Lederberg was born in  Montclair, New Jersey , to a  Jewish  family, son of Esther Goldenbaum Schulman Lederberg and  Rabbi  Zvi Hirsch Lederberg, in 1925, and moved to  Washington Heights, Manhattan  as an infant. [ 5 ]  He had two younger brothers. Lederberg graduated from  Stuyvesant High School  in  New York City  at the age of 15 in 1941. [ 6 ]  After graduation, he was allowed lab space as part of the American Institute Science Laboratory, a forerunner of the  Westinghouse Science Talent Search . He enrolled in  Columbia University  in 1941, majoring in zoology. Under the mentorship of  Francis J. Ryan , he conducted biochemical and genetic studies on the bread mold  Neurospora crassa . Intending to receive his MD and fulfill his military service obligations, Lederberg worked as a hospital corpsman during 1943 in the clinical pathology laboratory at St. Albans Naval Hospital, where he examined sailors' blood and stool samples for  malaria . He went on to receive his undergraduate degree in 1944.


Joshua Lederberg began medical studies at Columbia's  College of Physicians and Surgeons  while continuing to perform experiments. Inspired by  Oswald Avery 's  discovery  of the importance of  DNA , Lederberg began to investigate his hypothesis that, contrary to prevailing opinion, bacteria did not simply pass down exact copies of genetic information, making all cells in a lineage essentially  clones . After making little progress at Columbia, Lederberg wrote to  Edward Tatum , Ryan's post-doctoral mentor, proposing a collaboration. In 1946 and 1947, Lederberg took a leave of absence to study under the mentorship of Tatum at  Yale University . Lederberg and Tatum showed that the  bacterium   Escherichia coli  entered a sexual phase during which it could share genetic information through  bacterial conjugation . [ 8 ] [ 9 ]   With this discovery and some mapping of the  E. coli   chromosome , Lederberg was able to receive his Ph.D. from  Yale University  in 1947. [ 10 ]  Joshua married Esther Miriam Zimmer (herself a student of Edward Tatum) on December 13, 1946.


Instead of returning to Columbia to finish his medical degree, Lederberg chose to accept an offer of an assistant professorship in genetics at the  University of Wisconsin–Madison . His wife  Esther Lederberg  went with him to Wisconsin. She received her doctorate there in 1950.


Joshua Lederberg and  Norton Zinder  showed in 1951 that genetic material could be transferred from one strain of the bacterium  Salmonella typhimurium  to another using viral material as an intermediary step. [ 11 ]   This process is called  transduction . In 1956,  M. Laurance Morse , Esther Lederberg and Joshua Lederberg also discovered specialized  transduction . [ 12 ] [ 13 ]  The research in specialized transduction focused upon lambda phage infection of  E. coli . Transduction and specialized transduction explained how bacteria of different species could gain resistance to the same  antibiotic  very quickly.


During her time in Joshua Lederberg's laboratory,  Esther Lederberg  also discovered fertility factor F, later publishing with Joshua Lederberg and  Luigi Luca Cavalli-Sforza . In 1956, the Society of Illinois Bacteriologists simultaneously awarded Joshua Lederberg and Esther Lederberg the Pasteur Medal, for "their outstanding contributions to the fields of microbiology and genetics".


In 1957, Joshua Lederberg founded the Department of Medical Genetics at the  University of Wisconsin–Madison . He has held visiting professorship in Bacteriology at the  University of California, Berkeley  in summer 1950 [ 14 ]  and  University of Melbourne  (1957). Also in 1957, he was elected to the  National Academy of Sciences . [ 6 ]


Sir Gustav Nossal  views Lederberg as his mentor, describing him as "lightning fast" and "loving a robust debate." [ 15 ]


In 1958, Joshua Lederberg received the Nobel Prize and moved to  Stanford University , where he was the founder and chairman of the Department of Genetics. He collaborated with  Frank Macfarlane Burnet  to study viral antibodies. [ 16 ]


With the launching of  Sputnik  in 1957, Lederberg became concerned about the biological impact of space exploration. In a letter to the  National Academies of Sciences , he outlined his concerns that extraterrestrial microbes might gain entry to Earth onboard spacecraft, causing catastrophic diseases. He also argued that, conversely, microbial contamination of manmade satellites and probes may obscure the search for extraterrestrial life. He advised quarantine for returning astronauts and equipment and sterilization of equipment prior to launch. Teaming up with  Carl Sagan , his public advocacy for what he termed  exobiology  helped expand the role of biology in NASA. [ 17 ]


Lederberg was elected to the  American Academy of Arts and Sciences  in 1959 and the  American Philosophical Society  in 1960. [ 18 ] [ 19 ]


In the 1960s, he collaborated with  Edward Feigenbaum  in Stanford's computer science department to develop  DENDRAL . [ 16 ]


In 1978, he became the president of  Rockefeller University , until he stepped down in 1990 and became professor- emeritus  of  molecular genetics and informatics  at Rockefeller University, reflecting his extensive research and publications in these disciplines. [ 20 ] [ 21 ]


Throughout his career, Lederberg was active as a scientific advisor to the U.S. government. Starting in 1950, he was a member of various panels of the Presidential Science Advisory Committee. In 1979, he became a member of the U.S.  Defense Science Board  and the chairman of President  Jimmy Carter 's President's Cancer Panel. In 1989, he received  National Medal of Science  for his contributions to the scientific world. In 1994, he headed the Department of Defense's Task Force on Persian Gulf War Health Effects, which investigated  Gulf War Syndrome .


During a 1986 fact finding mission of the 1979  Soviet Union  epidemic of  anthrax bacteria  that killed 66 people in the city of Sverdlovsk, Russia now named  Yakaterinberg , [ 22 ]  Lederberg sided with Soviets that the anthrax outbreak was from animal to human transmission stating, “Wild rumors do spread around every epidemic." “The current Soviet account is very likely to be true." [ 23 ]
After the fall of the Soviet Union and subsequent US investigations in the early 1990s, a team of scientists confirmed the outbreak was caused by a release of an aerosol of anthrax pathogen from a nearby military facility, the lab leak is one of the deadliest ever documented. [ 24 ] [ 25 ]


Euphenics , which literally means "good appearance" or "normal appearing", is the science of making  phenotypic  improvements to humans after birth, generally to affect a problematic  genetic condition . Lederberg coined the term in the 1960s to differentiate this practice from  eugenics , which was both widely unpopular at the time and he had seen as having been "perverted to justify unthinkable inhumanity". [ 26 ] [ 27 ] [ 28 ]   He emphasized that the genetic manipulation he described was intended to work on phenotype rather than genotype; he felt it was more feasible to positively change an individual's phenotype through gene therapies or enzyme replacement rather than attempt to change the course of evolution as eugenics proposed. [ 29 ]   Theodosius Dobzhansky , an outspoken proponent of euphenics, argued that by improving genetic conditions so that people could live normal, healthy lives, people could lessen the impact of genetic conditions, thus lowering future interest in eugenics or other kinds of genetic manipulation. [ 30 ]


In the 1970s, considerable effort was put towards the developing field of euphenics since it was seen as a positive form of genetic engineering. [ 31 ]   One of the first publicized applications of euphenics was the use of vitamins containing  folic acid  during pregnancy to combat neural-tube deficiencies such as  spina bifida  in the 1970s. [ 32 ]  However, medical science had been using euphenic strategies years before the term itself was coined. [ 33 ]  Euphenics is used today in the medical community to more generally refer to methods of affecting a genetic condition in a positive manner through diet, lifestyle or environment, such as the use of insulin to control diabetes or installation of a pacemaker to offset a heart defect. [ 34 ]


Lederberg married fellow scientist  Esther Miriam Zimmer  in 1946; they divorced in 1966. He married psychiatrist Marguerite Stein Kirsch in 1968. He was survived by Marguerite, their daughter, Anne Lederberg, and his stepson, David Kirsch.


Phoebus Aaron Theodore Levene  (25 February 1869 – 6 September 1940) was a Russian-born American  biochemist  who studied the structure and function of  nucleic acids .  He characterized the different forms of nucleic acid,  DNA  from  RNA , and found that DNA contained  adenine ,  guanine ,  thymine ,  cytosine ,  deoxyribose , and a phosphate group. [ 1 ]


He was born into a  Litvak  (Lithuanian Jewish) family as  Fishel Rostropovich Levin  in the town of  Žagarė  in  Lithuania , then part of the  Russian Empire , but grew up in  St. Petersburg .  There he studied medicine at the Imperial Military Medical Academy (M.D., 1891) and developed an interest in biochemistry.  In 1893, because of anti-Semitic  pogroms , he and his family emigrated to the United States and he practiced medicine in  New York City .


Levene enrolled at  Columbia University  and in his spare time conducted biochemical research, publishing papers on the chemical structure of sugars.  In 1896 he was appointed as an Associate in the Pathological Institute of the New York State Hospitals, but he had to take time off to recuperate from tuberculosis.  During this period, he worked with several chemists, including  Albrecht Kossel  and  Emil Fischer , who were the experts in proteins.


In 1905, Levene was appointed as head of the biochemical laboratory at the Rockefeller Institute of Medical Research.  He spent the rest of his career at this institute, and it was there that he identified the components of  DNA .  In 1909, Levene and  Walter Jacobs  recognised  d - ribose  as a  natural product  and an essential component of  nucleic acids . [ 2 ] [ 3 ] [ 4 ]  They also recognised that the unnatural sugar that  Emil Fischer  and  Oscar Piloty  had reported in 1891 [ 5 ]  was the  enantiomer  of  d -ribose. [ 4 ]   Levene went on to discover  deoxyribose  in 1929. [ 6 ]   Not only did Levene identify the components of DNA, he also showed that the components were linked together in the order phosphate-sugar-base to form units. He called each of these units a  nucleotide , and stated that the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule.  His ideas about the structure of DNA were wrong; he thought there were only four nucleotides per molecule.  He even declared that it could not store the genetic code because it was chemically far too simple.  However, his work was a key basis for the later work that determined the structure of DNA.  Levene published over 700 original papers and articles on biochemical structures. Levene died in 1940, before the true significance of DNA became clear.


