The Beginnings of my Stirring

My first stirrings, so far as I remember, came when I happened to get my fifth year birthday present from my mother, a book (in Bengali) called Manus Elo Kotha-hote? (How did man come about?). The book was a treat. Until then I had never heard of dinosaurs; there was no TV show (I had not seen a TV until I was 17 years old), no radio program on dinosaurs, no books on dinosaurs before this one; my parents and relations had never studied science, so they did not talk about dinosaurs—in fact I doubt they even knew of their existence before I got the book, which they also read along with me.

By the time I was in fourth grade, I was reading science fiction stories translated from other languages into Bengali. I remember specifically “The Time Machine” and “From the Earth to the Moon”. Around this time, perhaps when still in the third grade, I had accidentally discovered that when colored plant parts, such as green leaves and stems or flower petals, are pounded into a mash, mixed with fountain-pen ink, bottled and put into a dark place, they change color—-sometimes the ink becomes discolored, sometimes the blue ink became red or straw yellow, or the red ink became orange. I was doing this because I loved to paint but had access to limited pigment colors for doing watercolor. So I thought mixing plant parts with ink might generate interesting color varieties. But the process was messy, and I did not want people to throw the mixtures away. So I put them in a box and hid them within a drainpipe between my bedroom and the balcony, thinking that no one will try to clean the dry drain pipe. Well, that led to my observations on the fascinating changes of color with time, which caused no end of wonder, and I did not figure out why this occurred until late in college.

But there were other leads. I loved animals; specifically, I used to watch birds, which were plentiful in variety in the little tropical town where I lived. I first became aware of the serious dangers that wild flora and fauna in India faced around the time I was in the eighth grade, through readings in Sandesh, the monthly literary magazine for children which was edited by Satyajit Ray, the noted film director from Bengal. A Bengali naturalist whose pen name was "Jeevan Sardar", frequently wrote a column whose title I no longer remember. I do not know who he was, but my guess is that he might have been someone in the Bose Institute. In any case, his writings deeply influenced me when I was in middle school, and his column was instrumental in my choosing science at the end of the eighth grade--before that, I was quite set on becoming an archeologist and was going to study history.

Jeevan Sardar used to take long walks in the Dum Dum and Salt Lake areas, and he described over the years how birds and small mammals were disappearing. Remember that in the early 1960s the Salt Lake areas of Calcutta were quite deserted, mostly marshland devoid of settlements; Jeevan Sardar described how the place had been changing over the past several decades since he was a young man. Subsequently, I became an avid follower of the natural history columns in Science Today and Science Reporter, two monthly popular science magazines published in India. While in high school, I would escape from classes and go to the riverside to collect fossils, rocks, catch mud skinks, and watch dolphins dunking in the water.

By the time I was in the 11th grade, I became passionately interested in nature conservation. But I had also realized that nature conservation was a full-time career, and I was not sure whether I had the right 'stuff' for it.

While also in the 10th grade I had a chance encounter with an old copy of the Life magazine, from the early sixties, with Sophia Loren on the cover—Princess from Hong Kong was released then—right next to it on my uncle's magazine rack was another copy of the Life in which there was an article on the new science of immunology. There was a two-page spread of a ball and stick model of an antibody molecule.

That was a watershed moment. The dry pages of organic chemistry I was cramming for my high school examinations came alive with that article. I am yet to decide which was more attractive to me at the time, Sophia Loren or the model of antibody!

I decided that I must do what these ‘scientists’ do—the whole concept of a scientist being incredibly romantic to me, having never seen any scientist in real life at that time. In another year, I accidentally came upon “The Double Helix” by Watson in the British Council Library on Theatre Road, whose Rs.15 annual membership I purchased (which my father approved reluctantly) because it was the only library where I could access the book stacks by myself, to which I would walk a mile from home, take a train for an hour, take a bus for 40 minutes, then walk another few miles, and return the same way, on the days that I didn’t have classes in school because the Maoist extremists had shut them shut down. I am forever grateful to the Maoists for making possible these trips; otherwise, I would probably have become a physician in a provincial town. The Double Helix sealed my future.

