History of Genetics from 1949 to Today
I have decided to divide the last 70-80 years of genetics into different eras. Each period started with a set of burning questions, which were resolved by the end of the era. However, those answers created another set of burning questions to be resolved by the newcomers to the field. Please tell me whether you agree my classifications, and what you expect the current era to be like.
1949-1966 - Birth of Molecular Biology
Oswald Avery’s 1944 experiment showed DNA to be the primary material carrying genetic information, whereas prior to that proteins were belived to serve the same purpose. DNA was previously considered to be the substrate. To give an analogy, DNA was thought to be the grocery bad carrying food, but Avery’s discovery showed that the grocery bag was really the food. This was a major change in thiking leading to flurry of activities.
I am using 1949 as the starting year, because that is when Chargaff made his discovery of ratio of nucleotides now known as Chargaff’s rules. it was the first spark starting a major scientific revolution. The field of “molecular biology” was born although Chargaff himself was fond of calling it “practicing biochemistry without a license”. Watson and Crick solved the DNA structure. Biomolecules like tRNA, mRNA, etc. were all discovered. Jacob and Monod came up with the lac operon model. Finally, with the discovery of genetic code, all burning questions were answered and the era of molecular biology was thought to be over.
1967-1984 - How do Genes Function?
The discoveries of 1949-1966 raised the next set of questions - (i) how do genes give rise to functionality we observe? (ii) how are they related to evolution? To systematically answer these questions, geneticists needed methods to cut and paste DNA sequences and to sequence DNA. During this time, E. coli was the primary research organism to figure out functionality of the genes.
A separate line of work started with Zuckerkandl and Pauling, who saw biomolecules as “documents of evolutionary history”. Following along this concept, in 1977, Woese and Fox made the revolutionary discovery of a distinct third domain of life. This discovery relied entirely on comparison of DNA sequencese.
1985-2002 - Era of Model Organisms
By mid-1980s, the basic biochemical mechanisms of transcription, translation, dna regulation, etc. were well understood leading to the new set of questions - how are multi-cellular body structures formed? Fortunately, biotechnology techniques matured enough to allow researchers to move on to other organisms, and especially large eukaryotic organisms. However, it was prohibitively expensive to apply these methods to every organism, and the concept of model organism was born. Arabidopsis was established as the model organism to study plants, and fruitfly was used to study animal development. Of course, the genetic study of fruit fly has a long history (reviewed here), but the access to recombination biology tools accelerated genetic research on its development. This era ended with getting the entire genomes of all well-established model organisms sequenced.
2003-2020 - Whole Genome Experiments
Genome sequencing of model organisms led to a puzzling observation. Nobody knew the functions of nearly 40% of genes in even the most well-studied model organisms. How do we find the functions of all these genes? That was the key burning question driving activities of the next era. The old method of a someone spending his entire career tracking one or two genes did not seem feasible.
Paucity of genes was the second puzzling observation. Geneticists expected hundreds of thousands of genes in the human genome, but the real number turned out to below 20,000. Therefore, it was clear that many these genes acted together to give rise to various functionalities.
Both of these questions resulted in efforts to study the actions of all genes together and preferably in as many separate cells as possible. That was the key driving force of 2002-2020. First, we got ESTs, followed by microarrays and then RNA sequencing, single-cell sequencing and so on.
Also, this period started with access to only a tiny number of expensive genomes and ended with thousands of genomes for each model organism.
2021-2038 - ?
We are already in the sixth year of the next era. What are the burning questions keeping you awake at night? Please tell me in this twitter thread and I will add them to the post.