Levene is known for his  tetranucleotide hypothesis [ 7 ]  which proposed that DNA was made up of  equal  amounts of adenine, guanine, cytosine, and thymine.  Before the later work of  Erwin Chargaff , it was widely thought that DNA was organized into repeating tetranucleotides in a way that could not carry genetic information. Instead, the protein component of  chromosomes  was thought to be the basis of heredity; most research on the physical nature of the  gene  focused on  proteins , and particularly  enzymes  and  viruses , before the 1940s. [ 8 ]


Levene was an elected member of both the United States  National Academy of Sciences  and the  American Philosophical Society . [ 9 ] [ 10 ]


References for the discovery of ribose and deoxyribose:


Life Story  (known as  The Race for the Double Helix  in the United States) is a 1987 television  historical drama  which depicts the progress toward, and the competition for, the discovery of the structure of  DNA  in the early 1950s. It was directed by  Mick Jackson  for the  BBC 's  Horizon  science series, and stars  Jeff Goldblum ,  Tim Pigott-Smith ,  Juliet Stevenson , and  Alan Howard . It won several awards in the UK and U.S., including the 1988  BAFTA TV Award  for  Best Single Drama .


The film dramatises the rivalries of the two teams of scientists attempting to discover the structure of  DNA :  Francis Crick  and  James D. Watson  at  Cambridge University ; and  Maurice Wilkins  and  Rosalind Franklin  at  King's College London . They are also competing with other scientists in the UK, and with international scientists such as American  Linus Pauling .


The film manages to convey the loneliness and competitiveness of scientific research but also educates the viewer about how  DNA 's structure was discovered. It explores the tension between the patient, dedicated laboratory work of Franklin and the sometimes uninformed intuitive leaps of Watson and Crick, against a background of institutional turf wars, personality conflicts, and sexism.


The film also highlights many examples of social injustice such as exemplifying gender binary system that supports male norming. The film shows many instances in which they highlight that due to a male built society James Watson and Francis Crick were able to pull ahead in the discovery.


In the film, Watson, extolling the path of intuition, says: "Blessed are they who believed before there was any evidence." It also shows how Watson and Crick made their discovery, overtaking their competitors in part by reasoning from genetic function to predict chemical structure, helping to establish the field of  molecular biology .


The film script was written by  William Nicholson , based on  James Watson 's 1968 memoir  The Double Helix: A Personal Account of the Discovery of the Structure of DNA . It was produced and directed by  Mick Jackson  for  Horizon , the long-running British documentary television series on  BBC Two  that covers science and philosophy. The film was produced by the BBC in association with the American  A&E  network


Original music was composed for the film by  Peter Howell  of the  BBC Radiophonic Workshop . The main music theme is the  Le Grand Choral  by  Georges Delerue , first used in the 1973 French film  Day for Night  directed by Truffaut.


Detailed 1950s-style molecular models were recreated for the film.


In his book  What Mad Pursuit , Francis Crick wrote that there were a few inaccuracies, such as portraying Watson as too manic and as always chewing gum, but wrote that overall "it tells a good story at a good pace so that people from all walks of life can enjoy it and absorb some of its lessons. All in all,  Life Story  must be considered a success. In other hands it could easily have been nothing quite as good." [ 1 ]


The film has had a number of VHS and DVD releases, but most have been exclusively for institutional educational use and are held by the libraries of colleges and universities. A VHS in PAL format, with the title  Life Story , was produced for the educational market. [ 2 ] [ 3 ]  A shortened 90-minute VHS in NTSC format was produced in 1993 by EDDE Entertainment under the title  The Race for the Double Helix . [ 4 ]  In the 2000s,  Films for the Humanities & Sciences  produced a full-length DVD exclusively for the institutional and educational market, under the title  Double Helix . [ 5 ] [ 6 ] [ 7 ]


In December 2024, the film was made available on the  BBC iPlayer


Salvador Edward Luria  (born  Salvatore Luria ; August 13, 1912 – February 6, 1991) was an Italian  microbiologist , later a  naturalized U.S. citizen . He won the  Nobel Prize in Physiology or Medicine  in 1969, with  Max Delbrück  and  Alfred Hershey , for their discoveries on the replication mechanism and the genetic structure of viruses. Salvador Luria also showed that bacterial resistance to viruses ( phages ) is genetically inherited.


Luria was born Salvatore Luria in  Turin , Italy to an influential Italian  Sephardi Jewish  family. His parents were Davide and Ester (Sacerdote) Luria. [ 1 ]  He attended the medical school at the   University of Turin  studying with  Giuseppe Levi . There, he met two other future  Nobel  laureates:  Rita Levi-Montalcini  and  Renato Dulbecco . He graduated from the  University of Turin  in 1935 and never got a master's degree or a PhD as they were not contemplated by the Italian high educational system (which, on the other hand, was very selective). From 1936 to 1937, Luria served his required time in the Italian army as a medical officer. He then took classes in  radiology  at the  University of Rome . Here, he was introduced to  Max Delbrück 's theories on the  gene  as a molecule and began to formulate methods for testing genetic theory with the  bacteriophages ,  viruses  that infect  bacteria .


In 1938, he received a fellowship to study in the United States, where he intended to work with Delbrück. Soon after Luria received the award,  Benito Mussolini 's  fascist  regime banned Jews from academic research fellowships. Without funding sources for work in the U.S. or Italy, Luria left his home country for Paris, France in 1938. As the  Nazi  German armies invaded France in 1940, Luria fled on bicycle to  Marseille  where he received an immigration  visa  to the United States.


Luria arrived in New York City on September 12, 1940, and soon changed his first and middle names. With the help of physicist  Enrico Fermi , whom he knew from his time at the University of Rome, Luria received a  Rockefeller Foundation  fellowship at  Columbia University . He soon met Delbrück and Hershey, and they collaborated on experiments at  Cold Spring Harbor Laboratory  and in Delbrück's lab at  Vanderbilt University . [ 2 ]


His famous experiment with Delbrück in 1943, [ 3 ] [ 4 ]  known as the  Luria–Delbrück experiment , demonstrated statistically that inheritance in bacteria must follow  Darwinian  rather than  Lamarckian  principles and that  mutant  bacteria occurring randomly can still bestow viral resistance without the virus being present. The idea that natural selection affects bacteria has profound consequences, for example, it explains how bacteria develop  antibiotic  resistance.


Luria and Latarjet in 1947 published a quantitative analysis on the effect of  ultraviolet  irradiation on  bacteriophage  multiplication during intracellular growth. [ 5 ]  During the early course of infection they found an increase in bacteriophage resistance to ultraviolet irradiation  and then later a decrease.  At the time this pattern, known as the Luria-Laterjet effect, was published little was known about the central role of  DNA  in biology.  Later work established that multiple specific  DNA repair  pathways, encoded by the infecting bacteriophage, contribute to the increase in UV resistance early in infection. [ 6 ]


From 1943 to 1950, he worked at  Indiana University . His first graduate student was  James D. Watson , who went on to discover the structure of  DNA  with  Francis Crick . In January 1947, Luria became a  naturalized citizen  of the United States.


In 1950, Luria moved to the  University of Illinois Urbana–Champaign . In the early 1950s, Luria and Giuseppe Bertani discovered the phenomenon of  host-controlled restriction  and modification of a bacterial virus: a culture of  E. coli  can significantly reduce the production of phages grown in other strains; however, once the phage become established in that strain, they also become  restricted in their ability to grow in other strains. [ 7 ] [ 8 ]   It was later discovered by other researchers that bacteria produce  enzymes  that cut viral DNA at particular sequences but not the bacteria's own DNA, which is protected by  methylation .  These enzymes became known as  restriction enzymes  and developed into one of the main molecular tools in  molecular biology . [ 9 ]


Luria won the  Nobel Prize in Physiology or Medicine  in 1969, with  Max Delbrück  and  Alfred Hershey , for their discoveries on the replication mechanism and the genetic structure of viruses. [ 10 ]


In 1959, he became chair of Microbiology at the  Massachusetts Institute of Technology  (MIT). At MIT, he switched his research focus from phages to  cell membranes  and  bacteriocins . [ citation needed ]  While on sabbatical in 1963 to study at the  Institut Pasteur  in Paris, he found that bacteriocins impair the function of cell membranes. Returning to MIT, his lab discovered that bacteriocins achieve this impairment by forming holes in the cell membrane, allowing  ions  to flow through and destroy the  electrochemical gradient  of cells. In 1972, he became chair of The  Center for Cancer Research  at MIT.  The department he established included future Nobel Prize winners  David Baltimore ,  Susumu Tonegawa ,  Phillip Allen Sharp  and  H. Robert Horvitz .


In addition to the Nobel Prize, Luria received a number of awards and recognitions. He was elected to the  American Academy of Arts and Sciences  in 1959. [ 11 ]  He was named a member of the  National Academy of Sciences  in 1960. [ 12 ]  In 1964, he was elected to the  American Philosophical Society . [ 13 ]  From 1968 to 1969, he served as president of the  American Society for Microbiology . In 1969, he was awarded the  Louisa Gross Horwitz Prize  from  Columbia University  together with  Max Delbrück , co-winner with Luria of the Nobel Prize in Physiology or Medicine in 1969. In the U.S. he won the 1974  National Book Award   in Science  for his  popular science  book  Life: the Unfinished Experiment [ 14 ]
and received the  National Medal of Science  in 1991. [ 15 ]


Throughout his career, Luria was an outspoken political advocate. [ 16 ] [ 17 ]  He joined with  Linus Pauling  in 1957 to protest against nuclear weapon testing.  Luria was an opponent of the  Vietnam War  and a supporter of  organized labor . In the 1970s, he was involved in debates over  genetic engineering , advocating a compromise position of moderate oversight and regulation rather than the extremes of a complete ban or full scientific freedom. Due to his political involvement, he was  blacklisted  from receiving funding from the  National Institutes of Health  for a short time in 1969.


Noam Chomsky  describes him as a friend, and claims that Luria attempted to influence Jewish American writer  Elie Wiesel 's public stance on Israel. [ 1 ] [ 18 ]


Luria died in  Lexington, Massachusetts  of a heart attack on 6 February, 1991 at the age of 78.


Johannes Heinrich Matthaei  (born 4 May 1929) is a German  biochemist . He is best known for his unique contribution to solving the  genetic code  on 15 May 1961.


Whilst a post-doctoral visitor in the laboratory of  Marshall Warren Nirenberg  at the  NIH  in  Bethesda, Maryland , he discovered that a synthetic  RNA  polynucleotide, composed of a repeating uridylic acid residue ( Uracil ), coded for a  polypeptide  chain encoding just one kind of amino acid,  phenylalanine . In scientific terms, he discovered that polyU codes for polyphenylalanine and hence the coding unit for this amino acid is composed of a series of Us or, as we now know the  genetic code  is read in triplets, the  codon  for phenylalanine is UUU. This single experiment opened the way to the solution of the genetic code. It was for this and later work on the genetic code for which Nirenberg shared the  Nobel Prize  for Medicine and Physiology. In addition, Matthaei and his co-workers in the following years published a multitude of results concerning the early understanding of the form and function of the genetic code. [ 1 ]


Why Matthaei, who personally deciphered the genetic code, was excluded from this scientific prize is one of the  Nobel Prize controversies .