I discussed this with Dr. Sivatosh Mukherjee, then the head of the department of Zoology in Presidency College, when I was in 11th grade (having been introduced to him by a Ph.D. student of his from Chandernagore), even before I was admitted to Presidency as a first-year student, and suggested to him a hare-brained idea about finding out why certain 'cold blooded' animals were disappearing faster than others--having to do with their being immune-compromised due to greenhouse effect and high temperature (in 1970-71, they had already detected massive greenhouse effects, and popular science magazines were awash with articles about them).

Professor Mukherjee was amused but not discouraging. He suggested I talk to Dr. Kanailal Mukherjee (KLM), a professor of immunology in the department of biochemistry of Calcutta University.

From Chandernagore I took the train, and a long journey by bus to somewhere near Park Circus, spending nearly four hours each way, to his research lab in a clinic. After trying to get his appointment (I had no access to telephones in those days) for three weeks (so 3 visits), I finally got his audience. Perhaps he was impressed by my perseverance, and so had felt bad to avoid me any longer. I am sure he knew the naïveté of my idea, yet he was encouraging to the extent that he invited me to work in his lab along with one of his female Ph.D. students.

The student was quite attractive but totally ruthless in critiquing me while I made numerous mistakes, but she also used to bring delicious food for me because she knew I used to come from very far away and did not have much money. Unfortunately, I do not recall her name any longer. I shadowed her for 3 months, 3 days a week; in this, I was lucky because our school was closed indefinitely--those 3 months, as it turned out--due to Maoist Naxalite disturbances.

At the end of the year, I wrote up my National Science Talent exam's project report based on this research experience--no results really, but it had an original theory, an equation that I proposed: however naive it was, it was my own. I got the scholarship. Based on this I convinced my father that I did not want to be a physician, and so despite having obtained admission to medical colleges, I went to study science at Presidency. My chief interest was to become a molecular biologist, with the view of understanding how the environment affects life.

While in Presidency, I along with my friends organized a weekly seminar program on current progress in biology at the nearby United States Information Service library. This little library was clearly a listening post of the CIA on the political pulse of Bengal; however, it suited our purpose quite well because they would bend over backward to entertain us.

During the summer after my first year in college, I went to Delhi University and worked for a few months in the laboratory of Professor S. Duraiswami, a biochemist trained in U. Wisconsin, Madison. It was a most incredible experience for me. Professor Duraiswami treated me as an adult and opened the whole lab to me. He told me to do whatever I wanted. I read random papers for a while, then decided to study the binding of actinomycin D, an antibiotic, with DNA. I designed two biophysical experiments, one involving viscometry, another using equilibrium binding kinetics through spectrophotometric shifts in absorbance. I worked out the algebra and conducted the experiments successfully. One incident I vividly remember. He gave me an Ostwald viscometer and told me not to break it. Within a few hours, I broke it. He smiled, gave me another one, and told me that now that I knew how to break it I would not break another one. Indeed, he was right. This simple philosophy has since guided my own behavior with respect to my students when many years later I had my own laboratory.

Upon returning to Presidency college, I fast-talked our head of the department into giving me a corner of his laboratory, a viscometer, and some chemicals, to study the hydrodynamics of protein shape change as a function of partitioning into two polar solvents. Unfortunately, this was too ambitious for the modest facilities we had and my limitation of knowledge of statistical mechanics. The latter I had to acquire entirely by reading by myself and talking to a senior student of physical chemistry whom I happened to know because he came from the same town as I did; so these experiments, although fun, did not go anywhere.

I end here, because after graduating with a B.Sc. I went to New Delhi, which is a different chapter in my life.

A Father's Day

Father died. It was a dark Monday evening in his room; it was a brilliant Monday morning in my car as it sped through the foothills of San Bernardino Mountains. The distant peaks were shadows over the horizon on the right and on the left west wind from Los Angeles brought the brown fog that curled low over the sprawling valley glittering under a dry desert sun.

Death came creeping up the stairs to father’s bedroom with three windows overlooking the tall coconut palms swaying in the moist wind. Low cloud hung heavy with warm rain in the stifling heat of late monsoon. He had felt it coming for the past five days; he had told Shikhadi last Friday when he was returning from his evening stroll by the river, “It’s been so many years; now it is time.” “Why talk like that?” She had rebuked him gently. “You’re so fit, you have many more years before you. You’ll have to see your grand daughter’s wedding.”

