Beneath my hands

Recently purchased an out-of-print Leonard Cohen collection from a yard sale

————

Beneath my hands
your small breasts
are the upturned bellies
of breathing fallen sparrows.

Wherever you move
I hear the sounds of closing wings
of falling wings.

I am speechless
because you have fallen beside me
because your eyelashes
are the spines of tiny fragile animals.

I dread the time
when your mouth
begins to call me hunter.

When you call me close
to tell me
your body is not beautiful
I want to summon
the eyes and hidden mouths
of stone and light and water
to testify against you.

I want them
to surrender before you
the trembling rhyme of your face
from their deep caskets.

When you call me close
to tell me
your body is not beautiful
I want my body and my hands
to be pools
for your looking and laughing.

- From The Spice-Box of Earth

Passing note – the semester continues and this year’s Nobel prizes

It’s only when the semester reaches its first quarter does it dawn upon you that you are trying to bite more than you could possibly chew. Nevertheless, that all the courses I am taking this fall are a lot of fun which, in addition to a cultivated nonchalance towards grades (which I confess developed only during the second semester at MIT) makes it worth the stretch.

1. I am sitting through a course in Systems Biology taught by Alexander van Oudenaarden which has a lot of new stuff coming up in the following weeks that I am excited about. The relative familiarity with the initial course material ( the diversity of the audience – from theoretical physicists to math-challenged molecular biologists forces the instructor to start from the very rudiments) is quite understandable but makes me restless sometimes during the lectures.

2. The listener course in music was supposed to be a fun course but surprisingly takes up a lot of my time during the week; I had foolishly pledged to submit all the homeworks and take all tests, forgetting that no course in MIT is ‘fun’ in the literal sense of the word. There is no one to blame but me here. Classes mostly involve sight singing and voice development – although I am pretty average at it (and how I wish I had some of my Carnatic training left in me), the learning component makes it satisfying to the mind.

3.  I have been forced to take the undergraduate introductory biology class alongside 650 odd freshmen. The reason? – Chemical Engineering at MIT requires every student to complete a biology course requirement. Why a graduate level  course in Immunology that I took in spring and scored decently well in will not complete the purpose? – I do not know! Nevertheless, far from being a complete waste of my time, I find Eric Lander’s lectures extremely rich and enjoyable. I guess the true mark of a great teacher is to be able to communicate at different levels to different needs of students and there is no doubt that he is one. His deep understanding of the history of genetics and molecular biology (while himself being a part of some of its seminal developments), his meticulous emphasis on conveying the evolution of a scientific principle and not just the details of a particular discovery and finally his energy as a lecturer make me look forward to his classes every week.

4. ‘Statistical Physics of Particles’ by Mehran Kardar is probably the most intellectually time consuming class that I am taking. The classes are quite rigorous and Kardar is known for his clarity and meticulousness as a teacher. On a passing note, for the first time in my life, I am making careful and complete notes in a class .

And I have not even mentioned about research yet. My proposal deadline is dangerously approaching close – I have a few ideas but I desperately need to develop them soon if I am to make any sense to my committee. For some reason my adviser has been sounding extremely nonchalant about it every time I try to flash the yellow-light;  that only drives the urgency further. More on this in the coming weeks.

—–

The Nobel prizes in chemistry and medicine this year have been awarded to investigations elucidating fundamental mechanisms in cell biology. The Chemistry Prize has been awarded for studies that have shed light on the structure and the function of the Ribosome – the multi-protein complex that ‘manufactures’ all cellular proteins from their RNA transcripts. Through high resolution crystallography, the award winners have, along with their respective co-investigators and collaborators elucidated the precise aspects of the structure of the multiple subunits that confer the profound characteristics it possesses, namely:

1. How the Ribosome structure designs the energetics of tRNA discrimination during codon recognition that enable it to synthesize proteins from the mRNA transcript with high fidelity.

2. The effect of mutations and antibiotics on the accuracy of translation mediated by changes in structure

3. Interestingly (though I don’t know the precise details), papers from the Ramakrishnan group have supposedly elucidated the mechanism of wobble which was hypothesized by Francis Crick during the early second half of the previous century.

The Swedish academy of the sciences summary of the findings is a very readable document and contains a detailed review of the investigations.

