"As for the comparative part of this treatise, or the interlacing the descriptions of the human muscles with these of the canine, that needs no apology. The many useful discoveries known from the dissection of quadrupeds, the knowledge of the true structure of divers parts of the body, of the course of the blood and the chyle, and of the use and proper action of the parts, that are chiefly owing to this sort of dissection; these, I say, give a very warrantable plea for insisting upon it, tho' it may be censured by the vulgar" (p. vi).

Digital facsimile from Google Books at this link.

Translated into English as Barbed wire disease: A psychological study of prisoners of war. Translated from the German, with additions. London: Bale & Danielson, 1919.

"By the time of the Armistice in 1918, around 6.5 million prisoners of war were held by the belligerents. Little has been written about these prisoners, possibly because the story is not one of unmitigated suffering and cruelty. Nevertheless, hardships did occur and the alleged neglect and ill-treatment of prisoners captured on the Western Front became the subject of major propaganda campaigns in Britain and Germany as the war progressed. "Barbed Wire Disease" looks at the conditions facing those British and German prisoners, and the claims and counter-claims relating to their treatment. At the same time, it sets the story in the wider context of the commitment by both governments to treat prisoners humanely in accordance with the recently agreed Hague and Geneva Conventions. The political and diplomatic efforts to abide by the new rules are examined in detail, along with the use of reprisals against prisoners, Britain's voluntary relief effort and the effect of face-to-face negotiations at the height of the war. This comprehensive analysis, using unpublished official files and cabinet papers, concludes by documenting the first ever efforts to bring war criminals to justice before international tribunals." (Nielsen Book Data).

(Part 1 by Frey & Gruber; Part 2 by Frey.) Frey and Gruber developed the first heart-lung machine. Their machine "consisted of a double-acting pump in the form on an injection syringe with a capacity of 10 ml, which imitated the heart action and two values. This pumping system produced a pulsatile flow. Because of this pulsatile driving force, 'as a result of the swing mvoement of the blood elements and through the constant change of the vessel diamenter, obstructions occurred les freqeuently and resolved quicker, as sedimentation and adhesions of the cells happened to a lesser extent.'

"An important component of this artificial circulation was the addition of the facility 'which was able to replace the lung.'  Von Frey...developed the first film oxygenator for this purpose. Blood in the form of a thin film was oxygenated inside a slowly rotating cylinder by an oxygen atmosphere. The temperature of the arterial blood was regulated by a 'preheater.' As with current heart-lung machines, the circulation incorporated several pressure and temperature measuring devices as well as sample ports. By insertion of glass cannulae into both the aorta and vena cava, artificial perfusion of a dog's rear part was performed. Following elecrical muscle stimulation during this experiment, measurements of 'the consumption of oxygen caused by its use by the tissue and the absorbed carbon dioxide' were performed, as stated in their reports dated 20 November, 1883" (Boettcher, W., Merkle, F., Weitkemper, H-H.," History of extracorporeal circulation: The conceptional and developmental period,", J. Amer. Soc. Extra-Corporeal Technology," 35 (2003) 172-183, quoting from p. 175).
See also Zimmer,H-G., "The heart-lung machine was invented twice--the first time by Max von Frey," Clin. Cardiol., 26 (2003) 443-45.

The first scientific book printed in Cuba. The striking illustrations are by the author's son, and depict fish, turtles, and crustacieans observed along the Cuban shoreline. The final section contains three alarming illsutrations of an enslaved man identified as Domingo Fernández, who is suffering from scrotal lymphedema.
Digital facsimile from Biodiversity Heritage Library at this link.

Denis discovered the presence of cholesterol (“cholestérine”) in the blood. This he announced on p. 110 of his Recherches expérimentales.

A founding work of botany of the American South, containing first botanical descriptions of many species. Initially published in parts from 1816 to 1824. Digital facsimile from Biodiversity Heritage Library at this link.

Catalogue compiled by Jacob Hooke. Digital facsimile from Google Books at this link.

In their Addendum on p. 46 the authors stated that 20 and 21 months post innocculation in the brain with brain material from Kuru patients two chimpanzees showed symptoms of an illness suggestive of Kuru. Digital facsimile from Google Books at this link.

The authors formally reported these results the following year in Gajdusek, Gibbs, & Alpers, "Experimental transmission of a Kuru-like syndrome to chimpanzees," Nature, 209 (1966), 794-96.

(Thanks to Juan Weiss for this reference and its interpretation.)

In this book Morgan first used the word gene. Previously he had used the term "Mendelian unit" or "factor." On the basis of genetic analysis Morgan presented a number of characteristics of genes:

1. A gene could have more than one effect. For instance, insects that had white-eye gene not only had white eyes, but al grew slower and had a lower viability.
2. The effects of the gene could be modified by external conditions, but these modiciations were not transmitted to future generations. The gene itself was stable; only the character that the gene controlled varied.
3. Characters that were indistinguishable phenotypically could be the product of different genes.
4. At the same time, each character was the product of many genes. For instance, 50 different genes were known to affect eye color; 15 affected body color, and 10 affected length of wing.
5. Heredity was therefore not some property of the 'organism as a whole,' but of the genes.
6. Genes of the pair did not jump out of one chromosome into another, but changed when the chromosome thread broke as a piece in front of or else behind them. Thus, crossing-over affected linked genes and groups, and was a product of the behavior of the chromosome as an entity.

Digital facsimile from Google Books at this link.

Chapters by Monique Kornell are: 1. The Illustration of Anatomy,  2. The Living Dead: Animated Anatomy, 3. Arts and Anatomy Books, 4. Anatomy and the Antique, 5. "As Large as Nature": Life Size Anatomical Illustration, 6. Surface Anatomy from the Inside Out. 
Erin Travers contributed Chapter 7, Restricted Access: The Body, Sex, and Reproduction in Frederk Ruysch's Anatomical Collection and Catalogues.
Thisbe Gensler contributed Chapter 8, Interior Visions: Representing the Body in Three Dimensions.

The remainder of this elegantly designed, illustrated, and produced book consists of a very extensively annotated catalogue by all the co-authors of 56 exhibited items, followed by an unusually extensive bibliography.

Cline and colleagues were the first to successfully transfer a functioning gene into a living mouse, creating the first transgenic organism.