Later, Matthaei was a member of the  Max Planck Society  in  Göttingen  as a director. [ 2 ]


This article about a German biochemist is a  stub . You can help Wikipedia by  expanding it .


Maclyn McCarty  (June 9, 1911 – January 2, 2005) [ 1 ]  was an American  geneticist , a research scientist described in 2005 as "the last surviving member of a Manhattan scientific team that overturned medical dogma in the 1940s and became the first to demonstrate that  genes  were made of  DNA ." He had worked at  Rockefeller University  "for more than 60 years." [ 1 ]  1994 marked 50 years since this work's release. [ 2 ]


McCarty devoted his life as a physician-scientist to studying infectious disease organisms, and was best known for his part in the monumental discovery that  DNA , rather than protein, constituted the chemical nature of a gene. Uncovering the molecular secret of the gene in question — that for the capsular polysaccharide of pneumococcal bacteria — led the way to studying heredity not only through genetics but also through chemistry. The team responsible for this feat is known as the  Avery–MacLeod–McCarty experiment . He died from congestive heart failure.


McCarty was born in  South Bend, Indiana . [ 1 ]  He was the second of four sons; his father was a branch manager for the Studebaker Corporation while it was still a firm for horse-drawn carriages.


As an undergraduate at  Stanford University , he began his studies in the nascent field of  biochemistry , working with  James Murray Luck  on protein turnover in the liver. He "graduated in 1933 from Stanford, where he majored in biochemistry" and then "went on to earn his medical degree at  Johns Hopkins University  in 1937." After four more years there and at  New York University  "he moved to Rockefeller"  where he met his future research teammates . [ 1 ]


MacLeod, over a number of years of research, had resolved several thorny technical issues, so that by the time McCarty arrived at the Rockefeller University, Avery's team had paved the way for McCarty. Their progress over the next three years is described in McCarty's memoir  The Transforming Principle , written in the early 1980s. [ 3 ]


McCarty's arrival at Rockefeller University was also marked by another milestone, namely, the development of a  reagent assay to positively correlate DNA with biological activity. In 1944 they published in the  Journal of Experimental Medicine  about their work. [ 4 ] [ 5 ] [ 6 ]


Acceptance of the concept that "genes are DNA" was a slow process. [ 7 ] [ 8 ]  Skepticism and being ignored, at least in the New York research institutions abounded. There were challenges associated with research, which made it especially difficult to attract other investigators to pursue it. Few people had the necessary expertise. One needed to use mice for corroboration. However, by 1953, influenced by the enormous impact of  Watson and Crick's bihelical structure of DNA , the majority of researchers had fully accepted the 1944 paper.


A 1946 retirement [ 9 ]  resulted in McCarty being asked to head a specialized 1922-established laboratory. This lab was the scientific home of  Rebecca Lancefield , who developed a major classification system. His work, combined with hers, made it clear that  conditions affecting the joints and the heart resulted from infections several weeks earlier. The causal chain of events still eludes us. McCarty attacked this problem by studying both the biology and Rockefeller Hospital patients with acute rheumatic fever.


Together with his students and collaborators, over the next 20 years, McCarty's work changed the understanding of the organism from a gram-positive streptococcus with a particular serological characteristic to one of the best characterized bacterial species. Work on bacterial cell-wall anatomy and chemistry was just beginning. His work led to the isolation of the streptococcal cell wall as a structural entity suitable for anatomic inspection by  electronmicroscopy . Chemical dissection led to characterization of the group A–specific  polysaccharide  and the  peptidoglycan , and the identification of its serological specificity in the terminal  hexosamine . In order to prove this specificity, he first had to identify and purify a specific enzyme that cleaved hexosamine (a hexosaminidase) from a soil organism. Treating the polysaccharide with this enzyme abrogated its serological reactivity. McCarty further demonstrated the precise configuration of the hexosamine linkage by synthesizing both α- and β-N-acetyl-glucosamine ovalbumin and showing that only the second reacted with group A antisera. A similar analytical strategy indicated that the polysaccharide of group C streptococci differed by having a terminal β-N-acetyl galactosamine as the serological determinant.


In parallel, McCarty studied patients with rheumatic fever admitted to the Rockefeller Hospital as well as valuable specimen collections from military outbreaks of the disease during World War II. He and his collaborators found that antibody responses to several streptococcal antigens were significantly higher in the group of individuals that developed acute rheumatic fever than in individuals with uncomplicated infection. However, the response to unrelated  antigens , for instance, diphtheria toxoid, was not enhanced. He found that group A streptococci secreted unusually high amounts of DNase, and established a test for the detection of antibodies produced in response to this antigen. This led to the discovery that streptococci were able to produce multiple isozymes of DNase. He purified human C-reactive protein through crystallization, produced a highly specific antiserum, and, using this much simpler and more sensitive test, found that C-reactive protein levels responded more rapidly and reliably than other inflammatory markers and could serve as the most accurate indicator of rheumatic inflammatory activity. Measuring C-reactive protein levels to detect inflammation is routine now in medical practice.


In his later years, McCarty increasingly served as a statesman of the biomedical sciences. He served for 14 years as the physician-in-chief of the Rockefeller University Hospital, and as a trusted adviser and the vice president of the Rockefeller University. Outside the university, his leadership was sought by the New York City Health Research Council, the  Helen Hay Whitney Foundation , the  Institute of Medicine  (as a charter member), and numerous university visiting boards. For more than 40 years, as editor, he placed his stamp of excellence and integrity on the  Journal of Experimental Medicine . He was a member of the United States  National Academy of Sciences , the  American Academy of Arts and Sciences , and the  American Philosophical Society . [ 10 ] [ 11 ] [ 12 ]


McCarty's scientific interests and energy had a counterpart in his rich personal life. Along with his second [ 1 ]   wife, Marjorie, McCarty had a wide circle of very close friends, both in the United States and abroad, who cherished his personal warmth, his low key, spare, and pragmatic character, his wit, and his wide-ranging intellect. He loved English literature, theater, and symphonies. He loved to wander the streets and the museums of the great cities of the world, particularly, Paris, New York, and London, and frequently visited overseas following his retirement. Moreover, he remained close to his family; the four brothers, living in different parts of the country, never failed to meet for annual reunions.


This article incorporates  text  by  Joshua Lederberg  and Emil C Gotschlich available under the  CC BY 2.0  license.


The  Meselson–Stahl experiment  is an experiment by  Matthew Meselson  and  Franklin Stahl  in 1958 which supported  Watson  and  Crick 's  hypothesis that  DNA replication  was  semiconservative . In semiconservative replication, when the double-stranded  DNA  helix is replicated, each of the two new double-stranded DNA helices consisted of one strand from the original helix and one newly synthesized. It has been called "the most beautiful experiment in biology". [ 1 ]  Meselson and Stahl decided the best way to trace the parent DNA would be to tag them by changing one of its atoms. Since  nitrogen  is present in all of the  DNA bases , they generated parent DNA containing a heavier  isotope  of nitrogen than would be present naturally. This altered mass allowed them to determine how much of the parent DNA was present in the DNA after successive cycles of replication.


Three hypotheses had been previously proposed for the method of replication of DNA.


In the  semiconservative  hypothesis, proposed by  Watson  and  Crick , the two strands of a DNA molecule separate during replication.  Each strand then acts as a template for synthesis of a new strand. [ 2 ]


The  conservative  hypothesis proposed that the entire DNA molecule acted as a template for the synthesis of an entirely new one.  According to this model,  histone  proteins bind to the DNA, revolving the strand and exposing the nucleotide bases (which normally line the interior) for hydrogen bonding. [ 3 ]


The  dispersive  hypothesis is exemplified by a model proposed by  Max Delbrück , which attempts to solve the problem of unwinding the two strands of the double helix by a mechanism that breaks the DNA backbone every 10 nucleotides or so, untwists the molecule, and attaches the old strand to the end of the newly synthesized one.  This would synthesize the DNA in short pieces alternating from one strand to the other. [ 4 ]


Each of these three models makes a different prediction about the distribution of the "old" DNA in molecules formed after replication.  In the conservative hypothesis, after replication, one molecule is the entirely conserved "old" molecule, and the other is all newly synthesized DNA.  The semiconservative hypothesis predicts that each molecule after replication will contain one old and one new strand.  The dispersive model predicts that each strand of each new molecule will contain a mixture of old and new DNA. [ 5 ]


Nitrogen  is a major constituent of DNA.  14 N  is by far the most abundant  isotope  of nitrogen, but DNA with the heavier (but non-radioactive)  15 N  isotope is also functional.


E. coli  was grown for several generations in a medium containing NH 4 Cl with  15 N.  When DNA is extracted from these cells and made to undergo  buoyant density centrifugation  on a salt ( CsCl ) density gradient, the DNA separates out at the point at which its density equals that of the salt solution. The DNA of the cells grown in  15 N medium had a higher density than cells grown in normal  14 N medium. After that,  E. coli  cells with only  15 N in their DNA were transferred to a  14 N medium and were allowed to divide; the progress of cell division was monitored by microscopic cell counts and by colony assay.


DNA was extracted periodically and was compared to pure  14 N DNA and  15 N DNA. After one replication, the DNA was found to have intermediate density. Since conservative replication would result in equal amounts of DNA of the higher and lower densities (but no DNA of an intermediate density), conservative replication was excluded.  However, this result was consistent with both semiconservative and dispersive replication. Semiconservative replication would result in double-stranded DNA with one strand of  15 N DNA, and one of  14 N DNA, while dispersive replication would result in double-stranded DNA with both strands having mixtures of  15 N and  14 N DNA, either of which would have appeared as DNA of an intermediate density.


The authors continued to sample cells as replication continued. DNA from cells after two replications had been completed was found to consist of equal amounts of DNA with two different densities, one corresponding to the intermediate density of DNA of cells grown for only one division in  14 N medium, the other corresponding to DNA from cells grown exclusively in  14 N medium.  This was inconsistent with dispersive replication, which would have resulted in a single density, lower than the intermediate density of the one-generation cells, but still higher than cells grown only in  14 N DNA medium, as the original  15 N DNA would have been split evenly among all DNA strands.  The result was consistent with the semiconservative replication hypothesis. [ 6 ]


Matthew Stanley Meselson  (born May 24, 1930) is a  geneticist  and  molecular biologist  currently at  Harvard University , known for his demonstration, with  Franklin Stahl , of  semi-conservative   DNA replication . After completing his Ph.D. under  Linus Pauling  at the  California Institute of Technology , Meselson became a Professor at Harvard University in 1960, where he has remained today as Professor of the Natural Sciences.


