In 1953,  Francis Crick ,  James Watson ,  Maurice Wilkins  and  Rosalind Franklin  discovered the  double helix  structure of the  DNA  macromolecule. Gamow attempted to solve the problem of how the ordering of four different bases ( adenine ,  cytosine ,  thymine  and  guanine ) in DNA chains might control the synthesis of proteins from their constituent amino acids. [ 28 ]  Crick has said that Gamow's suggestions helped him in his own thinking about the problem. [ 29 ]  As related by Crick, [ 30 ]  Gamow observed that the 4 3  = 64 possible  permutations  of the four DNA bases, taken three at a time, would be reduced to 20 distinct  combinations  if the order was irrelevant. [ 31 ]  Gamow proposed that these 20 combinations might code for the twenty amino acids which, he suggested, might well be the sole constituents of all proteins. Gamow's contribution to solving the problem of genetic coding gave rise to important models of  biological degeneracy . [ 32 ] [ 33 ]


The specific system that Gamow was proposing (called "Gamow's diamonds") proved to be incorrect. The triplets were supposed to be overlapping, so that in the sequence GGAC (for example), GGA could produce one amino acid and GAC another, and also  non-degenerate  (meaning that each amino acid would correspond to one combination of three bases – in any order). Later protein sequencing work proved that this could not be the case; the true  genetic code  is non-overlapping and degenerate, and changing the order of a combination of bases does change the amino acid.


In 1954, Gamow and Watson co-founded the  RNA Tie Club . This was a discussion group of leading scientists concerned with the problem of the genetic code, which counted among its members the physicists  Edward Teller  and  Richard Feynman . In his autobiographical writings, Watson later acknowledged the great importance of Gamow's insightful initiative. However, this did not prevent him from describing this colorful personality as a "zany", card-trick playing, limerick-singing, booze-swilling, practical–joking "giant imp". [ 34 ]


Gamow worked at George Washington University from 1934 until 1954, when he became a visiting professor at the  University of California, Berkeley . In 1956, he moved to the  University of Colorado Boulder , where he remained for the rest of his career. In 1956, Gamow became one of the founding members of the  Physical Science Study Committee  (PSSC), which later reformed teaching of high-school physics in the post- Sputnik  years.


In 1959, Gamow,  Hans Bethe , and  Victor Weisskopf  publicly supported the re-entry of  Frank Oppenheimer  into teaching college physics at the  University of Colorado , as the  Red Scare  began to fade ( J. Robert Oppenheimer  was the older brother of Frank Oppenheimer, and both of them had worked on the  Manhattan Project  before their careers in physics were derailed by  McCarthyism ). [ 35 ] : 130   While in Colorado, Frank Oppenheimer became increasingly interested in teaching science through simple hands-on experiments, and he eventually moved to  San Francisco  to found the  Exploratorium . [ 35 ] : 130–152    Gamow would not live to see his colleague's opening of this innovative new science museum, in late August 1969. [ 35 ] : 152


In his 1961 book  The Atom and its Nucleus , Gamow proposed representing the  periodic system  of the  chemical elements  as a continuous tape, with the elements in order of  atomic number  wound round in a three-dimensional helix whose diameter increased stepwise (corresponding to the longer rows of the conventional periodic table).


Gamow continued his teaching at the University of Colorado Boulder and focused increasingly on writing textbooks and books on science for the general public. After several months of ill health, surgeries on his circulatory system, diabetes, and liver problems, Gamow was dying from  liver failure , which he had called the "weak link" that could not withstand the other stresses.


In a letter written to Ralph Alpher on August 18, he had written, "The pain in the abdomen is unbearable and does not stop". Prior to this, there had been a long exchange of letters with his former student, in which he was seeking a fresh understanding of some concepts used in his earlier work, with Paul Dirac.  Gamow relied on Alpher for deeper understanding of mathematics.


On August 19, 1968, Gamow died at age 64 in  Boulder, Colorado , and was buried there in Green Mountain Cemetery. The physics department tower at the University of Colorado at Boulder is named after him.


Gamow had a son,  Igor Gamow , with his first wife Rho in 1935. Their son later became a professor of  microbiology  at the  University of Colorado , as well as an inventor.


In 1956, Gamow divorced his wife Rho. In 1958 he married  Barbara Perkins , an editor for one of his publishers.


Gamow was a well-known prankster, who delighted in practical jokes and humorous twists embedded in serious scientific publications. [ 36 ] [ 37 ]  His most famous prank was the pioneering  Alpher–Bethe–Gamow paper  (1948), which was serious in its style and content. However, Gamow could not resist adding his colleague  Hans Bethe  to the list of authors, as a  pun  on the first three letters of the  Greek alphabet . [ 36 ] [ 38 ] [ 37 ]


Gamow was an atheist. [ 39 ] [ 40 ] [ 41 ]


Gamow was a highly successful science writer, with several of his books still in print more than a half-century after their initial publication. As an educator, Gamow recognized and emphasized fundamental principles that were unlikely to become obsolete, even as the pace of science and technology accelerated. He also conveyed a sense of excitement with the revolution in physics and other scientific topics of interest to the common reader. Gamow himself sketched the many illustrations for his books, which added a new dimension to and complemented what he intended to convey in the text. He was unafraid to introduce mathematics wherever it was essential, but he tried to avoid deterring potential readers by including large numbers of equations that did not illustrate essential points.


In 1946 Gamow was a proponent of  human spaceflight  propelled by atomic energy. [ 42 ]  "We may prepare ourselves for a trip to the moon and to various planets of our solar system in a comfortable rocketship driven by atomic power." He also wrote "the ordinary chemical fuels which could be used in the motor of such a rocketship could not possibly give it the necessary velocity...". [ 43 ]
By 1965 he moderated his expectations though he re-stated his atomic-power prognostication:


Whereas we may be able to study the forms of life that may have developed on Mars and Venus (the best "inhabitable" planets of the solar system) in the not too distant future by means of an adventuresome trip to these planets on a "nuclear power propelled space ship," the question about the possible existence and the forms of life in other stellar worlds hundreds and thousands of light-years away, will probably remain forever an unsolvable problem of science. [ 44 ]


By that  time the  space race  was underway with conventional chemical rockets.


His book,  The Creation of the Universe , was first published in 1952, concluding: "It took less than an hour to make all the atoms in the universe, a few hundred million years to make the stars and planets but three billion years to make man." [ 45 ] [ 46 ]


In 1956, he was awarded the  Kalinga Prize  by  UNESCO  for his work in popularizing science with his  Mr. Tompkins...  series of books (1939–1967), his book  One, Two, Three...Infinity , and other works. [ 1 ]


Before his death, Gamow was working with Richard Blade on a textbook  Basic Theories in Modern Physics , but the work was never completed or published under that title.  Gamow was also writing  My World Line: An Informal Autobiography , which was published posthumously in 1970.


A collection of Gamow's writings was donated to The  George Washington University  in 1996.  The materials include correspondence, articles, manuscripts and printed materials both by and about George Gamow.  The collection is currently under the care of GWU's Special Collections Research Center, located in the Estelle and Melvin  Gelman Library . [ 47 ]


Throughout these books,  Mr Tompkins  is introduced as "C. G. H. Tompkins" to emphasize the notion of  cGh physics .


The Genetical Theory of Natural Selection  is a book by  Ronald Fisher  which combines  Mendelian genetics  with  Charles Darwin 's theory of  natural selection , [ 1 ]  with Fisher being the first to argue that "Mendelism therefore validates Darwinism" [ 2 ]  and stating with regard to  mutations  that "The vast majority of large mutations are deleterious; small mutations are both far more frequent and more likely to be useful", thus refuting  orthogenesis . [ 3 ]  First published in 1930 by  The Clarendon Press , it is one of the most important books of the  modern synthesis , [ 4 ]  and helped define  population genetics . It had been described by  J. F. Crow  as the "deepest book on evolution since Darwin". [ 5 ]


It is commonly cited in biology books, outlining many concepts that are still considered important such as  Fisherian runaway ,  Fisher's principle ,  reproductive value ,  Fisher's fundamental theorem of natural selection ,  Fisher's geometric model , the  sexy son hypothesis ,  mimicry  and the  evolution of dominance . It was dictated to his wife in the evenings as he worked at  Rothamsted Research  in the day. [ 6 ]


In the preface, Fisher considers some general points, including that there must be an understanding of natural selection distinct from that of  evolution , and that the then-recent advances in the field of  genetics  (see  history of genetics ) now allowed this. In the first chapter, Fisher considers the nature of inheritance, rejecting  blending inheritance , because it would eliminate genetic variance, in favour of particulate inheritance. The second chapter introduces Fisher's fundamental theorem of natural selection. The third considers the evolution of dominance, which Fisher believed was strongly influenced by modifiers. Other chapters discuss  parental investment , Fisher's geometric model, concerning how spontaneous  mutations  affect  biological fitness , Fisher's principle which explains why the  sex ratio  between  males  and  females  is almost always 1:1, reproductive value, examining the  demography  of having girl children. Using his knowledge of  statistics , the Fisherian runaway, which explores how  sexual selection  can lead to a  positive feedback  runaway loop, producing features such as the  peacock's   plumage . He also wrote about the evolution of dominance, which explores  genetic dominance .


The last five chapters (8-12) include Fisher's concern about  dysgenics  and proposals for  eugenics . Fisher attributed the fall of  civilizations  to the fertility of their upper classes being diminished, and used British 1911 census data to show an inverse relationship between fertility and social class, partly due, he claimed, to the lower financial costs and hence increasing social status of families with fewer children. He proposed the abolition of extra allowances to large families, with the allowances proportional to the earnings of the father. He served in several official committees to promote eugenics. In 1934, he resigned from the Eugenics Society over a dispute about increasing the power of scientists within the movement. [ 7 ] [ 8 ] [ 9 ]


A second, slightly revised edition was republished in 1958. In 1999, a third  variorum  edition ( ISBN   0-19-850440-3 ), with the original 1930 text, annotated with the 1958 alterations, notes and alterations accidentally omitted from the second edition was published, edited by professor John Henry Bennett of the  University of Adelaide .


The book is dedicated to Major  Leonard Darwin , Fisher's friend, correspondent and son of Charles Darwin, "In gratitude for the encouragement, given to the author, during the last fifteen years, by discussing many of the problems dealt with in this book."


The book was reviewed by  Charles Galton Darwin , who sent Fisher his copy of the book, with notes in the margin, starting a correspondence which lasted several years. [ 10 ]  The book also had a major influence on  W. D. Hamilton 's theories on the genetic basis of  kin selection .


