion of Babbage’s Difference Engine No. 1, or funding construction of his Analytical Engine, the British government paid for the construction of the Scheutzes' third difference engine.  

Medical statistician William Farr first used the Engine in 1859 to print a table for his paper, published in Philosophical Transactions, “On the Construction of Life-Tables, Illustrated by a New Life-Table of the Healthy Districts of England.”

In 1864 English statistician and epidemiologist William Farr published English life table. Tables of lifetimes, annuities, and premiums. . . . Published by authority of the Registrar-General of births, deaths and marriages in England. The colophon leaf of this book indicated that 500 copies were printed. Farr's English Life Table contained, what was for its time, a tremendous amount of data— 6.5 million deaths sorted by age. Included in English Life Table no. 3 were the first lengthy working tables produced by the Scheutz printing calculator— the first instance of such a machine being used extensively to do original work. However, none of the hoped-for benefits of mechanizing the calculation of the tables were realized, since the Scheutz machine failed to include any of Babbage's security mechanisms to guard against mechanical error, and it required constant maintenance.

The machine did accomplish some of the typesetting which it stamped into sterotype plates; however, the process was so problematic that there was little cost savings from automation. Of the 600 pages of printed tables in the book, only 28 pages were composed entirely by the machine; a further 216 pages were partially composed by the machine, and the rest were typeset by hand. Nor was there the hoped-for savings from using the machine to prepare stereotype plates. Her Majesty's Stationery Office, printer of the volume, stated that having the machine set the entire book automatically would have saved only 10 percent over the cost of conventional typesetting (Swade, The Cogwheel Brain [2000] 203-8).

Pages cxxxix-cxliv contained Farr's appendix entitled "Scheutz's calculating machine and its use in the construction of the English life table no. 3," in which he emphasized the usefulness of the new machine, but also the delicacy and skill necessary for its operation:

The Machine required incessant attention. The differences had to be inserted at the proper terms of the various series, checking was required, and when the mechanism got out of order it had to be set right. Of the first watch nothing is known, but the first steam-engine was indisputably imperfect; and here we had to do with the second Calculating Machine as it came from the designs of its constructors and from the workshop of the engineer. The idea had been as beautifully embodied in metal by Mr. Bryan Donkin as it had been conceived by the genius of its inventors; but it was untried. So its work had to be watched with anxiety, and its arithmetical music had to be elicited by frequent tuning and skilful handling, in the quiet most congenial to such productions.

This volume is the result; and thus—if I may use the expression—the soul of the Machine is exhibited in a series of Tables which are submitted to the criticism of the consummate judges of this kind of work in England and in the world (p. cxl)

Farr also noted Babbage's contribution to the venture—it was Babbage who "explained the principles [of the Scheutz calculator] and first demonstrated the practicability of performing certain calculations, and printing the results by machinery" (p. xiii).

Having invested so much time and money in the project while realizing only token gains, the British government showed little patience with the Scheutz calculating machine. The General Register Office soon reverted to manual calculations by human computers employing logarithms, which they used until the GRO's conversion to mechanical calculation methods in 1911.  Hook & Norman, Origins of Cyberspace (2002) No. 85.

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.

At the U.S. Census Bureau physician John Shaw Billings, founder and librarian of the Surgeons General's Library (now the National Library of Medicine), suggested to Herman Hollerith that there ought to be a machine for speeding up the process of tabulating population and similar statistics. 

Hollerith credited Billings for inspiring him to develop electric punched card tabulating for the census of 1890.

Austrian mathematician Johann Radon, professor at Technische Universität Wien, introduced the Radon transform. He also demonstrated that the image of a three-dimensional object can be constructed from an infinite number of two-dimensional images of the object.

About sixty-five years later Radon's work was applied in the invention of computed tomography.

At the suggestion of Wallace J. Eckert of Columbia University, physical chemist Linus Pauling and associates at Caltech used IBM electric punch card tabulating equipment to speed up the Fourier calculations in crystal structure analysis in their researches. The first paper resulting from these applications was David E. Hughes, "The Crystal Structure of Melamine," J. Amer. Chem. Soc. 63 (1941) 1737-52. 

Prior to this Leslie J. Comrie had attempted to introduce IBM Hollerith electric punched card tabulating to speed up Fourier calculations in crystal structure analysis in England, but the method did not gain acceptance.

Applications of IBM equipment in crystallographic research continued at Caltech but the method was not published until 1946:

Shaffer, Philip. A., Jr.; Schomaker, Verner; and Pauling, Linus  The use of punched cards in molecular structure determinations. I. Crystal structure calculations [II. Electron diffraction calculations], Journal of Chemical Physics 14 (1946) 648–658, 659–664.  The offprint version of the first paper contained a 10-page supplement with 5 full-age diagrams.

"Shaffer, Schomaker, and Pauling developed methods of carrying out Fourier calculations on IBM punched-card machines, using a Type 11 electric keypunch, a Type 80 electric sorting machine, and a Type 405 alphabetic direct-subtraction tabulating machine. This paper cites work as early as 1941 performed on the structure of various less-complex organic crystals using electric tabulation methods.

The supplement to Part I of this paper, which was included only in the offprint version, provided additional information on card design, plugboard wiring and operating procedures. 'The time factor is in all cases greatly in favor of the punched-card method relative to summation procedures used in the past. Fourier projections which by the Beevers-Lipson method required several days of calculation can now be made in 5 to 7 hours. At the same time the density of calculated points is much greater and the accuracy of the computation is assured. The machine steps in the least-squares calculations require only a few hours, as compared to one or two days with use of an adding machine, and again the accuracy of the work is assured. With the use of parameter cards and the structure-factor files the calculation of structure factors can be accomplished in about one-eighth of the time previously required.' (p. 658). Most of the detail in the technique of data processing, including information on card design, plugboard wiring, and operating procedures appears in the supplement" (Hook & Norman, Origins of Cyberspace [2002] no. 879).

Cranswick, "Busting out of crystallography’s Sisyphean prison: from pencil and paper to structure solving at the press of a button: past, present and future of crystallographic software development, maintenance and distribution," Acta Crystallographica Section A Foundations of Crystallography A64 (2008) 65-87. (Accessed 04-20-2010).

American neurophysiologist and cybernetician of the University of Illinois at Chicago Warren McCulloch and logician Walter Pitts published “A Logical Calculus of the ideas Imminent in Nervous Activity,” describing the McCulloch - Pitts neuron, the first mathematical model of a neural network.

Building on ideas in  Alan Turing’s “On Computable Numbers”, McCulloch and Pitts's paper provided a way to describe brain functions in abstract terms, and showed that simple elements connected in a neural network can have immense computational power. The paper received little attention until its ideas were applied by John von Neumann, Norbert Wiener, and others. (See Reading 7.4.)

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, 33-34).

In 1948 mathematician Norbert Wiener at MIT published Cybernetics or Control and Communication in the Animal and the Machine, a widely circulated and influential book that applied theories of information and communication to both biological systems and machines. Computer-related words with the “cyber” prefix, including "cyberspace," originate from Wiener’s book. Cybernetics was also the first conventionally published book to discuss electronic digital computing. Writing as a mathematician rather than an engineer, Wiener’s discussion was theoretical rather than specific. Strangely the first edition of the book was published in English in Paris at the press of Hermann et Cie. The first American edition was printed offset from the French sheets and issued by John Wiley in New York, also in 1948. I have never seen an edition printed or published in England. 

Independently of Claude Shannon, Wiener conceived of communications engineering as a brand of statistical physics and applied this viewpoint to the concept of information. Wiener's chapter on "Time series, information, and communication" contained the first publication of Wiener's formula describing the probability density of continuous information. This was remarkably close to Shannon's formula dealing with discrete time published in A Mathematical Theory of Communication (1948). Cybernetics also contained a chapter on "Computing machines and the nervous system." This was a theoretical discussion, influenced by McCulloch and Pitts, of differences and similarities between information processing in the electronic computer and the human brain. It contained a discussion of the difference between human memory and the different computer memories then available. Tacked on at the end of Cybernetics were speculations by Wiener about building a chess-playing computer, predating Shannon's first paper on the topic.

Cybernetics is a peculiar, rambling blend of popular and highly technical writing, ranging from history to philosophy, to mathematics, to information and communication theory, to computer science, and to biology. Reflecting the amazingly wide range of the author's interests, it represented an interdisciplinary approach to information systems both in biology and machines. It influenced a generation of scientists working in a wide range of disciplines. In it were the roots of various elements of computer science, which by the mid-1950s had broken off from cybernetics to form their own specialties. Among these separate disciplines were information theory, computer learning, and artificial intelligence.

It is probable that Wiley had Hermann et Cie supervise the typesetting because they specialized in books on mathematics.  Hermann printed the first edition by letterpress; the American edition was printed offset from the French sheets. Perhaps because the typesetting was done in France Wiener did not have the opportunity to read proofs carefully, as the first edition contained many typographical errors which were repeated in the American edition, and which remained uncorrected through the various printings of the American edition until a second edition was finally published by John Wiley and MIT Press in 1961. 

