Modularity, Reconfigurability and Institutional Robustness: A post-COVID19 model

COVID-19 crisis has revealed the vulnerabilities of our interdependent and globalized economies, where highly specialized and focused manufacturing industries are distributed across the world and supply chains that are managed through numerous tenuous links, where the resultant structure is only as strong as its weakest link. At this time of emergency, incentives to reconfigure businesses to produce essential items did not work as efficiently as we generally credit private enterprises: governments had to step in with war-time powers to compel businesses; broken supply chains had to be restored through intergovernmental airlifts. We are rudely awakened to limitations of private enterprises for rising to the challenges of a globalized emergency, and a renewed appreciation of efficient governance is in order.

How might such governance be organized?

There are two previous models where nationalism provided the impetus: wartime efforts in the west and in the east. The US and UK used war powers acts to first subdue and to ultimately kindle the awesome power of private industries manufacturing automobiles and railways to make tanks, battleships, fighter planes and bombs; the Soviet dictatorship did the same, perhaps even more effectively, to convert lumbering shipyards and steam engine manufacturing factories to make tanks and rifles. The problem was that at the end of the war both had to keep the war-time factories working for a while so as to feed the nations—so we and the Soviets had our Korean war and our Vietnam.

Is there a less destructive way out of war-time diversion of resources? Or must we always be burdened by our momentum? Is there a way that minimizes the retooling for reconfiguration of industries to enter and then to leave the war-economy, be it due to human conflict or a future pandemic?

A recent concept in evolutionary biology is ‘modularity’—a term borrowed from engineering and systems science. Like Lego blocks, are there basic building blocks of gene circuits that are reconfigured by evolution to produce the bewildering diversity in nature? Moreover, such modularity is thought to provide evolutionary robustness—the niche vacated by the extinction of a species is quickly replaced by organisms that evolve through reconfigured genetic modules. Modules reconfigured perform novel functions that their previous ensembles didn’t. There are lessons here to be learned.

What we need is an abstraction, a conceptualization of modularity of manufacturing industries, and of supply chain Lego pieces. A high-level government agency would need to examine each industry to identify the modularity and reconfiguration strategies for natural (pandemic, earthquake, global-warming) or man-made (foreign or civil war) catastrophes. They will be the intelligence gatherers, systems modelers, and will develop scenario-specific contingency plans based on data and model.

They will interface with FEMA, the NAS, the Congressional Budget Office, will be overseen directly by the Congress, and will work in direct consultation with a similar structural entity established through the UN. An agency for the analysis management and design for systemic robustness.

Estimated Loss to the US Economy due to COVID-19, If the Disease were to Take its Course

Here I attempt a back of the envelope estimation of the total GDP loss to the USA alone if COVID-19 is allowed to run its course without any containment measures in place.

This assumes a conservative figure (30%) of the oft-repeated range(25 – 75%) of the total incidence rate of COVID-19 if no quarantine or stay-at-home types of segregation measures are taken.

I have used the 2010 demography numbers of the US population by age and sex and used the life-expectancy table of 2010 for the US population from the US census.

Here are some broad stroke assumptions I made for this rough estimation:

1.     2010 US census age and sex distributions

2.     2010 US life expectancy distributions

3.     Infection rates follow a normal distribution (this is the epidemiological standard)

4.     Males and females are equally infected (though not equally affected)

5.     30% of the population are ultimately infected within 1 year (the range provided by epidemiologists are from a low of 25% to a high of 70%)

6.     All age groups are equally infected (though not equally affected)

7.     I have used a sliding scale of treatment weight for various age groups, assuming 100% treatment rates for all age groups, except the above 65 years, in which I assumed 80% treatment rates (an ad hoc assumption but something that is seen in Italy where the resources are saturated).

8.     Used a sliding scale of death rate (0.01 – 0.035) per age group. The upper range is a low estimate. Current mean rate according to WHO is 0.045 (which is widely considered to be an over-estimate, but current >75 years age group mortality rate is ~14.8%, so I have erred in favor of an under-estimation)

Using these parameters, I have calculated the DALY lost due to COVID-19 in one year. DALY, Disability-Adjusted Life Years is an economic measure used to estimate the loss to the economy due to a particular health issue.

