History of Genetics

"It's lots of fun to blow bubbles but it's wiser to prick them yourself before someone else tries to."
Oswald Avery

 

People have known about inheritance for a long time

Over millennia it must have been appreciated that children resemble their parents and share obvious characteristics.

inherited nose

This belief also held true for animals and plants allowing the domestication of various species since over 12,000 years ago. During this time it was widely obvious that one can selectively breed for good characteristics such as wool meat and even behaviour. 

800px-egyptian_domesticated_animals


One of the first written evidences that humans appreciated genetic diseases comes from around 100 AD. The revered Rabbi, Judah haNasi, exempted the circumcision of siblings of older brothers who had died of bleeding following the procedure, i.e the first description of X-linked inherited Hemophilia.


Despite the knowledge of inherited traits, an understanding of reproduction would remain an enigma for a surprising length of time

4th century BC - Hippocrates believed that heredity material collected from throughout the body.

3rd century BC - Aristotle modified the hypothesis to explain that this material was transmitted through semen. However, he considered this to be a purified form of blood which then mixed with the mother's menstrual blood.

9th century - Al-Jahiz, an Afro-Arab writer developed the idea of the inheritance of acquired characteristics noting that "Animals engage in a struggle for existence; for resources, to avoid being eaten and to breed. Environmental factors influence organisms to develop new characteristics to ensure survival, thus transforming into new species."

until the 19th century - the idea that inherited characters were aquired in reponse to parental environment was almost unanimously believed, even though it went in the face of all the aforementioned observations.

18th century - increased appreciation of taxonomy and the diversity of plant and animal species diversity led to the development of new ideas about heredity.

early 19th century - Augustin Sageret, the French naturalist noted that crossing certain parent plants, in which one had a particular characteristic, usually led to the appearance of the characteristic in the offspring. Although preceding the research of Gregor Mendel, we must accept that this phenomenon must have been widely noted appreciated among plant breeders who obviously made no attempts to analyse the foundation of such effects.


It was two major events in the middle of the 19th century that led directly to the development of modern genetics

1859 - Charles Darwin publishes The Origin of Species, describing the theory of evolution by natural selection.  This theory required genetic inheritance to work.

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Caricature of Charles Darwin as an ape published in The Hornet, 1871.

1866 - Gregor Mendel, an Austrian Monk, publishes Experiments in Plant Hybridization, laying out the basic theory of genetics. Incredibly, it was completely ignored until 1900.

DNA is discovered

1871 - Friedrich Miescher, a Swiss Physician, isolates “nucleic acid” whilst trying to wash the puss off dirty bandages at a local hospital

1879 - Walther Flemming, a German scientist, discovers chromosomes using aniline dyes, hence the name (Gr. Chrom; coloured body).

~1900 - August Weismann, the revered German biologist, proposes that inheritance only takes place through germ cells, i.e. egg and sperm cells.

1902 - Theodor Boveri (sea urchins) and Walter Sutton (grasshoppers), studying different species, both demonstrate that the hereditary material is carried in chromosomes: firstly, all the chromosomes had to be present for proper embryonic development to take place; secondly, chromosomes occur in matched pairs of maternal and paternal chromosomes which separate during meiosis (a special type of cell division producing germ cells).

1902 - Archibald Garrod is the first to publish a case of recessive inheritance in humans.

1910 - Thomas Hunt Morgan, an American biologist, supports the chromosome theory of heredity using the fruit fly (Drosophila) further demonstrating that genes are linked in a series on chromosomes and are responsible for identifiable, hereditary traits.

Chromosomes consist of DNA wrapped around protein histones. But is it the DNA or the protein that is the carrier of inheritance?

1928 - Frederick Griffith, discovers that a harmless strain of bacteria could be made virulent after being exposed to heat-killed virulent strains. Therefore, some kind of substance (he termed a "transforming principle") from the heat-killed strain was taken up by and incorporated in the harmless strain, making them virulent.

1944 - Oswald Avery, Colin MacLeod and Maclyn McCarty were able to identified the substance of Griffith's "transforming principle" as DNA.

Structure of DNA

1919 - Phoebus Levene identifies the units of DNA which he calls "nucleotides". These consisted of a base, a pentose sugar and a phosphate group base. He further offered a first real hypothesis for the structure of DNA, though suggested the chains should be short and the bases repeated in a fixed order.

1937 - William Astbury pioneers X-ray diffraction patterns revealing that DNA has a regular structure.

1950s - Erwin Chargaff determines that there is a pattern in the amounts of the 4 bases that rules out the possibility there being direct a repeated sequence.

1950s Rosalind Franklin, using X-rays shows that DNA has a helical structure.

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Photo 51

1953 - Watson and Crick publish their model of the double helix DNA structure.

1958 - Matthew Meselson and Franklin Stahl devise the "the most perfect experiment ever" to show how DNA is replicated.


How does DNA directed the expression of proteins?

Scientists knew there was a total of four bases (guanine, cytosine, adenine, and thymine). They also knew that were 20 amino acids and there was RNA, a molecule with a similar chemical structure to that of DNA but containing the sugar ribose (DNA contains the slightly different sugar deoxyribose) and unlike DNA, most RNA molecules are single-stranded.

1954 - George Gamow suggested that the genetic code was made of three nucleotides per amino acid. He reasoned that because there are 20 amino acids and only four bases, the coding units could not be single (4 combinations) or pairs (only 16 combinations). Rather, he thought triplets (64 possible combinations) were the coding unit of the genetic code. However, he proposed that the triplets were overlapping and non-degenerate.

1954 - The RNA tie Club  is established to "solve the riddle of the RNA structure and to understand how it built proteins.


The "RNA Tie Club," Portugal Place, Cambridge, England. 1955. Left to right: Francis Crick, Alexander Rich, Leslie E. Orgel, James Watson.

Late 1950s - Seymour Benzer, an American biologist, develops an assay using virus mutations to provide the first detailed linearly structured map of a genetic region. Crick then realizes that it is possible to use these methods to delineate the nature of the genetic code, concluding that the genetic code is a triplet code and that is degenerate, i.e not overlapping.

1966 - Marshall Nirenberg (not a member of the RNA Tie club)– deciphers a first part of the DNA code showing that UUU (three uracil bases in a row) codes for a specific amino acid - phenylalanine.

1961 to 1962 - a competition develops between the labs of Nirenberg at the NIH and Severo Ochoa at New York University Medical School to crack all the triplet nucleotide combinations coding for 20 amino acids.

codon_table

2003 - the entire human genome is sequenced.