Time that began to wait for him seventy-nine years ago came slowly into his bedroom over that Sunday and finally on that Monday evening. The fever came on Sunday but went away later that day. On Sunday evening and throughout Monday he had slowly tried to move about the room, flexing his feet and arms, standing up by the bed then sitting down; he looked for the shadow of death on his wrinkled face in the mirror. He had felt it crawl up his bed in the early afternoon; he’d asked mother to call his younger son back from work.

Kanchu had rushed home immediately, anxious at this unusual request. Late in the afternoon, the sky became menacingly dark, the palm trees swung in rhythms in the blowing wind, the egrets scattered against the rush of cloud, thunder struck over and over and one crashed with a terrific report nearby. The power failed. Rain came first in large drops over the hibiscus leaves, then in a torrent that roared on the rooftop for over an hour. He felt death crawl up his legs and he asked Kanchu to massage them a little. He fell asleep. Brother called up the doctor, who asked for a blood test—to be drawn tomorrow. Kanchu paced on the porch downstairs while father slept. Mother sat beside him on the bed. At eight, he woke and asked mother for a little water.

“Can you sit up to drink?”

He felt death near his chest and slowly shook his head. Mother gave him a few sips of water.

“How do you feel now?” she asked.

“Better. Much better.” He closed his eyes.

He saw his village home now clearly, his mother sitting beside his father on the moss-blackened window ledge across his room in his ancestral home, swinging their legs slowly under the moonlit night. That was nearly seventy years ago and their image had faded, but now he saw them clearly. He then saw me as the town physician, coming home each afternoon for the siesta, eating lunch with him and in the evening sitting with him in the living room, chatting with visiting neighbors who came to pay respect and with occasional patients; he saw his grandchildren returning home in the evening from school, dragging their umbrellas on the ground, kicking a piece of rock all the way, with shoes worn out at the toe, then they would eat as he would sit talking to them before they rush to the field for a game of soccer or climb the rooftop to gossip with their neighboring friends.

My car was swinging into route ten towards LA, pushing through the morning traffic, it lurched forward to pass a line of trucks on the middle lane, then changed three lanes to turn sharply into the Claremont exit on the right, stopped briefly at the red down the ramp bottom, then made slowly into the Institute parking lot. I called home in San Diego over the cell-phone several times, but nobody answered because my son would be sleeping late for the last few days before his school reopens next week following the summer break. The dog heard my voice over the answering machine and rose anxiously; he went to my son’s room and watched him snore for a while then sat down.

It was dark outside in father’s room, and mosquitoes were beginning to fly in. Sitting beside him on the bed, mother was watching him sleep. She stood up to close the window.

He could now see the tall tamarind tree in his village home, by the large pond beside the gravestones of his parents. It was evening, and a storm was coming. The cloud hung low, waiting for a rain. He was playing on the steps, slippery with moss with small water-snails creeping under the shadows, leading into the pond’s dark water, where small fish darted to and fro, a lone dragonfly dived and made a round across the water beside the floating lily leaves, then returned to its perch on a small bamboo stick projecting out the water. He leaned forward and tried to catch the dragonfly but it flew away at his shadow, made another round then it returned to its perch. He stepped into the water over the slippery steps to get closer to the dragonfly, but slipped and fell into the cool water…he flailed wildly with his legs and arms to float but he was sinking, he couldn’t hold his breath any longer, he tried one last time to grasp at the bamboo stick but it was too far away, and he could now see his parents clearly across the water on the other side smiling to him and he let go.

I poured my morning coffee; the students were waiting in the next room for the nine-o’clock meeting when the call from India finally came.

The Spark

“The spark had found in its wings
The rhythm of a momentary dance…”
--Tagore in Sphulinga (The Spark)

My mother died on the morning of the Bengali New Year, the first official day of summer. A bright day; the sun shone on the saffron colored wall lining the nursing home where she spent the last few days of her life, breathing through the oxygen tube.

