Mind reading, big pictures and little details

The one thing about being a postdoc is that you’re no longer green behind the ears, and have developed somewhat of a decent bullshit detector. You’re also a little less in awe of your boss or most other independent investigators. And hopefully most postdocs become rather good at reading between their lines when discussing projects or experiments with their bosses. At least, when the boss says “this won’t work”, or “just go and do this”, you don’t just take their word for this.

Here’s my thumb rule for those statements. If your boss has this really nice but far fetched idea, and is really excited about it, he/she will say “these experiments are easy, you need to go for it. All you need to do is purify a couple of proteins, throw in some reaction mixtures and read your data”, you can almost be sure that the experiments will involve about two years of backbreaking work involving 16 hour workdays that go on for months, and plenty of labor in the 4 degree cold room. On the other hand, if you go up to your boss and discuss a proposal/idea you have come up with and the boss says “that’s way too hard, and I don’t think it’s going to work”, it means (a) the boss isn’t really interested in that idea but wants you to work on his/her crazy idea (see above) or (b) hasn’t really thought much about it since you are the one who has come up with the idea or (c) both.

One sometimes wishes for those early days as a rookie graduate student, in awe of the boss, naïve, gullible and completely willing to try the most insane or undoable experiments possible as a thesis project, only because the boss is such a famous scientist, he/she has to be right.

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On a related note, you can safely assume the thumb rule that any senior investigator who is exceptionally creative with big picture ideas (and who hasn’t done benchwork for 20 odd years) is going to propose the maximum number of “that’s easy” experiments that hang on a slender thread of a hypothesis (the kind that goes “if this were true, then this and this and this will be true, and so this story will be awesome”. Except that the very first “if this were true” is a big if). You’re also certain to be doomed to some years of crazy and hard experiments that are going to tell you that the first “if” is false.

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The phenomenal growth of molecular biology through the nineties and now the past ten years has made many biological experiments amazingly easier, and I’m very grateful for that. But I think it has done enormous damage to good, quantitative biochemistry (and biology in general).

The beauty about a lot of modern molecular biology is that it is carried out using kits made by companies, which the average trained monkey can execute. You don’t need to know most of how it works. Also, the reagents and kits have been made so good that you don’t even have to worry too much about being quantitative in your experiments. They’ll usually work (somewhat). You can throw in a little bit of an enzyme or lots of it, or a little bit of salt or lots of it, use approximate concentrations and approximate conditions and still the experiment works. Here’s a real example. Set up a PCR reaction with a Taq polymerase kit, good primers and a plasmid template. Now spit into that reaction tube, double the volume of the reaction with your saliva, and then start the reaction. I can pretty much guarantee that the reaction will still work.

What this oversimplification of molecular biology has done is it’s created (or is creating) a pretty large number of extremely sloppy biochemists. I see far too many undergraduates or graduate students who (a) don’t really understand the concept of molarity, normality, salt concentrations, pH, metal or buffer effects and (b) also think that just because they think it doesn’t matter, it really doesn’t matter. For example, they think that they can purify a protein on an ion-exchange column using either a 100 mM sodium chloride solution or a 200 mM sodium chloride solution and it won’t matter much. Or their buffer can be at a pH of 6 or 7 or 8 and their protein will show the same activity. And most of them don’t think pH meters need to be calibrated (and don’t know how to calibrate it anyway).

All of this, combined with the extreme confidence of today’s kids, makes for very interesting presentations in student seminars where they show rubbish experiments, and then authoritatively state “I think our hypothesis is wrong” followed by “this company that supplies us with X reagent sucks. My experiment didn’t work because I think the reagent has gone bad”.

If you’re going to make a statement like that, you need to back it up with data. But who needs data these days?

We need some more hardass investigators, who won’t be scared to crack the whip.

Enjoying science podcasts

Ok, I've been very slow to jump onto the podcast bandwagon, mostly because I rarely use my mp3 player these days. I also didn't think I'd be able to pay attention to the podcasts while doing other things, and thought I'd hear about important science breakthroughs anyway, and would rather read the paper.

I'll have to eat those thoughts.

