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1900 - 1953 - Converging on DNA

While two World Wars killed millions and pushed medicine to new limits, various fields of science began to converge to explore the miracle and mechanism of reproduction: the nature and structure of DNA.


1900

The science of genetics was finally born when Mendel's work was rediscovered by three scientists - Hugo DeVries, Erich Von Tschermak, and Carl Correns - each one independently researching scientific literature for precedents to their own "original" work.


1900

William Sutton observed homologous pairs of chromosomes in grasshopper cells.

Major outbreaks of disease in overcrowded industrial cities led to the introduction of large-scale sewage purification systems based on microbial activity.

It was first shown that key industrial chemicals (glycerol, acetone, and butanol) could be generated using bacteria.


1901

Beijerinck identified free-living aerobic nitrogen fixers.

E. Wildiers discovered "a new substance indispensable for the development of yeast." Such growth factors eventually became known as vitamins.


1902

Walter Stanborough Sutton stated that chromosomes are paired and may be the carriers of heredity. He suggested that Mendel's "factors" are located on chromosomes. After observing chromosomal movements during meiosis, Sutton developed the chromosomal theory of heredity. Sutton noticed that chromosomes occur as pairs, and that gametes (egg and sperm cells) receive only one chromosome from each pair when they form during meiosis. This corroborated Mendel's theory that the genetic "factors" were segregated. Sutton gave Mendel's "factors" the name we use today: "genes."

Archibald Garrod made the connection between Mendelian heredity and the biochemical pathways of reproduction in the individual organism. He went on to inspire a distinguished line of research physicians whose work in the ensuing ninety years became indispensable to the growth of human genetics.


1903

Walter Sutton and Theodor Boveri, working independently, proposed that each egg or sperm cell contains only one of each chromosome pair. This connected two phemonema: the patterns by which pairs of Mendel's factors assort themselves and the precisely similar sorting and recombination of the chromosomes in the formation of the germ cells and the fertilization of the egg.


1904

William Bateson demonstrated that some characteristics are not independently inherited. This introduced the concept now called 'gene linkage' and led to the need for 'genetic maps' that describe the order of the linked genes.


1905

Edmund Wilson and Nellie Stevens proposed the idea that separate X and Y chromosomes determine sex. They showed that a single Y chromosome determines maleness, and two copies of the X chromosome determine femaleness.


1905-1908

William Bateson and Reginald Crudell Punnett, along with others, demonstrated that some genes modify the action of other genes.


1906

Paul Erlich investigated atoxyl compounds and discovered the beneficial properties of Salvarsan - the first chemotherapeutic agent.


1907

Thomas Hunt Morgan began his work with fruit flies that will prove that chromosomes have a definite function in heredity, establish mutation theory, and lead to a fundamental understanding of the mechanisms of heredity.


1908

Calmette and Guerin developed a vaccine against TB. This vaccine, called BCG, was not used until 1921.

A.E. Garrod described "inborn errors of metabolism" based on his analysis of family medical histories. This was a first recognition of a role for genetics in biochemistry, but the idea remained unappreciated until the work of Beadle and Tatum in the 1940's.


1909

Wilhelm Johannsen coined the terms 'gene' to describe the carrier of heredity; 'genotype' to describe the genetic constitution of an organism; and 'phenotype' to describe the actual organism, which results from a combination of the genotype and the various environmental factors.

Phoebus Levene discovered that the sugar ribose is found in some nucleic acids, those we now call RNA.

William Bateson first applied Mendel's laws to animals.


1910

Thomas Hunt Morgan proved that genes are carried on chromosomes, establishing the basis of modern genetics. With his co-workers, he pinpointed the location of various fruit fly genes on chromosomes, establishing the use of Drosophila fruit flies to study heredity. Morgan's group also demonstrated the existence of sex-linked genes, and over the next ten years expanded the idea to other trait linkages, using "crossing-over" to help determine the location of genes.