John Henry Bennett gave an account of the writing and reception of the book. [ 11 ]


Sewall Wright , who had many disagreements with Fisher, reviewed the book and wrote that it was "certain to take rank as one of the major contributions to the theory of evolution." [ 12 ]   J. B. S. Haldane  described it as "brilliant." [ 13 ]   Reginald Punnett  was negative, however. [ 14 ]


The book was largely overlooked for 40 years, and in particular Fisher's  fundamental theorem of natural selection  was misunderstood. The work had a great effect on  W. D. Hamilton , who discovered it as an undergraduate at the  University of Cambridge [ 15 ]  and noted in these excerpts from the rear cover of the 1999 variorum edition:


This is a book which, as a student, I weighed as of equal importance to the entire rest of my undergraduate Cambridge  BA  course and, through the time I spent on it, I think it notched down my degree. Most chapters took me weeks, some months;...And little modified even by  molecular genetics , Fisher's logic and ideas still underpin most of the ever broadening paths by which  Darwinism  continues its invasion of human thought.

For a book that I rate only second in importance in evolution theory to Darwin's " Origin " (this as joined with its supplement " of Man "), and also rate as undoubtedly one of the greatest books of the twentieth century the appearance of a variorum edition is a major event....

Unlike in 1958, natural selection has become part of the syllabus of our intellectual life and the topic is certainly included in every decent course in biology. By the time of my ultimate graduation, will I have understood all that is true in this book and will I get a First? I doubt it. In some ways some of us have overtaken Fisher; in many, however, this brilliant, daring man is still far in front.


The publication of the variorum edition in 1999 led to renewed interest in the work and reviews by  Laurence Cook , [ 16 ]   Brian Charlesworth , [ 17 ]   James F. Crow , [ 18 ]  and  A. W. F. Edwards . [ 1 ]


Genetics and the Origin of Species  is a 1937 book by the Ukrainian-American evolutionary biologist  Theodosius Dobzhansky . It is regarded as one of the most important works of  modern synthesis  and was one of the earliest. The book popularized the work of  population genetics  to other biologists and influenced their appreciation for the  genetic basis  of evolution. [ 1 ]  In his book, Dobzhansky applied the theoretical work of  Sewall Wright  (1889–1988) to the study of natural populations, allowing him to address evolutionary problems in a novel way during his time. Dobzhansky implements theories of mutation, natural selection, and speciation throughout his book to explain the habits of populations and the resulting effects on their genetic behavior. [ 2 ]  The book explains evolution in depth as a process over time that accounts for the diversity of all life on Earth. The study of evolution was present, but greatly neglected at the time. Dobzhansky illustrates that evolution regarding the origin and nature of species during this time in history was deemed mysterious, but had expanding potential for progress to be made in its field. [ 3 ] : 8


In Darwin's theory of  natural selection , more organisms are produced than can survive. Some have variations that give them a competitive advantage, and they have the best chance of surviving and procreating. The main element lacking in the theory was any mechanism that would allow organisms to pass on these favorable variations. Lacking such a mechanism, the theory of evolution faced competition from theories such as  neo-Lamarckism , in which the environment acted directly on organisms, changing their structures. Darwin did not know that the monk  Gregor Mendel  was already working on experiments that would explain inheritance in terms of units of heredity that we now call genes. [ 4 ]


When Mendelian genetics was rediscovered by several scientists, it initially increased the confusion. The Dutch botanist  Hugo de Vries  developed a theory called  mutationism  in which most variations were inconsequential and could not lead to species change. Instead, new species were formed by large  mutations . [ 4 ]  At first, geneticists tended to support mutationism; but in the 1920s and 1930s a group of theoretical geneticists – particularly  Ronald Fisher ,  J. B. S. Haldane  and  Sewall Wright  – showed that Mendel's laws could explain continuous variation in biological characteristics; and that natural selection could act cumulatively, giving rise to large changes. Their work provided a theoretical framework for incorporating genetics into the theory of evolution. [ 4 ]


Many biologists fell into two camps: the geneticists, who mostly worked in the laboratory; and  naturalists , who studied natural populations in the field and museums, and put much of their effort into  taxonomy . Each contributed concepts that were essential to the understanding of evolution. Naturalists introduced the  biological species concept , the definition of species as a community that is reproductively isolated and occupies a distinctive  ecological niche . [ 5 ] : 273   They also recognized that species are  polytypic , having variations in time and space; and that behavior and change of function can give rise to evolutionary change. [ 5 ] : 570


The two groups used such different methods and terminology that it was difficult for them to communicate. They were often battling over the same scarce academic resources, and each was often scornful of the other. As the  paleontologist   George Gaylord Simpson  put it, paleontologists believed that "a geneticist was a person who shut himself in a room, pulled down the shades, watched small flies disporting themselves in milk bottles, and thought that he was studying nature." Meanwhile, naturalists were "like a man who undertakes to study the principles of the internal combustion engine by standing on a street corner and watching the motor cars whiz by." [ 6 ]


The book began as a series of lectures at  Columbia University  in October and November 1936. Dobzhansky decided to attend the summer 1936 meeting of the  Genetics Society of America  in Woods Hole, Massachusetts. When the geneticist  Leslie Dunn  learned of this, he invited Dobzhansky to give a series of lectures at Columbia. He sent the invitation in April, and within a month he had suggested that the lectures be a springboard for writing a general treatise on evolutionary genetics. Dobzhansky was enthusiastic, and in May he wrote back, proposing the title "Genetics and the Origin of Species". He envisioned two parts – "part I containing data on the sources of evolutionary change, and part II containing a discussion of their interactions leading to race- and species formation." [ 7 ]  After the lectures (for which he received $500), Dobzhansky returned to Pasadena, and in December  Columbia University Press  accepted his proposal for a book. The pace of writing was helped by a riding accident in February 1937 in which he crushed his knee, rendering him immobile; and by April he was able to send a manuscript to Dunn for his perusal. [ 7 ]


While reading the manuscript, Dunn persuaded the university to revive the Jesup lectures, a series that had involved some notable lecturers in the past. It was back-dated so that Dobzhansky's lectures became the first in the series. The Columbia University Biological Series was also revived, and when  Genetics and the Origin of Species  was published in October 1937 it became the 11th volume in that series. [ 7 ]


Three main editions were published, in 1937, 1941 and 1951, each with significant changes. Dobzhansky considered  Genetics of the Evolutionary Process  (1970) a fourth edition, but one so much changed that it needed a new title. [ 8 ] : 166  [ 9 ]


Genetics and the Origin of Species  has two main points to make. The first is that speciation is a genuine problem that must be explained by the theory of evolution. In nature, there is not a single population of organisms separated from each other by small  variations . Instead, the natural world is divided into species, each with its own limited range of variability. The second point is that all the variations can be explained by the principles of genetics. [ 10 ] : xxvi–xxvii


The 1937 edition was divided into nine chapters, whose contents are described below.


The first chapter is a short outline of the main points of the book: Evolutionary theory must account for variations on the level of the individual and also that of populations and species. It must explain how reproductive isolation can occur. And the goal is to explain all this using genetic principles that can be verified in the laboratory. [ 10 ] : xxix


The second chapter argues that mutations occur frequently and are random in direction. Most are small in effect, but they affect all features of organisms and vary from beneficial to lethal. They are sufficient to provide the raw material for natural selection. [ 10 ] : xxix


In the third chapter, Dobzhansky demonstrates that the mutations that are observed in the laboratory also occur in nature, where they are acted on by natural selection. Thus, there is nothing intrinsically different about the process by which new species evolve. [ 10 ] : xxix–xxx


Dobzhansky continues the theme of continuity between the laboratory and nature in chapter 4, showing that variations in the structure, arrangement and number of  chromosomes  occur in both the laboratory and nature. He shows that  chromosomal translocation , a rearrangement of parts in chromosomes, accounts for racial differences in  Datura stramonium  (jimson-weed).  Chromosomal inversion , a reversal of a segment, is the basis for differentiation in  Drosophila . He also points out that these effects demonstrate that the chromosome parts are interdependent. [ 10 ] : xxx


Having established that the sources of natural variation are mutations and chromosomal rearrangements, Dobzhansky considers what shapes and preserves this variation. In the first edition of this book, he considers  genetic drift  as important as natural selection. As an example, he argued that drift was the reason for racial variations that were observed in  Partula , a  land snail , so these variations had no adaptive advantage. He argued that most such variations, which he called  microgeographic race , was nonadaptive. Because variation is not always controlled by selection, we need to know the size of a population before we can predict its evolutionary dynamics. [ 10 ] : xxxi


The sixth chapter discusses the evidence for natural selection from experiments in the laboratory and observations of nature. He considered examples of  camouflage  such as  industrial melanism , in which moths and other  arthropods  evolve darker pigmentation when exposed to an environment with a lot of soot in it. He refuted some Mendelian misconceptions about the effectiveness of natural selection, but he also rejected the strict selectionism of  Fisher . [ 10 ] : xxxi–xxxii


In the seventh chapter, Dobzhansky discusses  polyploidy , a condition (common in plants) where an organism has more than two complete sets of chromosomes. [ 11 ]  (Humans are  diploid , having one set each from the mother and father.)  He discusses case histories such as that of  Raphanobrassica , a hybrid between the radish and the cabbage. This is an example of "cataclysmic" speciation, an exception to his general rule that speciation is a slow process. [ 12 ] : 29


An  isolating mechanism  prevents members of two different species from successfully producing offspring. Dobzhansky invented the term, [ 10 ] : xxxiii   and in the eighth chapter he discusses their role in speciation. His views were sufficiently original for him to publish them in a journal article as well. [ 13 ]  Although previous authors had recognized the importance of isolation, their reasons were entirely different from his.  George Romanes  thought that isolation was a cause of change, whereas Dobzhansky sees two competing effects. Isolation reduces the rate of formation of harmful gene combinations, but it also restricts the scope of genetic variation. Thus, a species remains near a given peak in the  fitness landscape  and does not find new adaptive peaks. [ 12 ] : 29–30


Dobzhansky presents a classification of isolating mechanisms. The main division is between  hybrid  sterility, which he discusses in the next chapter, and mechanisms that prevent organisms from mating. These include geographic and ecological isolation. After two populations are changed sufficiently,  "physiological" isolating mechanisms prevent them from mating, so they will remain distinct even if they are no longer physically isolated. This isolation is the end of a continuous process that includes division into races, and involves multiple mutations. [ 12 ] : 30–31


In the chapter on isolating mechanisms, Dobzhansky deplores the "appallingly insufficient attention" that geneticists had devoted to isolation. [ 3 ] : 254   The only isolating mechanism that they had studied was sterility in  hybrid organisms , so he devotes the ninth chapter to a particularly detailed analysis of the literature on this subject. [ 10 ] : xxxiii–xxxiv