"... description of the museum formed by Lodovico Settala, a physician of Milan, and his son, Manfredo, a Canon of the Cathedral. It describes their collections of both artifical and natural curiosities, including plants, seeds, fruits, stuffed animals, minerals, fossils, shells, medals, intaglios, cameos, chemical preparations, various scientific insturments, and articles made of glass and metal. Based upon the beautiful engraved frontispiece depicting the the interior of the museum, the gallery consisted of 3 rooms stuffed with all manner of curiosities. Display cases set upon tables lined the walls with space taken up underneath by a variety of vases and urns. The walls above the cases held various pictures while the tops of the displays were packed with various insturments and clocks. Hanging from the ceiling are the required taxidermy, including a crocidile, various fish, and birds. A large elephant tusk greets visitors near the entrance to the middle gallery. It was Manfredo Settala's wish that upon his death, the museum would be deposited in the Ambrosian Library of Milan, but the arrangement fell through and the collection was dispersed (Murray)" (mineralogicalrecord.com).

Digital facsimile from Google Books at this link.

The first catalogue of Kircher's museum collected by Kircher at the Jesuit College in Rome between 1651 and 1680. Digital facsimile from the Internet Archive at this link.

Catalogue of the collection of natural history commenced by Anthony Breda and considerably enriched and expanded by his brother-in-law Levinus Vincent, a merchant of luxurious textiles. Digital facsimile from the Biodiversity Heritage Library at this link.

Catalogue of the cabinet of curiosities formed by the merchant and collector Johann Richter. Digital facsimile from Biodiversity Heritage Library at this link.

In 1901 Gorgas was sent to Havana to undertake a special campaign against the yellow fever mosquito Aëdes aegypti. His methods of sanitation were so successful that in three months yellow fever was practically eradicated from Havana. Gorgas outlined the main principles of his methods in the above paper, and his paper of 1909 (No. 5460).

Digital facsimile from Google Books at this link.

Written in Ottoman Turkish, and printed in Istabul, this was the first illustrated medical book printed in the Muslim world. 
Digital facsimile from the Bayerische StaatsBibliothek at this link.

In 1975 Goodman and his collaborators used sequence data to reconstruct the evolutionary history of hemoglobin (including possible ancestral sequences) and analyze which sites on the hemoglobin complex had evolved at which stages. Goodman called this the first "hard evidence of Darwinian evolution".

Axel, along with microbiologist Saul J. Silverstein and geneticist Michael H. Wigler, discovered a technique of cotransformation via transfection. This process, which allows foreign DNA to be inserted into a host cell to produce certain proteins, is fundamental to recombinant DNA research at pharamceutical and biotech companies. Order of authorship in the original publication: Wigler, ...Silverstein, Axel.

"In their landmark paper published in 1991, Buck and Axel cloned olfactory receptors, showing that they belong to the family of G protein coupled receptors. By analyzing rat DNA, they estimated that there were approximately one thousand different genes for olfactory receptors in the mammalian genome. This research opened the door to the genetic and molecular analysis of the mechanisms of olfaction" (Wikipedia article on Richard Axel, accessed 7-22).
For this and later work showing that each olfactory receptor neuron expresses only one kind of olfactory receptor protein...Axel and Buck received the 2004 Nobel Prize in Physiology or Medicine.

Capecchi shared the 2007 Nobel Prize in Physiology or Medicine for discovering a method to create mice in which a specific gene is turned off. These mice are known as knockout mice.

Discovery of ribozymes (ribonucleic acid enzymes). Cech shared the 1989 Nobel Prize in Chemistry for his discovery that RNA itself could cut strands of RNA, suggesting that life might have started as RNA. "In the 1970s, Cech had been studying the splicing of RNA in the unicellular organism Tetrahymena thermophila when he discovered that an unprocessed RNA molecule could splice itself. In 1982, Cech became the first to show that RNA molecules are not restricted to being passive carriers of genetic information – they can have catalytic functions and can participate in cellular reactions. RNA-processing reactions and protein synthesis on ribosomes in particular are catalysed by RNA. RNA enzymes are known as ribozymes and have provided a new tool for gene technology. They also have the potential to provide new therapeutic agents – for example, they have the ability to destroy and cleave invading, viral RNAs" (Wikipedia article on Thomas Cech, accessed 7-22).

This was the first paper to describe cdc mutants. The authors also coined the term 'execution point' — the stage in the cell cycle when the gene function is required. In this paper, three cdc genes were described, which paved the way for the identification of many more such genes, and for the discovery of the molecules and mechanisms controlling the cell

Order of authorship in the original publication: Hartwell, Culotti, Reid. Digital facsimile from PubMedCentral at this link .

Hartwell shared the 2001 Nobel Prize in Physiology and Medicine for discoveries of protein molecules that control the division (duplication) of cells.

In this paper the authors demonstrated a "synthetic model of the cell cycle. Genetics had divided the cycle into two parallel pathways, which comprised two sets of dependent steps and involved a total of 19 cdc genes. At the beginning of the cell cycle, both pathways depend on the completion of a step that Hartwell et al. termed 'start'. This event is defined by the famous cdc28 mutant (famous because the cdc28 gene was later shown to encode the founding member of the cyclin-dependent kinase family), and is also the event at which yeast mating factor arrests cell division to prepare cells for mating. With amazing prescience, the authors speculated that 'start' would turn out to be an important control point for the cell cycle in many eukaryotes" (Patterson, Mark. Nature Reviews Genetics, web focus on cell division, Milestone 5, accessed 7-22).

Order of authorship in the original publication: Hartwell, Culotti, Pringle, Reid.