The Medicine Prize, like the Chemistry one, was awarded to three scientists for their work on understanding the functions of telomeres and telomerase (the enzyme) activity on chromosomal stability. Telomeres are non-coding extensions to the chromosomes that buffer for the loss of base pairs from the lagging strand that routinely occurs during each replication cycle. The telomerase is the associated enzyme that ensures that the template strand of the DNA is sufficiently extended at the 3′ end so that precious coding bases are not lost. The award winners and their colleagues demonstrated through biochemistry (Blackburn and Greider) and Genetics (Szostak) how the function of the telomere has been evolutionarily conserved and how it protects the chromosome against routine degradation and recombination events that might lead to a loss or distortion of genetic information.  The Swedish academy document is again, IMHO, an excellent place to learn about the historical details and implications of this finding and following it requires no more molecular biology than what is gained at an introductory level (and as mentioned in the earlier part of this post, I am currently undergoing such a process ). Abnormal Telomerase activity and improper telomere maintenance have been implicated in a number of cancers and hereditary disorders and has profound implications on aging, hence all the razzmatazz.

New AIDS vaccine – promising, but some skepticism

There has recently been much excitement following the reported success and promise of a 3 year long clinical trial for AIDS vaccine that was carried out in Thailand, the largest trial of its kind in the history of AIDS. The trial, which has the backing of the Army and the National Institute of Allergy and Infectious Diseases among others cost upwards of $100  million. The New York Times reports:

The trial, the largest AIDS vaccine trial in history, cost $105 million and followed 16,402 Thai volunteers.

The men and women ages 18 to 30 were recruited from two provinces southeast of the capital, Bangkok, from the general population rather than from high-risk groups like drug injectors or sex workers. Half got six doses of two different vaccines; half were given placebos.

For ethical reasons, all were offered condoms, taught how to avoid infection and promised lifelong antiretroviral treatment if they got AIDS. They were then regularly tested for three years; 74 of those who got placebos became infected, but only 51 of those who got the vaccines did.

Commenting on the ‘partial success’ is an  article in Scientific American:

In an early-morning announcement today, researchers reported that an experimental HIV (human immunodeficiency virus) vaccine effectively reduced the number of people who contracted the virus by nearly a third.

I have some immediate skepticism on the numbers reported and I shall present them in this post in no particular order. But I must state here that no argument of mine will involve special knowledge of HIV literature or host-pathogen dynamics during infection that I have been reading  in some detail for my thesis project. These are simple argument and do not involve any fancy statistical inference tools. The SciAm article does mention some points of doubt but these are surprisingly absent in all other articles including that in NYT. Some comments are therefore in order:

1. Firstly, the work that has gone into the vaccine is commendable. Secondly, if historical relativism were some benchmark of success, then it behooves us to acknowledge that the absolute results are  promising and ought to be pursued. (Read about the failed Merck vaccine trial in 2007)

2. The vaccine itself is a combination of two vaccines that failed independently in the past. While this does not have to necessarily imply anything, the mechanistic evidence of the new vaccine is wholly unclear and needs to be delineated soon. Furthermore, it was reported that there was no difference in viral loads (or alternatively the chronic phase set point measured in viral RNA copies per ml)  between the two infected groups – one that got the vaccine and one that was administered the placebo. Now this is indeed the major reason that confounds the possibility of parsing any mechanistic insight considering that we know the individual drug compositions.

3. Let us consider the null hypothesis that the vaccine is ineffective and evaluate the statistical significance of the results obtained. The statistical significance of a result is a measure of vaccine efficacy. The metric to compute the statistical significance is the p-value which is simply defined as the probability of observing a result at least as extreme as the one observed in the experiment under the assumption that the null hypothesis is true (note however, that it is not the probability of the null hypothesis being true). If this probability is less than a critical value then scientists consider that as a reasonable case against the null hypothesis. As a universally agreed upon heuristic, the critical value of this probability is taken as 0.05.

Let us ask, what is the probability of observing a split of 51 vaccinated individuals and 74 individuals (or lower, in favor of the vaccine) administered a placebo in a cohort of 125 infected individuals, under the condition that the null hypothesis is true (that the vaccine is ineffective)? If this probability is lower than the critical value (0.05) then the results may be considered statistically significant.  The expression is the following, with n=125.

It turns out that this sum evaluates to approximately 0.048 (I just calculated a few dominant terms in the summation assuming the maximum term method is valid here). Now this is lower than 0.05 and I assume is the basis for the report of statistical significance as mentioned in the papers. Note however that most successful vaccines in the past have been validated against much lower p values.