Through his work on  Drosophila pseudoobscura , a species of fruitfly, Dobzhansky was able to identify that some populations of this species did not have identical sets of genes. Dobzhansky used experimental breeding in laboratories and gardens, and also surveys related to species in nature to help support aspects of organic evolution. The data in his book show the different genetic mutations and chromosomal changes that were observed. These experiments are vital to this book because they illustrate a transition from the laboratory to the greater field of genetics.  Drosophila  enabled researchers to gain a deeper understanding of how scientific knowledge about heredity has expanded and contributed to other areas of biology. By focusing on the opportunities and constraints of the research organism, persuasive accounts of the chromosomal genetics of  Drosophila  eventually evolved into the genetics of natural populations in the 1930s.  All of the results from his experiments support the theory of modern evolutionary synthesis. [ 14 ]


Through his experiments, Dobzhansky discovers that mutation of genes leads to evolution within a specific species. Adaptations play a large role in genetic drift, and it is known that genes and mutations influence this genetic drift in a particular environment. Mutations can result from external influences within the surrounding environment, especially if an organism inhabits an area with harsh living conditions. An organism can adapt to its environment in order to better suit its own needs. When an organism successfully adapts, it has higher survival and reproduction rates. Therefore, there is a higher chance that its genes will be passed on to its offspring. Specific genes and alleles are then passed on to future generations to continue the trend of modern evolution that Dobzhansky presents in the book. [ 15 ]


Dobzhansky said that natural mutation, aided by variation, can lead to change when acted upon by natural selection. [ 16 ]  Mutations were thought to be relatively rare and other variations were even considered to be harmful. Since an organism's overall genetic make-up was the result of natural selection, with damaging mutations weeded out, wild populations were assumed to have very few mutations. As a result, evolution was said to be a relatively slow process. One of Dobzhansky's major contributions in this book was to show that this view of slow-moving evolution was incorrect. While analyzing chromosome structure in wild populations of  Drosophila pseudoobscura , Dobzhansky discovered a surprising amount of undiscovered variability. These variations could not be observed in the outward appearance of the individual organisms. Dobzhansky suggested that the preservation of extensive variation would allow populations to evolve rapidly as environmental conditions change. This book was a landmark in the evolutionary synthesis, as it presented the union of Mendelian genetics and Darwinian theory. [ 17 ]


In  Genetics and the Origin of Species , polyploidy is considered as a type of mutation. Polyploid cells have a chromosome number that is more than twice the haploid number. The effects of polyploidy between two different species causes hybridization and even greater evolution. [ 3 ]


Natural selection in an environment produces reproductive success, which benefits the species. Speciation is a process of evolution through which new biological species are formed. Dobzhansky studied the specifics of sexual, physiological, and behavioral isolating mechanisms in  Drosophila pseudoobscura  and  Drosophila paulistrorum.  Like many of his other studies, Dobzhansky's work on reproductive isolation was aimed at studying the process of evolution in action. [ 17 ]  Bringing samples from each population back into the laboratory, Dobzhansky showed that he could vary environmental conditions so as to produce the same changes in frequency of inversion patterns that were observed with changing seasons in the field. Dobzhansky concluded that such seasonal fluctuations were the result of natural selection at work, with temperature acting as the selecting agent. These masterful studies provided concrete support for the theory of natural selection, at the same time illustrating the fruitfulness of combining field and laboratory work in the study of evolution. [ 17 ]  Adaptive evolution occurs through the dominance and survival of competing genes within a species. This is caused by increasing the frequency of those alleles whose phenotypic effects selfishly promote their own reproduction. He also believed new species could not arise from single mutations and must be isolated from others of its species by time, geography, habitat, or breeding season. [ 16 ]


Genetics and the Origin of Species  provided the outline for a synthesis of genetics with evolution, and was enthusiastically received by both geneticists and naturalists. Dobzhansky laid out an advanced account of the evolutionary process in genetic terms, and he backed up his work with experimental evidence supporting the theoretical arguments. This led to the stimulation of the field of evolutionary genetics, and contributions to the theory soon began to follow. This had a powerful impact on naturalists and experimental biologists, who quickly embraced this new understanding of the evolutionary process as one of genetic change in populations. [ 18 ]  It was not long before the synthesis was broadened to include paleontology,  systematics  and  botany  in a series of notable books:  Systematics and the Origin of Species  (1942) by  Ernst Mayr ;  Tempo and Mode in Evolution  (1944) by George Gaylord Simpson; and  Variation and Evolution in Plants  (1950) by  G. Ledyard Stebbins . [ 19 ]  The emerging synthesis was called the evolutionary synthesis by  Julian Huxley  in his book,  Evolution: The Modern Synthesis . [ 20 ] : 19   In 1947, a diverse collection of biologists met at a symposium in Princeton and declared their acceptance of this synthesis. However, it was not yet complete.  Developmental biologists  did not accept that the theory explained their observations, and it was not until the 1970s and 1980s that  molecular biology  bridged the gap. Also, for decades there was disagreement over whether the unit of selection was the gene or the individual as a whole. [ 21 ]


In 1974 all the living founders of the modern synthesis (with the exception of Simpson and  Bernhard Rensch ) met with historians of biology in a conference to evaluate their work. All acknowledged  Genetics and the Origin of Species  as the direct instigator of all the work that followed. [ 10 ]  Ernst Mayr, in  The Growth of Biological Thought , said that it was "clearly the most decisive event in the history of evolutionary biology since the publication of the  Origin of Species  in 1859.   [ 5 ] : 569


Dobzhansky was plagued by a form of  leukemia  in his later years, but he remained vigorously active until the day before his death on December 18, 1975. [ 17 ]  During his lifetime he was the recipient of many honors and awards. For  Genetics and the Origin of Species  Dobzhansky was awarded the  Daniel Giraud Elliot Medal  from the  National Academy of Sciences  in 1941. [ 22 ]  Sixty years after its publication, the  National Academy of Sciences  commissioned a book entitled  Genetics and the Origin of Species: From Darwin to Molecular Biology 60 Years After Dobzhansky . [ 23 ]


It was also included in the 1990 edition of  Great Books of the Western World , placing it with  Charles Darwin 's two great works  The Origin of Species  and  The Descent of Man . A third edition was published in 1951.


Frederick Griffith  (1877–1941) was a British  bacteriologist  whose focus was the  epidemiology  and  pathology  of bacterial  pneumonia . In January 1928 he reported what is now known as  Griffith's Experiment , the first widely accepted demonstrations of  bacterial transformation , whereby a bacterium distinctly changes its  form  and  function . [ 2 ]


He showed that  Streptococcus pneumoniae , implicated in many cases of  lobar pneumonia , [ 3 ]  could transform from one strain into a different strain. The observation was attributed to an unidentified underlying principle, [ 2 ]  later known in the Avery laboratory as the "transforming principle" (abbreviated as T. P.) [ 4 ]  and  identified  as  DNA . [ 5 ]
America's leading pneumococcal researcher,  Oswald T. Avery , speculated that Griffith had failed to apply adequate  controls . [ 6 ]  A cautious and thorough researcher, and a reticent individual, Griffith's tendency was to publish only findings that he believed truly significant, and Griffith's findings were rapidly confirmed by researchers in Avery's laboratory. [ 6 ]  His discovery was one of the first to show the central role of DNA in heredity. [ 5 ]


Frederick Griffith was born in  Prescot ,  Merseyside  (formerly in  Lancashire ) England, in late 1877 [ 1 ]  (Registered December quarter in Prescot, Lancashire registration district, vol 8b, page 670), and attended  Liverpool University . Thereafter, he worked at the  Liverpool Royal Infirmary , the Joseph Tie Laboratory, and the Royal Commission on  Tuberculosis .  In 1910 Fred Griffith was hired by the local government board.


During  World War I  (1914–18), the local government board's laboratory was assumed by the national government, namely UK government, and became the  Ministry of Health 's Pathological Laboratory—where Griffith was medical officer.  UK government spent money sparingly on the laboratory, which remained very basic, though Griffith and his colleague, William M. Scott, "could do more with a kerosene tin and a primus stove than most men could do with a palace". [ 6 ]


Griffith was sent pneumococci samples taken from patients throughout the country, amassed a large number, and would type—in other words classify—each pneumococci sample to search patterns of pneumonia epidemiology, and Griffith experimented on mice for improved understanding of its pathology. [ 7 ]  Griffith performed the pivotal experiments—actually very many experiments—during the 1920s.


With outbreak of  World War II  (1939–45), the laboratory was expanded into the Emergency  Public Health Laboratory Service .


Pneumococci has two general forms— rough  (R) and  smooth  (S).  The S form is more  virulent , and bears a  capsule , which is a slippery  polysaccharide  coat—outside the  peptidoglycan   cell wall  common among all classical bacteria—and prevents efficient  phagocytosis  by the host's  innate immune cells .  Injected  subcutaneously  with S form, mice succumbed to pneumonia and death within several days. However, the R form, lacking a capsule—its outer surface being cell wall—is relatively  avirulent , and does not cause pneumonia as often.


When Griffith injected heat-killed S into mice, as expected, no disease ensued. When mice were injected with a mixture of heat-killed S and live R, however, pneumonia and death ensued. The live R had transformed into S—and replicated as such—often characterized as Griffith's Experiment. More accurately, point six of Griffith's abstract reports that R tended to transform into S if a large amount of live R, alone, were injected, and that adding much heat-killed S made transformation  reliable [ 2 ]  Griffith also induced some pneumococci to transform back and forth. [ 2 ]


Griffith also reported transformation of  serological   type —bacterial  antigenicity —distinct from presence or absence of a capsule. Bacteriologist  Fred Neufeld , of the  Robert Koch Institute  in  Berlin , Germany, had earlier identified the pneumococcal types, confirmed and expanded by  Alphonse Dochez  at Oswald Avery's laboratory in  America  at The Rockefeller Hospital. [ 7 ]  Types I, II, and III were each a distinct antigenic grouping, whereas type IV was a catchall of varying antigenicities not matching other types. [ 7 ]


Illustrating the plasticity of  Streptococcus pneumoniae , the abstract of Griffith's paper reports, "The S form of Type I has been produced from the R form of Type II, and the R form of Type I has been transformed into the S form of Type II". [ 2 ]


One of America's most prominent pneumococcus experts,  Oswald Avery , in  New York  at The Rockefeller Hospital—which opened in 1910 on The Rockefeller Institute's campus—initially explained that Griffith's experiments must have been poorly conducted and succumbed to contamination. Avery biographer and colleague at The Rockefeller Institute, microbiologist  Rene Dubos , recruited by The Rockefeller Institute from France, later described Griffith's findings as "exploding a bombshell in the field of pneumococcal immunology". [ 8 ]