DALY = Number of cases x disease duration x Disability weight + YLL

Here, the number of cases was estimated according to the assumptions stated above; disease duration was assumed to be 2 weeks for below 65 years and 3 months for >65 years; disability weight was 0 for all age groups except for 65+ yeas which on average was assumed to be 20%.

YLL is more complex, and is automatically calculated by the R-package “DALY” within R, and is defined below (ref: https://www.ncbi.nlm.nih.gov/pubmed/23927817)

Below is a snapshot of the input data:

And below is the resulting distribution of DALY estimated with the above parameters:

The mean value of DALY loss turns out to be: 41,056,030 years.  This is the estimated mean loss of DALY to the economy due to COVID-19.

To translate that to the loss to the economy, we will need to multiply the per capita annual GDP of the US by this number:

The total estimated loss to GDP in one year due to COVID-19 if no specific additional measures to minimize the natural course of COVID-19 were in place

= 41,056,030 years x (per capita GDP of 2019) per year

= 41,056,030 x $65,116

= $2.67 x 10¹²

=$2.67 Trillion

Assuming again the US GDP of 2019, this means ~13% expected drop in GDP in 2020 relative to the previous year's GDP.

In Memoriam: Professor R. L. Brahmachary

On February 13, Professor R. L. Brahmachary passed away at the age of 85. I had known Professor Brahmachary since 1973. He was an impressive man who bounded with energy, his eyes flashed with excitement as he spoke. I often sought him out in his lab at the Indian Statistical Institute. He mentored me, and tried to bring a bit of discipline to my thoughts, edited my letters I was in the habit of writing to foreign scientists on their work while I was an undergraduate student in Calcutta.

Ratan Lal Brahmachary was born in Dhaka, Undivided India, in 1933. He was noticed by Professor S. N. Bose (of Bose-Einstein statistics/Boson fame) when he was an undergraduate student of Physics in Calcutta, a refugee from the newly divided East Pakistan with his widowed mother. On Professor Bose's recommendation, young Brahmachary went to do PhD in physics in Germany (Institut für Theoretische Physik, Universität Hamburg) shortly after WWII--neither Bose nor Bhrahmachary knew that German physics was in near ruins. Nonetheless, Brahmachary completed his thesis on relativistic field theory in record time in Germany (he published this in 1956 and 1957: "A generalization of Reissner-NordstrÖm solution I" & later "... II). At that time he received a letter from his mother that she was not well. Brahmachary left for India without completing the stipulated residence of 18 months on campus for qualifying for a PhD degree. So he never received his PhD, but had a solid amount of work under his belt worthy of good publications and a glowing recommendation from his German advisor (I don't remember who he was) and also professor Bose.

Brahmachary joined Indian Statistical Institute upon coming to the notice of its founding director, Professor Mohalanobis, the famed physicist/statistician who was once the Cambridge roommate of S. Ramanujan, the mathematics savant. He continued working on field equations (published, "A class of exact solutions of the combined gravitational and electro-magnetic field equations of general relativity" in 1958).

Very soon, Professor J. B. S. Haldane, the last of the English polymaths, joined ISI, and he influenced young Brahmachary's conversion to biology. Upon Haldane's recommendation, Brahmachary went to Paris, to work in Jean Brachet's laboratory, where he did pioneering work on demonstrating that there is a fraction of rather stable RNA in frog's eggs that appeared to be maternally inherited. This was entirely on the basis of fractionating pulse-labeled RNA into oocytes and eggs, at a time when one thought there were only two kinds of RNA--the mRNA (which was just discovered by Sydney Brenner, Jacque Monod, and Francis Crick, and the not-mRNA, which would soon be labeled as rRNA and tRNA by people in Jim Watson's lab. I am talking of 1958-1961.

Returning from Brachet's lab, Brahmachary went on a dizzying bit of activity, in which he worked with sciona, a protochordate, with Acetabularia mediterannia, and also common Indian snail, and showed evidence for the maternal inheritance of stable mRNA into the embryo. This work was collected together into one publication in a somewhat obscure journal, Progress in Biophysics and Molecular Biology in 1968, a copy of which I accidentally picked up in the British Council Library on Theatre Road in Calcutta, when I was a first year undergraduate. That was when I sought him out.

The city was in chaos at the time, with Naxalite, CPI-M, Youth Congress and CRP clashing in dingy lanes and young students disappeared every day. Colleges were closed on many days, classes cancelled, which gave me enough time to take the bus to ISI and talk to Professor Brahmachary and snoop around in his lab. When I moved to JNU in 1975, we kept in touch.