1911

Thomas Hunt Morgan explained the separation of certain inherited characteristics that are usually linked as caused by the breaking of chromosomes sometimes during the process of cell division. Morgan began to map the positions of genes on chromosomes of the fruit fly.


1912

Lawrence Bragg discovered that X-rays can be used to study the molecular structure of simple crystalline substances. This discovery led to the development of X-ray crystallography, which made it possible to further explore the three-dimensional structures of nucleic acids and proteins.


1913

Alfred H. Sturtevant, a student of Morgan's, constructed the first gene map by analyzing mating results for fruit flies with six different mutant factors each known to be recessive and X-linked. He traced each mutation and its normal alternate in relation to each of the other mutants, and thus calculated the exact percentage of crossing-over between the genes.


1915

Frederick Twort discovered a "disease" of bacteria called "glassy transformation" and showed the disease agent is transmissible, filterable, invisible with a light microscope and does not grow in the absence of the living host bacterium. Twort proposed three possible explanations, including a filterable virus and an enzyme.


1916

George Harrison Shull, a pioneering corn breeder and Princeton genetics professor, published the inaugural issue of the scientific journal Genetics.


1917

Plough demonstrated the rearrangement of chromosomes known as 'crossing over'.

F. D'Herelle described "an invisible microbe" that antagonizes the bacillus that causes dysentery and coined the term "bacteriophage" for the antagonist. Phage caused plaques on bacterial lawns, analogous to colonies on agar plates. Later plaques will prove useful in preparing pure cultures and characterizing different strains of the bacteriophages or bacterial viruses.


1917-1918

Sewall Wright analyzed the inheritance of coat colors in guinea pigs, mice, rats, rabbits, horses, and other mammals. Wright showed that production of the pigment determining coat color in mammals requires biochemical steps, taking place in fixed temporal order. He suggested that each step is mediated by a different, specific enzyme.


1918

Herbert M. Evans found (incorrectly) that human cells contain 48 chromosomes.

The German army used acetone produced by plants to make bombs. Yeast was grown in large quantities to produce glycerol, and activated sludge was produced in large quantities for sewage treatment processing.

A world-wide epidemic of influenza killed 20 million people, more than killed in The World War.


1920-1930

Plant hybridization became widespread in the United States, greatly improving the productivity of agriculture.


1921

Hermann J. Muller, another of Thomas Hunt Morgan's students, wrote a paper about the nature of the gene that proved to be astonishingly prescient. He conceived of the gene as a particle that, despite its ultramicroscopic size, exhibits a complex structure of different parts.


1924

Politicians encouraged by the eugenics movement passed the U.S. Immigration Act of 1924, limiting the influx of poorly educated immigrants from Southern and Eastern Europe on the grounds of suspected genetic inferiority.


1925

Nikolai Vavilov led Russian plant hunters on the first attempt to "cover the globe" in search of wild plants and primitive cultivators. For his scientific curiosity, he was later thrown in prison, dying there of malnutrition in 1943.

Congress voted to cut the Seed Distribution Program, which had consumed more than 10% of the USDA's total budget in 1921. The decades-old flood of free seed to the agricultural community suddenly stopped.


1926

Thomas Hunt Morgan published 'The theory of the gene', the culmination of work on the physical basis for Mendelian genetics based on breeding studies and optical microscopy.

Hermann Muller discovered that X-rays induce genetic mutations in fruit flies 1,500 times more quickly than under normal circumstances. This discovery provided researchers with a way to induce mutations, an important tool for discovering what genes do on their own.

Henry Agard Wallace, US Secretary of Agriculture during the Franklin Roosevelt's first two terms, and Vice-president during his third, founded the Hi-Bred Company - a hybrid corn seed producer and marketer known today as Pioneer Hi-Bred International, Inc.


1928

Fredrick Griffiths noticed that a rough type of bacterium changed to a smooth type when an unknown "transforming principle" from the smooth type was present. Sixteen years later, Oswald Avery identified that "transforming principle" as DNA.