After her cremation and other ceremonies that invariably accompany such passages, I had to leave India in a hurry. Although I wanted to carry with me a few snatches of her belongings, objects that possibly could have no meaning to anyone but she and by default now me, I did not take them with me due to a sense of deference to my brother’s family who lived in the same household with my mother. I should do that on my next trip, I thought.

Among her belongings there was a little hard-bound book of poems by Tagore, a collection of Bengali Haiku by the poet published posthumously, the collection entitled by the name of one of the poems—Sphulinga or The Spark.

A tidy mauve colored book jacket with a small print of Tagore’s own stylized painting that tastefully decorated the frontispiece.

It was not the book itself that interested me.

The book was a wedding gift to my mother. A short note accompanied it on the first page: “To Gopa, with best wishes”, then the scrawl of a simple name. A name that I never heard my mother talk about.

My mother took a course on Ancient Indian History and Culture, leading to a Master of Arts degree at the Calcutta University in the latter’s heyday. It was then a new and interdisciplinary program, an amalgam of history and fine art, literature and archaeology. The program was headed by Dr. Kalidas Nag, a renowned historian and Indologist. There was a string of visiting professors, among them was Professor Stella Kramrisch. She described to me how brilliantly irascible was Dr. Kramrisch, who would lecture to the students in fluent Sanskrit and fly into a rage, her hair tucked in a small bun that would bob up and down, as she would castigate her students for not following her exposition.

My mother wanted to be an archeologist, but to qualify one had to spend a stipulated period on fieldwork in remote locations, which was not open to women students in her time.

She did fairly well in her course—she once showed me a hand written appreciation by Dr. Nag—but for some mysterious illness she deferred her graduation for a year. Afterwards she got the opportunity to do PhD, but she didn’t. Instead she got married to my father, left Calcutta, and became a schoolteacher. At the age of twenty-six she became the principal of a high school, and retired in that position after 40 years of service.

As a child I had often heard allusions to this episode of sacrificing her career to marry my father. This would only come out on those instances when my mother would be annoyed with my father, usually due to a disagreement about how to raise their children.

There were other vague stories I had heard. That my father’s marriage was first arranged with my aunt, who is a year younger than my mother. But apparently my aunt refused to marry my father due to his short stature. Since my great grand mother had apparently promised that wedding to my father’s aunt, by then deceased, there was a sense of guilt in the family due to unmet promise, which had apparently compelled my mother to “volunteer” to marry my father. This version couldn’t be all true, because my mother would retort while quarreling with my father that he needn’t have wanted to marry her.

My aunt, however, tells me a different story, that my father was in love with my mother. So it could be that although my aunt was originally betrothed to my father, she realized the situation and made up a story so as not to stand between them. Whatever the reason, my aunt, though the second daughter, was married off first, which was quite an anomaly in those days. That period also coincided with my mother’s mysterious illness.

But I digress. I was curious to know who actually was the top student in my mother’s MA class before she deferred. This topic she would avoid. She had airily mentioned a man’s name once, on a summer night when a cool moisture-laden wind blew past the translucent curtain on the western window, who had become an archeologist and had left for France.

My mother was the paragon of a dutiful wife, valiantly accomplishing all that was required of her both within the family and outside. My father, an orphan who had lost both his parents by the age of ten, was devoted to my mother. And so was my mother to him. As they aged together their bond appeared to grow stronger. After my mother’s retirement from school, she turned her entire attention to my father and to the growing family of my brother. After the sudden demise of my father due to a stroke, my mother re-focused her attention to a life of writing historical works and memoirs with a similar single-minded devotion.

Somehow I had always associated the name inside the book of poems, scrawled in black fountain pen ink, to a mysterious man in my mother’s past. Tradition demanded that I never spoke to her about it. Some thirty years had elapsed between the time I had last thumbed that book in my mother’s bookshelf, having left the country, and my mother’s death. I had forgotten about the book; not really forgotten but it was not in the orb of my attention all these years.

On my flight back to San Diego after my mother’s funeral, I suddenly remembered about the book of haiku. I made up my mind to bring that book with me on my next visit home.

I returned nine months later. The book, Sphulinga, was not in my mother’s bookshelf downstairs. A number of old books were missing. In their place now stood shiny paperbacks by Jane Austen and Mario Puzo.