The podcasts from Cell, Science and Nature are superb. I've just come to the conclusion that they are a great way to find out about some of the latest breakthroughs in diverse areas of science. I used to be very good at at least scanning through the latest issues of all three magazines, and a few more, but sometimes it is hard to keep up with them all. The podcasts compile some neat work not just from the main journals, but also from other "family" journals (for example, the Cell podcast includes some interesting stories from Molecular Cell or Cell Metabolism etc).

And they are perfect to listen to in the lab, while number crunching on the computer, or catching up on email, or while doing trained monkey experiments like plasmid preps.

I'm hooked.

This week's Nature podcast in particular is fascinating, with everything from PZ talking about squid eyes to economist Jeffery Sachs and the "crowded planet challenge". Go read.

The beauty of compromise

Too many things have kept me away from regular blogging, so apologies to you all. I prefer posting essays, all of which take time to write (and so often remain unwritten, and unposted). Perhaps a better strategy would be to post shorter (but hopefully still sufficiently interesting posts), trying to post longer articles when time permits. Lets see how that goes.

*****

Meanwhile, here's a superb essay by one of India's foremost contemporary historians, Ramachandra Guha. Here he explores some of South Asia's well known conflicts; in Kashmir, in Nagaland, the formation of Bangladesh, the Narmada movement, and the Sri Lankan civil war, and shows how inflexibility and dogmatism of contending parties have dragged on and amplified disputes. Here's an excerpt:

Now, a group of engineers based in Pune advocated a compromise solution. Given that the dam had already come up to a height of about 260 feet, clearly it could not be stopped. But its negative effects could be minimized. Thus, the Pune engineers had designed a model of a dam smaller than that originally envisaged. The reduction in height would greatly reduce the area to be submerged, yet retain many of the benefits that were to accrue from the dam. The drought-prone regions of Kutch and Saurashtra would still get water. At the same time, many fewer families would be displaced.

Unfortunately, the compromise was rejected both by the Gujarat Government and by the NBA. The former insisted that the dam had to be built to its originally sanctioned height of 456 feet. The latter insisted that the dam must be brought down. As the Andolan's slogan went, 'Kohi Nahi Hatega! Baandh Nahin Banega!' (No one will leave their homes, for the dam will not be built). But a good chunk of the dam had already been built. Hundreds of tons of concrete had already been poured into its foundations. And thousands of families had already been displaced.

While the ability to compromise will certainly not guarantee results or solutions, it is often undervalued by too many policy makers or leaders. Anyway, get your cup of coffee, sit down and read the complete essay here. It is well worth your time.

Book review: HomeSpun

It is hard to resist the lure of a sepia tinted book cover with a black and white photograph of a couple with that glazed, nostalgic look on their eyes. The cover almost suggested something vintage, perhaps timeless. That was more than enough for me to start reading HomeSpun, by the debutante novelist Nilita Vachani.

The book starts with the death of Nanaji, and a scene of mourning. And just like that, you plunge into the lives of different families, and a story of different ideologies, of conflict and reconciliation, love, relationships, marriage and death, all narrated by Sweta Kalra, while the characters slowly emerge as the chapters roll on. Parallel stories develop, all of which you know are interconnected through Sweta. And while the book starts with tragedy, and has plenty of tragedy within, it takes us for a ride without plunging into darkness or depression.

The book is part coming of age, part exploring the complexities of human relationships, part conflict, and part exploring the idiosyncrasies of human nature. There is the story of Nanaji, and his struggles as a revolutionary and freedom fighter fighting against the British for an independent India. He tries to live an extremely principled life, following the idealistic example set by Mahatma Gandhi. The problems of the world and day-to-day life remain somehow esoteric to his mind. Yet his wife, Naneeji, is a polar opposite. She loves her jewellery and silk, and she wants herself and their kids to lead a good, comfortable life, the life she believes that a senior government official (which is what Nanaji becomes after independence) should live. Their lives are spent in open conflict, sometimes bitter, sometimes petty. You know their every relationship is strained. Yet the book starts off with Naneeji wailing and bemoaning the loss of her “wonderful” husband.