In 1976 he came to New Delhi on a review panel, but took this occasion to come and spend a weekend in my dorm room--we visited the Delhi Zoo and the ravines next to JNU looking for migrating birds. He had taken the slow train from Calcutta to Delhi--the Toofan Mail--because he wanted to estimate the breeding success of the Saras Cranes, the great migratory cranes that winter in northern India, by counting the number of nesting adults and chicks along the railway route. An ingenious idea.

He had by then visited East Africa (Congo, Rwanda/Urundi, and I think Tanzania) some four or five times to study mountain gorillas. Apparently a kind of gorilla he was observing ate only the leaves of the Mufumba tree (I still recall the name, which he pronounced with his characteristic gusto), which, he had determined, had extremely high content of ascorbic acid.

Soon after, he switched his research full time to the study of pheromones in tiger, and became an active player in tiger conservation in eastern India. He and the famous animal behaviorist George Schaller communicated frequently. In 1990, he published a report in Nature on tiger pheromones (Nature 344:26), which had as the main ingredient a fatty acid derivative that was also found in Basmati rice! Here is a clip on his intense dynamism and optimism, as he describes what science is like, at the time of his retirement in 1993. The interviewer is my daughter, who was a fifth-grade student at the time.

“Whence I am” The joy of multiple identities

An answer of sorts to Stephen Murphy-Shigematsu

The taxi picks me up at the blue hours. Blowing swirls of gray vapor in the air I shuffle in. “Airport?” He asks.

With a slight air of discomfort that exists between any two grown men who’d likely never see each other again, he eyes me with a respectful silence. The morning is crisp and fresh, but who knows how long has he been up in this shift.

“Where are you from?” I ask, trying to break the ice. He beams broadly and says, “Make a guess!” “Seattle, obviously,” I said with a smile. “Oh no my friend, you are avoiding the real question! Where am I really from?”

Where is anyone really from? As a fourteen year old, though born in a small city in India whose parents were both considered refugees from the freshly partitioned East Pakistan, though both had spent their formative youths in India, I did not fit in well with the local boys. I was always an outsider in a city where the insiders had lived for at least four or five generations. I looked at the national boundaries on a painted tin globe bought at the railway station, and thought of the invisible curvy planes that people imagine going up from the soil into the thin skin of air surrounding our planet, which then diffuse into confusion far below the troposphere. These imaginary planes had always seemed to me as arbitrary, as meaningless, as religion or nationalistic pride.

When I look into the mirror I don’t seen an Indian or an American; only brown eyes, slightly asymmetric, a wrinkled skin in need of a shave. I doubt if my daughter sees an Indian, an Australian, or an American either

Guessing where one is from is a game—trivial because of its superficiality and important at the same time because the answer might provide a clue to the person one might be. Sentient beings that we are, we instinctively go beyond the species identification by sight or smell as we encounter another individual. We try to make a mental image of the mind of the other—we try to guess, perhaps second guess, the persona, the biases, common interests, what might offend, perhaps even some idea of the stranger’s experiences. This is pure human curiosity—the one characteristic that has ensured our evolutionary survival despite the nakedness of our skin and our relative frailty in relation to those of other apes. Whether we ask, permitted by our arbitrary norms of politeness, or not—we cannot prevent ourselves thinking about it. We are curious apes.

Each one of us is a vector of identities: birth place, where we lived as a child, where we live now, ethnicity albeit its plastic boundaries, color of skin, how we speak, what we eat, how we dress, our belief systems, political persuasion, what books we like, whom we like, and so on. Each of us ranks the elements of the vector in a unique hierarchical order. Therefore, no two persons can probably match their respective identities, and yet we instinctively attempt to find the distance between our two vectors—because the result might crucially influence the outcome of our interaction. Possible friendship; a successful collaboration; a business deal; falling in love perhaps; avoid a cheat or a stab in the back; even finding something to talk about so as to rub out the boredom of an early morning taxi stint.

The question “where are you from” is one that is at once blatantly superficial as well as purely human; important for our survival and for functioning as humans.

To deny the existence of the question in our mind is to not look at the mirror to see ourselves as we really are.