My sister-in-law said that she had discarded some old books, because they were quite tattered, were eyesores, and because bookworms eating those would spread to the new books.

The spark is now truly extinguished.

Synthetic Life, First Edition

Ham Smith and Craig Venter, together with their coworkers, have made what is certainly the first ever living organism put together by a chemically synthesized genome.

The ingredients of the genome came from four bottles of chemicals, containing the equivalents of adenine (A), thymine (T), guanine (G) and cytosine (C), and a computer-stored information of the entire "tape" of the entire DNA sequence of Mycoplasma mycoides, a microorganism. (You can hear a podcast of Venter describing their work by clicking this link)

They chemically synthesized fragments of the genome in test tube, then used the "awesome power of yeast genetics" to stitch the fragments into a "complete" genome (with certain "water marks" and mutations created for specific purposes of identification and/or engineering) in baker's yeast (a totally different organism). Then the synthetic genome was introduced into a second microbe, Mycoplasma capricolum (as related to Mycoplsma mycoides as mouse is to humans) in various stages, debugged until the newly introduced synthetic genome took over the host cell and simultaneously the host genome was jettisoned.

What they now have is a completely new synthetic cell because most of the chemical building blocks of the new cell is now replaced by new molecules whose synthesis is directed by the synthesized genome.

This is a landmark technology achievement. It will also be touted as a landmark philosophical, psychological, ethical and moral watershed moment.

There is no doubt that it is a high moment in biotechnology. The scientific cleverness and engineering sophistication that went into this is of the finest order (I am still reading the pre-print and already much impressed).

However, its philosophical and extra-scientific implications are less than what some will surely claim.

There is no paradigm shift here: the concept has been consistent with scientific potentials of the day at least since 1991.

In fact, the crucial idea--that a host cell can be made to house a completely different genome and somehow be changed to the properties of the guest genome--was thinkable since a 1990 publication by Ron Davis in which his lab introduced full yeast genome into mouse cells, and I wrote a proposal to NSF, and got funded to introduce whole Arabidopsis chromosomes into yeast cells in stages by cell fusion (but did not succeed beyond the early stages due to technical reasons).

The fact that you can take over a host cell's "shell" ultimately by a new genome IS a challenging proposition which is first demonstrated by the present publication, and this is its most surprising novelty (beyond the technical tour-de-force).

None of it would likely persuade a sophisticated"believer" that man now can create life from fully inanimate objects (man cannot yet do so, because they needed living yeast cells and Mycoplsma capricolum cells, and M. mycoides genome information).

However, I can imagine now a fully synthetic life form being created some time in the future, where no previously living organism's "body part" materials will be used--in this direction recent work in Jack Szostak's laboratory in Harvard Medical School will be crucial. That synthetic organism will still have to use the "information" encoded in an already living organism's genome.

Perhaps the synthetic genome could use a mosaic of information from multiple organisms' genomes, and thus create a completely synthetic species. This would have to solve the issues of compatibility of gene regulation--a very difficult technical and theoretical problem. It will be a great achievement is successful.

Nevertheless, I still cannot imagine a completely synthetic organism in which both the genome (the software) and the "shell" (the hardware) are synthetic and did not exist before. Possible on paper, but not in reality. When that happens, man will have created life.

(If you click on the title, you should be directed to an editorial on the paper. IF you cannot access it, write in the comment and I will see what I can do)

$22

If ever there were
perfectly good 1.5 hour
lost to giddiness,
it was last night; feel-good nevertheless.
Babies suckling,
Babies crying,
Babies laughing,
Babies thumping
floor, babies thumping
themselves, babies thumping
each other, babies thumping
giddy cats; babies galore,
Babies with tinker toys,
Babies with nothin' more
than themselves: little boys,
And girls, and goats,
And mooing cows...

The lesson: never believe again
Women of childbearing age
Declaring: Surely you'll enjoy, I presage,
documentary notwithstandin'....

The hero of the movie, if there's one,
Was the heroic rooster, who done
ignore
The cute baby on bed peacefully a-snore,
Posed for the camera hidden behind door!!