Then there is the story of the Kalras, most importantly Ranjit “Ronu” Kalra. His father is a sub-inspector of police. Sub-inspector (later superintendent) Kalra could be described with clichés like conscientious, simple, earthy. The apple of inspector Kalra and his wife’s eyes is their son, Ranjit. A chance encounter with a film producer, who happens to adore Ranjit’s curly 5-year old locks, changes Ranjit’s life forever. He goes on to become the greatest child star of the black-and-white era transitioning between silent movies and sound dubbing. And while Ranjit’s brief celluloid career takes off, the author gives us a hilarious and fascinating view of the film (“phillum”) industry of the time, filled with histrionics and glycerine, political sensitivities, charlatans and bigger-than-life characters. Ranjit’s career as India’s favorite kid ends abruptly with him growing up, but his childhood stardom stays with him for life, and in a strange way directs his fate as an adult. In this mix enters Anamika (Anu) Reza, a spirited teenager, Ranjit’s first girlfriend and true love. Their lives entwine, and they go through passion and longing and separation. Both characters are immensely likeable, yet as different as chalk and cheese. Ranjit is almost immediately endearing. He has the burden of having to grow up as a former child star, and yet remains shy and simple. He’s one of those people who may have dreams, yet lives by avoiding conflict, and trying to keep everyone happy, never confronting tradition. Just by being with the fiery, modern and liberal Anu throws him into a cauldron of thoughts and conflicting emotions. When the time comes for him to make his decisions, he is unable to go with his dreams. His father decides his future, and soon Ranjit heads off to join the air force to become a pilot he would never have become on his own. In contrast Anu’s life, just like her, remains turbulent and feisty and fiercely independent, and she lives on her own terms without holding regrets.

In between all these stories is the pivotal subplot of a small but important character, Ranajit’s friend and fellow officer, Dusty, and the war with Pakistan. And then there is Sweta herself, mostly as a frumpy, slightly overweight but bright and curious girl, with usual and atypical growing up problems. There is her relationship with her beloved Nanaji, and Nanaji, or her mother, and most importantly, Anu.

The author, Vachani, takes us through a whole panorama of events and emotions, and the story progresses beautifully through the last days before independence, the turbulent fifties and sixties, and more contemporary India in the seventies or eighties. We start with tragedy and the death of Nanaji, and as the book progresses, the different stories interweave, interspersed with gentle or dramatic twists. “Homespun” is almost a perfect title for the book, the elaborate plot weaves through a post-independence middle/upper middle class India, and the lives of characters you understand and empathize with, or often relate to. And every one of the characters is beautifully developed and utterly believable. In between the characters, the author explores the myths and stories that we hear about the freedom struggle, or the war with Pakistan (through Anu); myths that are almost always rosy. What lies beneath those tales? Who actually won the war? How many people died? And how did they die? My only complaint with the book was the way the relationship of Anu and Sweta develops, and the slightly predictable direction it heads towards. But that is just a minor quibble with what was a thoroughly enjoyable read, and just the kind of story that will make a terrific movie.

Encouraging women in science

There’s been plenty of talk about difficulties women in (academic) science face, and how there are very few women scientists at senior positions in academia in most universities. Most major research universities now admit that there are difficulties women face in research that have nothing to do with their scientific abilities. Subsequently, most universities now say they are actively trying to rectify this, and look to hire more talented female faculty. Departments try to have career workshops for female graduate students and postdocs to encourage them to stay in academia, there are endless efforts to recruit more female students and so on.

All this is well and good, but are there some really simple things that universities could do to rectify this that aren’t in the spotlight? From what I can see, at least in the greater biological/biomedical/biochemical sciences there are plenty of female graduate students (approximately a 1:1 male: female ratio). This more or less remains when you start off as a postdoc (a few years of postdoctoral work is pretty much required before you can get that assistant professor position). But by the time you look at senior postdocs or junior faculty (3-4 years down the line from a starting postdoc), there are far more men than women. Of course, it doesn’t take a genius to figure out that most women have kids between their late twenties and mid thirties. That’s when they are most likely to be in the early-middle stages of their postdoc. There’s nothing new in this statement, we all know it, as do most universities. So a number of universities now say that they are working towards policies that make it easier for women postdocs or junior faculty to have kids.

But I was quite unaware of how bad the present policies are though until recently, when I was chatting with a postdoc friend of mine who is pregnant. Now, the three things that will make it easier for a female postdoc to have a baby are (1) the ability to easily take time off/maternity leave (2) the financial means to afford a baby (those things are expensive) and (3) a good medical insurance policy that would cover most of the massive medical expenses having a kid incurs.