Though the book contained a lot of technical mathematics, and was not written for a popular audience, the first American edition went through at least 5 printings during 1948,  and several later printings, most of which were probably not read in their entirety by purchasers. Sales of Wiener's book were helped by reviews in wide circulation journals such as the review in TIME Magazine on December 27, 1948, entitled "In Man's Image." The reviewer used the word calculator to describe the machines; at this time the word computer was reserved for humans.

"Some modern calculators 'remember' by means of electrical impulses circulating for long periods around closed circuits. One kind of human memory is believed to depend on a similar system: groups of neurons connected in rings. The memory impulses go round & round and are called upon when needed. Some calculators use 'scanning' as in television. So does the brain. In place of the beam of electrons which scans a television tube, many physiologists believe, the brain has 'alpha waves': electrical surges, ten per second, which question the circulating memories.

"By copying the human brain, says Professor Wiener, man is learning how to build better calculating machines. And the more he learns about calculators, the better he understands the brain. The cyberneticists are like explorers pushing into a new country and finding that nature, by constructing the human brain, pioneered there before them.

"Psychotic Calculators. If calculators are like human brains, do they ever go insane? Indeed they do, says Professor Wiener. Certain forms of insanity in the brain are believed to be caused by circulating memories which have got out of hand. Memory impulses (of worry or fear) go round & round, refusing to be suppressed. They invade other neuron circuits and eventually occupy so much nerve tissue that the brain, absorbed in its worry, can think of nothing else.

"The more complicated calculating machines, says Professor Wiener, do this too. An electrical impulse, instead of going to its proper destination and quieting down dutifully, starts circulating lawlessly. It invades distant parts of the mechanism and sets the whole mass of electronic neurons moving in wild oscillations" (http://www.time.com/time/magazine/article/0,9171,886484-2,00.html, accessed 03-05-2009).

Presumably the commercial success of Cybernetics encouraged Wiley to publish Berkeley's Giant Brains, or Machines that Think in 1949.

♦ In October 2012 I offered for sale the copy of the first American printing of Cybernetics that Wiener inscribed to Jerry Wiesner, the head of the laboratory at MIT where Wiener conducted his research. This was the first inscribed copy of the first edition (either the French or American first) that I had ever seen on the market, though the occasional signed copy of the American edition did turn up. Having read our catalogue description of that item, my colleague Arthur Freeman emailed me this story pertinent to Wiener's habit of not inscribing books:

"Norbert, whom I grew up nearby (he visited our converted barn in Belmont, Mass., constantly to play frantic theoretical blackboard math with my father, an economist/statistician at MIT, which my mother, herself a bit better at pure math, would have to explain to him later), was a notorious cheapskate. His wife once persuaded him to invite some colleagues out for a beer at the Oxford Grill in Harvard Square, which he did, and after a fifteen-minute sipping session, he got up to go, and solemnly collected one dime each from each of his guests. So when *Cybernetics* appeared on the shelves of the Harvard Coop Bookstore, my father was surprised and flattered that Norbert wanted him to have an inscribed copy, and together they went to Coop, where Norbert duly picked one out, wrote in it, and carried it to the check-out counter--where he ceremoniously handed it over to my father to pay for. This was a great topic of family folklore. I wonder if Jerry Wiesner paid for his copy too?"

At the Hixon Symposium in Pasadena, California, John von Neumann spoke on The General and Logical Theory of Automata. Within this speech von Neumann compared the functions of genes to self-reproducing automata.  This was the first of a series of five works (some posthumous) in which von Neumann attempted to develop a precise mathematical theory allowing comparison of computers and the human brain.

“For instance, it is quite clear that the instruction I is roughly effecting the functions of a gene. It is also clear that the copying mechanism B performs the fundamental act of reproduction, the duplication of the genetic material, which is clearly the fundamental operation in the multiplication of living cells. It is also easy to see how arbitrary alterations of the system E, and in particular of I, can exhibit certain typical traits which appear in connection with mutation, which is lethality as a rule, but with a possibility of continuing reproduction with a modification of traits.” (pp. 30-31).

Molecular biologist Sydney Brenner read this brief discussion of the gene within the context of information in the proceedings of the Hixon Symposium, published in 1951. Later he wrote about in his autobiography:

“The brilliant part of this paper in the Hixon Symposium is his description of what it takes to make a self-reproducing machine. Von Neumann shows that you have to have a mechanism not only of copying the machine, but of copying the information that specifies the machine. So he divided the machine--the automaton as he called it--into three components; the functional part of the automaton, a decoding section which actually takes a tape, reads the instructions and builds the automaton; and a device that takes a copy of this tape and inserts it into the new automaton. . . . I think that because of the cultural differences between most biologists on the one hand, and physicists and mathematicians on the other, it had absolutely no impact at all. Of course I wasn’t smart enough to really see then that this is what DNA and the genetic code was all about. And it is one of the ironies of this entire field that were you to write a history of ideas in the whole of DNA, simply from the documented information as it exists in the literature--that is, a kind of Hegelian history of ideas--you would certainly say that Watson and Crick depended upon von Neumann, because von Neumann essentially tells you how it’s done. But of course no one knew anything about the other. It’s a great paradox to me that in fact this connection was not seen” (Brenner, My Life, 33-36).

Physician and medical librarian at Johns Hopkins in Baltimore, Sanford Larkey, published The Army Medical Library Research Project at the Welch Medical Library. This was one of the earliest projects in library automation and information retrieval. 

At the second English computer conference held in Manchester, computer programmer J. M. Bennett and biochemist and crystallographer John Kendrew described their use of the Cambridge EDSAC for the computation of Fourier syntheses in the calculation of structure factors of the protein molecule myoglobin.

This was the first application of an electronic computer to computational biology or structural biology. The first published account of this research appeared in the very scarce Manchester University Computer Conference Proceedings (1951). (See Reading 10.3.)

Kendrew and Bennett formally published an extended version of their paper as "The Computation of Fourier Syntheses with a Digital Electric Calculating Machine," Acta Crystallographica 5 (1952) 109-116. Hook & Norman, Origins of Cyberspace (2002) nos. 744 & 745.

In 1962 Kendrew received the Nobel Prize in chemistry for his discovery of the 3-dimensional molecular structure of myoglobin, the first protein molecule to be "solved."

Russian-born 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, Eighth Day of Creation).

William H. Sweet and Gordon L. Brownell at Massachusetts General Hospital, Boston, described the first positron imaging device, and and the first attempt to record three dimensional data in positron detection in their paper entitled "Localization of brain tumors with positron emitters',' Nucleonics XI (1953) 40-45. This was the beginning of positron emission tomography (PET).

"Despite the relatively crude nature of this imaging instrument, the brain images were markedly better than those obtained by other imaging devices. It also contained several features that were incorporated into future positron imaging devices. Data were obtained by translation of two opposed detectors using coincidence detection with mechanical motion in two dimensions and a printing mechanism to form a two-dimensional image of the positron source. This was our first attempt to record three-dimensional data in positron detection" (Brownell, A History of Positron Imaging [1999], accessed 12-25-2008)

English psychiatrist and cybernetician W[illiam] Ross Ashby wrote of intelligence amplification by machines in his book, Introduction to Cybernetics.

The First International Congress on Cybernetics was held in Namur, Belgium. Few, if any, of the computer pioneers attended.  By this time the field of cybernetics was separated from those of computing and artificial intelligence to emphasize issues of control and communication in learning, automation, and biology.

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)

In 1958 and 1960 molecular biologist John Kendrew published  "A Three-Dimensional Model of the Myoglobin Molecule Obtained by X-ray Analysis" (with G. Bodo, H. M. Dintzis, R. G. Parrish, H. Wyckoff,) Nature 181 (1958) 662-666, and "Structure of Myoglobin: A Three-Dimensional Fourier synthesis at 2 Å Resolution" (with R. E. Dickerson, B. E. Strandberg, R. G. Hart, D. R. Davies, D. C. Phillips, V. C. Shore). Nature 185 (1960) 422-27.

These papers recorded the first solution of the three-dimensional molecular structure of a protein, for which Kendrew received the 1962 Nobel Prize in chemistry, together with his friend and colleague Max Perutz, who solved the structure of the related and more complex protein, hemoglobin, two years after Kendrew’s achievement. 

Understanding the means of storing the genetic information in the cell nucleus, and the means of transferring the genetic information (the double helical structure of DNA, messenger RNA, the genetic code), solving the structure of proteins which construct themselves following instructions from the nucleus, and recombinant DNA and its applications in genetic engineering, remain central elements of molecular biology. Today roughly 100,000 people worldwide are involved in scientific research solving the structure of proteins, which evolved out of Kendrew’s and Perutz’s pioneering work.  