4. The sample size is extremely large as compared to the rate of incidence (which is a given considering the nature of HIV infection). Considering the following thought problem. Assume that the vaccine is ineffective and that the rate of incidence of AIDS in a medium risk population is a binomial distribution with probability of infection as 63/8000.  Now, we have two groups of 8000, each administered a placebo ; Let us  ask what the probability of seeing 51 and 74 infected in the respective groups is. Both numbers are close to being one standard deviation () from the mean (63) thus indicating that it is highly likely the result might be confounded by numerical variance. In contrast if the split was 20 and 74, the hypothesis that the former group was administered a placebo would be far more weakened.

5. There is increasing and indisputable evidence that the progression of HIV is profoundly dependent on the genetic constitution of the host, particularly focused on a locus of the human genome coding for a class of proteins called the Major Histocompatibility Complex (MHC). MHC is a highly polymorphic locus – it is very unlikely that two individuals in a population will possess identical MHC genotype (though they may have some alleles, or haplotypes in this context, common). Furthermore, there is a high variation of MHC distribution across geographic locations. Therefore a vaccine that looks successful for a rapidly evolving virus like HIV in Thailand cannot be extrapolated blindly to South Africa or India.

6. Any successful response against HIV has to invoke all the arms of the immune system – the antibody or humoral response and the lymphocyte or cellular response in extremely strategic ways so as to corner the virus. What is more precious than success in a particular trial is coming up with a mechanistic rationale for such a vaccine which also includes modifications across genotypes. In this case, one has to (as I am eagerly) wait for the publication of details of the methods and results of the trial.

The Great Algorist

I find that there is always something worth learning in E. T. Bell’s Men of Mathematics on re-readings

Jacobi seems to have been the first regular mathematical instructor in a university to train students in research by lecturing on his own latest discoveries and letting the students see the creation of a new subject taking place before them. He believed in pitching young men into the icy water to learn to swim or drown by themselves. Many students put off attempting anything on their own account till they have mastered everything relating to their problem that has been done by others. The result is that but few ever acquire the knack of independent work. Jacobi combated this dilatory erudition. To drive home the point to a gifted but diffident young man who was always putting off doing anything until he had learned something more, Jacobi delivered himself of the following parable. “Your father would never have married, and you wouldn’t be here now, if he had insisted on knowing all the girls in the world before marrying one.”

Looking Back, Looking Foward – James Watson and E. O. Wilson at Harvard

Thanks to Dipti, a friend who studies at Harvard, I managed to get a coveted pass to watch a discussion between two scientists, who rank unequivocally among the most influential biologists of the 20th century – James D. Watson and E. O. Wilson. It was an hour long,  free flowing conversation on no particular topic and was moderated by award winning journalist Robert Krulwich. The venue was Sanders Theater, a beautiful 19th century Hall that looks straight out of a Harry Potter book. For the first time in my twelve months in Cambridge, I felt envious of Harvard over MIT. The Mahogany seating rows with leather cushions, the Greek statues flanking the brightly lit stage and the grand chandelier that dropped from the roof seemed to possess an unusual power to confer an aura of elevated grandiosity to any happening in its confines. I am certain even Rakhi Sawant’s swayamvar would have seemed a very scholarly enterprise if it was conducted in this beautiful sanctuary(Now that’s how you stick a fart in the orchestra ). Stop.

Though both biologists by profession, Wilson and Watson represent two very different domains of the subject. Wilson did pioneering work in entomology (particularly on ants) and is famous for his writings on biodiversity and conservation. Watson on the other hand is a molecular biologist, most famous for his contribution in predicting the structure of the DNA molecule for which he shared the 1962 Nobel Prize with physicist (and later neuroscientist) Francis Crick and biologist Maurice Wilkins. The two were young professors back in the 50’s in Harvard and while they did not see eye to eye back then (mostly because of Watson’s fervent attempts to encourage recruitment of molecular biologists over other kinds whom he described as ’stamp collectors’), they developed a warm and friendship as their careers matured. They apparently met for a similar discussion at the same venue about fifteen years ago. Considering their present age (and with due respect to propriety), a third reunion seems unlikely and at any rate my being witness to it is uncertain. Therefore, it was quite fortunate that the opportunity to attend presented itself.