Klug and deRosier invented methods for two-dimensional and three-dimensional digital image processing of electron microscope images. The latter method provided the theory behind the development of computed tomography (CT) by Hounsfield in the early 1970s. Hounsfield's invention of CT in the early 1970s benefited from several discussions with Klug about digital imaging (personal communication from Klug to Jeremy Norman). Hounsfield received a share of the 1979 Nobel Prize in physiology/medicine for his invention of CT, which provided the first means for visualizing, in three dimensions, virtually all types of tissue within the body (see GM 2700.4 and Grolier Medical Hundred 100). Klug received the Nobel Prize for chemistry in 1982 "for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes." A press release written at the time refers to Klug's two- and three-dimensional imaging methods as an important part of his work: "Electron microscopy has long been used to obtain a two-dimensional picture of biological objects. The power of the method to give a clear picture of the structure is, however, limited by several factors. The molecules of life consist mainly of light atoms, which makes the picture lacking in contrast. Increased contrast can be achieved with long exposure times, but this entails the danger that the structure is destroyed by radiation damage. Instead the contrast is generally improved by "staining" with heavy metals, which can also lead to a distortion of the structure. Klug has shown that pictures of biological objects seemingly lacking in contrast often contain a large amount of structural information, which can be made available by a mathematical manipulation of the original picture. His method allows electron microscope pictures of high quality to be obtained with very low radiation doses and without the use of heavy metal stains. In this way changes in the sample are minimized, so that the electron microscope picture at high resolution is a true representation of the original biological structure. The method gives a two-dimensional projection of the sample only, but Klug has shown that a three-dimensional reconstruction of the object can be obtained by collecting pictures in several different directions of projection" (Nobel e-museum). 

Discovery of Zinc fingers, a protein structural motif. "Zinc fingers were first identified in a study of transcription in the African clawed frog, Xenopus laevis in the laboratory of Aaron Klug. A study of the transcription of a particular RNA sequence revealed that the binding strength of a small transcription factor (transcription factor IIIA; TFIIIA) was due to the presence of zinc-coordinating finger-like structures.^[6] Amino acid sequencing of TFIIIA revealed nine tandem sequences of 30 amino acids, including two invariant pairs of cysteine and histidine residues. Extended x-ray absorption fine structure confirmed the identity of the zinc ligands: two cysteines and two histidines.^[5] The DNA-binding loop formed by the coordination of these ligands by zinc were thought to resemble fingers, hence the name" (Wikipedia article on Zinc finger, accessed 7-22).

Lwoff successfully explained how the process of lysogeny works. The bacteriophage’s genes are incorporated into the bacteria’s genetic material, but remain latent until a trigger factor causes a new phage to be formed. Lwoff also showed that ultraviolet light can be a trigger factor. See also Lwoff's "Lysogeny," Bacteriological Reviews, 17 (1953) 269-337. Digital facsimile of Lysogeny from PubMedCentral at this link.

Lwoff (Nobel Prize 1965) gave the name "prophage" to the form in which the genome of the bacteriophage is perpetuated in lysogenic bacteria. The bacteriophages produced by these bacteria, known as temperate bacteriophages, can therefore follow one of two pathways when they infect sensitive bacteria. Either, like virulent bacteriophages, they multiply in the bacteria which lyse releasing infectious bacteriophages, or their genome is incorporated into the bacteria that they perpetuate in non-infectious form, the prophage.

Marcker discovered that the biosynthesis of proteins is always initiated by a tRNA molecule that carries the modified amino acid formyl-methionine. 

Smithies (Nobel Prize 2007) discovered, simultaneously with Mario Capecchi and Martin Evans, the technique of homologous recombination of transgenic DNA with genomic DNA, a much more reliable method of altering animal genomes than previously used, and the technique behind gene targeting and knockout mice.
Order of authorship of the original publication: Doetschman, Gregg...Smithies.

Since the turn of the twentieth century, chromosomes prepared on microscope slides formed clumps that made it extremely difficult to distinguish them. Although the preparations made the identification of individual chromosomes difficult, by the 1920s cytologists consistently reported a diploid number of 48 human chromosomes. In April 1952, Hsu discovered a technique—the hypotonic solution—that separated the clumped chromosomes, allowing him to observe each one individually. Even though he now could distinguish human chromosomes to a much greater degree than his predecessors, Hsu still reported a diploid number of 48 human chromosomes (see Figure 14 in his 1952 paper). The correct diploid chromosome number of 46 human chromosomes was first reported three years later by Joe Hin Tjio and Albert Levan.

See Hsu, T. C. Human and mammalian cytogenetics: An historical perspective (1979). See also Kottler, Malcolm Jay, "From 48 to 46: Cytological technique, preconception, and the counting of human chromosomes," Bull. Hist. Med., 48 (1974) 465-502.

Benzer developed "the T4 rII system, a new genetic technique involving recombination in T4 bacteriophage rII mutants. After observing that a particular rII mutant, a mutation that caused the bacteriophage to eliminate bacteria more rapidly than usual, was not exhibiting the expected phenotype, it occurred to Benzer that this strain might have come from a cross between two different rII mutants (each having part of the rII gene intact) wherein a recombination event resulted in a normal rII sequence. Benzer realized that by generating many r mutants and recording the recombination frequency between different r strains, one could create a detailed map of the gene, much as Alfred Sturtevant had done for chromosomes.^[8] Taking advantage of the enormous number of recombinants that could be analyzed in the rII mutant system, Benzer was eventually able to map over 2400 rII mutations. The data he collected provided the first evidence that the gene is not an indivisible entity, as previously believed, and that genes were linear" (Wikipedia article on Seymour Benzer, accessed 7-22).

Digital facsimile of the 1959 paper from PubMedCentral at this link. See also Benzer's "On the topography of the genetic fine structure," Proc. Nat. Acad. Sci., 47 (1961) 403-415. Digital facsimile of the 1961 paper from PubMedCentral at this link.

In 1999, With Marina Cavazzana-Calvo and Salima Hacein-Bey, Fischer achieved the first clinical successes in the world of gene therapies for about ten bubble children,^[8] two of whom unfortunately developed leukaemias after a few months, one of whom had died. The test was stopped urgently in 2002. The trial was restarted in 2004, according to a modified protocol using better retroviral vectors, and was stopped again in 2005 due to new complications. 

Yanofsky and colleagues established that gene sequences and protein sequences are colinear in bacteria. Order of authorship in the original publication: Yanofsky, Carlton, ... Henning. In genetics, coliniarity is a property of the genetic code to preserve the order of codons.

Digital facsimile from PubMedCentral at this link.

Yanofsky showed that changes in DNA sequence can produce changes in protein sequence at corresponding positions. His work is considered the best evidence in favor of the one gene-one enzyme hypothesis. Order of authorship in the original publication: Yanofsky, Drapeau, Guest, Carlton. Digital facsimile from PubMedCentral at this link.