In the famous  Meselson–Stahl experiment  of 1958 he and  Frank Stahl  demonstrated through nitrogen  isotope  labeling that DNA is replicated semi-conservatively. [ 1 ]  In addition, Meselson,  François Jacob , and  Sydney Brenner  discovered the existence of  messenger RNA  in 1961. Meselson has investigated DNA repair in cells and how cells recognize and destroy foreign DNA, and, with  Werner Arber , was responsible for the discovery of  restriction enzymes .


Since 1963 he has been interested in chemical and biological defense and arms control, has served as a consultant on this subject to various government agencies. Meselson worked with  Henry Kissinger  under the Nixon administration to convince President  Richard Nixon  to renounce biological weapons, suspend chemical weapons production, and support an international treaty prohibiting the acquisition of biological agents for hostile purposes, which in 1972 became known as the  Biological Weapons Convention .


Meselson has received the Award in Molecular Biology from the  National Academy of Sciences , the Public Service Award of the  Federation of American Scientists , the Presidential Award of the  New York Academy of Sciences , the 1995  Thomas Hunt Morgan Medal  of the Genetics Society of America, as well as the  Lasker Award  for Special Achievement in Medical Science. His laboratory at Harvard currently investigates the biological and evolutionary nature of sexual reproduction, genetic recombination, and aging. Many of his past students are notable biologists, including Nobel Laureate  Sidney Altman , as well as  Mark Ptashne ,  Susan Lindquist ,  Stephen F. Heinemann , and  Richard I. Morimoto .


Meselson was born in Denver, Colorado, on May 24, 1930, and attended elementary and high school in Los Angeles, California. While a young child he was interested in chemistry and physics, and conducted many experiments in the natural sciences at home. During  World War II , Meselson attended summer school during summer vacations and received enough high school credits to graduate a year and a half ahead of time. When he attempted to acquire his diploma from the registrar at his high school, however, he was informed that in order to receive his high school diploma, he needed three full years of physical education, which he lacked. After searching for options, he enrolled at the  University of Chicago  at the age of 16 in 1946 intending to study chemistry, since it did not require a high school diploma to attend. [ 2 ]


At the  University of Chicago , Meselson studied liberal arts including history and classics as an undergraduate from 1946 to 1949 after realizing upon arriving that the university had abolished bachelor's degrees in specialized field such as chemistry and physics. After completing his studies, Meselson spent half a year traveling in Europe. where he spent most of his time reading and making friends. The devastation of the war was still evident in Europe in 1949, as were the beginning tensions of the  Cold War . The following year, Meselson returned to Caltech to begin freshman studies again, but disliked the pedagogical approach in most of the courses he took. He enrolled, however, in  Linus Pauling 's freshman chemistry course, which he loved, and worked on a project for Pauling the same year on  hemoglobin  structure. [ 3 ]


Meselson subsequently returned to the University of Chicago for a year to enroll in courses in chemistry, physics, and math, though he did not receive another degree. The following year, he was accepted into a graduate physics program at the  University of California at Berkeley  where he remained for a year. In the summer of 1953, Meselson was at a swimming pool party at the Pauling home in  Sierra Madre  (he was friends with Pauling's son Peter and with his daughter Linda), and Pauling asked him what he intended to do the following year. Upon hearing Meselson respond that he intended to return to the  University of Chicago , Pauling immediately asked him to come to Caltech to begin graduate studies with him, to which Meselson agreed. As a graduate student of  Linus Pauling  in chemistry at the California Institute of Technology (1953-1957), Meselson's doctoral dissertation was on equilibrium density gradient centrifugation and on  x-ray crystallography . Besides Pauling, Meselson's dissertation committee also included  Jerome Vinograd ,  Richard Feynman , and  Harden M. McConnell . [ 4 ]  Meselson then served as Assistant Professor of Physical Chemistry and then Senior Research Fellow at Caltech until he joined the  Harvard  faculty in 1960.


In 1957, Meselson and  Franklin Stahl  (as part of the  phage group ) showed that DNA replicates semi-conservatively. [ 5 ]  In order to test hypotheses for how DNA replicates, Meselson and Stahl, together with  Jerome Vinograd , invented a method that separates macromolecules according to their buoyant density. [ 6 ]  The method, equilibrium density gradient centrifugation, was sufficiently sensitive that Meselson and Stahl were able to separate DNA containing the heavy isotope of nitrogen,  15 N, from DNA made of the lighter isotope,  14 N. In their classic experiment, described and analyzed in a book by science historian Frederic L. Holmes, [ 7 ]  they grew the bacterium  Escherichia coli  for many generations in medium containing  15 N as the only nitrogen source and then switched the bacteria to growth medium containing  14 N instead. They extracted DNA from bacteria prior to switching and, at intervals, for several generations thereafter. After one generation of growth, all the DNA was seen to have a density halfway between that of  15 N DNA and  14 N DNA. In successive generations, the fraction of DNA that was "half-heavy" fell by a factor of ½, as the total amount of DNA increased two-fold. When the half-heavy DNA was made single stranded by heating, it separated into two density species, one heavy (containing only  15 N) and one light (containing only  14 N). The experiment implied that, upon replication, the two complementary strands of the bacterial DNA separate, and that each of the single strands directs the synthesis of a new, complementary strand, a result that verified the suggestion for DNA replication put forward five years earlier by  James Watson  and  Francis Crick [ 8 ]  and lent important early support for the Watson-Crick model of the DNA molecule.


In collaboration with  Jean Weigle , Meselson then applied the density gradient method to studies of genetic recombination in the bacteriophage Lambda. [ 9 ]  The question was whether such recombination involved breakage of the recombining DNA molecules or cooperative synthesis of new molecules. The question could be answered by examining phage particles derived from co-infection of bacteria with genetically marked Lambda phages that were labeled with heavy isotopes ( 13 C and  15 N). The density-gradient method allowed individual progeny phages to be characterized for their inheritance of parental DNA and of parental genetic makers. Meselson's initial demonstration of breakage-associated, replication-independent recombination was later found to reflect the activity of a special system that can recombine Lambda DNA at only one spot, normally used by the phage to insert itself into the chromosome of a host cell. Subsequently, variations of the experiment by Franklin Stahl revealed reciprocal dependencies between DNA replication and most genetic recombination. [ 10 ]  With Charles Radding, Meselson developed a model for recombination between DNA duplexes that guided research in the field for the decade from 1973 to 1983. [ 11 ]


In 1961,  Sydney Brenner ,  François Jacob  and Meselson used the density-gradient method to demonstrate the existence of messenger RNA. [ 12 ] [ 13 ]  In subsequent work, Meselson and his students demonstrated the enzymatic basis of host-directed restriction, [ 14 ]  a process by which cells recognize and destroy foreign DNA and then predicted and demonstrated methyl-directed mismatch repair, [ 15 ] [ 16 ] [ 17 ]  a process that enables cells to correct mistakes in replicating DNA. Meselson's current research is aimed at understanding the advantage of sexual reproduction in evolution. Meselson and his colleagues have recently demonstrated that Bdelloid rotifers do, in fact, engage in sexual reproduction employing meiosis of an atypical sort. [ 18 ]


In 1963 Meselson served as a resident consultant in the  US Arms Control and Disarmament Agency , where he became interested in chemical and biological weapons programs and policies. Since then he has been involved in chemical and biological weapons defense and disarmament matters as a consultant to various US government agencies and through the  Harvard Sussex Program , an academic research organization based at Harvard and at the University of Sussex in the UK of which he and Julian Perry Robinson in the UK are co-directors.


Concluding that biological weapons served no substantial military purpose for the US and that their proliferation would pose a serious threat and that, in years ahead, the exploitation of advanced biology for hostile purposes would be inimical to society generally, he worked to persuade members of the Executive Branch, the Congress and the public that the US had no need for such weapons and that there would be benefits in renouncing them and working for worldwide prohibition. After President  Richard Nixon  in 1969 canceled the US BW offensive program and endorsed a UK proposal for an international ban, Meselson was among those who successfully advocated international agreements to ban biological and then chemical weapons, leading to the  Biological Weapons Convention  of 1972 and the  Chemical Weapons Convention  of 1993.


Meselson and his colleagues have undertaken three on-site investigations with implications for chemical and biological weapons arms control. During August and September 1970, on behalf of the American Association for the Advancement of Science, Meselson led a team in the Republic of Vietnam in a pilot study of the ecological and health effects of the military use of herbicides. [ 19 ] [ 20 ] [ 21 ]  Upon returning to Harvard, he and Robert Baughman developed an advanced mass-spectrometric method for analysis of the toxic herbicide contaminant dioxin and applied it to environmental and biomedical samples from the Vietnam and the US. In December 1970, President Richard Nixon ordered a "rapid but orderly" phase-out of herbicide operations in Vietnam. [ 22 ]


During the 1980s, Meselson investigated allegations that " yellow rain " was a Soviet toxin weapon being used against Hmong tribespeople in Laos. Citing the physical appearance and high pollen content of samples of the alleged agent; the resemblance of the alleged attacks to showers of feces from swarms of honeybees that he and entomologist Thomas Seeley documented during a 1983 field study in Thailand; the inability of US and UK government laboratories to corroborate initial reports of the presence of trichothecene mycotoxins in samples of the alleged agent and in biomedical samples from alleged victims; the lack of any supporting evidence from extensive interviews with Vietnamese military defectors and prisoners; and other considerations, Meselson and his colleagues argued that the allegations were mistaken. [ 23 ] [ 24 ] [ 25 ] [ 26 ]


In April 1980 Meselson served as a resident consultant to the CIA investigating a major outbreak of anthrax among people in the Soviet city of Sverdlovsk. He concluded that on the basis of available evidence the official Soviet explanation that the outbreak was caused by consumption of meat from infected cattle was plausible but that there should be an independent on-site investigation. After the collapse of the Soviet Union, he was allowed to bring a team to Sverdlovsk in 1992 and again in 1993. Their reports conclusively showed that the official Soviet explanation was wrong and that the outbreak was caused by the  release of an anthrax aerosol  at a military biological facility in the city. [ 27 ] [ 28 ]


Meselson is a member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, the Académie des Sciences (Paris), the Royal Society (London) and the Russian Academy of Sciences and has received numerous awards and honors in the field of science and in public affairs. He has served on the Council of the National Academy of Sciences, the Council of the Smithsonian Institution, the Arms Control and Non-Proliferation Advisory Board to the US Secretary of State and the Committee on International Security and Arms Control of the US National Academy of Sciences. He is past President of the Federation of American Scientists, and presently is co-director of the Harvard Sussex Program on Chemical and Biological Weapons and a member of the board of directors of the  Belfer  Center for Science and International Affairs at the John F. Kennedy School of Government at Harvard University.