Having said that, I was mildly disappointed (but only a teeny-weeny bit) by the way the conversation turned out. Don’t get me wrong, it was extremely enjoyable to see the two old scientists engaged in an animated conversation that  hopped flippantly between their personal philosophies and attitudes towards science, their deep reverence for scholarship, why scientists deserved to be paid more if not equal to business school faculty, what problems they considered worthwhile, all decorated with intermittent scientific bitching (which seems to be more fundamental to any competitive enterprise than a deeper philosophy, academic or corporate). What I was hoping for was a possible discussion of the immediate big challenges confronting the fields of their respective expertise; while there was some venture into those areas, the moderator maneuvered from more probing details – possibly out of design, given the composition of the audience was predominantly lay. There were many little anecdotes that I should like to narrate but that would demand more length and better structure than this half-baked midnight ramble. Just one for the sake of it.

Both Watson and Wilson’s scientific careers have been associated with a certain degree of flamboyance, possibly because they have not shied away from the media – controversy or otherwise. Further, both agreed from a personal philosophical standpoint that in addition to intelligence, strong ambition and competitiveness were essential for what they considered the route to success in a scientific enterprise (More so with Watson than Wilson). Krulwich then put forward a cheeky question to both(rephrasing) – “Now the two of you seem to advocate shine over simmer. But surely you have noticed the case of Darwin whom both of you undoubtedly revere but who was exactly opposite in personality. He showed neither ambition nor competitiveness in the conventional sense. He simmered for years, through silent persistence despite having landed at the holy-grail of the life sciences.” After a couple of moments of silence, Watson exclaimed, “Sure he simmered, but when he heard of Wallace he did not lose any more time and published immediately!“. The audience clapped.

Orhan Pamuk

The September 7th edition of the New Yorker has a short story by Orhan Pamuk in its fiction section (Distant Relations). I just finished reading it in my subscription copy. Those interested can find it here.

Little by little, sophisticated girls from wealthy Westernized families who had spent time in Europe were beginning to break this taboo and sleep with their boyfriends before marriage. Sibel, who occasionally boasted of being one of those “brave” girls, had first slept with me eleven months earlier. But, by this point, she felt that the arrangement had gone on long enough and it was about time we married. I do not want to exaggerate my fiancée’s daring or make light of the sexual oppression of women, because it was only when Sibel saw that my “intentions were serious,” when she was confident that I was “someone who could be trusted”—in other words, when she was absolutely sure that there would, in the end, be a wedding—that she gave herself to me. Believing myself a decent and responsible person, I had every intention of marrying her; but, even if I hadn’t wished to, there was no question of my having a choice now that she had “given me her virginity.” Before long, this burden cast a shadow over the common ground between us, which we were so proud of—the illusion of being “free and modern” (though, of course, we would never have used such words for ourselves), on account of having made love before marriage—and in a way this, too, brought us closer.

A Dream Deferred

What happens to a dream deferred?

Does it dry up
like a raisin in the sun?
Or fester like a sore–
And then run?
Does it stink like rotten meat?
Or crust and sugar over–
like a syrupy sweet?

Maybe it just sags
like a heavy load.

Or does it explode?

- Langston Hughes

—

Wanted to share this for a while since I read it in Zinn’s People’s History (Chapter 17, Or does it Explode?).

Photo-exhibition on Chattisgarh

Over the next couple of months, various AID chapters across the country are organizing a traveling photo-exhibition of the work of Javed Iqbal, a photojournalist who has been spending his time in Bastar, Chattisgarh, the epicenter of Salwa Judum-Naxal clashes. MIT would be host to the photographs for a few days during October 2-11.

I got an opportunity to see the final slideshow yesterday and it was quite stunning; not to mention that the experience was quite harrowing despite sitting in the confines of a Harvard Classroom. Some of the photographs (with captions) are in Javed’s webpage. Further, I would also recommend the following articles written by him – 1, 2 and 3.

Previous related posts – 1,2

Ob-La-Di, Oh-La-Da

Just finished the fifth consecutive R. K. Narayan – The Financial Expert. Thoroughly enjoyed it. The need to change course in literature has arrived and I don’t think I can consume another story set in Malgudi. With an overwhelmingly busy semester set to begin, managing a Brothers Karamazov on the side would be a tall call. Perhaps I should leave fiction aside for a while and make progress through Howard Zinn’s People’s History (for those unaware or curious, it is a fantastic account of U. S. History – the only dedicated one I have read  partly and an immensely scholarly work).