In the mean time, having spent nearly half of my life in America, having grown up in West Bengal, having spent significant time in Northern India and in Australia, I still imagine myself from a little village in Bangladesh, by the side of a pond, where the evening light falls slowly, a fog might rise above the dark water, a bell might ring in the temple of the family deity, muffled puffs on the conch shell might float across the water and hordes of spiraling mosquitoes might rise from the amorphophalous bush near my grandparents' gravestones and swarm over my head.

I had been to that spot only twice in my life, separated by a span of forty years.

If I wrote that yesterday was an interesting day with the Grand Finalists at the Intel Science Fair, it would be an understatement.

A veritable collection of near geniuses in their mid-to-late teens.

I also got to test a little question that has been bothering me for a while...the impact of society on science.

Here's how I tested it. I took the division of mathematics as the subject population because mathematicians on average reach their heights starting around 21 or 22 years, and these kids are within five or six years of reaching this age. So they are a good choice for assessing their future potentials. I classified some 64 Grand Finalists in mathematics into two groups: Pure Math and Applied Math.

In no other discipline the difference between pure and applied is as clear-cut. A pure math is nearly always recognizable from applied math as a different beast from a mile away--a distinction not usually possible in any other discipline of science.

There were 30 pure math, 29 applied math and 5 that I couldn't classify unambiguously, so I had to eliminate these 5.

Among the 30 pure math kids, 20 were from foreign countries (Russia, Bulgaria, Iraq, India, China, Sweden, Germany etc) and 10 from the USA.

Among the 29 applied math kids, only six were from foreign countries and the rest 23 all from the USA.

By Fisher's two-tailed exact test, the difference in the distribution between the two groups (Foreigners over-represented among Pure Math and USA being over-represented among Applied Math) is statistically highly significant (P =  0.0006).

So we in the US influence genius kids to become applied mathematicians and elsewhere they are influenced to become pure mathematicians.

I am not making any value judgement here, but the effect might be lamentable in some respects: at this rate US might run out of novel directions in mathematics for application to practice were it to be that the rest of the nations conspire to secretly hide the output of their pure mathematicians! In this connection, it is worth reading a brilliant editorial by Uncle Syd written 16 years ago: http://www.sciencemag.org/content/282/5393/1411.full

Why do journals no longer publish hypothesis without validation?

In the past journals regularly published hypotheses.

The first Watson and Crick paper was little more than a hypothesis (The first sentence of that paper was: "We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.)."). So was the Corey-Pauling alpha-helix paper. 

The "one-gene, one-enzyme" paper by Beadle and Tatum was a hypothesis. The first DNA coding paper by Gamow was a hypothesis. 

Although not formally published, Crick's famed tRNA paper, which introduced the "wobble-hypothesis" for the third anticodon position, which allowed deciphering of the genetic code, was a hypothesis, was widely circulated among the practitioners. 

The central dogma paper by Crick was a hypothesis. The so-called French-flag model of morphogen gradient in developmental biology was a hypothesis by Lewis Wolpert. Crick wrote a paper in Nature in early 1970s on the probable physical size limit of morphogens, which was entirely a hypothesis (no morphogen was yet identified). The proposal that eukaryotic chromosome ends must have a special structure (specifically, a hair-pin, which some 15 years later was discovered as telomeres) was a hypothesis advanced by Jim Watson in the late 1960s in Nature. In 1964, Robin Holliday proposed the now famous Holliday junction model of DNA recombination, which could be directly tested some 25 years after the publication of the hypothesis.  The second realistic model  of DNA recombination, the so-called Meselson-Radding model, published in PNAS was entirely hypothetical.

In other areas of science publishing hypothesis was the norm.  

The famous Bohr's paper on atomic theory was strictly speaking a hypothesis (consistent with past data), the general theory of relativity was a hypothesis (proved a few years later by observing the bending of light past the sun during a complete solar eclipse). Schroedinger's equation paper was a hypothesis (it can't be derived). Plank's famous paper that introduced quantization of energy was a hypothesis. 

 I could go on and on. 

In recent times, journal editors and reviewers have generally and unintentionally conspired together to not publish hypothesis without validation, because of impact factor considerations.  A hypothesis without validation is hard to evaluate, and so it is risky for a journal to publish because it might be proved wrong. If proved wrong, the article would not be cited further, and this should lower the journal's impact factor rating.