Kendrew began his investigation into the structure of myoglobin in 1949, choosing this particular protein because it was “of low molecular weight, easily prepared in quantity, readily crystallized, and not already being studied by X-ray methods elsewhere” (Kendrew, “Myoglobin and the structure of proteins. Nobel Prize Lecture [1962],” pp. 676-677). Protein molecules, which contain, at minimum, thousands of atoms, have enormously convoluted and irregular formations that are extremely difficult to elucidate. In the 1930s J. D. Bernal, Dorothy Hodgkin and Max Perutz performed the earliest crystallographic studies of proteins at Cambridge’s Cavendish Laboratory; however, the intricacies of three-dimensional structure of proteins were too complex for analysis by conventional X-ray crystallography, and the process of calculating the structure factors by slide-rules and electric calculators was far too slow. It was not until the late 1940s, when Kendrew joined the Cavendish Laboratory as a graduate student, that new and more sophisticated tools emerged that could be used to attack the problem. The first of these tools was the technique of isomorphous replacement, developed by Perutz during his own researches on hemoglobin, in which certain atoms in a protein molecule are replaced with heavy atoms. When these modified molecules are subjected to X-ray analysis the heavy atoms provide a frame of reference for comparing diffraction patterns. The second tool was the electronic computer, which Kendrew introduced to computational biology in 1951. The first electronic computer, the ENIAC, which became operational in Philadelphia in 1945, was 10,000 times the speed of a human performing a calculation. In 1951 Cambridge University was one of only three or four places in the world with a high-speed stored-program electronic computer, and Kendrew took full advantage of the speed of Cambridge’s EDSAC computer, and its more powerful successors, to execute the complex mathematical calculations required to solve the structure of myoglobin. Kendrew was the first to apply an electronic computer to the solution of a complex problem in biology.

Nevertheless, even with the EDSAC computer performing the calculations, the research progressed remarkably slowly. Only by the summer of 1957 did Kendrew and his team succeed in creating a three-dimensional map of myoglobin at a resolution the so-called “low resolution”of 6 angstroms; thus myoglobin became “the first protein to be solved” (Judson, p. 538).

“A cursory inspection of the map showed it to consist of a large number of rod-like segments, joined at the ends, and irregularly wandering through the structure; a single dense flattened disk in each molecule; and sundry connected regions of uniform density. These could be identified respectively with polypeptide chains, with the iron atom and its associated porphyrin ring, and with the liquid filling the interstices between neighboring molecules. From the map it was possible to ‘dissect out’ a single protein molecule . . . The most striking features of the molecule were its irregularity and its total lack of symmetry” (Kendrew, “Myoglobin,” p. 681).  

The 6-angstrom resolution was too low to show the molecule’s finer features, but by 1960 Kendrew and his team were able to obtain a map of the molecule at 2-angstrom resolution. “To achieve a resolution of 2 Å it was necessary to determine the phases of nearly 10,000 reflections, and them to compute a Fourier synthesis with the same number of terms . . . the Fourier synthesis itself (excluding preparatory computations of considerable bulk and complexity) required about 12 hours of continuous computation on a very fast machine (EDSAC II)” (Kendrew, “Myoglobin,” p. 682).

Robert S. Ledley and Lee B. Lusted published "Reasoning Foundations of Medical Diagnosis," Science, 130, no. 3366, 9-21.

This was highly influential in the development of clinical decision support systems (CDSS) — interactive computer programs, or expert systems, designed to assist physicians and other health professionals with decision making tasks.

Electrical engineer Wilson Greatbatch and Drs. William Chardack and Andrew Gage of the University at Buffalo reported the success of the first successful long-term implant in a human patient of a self-contained, internally powered artificial pacemaker in their paper entitled A Transistorized, Self-contained, Implantable Pacemaker for the Long-term Correction of Complete Heart Block. (U. S. patent no. 3,057,356).

The first symposium on bionics (biological electronics) took place at Wright-Patterson Air Force Base in Ohio. (See Reading 11.7.)

At Cambridge 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.

Francis Crick, L. Barnett, Sydney. Brenner and R. J. Watts-Tobin, “General Nature of the Genetic code for Proteins,” Nature 192 (1961): 122732.

“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).

In work initiated at the University of Cape Town and Groote Schuur Hospital in early 1956, and continued briefly in mid-1957, South African-born American physicist Allen M. Cormack showed that changes in tissue density could be computed from x-ray data. His results were subsequently published in two papers:

"Representation of a Function by its Line Integrals, with Some Radiological Applications," Journal of Applied Physics 34 (1963) 2722-27; "Representation of a Function by its Line Integrals, with Some Radiological Applications. II,"  Journal of Applied Physics 35 (1964) 2908-13.  

No machine was constructed at this time because of limitations in computing power, and these papers generated little interest until Godfrey Hounsfield and colleagues invented computed tomography, and built the first CT scanner in 1971, taking Cormack's theoretical calculations into a real application.

Medical Literature Analysis and Retrieval System (MEDLARS) was operational at the National Library of Medicine, Bethesda, Maryland.

MEDLARS was the first large scale, computer-based, retrospective search service available to the general public.

Texas Instruments in partnership with Zenith Radio introduced the first consumer product containing an integrated circuit— a hearing aid.

English molecular biologist Aaron Klug at the University of Cambridge formulated a method for digital image processing of two-dimensional images.

A. Klug and D. J. de Rosier, “Optical filtering of electron micrographs: Reconstruction of one-sided images,” Nature 212 (1966): 2932.

Using the Project MAC, an early time-sharing system at MIT, Cyrus Levinthal built the first system for the interactive display of molecular structures. 

"This program allowed the study of short-range interaction between atoms and the "online manipulation" of molecular structures. The display terminal (nicknamed Kluge) was a monochrome oscilloscope (figures 1 and 2), showing the structures in wireframe fashion (figures 3 and 4). Three-dimensional effect was achieved by having the structure rotate constantly on the screen. To compensate for any ambiguity as to the actual sense of the rotation, the rate of rotation could be controlled by globe-shaped device on which the user rested his/her hand (an ancestor of today's trackball). Technical details of this system were published in 1968 (Levinthal et al.). What could be the full potential of such a set-up was not completely settled at the time, but there was no doubt that it was paving the way for the future. Thus, this is the conclusion of Cyrus Levinthal's description of the system in Scientific American (p. 52):

It is too early to evaluate the usefulness of the man-computer combination in solving real problems of molecular biology. It does seems likely, however, that only with this combination can the investigator use his "chemical insight" in an effective way. We already know that we can use the computer to build and display models of large molecules and that this procedure can be very useful in helping us to understand how such molecules function. But it may still be a few years before we have learned just how useful it is for the investigator to be able to interact with the computer while the molecular model is being constructed.

"Shortly before his death in 1990, Cyrus Levinthal penned a short biographical account of his early work in molecular graphics. The text of this account can be found here."

You can watch a six minute film produced with the interactive molecular graphics and modeling system devised by Cyrus Levinthal and his collaborators in the mid-1960s at this link.

English molecular biologist Aaron Klug described techniques for the reconstruction of three-dimensional structures from electron micrographs, thus founding the processing of three-dimensional digital images.

D. J. de Rosier and A. Klug, “Reconstruction of three dimensional structures from electron micrographs,” Nature 217 (1968) 13034.

English electrical engineer Godfrey Hounsfield at EMI's Central Research Laboratories in Hayes, Middlesex, invented computed tomography (CT), the first application of computers to medical imaging.

Armenian-American medical practitioner and inventor Raymond V. Damadian filed a patent for "An Apparatus and Method for Detecting Cancer in Tissue."

Damadian's patent 3,789,832 was granted on February 5, 1974. This was the first patent filed on the use of Nuclear Magnetic Resonance for scanning the human body, but it did not not describe a method for generating pictures from such a scan or precisely how such a scan might be achieved.

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

American chemist Paul Lauterbur, working at the State University of New York at Stony Brook, developed a way to generate the first Magnetic Resonance Images (MRI), in 2D and 3D, using gradients.

Lauterbur described an imaging technique that removed the usual resolution limits due to the wavelength of the imaging field. He used

"two fields: one interacting with the object under investigation, the other restricting this interaction to a small region. Rotation of the fields relative to the object produces a series of one-dimensional projections of the interacting regions, from which two- or three-dimensional images of their spatial distribution can be reconstructed" (http://www.nature.com/physics/looking-back/lauterbur/index.html, accessed 11-23-2008).

This was the beginning of magnetic reasonance imaging.

"When Lauterbur first submitted his paper with his discoveries to Nature, the paper was rejected by the editors of the journal. Lauterbur persisted and requested them to review it again, upon which time it was published and is now acknowledged as a classic Nature paper.  The Nature editors pointed out that the pictures accompanying the paper were too fuzzy, although they were the first images to show the difference between heavy water and ordinary water. Lauterbur said of the initial rejection: 'You could write the entire history of science in the last 50 years in terms of papers rejected by Science or Nature' (Wikipedia article on Paul Lauterbur, accessed 03-08-2012).