He married three times, first to Katherine Kaynis, then to Sarah Page, with whom he had two daughters,  Amy  and Zoe. His third marriage was to  Jeanne Guillemin , with whom he shares two stepsons. [ 30 ]


Johannes Friedrich Miescher  (13 August 1844 – 26 August 1895) was a Swiss physician and biologist. He was the first  scientist  to isolate  nucleic acid  in 1869. Miescher also identified  protamine  and made several other discoveries.


Miescher had isolated various phosphate-rich chemicals, which he called  nuclein  (now  nucleic acids ), from the nuclei of  white blood cells  in  Felix Hoppe-Seyler 's laboratory at the  University of Tübingen , Germany, [ 1 ]  paving the way for the identification of  DNA  as the carrier of inheritance. The significance of the discovery, first published in 1871, was not at first apparent, and  Albrecht Kossel   made the initial inquiries into its chemical structure. Later, Miescher raised the idea that the nucleic acids could be involved in heredity [ 2 ]  and even posited that there might be something akin to an alphabet that might explain how variation is produced. [ 3 ]


Friedrich Miescher came from a scientific family; his father and his uncle held the chair of anatomy at the  University of Basel . As a boy, Miescher was shy but intelligent. He had an interest in music as his father performed publicly. Miescher studied medicine at Basel, and in the summer of 1865, he worked for the organic chemist Adolf Stecker at the  University of Göttingen . However, Miescher's studies were interrupted for the year when he contracted typhoid fever, leaving him hearing-impaired. Miescher received his MD in 1868. [ 1 ]


Miescher felt that his partial deafness would be a disadvantage as a doctor, so he turned to physiological chemistry. Miescher originally wanted to study  lymphocytes , but was encouraged by  Felix Hoppe-Seyler  to study  neutrophils . Miescher was interested in studying the chemistry of the  nucleus . Lymphocytes were difficult to obtain in sufficient numbers to study, while neutrophils were known to be one of the main and first components in  pus  and could be obtained from bandages at the nearby hospital. However, the problem was washing the cells off the bandages without damaging them. [ 1 ]


Miescher devised different salt solutions, eventually producing one with sodium sulfate. The cells were filtered, and since  centrifuges  were not available at the time, the cells were allowed to settle to the bottom of a beaker. He then tried to isolate the nuclei free of  cytoplasm . Miescher subjected the purified nuclei to an  alkaline extraction  followed by acidification, resulting in the formation of a precipitate that he called  nuclein  (now known as  DNA ). [ 4 ]  Miescher found that this contained phosphorus and nitrogen, but not sulfur. The discovery was so unlike anything else at the time that Hoppe-Seyler repeated all of Miescher's research himself before publishing it in his journal. Miescher then went on to study physiology at Leipzig in the laboratory of Carl Ludwig for a year before being appointed professor of physiology. [ 1 ]


While analyzing the composition of salmon sperm, Miescher also discovered the alkaline substance  protamine , the account of which he published in 1874. [ 5 ] [ 6 ]  It later found use, as  protamine sulfate , in the stabilization of  insulin  ( NPH insulin ) and also as a reversal agent for the anticoagulant medicine  heparin . [ 7 ]


Miescher and his students researched much nucleic acid chemistry, but its function remained unknown. However, Miescher's discovery played an important part in the identification of nucleic acids as the carriers of inheritance. The importance of his discovery was not apparent until  Albrecht Kossel  (a German physiologist specializing in the physiological chemistry of the cell and its nucleus and of proteins) researched the chemical structure of nuclein. [ 8 ]


Miescher is also known for demonstrating that carbon dioxide concentrations in blood regulate breathing. [ 1 ]


Miescher was married to Maria Anna Rüsch. [ 6 ]  He died of  tuberculosis  in 1895 at the age of 51.


As of 2008, two laboratories have been named after Miescher: [ 1 ]
The  Friedrich Miescher Laboratory of the Max Planck Society  in Tübingen and the Friedrich Miescher Institute for Biomedical Research in Basel, founded in 1970 by  Ciba-Geigy . [ 9 ]


" Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid " was the first article  published  to describe the discovery of the  double helix  structure of  DNA , using  X-ray diffraction  and the mathematics of a  helix  transform. It was published by  Francis Crick  and  James D. Watson  in the  scientific journal   Nature  on pages 737–738 of its 171st volume (dated 25 April 1953). [ 1 ] [ 2 ]


This article is often termed a "pearl" of science because it is brief and contains the answer to a fundamental mystery about  living   organisms . This mystery was the question of how it is possible that  genetic  instructions are held inside organisms and how they are passed from generation to generation. The article presents a simple and elegant solution, which surprised many biologists at the time who believed that DNA transmission was going to be more difficult to deduce and understand. The discovery had a major impact on  biology , particularly in the field of  genetics , enabling later researchers to understand the  genetic code .


The application of physics and chemistry to biological problems led to the development of molecular biology, which is particularly concerned with the flow and consequences of biological information from DNA to  proteins . The discovery of the DNA double helix made clear that genes are functionally defined parts of DNA molecules, and that there must be a way for cells to translate the information in DNA to specific amino acids, which make proteins.


Linus Pauling  was a chemist who was very influential in developing an understanding of the structure of biological molecules. In 1951, Pauling published the structure of the  alpha helix , a fundamentally important structural component of proteins. In early 1953, Pauling published a triple helix model of DNA, which subsequently turned out to be incorrect. [ 3 ]  Both Crick, and particularly Watson, thought that they were racing against Pauling to discover the structure of DNA.


Max Delbrück  was a physicist who recognized some of the biological implications of  quantum physics . Delbruck's thinking about the physical basis of life stimulated  Erwin Schrödinger  to write  What Is Life? . Schrödinger's book was an important influence on Crick and Watson. Delbruck's efforts to promote the " Phage  Group" (exploring genetics by way of the viruses that infect bacteria) was important in the early development of  molecular biology  in general and the development of Watson's scientific interests in particular. [ 4 ]


Crick, Watson, and  Maurice Wilkins  won the  Nobel Prize for Medicine  in recognition of their discovery of the DNA double helix.


It is not always the case that the structure of a molecule is easy to relate to its function. What makes the structure of DNA so obviously related to its function was described modestly at the end of the article: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material".


The "specific pairing" is a key feature of the Watson and Crick model of DNA, the pairing of  nucleotide  subunits. [ 5 ]  In DNA, the amount of  guanine  is equal to  cytosine  and the amount of  adenine  is equal to  thymine . The A:T and C:G pairs are structurally similar. In particular, the length of each base pair is the same and they fit equally between the two sugar-phosphate backbones. The  base pairs  are held together by  hydrogen bonds , a type of chemical attraction that is easy to break and easy to reform. After realizing the structural similarity of the A:T and C:G pairs, Watson and Crick soon produced their  double helix  model of DNA with the hydrogen bonds at the core of the helix providing a way to unzip the two complementary strands for easy  replication : the last key requirement for a likely model of the genetic molecule.


Indeed, the base-pairing did suggest a way to copy a DNA molecule. Just pull apart the two sugar-phosphate backbones, each with its hydrogen bonded A, T, G, and C components. Each strand could then be used as a template for assembly of a new base-pair complementary strand.


When Watson and Crick produced their double helix model of DNA, it was known that most of the specialized features of the many different life forms on Earth are made possible by  proteins . Structurally, proteins are long chains of  amino acid  subunits. In some way, the genetic molecule, DNA, had to contain instructions for how to make the thousands of proteins found in cells. From the DNA double helix model, it was clear that there must be some correspondence between the linear sequences of nucleotides in DNA molecules to the linear sequences of amino acids in proteins. The details of how sequences of DNA instruct cells to make specific proteins was worked out by molecular biologists during the period from 1953 to 1965. Francis Crick played an integral role in both the theory and analysis of the experiments that led to an improved understanding of the  genetic code . [ 6 ]


Other advances in molecular biology stemming from the discovery of the DNA double helix eventually led to ways to  sequence  genes. James Watson directed the  Human Genome Project  at the  National Institutes of Health . [ 7 ]  The ability to sequence and manipulate DNA is now central to the  biotechnology  industry and modern  medicine . The austere beauty of the structure and the practical implications of the DNA double helix combined to make  Molecular structure of Nucleic Acids; A Structure for Deoxyribose Nucleic Acid  one of the most prominent biology articles of the twentieth century.


Although Watson and Crick were first to put together all the scattered fragments of information that were required to produce a successful molecular model of DNA, their findings had been based on data collected by researchers in several other laboratories. For example, they drew on published research relating to the discovery of Hydrogen bonds in DNA by  John Masson Gulland ,  Denis Jordan  and their colleagues at  University College Nottingham  in 1947. [ 8 ] [ 9 ] [ 10 ]  However the discovery of the DNA double helix also used a considerable amount of material from the unpublished work of  Rosalind Franklin ,  A.R. Stokes ,  Maurice Wilkins , and  H.R. Wilson  at  King's College London . Key data from Wilkins, Stokes, and Wilson, and, separately, by Franklin and  Gosling , were published in two separate additional articles in the same issue of  Nature  with the article by Watson and Crick. [ 11 ] [ 12 ]  The article by Watson and Crick acknowledged that they had been "stimulated" by experimental results from the King's College researchers, and a similar acknowledgment was published by Wilkins, Stokes, and Wilson in the following three-page article.