Avery's associate  Martin Dawson  at The Rockefeller Hospital confirmed each of Griffith's reported findings. [ 9 ] [ 10 ]  Even before Griffith's publication, Fred Neufeld had confirmed them as well, and was merely awaiting publication of Griffith's findings before publishing his confirmation. [ 6 ] [ 11 ]  Over the following years, Avery's illness,  Graves' disease , kept him much out of his laboratory as other researchers in it experimented to determine, largely by process of elimination, which constituent was the transforming factor. [ 12 ]


Microbiologists endeavored during the 1930s to dispel the monomorphist tenet, prevailing as institutional dogma, [ 13 ]  largely prevailing into the 21st century. [ 14 ]


The first Griffith Memorial Lecture indicates that Fred Griffith died on the night of 17 April 1941 [ 15 ] —though the fourth lecture indicates that he died in his apartment in February 1941 [ 6 ] —alongside friend and colleague William M. Scott amid an  air raid  during World War II's  London Blitz . A few weeks earlier, Scott had become director of the laboratory, which, with the outbreak of war, had become Emergency Public Health Laboratory Service. Both dated 3 May 1941, his  obituary  in  The Lancet  mentioned the historical discovery briefly, [ 16 ]  and his obituary in  British Medical Journal  failed to mention it. [ 17 ]


In 1944 identification of the transforming factor was published in the  Journal of Experimental Medicine  by Avery,  Colin MacLeod , and  Maclyn McCarty  of The Rockefeller Hospital. [ 18 ]  This identification departed from the prevailing belief that the  protein  content of  chromosomes  probably was the anatomical structure of genes, although it would take another decade—till  Watson  and  Crick 's 1953  paper  in  Nature  indicating DNA's molecular structure suggesting how a molecule as seemingly simple as DNA could encode the structure of proteins—for the interpretation of DNA as genes to become widely accepted. [ 19 ] [ 20 ]


Biologists made little more than speculation of Griffith's report of transformation until genetics research in 1951. [ 21 ]  Griffith's report was virtually ignored by  clinicians , and by the medical sector as a whole. [ 6 ]


In 1931 Frederick Griffith coauthored a paper on acute  tonsillitis —its  sequelae , epidemiology, and bacteriology. [ 22 ]  In 1934, Griffith reported voluminous findings on the serological typing of  Streptococcus pyogenes . [ 23 ]  More casually as well as medically called simply streptococcus, [ 24 ]   S pyogenes  is implicated in conditions ranging from the usually minor  strep throat , to the sometimes fatal  scarlet fever , to the often fatal  puerperal fever , to the usually fatal  streptococcal sepsis . [ 25 ]  Streptococcal infection was a frequent coinfection complicating recovery from lobar pneumonia by pneumococci infection. [ 26 ]


By 1967 pneumococcal transformation had been shown to occur  in vivo  naturally, and it was further shown that treatment with  streptomycin  during dual infection by two pneumococcal strains could increase transformation—and virulence—while for the first time pneumococcal transformation was shown to occur in the respiratory tract. [ 27 ]  In 1969 it was shown  in vivo  that during drug treatment of a host, pneumococci could acquire genes from  antibiotic-resistant  streptococci, already in the host, and thereby the pneumococci could become resistant to  erythromycin . [ 28 ]


Griffith's experiment , [ 1 ]  performed by  Frederick Griffith  and reported in 1928, [ 2 ]  was the first experiment suggesting that bacteria are capable of transferring genetic information through a process known as  transformation . [ 3 ] [ 4 ]   Griffith's findings were followed by  research in the late 1930s and early 40s  that isolated  DNA  as the material that communicated this genetic information.


Pneumonia  was a serious cause of death in the wake of the  post-WWI Spanish influenza pandemic , and Griffith was studying the possibility of creating a  vaccine .  Griffith used two  strains  of pneumococcus ( Diplococcus pneumoniae ) bacteria which infect  mice  – a type III-S (smooth) which was  virulent , and a type II-R (rough) strain which was nonvirulent. The III-S strain synthesized a  polysaccharide  capsule that protected itself from the host's  immune system , resulting in the death of the host, while the II-R strain did not have that protective capsule and was defeated by the host's immune system. A German bacteriologist,  Fred Neufeld , had discovered the three pneumococcal types (Types I, II, and III) and discovered the  quellung reaction  to identify them  in vitro . [ 5 ]  Until Griffith's experiment, bacteriologists believed that the types were fixed and unchangeable, from one generation to another.


In this experiment,  bacteria  from the III-S strain were killed by heat, and their remains were added to II-R strain bacteria. While neither alone harmed the mice, the combination was able to kill its host. Griffith was also able to isolate both live II-R and live III-S strains of pneumococcus from the blood of these dead mice. Griffith concluded that the type II-R had been "transformed" into the lethal III-S strain by a "transforming principle" that was somehow part of the dead III-S strain bacteria.


Today, we know that the "transforming principle" Griffith observed was the  DNA  of the III-s strain bacteria. While the bacteria had been killed, the DNA had survived the heating process and was taken up by the II-R strain bacteria. The III-S strain DNA contains the genes that form the smooth protective polysaccharide capsule. Equipped with this gene, the former II-R strain bacteria were now protected from the host's immune system and could kill the host. The exact nature of the transforming principle (DNA) was verified in the experiments done by  Avery, McLeod and McCarty  and by  Hershey and Chase .


John Masson Gulland   FRS   FRSE   FRIC   (14 October 1898 – 26 October 1947) was a  Scottish   chemist  and  biochemist . His main work was on  nucleic acids ,  morphine  and  aporphine alkaloids . His work at  University College Nottingham  on electrometric titration was important in leading to the discovery of the  DNA double helix  by  James Watson  and  Francis Crick , and he was described as "a great nucleic acid chemist." [ 1 ]  He established the Scottish Seaweed Research Association and the Lace Research Council.


Gulland was born at 6 Alva Street in  Edinburgh 's  West End , the only son of Helen Orme Masson and Dr. George Lovell Gulland. His maternal grandparents were  David Masson  and suffrage campaigner  Emily Rosaline Orme , his maternal uncle was  David Orme Masson  and maternal aunts  Flora Masson  and  Rosaline Masson . [ 2 ]  His paternal uncle was  John William Gulland  MP. His father later became Professor of Medicine at the  University of Edinburgh . [ 3 ]


He attended  Edinburgh Academy  1906 to 1917 and was then conscripted into the army in the  First World War . He applied for a commission and served as a 2nd Lieutenant in the  Royal Engineers . He was assigned to the Divisional Signals Company and saw little if any enemy action. After the war he graduated with a BSc from the  University of Edinburgh  in 1921. He then won a  Carnegie Research Scholarship  and undertook further studies at the  University of St Andrews  (PhD 1925) and the  University of Manchester . He worked in both places with  Professor Robert Robinson  with whom he would also later work at the Dyson Perrins Laboratory at the  University of Oxford  from where he graduated MA. He became a demonstrator in chemistry in the University of Oxford in 1924, and in 1926 was appointed as a Lecturer based at  Balliol College . [ 4 ]


In 1927 he was elected a Fellow of the  Royal Society of Edinburgh . His proposers were  Sir James Walker ,  George Barger ,  Alexander Lauder , and  Ralph Allan Sampson . [ 3 ]
In 1931 he moved to the  University of London  as a Reader in Biochemistry, also acting then as Senior Biochemist to the  Lister Institute . In 1936 he moved to  University College Nottingham  as Professor of Chemistry (the Jesse Boot Chair).


In the  Second World War  he worked for the Ministry of Home Security as Gas Advisor 1939 to 1943 [ 5 ]  and the Ministry of Supply 1943 to 1945. He was elected a Fellow of the  Royal Society of London  in 1945.


In 1947 he became Research Director for the Institute of Brewing. His career was cut short when he was killed in the  Goswick rail crash  near  Berwick-on-Tweed , aged 49. [ 6 ]


He is buried in the  Grange Cemetery  in south  Edinburgh  with his parents and uncle,  John William Gulland .


Gulland played a pivotal role in some of the research which led to the decoding of DNA by Watson and Crick in 1953. The Nottingham team, which included his colleagues  Denis Jordan , Cedric Threlfall, and  Michael Creeth , produced three papers in 1947: one led to high quality non-degraded DNA samples extracted without using acids or alkalis, [ 7 ]  the next measured the viscosity of DNA  [ 8 ]  and the third proved the all-important hydrogen bond structures within it. [ 9 ]


Five years later Watson dismissed the Nottingham team’s work incorrectly, and it took a year for him to realise his mistake. Eventually however "...a rereading of J. M. Gulland's and D. O. Jordan's papers...made me finally realize the strength of their conclusion that a large fraction, if not all, of the bases formed hydrogen bonds to other bases." Once Watson had recognised the key role of the hydrogen bonds then the decoding of DNA seems to have come within about a week or ten days. [ 10 ]


The Nottingham team’s work was also acknowledged in the first papers concerning the decoding of DNA by  Rosalind Franklin  and  Raymond Gosling  who reported that "Gulland and his collaborators … showed that … CO and NH2 groups of the bases are inaccessible … whereas the phosphate groups are fully accessible." [ 11 ]


Following these early citations rather less attention was given to the significance of the work of Gulland and his colleagues. [ 12 ]  By the time of the DNA decoding in 1953 events had moved on with the break-up of the Nottingham team: Gulland had moved on to become Research Director at the Institute of Brewing shortly before his untimely death in 1947, whilst Jordan and Creeth were both working outside the UK. However commemorations in 2010 and 2017 at the University of Nottingham posthumously acknowledged all their contributions, [ 13 ]  as did  The Annotated and Illustrated Double Helix  (2012). [ 14 ]


There has been some speculative debate as to whether, if these events had turned out differently, the Nottingham team might have gone on to make the DNA decoding discovery themselves. [ 15 ] [ 16 ]


In 1924 he married Ruth Madeline Ida Russell, daughter of Sir James A. Russell. She was a fellow chemistry student whom he met in Edinburgh. They had two daughters. [ 6 ]


His sister Flora Gulland married her cousin  Irvine Masson . [ citation needed ]


Alfred Day Hershey  (December 4, 1908 – May 22, 1997) was an American  Nobel Prize –winning  bacteriologist  and  geneticist .


Hershey was born in  Owosso, Michigan  to Robert Day and Alma Wilbur Hershey. He earned a B.S. in chemistry in 1930, and Ph.D. in bacteriology in 1934 from  Michigan State University . Shortly after, Hershey accepted a faculty position at  Washington University in St. Louis , [ 1 ] [ 2 ]  serving as an instructor of bacteriology and immunology from 1934 to 1950.