Unfortunately, apparently most major research universities still have lousy policies for all three of those. Here’s how it works. Most institutes have a policy stating that a female employee cannot be fired if she decides to have a baby, and also that she will be allowed to take the required time off post childbirth. That’s the good part. But here’s how the fine print goes. The only paid leave the person is allowed to take is the leave that she has accrued over the year. Postdocs (at least here) are technically allowed to take 12 days of vacation time, and week of sick leave a year, and there’s no roll-over policy for holidays not taken during previous years. So that gives a grand total of less than three weeks off. There isn’t a concept of overtime/leave accrual for working weekends; all you can get credit for is if you work on public holidays (probably half a dozen for the year). That’s it. Subsequently, if you need more time off, you can take unpaid leave for a maximum of 12 weeks.

You might argue that the option of taking unpaid leave for 12 weeks should be sufficient; after all, you shouldn’t be paid for not working. That’s ok, except that the salaries/fellowships of postdocs aren’t that high in the first place (some might call it unreasonably low). So, since you’re paid a pittance for endless hours as it is, the least you might hope for is continuing to get that salary while having a baby, so that you can take care of points (2) and (3), the financial details.

Which leads to point (3), medical insurance. A lot of postdoc researchers in the greater biological sciences work in premier medical schools/centers across the country. An outsider might be tempted to assume that medical costs for an employee of a medical center would at least be subsidized. Invariably that isn’t the case at all. Students and postdocs usually are offered a mediocre insurance policy, fine for minor ailments, but not that great for extended medical care. Most postdoc policies pay only about 75% of the medical costs (and the remaining 25% runs into thousands of dollars). Students or postdocs don’t get any benefits even if they choose to get their treatment from the same medical center they work in.

Sucks, doesn’t it?

These seem like rather obvious reason why a lot of women decide against plunging into academic scientific research careers, when just about any job in industry or even teaching offers better policies and benefits. Here’s one suggestion for NIH. Come up with a policy that states that all female postdocs who have their salaries paid by NIH grants must get 12 weeks of fully paid maternity leave, and flexible work-hours for 6 months after returning to work. And universities can start coughing up a little bit of money on better health insurance policies. Finally, it makes no sense for universities with major medical centers not providing any subsidized health care to their own postdocs and students in their own medical centers.

Obviously, this alone isn’t going to create a flood of female scientists wanting to spend their lives in academia, but I think it certainly might help.

Now these suggestions are fairly simple and easy to implement. So, if it is that simple, why hasn’t it been implemented yet? And I’m familiar with policies only in a handful of universities in the US. What’s it like in other schools? Other countries?

Rejection letter

(Hopefully this will be a prelude to more regular blogging)

I just got back from an excellent seminar by Randy Sheckman. Before he started talking about his research, he commented on how some people react angrily upon receiving rejection letters from editors of journals who decide not to publish their research (Sheckman is now chief editor of PNAS). And then he put up a slide with what must be the ultimate response to an unfavorable review, and had us in splits.

Sheckman attributed this priceless quote to George Bernard Shaw (though I googled it to discover that it was Max Reger who wrote this letter to a music critic). Anyway, here’s the quote, the all time best response to a rejection letter.

“I am sitting in the smallest room of my house. I have your review before me. In a moment it will be behind me.”

Goodbye Arthur C. Clarke

(Apologies for the infrequent posts, and this may continue for the next couple of months. But I’ll post when I can)

Arthur C. Clarke’s death yesterday didn’t really come as a shock or surprise to me. The man was over 90 years old, so it was time. But his death did trigger some fond memories of his books, and the influence they had on me.

I got introduced to science fiction probably in my very early teens. But that was mostly through the “classic” science fiction writers, like H.G. Wells and Jules Verne. Verne in particular was (and remains) a huge favorite of mine. His stories were all about adventure, and to a teenager with an over imaginative mind, little could be more exciting than going off to the center of the earth or crossing oceans in a sea-monster shaped submarine. But somewhere around then, I decided that I wanted to read some novels where there was more science. At the time “cool” science meant space, so I wanted something to read that had space in it. Science fiction used to be hard to come by in those days, but luckily for me my school had a library well stocked with fiction. While rummaging through the shelves of books there, I came across a hardcover book which had a picture of a meteor and some planets in the background, with the irresistibly intriguing title of The Hammer of God. Pretty soon I was devouring the story, and I vividly remember being rather taken in by the Indian theme that ran in the background. A meteor named Kali bound to destroy earth seemed particularly apt. But I was more struck by the fact that many of the characters seemed to be of Indian origin (the hero of that novel was Robert Singh). That was perhaps the first time I had read a book by a non-Indian author where important characters had Indian names, but more importantly, their nationality didn’t matter. In other books by western authors, if at all there was a character with an Indian name, that character would be particularly Indian and often pander to some stereotype. But here the nationality or ethnic origin didn’t matter. The person just happened to have an Indian name, and it wasn’t the least bit odd. I thought that was just the way it should be.