Franklin and Gosling's completed Patterson synthesis of the A-form of DNA, based on work begun in 1952, represents the first independent confirmation that the Watson-Crick double-helix model was correct. "We suggest that the unit in structure A is, as in Structure B, two co-axial helical chains running in opposite directions" (p. [5]). "The demonstration of the correctness of the structure is thus doubly convincing because the double-helical structure may be arranged to fit the X-ray data of both forms." (Klug, "Rosalind Franklin and the Discovery of the Structure of DNA" Nature 219 [1968]: 808). Judson, Eighth Day of Creation, p. 161. 

Dulbecco and his group demonstrated that the infection of normal cells with certain types of viruses (oncoviruses) led to the incorporation of virus-derived genes into the host-cell genome, and that this event lead to the transformation (the acquisition of a tumor phenotype) of those cells. Order of authorship in the original publication: Sambrook, Westphal, Srinvasan, Dulbecco. Digital facsimile from PubMedCentral at this link.

While a postdoctoral fellow working with Aaron Klug and Francis Crick at the MRC in the 1970s, Kornberg discovered the nucleosome as the basic protein complex packaging chromosomal DNA in the nucleus of eukaryotic cells. Chromosomal DNA is often termed "Chromatin" when it is bound to proteins in this manner, reflecting Walther Flemming's discovery that certain structures within the cell nucleus would absorb dyes and become visible under a microscope.

Kornberg discovered that transmission of gene regulatory signals to the RNA polymerase machinery is accomplished by an additional protein complex dubbed the Mediator. As noted by the Nobel Prize committee, "the great complexity of eukaryotic organisms is actually enabled by the fine interplay between tissue-specific substances, enhancers in the DNA and Mediator. The discovery of Mediator is therefore a true milestone in the understanding of the transcription process."

Within the nucleosome Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins. With Yahli Lorch, Kornberg showed that a nucleosome on a promoter prevents the initiation of transcription, leading to the recognition of a functional role for the nucleosome, which serves as a general gene repressor. Order of authorship in the original publication: Lorsch, Lapointe, Kornberg.

With his Ph.D. student Benno Müller-Hill, Gilbert was the first to purify the lac repressor, just beating out Mark Ptashne for purifying the first gene regulatory protein.

With Wimberly, Brian T.,  Brodersen, Ditlev E., Clemons, William M.,  Morgan-Warren, Robert J.,  Carter, Andrew P., Vonrhein, Clemens,  Hartsch, Thomas.

Ramakrishnan and colleagues determined the complete molecular structure of the 30S subunit of the ribosome and its complexes with several antibiotics. Ramakrishnan shared the 2009 Nobel Prize in Chemistry with Thomas A. Steitz and Ada Yonath, "for studies of the structure and function of the ribosome."
The Abstract:
"Genetic information encoded in messenger RNA is translated into protein by the ribosome, which is a large nucleoprotein complex comprising two subunits, denoted 30S and 50S in bacteria. Here we report the crystal structure of the 30S subunit from Thermus thermophilus, refined to 3Å resolution. The final atomic model rationalizes over four decades of biochemical data on the ribosome, and provides a wealth of information about RNA and protein structure, protein-RNA interactions and ribosome assembly. It is also a structural basis for analysis of the functions of the 30S subunit, such as decoding, and for understanding the action of antibiotics. The structure will facilitate the interpretation in molecular terms of lower resolution structural data on several functional states of the ribosome from electron microscopy and crystallography."

See also:
Ramakirshan, V., Wimberly, Brian T., Carter, et al, "Functional insights from the structure of the 20S ribosomal subunit and its interactions with antibiotics," Nature, 407 (2000) 340-348. And, Ramakirschan, Venki. Gene machine: The race to decipher the secrets of the ribsome (2018).

With Poul Nissen, Jeffrey Hansen, Nenad Ban, Peter B. Moore.

Steitz shared the 2009 Nobel Prize in Chemistry with Venkatraman Ramakrishnan and Ada Yonath "for studies of the structure and function of the ribosome."

Rich and Crick solved the structure of collagen, the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of amino acids bound together to form a triple helix of elongated fibril known as a collagen helix. 
See also:
Rich, Alexander - Crick, Francis H.C. The Structure of Collagen. 1957. Offprint from "Recent Advances in Gelatin and Glue Research" (Pergamon Press: London, 1957), the Proceedings of a Conference sponsored by the British Gelatine and Glue Research Association and held at the University of Cambridge, 1-5 July 1957, pp. 20-24.

Alexander Rich discovered polysomes, clusters of ribosomes which read one strand of mRNA simultaneously. Order of authorship in the original publication: Warner, Knopf, Rich.

Digital facsimile from PubMedCentral at this link.

Order of authorship in the original publication: Rosenberg, Seeman,...Rich. This paper was the first confirmation of the double-helix structure at atomic resolution.
See also:
Roberta Ogilvie Day, Nadrian C. Seeman,... Alexander Rich, "A crystalline fragment of the double helix: The structure of the dinucleoside phosphate guanylyl-3'5'-cytidine," Proc. Nat. Acad. Sci. (U.S.A.) 70, 849-853. Digital facsimile from PubMedCentral at this link.

(Thanks to Juan Weiss for this reference and its interpretation.)

Order of authorship in the original publication: Fire, XU....Mello.  In 2006, Fire and Mello shared the Nobel Prize in Physiology or Medicine for the discovery of the mechanism of RNA Interference. The authors reported that tiny snippets of double-stranded RNA (dsRNA) effectively shut down specific genes, driving the destruction of messenger RNA (mRNA) with sequences matching the dsRNA. As a result, the mRNA cannot be translated into protein. Fire and Mello found that dsRNA was much more effective in gene silencing than the previously described method of RNA interference (RNAi) with single-stranded RNA. Because only small numbers of dsRNA molecules were required for the observed effect, Fire and Mello proposed that a catalytic process was involved. This hypothesis was confirmed by subsequent research.

In 1982 Vane shared the Nobel Prize in Physiology or Medicine with Sune Bergström and Bengt Samuelsson for "their discoveries concerning prostaglandins and related biologically active substances."

For his discovery of reverse transcriptase, in 1975 Temin shared the 1975 Nobel Prize with Renato Dulbecco and David Baltimore.