At Washington University, Hershey worked closely with department head Jacques Bronfenbrenner to investigate bacteriophages, or phages — viruses that infect and replicate inside bacteria. [ 3 ]  Hershey's work on the factors impacting the virus' ability to infect its targets brought him to the attention of fellow phage researchers  Max Delbrück  and  Salvador Luria .


In 1943, Delbrück invited Hershey to Vanderbilt University to discuss his phage research. [ 3 ]  Together, with Luria, they would form the core of an informal network of researchers called "the  Phage group ". Three years later, Hershey and Delbrück would independently discover that different strains of bacteriophage can both exchange genetic material when infecting the same bacterial cell. This process results in hybrid phages containing genetic material from both sources, which Hershey referred to as "genetic recombination".


Hershey left Washington University in 1950 for the Department of Genetics of the  Carnegie Institution of Washington , a predecessor of  Cold Spring Harbor Laboratory . Two years later, he and Martha Chase would conduct the famous  Hershey–Chase, or "Waring Blender" experiment . [ 4 ]  Their work confirmed that DNA, not protein, was the genetic material of life. [ 5 ] [ 6 ]


In 1962, Hershey was named director of the Department of Genetics, a position he held until his retirement in 1970. He would live on the grounds of Cold Spring Harbor Laboratory (CSHL) for the rest of his life.


Hershey's work with bacteriophage would earn him a share of the 1969 Nobel Prize in Physiology or Medicine with Delbrück and Luria, "for their discoveries concerning the replication mechanism and the genetic structure of viruses." [ 7 ] [ 8 ]


Although officially retired from scientific research, Hershey would continue to pursue new projects. In 1971, he edited  The Bacteriophage λ , an extensive volume on the subject, published by CSHL Press that same year. [ 1 ]  In 1981, Hershey became a founding member of the  World Cultural Council . [ 9 ]


Hershey died from congestive heart failure on May 22, 1997 at his home in Laurel Hollow, New York. [ 10 ]  He was 88 years old. At the time, he was survived by his wife Harriet Davidson (1918–2000) and their only child, Peter Manning Hershey (1956–1999).


Following his death,  Frank Stahl , a member of The Phage Group, wrote: "The Phage Church, as we were sometimes called (see  Phage group ), was led by the Trinity of Delbrück, Luria, and Hershey. Delbrück's status as founder and his  ex cathedra  manner made him the pope, of course, and Luria was the hard-working, socially sensitive priest-confessor. And Al (Hershey) was the saint." [ 2 ]


Numerous key discoveries in  biology  have emerged from studies of  RNA  (ribonucleic acid), including seminal work in the fields of  biochemistry ,  genetics ,  microbiology ,  molecular biology ,  molecular evolution , and  structural biology . As of 2010, 30 scientists have been awarded  Nobel Prizes  for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.


For related information, see the articles on  History of molecular biology  and  History of genetics . For background information, see the articles on  RNA  and  nucleic acids .


When first studied in the early 1900s, the chemical and biological differences between RNA and DNA were not apparent, and they were named after the materials from which they were isolated; RNA was initially known as " yeast  nucleic acid" and DNA was " thymus  nucleic acid". [ 1 ]  Using diagnostic chemical tests,  carbohydrate  chemists showed that the two nucleic acids contained different  sugars , whereupon the common name for RNA became "ribose nucleic acid". Other early biochemical studies showed that RNA was readily broken down at high  pH , while DNA was stable (although denatured) in  alkali . Nucleoside composition analysis showed first that RNA contained similar  nucleobases  to DNA, with  uracil  instead of  thymine , and that RNA contained a number of minor nucleobase components, e.g. small amounts of  pseudouridine  and  dimethylguanine . [ 2 ]


In 1933, while studying virgin  sea urchin  eggs,  Jean Brachet  suggested that  DNA  is found in  cell nucleus  and that  RNA  is present exclusively in the  cytoplasm . At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH. [ 3 ] [ 4 ]  During the 1930s,  Joachim Hämmerling  conducted experiments with  Acetabularia  in which he began to distinguish the contributions of the nucleus and the cytoplasm substances (later discovered to be DNA and mRNA, respectively) to cell morphogenesis and development. [ 5 ] [ 6 ]


The concept of messenger RNA emerged during the late 1950s, and is associated with  Crick 's description of his "Central Dogma of Molecular Biology", which asserted that DNA led to the formation of RNA, which in turn led to the synthesis of  proteins . During the early 1960s, sophisticated genetic analysis of mutations in the  lac operon  of  E. coli  and in the rII locus of  bacteriophage T4  were instrumental in defining the nature of both  messenger RNA  and the  genetic code . The short-lived nature of bacterial RNAs, together with the highly complex nature of the cellular mRNA population, made the biochemical isolation of mRNA very challenging. This problem was overcome in the 1960s by the use of  reticulocytes  in vertebrates, [ 7 ]  which produce large quantities of mRNA that are highly enriched in RNA encoding alpha- and beta-globin (the two major protein chains of  hemoglobin ). [ 8 ]   The first direct experimental evidence for the existence of mRNA was provided by such a hemoglobin synthesizing system. [ 9 ]


In the 1950s, results of labeling experiments in rat liver showed that radioactive  amino acids  were found to be associated with "microsomes" (later redefined as  ribosomes ) very rapidly after administration, and before they became widely incorporated into cellular proteins. Ribosomes were first visualized using  electron microscopy , and their ribonucleoprotein components were identified by biophysical methods, chiefly sedimentation analysis within  ultracentrifuges  capable of generating very high accelerations (equivalent to hundreds of thousands times gravity).  Polysomes  (multiple ribosomes moving along a single mRNA molecule) were identified in the early 1960s, and their study led to an understanding of how ribosomes proceed to read the mRNA in a 5′ to 3′ direction, [ 10 ]  processively generating proteins as they do so. [ 11 ]


Biochemical fractionation experiments showed that radioactive amino acids were rapidly incorporated into small RNA molecules that remained soluble under conditions where larger RNA-containing particles would precipitate. These molecules were termed soluble (sRNA) and were later renamed transfer RNA ( tRNA ). Subsequent studies showed that (i) every cell has multiple species of tRNA, each of which is associated with a single specific amino acid, (ii) that there are a matching set of  enzymes  responsible for linking tRNAs with the correct amino acids, and (iii) that tRNA  anticodon  sequences form a specific decoding interaction with mRNA  codons . [ 12 ]


The  genetic code  consists of the translation of particular  nucleotide sequences  in mRNA to specific amino acid sequences in  proteins  (polypeptides). The ability to work out the genetic code emerged from the convergence of three different areas of study: (i) new methods to generate synthetic RNA molecules of defined composition to serve as artificial mRNAs, (ii) development of  in vitro  translation systems that could be used to translate the synthetic mRNAs into protein, and (iii) experimental and theoretical genetic work which established that the code was written in three letter "words" ( codons ). Today, our understanding of the genetic code permits the prediction of the amino sequence of the protein products of the tens of thousands of genes whose sequences are being determined in  genome  studies. [ 13 ]


The biochemical purification and characterization of  RNA polymerase  from the bacterium  Escherichia coli  enabled the understanding of the mechanisms through which RNA polymerase initiates and terminates  transcription , and how those processes are regulated to regulate  gene expression  (i.e. turn genes on and off). Following the isolation of  E. coli  RNA polymerase, the three RNA polymerases of the eukaryotic nucleus were identified, as well as those associated with viruses and organelles. Studies of transcription also led to the identification of many protein factors that influence transcription, including repressors, activators and enhancers.  The availability of purified preparations of RNA polymerase permitted investigators to develop a wide range of novel methods for studying RNA in the test tube, and led directly to many of the subsequent key discoveries in RNA biology. [ 14 ]


Although determining the sequence of proteins was becoming somewhat routine, methods for sequencing of nucleic acids were not available until the mid-1960s. In this seminal work, a specific tRNA was purified in substantial quantities, and then sliced into overlapping fragments using a variety of ribonucleases. Analysis of the detailed nucleotide composition of each fragment provided the information necessary to deduce the sequence of the tRNA. Today, the sequence analysis of much larger nucleic acid molecules is highly automated and enormously faster. [ 15 ]


Additional tRNA molecules were purified and sequenced. The first comparative sequence analysis was done and revealed that the sequences varied through evolution in such a way that all of the tRNAs could fold into very similar secondary structures (two-dimensional structures) and had identical sequences at numerous positions (e.g. CCA at the 3′ end). The radial four-arm structure of tRNA molecules is termed the 'cloverleaf structure', and results from the evolution of sequences with common ancestry and common biological function. Since the discovery of the tRNA cloverleaf, comparative analysis of numerous other homologous RNA molecules has led to the identification of common sequences and folding patterns. [ 16 ]


The 3569 nucleotide sequence of all of the genes of the RNA  bacteriophage   MS2  was determined by a large team of researchers over several years, and was reported in a series of scientific papers. These results enabled the analysis of the first complete genome, albeit an extremely tiny one by modern standards. Several surprising features were identified, including genes that partially overlap one another and the first clues that different organisms might have slightly different codon usage patterns. [ 17 ]


Retroviruses were shown to have a single-stranded RNA genome and to replicate via a DNA intermediate, the reverse of the usual DNA-to-RNA transcription pathway. They encode a RNA-dependent DNA polymerase ( reverse transcriptase ) that is essential for this process. Some retroviruses can cause diseases, including several that are associated with cancer, and HIV-1 which causes AIDS. Reverse transcriptase has been widely used as an experimental tool for the analysis of RNA molecules in the laboratory, in particular the conversion of RNA molecules into DNA prior to  molecular cloning  and/or  polymerase chain reaction  (PCR). [ 18 ]


Biochemical and genetic analyses showed that the enzyme systems that replicate viral RNA molecules (reverse transcriptases and RNA replicases) lack molecular proofreading (3′ to 5′ exonuclease) activity, and that RNA sequences do not benefit from extensive repair systems analogous to those that exist for maintaining and repairing DNA sequences. Consequently, RNA genomes appear to be subject to significantly higher mutation rates than DNA genomes. For example, mutations in HIV-1 that lead to the emergence of viral mutants that are insensitive to antiviral drugs are common, and constitute a major clinical challenge. [ 19 ]


Analysis of  ribosomal RNA  sequences from a large number of organisms demonstrated that all extant forms of life on Earth share common structural and sequence features of the ribosomal RNA, reflecting a  common ancestry . Mapping the similarities and differences among rRNA molecules from different sources provides clear and quantitative information about the  phylogenetic  (i.e. evolutionary) relationships among organisms. Analysis of rRNA molecules led to the identification of a third major kingdom of organisms, the  archaea , in addition to the  prokaryotes  and  eukaryotes . [ 20 ]


