Thursday, November 17, 2011

In Memorium: H. G. Khorana (1922-2011)

I came to know of Khorana’s work from the pages of Science Reporter even before Neil Armstrong walked on the moon.

I was however not aware of how exactly he had deciphered the triplet genetic codons when I lined up in front of the Bose Institute in Calcutta on a winter afternoon in 1973. It was the Bose Memorial lecture, and Khorana was the speaker. Like most other lectures at Bose Institute, my fellow second year undergraduate student Siddhartha and I were expecting a small turn out, mostly of stuffy professors and a few graduate students. We were not prepared for the spectacle: an unruly crowd of at least 1,000 were trying to get a glimpse of this man, who was ushered from a black Ambassador into the lecture theater by a gang of burly security people. After a delay of another hour or so, it was announced that Professor Khorana had requested that the lecture be moved to a larger hall where the entire crowd could be accommodated, and so the timing of the lecture was delayed by 3 hours. The new venue would be at the Saha Institute of Nuclear Physics, a few blocks away, where there was a large enough lecture hall to accommodate the huge gathering.

There was a stampede. By the time Siddhartha and I arrived at the new venue, the crowd was almost breaking down the collapsible gate at the front entrance. Since we were both rather thin, we were able to slip through the chain-link fence behind the building and gain admission through the back door. Khorana arrived, along with a galaxy of professors. Behind him was a long blackboard, on which a professor had neatly written out the table of triplet codons. There were eulogies upon eulogies. I felt that the thin short man with a rather well defined jaw line, sporting a plain brown jacket and a dark tie, was shrinking more and more unto the table as eulogies were heaped upon him. My vivid memory is that of the top of his triangular head, because his face was mostly turned down in embarrassment.

When at last it was Khorana’s turn, the little man nearly sprang up from his chair, and charged ahead without spending so much as even one sentence of pleasantry. For an hour he blazed at the blackboard with a piece of chalk, explaining the intricacies of a mind-boggling series of ingenious experiments that had led to the deciphering of the genetic code, and an almost immediate Nobel Prize in Physiology and Medicine. He was dynamic in a manner I had never seen someone lecturing before then. Newspapers the next day ran an full page article on Khorana and his discoveries, and how he failed to obtain a job in India when he tried to return after his PhD in England and a postdoctoral stint in Switzerland.

Nearly twenty years later, I was in my first month at MIT, in an elevator at the ground floor of B56. The door was about to close when slid in Khorana, his wet hair still dripping a little. I nervously smiled at him. He smiled back, “From India?” and immediately began to ask me a staccato series of questions about what am I doing in Ethan’s lab. So far as I recall, his lab could be reached from the fourth floor along a walkway to the chemistry building. We came out of the elevator, I trying to explain as briefly as I could the questions I was then addressing and my experimental plans. He listened attentively and asked a few probing questions. Of course like everyone who meets “Gobind” for the first time, I was in awe: this was the man who once took up an entire fat issue of the Journal of Biological Chemistry and published a series of papers announcing the “Total Synthesis” of a gene—a feat that has never been repeated in the history of science for its sheer “weight”.

I used to see him often after that day, returning from his daily swim to his office, and also at 4 PM seminars, where he was a regular. But I did not get to talk to him again until the departmental retreat somewhere in New Hampshire (the location eludes me now). At that meeting Khorana spoke about his then recent results on using bacteriorhodopsin to understand how light is perceived and “decoded” into chemical and electrical signals. I had asked a few questions, and had expressed some concerns about the apparent differences in the time scale of electron transition actuated by the photon and the enzymatic reactions that ultimately triggers—whether the models he was using were sufficient to span the time scale difference. At lunch Khorana sought me out. After a brief discussion on the topic of his talk, he started asking me detailed questions on how my work was progressing. Amazingly, he appeared to remember nearly everything I told him about my work on the first day at the elevator. Gradually the conversation turned to his early life in Punjab, near Lahore in undivided India; how he would run from one school to another ahead of the district inspector, because he was trusted by the headmaster to present the best face forward. He also spoke about his time in post war Switzerland as a postdoc, where for a while he did not receive any salary, but managed to obtained free board at a monastery and survived for several months on milk and bread. His easy personality, and keen interest in other people’s work was a marvelous example. I had last seen him a few weeks before I had left MIT for my first job at the University of Rochester in 1991. He was trying to figure out how to calculate the dose of UV radiation from a conversion table in the handbook of nucleic acid chemistry, when he looked up and asked me when I was leaving.