For example, in early 1970s,there was a paper published in Nature entitled "A quantum mechanical muscle model" (by CWF McClare), which proposed that actin and myosin molecules generate force through a quantum mechanical "resonance" process, which turned out to be untestable (not incorrect, mind you), and was hardly cited (the untimely death by suicide of the author due to mental depression might have also contributed to the paper being not much cited, however). 

This does not necessarily need to be the case.  For example, the Meselson-Radding model of DNA recombination turned out to be incorrect in general (though there are some specific cases wherein it is likely true), and yet was widely cited because this (ultimately incorrect) model prompted a flurry of experimental and theoretical investigations.  

As Carl Popper, the preeminent philosopher of modern science, has shown (See, "Conjectures and Refutations" by Popper), hypotheses that are proven wrong are more useful hypotheses for the progress of science than are hypotheses that are difficult to test. 

So when the mud settles, we might look back to this age and conclude that the current journal trends might indeed have impeded the progress of science!

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 a full page article on Khorana and his discoveries, and how he had 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 using 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.

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.

A sense of time

Raymond Depardon’s iconic photograph of a couple with their son on a scooter in Saigon, 1972, brings back a rush of imagery of those days. A sense of time, perhaps, has been missing in my life.

I used to suck in history. I was more interested in Fourier transform and Maxwell’s demon and pseudouridine in tRNA-gly.

The road to immortality seemed in those days to be paved with one scientific insight that survives the test of time. A delusion that comes of not knowing the history of time.

Absence of Heroism and the Road Inward

The debt crisis, largely artificial because it is not that the US government is unable to pay its dues but that it is not allowed to pay, is a failure of the political leadership to be rational.

This emerging trend of irrational governance is apparent in the US, Japan, and in Europe (see “Turning Japanese” The Economist July 30, 2011).

In the US at least, this is partly the result of electing into office a vocal minority of fiscal extremists, the Tea Party representatives. But it would be overly simplistic to stop there. One needs to probe the reason as to why the extremists got elected in the first place.

In a psychological sense, all extremists appear to suffer from various degrees of delusion of grandeur, a narcissistic view that the ills of the society can be bettered by making heroic demonstrations.

We in the US have had little occasion to be heroic lately. We fight a war for which no sacrifice has been required for the vocal middle class, because we have let the poor and the minority to die in it; we get a tax rebate instead. The face of the war does not leave much room for heroism either, because we fight an enemy that is not afraid of death as the ultimate sacrifice—a supposedly Western prerogative that has received much mythological support in our culture. What is worse, we are now led by a black intellectual, who is often identified as a half-Moslem. Racial inferiority and religious antagonism are the most difficult cultural instincts to overcome. If the media are to be believed, our businesses are increasingly run over by the Chinese and the Indians; Latinos are on the rise; we don’t even have a rocket science any longer. Where should we now vent our delusions of being a hero?

The answer presented to us is simple: dismantle the status quo. This Samson-like act of narcissism appears preferable even at the risk of collapsing the institutional dome of legitimacy above us.

My DNA: The Rashomon Factor

So here I am, having both paternal and maternal ancestries traced to the central Asian mountains and valleys, to the Hunzas and the Persians. How did I get here?

The 64 : 36 admixture of European and Asian polymorphic markers in my genome has evidently been preserved over many generations, because there is no European history known in either of my lineage within at least 10 generations. Were it the case that there was a single homozygous European who married a homozygous Asian, then their child would have both markers. Since there are many more Asians than Europeans in Bengal, and if all were homozygous Asians, then in every subsequent generation there is an overwhelming probability that the descendent of that lineage will breed with a homozygous Asian, thus at every subsequent generation the proportion of European markers will be halved (if the markers are all unlinked). This is akin to successive back-crosses with the Asian stock. Thus, after 10 generations, 2^(-10) or only 1 in approximately 1,000 or 0.1% of the European markers, if all are unlinked, will still exist.

The actual proportion might be somewhat more, because of linkage and linkage disequilibrium, which can be calculated, which will lead to loss of heterozygosity at the rate of (1 – r)^t, where t is the number of generations and r is the recombination frequency between marker pairs. But the frequency of retention under the above simplifying assumption will be far below 64%. This is because r for most marker pairs (~700,000 markers if randomly distributed over 23 chromosome pairs) would be approximately 0.04 for human chromosomes (~1 centiMorgan per megabase pairs). Therefore, the erosion will be approximately at a rate of (1 – 0.04)^t, which translates to 0.96^t. For 10 generations, we need to divide 0.1% by approximately 66%, which leads to a retention of 0.15% of the heterozygous markers on average. Although I arbitrarily chose 10 generations (i.e., t = 10), it is probably true that anyone in my ancestry mating with a person homozygous for European markers goes far deeper into the past because the very first Europeans in historical times came to Bengal only about 20 generations ago. The overwhelming conclusion is that my assumptions are incorrect. Where are they incorrect?