While studying the Rous sarcoma virus Temin began to refer to the genetic material that the virus introduced to the cells, the "provirus". Using the antibiotic, actinomycin D, which inhibits the expression of DNA, he determined that the provirus was DNA or was located on the cell's DNA. These results implied that the infecting Rous sarcoma virus was somehow generating complementary double-stranded DNA. Temin's description of how tumor viruses act on the genetic material of the cell through reverse transcription was revolutionary. This upset the widely held belief at the time of a popularized version of the "Central Dogma" of molecular biology posited by Nobel laureate Francis Crick, one of the co-discoverers of the structure of DNA, with James Watson and Rosalind Franklin. Crick claimed only that sequence information cannot flow out of protein into DNA or RNA, but he was commonly interpreted as saying that information flows exclusively from DNA to RNA to protein. Many highly respected scientists disregarded Temin's work and declared it impossible. Despite the lack of support from the scientific community, Temin continued to search for evidence to support his idea. In 1969, Temin and a postdoctoral fellow, Satoshi Mizutani, began searching for the enzyme that was responsible for the phenomenon of viral RNA being transferred into proviral DNA. Later that year, Temin showed that certain tumor viruses carried the enzymatic ability to reverse the flow of information from RNA back to DNA using reverse transcriptase.

Messing and colleagues employed shotgun sequencing to sequence the genome of cauliflower mosaic virus, the first genome sequenced by the shotgun method. They developed the shotgun DNA sequencing method with single and paired synthetic universal primers. The method is based on fragmenting DNA into small sizes, purifying them by cloning, and defining the start of sequencing with a short oligonucleotide. Because fragmentation produces overlapping fragments, sequences can be concatenated by overlapping sequence information, thereby reconstructing contiguous sequences (contigs).
Order of authorship in the original publication: Messing, Gardner, Howarth....

Digital facsimile from PubMedCentral at this link.

Martin used a different approach that avoided in vivo alteration. She reasoned that an ES cell line might be obtained by culturing cells isolated from blastocysts in a medium that had previously been conditioned by an established teratocarcinoma stem-cell line (such a medium might contain a factor that stimulates ES-cell proliferation and/or suppress their differentiation). Using this approach, she established a cell line directly from normal pre-implantation mouse embryos and confirmed its pluripotency by showing that individual cells of this line could differentiate to form a wide variety of cell types in vitro and in vivo.  Digital facsimile from PubMedCentral at this link.

While working in the laboratory of Paul Doty at Harvard University, Marmur discovered that the denaturation of DNA was reversible (DNA hybridization) and depended on salt- and GC-content. Marmur and Doty accurately described the conditions for the optimal renaturation of DNA complementary strands, upon denaturation by high temperatures. They proposed that high temperature was required to block the formation of weak bonds between non-complementary strands and to guarantee the proper pairing of complementary molecules. With J. Eigner and C. Schildkraut. Digital facsimile from PubMedCentral at this link.
See also J. Marmur and D. Lane, "Strand separation and specific recombination in deoxyribonucleic acids: Biological studies," Proc. Nat. Acad. Sci (U.S.A.) 46, 453-461. Digital facsimile of that paper from PubMedCentral at this link.

Discovery of DNA supercoiling. DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a strand’s supercoiling affects a number of biological processes, such as compacting DNA and regulating access to the genetic code (which strongly affects DNA metabolism and possibly gene expression). With R. Radloff, R. Watson & P. Laipis. Digital facsimile from PubMedCentral at this link. See also, Jacob Lebowitz, "Through the looking glass: The discovery of supercoiled DNA," Trends in Biochemical Sciences, 15 (1990) 202-207.

In this paper Knudson first described his  "two-hit hypothesis," also known as the "Knudson hypothesis," which explains the incidence of hereditary cancers, such as retinoblastoma. 

"Humans inherit two copies of every gene, one from each parent (except for genes on the X and Y chromosomes in males). Some people inherit one mutated version and one normal version of the retinoblastoma gene, which produces the retinoblastoma protein involved in controlling cell cycle progression. The inherited mutation is "the first hit." Over time, a mutation may arise in the normal version in one cell, thus producing "the second hit," which leaves the cell unable to control the process of cell division in an orderly manner, leading to cancer.

"Knudson's insight was to compare the incidence of retinoblastomas, including the number of tumors, the ages of occurrence, and whether tumors occurred in both eyes, among children in families with and without hereditary predisposition to retinoblastomas. Children in families with a hereditary predisposition have more tumors at a younger age and usually have tumors in both eyes. Children in families without the hereditary predisposition usually have only one tumor at a later age.

"The differences in occurrence can be explained by the rate of gene mutation during cell division (a somatic mutation), and a model that requires only one somatic mutation per tumor in hereditary cases but requires two somatic mutations, one on each copy of a particular cell cycle control gene, in one cell lineage in non-hereditary cases, i.e. the co-occurrence of two rare events. Knudson subsequently showed that the model was not only applicable to retinoblastoma but also to Wilms' tumors of the kidney. These studies led to the concept of tumor suppressor genes, which Knudson called "anti-oncogenes." (Wikipedia article on Alfred G. Knudson, accessed 7-22).

King and Briggs cloned a frog by nuclear transfer of embryonic cells. Their experiment was the first successful nuclear transplanation performed in metazoans. The same cloning technique, using somatic cells, was later used to create Dolly the Sheep.

King showed that breast cancer can be inherited due to mutations in the Breast cancer type 1 susceptibility protein, a protein that in humans is encoded by the BRAC1 gene. BRCA1 is a human tumor suppressor gene (also known as a caretaker gene) that is responsible for repairing DNA.

"In the genetic code, there are 4³ = 64 possible codons (3 nucleotide sequences). For translation, each of these codons requires a tRNA molecule with an anticodon with which it can stably complement. If each tRNA molecule is paired with its complementary mRNA codon using canonical Watson-Crick base pairing, then 64 types of tRNA molecule would be required. In the standard genetic code, three of these 64 mRNA codons (UAA, UAG and UGA) are stop codons. These terminate translation by binding to release factors rather than tRNA molecules, so canonical pairing would require 61 species of tRNA. Since most organisms have fewer than 45 types of tRNA, ⁣some tRNA types can pair with multiple, synonymous codons, all of which encode the same amino acid. In 1966, Francis Crick proposed the Wobble Hypothesis to account for this. He postulated that the 5' base on the anticodon, which binds to the 3' base on the mRNA, was not as spatially confined as the other two bases and could, thus, have non-standard base pairing. Crick creatively named it for the small amount of "play" or wobble that occurs at this third codon position. Movement ("wobble") of the base in the 5' anticodon position is necessary for small conformational adjustments that affect the overall pairing geometry of anticodons of tRNA" (Wikipedia article on Wobble base pair, accessed 7-22).

