When patience, passion and perseverance pay

Biochemistry was at its nascent stage around the 1930s and nobody knew whether proteins had a structure or were they colloids. Dr Frederick Sanger charted the less travelled path and laid new rules for arriving at the full structure of proteins.
He rated himself as a very ordinary human being and believed that one need not be brilliant to discover but must have patience, passion and perseverance. Dr. Sanger moved away from conventional natural product chemistry and did most of his work with paper chromatography to separate, purify, and characterise the degradation products.

As amino acids and fragments of proteins were colourless, he developed a chemical reagent FDNB (Known as Sanger Reagent) which on reacting would selectively label one end and gave a yellow spot on paper and the label remained even after degrading the labelled peptide with acid. He worked on insulin for eight years before publishing the results with just two students. For the first time he established that proteins are linked together in a specific way with an amino group at one end and carboxyl group at another. To date there is no exception to this linkage. This opened up the way for molecular medicine and could explain the molecular basis of many diseases; most well-known among them being sickle cell anaemia and thalassaemia, to name a few. Dr.Sanger won the Nobel Prize for developing methods to sequence proteins in the year 1958.

He now decided to focus on RNA sequencing. Though he was a Nobel laureate, nobody seemed to want to join his group! He was not willing to go back to protein sequencing even though there were many who wanted to join him for protein work! Ultimately he got a technician, Bob Barrel, a school pass out, who agreed to join him. Such was his ability to pick up talents. Later George Brownlee joined and thus began the journey of RNA and DNA sequencing in the 1960s.Interestingly, he had bright ideas even while sequencing proteins but many had to be forcefully abandoned as they were not in keeping with the safety norms. But he used the same ideas for DNA sequencing using DNA polymerase and its property brilliantly and in arrived at the full sequence of Phi X 174, a bacteriophage, which was the first DNA-based genome to be sequenced.

"Scientific research is one of the most exciting and rewarding of occupations."
“Scientific research is one of the most exciting and rewarding of occupations.”

The method came to be called the Plus Minus method. He once again shared the Nobel Prize for this work in the year 1980.

He opened up a new window of opportunity and improved his method by introducing the so-called dideoxy method. This helped in developing an automated DNA sequencer and enabled the whole human genome project to be completed .Ability to sequence a whole human genome in a day will be a routine diagnostic tool and personalised medicine will soon become a reality.

As a researcher I was very fascinated by the work of Dr. Sanger and applied for research under him in 1978. Later I met him when I had invited him to deliver a talk in 1980 at Imperial College, London, where I was the Biochemical Society president. The announcement of the Nobel Prize in 1980 made me worry but he honoured his commitment and rehearsed the Nobel Lecture on December 4, 1980. I was elated and we made a hand sketch of him and posted it all over the campus. He was so touched by the poster that he took the original one and displayed it in his house.

On his arrival there was a huge crowd to talk to him and I knew I may not be able to talk to him. Then came the next surprise when he called me and explained why he was unable to accommodate me. Even more surprising to me was the keen interest he continued to take in my work on Ubiquitin. We chatted for how long I cannot remember but time stood still and I was mesmerised. He made me feel so important that the memory of this meeting remained etched in my memory forever. I was truly surprised when he said that he will retire at the age of 65 and would pursue rose gardening.On the day of the lecture, the auditorium at Imperial College was jam packed and I had the pleasure of introducing my hero to the audience. I requested Prof. Hartley, his long term associate to say a few words. Joking Prof Hartley said, if Dr. Sanger went to heaven, God would ask him why he did not complete sequencing complex carbohydrates! For that was the only area he left untouched.

Dr. Sanger, you live through those who came in contact with you and will continue to affect humanity through your contributions to personalized medicine.

This post was earlier published in the Hindu on December 12th, 2013. Dr. Fredrick Sanger, twice Nobel Prize winner, died on November 19. The author, Dr. K Kannan, is a Professor, University School of Biotechnology, GGS Indraprastha University, New Delhi and a former Vice Chancellor, Nagaland University ( kkannan@ipu.ac.in )


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