The main assumptions were that there was one rare mating between a European and an Asian, and that most people in Bengal are homozygous for Asian markers. Both are nearly certainly incorrect.

The heterozygosity of markers over many generations, in the absence of direct natural selection due to selective advantage (unlikely because it would predict an enormous selective advantage to rare heterozygous markers), is probably the result of selective breeding or kin-selection—the inevitable result of the caste system in India. It is because of this selective breeding and kin-selection that the heterozygous markers were conserved over many generations. Therefore in a moment of somewhat dampened literary inspiration, I am compelled to moderate my romantic scenarios of a Hunza couple eloping together and settling in Bengal, or a wayward Yemeni sailor marrying an Asian woman.

The reality is likely to be quite different. The most likely scenario is that my ancestors descended from individuals in south central Asia, the inhabitants of Afghanistan, Persia, and central Asian plateaus at some remote Vedic or pre-Vedic time, through selective marriages among a small number of communities who rarely married into the indigenous Asian stock. This ensured that the members of these communities are all highly heterozygous. If nearly all of these people are heterozygous at most markers, then the chance that any individual will be heterozygous at any marker is nearly 50%. The observed 64 : 36 distribution of markers is close enough to this expectation, if one assumes a slight bias towards marrying into families with more European (i.e., Brahmin) than Asian markers. Thus, for my ancestors, intermarriages largely restricted within the community in most generations with only rare breeding with non-Brahmins (having somewhat higher frequency of Asian markers) is a good explanation for my lineage.

This scenario is well attuned to an oral myth of the Vaidya or Baidya communities of Bengal. Tradition has it that the ancestor of the Vaidya caste was the result of an illegitimate union between a Vaishya woman by the name of Birabhadra and a Brahmin Galava Muni. The latter was reputed to be a Vedic Brahmin, apparently from the area currently known as northern Pakistan/Afghanistan (but see also: this). The child born became known as Dhanavantri. Since the child had no legal father, (s)he belonged to the family of his/her mother. Of course that is only one of the narratives, and there are several competing narratives. One fact is clear: the Vaidyas generally intermarried among their own communities, thus maintaining their genetic heterogeneity.

This is all a remarkable congruence of oral tradition and science, perhaps even more interesting than my romantic story of the eloping Hunza couple.

My DNA: My Ancestry

My DNA result is out. I have 64% European and 36% Asian markers, which put me squarely in the Indian subcontinent, somewhat more heterogeneous than the upper caste Brahmins who have roughly 80% or more European and ~20% or less Asian markers on average. This is not surprising, because I am not a Brahmin, but am supposed to be a Vaidya, or, historically a class of Brahmins who were shunned from wed locks with other Brahmins for either reasons of envy, for accepting fees for medical treatment (you see, the Brahmins are supposed only to receive the gifts of gratitude and never a fee for labor) or, more likely, because a wayward Brahmin in my remote ancestry fell for a lower caste boy or girl…

I seem not to have any known marker for any debilitating disease, or even a carrier of any known disease markers. I might be more than average sensitive to Warfarin, a blood thinner given in cases of blood clot diseases or stroke, too much of which could cause bleeding, and knowing this the doctors would be cautious in case they catch me on a stretcher one of these days.

I seem to be a slow metabolizer of caffeine, which explains why I spend so much time in cafés.

So far that is almost all I know that is of significance to my health…the rest are all typical.

The real fun begins when I look at my maternal and paternal ancestries.

Maternal ancestry is provided by the mitochondrial DNA sequence, which rarely changes, and is always contributed by the mother (never the father). Thus my mitochondrial DNA ancestry forms a continuous chain up the line of my mother’s mother’s mother’s mother’s…..mother the Eve in Africa. The same with yours.