Lauterbur, Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance, Nature 242 (1973), 190–191.

♦ Lauterbur's Nobel Lecture is available from the Nobel website. You can also watch a 65 minute video of Lauterbur delivering the lecture from this link.

American dentist and biophysicist Robert S. Ledley of Georgetown University developed the ACTA 0100 CT Scanner (Automatic Computerized Traverse Axial)— the first whole-body computed tomography scanner. 

"This machine had 30 photomultiplier tubes as detectors and completed a scan in only 9 translate/rotate cycles, much faster than the EMI-scanner. It used a DEC PDP11/34 minicomputer both to operate the servo-mechanisms and to acquire and process the images. The Pfizer drug company acquired the prototype from the university, along with rights to manufacture it. Pfizer then began making copies of the prototype, calling it the "200FS" (FS meaning Fast Scan), which were selling as fast as they could make them. This unit produced images in a 256x256 matrix, with much better definition than the EMI-Scanner's 80" (Wikipedia article on Computed Tomography, accessed 04-15-2009).

Ledley RS, Di Chiro G, Luessenhop AJ, Twigg HL. "Computerized transaxial x-ray tomography of the human body," Science 186, No. 4160 (1974) 207-212.

Computer scientist Jacques J. Vidal of UCLA coined the term brain-computer interface (BCI) in his paper "Toward Direct Brain-Computer Communication," Annual Review of Biophysics and Bioengineering 2: 157–80. doi:10.1146/annurev.bb.02.060173.001105. PMID 4583653.

Records, Computers, and the Rights of Citizens was published. This was the report of the Advisory Committee on Automated Personal Data Systems appointed by Elliot L. Richardson, secretary of the Department of Health, Education and Welfare. The report explored the impact of computerized record keeping on individuals, and recommended a Code of Fair Information Prractice, consisting of five basic principles:

1."There must be no data record-keeping systems whose very existence is secret." 

2."There must be a way for an individual to find out what information about him is in a record and how it is used."

3."There must be a way for an individual to prevent information about him obtained for one purpose from being used or made available for other purposes without his consent." 

4. "There must be a way for an individual to correct or amend a record of identifiable information about him."

5. "Any organization creating, maintaining, using or disseminating records of identifiable personal data must assure the reliability of the data for their intended use and must take reasonable precautions to prevent misuse of the data."

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

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).

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.

Walter Gilbert and Allan M. Maxam devised a technique for sequencing DNA.

“The Gilbert-Maxam method involved multiplying, dividing, and carefully fragmenting DNA. A stretch of DNA would be multiplied a millionfold in bacteria. Each strand was radioactively labeled at one end. Nested into four groups, chemical reagents were applied to selectively cleave the DNA strand along its bases--adenine (A), guanine (G), cytosine (C) and thymine (T). Carefully dosed, the reagents would break the DNA into a large number of smaller fragments of varying length. In gel electrophoresis, as a function of DNA’s negative charge, the strands would separate according to length, revealing, via the terminal points of breakage, the position of each base.”

Frederick Sanger and colleagues at the University of Cambridge independently developed the methods 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, F., Nicklen, S., and Coulson, A.R. "DNA Sequencing with Chain-Terminating Inhibitors," Proc. Nat. Acad. Sci. (USA) 74 (1977) 546-67.

British physicist Peter Mansfield developed a mathematical technique that would allow NMR scans to take seconds rather than hours and produce clearer images than the technique  Paul Lauterbur developed in 1973.

Mansfield showed how gradients in the magnetic field could be mathematically analysed, which made it possible to develop a useful nuclear magnetic resonance imaging technique. Mansfield also showed how extremely fast imaging could be achievable. This became technically possible a decade later.

P Mansfield and A A Maudsley, Medical imaging by NMR, Brit. J. Radiol. 50 (1977) 188.
P Mansfield, Multi-planar imaging formation using NMR spin echoes J. Physics C. Solid State Phys. 10 (1977) L55–L58.

The references from Mansfield's Nobel Lecture. You can also watch a 64 minute video of Mansfield delivering his lecture at this link.

The science fiction film Blade Runner, starring Harrison Ford and directed by Ridley Scott, loosely based on the novel Do Androids Dream of Electric Sheep? by Philip K. Dick, depicted a dreary, rainy, and polluted Los Angeles in 2019. In the film genetically manufactured, bioengineered biorobots called replicants—visually indistinguishable from adult humans—are used for dangerous and degrading work in Earth's "off-world colonies."  After a minor replicant uprising, replicants are banned on Earth; and specialist police units called "blade runners" are trained to hunt down and "retire" (kill) escaped replicants on Earth.

The film, which  became a cult classic for many reasons, including its unique sets, lighting, costumes and visual effects, is considered the last great science fiction film in which the special effects were produced entirely through analog, rather than digital or computer graphics methods, using elaborate model-making, multiple exposures, etc.

Scott's original director's cut of the film was first issued as a DVD in 1999. In 2007 the so-called "Final Cut" with a great deal of supplementary material, including three previous versions of the film, and a "definitive" documentary, even longer than the original film, was issued on DVD, HD-DVD and Blue-ray. The documentary, and the collection of versions of the film, present a superb opportunity to gain insight into way that Ridley Scott creates a film.

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, “Nucleotide Sequence of Bacteriophage Lambda,” J. Mol. Biol. 162 (1982) 729-73.

In 1982 Vision: A Computational Investigation into the Human Representation and Processing of Visual Information by the British neuroscientist David Marr, a professor at MIT, was published posthumously in New York. This work defined a general framework for studying complex biological systems.

"According to Marr, a complex biological system can be understood at three distinct levels. The first level ("computational level") describes the input and output to the system, which define the task the system is performing. In the case of the visual system, the input might be the image projected on our retina and the output might our brain's identification of the objects present in the image we had observed. The second level ("algorithmic level") describes the procedure by which an input is converted to an output, i.e. how the image on our retina can be processed to achieve the task described by the computational level. Finally, the third level ("implementation level") describes how our own biological hardware of cells implements the procedure described by the algorithmic level" (Yarden Katz, "Noam Chomsky on Where Artificial Intelligence Went Wrong," Atlantic Monthly, 11-1-2012).

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.

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).

J. G. White, E. Southgate, J. N. Thomson and S[idney] Brenner published "The Structure of the nervous System of the Nematode Caenorhabditis elegans," Philosophical Transactions B: Biological Sciences, 314 (1986) no. 1165, 1-340. The first map of the functioning structure of an entire brain at the cellular level, this paper has been called the beginning of connectomics.

"The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with similar morphologies and connectivities have been grouped together into classes; there are 118 such classes. Neurons have simple morphologies with few, if any, branches. Processes from neurons run in defined positions within bundles of parallel processes, synaptic connections being made en passant. Process bundles are arranged longitudinally and circumferentially and are often adjacent to ridges of hypodermis. Neurons are generally highly locally connected, making synaptic connections with many of their neighbours. Muscle cells have arms that run out to process bundles containing motoneuron axons. Here they receive their synaptic input in defined regions along the surface of the bundles, where motoneuron axons reside. Most of the morphologically identifiable synaptic connections in a typical animal are described. These consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions" (Abstract).

Applied Biosystems, Foster City, California, marketed the first commercial DNA sequencing machine, based on Leroy Hood’s technology.

Formal proposals were made by the Department of Energy in US to sequence the human genome. It was estimated that one worker could produce about 50,0000 bases of finished DNA sequence per year at a cost of about $1-$2 per base. Based on these costs, the human genome would take 60,000 person-years and cost $36 billion to complete.

Recognizing the importance of computerized information processing methods for the conduct of biomedical research, Senator and Representative Claude Pepper sponsored legislation that established the National Center for Biotechnology Information (NCBI) as a division of the National Library of Medicine (NLM), Bethesda, Maryland. NLM was chosen for its experience in creating and maintaining biomedical databases, and because as part of NIH, it could establish an intramural research program in computational molecular biology. 

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.

J. Craig Venter left the National Institutes of Health and founded The Institute for Genomic Research (TIGR), Rockville, Maryland.

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

IBM announced the start of a five-year effort to build a massively parallel computer, Blue Gene, which was 500 times more powerful than the world’s fastest computers at the time of the announcement.

Initially Blue Gene was applied to the study of bio-molecular phenomena such as protein folding.

"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).

IBM formed a Life Sciences Solutions division, incorporating its Computational Biology Center.

"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)

References:

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).

The National Science Foundation funded research headed by Gabor Forgacs at the University of Missouri-Columbia on what was called "Organ Printing," to "further advance our understanding of self-assembly during the organization of cells and tissues into functional organ modules."