Order of authorship in the original publication: Sarabhai, Stretton, Brenner, Bolle. Brenner (Nobel Prize 2002) and colleagues performed the first study to show co-linearity; i.e., that there is a simple congruence between the amino acid sequence of a protein and the nucleotide sequence of the gene determining that protein. Brenner and his team were working with "nonsense" mutants, called amber mutants, that terminated protein synthesis in E. coli genes.

            "The presence of random nonsense mutants would therefore yield multiple random protein fragments of different sizes. . . . [W]e now suddenly realized that since we had all these amber mutants in this gene we could give a topological proof of co-linearity. And we wouldn't have to do any protein sequencing! The only assumption we would have to make is that the protein is always read from the same end, which seemed a very reasonable one. So in 1964 we published a paper which proved that the gene and the protein were co-linear by an argument that was totally unexpected at that time. We showed that as the amber mutations moved further and further to the right in the position of the gene, we got progressively more and more of the protein made. (Brenner, My Life, p. 103). 

Zamecnick and Stephenson reported the first example of specific inhibition of gene expression by an oligonucleotide when they demonstrated that a short oligonucleotide inhibited Rous sarcoma virus replication in cell culture. This work on gene expression modulation led to antisense therapy, or antisense therapeutics. Digital facsimile from PubMedCentral at this link.
Followed in the same journal issue by Zamecnik and Stephenson, "Inhibition of Rous viral RNA translation by a specific oligodeoxyribonucleotide (in vitro protein synthesis / nucleic acid hybridization / DNA nucleotidyltransferase)," Proc. Nat. Acad. Sci. (USA), 75, 285-288. Digital facsimile from pnas.org at this link.

Working as a graduate student with Lederberg, Zinder discovered that a bacteriophage can carry genes from one bacterium to another. Initial experiments were carried out using Salmonella. Zinder and Lederberg named this process of genetic exchange transduction. Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. It is a common tool used by molecular biologists to stably introduce a foreign gene into a host cell's genome. Digital facsimile from PubMedCentral at this link.

Order of authorship in the original publication: Shapiro, MacHattie, Eron, Ihler, Ippen, Beckwith. Beckwith led the research group that in 1969 isolated the first gene from an organism, specifically a gene from a bacterial chromosome. The gene they isolated was lacZ, which codes for the β-galactosidase enzyme used by E. coli bacteria to digest the sugars in milk. Their technique involved transduction to clone oppositely oriented copies of the gene inserted into two specialized transducing bacteriophages, then mixing single-stranded DNA from the two phages so that only the bacterial sequences would form a double helix, and finally using a nuclease to degrade the single-stranded phage sequences, leaving only the double-stranded lacZ DNA" (Wikipedia article on James A. Shapiro, accessed 7-22).

First description of a "complete" genomic library. This paper includes the Carbon-Clarke equation used for calculating the number of clones required when constructing a clone library to ensure a given probability (usually > 99% is desired) of containing any sequence, given the size of the genome and the average size of a clone.

Edmonds discovered the poly-A tails on eukaryotic mRNA. The addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA), is called polyadenylation.

Poly(A)polymerase was first identified in 1960 as an enzymatic activity in extracts made from cell nuclei that could polymerise ATP, but not ADP, into polyadenine. Although identified in many types of cells, this activity had no known function until 1971, when Edmonds found poly(A) sequences in mRNAs. The only function of these sequences was thought at first to be protection of the 3′ end of the RNA from nucleases, but later the specific roles of polyadenylation in nuclear export and translation were identified. The polymerases responsible for polyadenylation were first purified and characterized in the 1960s and 1970s, but the large number of accessory proteins that control this process were discovered only in the early 1990s. Digital facsimile from PubMedCentral at this link.

Isolation of the first human tumor suppressor gene. Order of authorship in the original publication: Friend, Bernards, Rogeli, Weinberg, Rapaport, Albert, Dryja.

Brinster and Palmiter created the first "transgenic" animals, transferring non-native genes into mice through genetic engineering techniques. The cover of the issue of Science magazine in which this paper was published includes a picture of a normal mouse and a human growth-hormone enhanced mouse. With G. Norstedt, R. E. Gelinas, R. E. Hammer.

Furuichi, working in Shatkin's laboratory, discovered that the viral mRNAs synthesized in vitro by the virion-associated RNA polymerase of reovirus contain a unique 5′-terminal structure m7GpppNm or cap. The precise biosynthetic pathways leading to the cap formation were then elucidated. These and other breakthroughs eventually led to the finding that this unique cap structure is also present in both the eukaryotic cytoplasmic mRNAs and heterogeneous nuclear RNAs, which in turn led to the discovery of mRNA splicing, critical to mRNA vaccines.  With M. Morgan and S. Muthukrishnan.

Digital facsimile from PubMedCentral at this link.

Order of authorship in the original publication: Shamblott, Axelman,... Gearheart. Gearheart led the team that successfully developed human embryonic germ cells, pluripotent stem cells derived from primordial germ cells (PGCs). Digital facsimile from PubMedCentral at this link.

Order of authorship in the original publication: Gellert, Mizuuchi, O'Dea, Nash. Discovery of DNA gyrase, the first type II topoisomerase to be discovered. 

"It is the only type II enzyme to retain its historical name. In contrast to other type II topoisomerases, DNA gyrase is the only enzyme that is capable of actively underwinding (i.e., negatively supercoiling) the double helix. It accomplishes underwinding by wrapping DNA around itself in a right-handed fashion (creating a positive supercoil) and carrying out its strand-passage reaction in a unidirectional manner (thus converting a positive to a negative supercoil). A motif in the C-terminal domain of the GyrA subunit, termed the GyrA box, is required for the enzyme to carry out this unique function.