Lewis Stadler showed that ultraviolet radiation can also cause mutations.

Alexander Fleming noticed that all the bacteria in a radius surrounding a bit of mold in a petrie dish had died. The age of penicillin thus began, although it would be almost 15 years before it was made available to the community for medicinal use.


1928-35

Linus Pauling elucidated the physical laws governing how atoms are arranged within molecules. He also described sickle cell anemia, defining it a molecular disease.


1929

Phoebus Levene discovered a previously unknown sugar, deoxyribose, in nucleic acids that do not contain ribose; those nucleic acids are now known as deoxyribonucleic acids, or DNA.


1931

Thirty states in the U.S. had adopted compulsory sterilization laws.


1933

Germany established eugenics laws, sterilizing 56,244 individuals as "hereditary defectives."


1933

T.S. Painter announced in a brief article in Science that he had charted perceptible differences among chromosomes under the microscope - differences detailed enough to correlate crossing-over of genes as shown in the statistical tables with physical interchanges in the material of the chromosomes.


1934

Desmond Bernal showed that giant molecules, such as proteins, can be studied using X-ray crystallography.

Martin Schlesinger purified bacteriophage and found about equal amounts of protein and DNA. Which of these was the informational molecule remained unclear.


1935

Wendell Meredith Stanley crystallized tobacco mosaic virus, the first such purification of a virus. He believed, incorrectly, that protein was the active agent of the virus

George Beadle and Boris Ephrussi transplanted tissue between larvae of fruit flies bred with various mutations of eye color and observed the mature flies development.

Andrei Nikolaevitch Belozersky isolated DNA in the pure state for the first time.


1936

Wendell M. Stanley isolated nucleic acids from the tobacco mosaic virus, which later (1955) will be found to cause the viral activity.


1937

Frederick Charles Bawden discovered that tobacco mosaic virus contains RNA.


1938

Howard Florey and Ernst Chain of Oxford University in England isolated the antimicrobial agent penicillin.


1938

Proteins and DNA were studied in various labs with X-ray crystallography.

The term "molecular biology" was coined.


1939

Gauteret cultivated carrot callus cultures.

Andrei Nikolaevitch Belozersky started his experimental work showing that both DNA and RNA are always present in bacteria.


1940-1945

Large-scale production of penicillin was achieved.


1940-1950

Countries in the West made the transition from animal power to mechanical power on farms.


1941

George Beadle and Edward Tatum experimented with Neurospora, a mold that grows on bread in the tropics, developing the "one-gene-one-enzyme" hypothesis: each gene is translated into an enzyme to perform tasks within an organism. They examined X-ray-damaged mold specimens that would not grow on the sample medium, but would grow if they added a certain vitamin. They hypothesized that the X-rays had damaged the genes that synthesized the proteins.


1943

The Rockefeller Foundation, collaborating with the Mexican government, initiated the Mexican Agricultural Program. This was the first use of plant breeding as foreign aid.


1943-1953

Cortisone was first manufactured in large amounts.


1943

Salvador Luria and Max Delbruck performed "the fluctation test," the first quantitative study of mutation in bacteria. This was the beginning of bacterial genetics as a distinct discipline.


1944

Oswald Theodore Avery, Colin MacLeod and Maclyn McCarty determined that DNA is the hereditary material involved in transformation in pneumococcus bacteria. At first this theory gained little attention because scientists believed that DNA was too simple a molecule to contain all of the genetic information for an organism. Most scientists believed that only proteins were complex enough to express all of the genetic combinations.


1944

Waksman isolated streptomycin, an effective antibiotic for TB.


1944

Frederick Sanger used a new method called chromatography to determine the amino acid sequences of the bovine insulin molecule.


1944

Barbara McClintock, working in Cold Spring Harbour, New York, discovers that genes can be transposed from one position to another on a chromosome. McClintock was awarded the Nobel Prize for Physiology or Medicine in 1983 for her discovery.