From ABC News 2-10-2006:

"In what could be the first step toward human immortality, scientists say they've found a way to do all of these things and more with the use of a technology found in many American homes: an ink-jet printer.

"Researchers around the world say that by using the technology, they can actually 'print' living human tissue and one day will be able to print entire organs.

" 'The promise of tissue engineering and the promise of 'organ printing' is very clear: We want to print living, three-dimensional human organs,' Dr. Vladimir Mironov said. 'That's our goal, and that's our mission.' "

"Though the field is young, it already has a multitude of names.

" 'Some people call this 'bio-printing.' Some people call this 'organ printing.' Some people call this 'computer-aided tissue engineering.' Some people call this 'bio-manufacturing,' said Mironov, associate professor at the Medical University of South Carolina and one of the leading researchers in the field."

Scientists at the Armed Forces Institute of Pathology 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. They reconstructed the virus in the laboratory and published the genetic sequence.

Dirk Brockmann, a theoretical physicist and computational epidemiologist at Northwestern University in Evanston, Illinois, L. Hufnagel, and T. Geisel published "The scaling laws of human travel," Nature 439 (2006) 46265. 

Using statistical data from the American currency tracking website, Where's George?, the paper described statistical laws of human travel in the United States, and developed a mathematical model of the spread of infectious disease.

[By January 31, 2009, Where's George? tracked over 149 million bills totaling more than $810 million. (Wikipedia).]

At Siggraph2006, held in Boston, Massachusetts, BioVisions, a scientific visualization program at Harvard’s Department of Molecular and Cellular Biology, and Xvivo, a Connecticut-based scientific animation company, introduced the three-minute molecular animation video, The Inner Life of the Cell.

The film depicted marauding white blood cells attacking infections in the body. 

A technology developed at Keio University, Tokyo, Japan, carried with it the possibility that bacterial DNA could be used as a medium for storing digital information long-term—potentially thousands of years.

"Keio University Institute for Advanced Biosciences and Keio University Shonan Fujisawa Campus announced the development of the new technology, which creates an artificial DNA that carries up to more than 100 bits of data within the genome sequence, according to the JCN Newswire. The universities said they successfully encoded "e= mc2 1905!" -- Einstein's theory of relativity and the year he enunciated it -- on the common soil bacteria,  Bacillius subtilis."

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.

Timothy J. Ley and numerous collaborators from different countries published in the journal Nature, DNA sequencing of a cytogenetically normal acute myeloid luekaemia genome.

This was first time that researchers decoded all the genes of a person with cancer and found a set of mutations that might have caused the disease or aided its progression. The New York Times online reported:

"Using cells donated by a woman in her 50s who died of leukemia, the scientists sequenced all the DNA from her cancer cells and compared it to the DNA from her own normal, healthy skin cells. Then they zeroed in on 10 mutations that occurred only in the cancer cells, apparently spurring abnormal growth, preventing the cells from suppressing that growth and enabling them to fight off chemotherapy.

"The findings will not help patients immediately, but researchers say they could lead to new therapies and would almost certainly help doctors make better choices among existing treatments, based on a more detailed genetic picture of each patient’s cancer. Though the research involved leukemia, the same techniques can also be used to study other cancers."

Google.org unveiled Google Flu Trends, using aggregated Google search data to estimate flu activity up to two weeks faster than traditional flu surveillance systems.

"Each week, millions of users around the world search for online health information. As you might expect, there are more flu-related searches during flu season, more allergy-related searches during allergy season, and more sunburn-related searches during the summer. You can explore all of these phenomena using Google Trends. But can search query trends provide an accurate, reliable model of real-world phenomena?

"We have found a close relationship between how many people search for flu-related topics and how many people actually have flu symptoms. Of course, not every person who searches for "flu" is actually sick, but a pattern emerges when all the flu-related search queries from each state and region are added together. We compared our query counts with data from a surveillance system managed by the U.S. Centers for Disease Control and Prevention (CDC) and discovered that some search queries tend to be popular exactly when flu season is happening. By counting how often we see these search queries, we can estimate how much flu is circulating in various regions of the United States.

"During the 2007-2008 flu season, an early version of Google Flu Trends was used to share results each week with the Epidemiology and Prevention Branch of the Influenza Division at CDC. Across each of the nine surveillance regions of the United States, we were able to accurately estimate current flu levels one to two weeks faster than published CDC reports" (Google Flu Trends website).

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. This 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)

Ross D. King, Jem Rowland and 11 co-authors from the Department of Computer Science at Aberystwyth University, Aberystwyth, Wales, and the University of Cambridge, published "The Automation of Science," Science 3 April 2009: Vol. 324. no. 5923, pp. 85 - 89 DOI: 10.1126/science.1165620.

They described a Robot Scientist which the researchers believed was the first machine to have independently discovered new scientific knowledge. The robot, called Adam, was a computer system that fully automated the scientific process. 

"Prof Ross King, who led the research at Aberystwyth University, said: 'Ultimately we hope to have teams of human and robot scientists working together in laboratories'. The scientists at Aberystwyth University and the University of Cambridge designed Adam to carry out each stage of the scientific process automatically without the need for further human intervention. The robot has discovered simple but new scientific knowledge about the genomics of the baker's yeast Saccharomyces cerevisiae, an organism that scientists use to model more complex life systems. The researchers have used separate manual experiments to confirm that Adam's hypotheses were both novel and correct" (http://www.eurekalert.org/pub_releases/2009-04/babs-rsb032709.php).

"The basis of science is the hypothetico-deductive method and the recording of experiments in sufficient detail to enable reproducibility. We report the development of Robot Scientist "Adam," which advances the automation of both. Adam has autonomously generated functional genomics hypotheses about the yeast Saccharomyces cerevisiae and experimentally tested these hypotheses by using laboratory automation. We have confirmed Adam's conclusions through manual experiments. To describe Adam's research, we have developed an ontology and logical language. The resulting formalization involves over 10,000 different research units in a nested treelike structure, 10 levels deep, that relates the 6.6 million biomass measurements to their logical description. This formalization describes how a machine contributed to scientific knowledge" (Abstract in Science).

Dirk Brockmann, and the epidemic modeling team at the Northwestern Institute on Complex Systems, used air traffic and commuter traffic patterns for the entire country, and data from the American currency tracking website, Where’s George?, to predict the spread of the H1N1 flu or "swine flu" across the United States.

Bioengineer Stephen R. Quake of Stanford University invented a new technology for decoding DNA that could sequence a human genome at a cost of $50,000.

"Dr. Quake’s machine, the Heliscope Single Molecule Sequencer, can decode or sequence a human genome in four weeks with a staff of three people. The machine is made by a company he founded, Helicos Biosciences, and costs 'about $1 million, depending on how hard you bargain,' he said.

"Only seven human genomes have been fully sequenced. They are those of J. Craig Venter, a pioneer of DNA decoding; James D. Watson, the co-discoverer of the DNA double helix; two Koreans; a Chinese; a Yoruban; and a leukemia victim. Dr. Quake’s seems to be the eighth full genome, not counting the mosaic of individuals whose genomes were deciphered in the Human Genome Project."

"For many years DNA was sequenced by a method that was developed by Frederick Sanger in 1975 and used to sequence the first human genome in 2003, at a probable cost of at least $500 million. A handful of next-generation sequencing technologies are now being developed and constantly improved each year. Dr. Quake’s technology is a new entry in that horse race.

"Dr. Quake calculates that the most recently sequenced human genome cost $250,000 to decode, and that his machine brings the cost to less than a fifth of that.

“ 'There are four commercial technologies, nothing is static and all the platforms are improving by a factor of two each year,' he said. 'We are about to see the floodgates opened and many human genomes sequenced.'

"He said the much-discussed goal of the $1,000 genome could be attained in two or three years. That is the cost, experts have long predicted, at which genome sequencing could start to become a routine part of medical practice" (Nicholas Wade, NY Times, http://www.nytimes.com/2009/08/11/science, /11gene.html?8dpc).

Gary Wolf published "The Data-Driven Life" in The New York Times Magazine.

". . . . Another person I’m friendly with, Mark Carranza — he also makes his living with computers — has been keeping a detailed, searchable archive of all the ideas he has had since he was 21. That was in 1984. I realize that this seems impossible. But I have seen his archive, with its million plus entries, and observed him using it. He navigates smoothly between an interaction with somebody in the present moment and his digital record, bringing in associations to conversations that took place years earlier. Most thoughts are tagged with date, time and location. What for other people is an inchoate flow of mental life is broken up into elements and cross-referenced.  

"These men all know that their behavior is abnormal. They are outliers. Geeks. But why does what they are doing seem so strange? In other contexts, it is normal to seek data. A fetish for numbers is the defining trait of the modern manager. Corporate executives facing down hostile shareholders load their pockets full of numbers. So do politicians on the hustings, doctors counseling patients and fans abusing their local sports franchise on talk radio. Charles Dickens was already making fun of this obsession in 1854, with his sketch of the fact-mad schoolmaster Gradgrind, who blasted his students with memorized trivia. But Dickens’s great caricature only proved the durability of the type. For another century and a half, it got worse.