"The ability of gyrase to wrap DNA during its strand passage reaction allows it to remove positive supercoils that accumulate in front of replication forks and transcription complexes even faster than it can introduce negative supercoils into relaxed DNA. Thus, DNA gyrase plays a critical role in opening the double helix for these two physiological processes. In addition, DNA gyrase works in conjunction with the ω protein (a type I topoisomerase that removes negative supercoils from the double helix), to maintain the global balance of DNA supercoiling in bacterial cells. Because of its DNA wrapping mechanism, DNA gyrase works primarily on DNA supercoiling; it is far less efficient at removing knots and tangles from the genome. In bacteria, these reactions are carried out primarily by the other type II topoisomerase, topoisomerase IV" (Encyclopedia of Biological Chemistry, [2004]).
Digital facsimile of the 1976 paper from PubMedCentral at this link.

Working at Genentech, Kleid and Goeddel and colleagues were the first scientists to apply genetic engineering techniques, incorporating chemically synthesized DNA encoding human insulin into E. coli, that expressed, after appropriate treatment, synethetic human insulin. Digital facsimile from PubMedCentral at this link.

Kornberg (Nobel Prize 2007) devoted two decades to the development of methods to visualize the atomic structure of RNA polymerase and its associated protein components. Initially, Kornberg took advantage of expertise with lipid membranes gained from his graduate studies to devise a technique for the formation of two-dimensional protein crystals on lipid bilayers. These 2D crystals could then be analyzed using electron microscopy to derive low-resolution images of the protein's structure. Eventually, Kornberg was able to use X-ray crystallography to solve the 3-dimensional structure of RNA polymerase at atomic resolution. Through these studies, Kornberg created an actual picture of how transcription works at a molecular level. According to the Nobel Prize committee, "the truly revolutionary aspect of the picture Kornberg has created is that it captures the process of transcription in full flow. What we see is an RNA-strand being constructed, and hence the exact positions of the DNA, polymerase and RNA during this process.” With P Cramer , D A Bushnell, J Fu, A L Gnatt, B Maier-Davis, N E Thompson, R R Burgess, A M Edwards, P R David. Digital facsimile from PubMedCentral at this link.

Hayes "developed the concept of a donor–recipient partnership with uni-directional transfer of genetic material. The importance of this discovery was quickly emphasised and widely recognised when he found that only a part of the genetic material was transferred from the donor strain (male) to the recipient" (Wikipedia article William Hayes, accessed 7-22).

Holliday described a mechanism of DNA-strand exchange that attempted to explain gene-conversion events that occur during meiosis in fungi. That model became known as the Holliday Junction. 

"A Holliday junction is a branched nucleic acid structure that contains four double-stranded arms joined. These arms may adopt one of several conformations depending on buffer salt concentrations and the sequence of nucleobases closest to the junction....In biology, Holliday junctions are a key intermediate in many types of genetic recombination, as well as in double-strand break repair. These junctions usually have a symmetrical sequence and are thus mobile, meaning that the four individual arms may slide through the junction in a specific pattern that largely preserves base pairing. Additionally, four-arm junctions similar to Holliday junctions appear in some functional RNA molecules" (Wikipedia article on Holliday Junction, accessed 7-22).

Tony Hunter discovered that tyrosine phosphorylation is a fundamental mechanism for transmembrane-signal transduction in response to growth factor stimulation, and that disregulation of such tyrosine phosphorylation, by activated oncogenic protein tyrosine kinases, is a pivotal mechanism utilized in the malignant transformation of cells. This cell-signaling mechanism revolutionized basic research on cancer. Digital facsimile from PubMedCentral at this link.

Smith and Hutchison introduced site-directed mutagenesis, or oligonucleotide-directed mutagenesis, into molecular biology, resolving the problem of how to determine the effect of a single mutant gene with efficiency. They developed a synthetic DNA technique for introducing site-specific mutations into genes. This permitted comparison of different protein molecules, revealing the role of the initial mutation. The technique is used for investigating the structure and biological activity of DNA, RNA, and protein molecules, and for protein engineering.

The new technology enabled rapid identification and deliberate alteration of genes for the purpose of changing the characteristics of an organism. It raised the level of possibility of new diagnostic strategies and new treatments for genetic diseases, and even creation of novel artificial forms of life, as the progenitor technique for polymerase chain reaction (PCR). For developing site-directed mutagenesis Smith shared the 1993 Nobel Prize in Chemistry with Kary Mullis, the inventor of polymerase chain reaction. Digital facsimile from PubMedCentral at this link.

The Okazakis discovered what became known as Okazaki fragments, short sequences of DNA nucleotides (approximately 150 to 200 base pairs long in eukaryotes) which are synthesized discontinuously and later linked together by the enzyme DNA to create the lagging strand during DNA replication. Before this discovery it was commonly thought that replication was a continuous process for both strands, but the discoveries involving E. coli led to a new model of replication. The Ozakis found that there was a discontinuous replication process by pulse-labeling DNA and observing changes that pointed to non-contiguous replication.

The Ozakis published their results in 4 papers:

2. "Mechanism of DNA Chain Growth, II. Accumulation of Newly Synthesized Short Chains in E. coli Infected with Ligase-Defective T4 Phages," Proc. Nat. Acad. Sci. (USA) 60, (1968) 1356-1362.
3. "Mechanism of DNA Chain Growth, III. Equal Annealing of T4 Nascent Short DNA Chains with the Separated Complementary Strands of the Phage DNA," Proc. Nat. Acad. Sci. (USA), 63 (1969) 1343-1350.
4. "Mechanism of DNA Chain Growth, IV. Direction of Synthesis of T4 Short DNA Chains as Revealed by Exonucleolytic Degradation," Proc. Nat. Acad. Sci. (USA) 64 (1969) 1242-1248.
Digital facsimiles of all 4 papers are available from PubMedCentral.

Ptashne was the first to demonstrate specific binding between protein and DNA.  Abstract for the paper: "Genetic experiments show that a group of genes may be switched off by the product of a regulator gene, called a repressor. An isolated repressor is shown here to bind specifically and with high affinity to DNA, strongly suggesting that, in vivo, repressors block the transcription from DNA to RNA by binding directly to the DNA."

Schell and Montagu discovered the gene transfer mechanism between Agrobacterium and plants, which resulted in the development of methods to alter Agrobacterium into an efficient delivery system for gene engineering in plants.