Some fourteen years later, I had the honor of reviewing a grant proposal that he wrote. That was just before I heard that he apparently has been taken ill. I had been dreading this day; he passed away on November 9.

Sunday, November 13, 2011

On Growth and Emergence

It is often thought by people who are casually concerned with the environment and its degradation that it is important to live in harmony—in a steady-state of sorts; they ignore the primary characteristics of living organisms: living organisms grow.

One tends to imagine the idealized steady-state population dynamics of animals and plants in isolated geographical regions the ideal for human population. Unfortunately the reality is different. Nearly always such steady-state communities are extremely vulnerable to external influences; they lose their robustness because there is little selection pressure to keep such “robustness” genes in the population in the absence of changing circumstances.

Even in steady-state populations, individual organisms grow—either in number (where death rate balances growth rate) or in size (think of the massive conifers in old growth forests). Large conifers that have been around since Buddha walked the earth are still growing. The meristematic cells at the tips of their main shoot or branches are continuously dividing and are contributing to their growth in size.

To make this analogy somewhat more general, economic systems, which are indeed properties inherent of living systems (more appropriately, of communities of living systems), grow.

When economies do not grow, they become vulnerable. Free economies, like ant hills, tend to grow in fits and bursts.

On one late Fall evening in a lonely corridor across the hallowed halls of MIT, Philip Morrison, the wheel-chair bound astrophysicist, explained to me that ant hills grow by a few rather simple rules. Rule 1: make mounds. So numerous ants begin making numerous mounds over a range of area. Some mounds grow a little bit faster and others a bit slower just due to random fluctuation. Rule 2: Go to the nearest fastest growing mound. Probably they see the shadows of nearby mounds and thus find the locally tallest mounds. A recursive application of rules 1 and 2 will tend to generate a few very tall mounds with the most number of ants.

So do the economies. The fastest growing economies tend to whip up the businesses to participate and concentrate. This is true of geographical localization of economies as well. Think for example of the silicon valley, or the biotechnology mesa of San Diego.

Here comes the next analogy: self-organized behavior of crystal growth. Crystals also grow using rather simple rules of thermodynamic energy minimization. Rare and minor initial fluctuations in the rates of growth of a few crystal nuclei tend to determine the overall size distribution of crystals arising in a super-saturated sugar solution. Now, shake the solution a bit. Some of the growing crystals break up; the nuclei are redistributed. In a while a different distribution of size arises.

So it is with economies in recession. Recession has the effect of shaking up the economies. Bright folks left unemployed in Torrey Mesa in San Diego go to the medical school complexes in Alabama or biotech incubators in Madison and take root their. So too for global economies.

Very much like the dreams of the universal communes of communist manifesto, the most natural direction for the future of global economies lie in the migration of people and economies across the current archaic national boundaries. The difference here is that we are talking of pure capitalistic economy, accepting its boom and bust cycles as natural growth processes. I do not however agree that we will need to accept the social alienation that is generally associated with this view of capitalism. I believe there is room for active role of the nation states to alleviate human suffering, to act as buffers, and to promote human migration, spread of education and in promoting social acceptance associated with this migration.

What if the most vibrant of Chinese or Indian businesses find partners in Greece or Italy, and a portion of teeming Indonesian masses were to set up houses in population depleted Europe?

Perhaps the biggest barriers to internationalism are the color of our skin and the shapes of our jaws.