"Or, by another standard, you could say it got better. We tolerate the pathologies of quantification — a dry, abstract, mechanical type of knowledge — because the results are so powerful. Numbering things allows tests, comparisons, experiments. Numbers make problems less resonant emotionally but more tractable intellectually. In science, in business and in the more reasonable sectors of government, numbers have won fair and square. For a long time, only one area of human activity appeared to be immune. In the cozy confines of personal life, we rarely used the power of numbers. The techniques of analysis that had proved so effective were left behind at the office at the end of the day and picked up again the next morning. The imposition, on oneself or one’s family, of a regime of objective record keeping seemed ridiculous. A journal was respectable. A spreadsheet was creepy.  

"And yet, almost imperceptibly, numbers are infiltrating the last redoubts of the personal. Sleep, exercise, sex, food, mood, location, alertness, productivity, even spiritual well-being are being tracked and measured, shared and displayed. On MedHelp, one of the largest Internet forums for health information, more than 30,000 new personal tracking projects are started by users every month. Foursquare, a geo-tracking application with about one million users, keeps a running tally of how many times players “check in” at every locale, automatically building a detailed diary of movements and habits; many users publish these data widely. Nintendo’s Wii Fit, a device that allows players to stand on a platform, play physical games, measure their body weight and compare their stats, has sold more than 28 million units.  

"Two years ago, as I noticed that the daily habits of millions of people were starting to edge uncannily close to the experiments of the most extreme experimenters, I started a Web site called the Quantified Self with my colleague Kevin Kelly. We began holding regular meetings for people running interesting personal data projects. I had recently written a long article about a trend among Silicon Valley types who time their days in increments as small as two minutes, and I suspected that the self-tracking explosion was simply the logical outcome of this obsession with efficiency. We use numbers when we want to tune up a car, analyze a chemical reaction, predict the outcome of an election. We use numbers to optimize an assembly line. Why not use numbers on ourselves?  

"But I soon realized that an emphasis on efficiency missed something important. Efficiency implies rapid progress toward a known goal. For many self-trackers, the goal is unknown. Although they may take up tracking with a specific question in mind, they continue because they believe their numbers hold secrets that they can’t afford to ignore, including answers to questions they have not yet thought to ask.

"Ubiquitous self-tracking is a dream of engineers. For all their expertise at figuring out how things work, technical people are often painfully aware how much of human behavior is a mystery. People do things for unfathomable reasons. They are opaque even to themselves. A hundred years ago, a bold researcher fascinated by the riddle of human personality might have grabbed onto new psychoanalytic concepts like repression and the unconscious. These ideas were invented by people who loved language. Even as therapeutic concepts of the self spread widely in simplified, easily accessible form, they retained something of the prolix, literary humanism of their inventors. From the languor of the analyst’s couch to the chatty inquisitiveness of a self-help questionnaire, the dominant forms of self-exploration assume that the road to knowledge lies through words. Trackers are exploring an alternate route. Instead of interrogating their inner worlds through talking and writing, they are using numbers. They are constructing a quantified self.  

"UNTIL A FEW YEARS ago it would have been pointless to seek self-knowledge through numbers. Although sociologists could survey us in aggregate, and laboratory psychologists could do clever experiments with volunteer subjects, the real way we ate, played, talked and loved left only the faintest measurable trace. Our only method of tracking ourselves was to notice what we were doing and write it down. But even this written record couldn’t be analyzed objectively without laborious processing and analysis.  "Then four things changed. First, electronic sensors got smaller and better. Second, people started carrying powerful computing devices, typically disguised as mobile phones. Third, social media made it seem normal to share everything. And fourth, we began to get an inkling of the rise of a global superintelligence known as the cloud.

"Millions of us track ourselves all the time. We step on a scale and record our weight. We balance a checkbook. We count calories. But when the familiar pen-and-paper methods of self-analysis are enhanced by sensors that monitor our behavior automatically, the process of self-tracking becomes both more alluring and more meaningful. Automated sensors do more than give us facts; they also remind us that our ordinary behavior contains obscure quantitative signals that can be used to inform our behavior, once we learn to read them."

". . . . Adler’s idea that we can — and should — defend ourselves against the imposed generalities of official knowledge is typical of pioneering self-trackers, and it shows how closely the dream of a quantified self resembles therapeutic ideas of self-actualization, even as its methods are startlingly different. Trackers focused on their health want to ensure that their medical practitioners don’t miss the particulars of their condition; trackers who record their mental states are often trying to find their own way to personal fulfillment amid the seductions of marketing and the errors of common opinion; fitness trackers are trying to tune their training regimes to their own body types and competitive goals, but they are also looking to understand their strengths and weaknesses, to uncover potential they didn’t know they had. Self-tracking, in this way, is not really a tool of optimization but of discovery, and if tracking regimes that we would once have thought bizarre are becoming normal, one of the most interesting effects may be to make us re-evaluate what “normal” means" (http://www.nytimes.com/2010/05/02/magazine/02self-measurement-t.html?pagewanted=7&ref=magazine, accessed 05-07-2010).

In November 2010 the first video of a woman giving birth in an open MRI machine was taken at the Charité Hospital in Berlin, Germany.  The team led by Christian Bamberg, M.D. first published the results as "Human birth observed in real-time open magnetic resonance imaging," in the American Journal of Obstetrics & Gynecology in January 2012.  Supplementary material, including the video of the final 45 minutes of labor, was published  as Vol. 206, issue, pp. 505.e1-505e6, June 2012.

A highly interdisciplinary group of scientists, primarily from Harvard University: Jean-Baptiste Michel,Yuan Kui Shen, Aviva P. Aiden, Adrian Veres, Matthew K. Gray, The Google Books Team, Joseph P. Pickett, Dale Hoiberg, Dan Clancy, Peter Norvig, Jon Orwant, Steven Pinker, Martin A. Nowak and Erez Lieberman Aiden published "Quantitative Analysis of Culture Using Millions of Digitized Books," Science, Published Online December 16 2010 Science 14 January 2011: Vol. 331 no. 6014 pp. 176-182 DOI: 10.1126/science.1199644

The authors were associated with the following organizations: Program for Evolutionary Dynamics, Institute for Quantitative Social Sciences Department of Psychology, Department of Systems Biology Computer Science and Artificial Intelligence Laboratory, Harvard Medical School, Harvard College Google, Inc. Houghton Mifflin Harcourt Encyclopaedia Britannica, Inc. Department of Organismic and Evolutionary Biology Department of Mathematics, Broad Institute of Harvard and MITCambridge School of Engineering and Applied Sciences Harvard Society of Fellows, Laboratory-at-Large.

This paper from the Cultural Observatory at Harvard and collaborators represented the first major publication resulting from The Google Labs N-gram (Ngram) Viewer,

"the first tool of its kind, capable of precisely and rapidly quantifying cultural trends based on massive quantities of data. It is a gateway to culturomics! The browser is designed to enable you to examine the frequency of words (banana) or phrases ('United States of America') in books over time. You'll be searching through over 5.2 million books: ~4% of all books ever published" (http://www.culturomics.org/Resources/A-users-guide-to-culturomics, accessed 12-19-2010).

"We constructed a corpus of digitized texts containing about 4% of all books ever printed. Analysis of this corpus enables us to investigate cultural trends quantitatively. We survey the vast terrain of "culturomics", focusing on linguistic and cultural phenomena that were reflected in the English language between 1800 and 2000. We show how this approach can provide insights about fields as diverse as lexicography, the evolution of grammar, collective memory, the adoption of technology, the pursuit of fame, censorship, and historical epidemiology. "Culturomics" extends the boundaries of rigorous quantitative inquiry to a wide array of new phenomena spanning the social sciences and the humanities" (http://www.sciencemag.org/content/early/2010/12/15/science.1199644, accessed 12-19-2010).  

"The Cultural Observatory at Harvard is working to enable the quantitative study of human culture across societies and across centuries. We do this in three ways: Creating massive datasets relevant to human culture Using these datasets to power wholly new types of analysis Developing tools that enable researchers and the general public to query the data" (http://www.culturomics.org/cultural-observatory-at-harvard, accessed 12-19-2010).

Wal-Mart, the world’s largest retailer, agreed to buy Kosmix.com, a social media start-up focused on ecommerce, creating @WalmartLabs.

"Eric Schmidt famously observed that every two days now, we create as much data as we did from the dawn of civilization until 2003. A lot of the new data is not locked away in enterprise databases, but is freely available to the world in the form of social media: status updates, tweets, blogs, and videos.