Abstract of the paper: "Foreign genes introduced into plant cells with Ti-plasmid vectors are not expressed. We have constructed an expression vector derived from the promoter sequence of nopaline synthase, and have inserted the coding sequences of the octopine synthase gene and a chloramphenicol acetyltransferase gene into this vector. These chimaeric genes are functionally expressed in plant cells after their transfer via a Ti-plasmid of Agrobacterium tumefaciens."

Invention of the first semi-automated DNA sequencing machine by Leroy H. Hood, Lloyd M. Smith and colleagues.
Abstract of the paper:
"We have developed a method for the partial automation of DNA sequence analysis. Fluorescence detection of the DNA fragments is accomplished by means of a fluorophore covalently attached to the oligonucleotide primer used in enzymatic DNA sequence analysis. A different coloured fluorophore is used for each of the reactions specific for the bases A, C, G and T. The reaction mixtures are combined and co-electrophoresed down a single polyacrylamide gel tube, the separated fluorescent bands of DNA are detected near the bottom of the tube, and the sequence information is acquired directly by computer."
With Jane Z. Sanders, Robert J. Kaiser, Peter Hughes, Chris Dodd, Charles R. connell, Cheryl Heiner, and Stephen B. H. Kent.

Solter discovered mammalian genomic imprinting that causes parent-of-origin specific gene expression, with consequences for development and disease.

"Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the mother or the father. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. ...
Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. These epigenetic marks are established ("imprinted") in the germline (sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the somatic cells of an organism.

"Appropriate imprinting of certain genes is important for normal development. Human diseases involving genomic imprinting include Angelman syndrome, Prader–Willi syndrome and male infertility. (Wikipedia article Genomic imprinting, accessed 7-22).

Spiegelman's Monster, the name given to an RNA chain of only 218 nucleotides that can be reproduced by the RNA replication enzyme RNA-dependent RNA polymerase, also called RNA replicase. Spiegelman achieved the first synthesis of a biologically competent, infective viral nucleic acid. See https://profiles.nlm.nih.gov/spotlight/px/feature/monster

With I. Haruna, I. B. Holland, G. Beaudreau, and D. Mlls. Digital facsimile from PubMedCentral at this link.

Steitz and Lerner used immunoprecipitation with human antibodies from patients with autoimmunity to isolate and identify the novel entities snRNPs (pronounced "snurps") and detect their role in splicing. A snRNP is a specific short length of RNA, around 150 nucleotides long, associated with protein, that is involved in splicing introns out of newly transcribed RNA (pre-mRNA), a component of the spliceosomes. Steitz's paper "set the field ahead by light years and heralded the avalanche of small RNAs that have since been discovered to play a role in multiple steps in RNA biosynthesis," noted Susan Berget. Order of authorship in the original publication: Streitz, Wolin...Lerner.

Wollman and Jacob discovered zygotic induction. This occurs when a bacterial cell carrying the silenced DNA of a bacteriophage transfers the viral DNA along with its own DNA in its chromosome to another bacterial cell lacking the virus, causing the recipient of the DNA to break open. In the donor cell, a repressor protein encoded by the prophage (viral DNA) keeps the viral genes turned off so that virus is not produced. When DNA is transferred to the recipient cell by conjugation, the viral genes in the transferred DNA are immediately turned on because the recipient cell lacks the repressor. As a result, many viruses are made in the recipient cell, and lysis eventually occurs to release the new virus.... Zygotic induction provided insight into the nature of bacterial conjugation. It also contributed to the development of the early repression model of gene regulation that explained how the lac operon and λ bacteriophage genes are negatively regulated.

Jacob and Monod received their share of the Nobel Prize in 1965 for their discoveries concerning the operon and viral synthesis. The first operon they described was the lac operon in E. coli. Their operon theory suggested that in all cases, genes within an operon are negatively controlled by a repressor acting at a single operator located before the first gene. Later, it was discovered that genes could be positively regulated, and also regulated at steps that follow transcription initiation. Therefore, no generalized regulatory mechanism is possible because different operons have different mechanisms. Today, an operon is defined as a functioning unit of DNA containing a cluster of genes under the control of a single promotor, transcribed together into a single mRNA strand. 

"Morton's toe,"  the condition of having a first metatarsal which is short in relation to the second metatarsal.  It is a type of brachymetatarsia. 
See also Morton, The human foot: Its evolutionary development, physiology, and function disorders. New York: Columbia University Press, 1935. Morton believed that two major causes of foot problems were the short first metatarsal bone and hypermobility of the first metatarsal bone.

Edition by Francisco Guerra and first publication of a manuscript by Eleuterio in the Wellcome Library. According to the catalogue of the Wellcome archives the contents are as follows:

"Los médicos y las enfermedades de Monterrey". Produced in Monterrey, Nuevo León, Mexico.

"Holograph MS with presentation inscription on first leaf, 'A mi muy querido Discípulo y amigo el Dr.Juan de Dios Treviño. Monterey Marzo 8 de 1881'; signed, with rúbrica.

"F. 2r-f. 7r: Los médicos de Monterrey.

"F. 8r-f. 17r: Las enfermedades de Monterrey.

"F. 18r-f. 25v: [Lists of physicians and pharmacists practising in Monterrey before and after the foundation of the Escuela de Medicina in 1859, and lists of staff and graduates of the School before and after its separation from the Colegio Civil in 1877].

"The first two sections provide detailed accounts of major events in the medical life of Monterrey."

This paper gives the formulae for the Fourier transforms of a number of helical structures, and provides evidence that the structure of a synthetic polypeptide was based on the alpha helix of Pauling and Corey. "It was, I believe, the first fairly conclusive experimental evidence for the existence of a helical structure at the molecular level.... The value of this work, seen in retrospect, is that it was a first step on the road to the discovery of the structure of DNA by Jim Watson and Crick" (Cochran, "This week's citation classic," Current Contents, May 18, 1987, 16).

Following Max Delbruck's advice, Dulbecco visited the major centers of animal virus work in the US in order to discover a way to quantitatively assay animal viruses by a plaque technique, similar to the technique that had recently been developed for bacterial viruses (bacteriophages). Within less than a year Dulbecco worked out such a method for Western equine encephalitis virus, which then opened up animal virology to quantitative work. The technique was then used by Dulbecco and Vogt to study the biological properties of poliovirus. Digital facsimile from PubMedCentral at this link.