From Cave Paintings to the Internet A Chronological and Thematic Database on the History of Information and Media Computing & Medicine / Biology Timeline

The anonymous author of the sensational evolutionary treatise Vestiges of the Natural History of Creation (Robert Chambers) includes 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.

English statistician and epidemiologist William Farr uses the third Scheutz difference engine in the calculation of his English Life Table—the first instance of a printing calculator used extensively to do original work.

However, the machine was very troublesome, and the tables were completed by human computers. (See Reading 4.2)

At the U.S. Census Bureau John Shaw Billings, founder and librarian of the Surgeons General's Library (now the National Library of Medicine), suggests to Herman Hollerith that there ought to be a machine for doing the purely mechanical work of tabulating population and similar statistics. 

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

Johann Radon demonstrates 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 this will be demonstrated with the invention of computed tomography.

Warren McCulloch and Walter Pitts publish “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.)

Erwin Schrödinger publishes What is Life? The Physical Aspect of the Living Cell, a popularization of ideas about the physical basis of biological phenomena developed by Max Delbrück and N. V. Timofeev-Ressovsky in a paper published in 1935. Schrrodinger's work influenced  James D. Watson and others.

In his autobiography 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] 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).

Norbert Wiener publishes Cybernetics or Control and Communication in the Animal and the Machine, a widely read and influential book that applied theories of information and communication to both biological systems and machines. 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.

Computer-related words with the “cyber” prefix, including "cyberspace," originate from Wiener’s book.

Wiener's book was reviewed in TIME Magazine on December 27, 1948. The review was 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).

At the Hixon Symposium in Pasadena, California, John von Neumann delivers his General and Logical Theory of Automata. This was the first of a series of five works (some posthumous) in which he attempted to develop a precise mathematical theory allowing comparison of computers and the human brain.

Librarian Sanford Larkey publishes 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 Hixon Symposium in Pasadena, California, John von Neumann speaks on The General and Logical Theory of Automata.

Within this speech von Neumann compared the functions of genes to self-reproducing automata.

“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).

At the second English computer conference held in Manchester, J. M. Bennett and John Kendrew describe 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. (See Reading 10.3.)

William H. Sweet and Gordon L. Brownell at Massachusetts General Hospital, Boston, describe 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)

George Gamow comes 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 Ross Ashby writes of intelligence amplification by machines in his book, Introduction to Cybernetics.

The First International Congress on Cybernetics is 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 delivers 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)

Robert S. Ledley and Lee B. Lusted publish "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.

Drs. William Chardack and Andrew Gage, and electrical engineer Wilson Greatbatch, report the success of the world’s 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.

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

Francis Crick, Sydney Brenner and colleagues propose 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).

Allen M. Cormack shows that changes in tissue density can be computed from x-ray data.

No machine was constructed at this time because of limitations in computing power. This discovery led in 1972 to the invention of computed tomography (CT).

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

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

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

Aaron Klug formulates 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 builds 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.

Aaron Klug describes 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.

Godfrey Hounsfield invents computed tomography (CT), the first application of computers to medical imaging.

Raymond V. Damadian files 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 demonstrate 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

Paul Lauterbur develops 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.

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.

Robert S. Ledley at Georgetown University develops the ACTA (Automatic Computerized Traverse Axial)— the first whole-body computerized 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.

Records, Computers, and the Rights of Citizens is 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 is granted, leading to the foundation of the biotechnology industry.

Venture capitalist Robert A. Swanson and biochemist Herbert W. Boyer found the first genetic engineering company, Genentech, to use recombinant DNA methods to make medically important drugs.

Walter Gilbert and Allan M. Maxam devise 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 independently develop 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.

Physicist Peter Mansfield develops a mathematical technique that will allow NMR scans to take seconds rather than hours and produce clearer images than Lauterbur.

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.

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, depicts 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 sequence 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 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 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 develop the first semi-automatic DNA sequencer working with a laser that recognizes 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).

Applied Biosystems markets the first commercial DNA sequencing machine, based on Leroy Hood’s technology.

Formal proposals are 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.

J. Craig Venter and colleagues describe 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 leaves the National Institutes of Health and founds The Institute for Genomic Research (TIGR).

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

IBM announces the start of a five-year effort to build a massively parallel computer, Blue Gene, which will be 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 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 forms 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).

The National Science Foundation funds research headed by Gabor Forgacs at the University of Missouri-Columbia on what is 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 decipher 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 reconstruct the virus in the laboratory and will publish the genetic sequence.

Dirk Brockmann, L. Hufnagel, and T. Geisel publish "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).]

A new technology developed at Keio University carries 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."

The genome of James D. Watson, co-discover of the double-helical structure of DNA, is sequenced and presented to Watson. It is the second individual human genome to be sequenced. The first was that of J. Craig Venter, which was sequenced in the human genome project completed in 2001.

Timothy J. Ley and numerous collaborators from different countries publish 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 unveils 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 report 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. It is the first sequence of the genome of an extinct animal.This opens 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)

Michael Schmidt and Hod Lipson of Cornell University publish "Distilling Free-Form Natural Laws from Experimental Data," Science 3 April 2009: Vol. 324. no. 5923, pp. 81 - 85 DOI: 10.1126/science.1165893.  The paper describes a computer program that sifts raw and imperfect data to uncover fundamental laws of nature.

"For centuries, scientists have attempted to identify and document analytical laws that underlie physical phenomena in nature. Despite the prevalence of computing power, the process of finding natural laws and their corresponding equations has resisted automation. A key challenge to finding analytic relations automatically is defining algorithmically what makes a correlation in observed data important and insightful. We propose a principle for the identification of nontriviality. We demonstrated this approach by automatically searching motion-tracking data captured from various physical systems, ranging from simple harmonic oscillators to chaotic double-pendula. Without any prior knowledge about physics, kinematics, or geometry, the algorithm discovered Hamiltonians, Lagrangians, and other laws of geometric and momentum conservation. The discovery rate accelerated as laws found for simpler systems were used to bootstrap explanations for more complex systems, gradually uncovering the "alphabet" used to describe those systems" (Abstract from Science)

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

They describe a Robot Scientist which the researchers believe is the first machine to have independently discovered new scientific knowledge. The robot, called Adam, is a computer system that fully automates 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, use 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 invents a new technology for decoding DNA that can 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).