Nobel Prize: the problem with the rule of three

Every year, the first ten days of October are a period of excitement and expectation in scientific circles. This year was no different, except it also warmed the hearts of many Indians since the Nobel Prize in Chemistry was shared by Venkatraman Ramakrishnan of Cambridge, UK. The news came as a very pleasant surprise since many ‘armchair forecasters’ did not have his name on their prediction list.

But the Nobel Committee chose the trio Ada Yonath, Thomas Steitz and Ramakrishnan in the true spirit of the Prize Founder Alfred Nobel who had wanted to award the “prizes to those who, during the preceding year, shall have conferred the greatest benefit on mankind.”

The committee for physics gave one half of the prize to Charles Kao for having developed the fibre-optic communication networks that carry voice, video and high-speed Internet data around the world, and the other half to Willard Boyle and George Smith for inventing the charged-couple device which led to the digital electronic eye of the camera, that revolutionized the way we handle photographs and medical images.

Likewise, the committee for physiology/medicine gave the prize to Elizabeth Blackburn, Carol Greider and Jack Szostak for having solved a major problem in biology — how the chromosomes can be copied exactly and completely during cell divisions and how they are protected from degradation. Their work makes us understand the biology of ageing, and also offers clues on cancer and the development of new therapies.

Protein factory

Turning to the chemistry prize, the Yonath- Steitz- Ramakrishnan trio has helped us understand how the cell’s protein factory, called the ribosome, is put together and how one can devise new antibiotics by targeting the ribosomes of pathogenic microbes. The chemistry aspect comes in here due to the method used, namely that of X-ray crystallography.

The idea that this time-tested method can be used to study a huge biological assembly was itself a leap of faith. This was the great gamble that Ada Yonath took in the late 1970s.

Dr. Jeremy Berg of NIGHS, NIH, U.S., is quoted as saying: “I remember at the time being completely stunned that she was somewhere between brave enough and crazy enough because it was way, way, way beyond the technology available at that point.”

But she did, and succeeded in crystallizing the major, large portion of the ribosome called the large subunit — a tour de force in itself. Its crystals diffracted X-rays well, but in order to locate the atoms in its RNA molecules in proper 3-dimensional space, one had to solve what the practitioners call as the “phase problem”. This is where Thomas Steitz’s expertise came in. He solved this problem and published the detailed atomic anatomy of the large subunit.

Following this, Yonath and Ramakrishnan did the same to solve the 3-dimensional structure of the small subunit of the ribosome. Thus the structure of the protein factory was solved.

There remained another major issue, and that is how the ribosome translates the message of the gene faultlessly, with seldom any error in the corresponding protein. Factories tend to make mistakes occasionally, but such mistakes in the ribosome mean mutations in the proteins made, and bad news for the health of the organism. It is here that Ramakrishnan’s contribution is valuable.

Molecular ruler

He identified what he calls as the ‘molecular ruler’ in the ribosomal assembly. He located and described a part of the smaller subunit that measures the distance between the ‘lock’ in the message and the ‘key’ in the transfer molecule that brings in the right amino acid to make the protein. If the fit is not right, translation is halted until the correct fit occurs. The ruler thus ensures error-free protein.

I read with admiration the answers that Ramakrishnan gave to the press, notably The Hindu. He comes out as a modest person who says that it is important to give youngsters the freedom to follow their ideas and pursue their interests.

He says that he values the National Science Talent Scholarship he enjoyed while at college, and the teachers he had in physics and mathematics.

He said something even more important: “It is a mistake to judge science by Nobel Prizes.” I was struck by the magnanimity and the truth in it.

Fourth factor

There is another aspect to the Nobel, which I call as the “fourth person phenomenon.” Even as Yonath, Steitz and Ramakrishnan were rewarded, Jeremy Berg says: “How to get four deserving candidates for the Nobel down to three? One key person, Harry Noller of UC Santa Cruz, was not chosen for the award.” And Peter Moore of Yale says: “If the Nobel Committee did not have the rule of three, Harry Noller would have most certainly been included today”.

Last year too

Such a thing happened last year too, again in chemistry. Dr. P. Balaram wrote about it in Current Science (Vol.95, issue 8): The prize was awarded to Osamu Shimamura, Martin Chalfie and Roger Tsien for their work on the green fluorescent protein, GFP.

But the man who cloned GFP in 1992, and readily parted with it to Chalfie in 1996, Dr. Douglas Prasher, was not. “Prasher was generous when he said: ‘Do I feel cheated, or left out? Not at all.

I had run out of funds and these guys showed how the protein could be used, and that was the key thing”. Magnanimity there!



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