Molecular analysis of mRNA molecules showed that, following transcription, mRNAs have non-DNA-encoded nucleotides added to both their 5′ and 3′ ends (guanosine caps and poly-A, respectively). Enzymes were also identified that add and maintain the universal CCA sequence on the 3′ end of tRNA molecules. These events are among the first discovered examples of  RNA processing , a complex series of reactions that are needed to convert RNA primary transcripts into biologically active RNA molecules. [ 21 ]


Small nuclear RNA  molecules (snRNAs) were identified in the eukaryotic  nucleus  using immunological studies with autoimmune  antibodies , which bind to  small nuclear ribonucleoprotein  complexes (snRNPs; complexes of the snRNA and protein). Subsequent biochemical, genetic, and phylogenetic studies established that many of these molecules play key roles in essential  RNA processing  reactions within the nucleus and  nucleolus , including  RNA splicing ,  polyadenylation , and the maturation of  ribosomal RNAs . [ 22 ]


The detailed three-dimensional structure of  tRNA  molecules was determined using  X-ray crystallography , and revealed highly complex, compact three dimensional structures consisting of tertiary interactions laid upon the basic cloverleaf secondary structure. Key features of tRNA tertiary structure include the coaxial stacking of adjacent helices and non-Watson-Crick interactions among nucleotides within the apical loops. Additional crystallographic studies showed that a wide range of RNA molecules (including  ribozymes ,  riboswitches  and  ribosomal RNA ) also fold into specific structures containing a variety of 3D structural motifs. The ability of RNA molecules to adopt specific tertiary structures is essential for their biological activity, and results from the single-stranded nature of RNA. In many ways, RNA folding is more highly analogous to the folding of proteins rather than to the highly repetitive folded structure of the DNA double helix. [ 12 ]


Analysis of mature eukaryotic  messenger RNA  molecules showed that they are often much smaller than the DNA sequences that encode them. The genes were shown to be discontinuous, composed of sequences that are not present in the final mature RNA ( introns ), located between sequences that are retained in the mature RNA ( exons ). Introns were shown to be removed after transcription through a process termed  RNA splicing . Splicing of RNA transcripts requires a highly precise and coordinated sequence of molecular events, consisting of (a) definition of boundaries between exons and introns, (b) RNA strand cleavage at exactly those sites, and (c) covalent linking (ligation) of the RNA exons in the correct order. The discovery of discontinuous genes and RNA splicing was entirely unexpected by the community of RNA biologists, and stands as one of the most shocking findings in molecular biology research. [ 23 ]


The great majority of protein-coding genes encoded within the nucleus of  metazoan  cells contain multiple  introns . In many cases, these introns were shown to be processed in more than one pattern, thus generating a family of related mRNAs that differ, for example, by the inclusion or exclusion of particular exons. The result of  alternative splicing  is that a single  gene  can encode a number of different protein  isoforms  that can exhibit a variety of (usually related) biological functions. Indeed, most of the proteins encoded by the human genome are generated by alternative splicing. [ 24 ]


An experimental system was developed in which an intron-containing rRNA precursor from the nucleus of the ciliated protozoan  Tetrahymena  could be spliced  in vitro . Subsequent biochemical analysis shows that this  group I intron  was self-splicing; that is, the precursor RNA is capable of carrying out the complete splicing reaction in the absence of proteins. In separate work, the RNA component of the bacterial enzyme  ribonuclease P  (a  ribonucleoprotein  complex) was shown to catalyze its tRNA-processing reaction in the absence of proteins. These experiments represented landmarks in RNA biology, since they revealed that RNA could play an active role in cellular processes, by catalyzing specific biochemical reactions. Before these discoveries, it was believed that biological catalysis was solely the realm of  protein   enzymes . [ 25 ] [ 26 ]


The discovery of catalytic RNA ( ribozymes ) showed that RNA could both encode genetic information (like DNA) and catalyze specific biochemical reactions (like protein  enzymes ). This realization led to the  RNA World Hypothesis , a proposal that RNA may have played a critical role in  prebiotic evolution  at a time before the molecules with more specialized functions (DNA and proteins) came to dominate biological information coding and catalysis. Although it is not possible for us to know the course of prebiotic evolution with any certainty, the presence of functional RNA molecules with common ancestry in all modern-day life forms is a strong argument that RNA was widely present at the time of the  last common ancestor . [ 27 ]


Some self-splicing introns can spread through a population of organisms by "homing", inserting copies of themselves into genes at sites that previously lacked an intron. Because they are self-splicing (that is, they remove themselves at the RNA level from genes into which they have inserted), these sequences represent  transposons  that are genetically silent, i.e. they do not interfere with the expression of the gene into which they become inserted. These introns can be regarded as examples of  selfish DNA . Some mobile introns encode  homing endonucleases , enzymes that initiate the homing process by specifically cleaving double-stranded DNA at or near the intron-insertion site of alleles lacking an intron. Mobile introns are frequently members of either the  group I  or  group II  families of self-splicing introns. [ 28 ]


Introns are removed from nuclear pre-mRNAs by  spliceosomes , large  ribonucleoprotein  complexes made up of  snRNA  and protein molecules whose composition and molecular interactions change during the course of the  RNA splicing  reactions. Spliceosomes assemble on and around splice sites (the boundaries between introns and exons in the unspliced pre-mRNA) in mRNA precursors and use RNA-RNA interactions to identify critical nucleotide sequences and, probably, to catalyze the splicing reactions. Nuclear pre-mRNA introns and spliceosome-associated snRNAs show similar structural features to self-splicing group II introns. In addition, the splicing pathway of nuclear pre-mRNA introns and group II introns shares a similar reaction pathway. These similarities have led to the hypothesis that these molecules may share a common ancestor. [ 29 ]


Messenger RNA precursors from a wide range of organisms can be  edited  before being translated into protein. In this process, non-encoded nucleotides may be inserted into specific sites in the RNA, and encoded nucleotides may be removed or replaced.  RNA editing  was first discovered within the mitochondria of  kinetoplastid  protozoans, where it has been shown to be extensive. [ 30 ]  For example, some protein-coding genes encode fewer than 50% of the nucleotides found within the mature, translated mRNA. Other RNA editing events are found in mammals, plants, bacteria and viruses. These latter editing events involve fewer nucleotide modifications, insertions and deletions than the events within  kinetoplast  DNA, but still have high biological significance for gene expression and its regulation. [ 31 ]


Telomerase is an enzyme that is present in all eukaryotic nuclei which serves to maintain the ends of the linear DNA in the linear  chromosomes  of the eukaryotic nucleus, through the addition of terminal sequences that are lost in each round of DNA replication.  Before telomerase was identified, its activity was predicted on the basis of a molecular understanding of DNA replication, which indicated that the DNA polymerases known at that time could not replicate the 3′ end of a linear chromosome, due to the absence of a template strand. Telomerase was shown to be a  ribonucleoprotein  enzyme that contains an RNA component that serves as a  template strand , and a protein component that has  reverse transcriptase  activity and adds nucleotides to the chromosome ends using the internal RNA template. [ 32 ]


For years, scientists had worked to identify which protein(s) within the  ribosome  were responsible for  peptidyl transferase  function during  translation , because the covalent linking of amino acids represents one of the most central chemical reactions in all of biology. Careful biochemical studies showed that extensively-deproteinized large ribosomal subunits could still catalyze peptide bond formation, thereby implying that the sought-after activity might lie within ribosomal RNA rather than ribosomal proteins. Structural biologists, using  X-ray crystallography , localized the peptidyl transferase center of the ribosome to a highly- conserved  region of the large subunit  ribosomal RNA  (rRNA) that is located at the place within the ribosome where the amino-acid-bearing ends of tRNA bind, and where no proteins are present. These studies led to the conclusion that the  ribosome  is a  ribozyme . The rRNA sequences that make up the ribosomal  active site  represent some of the most highly conserved sequences in the biological world. Together, these observations indicate that peptide bond formation catalyzed by RNA was a feature of the  last common ancestor  of all known forms of life. [ 33 ]


Experimental methods were invented that allowed investigators to use large, diverse populations of RNA molecules to carry out in vitro molecular experiments that utilized powerful selective replication strategies used by geneticists, and which amount to evolution in the test tube. These experiments have been described using different names, the most common of which are "combinatorial selection", "in vitro selection", and SELEX (for  Systematic Evolution of Ligands by Exponential Enrichment ). These experiments have been used for isolating RNA molecules with a wide range of properties, from binding to particular proteins, to catalyzing particular reactions, to binding low molecular weight organic ligands. They have equal applicability to elucidating interactions and mechanisms that are known properties of naturally occurring RNA molecules to isolating RNA molecules with biochemical properties that are not known in nature. In developing in vitro selection technology for RNA, laboratory systems for synthesizing complex populations of RNA molecules were established, and used in conjunction with the selection of molecules with user-specified biochemical activities, and in vitro schemes for RNA replication. These steps can be viewed as (a)  mutation , (b) selection, and (c)  replication . Together, then, these three processes enable in vitro  molecular evolution . [ 34 ]


Transposable genetic elements  (transposons) are found which can replicate via transcription into an  RNA intermediate  which is subsequently converted to DNA by reverse transcriptase. These sequences, many of which are likely related to retroviruses, constitute much of the DNA of the eukaryotic nucleus, especially so in plants. Genomic sequencing shows that retrotransposons make up 36% of the human genome and over half of the genome of major cereal crops (wheat and maize). [ 35 ]


Segments of RNA, typically embedded within the 5′-untranslated region of a vast number of bacterial mRNA molecules, have a profound effect on gene expression through a previously-undiscovered mechanism that does not involve the participation of proteins. In many cases,  riboswitches  change their folded structure in response to environmental conditions (e.g. ambient temperature or concentrations of specific metabolites), and the structural change controls the translation or stability of the mRNA in which the riboswitch is embedded. In this way, gene expression can be dramatically regulated at the post-transcriptional level. [ 36 ]


Another previously unknown mechanism by which RNA molecules are involved in genetic regulation was discovered in the 1990s. Small RNA molecules termed microRNA (miRNA) and  small interfering RNA  (siRNA) are abundant in eukaryotic cells and exert post-transcriptional control over mRNA expression. They function by binding to specific sites within the mRNA and inducing cleavage of the mRNA via a specific silencing-associated RNA degradation pathway. [ 37 ]


In addition to their well-established roles in translation and splicing, members of  noncoding RNA  (ncRNA) families have recently been found to function in genome defense and chromosome inactivation. For example,  piwi-interacting RNAs  (piRNAs) prevent genome instability in germ line cells, while  Xist  (X-inactive-specific-transcript) is essential for X-chromosome inactivation in mammals. [ 38 ]


Robert William Holley  (January 28, 1922 – February 11, 1993) was an American  biochemist . He shared the  Nobel Prize in Physiology or Medicine  in 1968 (with  Har Gobind Khorana  and  Marshall Warren Nirenberg ) for describing the structure of alanine  transfer RNA , linking  DNA  and  protein synthesis .