1945

Max Delbruck and Salvador Luria developed a simple model system using phage for studying how genetic information is transferred to host bacterial cells. They organized a course to study a type of bacterial virus the T phages that consists of a protein coat containing DNA. Delbruck and Luria's course attracted many scientists to Cold Spring Harbor, which soon became a center for new ideas about explaining heredity at the cellular and molecular levels.


1945

The U.N. Food and Agriculture Organization (FAO) was formed in Quebec, Canada.


1945 - 1950

Isolated animal cell cultures were grown in laboratories.


1946

D.C. Salmon, a U.S. military adviser stationed in Japan, sent home Norin 10 - the source of the dwarfing gene that later helped produce the Green Revolution wheat varieties.


1946

Edward Tatum and Joshua Lederberg showed that bacteria sometimes exchange genetic material directly, in a process they called conjugation.

Max Delbruck and Alfred Day Hershey independently discovered that the genetic material from different viruses can be combined to form a new type of virus. This process was another example of genetic recombination.


1947

Barbara McClintock first reported on "transposable elements" - known today as "jumping genes." The scientific community failed to appreciate the significance of her discovery at the time.


1950

Erwin Chargaff found that in DNA the amounts of adenine and thymine are about the same, as are the amounts of guanine and cytosine. These relationships are later known as "Chargaff's Rules" and serve as a key principle for Watson and Crick in assessing various models for the structure of DNA.

Earle and Enders studied monkey, mouse, and chick cells in cell cultures.

Artificial insemination of livestock using frozen semen, a long-time dream of farmers, was successfully accomplished.


1951

Esther M. Lederberg discovered lambda phage, a virus of E. coli.


1952

Joshua Lederberg and Norton Zinder showed that bacteria sometimes exchange genes by an indirect method, which they termed "transduction," in which a virus mediates the exchange by snaring bits of DNA from one bacterial cell and transporting the bacterial genes into the next cell it infects.

Alfred Hershey and Martha Chase performed the infamous "blender experiments" using phages. They postulated that if one could separately "tag" both the DNA and protein in the phages, then one could follow the DNA and proteins through the phages' replication process. Using virus particles with DNA tagged or 'labeled' with 32P phosphorous and protein labeled with 35S, Hershey and Chase showed that only the DNA of the virus enters the cell in significant amounts. This result supported a role for DNA has the genetic material, and refuted a role for protein.

J. Lederberg introduces the term plasmid to describe the bacterial structures he has discovered that contain extrachromosomal genetic material.

William Hayes discovered conjugation, the process whereby one bacterial cell pipes a copy of some of its genes into a second bacterial cell.

Electron microscopy showed the insides of cells to be filled with minute but well-formed anatomical structures, including vast numbers of a complex molecular organ now termed the ribosome.

Jean Brachet suggested that RNA, a nucleic acid, plays a part in the synthesis of proteins.


1953

James Watson and Francis Crick proposed the double-stranded, helical, complementary, anti-parallel model for DNA.

William Hayes discovered that plasmids can be used to transfer introduced genetic markers from one bacterium to another.

L. Cavalli, J. Lederberg, and E. Lederberg discovered the F factor in E. coli.


Compiled from various sources, including:

Brock, Thomas D. 1961. Milestones in Microbiology. Science Tech Publishers. Madison, Wisconsin. Pp. 273.

Brock, Thomas D. 1990. The Emergence of Bacterial Genetics. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, New York. Pp. 346.

Bunch, Bryan and Hellemans, Alexander. 1993. The Timetables of Technology. Simon & Schuster. New York, New York. Pp. 490.

Hellemans, Alexander, and Bunch, Bryan. 1988. The Timetables of Science. Simon & Schuster. New York, New York. Pp. 660.


Go to next timeline: 1953 - 1976: Expanding the Boundaries of DNA Research

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