In 1968, Watson published a highly controversial autobiographical account of the discovery of the  double-helical , molecular structure of DNA called  The Double Helix , which was not publicly accepted either by Crick or Wilkins. [ 13 ]  Furthermore,  Erwin Chargaff  also printed a rather "unsympathetic review" of Watson's book in the 29 March 1968 issue of  Science . In the book, Watson stated among other things that he and Crick had access to some of Franklin's data from a source that she was not aware of, and also that he had seen—without her permission—the B-DNA X-ray diffraction pattern obtained by Franklin and Gosling in May 1952 at King's in London. In particular, in late 1952, Franklin had submitted a progress report to the  Medical Research Council , which was reviewed by  Max Perutz , then at the  Cavendish Laboratory  of the  University of Cambridge . Watson and Crick also worked in the MRC-supported Cavendish Laboratory in Cambridge whereas Wilkins and Franklin were in the MRC-supported laboratory at King's in London. Such MRC reports were not usually widely circulated, but Crick read a copy of Franklin's research summary in early 1953. [ 13 ] [ 14 ]


Perutz's justification for passing Franklin's report about the crystallographic unit of the B-DNA and A-DNA structures to both Crick and Watson was that the report contained information which Watson had heard before, in November 1951, when Franklin talked about her unpublished results with  Raymond Gosling  during a meeting arranged by M.H.F. Wilkins at King's College, following a request from Crick and Watson; [ 15 ]  Perutz said he had not acted unethically because the report had been part of an effort to promote wider contact between different MRC research groups and was not confidential. [ 16 ]  This justification would exclude Crick, who was not present at the November 1951 meeting, yet Perutz also gave him access to Franklin's MRC report data. Crick and Watson then sought permission from Cavendish Laboratory head  William Lawrence Bragg , to publish their double-helix molecular model of DNA based on data from Franklin and Wilkins.


By November 1951, Watson had acquired little training in X-ray crystallography, by his own admission, and thus had not fully understood what Franklin was saying about the structural symmetry of the DNA molecule. [ 14 ]  Crick, however, knowing the  Fourier transforms  of  Bessel functions  that represent the X-ray diffraction patterns of helical structures of atoms, correctly interpreted further one of Franklin's experimental findings as indicating that DNA was most likely to be a double helix with the two polynucleotide chains running in opposite directions. Crick was thus in a unique position to make this interpretation because he had formerly worked on the X-ray diffraction data for other large molecules that had helical symmetry similar to that of DNA. Franklin, on the other hand, rejected the first molecular model building approach proposed by Crick and Watson: the first DNA model, which in 1952 Watson presented to her and to Wilkins in London, had an obviously incorrect structure with hydrated charged groups on the inside of the model, rather than on the outside. Watson explicitly admitted this in his book  The Double Helix . [ 14 ]


Jacques Lucien Monod  ( French:   [mɔno] ; 9 February 1910 – 31 May 1976) was a French  biochemist  who won the  Nobel Prize in Physiology or Medicine  in 1965, sharing it with  François Jacob  and  André Lwoff  "for their discoveries concerning genetic control of enzyme and virus synthesis". [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]


Monod and Jacob became famous for their work on the  E. coli   lac  operon , which encodes proteins necessary for the transport and breakdown of the sugar  lactose  (lac). From their own work and the work of others, they came up with a model for how the levels of some proteins in a cell are controlled. In their model, the manufacture of a set of related proteins, such as the ones encoded within the  lac  (lactose)  operon , is prevented when a  repressor  protein, encoded by a regulatory  gene , binds to its  operator , a specific site in the DNA sequence that is close to the genes encoding the proteins. (It is now known that a repressor bound to an operator physically blocks  RNA polymerase  from binding to the  promoter , the site where  transcription  of the adjacent genes begins.)


Study of the control of expression of genes in the  lac  operon provided the first example of a system for the  regulation  of  transcription . Monod also suggested the existence of  messenger RNA  molecules that link the information encoded in  DNA  and  proteins . For these contributions he is widely regarded as one of the founders of  molecular biology . [ 7 ] [ 8 ]


As a student at the  University of Paris , Monod discovered that the coursework was decades behind the current biological science. He learned from other students a little older than himself, rather than from the faculty. "To  George Teissier  he owes a preference for quantitative descriptions;  André Lwoff  initiated him into the potentials of microbiology; to  Boris Ephrussi  he owes the discovery of physiological genetics, and to  Louis Rapkine  the concept that only chemical and molecular descriptions could provide a complete interpretation of the function of living organisms." [ 9 ]


Before his doctoral work, Monod spent a year in the laboratory of  Thomas Hunt Morgan  at the  California Institute of Technology  working on  Drosophila  genetics. This was a true revelation for him and probably influenced him on developing a genetic conception of biochemistry and metabolism. [ 10 ]


Monod's interest in the  lac  operon originated from his doctoral dissertation, which explored the growth of bacteria on mixtures of sugars and documented the sequential utilization of two or more sugars. [ 9 ] [ 11 ] [ 12 ]  The work was conducted at the University of Paris, with  André Lwoff  of the  Pasteur Institute  having provided important advice. [ 13 ]  Monod coined the term  diauxie  to denote the frequent observations of two distinct growth phases of bacteria grown on two sugars. He theorized on the growth of bacterial cultures and promoted the  chemostat  theory as a powerful continuous culture system to investigate bacterial physiology. [ 14 ]


Monod joined the Pasteur Institute in 1943 and Jacob in 1949. The experimental system ultimately used by Jacob and Monod was a common bacterium,  E. coli , but the basic regulatory concept (described in the  Lac operon  article) that was discovered by Jacob and Monod is fundamental to  cellular  regulation for all organisms. The key idea is that  E. coli  does not waste energy making such enzymes if there is no need to metabolize  lactose , such as when other sugars like  glucose  are available. The type of regulation is called negative  gene regulation , as the operon is inactivated by a protein complex that is removed in the presence of lactose (regulatory induction).


With  Jean-Pierre Changeux  and  François Jacob , [ 15 ]  Monod proposed a theory of  allosteric transitions  to explain how conformational effects could allow enzyme effectors that are structurally quite different from the enzyme's substrates and products to activate or inhibit the reaction: binding at an  allosteric site  of the enzyme remote from the active site could bring about a change at the active site. He made an important contribution to  enzymology  when he collaborated with  Jeffries Wyman  and Changeux to extend this concept to explain  cooperative behaviour  of some multi-subunit proteins. [ 16 ]  This has become the most widely accepted explanation of cooperativity. [ 17 ]


Monod was not only a biologist but also a musician and writer on the  philosophy of science . He was a political activist and  chief of staff  of operations for the  Forces Françaises de l'Interieur  during  World War II . In preparation for the Allied landings, he arranged parachute drops of weapons, railroad bombings, and mail interceptions.


In 1970, Monod published  Le hasard et la nécessité  – English translation  Chance and Necessity  (1971) –, a book based on a series of lectures that he had given at  Pomona College  in 1969. [ 18 ]  The book is a short but influential examination of the  philosophical implications of modern biology , written for a general readership. [ 19 ]  Monod acknowledges his connection to the French  existentialists  in the epigraph of the book, which quotes the final paragraphs of  Camus 's  The Myth of Sisyphus . In summarizing recent progress in several areas of biology, including his own research, Monod highlights the ways in which information is found to take physical form and hence become capable of influencing events in the world. For example, the information allowing a protein enzyme to "select" only one of several similar compounds as the substrate of a chemical reaction is encoded in the precise three-dimensional shape of the enzyme; that precise shape is itself encoded by the linear sequence of amino acids constituting the protein; and that particular sequence of amino acids is encoded by the sequence of nucleotides in the gene for that enzyme.


In the title of the book, "necessity" refers to the fact that the enzyme  must  act as it does, catalyzing a reaction with one substrate but not another, according to the constraints imposed by its structure. While the enzyme itself cannot be said in any meaningful way to have a choice about its activity, the thrust of Jacob and Monod's Nobel prize-winning research was to show how a bacterial cell can "choose" whether or not to carry out the reaction catalyzed by the enzyme.  As Monod explains, one way the cell can make such a choice is by either synthesizing the enzyme or not, in response to its chemical environment.  However, the synthesis/no synthesis choice is in turn governed by necessary biochemical interactions between a repressor protein, the gene for the enzyme, and the substrate of the enzyme, which interact so that the outcome (enzyme synthesis or not) differs according to the variable composition of the cell's chemical environment.  The hierarchical, modular organization of this system clearly implies that additional regulatory elements can exist that govern, are governed by, or otherwise interact with any given set of regulatory components.  Because, in general, the bacterial activity that results from these regulatory circuits is in accord with what is beneficial for the bacterial cell's survival at that time, the bacterium as a whole can be described as making rational choices, even though the bacterial components involved in deciding whether to make an enzyme (repressor, gene, and substrate) have no more choice about their activities than does the enzyme itself.


Monod shows a paradigm of how choice at one level of biological organization (metabolic activity) is generated by necessary (choiceless) interactions at another level (gene regulation); the ability to choose arises from a complex system of feedback loops that connect these interactions.  He goes on to explain how the capacity of biological systems to retain information, combined with chance variations during the replication of information (i.e. genetic mutations) that are individually rare but commonplace in aggregate, leads to the differential preservation of that information which is most successful at maintaining and replicating itself.  Monod writes that this process, acting over long periods of time, is a sufficient explanation (indeed the only plausible explanation) for the complexity and teleonomic activity of the biosphere.  Hence, the combined effects of chance and necessity, which are amenable to scientific investigation, account for our existence and the universe we inhabit, without the need to invoke mystical, supernatural, or religious explanations.


While acknowledging the likely evolutionary origin of a human need for explanatory myths, in the final chapter of  Chance and Necessity  Monod advocates an objective (hence value-free) scientific worldview as a guide to assessing truth.  He describes this as an "ethics of knowledge" that disrupts the older philosophical, mythological and religious ontologies, which claim to provide both ethical values and a standard for judging truth. For Monod, assessing truth separate from any value judgement is what frees human beings to act authentically, by requiring that they  choose  the ethical values that motivate their actions. He concludes that "man at last knows he is alone in the unfeeling immensity of the universe, out of which he has emerged only by chance. His destiny is nowhere spelled out, nor is his duty. The kingdom above or the darkness below: it is for him to choose". [ 20 ]   While apparently bleak, in comparison to the concepts that humanity belongs to some inevitable, universal process, or that a benevolent God created and protects us, an acceptance of the scientific assessment described in the first part of the quotation is, for Monod, the only possible basis of an authentic, ethical human life.  It is reasonable to conclude that Monod himself did not find this position bleak; the quotation he chose from Camus to introduce  Chance and Necessity  ends with the sentence: "One must imagine Sisyphus happy."