Holley was born in  Urbana, Illinois , and graduated from Urbana High School in 1938. He went on to study  chemistry  at the  University of Illinois at Urbana-Champaign , graduating in 1942 and commencing his  PhD  studies in  organic chemistry  at  Cornell University . During  World War II  Holley spent two years working under Professor  Vincent du Vigneaud  at Cornell University Medical College, where he was involved in the first chemical synthesis of  penicillin . Holley completed his PhD studies in 1947. [ 1 ] [ 2 ] [ 3 ]


Following his graduate studies Holley remained associated with Cornell. He became an assistant professor of organic chemistry in 1948, and was appointed as professor of biochemistry in 1962. He began his research on  RNA  after spending a year's sabbatical (1955–1956) studying with  James F. Bonner  at the  California Institute of Technology .


Holley's research on  RNA  focused first on isolating  transfer RNA  (tRNA), and later on determining the sequence and structure of alanine  tRNA , the molecule that incorporates the  amino acid   alanine  into  proteins . Holley's team of researchers determined the tRNA's structure by using two   ribonucleases  to split the tRNA molecule into pieces. Each enzyme split the molecule at location points for specific nucleotides. By a process of "puzzling out" the structure of the pieces split by the two different enzymes, then comparing the pieces from both enzyme splits, the team eventually determined the entire structure of the molecule. The group of researchers include  Elizabeth Beach Keller , who developed the cloverleaf model that describes transfer RNA, during the course of the research. [ 4 ]


The structure was completed in 1964, [ 5 ] [ 6 ]  and was a key discovery in explaining the  synthesis  of proteins from  messenger RNA . It was also the first nucleotide sequence of a  ribonucleic acid  ever determined. Holley was awarded the Nobel Prize in Physiology or Medicine in 1968 for this discovery, [ 7 ]  and  Har Gobind Khorana  and  Marshall W. Nirenberg  were also awarded the prize that year for contributions to the understanding of protein synthesis.


Using the Holley team's method, other scientists determined the structures of the remaining tRNA's. A few years later the method was modified to help track the sequence of nucleotides in various bacterial, plant, and human  viruses .


In 1968 Holley became a resident fellow at the  Salk Institute  for Biological Studies in  La Jolla, California .


According to the New York Times obituary, "He was an avid outdoorsman and an amateur sculptor of bronze." His widow Ann died in 1996.


Walter Abraham Jacobs  (December 24, 1883 – July 12, 1967) was an American chemist who discovered the  Gould-Jacobs reaction . Much of his career was spent at the  Rockefeller Institute for Medical Research , New York City. [ 1 ]


This biographical article about an American chemist is a  stub . You can help Wikipedia by  expanding it .


Rudolf Jaenisch  (born on April 22, 1942) is a professor of biology at  MIT  and a founding member of the  Whitehead Institute for Biomedical Research . [ 1 ]  He is a pioneer of  transgenic science , in which an animal’s genetic makeup is altered. Jaenisch has focused on creating  genetically modified mice  to study  cancer , epigenetic reprogramming and  neurological diseases . [ 2 ] [ 3 ] [ 4 ]


Jaenisch's first breakthrough occurred in 1974, when he and  Beatrice Mintz  showed that foreign  DNA  could be integrated into the DNA of early mouse  embryos [ 5 ]  They injected  retrovirus  DNA into early mouse embryos and showed that leukemia DNA sequences had integrated into the mouse  genome  and also into that of its offspring. These mice were the first transgenic mammals in history. [ 6 ]


His current research focuses on the  epigenetic  regulation of  gene expression , [ 7 ]  which has led to major advances in creating embryonic stem cells and " induced pluripotent stem " (IPS) cells, as well as their therapeutic applications. In 2007, Jaenisch’s laboratory was one of the first three laboratories worldwide to report reprogramming cells taken from a mouse's tail into IPS cells. Jaenisch has since shown therapeutic benefits of IPS cell-based treatment for  sickle-cell anemia  and  Parkinson's disease  in mice. Additional research focuses on the epigenetic mechanisms involved in cancer and brain development. [ 3 ]


Jaenisch’s therapeutic cloning research deals exclusively with mice, but he is an advocate for using the same techniques with human cells in order to advance embryonic stem cell research. [ 8 ]  However, in 2001, Jaenisch made a public case against  human reproductive cloning , testifying before a U.S. House of Representatives subcommittee [ 9 ]  and writing an editorial in  Science  magazine . [ 10 ]


Jaenisch received his doctorate in medicine from the  University of Munich  in 1967, preferring the laboratory to the clinic. He became a postdoc at the Max Planck Institute in Munich, studying bacteriophages. [ 11 ]  He left Germany in 1970 for research positions at  Princeton University ,  Fox Chase Institute for Cancer Research  and the  Salk Institute . He returned to Germany in 1977 to become the head of the Department of Tumor Virology at the  Heinrich Pette Institute  at the  University of Hamburg . He arrived at MIT in 1984. [ 12 ]  He participated in the 2005 science conference on human cloning at the  United Nations  and serves on the science advisory boards of the Genetics Policy Institute [ 13 ]  and Stemgent. [ 14 ]  He also served on the Life Sciences jury for the  Infosys Prize  in 2010.


John Leonard Jinks   CBE   FRS [ 1 ]  ( Stoke-on-Trent , 21 October 1929 – 6 June 1987) was a British  geneticist . His untimely death at 57 cut short a distinguished career with many contributions in the fields of microbial genetics, cytoplasmic inheritance, and  biometrical genetics .


He was educated at  Birmingham University  and remained there for the majority of his career, contributing to the development of biometrical genetics, human  behavioural genetics , and supervising a number of students who went on to make their own contributions, among them  David Fulker . He was a scientific officer/principal scientific officer in the ARC Unit of Biometrical Genetics from 1953 to 1965. In 1960 he was made an honorary lecturer in the Birmingham University Department of Genetics, eventually becoming Dean of the Faculty of Science and Engineering and  Pro-Vice Chancellor. Elected to Fellowship of the Royal Society in 1970 he is best known for his studies of cytoplasmic inheritance [ 2 ]  and  quantitative genetics . [ 3 ]


In recounting his own career,  Nobel Prize  winner  Sir Paul Nurse  recounts how his lack of a foreign language (essential for university study in the UK in those days) had seen him rebuffed from several universities. He met Jinks fortuitously, and, recognising a promising intellect, Jinks smoothed the obstacles from Nurse's path, leading to his successful enrollment and, subsequently, Nobel winning discoveries regarding  cell cycle  regulation by  cyclin  and  cyclin dependent kinases . [ 4 ]


Denis Oswald Jordan  (23 September 1914,  London  – 12 February 1982,  St Georges, South Australia ) was an Anglo-Australian chemist with a distinguished career as a researcher and lecturer in Chemistry at both  University College Nottingham  (1940–53) and the  University of Adelaide , where he was  Angas Professor of Chemistry  from 1958 to 1982. Jordan also served as president of Australian Institute of Nuclear Science and Engineering from 1958 to 1962, and  Royal Australian Chemical Institute  from 1978 to 1979. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]


Whilst at Nottingham 'Doj' Jordan was a key member of the team whose research made important contributions to the eventual decoding of  DNA  in 1953. Jordan worked with  John Masson Gulland ,  Michael Creeth  and others on a series of experiments in 1947 which firstly created high quality DNA, then measured its viscocity, and finally demonstrated the hydrogen bonds within the molecule. [ 6 ] [ 7 ] [ 8 ]  Their discoveries were ultimately acknowledged by  James Watson  as critical contributions even if he did at first dismiss them incorrectly: "...a rereading of J. M. Gulland's and D. O. Jordan's papers...made me finally realize the strength of their conclusion that a large fraction, if not all, of the bases formed hydrogen bonds to other bases." [ 9 ] [ 10 ]  Gulland and Jordan's work was also acknowledged in the first papers concerning the decoding of DNA by  Rosalind Franklin  and  Raymond Gosling . [ 11 ]  It has however been argued that the work of the Nottingham team was subsequently overlooked until commemorations were held in 2010 and 2017. [ 12 ]


Jordan continued to work at Nottingham University on deoxyribonucleic acid after the untimely death of Gulland in the  Goswick rail crash  in October 1947, but in 1953 he was appointed to a professorship in Adelaide where he arrived in 1954. [ citation needed ]


In 1981, the  University of Adelaide , named its physical and inorganic Chemistry building after Jordan. [ 13 ]


In November 2017 a plaque was unveiled in the Trent Building at University of Nottingham commemorating the 70th anniversary of the "Discovery of Hydrogen Bonds in DNA by JM Creeth, DO Jordan and JM Gulland". [ citation needed ]


Jordan was awarded a number of honours, [ 15 ]  including:


Ludwig Karl Martin Leonhard Albrecht Kossel  ( German pronunciation:   [ˈalbʁɛçt   ˈkɔsl̩]   ⓘ ; 16 September 1853 – 5 July 1927) was a German  biochemist  and pioneer in the study of  genetics . He was awarded the Nobel Prize for  Physiology or Medicine  in 1910 for his work in determining the chemical composition of  nucleic acids , the genetic substance of  biological cells .


Kossel isolated and described the five  organic compounds  that are present in  nucleic acid :  adenine ,  cytosine ,  guanine ,  thymine , and  uracil . These compounds were later shown to be  nucleobases , and are key in the formation of  DNA  and  RNA , the genetic material found in all living cells.


Kossel was an important influence on and collaborator with other important researchers in biochemistry, including  Henry Drysdale Dakin ,  Friedrich Miescher ,  Edwin B. Hart , and his professor and mentor,  Felix Hoppe-Seyler . Kossel was editor of the  Zeitschrift für Physiologische Chemie  (Journal of Physiological Chemistry) from 1895 until his death.  Kossel also conducted important research into the composition of  protein , and his research predicted the discovery of the  polypeptide  nature of the protein molecule.


The  Albrecht Kossel Institute for Neuroregeneration  at the  University of Rostock  is named in his honor.