(Tickets for two--$22)

The Hungry Tide

The Hungry Tide: A Novel by Amitav Ghosh


My rating: 4 of 5 stars
Amitav Ghosh, the author of The Circle of Reason and The Shadow Lines, weaves a complex fabric with some of the fundamentals of the deepest corners of our mind: the animistic instinct, the urge to discover, and the magnetism of finding one's roots. All this woven against a primitive landscape of water and silt, time set against tidal surges and mangrove forest, a flat land low against a stormy sky in the Bengal delta, a place that Ghosh brings alive with the apparent deftness of long familiarity. The plot is brilliant--a young woman smitten with the bug of a naturalist's passion is looking for the elusive fresh water porpoise in the riverine Sunderbans, an uneducated fisherman youth, his youthful wife and the locals with convoluted past in the backdrop of 1970s Bengal, create a drama that is wholly compelling yet mysteriously magical. Ghosh draws with broad swaths of a charcoal, as it were, constructing a dark world of primitive elements that probe deeply into our human self with the ease and flourish of a master craftsman. Magic is in the air and water, in the sky and in dolphin's breath. The story attains a crescendo in the form of a huge storm that changes not merely the landscape. A book written with deft craftsmanship and intimate knowledge. Read it.


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A Sea of Poppies

Sea of Poppies by Amitav Ghosh


My rating: 2 of 5 stars
Apparently the first of a trilogy, Sea of Poppies has a meritorious plot. Beginning in the poppy plantations of north eastern India in 1830s, the novel explores pre-mutiny India under the East India Company rule, and follows its protagonists into a ship crossing the 'black waters' on its voyage to the Mauritius islands. Ghosh has done his homework well; his description of opium plantations is credible and so is his depiction of the landed gentry of precolonial Bengal and its contrast with its unsophisticated but wily new masters. Geography of 1830s Calcutta is fascinating to read. Where the book falls flat is in its overly dramatic, bollywood script of a story line, in its mix of authentic period pieces of linguistic constructs with lamentably modern colloquialisms given to post-bollywood mannerisms (and tollywood Bengali of 1980s) that ring hollow to the cognizant ear. Attempting to be Rushdiesque, Ghosh has fallen prey to the Bollywood film script genre (if that exists!). I bet someone in Bombay would be calling Ghosh's agent by this time. It would be a spicy flick; a sad loss, given that Ghosh had a plot as strong as any of his previous novels.

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I should've been an economist

Had I read Asimov’s The Foundation series when I was in high school, or had I met an economist who was not a banker or a financial advisor but an economic theorist, I most likely would have chosen economics as a career option.

As it turned out, back in high school I thought economics is a boring field of stiff accountants, where you learn how to balance books and make investments. Since I equated money with vulgar incentives, a man-made device meant for corrupting the mind, I avoided all contact with economics though some contact with money was pleasurable. I knew no better until my late 30s, when I chanced upon Amartya Sen’s articles in the Scientific American.

Having always had that love for neat theories with the power of explaining large things, I gravitated towards biology because I thought the complexity of biology is ripe for theory. I was mistaken. In biology nearly anything goes. Evolution finds one solution among many. There are very few general principles.

Surely there are some principles. Evolution by natural selection on rare spontaneous variants is a powerful principle. Then the idea of information as an organizing principle is another. Coding theory. Mendel’s laws and Hardy-Weinberg equilibrium. Haldane’s rule. But these can be counted on one’s digits.

This general lack of theories gave biology its charms too. Just when I think of myself as so clever having figured out something, there comes the unexpected surprise. During my own career there were many such surprises. Splicing; RNA enzymes; PCR (dang! I should’ve thought ‘bout it!!); combinatorial design; miRNA. Perhaps the prion fold as a “bit-flipping” memory molecule is just over the horizon; hope it turns out to be true.

Biotechnology has profited from these unexpected insights in due courses, and more will surely come. It is even more surprising how staid most research in successful biotech companies usually is, and, paradoxically, how invigorating research can be in many unsuccessful biotech companies. This happens so much so that some say, for a biotech company to succeed one doesn’t need good science. One only needs simple, practical solutions and managed development.