In 1973, Jacques Monod was one of the signatories of the  Humanist Manifesto II . [ 21 ]


Sociologist Howard L. Kaye has suggested that Monod failed in his attempt to banish "mind and purpose from the phenomenon of life" in the name of science. [ 22 ]  It may be more accurate to suggest that Monod sought to include mind and purpose within the purview of scientific investigation, rather than attributing them to supernatural or divine causes. While Monod does not explicitly address mind or consciousness, his scientific research demonstrated that biology includes feedback loops that govern interacting systems of biochemical reactions, so that the system as a whole can be described as having a purpose and making choices. Monod's philosophical writing indicates that he recognized the implication that such systems could arise and be elaborated upon by evolution through natural selection. The importance of Monod's work as a bridge between the chance and necessity of evolution and biochemistry on the one hand, and the human realm of choice and ethics on the other, can be judged by his influence on philosophers, biologists and computer scientists such as  Daniel Dennett ,  Douglas Hofstadter ,  Marvin Minsky  and  Richard Dawkins .


In addition to sharing a Nobel Prize, Monod was also a recipient of the  Légion d'honneur  and elected member of the  American Academy of Arts and Sciences  in 1960. [ 23 ]  He was elected a member of the  National Academy of Sciences , [ 24 ]  the  American Philosophical Society , [ 25 ]  and a  Foreign Member of the Royal Society in 1968 . [ 26 ]  The Institut Jacques Monod, funded jointly by the CNRS and the University of Paris, is one of the main centers for basic research in biology in the Paris area. It is headed by Michel Werner, Research Director.


Monod was born in Paris to an American mother from  Milwaukee , Charlotte (Sharlie) MacGregor Todd, and a French  Huguenot  father,  Lucien Monod , who was a painter and inspired him artistically and intellectually. [ 26 ] [ 9 ]  He attended the  lycée  at  Cannes  until he was 18. [ 26 ]  In October 1928 he started his studies in biology at the University of Paris. [ 26 ]


In 1938 he married Odette Bruhl (d.1972). [ 27 ]


During  World War II , Monod was active in the  French Resistance , eventually becoming the chief of staff of the  French Forces of the Interior . [ 13 ]  He was a Chevalier in the  Légion d'Honneur  (1945) and was awarded the  Croix de Guerre  (1945) and the American  Bronze Star Medal . [ 28 ] [ 9 ]  Monod became a member of the  French Communist Party  after the end of the Second World War, but distanced himself from the  party after the  Lysenko Affair . [ 29 ]  He became a close friend of  Albert Camus , Nobel laureate in literature who had also been active in the French Resistance and shared Monod's criticism of the Soviet system. [ 13 ]


Monod, then a professor at the University of Paris, supported the student protests of  May 68  and, along with several fellow Nobel laureates, appealed to president  Charles de Gaulle  on the students' behalf. [ 13 ]


Jacques Monod died of  leukemia  in 1976 and was buried in the  Cimetière du Grand Jas  in  Cannes  on the  French Riviera .


Thomas Hunt Morgan   (September 25, 1866 – December 4, 1945) [ 2 ]  was an American  evolutionary biologist ,  geneticist ,  embryologist , and science author who won the  Nobel Prize in Physiology or Medicine  in  1933 for discoveries elucidating the role that the  chromosome  plays in  heredity . [ 3 ]


Morgan received his Ph.D. from  Johns Hopkins University  in  zoology  in 1890 and researched embryology during his tenure at  Bryn Mawr . Following the rediscovery of  Mendelian inheritance  in 1900, Morgan began to study the genetic characteristics of the fruit fly  Drosophila melanogaster . In his famous Fly Room at  Columbia University 's  Schermerhorn Hall , Morgan demonstrated that  genes  are carried on  chromosomes  and are the mechanical basis of heredity. These discoveries formed the basis of the modern science of  genetics .


During his distinguished career, Morgan wrote  22 books  and 370 scientific papers. [ 2 ]  As a result of his work,  Drosophila  became a major  model organism  in contemporary genetics. The Division of Biology which he established at the  California Institute of Technology  has produced seven Nobel Prize winners.


Morgan was born in  Lexington ,  Kentucky , to Charlton Hunt Morgan and Ellen Key Howard Morgan. [ 3 ] [ 4 ]  Part of a line of  Southern  plantation and slave owners on his father's side, Morgan was a nephew of  Confederate  General  John Hunt Morgan ; his great-grandfather  John Wesley Hunt  had been one of the first millionaires west of the  Allegheny Mountains . Through his mother, he was the great-grandson of  Francis Scott Key , the author of the " Star Spangled Banner ", and  John Eager Howard , governor and senator from  Maryland . [ 4 ]  Following the Civil War, the family fell on hard times with the temporary loss of civil and some property rights for those who aided the Confederacy. His father had difficulty finding work in politics and spent much of his time coordinating veterans' reunions. [ citation needed ]


Beginning at age 16 in the Preparatory Department, Morgan attended the State College of Kentucky (now the  University of Kentucky ). He focused on science; he particularly enjoyed natural history, and worked with the  U.S. Geological Survey  in his summers. He graduated as  valedictorian  in 1886 with a Bachelor of Science degree. [ 5 ]  Following a summer at the Marine Biology School in  Annisquam, Massachusetts , Morgan began graduate studies in  zoology  at the recently founded  Johns Hopkins University . After two years of experimental work with  morphologist   William Keith Brooks  and writing several publications, Morgan was eligible to receive a Master of Science from the State College of Kentucky in 1888. The college required two years of study at another institution and an examination by the college faculty.  [ citation needed ]  The college offered Morgan a full professorship; however, he chose to stay at Johns Hopkins and was awarded a relatively large fellowship to help him fund his studies. [ citation needed ]


Under Brooks, Morgan completed his thesis work on the embryology of  sea spiders —collected during the summers of 1889 and 1890 at the  Marine Biological Laboratory  in  Woods Hole, Massachusetts —to determine their  phylogenetic  relationship with other  arthropods . He concluded that concerning embryology, they were more closely related to  spiders  than crustaceans. Based on the publication of this work, Morgan was awarded his  Ph.D.  from Johns Hopkins in 1890 and was also awarded the Bruce Fellowship in Research. He used the fellowship to travel to  Jamaica , the  Bahamas  and  Europe  to conduct further research. [ 6 ]


Every summer from 1910 to 1925, Morgan and his colleagues at the famous Fly Room at Columbia University moved their research program to the  Marine Biological Laboratory . Aside from being an independent investigator at the MBL from 1890 to 1942, he became very involved in the governance of the institution, including serving as an MBL trustee from 1897 to 1945. [ 7 ]


In 1890, Morgan was appointed associate professor (and head of the biology department) at Johns Hopkins' sister school  Bryn Mawr College , replacing his colleague  Edmund Beecher Wilson . [ 8 ]  Morgan taught all morphology-related courses, while the other member of the department,  Jacques Loeb , taught the physiological courses. Although Loeb stayed for only one year, it was the beginning of their lifelong friendship. [ 9 ]   Morgan lectured in biology five days a week, giving two lectures a day. He frequently included his recent research in his lectures. Although an enthusiastic teacher, he was most interested in research in the laboratory. During the first few years at Bryn Mawr, he produced descriptive studies of  sea acorns , ascidian worms, and frogs. [ citation needed ]


In 1894 Morgan was granted a year's absence to conduct research in the laboratories of  Stazione Zoologica  in  Naples , where Wilson had worked two years earlier. There he worked with German biologist  Hans Driesch , whose research in the experimental study of development piqued Morgan's interest. Among other projects that year, Morgan completed an experimental study of  ctenophore  embryology. In Naples and through Loeb, he became familiar with the  Entwicklungsmechanik  (roughly, "developmental mechanics") school of experimental biology. It was a reaction to the vitalistic  Naturphilosophie , which was extremely influential in 19th-century morphology. Morgan changed his work from traditional, largely descriptive morphology to experimental embryology that sought physical and chemical explanations for organismal development. [ 10 ]


At the time, there was considerable scientific debate over the question of how an embryo developed. Following  Wilhelm Roux 's mosaic theory of development, some believed that hereditary material was divided among embryonic cells, which were predestined to form particular parts of a mature organism. Driesch and others thought that development was due to epigenetic factors, where interactions between the protoplasm and the nucleus of the egg and the environment could affect development. Morgan was in the latter camp; his work with Driesch demonstrated that  blastomeres  isolated from  sea urchin  and ctenophore eggs could develop into complete larvae, contrary to the predictions (and experimental evidence) of Roux's supporters. [ 11 ]   A related debate involved the role of  epigenetic  and environmental factors in development; on this front Morgan showed that  sea urchin  eggs could be induced to divide without fertilization by adding  magnesium chloride . Loeb continued this work and became well known for creating fatherless frogs using the method. [ 12 ]
 [ 13 ]


When Morgan returned to Bryn Mawr in 1895, he was promoted to full professor. Morgan's main lines of experimental work involved  regeneration  and larval development; in each case, his goal was to distinguish internal and external causes to shed light on the Roux-Driesch debate. He wrote his first book,  The Development of the Frog's Egg  (1897). He began a series of studies on different organisms' ability to regenerate. He looked at grafting and regeneration in tadpoles, fish, and earthworms; in 1901 he published his research as  Regeneration .


Beginning in 1900, Morgan started working on the problem of  sex determination , which he had previously dismissed when  Nettie Stevens  discovered the impact of the Y chromosome on sex. He also continued to study the evolutionary problems that had been the focus of his earliest work. [ 14 ]


Morgan worked at Columbia University for 24 years, from 1904 until 1928 when he left for a position at the California Institute of Technology. [ citation needed ]


In 1904, his friend, Jofi Joseph died of tuberculosis, and he felt he ought to mourn her, though E. B. Wilson—still blazing the path for his younger friend—invited Morgan to join him at  Columbia University . This move freed him to focus fully on experimental work. [ 15 ]


When Morgan took the professorship in experimental zoology, he became increasingly focused on the mechanisms of heredity and evolution. He published  Evolution and Adaptation  (1903); like many biologists at the time, he saw evidence for biological evolution (as in the  common descent  of similar species) but rejected Darwin's proposed mechanism of  natural selection  acting on small, constantly produced variations.


Extensive work in  biometry  seemed to indicate that continuous natural variation had distinct limits and did not represent heritable changes. Embryological development posed an additional problem in Morgan's view, as selection could not act on the early, incomplete stages of highly complex organs such as the eye. The common solution of the  Lamarckian  mechanism of  inheritance of acquired characters , which featured prominently in Darwin's theory, was increasingly rejected by biologists. According to Morgan's biographer  Garland Allen , he was also hindered by his views on taxonomy: he thought that species were entirely artificial creations that distorted the continuously variable range of real forms, while he held a "typological" view of larger taxa and could see no way that one such group could transform into another. But while Morgan was skeptical of natural selection for many years, his theories of heredity and variation were radically transformed through his conversion to Mendelism. [ 16 ]


In 1900 three scientists,  Carl Correns ,  Erich von Tschermak  and  Hugo De Vries , had rediscovered the work of  Gregor Mendel , and with it the foundation of  genetics . De Vries proposed that new species were created by mutation, bypassing the need for either Lamarckism or Darwinism. As Morgan had dismissed both evolutionary theories, he was seeking to prove De Vries'  mutation theory  with his experimental heredity work. He was initially skeptical of Mendel's laws of heredity (as well as the related chromosomal theory of sex determination), which were being considered as a possible basis for natural selection.


