Wednesday, September 9, 2015

Triple helix and the Nobel that India never won

There is a long list of Indians with significant contributions to Science but could never win a Nobel Prize. On the sixtieth anniversary of Triple helix, an analysis of the work of Biophysicist Dr. G N Ramachandran may throw some light on certain setbacks of India even when blessed with richest human resources on earth.

Gopalasamudram Narayana Iyer Ramachandran, popularly known among contemporaries as GNR, breathed science. Pauling’s α-helix, Watson and Crick’s Double helix and Ramachandran’s Triple helix are regarded as the most outstanding contributions in Structural Biology. On noticing the brilliant and illustrious young GNR, the pioneer of optics Sir C V Raman handpicked and mentored him at Indian Institute of Science. With a strong foundation in complex mathematical theorems, GNR worked on X-ray topography in Raman Lab which set the basics of crystallography. He befriended Linus Pauling at Cambridge during his postdoctoral days, who brought his attention towards the structure of collagen, the most abundant protein in animals. When A L Mudaliar, the visionary Vice Chancellor of University of Madras decided to start an experimental Physics division in Madras, Sir C V Raman himself recommended GNR to head the team. At the young age of 29, GNR joined as a Professor at the university and started his work on deciphering the structure of collagen. In 1954, GNR and his postdoctoral research fellow Gopinath Kartha published the first proposed structure of collagen elucidated from X-ray diffraction patterns and physicochemical data. They proposed three parallel left-handed polypeptide chains packed in a hexagonal array. Each helix had 32 symmetry and hence three residues per turn of the helix with every third residue being a centrally-facing glycine. They reworked on the structure using fiber diffraction patterns and published a more accurate structure in the August issue of Nature in 1955.  They proposed 3.3 residues per turn with each of the three parallel left-handed helices coiled right handedly around a central axis. This structure later became popular as the coiled coil structure of “Madras Helix”.

In the November issue of Nature the same year, Francis H Crick and Alexander Rich came up with a harsh criticism of the structure citing steric constraints. “We believe this idea to be basically correct but the actual structure suggested by them to be wrong”. The structure proposed by GNR had two interchain hydrogen bonds. Crick and Rich pointed out that the hydrogen bond angles were outside acceptable limits and the structure was too compact to accommodate large constituent amino acids. The Cα – Cα contact originally proposed by GNR was 3.3A where as the acceptable limit was 3.6A. They proposed only one hydrogen bond for the structure to be stereochemically stable. The criticism was healthily received by GNR. He came up with the blockbuster Ramachandran plot in 1963 to visualize the backbone dihedral angles of amino acids in protein structure to predict its stability and hence feasibility. He also revised the collagen structure to propose the currently accepted 1.5 hydrogen bonds-structure from the weak van der Waal’s forces of water in 1968. Was it just half of a hydrogen bond or the 0.3A distance that made GNR lose international acclaim and the Nobel itself?

The answer is of course no. It was not a secret that after deciphering the structure of DNA, Crick and his team were working on collagen structure to which GNR raised a huge competition. Nature did not accept GNR’s complete paper on collagen structure but only published a short letter. GNR’s colleague Professor Balaram of Indian Institute of Science says that even that letter was kept on hold for more than six months without publishing even though the content was immensely pertinent. It cannot be ignored that at the same time Crick’s criticism was published in a month. The controversies only strengthened GNR and brought out the golden age of protein structures. The minimum nonbonded distance between atoms and the feasible molecular structures became crisper in limits and definition and of course paved way to the genesis of Ramachandran Plot. But his contemporaries including Linus Pauling believe that the master missed the prize because he was not as aggressive in life as he was in science. Moreover, before the internet era, geographical location was a huge setback for Indian scientists. GNR did not even enjoy his moment of victory as he received the journal with his paper in print only months after Crick’s criticism came since it took months for regular mails from west to reach India.

Gone are those days. Today Indian scientists enjoy all the advantages as of any other developed nation. But still India has not won a Nobel Prize in science for the past 85 years. Nobel Laureate Venkataraman Ramakrishnan is of the opinion that India doesn’t need a Nobel Prize to become a scientific power, but even if India wins one, it wouldn’t suddenly mean that Indian science is okay. The extent of administrative hurdles in Indian scientific institutions is significant. As the Indian scientific journalist K S Jayaraman pointed out in his 1997 Nature paper, Indians hesitate to take risks. Most of Indian scientists strive for a secured job and stable income. They build their own comfort zones and stay satisfied, enjoying the comforts of the journey and forgetting the destination.  An alumnus of IIT Chennai says that lack of co-ordination and teamwork is a big handicap in India from our prestigious research enterprises to teaching institutes. As Nobel Laureate Venkataraman Ramakrishnan says, “There’s no magical formula for a Nobel Prize”. We have the richest biodiversity and human resources. We do not lack intelligence or opportunities. All we need now is the right attitude. 

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