A journey from a doctor to a researcher:
It was a time of 1940’s, it was a second world war going on in the world. No place was safer. United States was also facing the heat of the wartimes. However every American had devoted to serve the nation and one of them was Arthur Kornberg. A man who was not a trained scientists but found a crucial enzyme in bacteria.
Besides being one of remarkable scientists of his time Arthur Kornberg studied his academics in medical sciences and received his MD from University of Rochester in the year 1941. To use his expertise for the betterment of the united states, he served as doctor on a ship. But due to his uncanny behaviour, Arthur would be frequently involved in arguments with fellow shipmates including captain of the ship.
Arthur was never inclined towards pursuing a career in the research field, as luck would have it, he was having a disorder named Gilbert syndrome with mild but similar symptoms as jaundice. While in his medical academics Arthur studied the Gilbert syndrome and his work was published in 1942 and he soon became popular in the local scientific community.
Clue in Vitamins:
In the period of 1942, a yellow fever vaccine was being administered to the people which suddenly led to an outbreak of Jaundice. This had raised a serious concern among the senior military officials and also director of National Institute of Health (NIH). Soon they offered a research position to Arthur in NIH. This was his first exposure to studies on the role of vitamins in blood disorder and in enzyme based catalysis. His research work was primarily focused upon vitamin deficiency caused by the use of sulfa drugs. With time, he gained experience in enzyme catalysed reactions which require vitamins as coenzyme.
During the same time ‘how living organisms reproduce’ was one of the greatest mystery. Avery, MacLeod, and McCarty along with other eminent scientists showed that DNA is THE chemical which transfers the genetic information over the generations and no any other molecule in 1944 but no one knew if the DNA is made by any enzyme. It was also known from the contribution of Erwin Chargaff that amount of adenine always equalled to that of thymine and amount of guanine always equalled to the amount of cytosine in any DNA sample. After knowing the DNA is a genetic material, ‘how DNA is made’ was still a mystery. No one had a clue how the DNA is made.
Arthur thought as enzymes can incorporate the vitamins as important functional component, then there must be some enzyme which can string the nucleotides together and make up the nucleic acid strands. And that’s how Arthur realised that he needs to learn more about isolating and characterising the enzyme. To equip himself with necessary skills Arthur moved to New York University and started working with Severo Ochoa.
Finding building blocks of DNA:
In search of the first DNA building enzyme he had to know more about the synthesis of the building blocks and so he started working on synthesis of nucleotides. Someone already working with RNA synthesis published the findings which forced Kornberg to shift his focus only on DNA synthesis. Kornberg with his brilliant team found out the enzymes involved in the synthesis of Uridine monophosphate – a complete uracil nucleotide and soon after that they were able to synthesise adenine, cytosine and guanine. Someone else had discovered the enzyme involved in the thymine biosynthesis.
Discovering an exceptional enzyme DNA polymerase:
Now, fully equipped with all the nucleotides, Arthur diverted his all attention to the DNA synthesis. He used radio-labelled nucleotides to detect the incorporation of nucleotides stringed in a chain. He added ATP and crude enzymes extracted from E. coli bacteria with all the nucleotides but initially he failed to obtain an ample quantity of the synthesised DNA strand.
Finally he was able to obtain the desired result and submitted his research findings to the Journal of Biological Chemistry. Unfortunately, these findings were underestimated by the referees and other people from the scientific community as it was believed that DNA synthesis was impossible to be conducted in the lab. Some doubted the functional capability of this artificially synthesised DNA fragments.
The situation was disgusting for Arthur but as luck would have it, those referees were retired paving the way for his publication. For this great work he shared a Nobel prize with Severo Ochoa in 1959 in Physiology or Medicine. Now, it is known how Arthur’s contribution revolutionised the molecular biology work for which all scientific community owes a sincere gratitude to him.
Read more about how enzymes function here.
References:
- Arthur Kornberg- Biographical, The Nobel prize in physiology or medicine 1959. (https://www.nobelprize.org/prizes/medicine/1959/kornberg/biographical/)
- The synthesis of DNA, 1953-1959, The Arthur Kornberg papers, Profiles in science, National library of medicine. (https://profiles.nlm.nih.gov/spotlight/wh/feature/synthesis)
- Biographical overview. The Arthur Kornberg papers, Profiles in science, National library of medicine. (https://profiles.nlm.nih.gov/spotlight/wh/feature/biographical-overview)