The funny thing is that the mitochondrial DNA does change sometimes, but very very rarely. When it does, and the mitochondrion still functions, then the mutated (changed) mitochondrial DNA “diverges” in sequence a little bit from the previous generation, and this changed sequence is then inherited down the line, until all females in that line have all male children, in which case the mitochondrial DNA chain is annihilated. This provides a way to sleuth out the maternal ancestry of the current population on the earth because if my mitochondrial DNA is related to yours then we must have shared the same maternal lineage, and by checking this we can actually chart the migration patterns of groups of people across the globe.

My mitochondrial DNA belongs to the so called haplogroup R6, which is a minor part of a very ancient lineage R that arose in Southeast Asia not long after the first human migrations out of Africa into Asia, who then migrated to Europe, Australia, and the Americas. The haplogroup R arose some 60,000 years ago in Asia, before migration to Europe, Australia and the America; therefore it is found in all these places except in Africa. R6 is a variant of the the original R. R6 is quite rare, and is now found most frequently among some tribes in the mountainous regions of Afghanistan-Pakistan-India border and also in small pockets near Tamil Nadu of southern India and in northern Sri Lanka (source: Metspalu et al. BMC Genetics 2004, 5:26 doi:10.1186/1471-2156-5-26).

Therefore, a woman in my distant ancestry from either the mountains of Kashmir or Afghanistan region, or from Southern India, or one of their common ancestors, must have migrated to the plains of north-eastern Bengal, perhaps over many generations through bearing daughters who migrated slowly, or perhaps it was a single romantic affair that led to one couple eloping together and settling in Bengal, producing a daughter who bore another daughter, and so on. While eye and skin colors are not at all known to be inherited through the mitochondrial DNA—the mitochondrial DNA merely asserts the maternal inheritance line—other genes that do might also have descended from this couple. My maternal grand mother (who was born in north-eastern India in current Assam, in the Dibrugarh area, so far as I recall), from whom I must have inherited my mitochondrial DNA, had bluish green eyes and fair skin, something like what is seen among the tribes of Kashmir region of India, Afghanistan and Pakistan. But the couple might also have come equally likely from southern India, where the incidence of bluish-green eyes is rarer though.

How about my paternal line? This is even more interesting. My paternal line, derived from my Y chromosome, which was given to me by my father (by his father, and so on up to some Adam in Africa), who were all from the Chittagong region of current Bangladesh, belongs to a very rare group H1a*. The haplogroup H, from which H1a* is derived, is mainly restricted to the Indian subcontinent, mostly among the tribes of India and is rarely (~10%) found among the Brahmins, but also its variants are found among the Central Asians including the Afghanis, the Romani gypsies of the Balkans, some central Asians and Iranians, among the Saudis (including their royal families), and in Yemen, and a somewhat distant line in Cambodia/Vietnam. But if one looks more closely at the specific rare variant H1a*, then one finds the closest similarity to a group of "Balkarians" (a Turkish people of the Caucasus mountains), southern Iranians, and Serbians, all of whom contain the mutation M82 in H1a subgroup that is the closest ancestor of H1a* which is mine. Further derivatives of H1a, such as H1a1, H1a2, and H1a3 are found in Nepal, and Southeast Asian countries including Bali, Indonesia and Cambodia, but these are in parallel lineages to that of H1a*, all derived from the common H1a, which likely originated in Northern India or Central Asia.

Whatever I know of my immediate paternal ancestry, my great great grandfather was childless, and adopted a child who was my great grandfather. The only surviving photograph of my great grandfather shows him to be a man of about 50, who was reputed to have had greenish brown eyes, as did my father and as does my daughter.

Was there a lost sailor from Yemen who married a village girl in southern Bengal during his oceanic voyages along the spice route? Or was there a Balkarian soldier in the army of Babur who descended on the Bengal delta and married a woman who produced a son who provided the Y chromosome that ultimately gave rise to my great grandfather?

When I download the entire DNA marker set of my genome (some 700,000 of them) and do principal component analysis (PCA) against all known DNA markers of the world, my DNA markers appear to cluster on the first and second eigen vector spaces right near where the DNA of the indigenous people of central Asia (north of Afghanistan), closest to the Burushos of the Hunza valley of Pakistan-Afghanistan, appear to originate.

These are the stuff of which epic novels are made!

----
*The above account, as might be expected after a reading, is colored with quite a flight of fancy. To get a slightly more nuanced scientific perspective, read the next entry, My DNA: The Rashomon Factor.

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!