Following  C. W. Woodworth  and  William E. Castle , around 1908 Morgan started working on the fruit fly  Drosophila melanogaster , and encouraging students to do so as well. With  Fernandus Payne , he mutated  Drosophila  through physical, chemical, and radiational means. [ 17 ] [ 18 ]  He began cross-breeding experiments to find heritable mutations, but they had no significant success for two years. [ 17 ]   Castle had also had difficulty identifying mutations in  Drosophila , which were tiny. Finally, in 1909, a series of heritable mutants appeared, some of which displayed Mendelian inheritance patterns; in 1910 Morgan noticed a white-eyed  mutant  male among the red-eyed  wild types . When white-eyed flies were bred with a red-eyed female, their progeny were all red-eyed. A second-generation cross produced white-eyed males—a sex-linked recessive trait, the gene for which Morgan named  white . Morgan also discovered a pink-eyed mutant that showed a different pattern of inheritance. In a paper published in  Science  in 1911, he concluded that (1) some traits were  sex-linked , (2) the trait was probably carried on one of the  sex chromosomes , and (3) other genes were probably carried on specific chromosomes as well.


Morgan and his students became more successful at finding mutant flies; they counted the mutant characteristics of thousands of fruit flies and studied their inheritance. As they accumulated multiple mutants, they combined them to study more complex inheritance patterns. The observation of a miniature-wing mutant, which was also on the sex chromosome but sometimes sorted independently to the white-eye mutation, led Morgan to the idea of  genetic linkage  and to hypothesize the phenomenon of  crossing over . He relied on the discovery of  Frans Alfons Janssens , a Belgian professor at the  University of Leuven , who described the phenomenon in 1909 and had called it  chiasmatypy . Morgan proposed that the amount of crossing over between linked genes differs and that crossover frequency might indicate the distance separating genes on the chromosome. The later English geneticist  J. B. S. Haldane  suggested that the unit of measurement for linkage be called the  morgan . Morgan's student  Alfred Sturtevant  developed the first  genetic map  in 1913. [ 19 ]


In 1915 Morgan, Sturtevant,  Calvin Bridges  and  H. J. Muller  wrote the seminal book  The Mechanism of Mendelian Heredity . [ 21 ]  Geneticist  Curt Stern  called the book "the fundamental textbook of the new genetics". [ 22 ]


In the following years, most biologists came to accept the  Mendelian-chromosome theory , which was independently proposed by  Walter Sutton  and  Theodor Boveri  in 1902/1903, and elaborated and expanded by Morgan and his students.  Garland Allen  characterized the post-1915 period as one of  normal science , in which "The activities of 'geneticists' were aimed at further elucidation of the details and implications of the Mendelian-chromosome theory developed between 1910 and 1915."  But, the details of the increasingly complex theory, as well as the concept of the  gene  and its physical nature, were still controversial. Critics such as  W. E. Castle  pointed to contrary results in other organisms, suggesting that genes interact with each other, while  Richard Goldschmidt  and others thought there was no compelling reason to view genes as discrete units residing on chromosomes. [ 24 ]


Because of Morgan's dramatic success with  Drosophila , many other labs throughout the world took up fruit fly genetics. Columbia became the center of an informal exchange network, through which promising mutant  Drosophila  strains were transferred from lab to lab;  Drosophila  became one of the first and for some time the most widely used,  model organisms . [ 25 ]   Morgan's group remained highly productive, but Morgan largely withdrew from doing fly work and gave his lab members considerable freedom in designing and carrying out their own experiments.


He returned to embryology and worked to encourage the spread of genetics research to other organisms and the spread of mechanistic experimental approach ( Enwicklungsmechanik ) to all biological fields. [ 26 ]   After 1915, he also became a strong critic of the growing  eugenics  movement, which adopted genetic approaches in support of  racist  views of "improving" humanity. [ 27 ]


Morgan's  fly-room  at Columbia became world-famous, and he found it easy to attract funding and visiting academics. In 1927 after 25 years at Columbia, and nearing the age of retirement, he received an offer from  George Ellery Hale  to establish a school of biology in California.


In 1928 Morgan joined the faculty of the  California Institute of Technology  where he remained until his retirement 14 years later in 1942.


Morgan moved to California to head the Division of Biology at the  California Institute of Technology  in 1928. In establishing the biology division, Morgan wanted to distinguish his program from those offered by Johns Hopkins and Columbia, with research focused on genetics and evolution; experimental embryology; physiology; biophysics, and biochemistry. He was also instrumental in the establishment of the  Marine Laboratory   at  Corona del Mar . He wanted to attract the best people to the Division at Caltech, so he took Bridges, Sturtevant,  Jack Shultz  and  Albert Tyler  from Columbia and took on  Theodosius Dobzhansky  as an international research fellow. More scientists came to work in the Division including  George Beadle ,  Boris Ephrussi ,  Edward L. Tatum ,  Linus Pauling ,  Frits Went ,  Edward B. Lewis , and Sidney W. Byance with his reputation, Morgan held numerous prestigious positions in American science organizations. From 1927 to 1931 Morgan served as the President of the National Academy of Sciences; in 1930 he was the President of the  American Association for the Advancement of Science ; and in 1932 he chaired the Sixth  International Congress of Genetics  in  Ithaca, New York . In 1933 Morgan was awarded the  Nobel Prize in Physiology or Medicine ; he had been nominated in 1919 and 1930 for the same work. As an acknowledgment of the group nature of his discovery, he gave his prize money to Bridges, Sturtevant, and his own children. Morgan declined to attend the awards ceremony in 1933, instead attending in 1934. The 1933 rediscovery of the giant  polytene chromosomes  in the salivary gland of  Drosophila  may have influenced his choice. Until that point, the lab's results had been inferred from phenotypic results, the visible polytene chromosome enabled them to confirm their results on a physical basis. Morgan's Nobel acceptance speech entitled "The Contribution of Genetics to Physiology and Medicine" downplayed the contribution genetics could make to medicine beyond  genetic counseling . In 1939 he was awarded the  Copley Medal  by the Royal Society. [ citation needed ]


He received two extensions of his contract at Caltech, but eventually retired in 1942, becoming a professor and chairman emeritus. George Beadle returned to Caltech to replace Morgan as chairman of the department in 1946. Although he had retired, Morgan kept offices across the road from the Division and continued laboratory work. In his retirement, he returned to the questions of sexual differentiation, regeneration, and embryology.


Morgan had throughout his life suffered from a chronic  duodenal ulcer . In 1945, at age 79, he experienced a severe heart attack and died from a ruptured artery.


Morgan was interested in evolution throughout his life. He wrote his thesis on the phylogeny of sea spiders ( pycnogonids ) and wrote four books about evolution. In  Evolution and Adaptation  (1903), he argued the anti-Darwinist position that selection could never produce wholly new species by acting on slight individual differences. [ 28 ]  He rejected Darwin's theory of sexual selection [ 29 ]  and the Neo-Lamarckian theory of the inheritance of acquired characters. [ 30 ]  Morgan was not the only scientist attacking natural selection. The period 1875–1925 has been called ' The eclipse of Darwinism '. [ 31 ]  After discovering many small stable heritable mutations in  Drosophila , Morgan gradually changed his mind. The relevance of mutations for evolution is that only characters that are inherited can have an effect on evolution. Since Morgan solved the problem of heredity (1915), he was in a unique position to examine critically Darwin's theory of natural selection.


In  A Critique of the Theory of Evolution  (1916), Morgan discussed questions such as: "Does selection play any role in evolution? How can selection produce anything new? Is selection no more than the elimination of the unfit? Is selection a creative force?" After eliminating some misunderstandings and explaining in detail the new science of Mendelian heredity and its chromosomal basis, Morgan concludes, "the evidence shows clearly that the characters of wild animals and plants, as well as those of domesticated races, are inherited both in the wild and in domesticated forms according to the Mendel's Law". "Evolution has taken place by the incorporation into the race of those mutations that are beneficial to the life and reproduction of the organism". [ 32 ]  Injurious mutations have practically no chance of becoming established. [ 33 ]  Far from rejecting evolution, as the title of his 1916 book may suggest, Morgan, laid the foundation of the science of genetics. He also laid the theoretical foundation for the mechanism of evolution: natural selection. Heredity was a central plank of  Darwin 's theory of natural selection, but Darwin could not provide a working theory of heredity.  Darwinism  could not progress without a correct theory of genetics. By creating that foundation, Morgan contributed to the  neo-Darwinian  synthesis, despite his criticism of Darwin at the beginning of his career. Much work on the Evolutionary Synthesis remained to be done.


Morgan left an important legacy in genetics. Some of Morgan's students from Columbia and Caltech went on to win their own Nobel Prizes, including  George Wells Beadle  and  Hermann Joseph Muller . Nobel prize winner  Eric Kandel  has written of Morgan, "Much as Darwin's insights into the evolution of animal species first gave coherence to nineteenth-century biology as a descriptive science, Morgan's findings about genes and their location on chromosomes helped transform biology into an experimental science." [ 34 ]


On June 4, 1904, Morgan married  Lillian Vaughan Sampson  (1870–1952), who had entered graduate school in biology at Bryn Mawr the same year Morgan joined the faculty; she put aside her scientific work for 16 years of their marriage when they had four children. Later she contributed significantly to Morgan's  Drosophila  work. One of their four children (one boy and three girls) was  Isabel Morgan  (1911–1996) (Marr. Mountain), who became a  virologist  at Johns Hopkins, specializing in  polio  research. Morgan was an atheist. [ 38 ] [ 39 ] [ 40 ] [ 41 ]


Hermann Joseph Muller  (December 21, 1890 – April 5, 1967) was an American  geneticist  who was awarded the 1946  Nobel Prize in Physiology or Medicine , "for the discovery that mutations can be induced by X-rays". [ 2 ]  Muller warned of long-term dangers of  radioactive fallout  from  nuclear war  and  nuclear testing , which resulted in greater public scrutiny of these practices.