"At Kosmix, we’ve been building a platform, called the Social Genome, to organize this data deluge by adding a layer of semantic understanding. Conversations in social media revolve around 'social elements' such as people, places, topics, products, and events. For example, when I tweet 'Loved Angelina Jolie in Salt,' the tweet connects me (a user) to Angelia Jolie (an actress) and SALT (a movie). By analyzing the huge volume of data produced every day on social media, the Social Genome builds rich profiles of users, topics, products, places, and events. The Social Genome platform powers the sites Kosmix operates today: TweetBeat, a real-time social media filter for live events; Kosmix.com, a site to discover content by topic; and RightHealth, one of the top three health and medical information sites by global reach. In March, these properties together served over 17.5 million unique visitors worldwide, who spent over 5.5 billion seconds on our services.

"Quite a few of us at Kosmix have backgrounds in ecommerce, having worked at companies such as Amazon.com and eBay. As we worked on the Social Genome platform, it became apparent to us that this platform could transform ecommerce by providing an unprecedented level of understanding about customers and products, going well beyond purchase data. The Social Genome enables us to take search, personalization and recommendations to the next level.

"That’s why we were so excited when Walmart invited us to share with them our vision for the future of retailing. Walmart is the world’s largest retailer, with 10.5 billion customer visits every year to their stores and 1.5 billion online – 1 in 10 customers around the world shop Walmart online, and that proportion is growing. More and more visitors to the retail stores are armed with powerful mobile phones, which they use both to discover products and to connect with their friends and with the world. It was very soon apparent that the Walmart leadership shared our vision and our enthusiasm. And so @WalmartLabs was born. . . .

"We are at an inflection point in the development of ecommerce. The first generation of ecommerce was about bringing the store to the web. The next generation will be about building integrated experiences that leverage the store, the web, and mobile, with social identity being the glue that binds the experience. Walmart’s enormous global reach and incredible scale of operations -- from the United States and Europe to growing markets like China and India -- is unprecedented. @WalmartLabs, which combines Walmart’s scale with Kosmix’s social genome platform, is in a unique position to invent and build this future" (http://walmartlabs.blogspot.com/search?updated-max=2011-11-30T21:01:00-08:00&max-results=7, accessed 01-20-2012).

In July 2011 construction began for the The Francis Crick Institute (formerly the UK Centre for Medical Research and Innovation), a biomedical research center in London. The Institute is a partnership between Cancer Research UK, Imperial College London, King's College London, the Medical Research Council, University College London (UCL) and the Wellcome Trust. It will be the largest center for biomedical research and innovation in Europe.

The Francis Crick Institute, named after British molecular biologist, biophysicist, and neuroscientist Francis Crick, will be located in a new state-of-the-art 79,000 square meters facility next to St Pancras railway station in the Camden area of Central London. It is expected that researchers will to be able to start work in 2015. Complete cost of the facility is budgeted at approximately £600 million. The institute is expected to employ 1500 people, including 1,250 scientists, with an annual budget of over £100 million. 

"IBM researchers unveiled a new generation of experimental computer chips designed to emulate the brain’s abilities for perception, action and cognition. The technology could yield many orders of magnitude less power consumption and space than used in today’s computers. 

"In a sharp departure from traditional concepts in designing and building computers, IBM’s first neurosynaptic computing chips recreate the phenomena between spiking neurons and synapses in biological systems, such as the brain, through advanced algorithms and silicon circuitry. Its first two prototype chips have already been fabricated and are currently undergoing testing.  

"Called cognitive computers, systems built with these chips won’t be programmed the same way traditional computers are today. Rather, cognitive computers are expected to learn through experiences, find correlations, create hypotheses, and remember – and learn from – the outcomes, mimicking the brains structural and synaptic plasticity.  

"To do this, IBM is combining principles from nanoscience, neuroscience and supercomputing as part of a multi-year cognitive computing initiative. The company and its university collaborators also announced they have been awarded approximately $21 million in new funding from the Defense Advanced Research Projects Agency (DARPA) for Phase 2 of the Systems of Neuromorphic Adaptive Plastic Scalable Electronics (SyNAPSE) project.

"The goal of SyNAPSE is to create a system that not only analyzes complex information from multiple sensory modalities at once, but also dynamically rewires itself as it interacts with its environment – all while rivaling the brain’s compact size and low power usage. The IBM team has already successfully completed Phases 0 and 1.  

" 'This is a major initiative to move beyond the von Neumann paradigm that has been ruling computer architecture for more than half a century,' said Dharmendra Modha, project leader for IBM Research. 'Future applications of computing will increasingly demand functionality that is not efficiently delivered by the traditional architecture. These chips are another significant step in the evolution of computers from calculators to learning systems, signaling the beginning of a new generation of computers and their applications in business, science and government.' " (http://www-03.ibm.com/press/us/en/pressrelease/35251.wss, accessed 08-21-2011).

Health Care insurance provider WellPoint, Inc. and IBM announced an agreement to create the first commercial applications of the IBM Watson question answering system. Under the agreement, WellPoint would develop and launch Watson-based solutions to help improve patient care through the delivery of up-to-date, evidence-based health care for millions of Americans, while IBM would develop the Watson healthcare technology on which WellPoint's solution will run.

"The cost of sequencing a human genome — all three billion bases of DNA in a set of human chromosomes — plunged to $10,500 last July from $8.9 million in July 2007, according to the National Human Genome Research Institute.  

"That is a decline by a factor of more than 800 over four years. By contrast, computing costs would have dropped by perhaps a factor of four in that time span.  

"The lower cost, along with increasing speed, has led to a huge increase in how much sequencing data is being produced. World capacity is now 13 quadrillion DNA bases a year, an amount that would fill a stack of DVDs two miles high, according to Michael Schatz, assistant professor of quantitative biology at the Cold Spring Harbor Laboratory on Long Island.

"There will probably be 30,000 human genomes sequenced by the end of this year, up from a handful a few years ago, according to the journal Nature. And that number will rise to millions in a few years" (http://www.nytimes.com/2011/12/01/business/dna-sequencing-caught-in-deluge-of-data.html?_r=1&hp, accessed 12-02-2011).

Health Insurance provider WellPoint announced that the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles would provide clinical expertise to help shape WellPoint's new health care solutions utilizing IBM's Watson question answering system.

"It is estimated that new clinical research and medical information doubles every five years, and nowhere is this knowledge advancing more quickly than in the complex area of cancer care.  

"WellPoint believes oncology is one of the medical fields that could greatly benefit from this technology, given IBM Watson's ability to respond to inquiries posed in natural language and to learn from the responses it generates. The WellPoint health care solutions will draw from vast libraries of information including medical evidence-based scientific and health care data, and clinical insights from institutions like Cedars-Sinai. The goal is to assist physicians in evaluating evidence-based treatment options that can be delivered to the physician in a matter of seconds for assessment. WellPoint and Cedars-Sinai envision that this valuable enhancement to the decision-making process could empower physician-patient discussions about the best and most effective courses of treatment and improve the overall quality of patient care.  

"Cedars-Sinai was selected as WellPoint's partner based on its reputation as one of the nation's premier cancer institutions and its proven results in the diagnosis and treatment of complex cancers. Cedars-Sinai has experience and demonstrated success in working with technology innovators and shares WellPoint's commitment to improving the quality, efficiency and effectiveness of health care through innovation and technology.  

"Cedars-Sinai's oncology experts will help develop recommendations on appropriate clinical content for the WellPoint health care solutions. They will also assist in the evaluation and testing of the specific tools that WellPoint plans to develop for the oncology field utilizing IBM's Watson technology. The Cedars-Sinai cancer experts will enter hypothetical patient scenarios, evaluate the proposed treatment options generated by IBM Watson, and provide guidance on how to improve the content and utility of the treatment options provided to the physicians.  

"Leading Cedars-Sinai's efforts is M. William Audeh, M.D., medical director of its Samuel Oschin Comprehensive Cancer Institute. Dr. Audeh will work closely with WellPoint's clinical experts to provide advice on how the solutions may be best utilized in clinical practice to support increased understanding of the evolving body of knowledge in cancer, including emerging therapies not widely known by community physicians. As the solutions are developed, Dr. Audeh will also provide guidance on how the make the WellPoint offering useful and practical for physicians and patients.

" 'As we design the WellPoint systems that leverage IBM Watson's capabilities, it is essential that we incorporate the highly-specialized knowledge and real-life practice experiences of the nation's premier clinical experts,' said Harlan Levine, MD, executive vice president of WellPoint's Comprehensive Health Solutions. 'The contributions from Dr. Audeh, coupled with the expertise throughout Cedars-Sinai's Samuel Oschin Comprehensive Cancer Institute, will be invaluable to implementing this WellPoint offering and could ultimately benefit millions of Americans across the country.'

"WellPoint anticipates deploying their first offering next year, working with select physician groups in clinical pilots" (http://ir.wellpoint.com/phoenix.zhtml?c=130104&p=irol-newsArticle&ID=1640553&highlight=, accessed 12-17-2011).