Kossel was born in  Rostock , Germany as the son of the  merchant  and  Prussian   consul  Albrecht Karl Ludwig Enoch Kossel and his wife Clara Jeppe Kossel. As a youth, Kossel attended the Gymnasium at Rostock, where he evidenced substantial interest in chemistry and botany. [ 1 ]


In 1872, Kossel attended the  University of Strassburg  to study medicine. He studied under  Felix Hoppe-Seyler , who was head of the department of biochemistry, the only such institution in Germany at the time. He attended lectures by  Anton de Bary ,  Waldeyer ,  August Kundt , and  Baeyer . He completed his studies at  University of Rostock , and passed his German medical license exam in 1877. [ 1 ]


After completing his university studies, Kossel returned to the University of Strassburg as research assistant to Felix Hoppe-Seyler. At the time, Hoppe-Seyler was intensely interested in research concerning an acidic substance that had first been chemically isolated from pus cells by one of his former students,  Friedrich Miescher , in 1869. Unlike protein, the substance contained considerable amounts of  phosphorus , but with its high acidity, it was unlike any cellular substance that had yet been observed. [ 1 ]


Kossel showed that the substance, called "nuclein", consisted of a protein component and a non-protein component. Kossel further isolated and described the non-protein component. This substance has become known as  nucleic acid , which contains the genetic information found in all living cells. [ 2 ]


In 1883, Kossel left Strassburg to become Director of the Chemistry Division of the Physiological Institute at the  University of Berlin . In this post, he succeeded  Eugen Baumann  and worked under the supervision of  Emil du Bois-Reymond . [ 1 ]


Kossel continued his previous work on the nucleic acids. During the period 1885 to 1901, he was able to isolate and name its five constituent  organic compounds :  adenine ,  cytosine ,  guanine ,  thymine , and  uracil . These compounds are now known collectively as  nucleobases , and they provide the molecular structure necessary in the formation of stable  DNA  and  RNA  molecules. [ 2 ]


In 1895, Kossel was professor of physiology as well as director of the Physiological Institute at the  University of Marburg . Around this time, he began investigations into the chemical composition of  proteins , the alterations in proteins during transformation into  peptone , the  peptide  components of cells, and other investigations. [ 1 ]


In 1896, Kossel discovered  histidine , then worked out the classical method for the quantitative separation of the "hexone bases" (the  alpha-amino acids   arginine ,  histidine , and  lysine ). He was also the first to isolate  theophylline , a therapeutic drug found naturally in tea and cocoa beans.


In 1901, Kossel was named to a similar post at  Heidelberg University , and became director of the Heidelberg Institute for Protein Investigation. His research predicted the discovery of the  polypeptide  nature of the protein molecule. [ 1 ]


The processes of life are like a drama, and I am studying the actors, not the plot. There are many actors, and it is their characters which make this drama. I seek to understand their habits, their peculiarities.


Kossel was awarded the  Nobel Prize in Physiology or Medicine  in 1910 for his research in  cell biology , the chemical composition of the  cell nucleus , and for his work in isolating and describing  nucleic acids . The award was presented on 10 December 1910. [ 2 ]


In the autumn of 1911, Kossel was invited to the United States to deliver the  Herter Lecture  at  Johns Hopkins . Traveling with his wife Luise and daughter Gertrude, he took the opportunity to travel and to visit acquaintances, one of which was  Eugene W. Hilgard ,  professor emeritus  of  agricultural chemistry  at the  University of California at Berkeley , who was also his wife's cousin. He also visited and delivered lectures at several other universities, including the  University of Chicago . [ 1 ]


On the occasion of his visit to New York City, Kossel was interviewed by a reporter from  The New York Times . Kossel's English was reportedly very good, and his self-effacing modesty is voluminously mentioned in the reporter's account. [ 3 ]


His Herter lecture at Johns Hopkins was titled, "The Proteins". This was the only time Kossel ever visited the United States. [ 1 ]


With his distinguished English pupil  Henry Drysdale Dakin , Kossel investigated  arginase , the  ferment  which hydrolyses  arginine  into  urea  and  ornithine . Later, he discovered  agmatine  in herring roe and devised a method for preparing it. [ 2 ]


Another of Kossel's students was American  biochemist   Edwin B. Hart , who would later return to the United States to participate in the " Single-grain experiment " (1907–1911) and be part of research teams that would determine the  nutritive  causes of  anemia  and  goiter . Another was  Otto Folin , an American chemist who discovered  Phosphocreatine .


In 1923, Kossel was honored by being named Germany's representative to the Eleventh Physiological Congress in  Edinburgh , Scotland. When he appeared before the assembled scientists, they gave him an ovation that lasted several minutes. At the congress, he was conferred an honorary degree by the  University of Edinburgh . [ 1 ]


In 1924, Kossel became  professor emeritus , but continued to lecture at  Heidelberg University . In April 1927, he attended the  Lister  Centenary Celebration held in England. [ 1 ]


During the last years of Kossel's life, he conducted important research into the composition of the protein types  protamines  and  histones , and introduced  flavianic acid   for the quantitative separation of arginine, histidine and lysine in proteins. [ 4 ]   A  monograph describing this work was published shortly after his death. [ 1 ]


Kossel contributed to early issues of the  Zeitschrift für Physiologische Chemie  (Journal of Physiological Chemistry). This publication was founded by his professor and mentor,  Felix Hoppe-Seyler , in 1877, the same year that Kossel started work as his research assistant. After Hoppe-Seyler's death in 1895, Kossel took over editorship of the Zeitschrift and continued in that role until his own death in 1927. [ 1 ]


In 1886, Kossel married Luise Holtzman, daughter of  Adolf Holtzmann . Holtzmann was Professor at the  University of Heidelberg , lecturing in  German literature  as well as  Sanskrit . He was also a noted  philologist  of his day. The couple had three children, two of whom survived to maturity: Walther, born in 1888, and daughter Gertrude, born in 1889. [ 1 ]


Son  Walther Kossel  (1888–1956) became a prominent  physicist  and was professor of  theoretical physics  and director of the Physics Institute at the  University of Tübingen . He is known for his theory of the  chemical bond  ( ionic bond / octet rule ), the  Sommerfeld–Kossel displacement law , and other achievements. [ citation needed ]


Albrecht Kossel was apparently not greatly interested in politics, but in 1914 he did not sign the propaganda Pronunciamento of German professors at the start of the war. He suffered under the lies which filled the world in war time. In 1917 Kossel was summoned by the government to pronounce that the allotted food provisions were sufficient. He refused this demand, would never declare untruths as truths [ 1 ]


Through his marriage to Luise, Kossel was related to several prominent Americans, including  soil science  pioneer  Eugene W. Hilgard , journalist and financier  Henry Villard , and abolitionist  William Lloyd Garrison . [ 1 ]


Luise Kossel died in 1913 of  acute pancreatitis . Kossel died quietly on 5 July 1927, after a recurring attack of  angina pectoris . [ 1 ]  He is buried in  Heidelberg , Germany. [ citation needed ]


The study of the living organism has more and more led to the view that its smallest independent units morphologically speaking – the cells – also to a certain degree lead an independent life and are the real seats of the vital processes. The cells therefore attract special attention in biological research, and studies which widen our knowledge of the cells to any important extent deserve to be given prominence.
Prof. Kossel has chosen to devote himself to this field of research, and it is for his work in this respect that the Nobel Prize has been awarded to him this year.


Albrecht Kossel is considered one of the great scientists of biochemistry and genetics. [ 1 ]  By isolating and defining  nucleic acid  and the  nucleobases , he provided the necessary precursors that led to the  double-helix model  of  DNA , devised by  James D. Watson  and  Francis Crick  in 1953. [ 2 ]


" … his elucidation of the chemical nature of some building blocks that make up nucleic acids and chromatine has secured immortality for this exeedingly modest and almost shy man." [ 6 ]


Philip Leder  (November 19, 1934 – February 2, 2020) was an American  geneticist .


Leder was born in  Washington, D.C. , and studied at  Harvard University , graduating in 1956.  In 1960, he graduated from  Harvard Medical School  and completed his medical residency at the University of Minnesota.


Leder made several contributions in each decade of the modern genetics era from the 1960s through the 1990s. He may be best known for his early work with  Marshall Nirenberg  in the elucidation of the  genetic code  and the  Nirenberg and Leder experiment .  Since then, he has made several contributions in the fields of  molecular genetics ,  immunology  and the  genetics of cancer . His group defined the  base sequence  of a complete mammalian gene (the gene for  beta globin ), which enabled him to determine its organization in detail, including its associated control signals. His research into the structure of genes which carry the code for antibody molecules was of major significance. The main focus of this inquiry was the question of how the vast diversity of antibody molecules is formed by a limited number of encoded genes. Leder's work on antibody genes was later extended to research into  Burkitt's lymphoma , a tumour of antibody-producing cells, which involves the  oncogene   c-myc . This was crucial in understanding the origin of this type of tumor. In 1988, Leder and  Timothy Stewart  were granted the first patent on a  genetically engineered animal . This animal, a mouse which had genes injected into its embryo to increase susceptibility to cancer, became known as the " oncomouse " and has been used in the laboratory study of cancer therapies.


In 1968, Leder headed the Biochemistry Department of the Graduate Program of the Foundation for Advanced Education in the Sciences at the  National Institute of Health . In 1972 he was appointed director of the Laboratory for Molecular Genetics at the same institution and remained in that post until 1980, when he returned to Harvard Medical School as the founder of the newly formed Department of Genetics, occupying the John Emory Andrus Chair.
He retired from this position in 2008 and died of complications from  Parkinson's disease  on February 2, 2020. [ 2 ]


Leder has been awarded various honors and was a member of the  National Academy of Sciences , the  American Academy of Arts and Sciences  and the  Institute of Medicine .
His many prizes include the Golden Plate Award of the  American Academy of Achievement  (1981), [ 3 ]  the  Lasker Award  (1987), the  National Medal of Science  (1991), the  Harvey Prize , and the Heineken Prize awarded by the  Royal Netherlands Academy of Arts and Sciences . In November 2015 he has been awarded an honorary doctoral degree from the Medical Faculty of the University of Basel for his lifetime achievements.


Joshua Lederberg   ForMemRS [ 1 ]  (May 23, 1925 – February 2, 2008) [ 2 ]  was an American  molecular biologist  known for his work in microbial genetics,  artificial intelligence , and the United States space program. He was 33 years old when he won the 1958  Nobel Prize in Physiology or Medicine  for discovering that  bacteria  can mate and exchange genes ( bacterial conjugation ). [ 3 ]  He shared the prize with  Edward Tatum  and  George Beadle , who won for their work with genetics.


In addition to his contributions to  biology , Lederberg did extensive research in  artificial intelligence . This included work in the  NASA  experimental programs seeking  life on Mars  and the  chemistry   expert system   Dendral .


Later in his life, he was a proponent of  eugenics . [ 4 ]