Nothing can be further than the truth. The truth is that one never knows what would succeed. So the initial investment, at least in terms of time, must be long and tolerant of blind alleys—merely because there are very few theories in biology—there is only chance and surprise—there are few principled risk factor calculators, unlike in hedge fund investment. When one doesn’t know what will work, the best that one can do is to nurture the creative energy of the scientists. Less the management, more the nurture, the better. Scientists in powerful positions in biotech know this well. Managers in powerful position rarely appreciate this. Venture capital fund managers are even less tolerant. The balance between the next quarter’s books and the creative energy of science is a tough one to achieve; tough to tolerate the latter in the absence of a theory.

Nothin’ beats the austere satisfaction of constructing a purely algebraic formalism of a paradox, resolving it by logic, and finding its application to a thing as complicated as the voting behavior of people; as Arrow’s impossibility theorem shows, for example. Imagine an ‘impossibility theorem for a peptide drug for HIV-AIDs treatment’!

I should’ve been an economist.

Dang!

Road Warriors

Icelandic ash produces chaos in air travel. So it is time for the road warriors to have some enforced adventure (see the link on this blog's title).

I am reminded of a few adventures myself. That time in 1977, the express train from New Delhi gets stranded in Bengal-Bihar border due to some problem on the track. We wait for some four hours, walking around the train in the middle of nowhere. The track seems beyond salvage any time soon. An engine is apparently en route from the direction we have just come so our train can be hauled back to the previous junction in Bihar. So it is a choice between getting stranded in Bihar versus finding our own way to Calcutta. My friend and I jump ship. We walk along the railway track about five miles to the next town, catch a bus that travels along bumpy way through glacial moraines of Bihar and then the coal fields to a rail junction after some six hours. It is night by that time. We wait until the next passenger train rattles into the platform in the middle of night, its coal engine hissing. We set off, to arrive in Burdwan at the crack of dawn. Sweet tea and jhal muri along the way. What fun.

The Power of Sequencing

Back in 1992 I was in a conference where someone famously powerful was proposing to sequence the genome of the model organism with which I used to study my favorite questions in research. Sitting in the dark hall I quickly made a back-of-the-envelope calculation: how long would it take to discover the function of an unknown gene, known only by its sequence, given the rate of gene function discovery for the first organism's DNA ever sequenced completely (the lambda virus) in 1979. The answer was several hundred centuries. So at the end of the talk, I announced the result of my calculation, and asked why not spend the money, millions of dollars, on simple investigator-initiated research that asks straight questions and gets straight answers. There was silence in the hall, and I felt smug and smart. Until the last talk in the conference, which announced the discovery of microarrays, for parallel measurement of RNA transcripts made from hundreds (at that time) of genes. Quite uncomfortably, I realized my mistake--the vice of linear extrapolation. That changed my mind.

So today I read and discussed a paper published this last January, which reported the successful identification of a gene that appears to harbor the causative mutations for Miller Syndrome (Google it, if you don't know it), a particularly debilitating rare and inherited disease that severely affects the lives of some children. The methods that the researchers used, based on sequencing nearly the entire protein-coding gene set of the patients, were unimaginable back in 1992--it would have been considered a science fiction dream in popular forums and would have been derided as madness in scientific company. But it is a reality today. What surprise will the next month bring?
[Update, April 16: Here is a link to an editorial on this paper published in today's Nature Genetics: http://www.nature.com/nrg/journal/v11/n5/full/nrg2783.html]

They say it is the cruelest month

Today is the Bengali New Years day. It is not held on every April 13, because it goes by the lunar calendar. Vagaries of celestial bodies mean that my mother, who passed away on April 15 morning last year, on the Bengali New Year's day, has two more days to live as it were in the year since her passage. This year it was Winko's turn, but he just missed the New Year's day. He perhaps could have made it but it was better for his own sake that he didn't. I also wish that mother suffered fewer days the agony that she endured last. I miss Winko's silent paws as he paced behind me, up and down the room, as I am given to do often, and he so followed. A shadow. Funny. I miss my mother's distant look on the empty balcony, waiting for April nor'wester to break against the sky. Winko's paws, strangely soft, as soft as mother's hands on my forehead a distant memory. Kisses that I would disown when grown were to be sought again from a mouth with a hanging tongue. Selfless devotion? Yes, that. Dog and mother. That is why this pain in April.