Jonathan M. Rothberg, CEO of Guilford, Connecticut-based biotech company Ion Torrent, announced a new tabletop sequencer called the Ion Proton. The company introduced the device at the Consumer Electronics Show in Las Vegas on January 10, although the sequencer is only available to researchers at this point. At $149,000, the new machine is about three times the price of the Personal Genome Machine, the sequencer that the company debuted about a year ago. But the DNA-reading chip inside it is 1,000 times more powerful, according to Rothberg, allowing the device to sequence an entire human genome in a day for $1,000—a price the biotech industry has been working toward for years because it would bring the cost down to the level of a medical test.

'The technology got better faster than we ever imagined,'Rothberg says. 'We made a lot of progress on the chemistry and software, then developed a new series of chips from a new foundry.' The result is a technology progression that has moved faster than Moore's law, which predicts that microchips will double in power roughly every two years.

"Ion Torrent's semiconductor-based approach for sequencing DNA is unique. Currently, optics-based sequencers, primarily from Illumina, a San Diego-based company, dominate the human genomics field. But, while the optics-based sequencers are generally considered more accurate, these machines cost upwards of $500,000, putting them out of reach for most clinicians. Meanwhile, at Ion Torrent's price, "you can imagine one in every doctor's office," says Richard Gibbs, director of Baylor College of Medicine's human genome sequencing center in Houston, which will be among the first research centers to receive a Proton sequencer.  

"The new Ion Torrent sequencer will also allow researchers to buy a chip that sequences only exons, the regions of the genome that encode proteins. Exons only account for about 5 percent of the human genome, according to the National Human Genome Research Institute, but they are where most disease-causing mutations occur, making so-called exome sequencing a faster and potentially cheaper option for many researchers. Although it's the same price as the genome chip, the Ion Torrent exome chip can sequence two exomes at a time, bringing the per-sequence cost down to $500.  

" 'Some researchers want to sequence single genes, others want to do exomes, and others—for example, cancer researchers—will want to sequence whole genomes, so all three are going to coexist,' says Rothberg. 'It's about finding the right tool for the problem.'  

"Whether Ion Torrent's new technology will be enough to make it the dominant supplier of these tools remains to be seen. A day after the company debuted the Proton sequencer, Illumina also announced that it, too, had reached the $1,000 genome milestone" (http://www.technologyreview.com/biomedicine/39458/?nlid=nldly&nld=2012-01-13, accessed 01-13-2013).

American molecular geneticist George M. Church, director of the U.S. Department of Energy Center on Bioenergy at Harvard & MIT, and director of the National Institutes of Health (NHGRI) Center of Excellence in Genomic Science at Harvard,  Yuan Gao from the Wyss Institute for Biologically Inspired Engineering, and Sriram Kosuri from the Department of Biomedical Engineering, Johns Hopkins University, encoded an entire book into the genetic molecules of DNA, the basic building blocks of life, and then accurately read back the text. Church's book, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves, stored in a laboratory tube, contained 53,426 words, 11 illustrations and a JavaScript program, all of which totalled 5.27 megabits of data. Written with Ed Regis, it was scheduled to be published in printed and electronic editions in October 2012. Church's book was 600 times larger than the largest data set previously encoded in DNA.

"Digital data is traditionally stored as binary code: ones and zeros. Although DNA offers the ability to use four "numbers": A, C, G and T, to minimise errors Church's team decided to stick with binary encoding, with A and C both indicating zero, and G and T representing one.  

"The sequence of the artificial DNA was built up letter by letter using existing methods with the string of As, Cs, Ts and Gs coding for the letters of the book.  

"The team developed a system in which an inkjet printer embeds short fragments of that artificially synthesised DNA onto a glass chip. Each DNA fragment also contains a digital address code that denotes its location within the original file.  

"The fragments on the chip can later be "read" using standard techniques of the sort used to decipher the sequence of ancient DNA found in archeological material. A computer can then reassemble the original file in the right order using the address codes.  

"The book – an HTML draft of a volume co-authored by the team leader – was written to the DNA with images embedded to demonstrate the storage medium's versatility.  

"DNA is such a dense storage system because it is three-dimensional. Other advanced storage media, including experimental ones such as positioning individual atoms on a surface, are essentially confined to two dimensions" (http://www.guardian.co.uk/science/2012/aug/16/book-written-dna-code?INTCMP=SRCH, accessed 09-09-2012).

Church, Gao, Kosuri, "Next-Generation Digital Information Storage in DNA," Science, August 16, 2012: DOI: 10.1126/science.1226355

♦ When the physical book edition of the Church and Regis book was published by Basic Books in October 2012 I acquired a copy. On pp. 269-272 the printed book contained an unusual "afterward", apparently written by Church, entitled "Notes: On Encoding This Book into DNA."  This discussed "some of the legal, policy, biosafety, and other issues and opportunities" pertaining to the process.  The ideas discussed were so distinctive and original that I would have liked to quote it in its entirety but that would have been an infringement of copyright. The section ended with the following statement:

"For more information, and to explore the possibility of getting your own DNA copy of this book, please visit http://periodicplayground.com."  

When I visited the site on October 20, 2012 I viewed a message from networksolutions.com that the site was "under construction."

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).

"A robot that allows patients to communicate with doctors via a telemedicine system that can move around on its own has just received 510(k) clearance by the FDA (Food and Drug Administration).  

"The robot, called RP-VITA, was created by InTouch Health [Santa Barbara, California] and iRobot [Bedford, Massachusetts] and allows doctors from anywhere in the world to communicate with patients at their hospital bedside via a telemedicine solution through an iPad interface.  

"According to iRobot and InTouch Health, RP-VITA combines the latest from iRobot in autonomous navigation and mobility technology with state-of-the-art telemedicine, and InTouch Health developed telemedicine and electronic health record integration.  

"RP-VITA makes it possible for doctors to have "doctor-to-patient consults, ensuring that the physician is in the right place at the right time and has access to the necessary clinical information to take immediate action."  

The robot is used in ways that scientists have never before seen. In order to not get in the way of other people or objects, it outlines its own environment and utilizes a range of advanced sensors to autonomously move about a crowded space.  

"Irrespective of a doctor's location, using an intuitive iPad® interface allows them to visit patients and communicate with their co-workers with a single click.  

"A clearance from the FDA means that RP-VITA can be used for active patient monitoring in pre-operative, peri-operative, and post-surgical settings, such as prenatal, neurological, psychological, and critical care evaluations and examinations.  

"InTouch Health is selling RP-VITA into the healthcare market as its new top-of-the-line remote presence device." (http://www.medicalnewstoday.com/articles/255457.php, accessed 01-27-2013).

On January 28, 2013 The European Commission announced funding for The Human Brain Project.

From the press release:

"The goal of the Human Brain Project is to pull together all our existing knowledge about the human brain and to reconstruct the brain, piece by piece, in supercomputer-based models and simulations. The models offer the prospect of a new understanding of the human brain and its diseases and of completely new computing and robotic technologies. On January 28, the European Commission supported this vision, announcing that it has selected the HBP as one of two projects to be funded through the new FET Flagship Program.

''Federating more than 80 European and international research institutions, the Human Brain Project is planned to last ten years (2013-2023). The cost is estimated at 1.19 billion euros. The project will also associate some important North American and Japanese partners. It will be coordinated at the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, by neuroscientist Henry Markram with co-directors Karlheinz Meier of Heidelberg University, Germany, and Richard Frackowiak of Centre Hospitalier Universitaire Vaudois (CHUV) and the University of Lausanne (UNIL).

The Swiss Contribution

"Switzerland plays a vital role in the Human Brain Project. Henry Markram and his team at EPFL will coordinate the project and will also be responsible for the development and operation of the project’s Brain Simulation Platform. Richard Frackowiak and his team will be in charge of the project’s medical informatics platform; the Swiss Supercomputing Centre in Lugano will provide essential supercomputing facilities. Many other Swiss groups are also contributing to the project. Through the ETH Board, the Swiss Federal Government has allocated 75 million CHF (approximately 60 million Euros) for the period 2013-2017, to support the efforts of both Henry Markram’s laboratory at EPFL and the Swiss Supercomputing Center in Lugano. The Canton of Vaud will give 35 million CHF (28 million Euros) to build a new facility called Neuropolis for in silico life science, and centered around the Human Brain Project. This building will also be supported by the Swiss Confederation, the Rolex Group and third-party sponsors.

"The selection of the Human Brain Project as a FET Flagship is the result of more than three years of preparation and a rigorous and severe evaluation by a large panel of independent, high profile scientists, chosen by the European Commission. In the coming months, the partners will negotiate a detailed agreement with the Community for the initial first two and a half year ramp-up phase (2013-mid 2016). The project will begin work in the closing months of 2013."