——

The second-last R. K. Narayan novel that I read was The English Teacher. It definitely ranks as one of his most important and endearing works; its most important aspect is the emotional and spiritual feeling that the story is pregnant with. It’s a story about the loss of a loved one, subsequent reconciliation and self-realization; from what I understand, it is considered a semi-autobiographical work (the author dedicates the book to his wife Rajam, who he lost to typhoid in 1938 in circumstances similar to the death of Susila in the novel). By the time I had finished reading the first half, the book seemed superior to all the other R. K. Narayan novels I had read before; nevertheless,  I felt the second half was slightly disappointing and the story lost the depth I had assumed it would explore. So, Swami and The Dark Room continue to hold their hallowed positions .

‘There is no escape from loneliness and separation. Wife, child, brothers, parents, friends… We come together only to go apart again. It is one continuous movement. They move away from us as we move away from them. The law of life can’t be avoided. The law comes into operation the moment we detach ourselves from our mother’s womb. All struggle and misery in life is due to our attempt to arrest this law or get away from it or in allowing ourselves to be hurt by it. The fact must be recognized. A profound unmitigated loneliness is the only truth of life. All else is false. My mother got away from her parents, my sisters from our house, I and my brother away from each other, my wife was torn away from me, my daughter is going away with my mother, my father has gone away from his father, my earliest friends – where are they? The scatter apart like the droplets of a water-spray. The law of life. No sense in battling against it…’

No, I don’t quote this paragraph for any esoteric wisdom that I feel it possesses and which I wish to dispense across to the world. Last month, a corresponding friend teased me when I wrote to her about Alice Muro’s The Bear Came over the Mountain, of how the story had provided me a much needed perspective during a particularly rough personal phase that I was wrestling with. One cannot depend on literature to provide the antidote to all problems – if anything, the comfort that it provides is a purely placebo effect. Nevertheless, what usually happens is that one gets affected by the parts one can strongly associate with.

——

The last two months happened to be one of the most depressing phases of my life yet – a number of things did not work and I do not wish to get into the details. Probably because I already feel worn out by the amount of useless thought that I have wasted on keeping those feelings alive for longer than what they deserved. Further, my close proximity to that period dictates that personal biases and selfishness will inevitably weigh on any description; there is a lurking fear that dishonesty and self-righteousness will cover up many personal shortcomings and failures that were as important as external factors in putting me through those terrible weeks. They felt terrible of course, but if I was a third person hearing my woes I would tell myself to take a break, move on and not make a big deal out of it.

As I went down a personal drain, I lost sensitivity to all the good things around me. I became sore and calculating in my behavior and the worst part of it was a growing romantic association with grief and sadness, which among other things, is severely debilitating and cannibalizing. Concentration and creativity break down and every insignificant perturbation serves as a distraction that grips your memory with the strongest of emotions until you feel choked. On normal days, I would have finished The English Teacher in one sitting; it took me nearly two weeks to read it. I would lie down on my bed with the book but post a couple of pages would find myself lost in thought, feeling the loneliness of Krishnan as my own and would lie aimlessly staring at the ceiling until my own thoughts fatigued me and lulled me into a restless sleep.

With a lot of inefficient and incoherent reflection, a little literature and more than a little help from some friends, I am back again . And since any further attempt to convert the mood of this post into a lighter one is going to be useless, I promise to write another one pretty soon.

Disturbing numbers

I was browsing through the August 13 issue of Nature and it had a short news article warning the fast depletion of groundwater reserves in India. An excerpt:

Their research, published online in Nature this week (M. Rodell et al. Nature doi:10.1038/nature08238; 2009), found gravity anomalies suggesting a net loss of 109 cubic kilometres of water — equivalent to a mass of 109 billion tonnes — from August 2002 to October 2008. The amount lost is double the capacity of India’s largest surface-water reservoir, the Upper Wainganga, and almost three times the capacity of Lake Mead in Nevada, the largest reservoir in the United States.

That one has to read something like this in Nature and not TOI/IE is equally disconcerting (but I may well have missed the news if it came out).

A second study using GRACE data, by scientists at the University of Colorado and the National Center for Atmospheric Research in Boulder, has found that the most intensively irrigated areas in northern India, eastern Pakistan and parts of Bangladesh are losing groundwater at an overall rate of 54 cubic kilometres per year, consistent with Rodell’s results (V. M. Tiwari et al. Geophys. Res. Lett. doi:10.1029/2009GL039401; in the press).