That said, when I finished reading “The hammer of God” I wasn’t particularly overwhelmed. It was an interesting book, and kept me engaged through its pages, but nothing more. Still, it had been sufficiently exciting for me to want to read another book by Clarke. Rendezvous with Rama followed, and that book left me far more interested in the genre. From there it was but a few steps to exploring the worlds of Clarke, Asimov, Franz Herbert, Philip K. Dick and so many more. Science fiction became a wholly enjoyable part of my reading habits, and sometimes a valuable source of knowledge and information. And yes, I realized there was more to space than warp-speed, Captain Kirk and death-stars.

Of course, writing about Clarke without mentioning “2001: A space odyssey” is futile. Surprisingly, I’ve never read the book. Through high school and college I filled my head with trivia about the book and the movie, and the naming of HAL and whatever else, but some how never got around to reading the book. But I did see the movie in a most atypical way. Roger Ebert, the noted film critic, hosts what he calls “Ebert’s overlooked film festival” in the little college town of Champaign-Urbana, Illinois. In the year 2001, I actually went to this gem of a film festival, and was treated to a superb selection of films of Ebert’s choice. One of the highlights of the festival was, yes, a screening followed by a discussion of Kubrick’s “2001: A Space Odyssey”. “Odyssey” and Urbana of course had the deepest of connections, as in the book the computer, HAL 9000, becomes operational in the HAL plant in Urbana, Illinois (don’t ask me how I know that without reading the book. It is essential Odyssey trivia). I watched the movie, mesmerized, almost hypnotized by the surreal rolling colors and visuals of the movie, and the hypnotic voice of HAL 9000. In between I remembered scenes from “2010” (which I had seen earlier) and wondered about how Chandra, the Indian scientist who creates HAL, became a white dude in the movie. The discussion that followed the movie was unsurprisingly fascinating, since the room was filled with movie buffs and science and SciFi geeks, a dozen computer scientists who felt possessive about the movie (because Chandra and HAL were fictionally from Urbana-Champaign), and a benignly portly Ebert lording over all proceedings.

That was the last time I saw or read something by Clarke. I hadn’t read a book of his since then, and the only other time I thought about him was when I was with some friends and the conversation meandered towards the utility of space flights and then to how satellites (in a geosynchronous orbit) changed our world for ever. My only contribution in that discussion was that the geostationary orbit of satellites are in what is now called the Clarke belt. The man, like all great science fiction writers, was a visionary.

Today Arthur C. Clarke is dead. But thank you for playing a little role in nurturing and directing my fascination for science.

Saying it as it is

I’m trying to figure out which system is better.

Growing up in India, I realized the "educational" system had a wonderful way of killing any semblance of self-esteem and confidence in most kids. A very large fraction of the teachers out there had an uncanny ability to grind a student’s opinion of oneself into dust (tossing in a whack or two on the head as a bonus). Except for a chosen few in a class, most students were reminded in numerous way of how utterly incompetent they were. Every child was certainly not “gifted”, except in the eyes of their extremely adoring parents. Even there, a number of parents would publicly state how worthless their kid was. In college, you’d routinely be reminded that you were no better than an earthworm lost in the sand, ready to be crushed under some heel. Professors would look at you with an expression that read “you are a state topper and this is the best you can do?” (or would sometimes even actually say that). Most of our grades in college weren’t artificially inflated too much. If you sucked, you flunked the course, simple as that. And then you’d be clearly told that you sucked, and you’d have a better future selling peacock feathers at the railway station. A majority of the students’ grades were what the majority should be, average. In the end, you came out of the system typically underestimating your own abilities. You either were resigned to a life of mediocrity, or would strive insanely hard to be that much more successful. I’m not sure how many people have come out of college in India with such low self esteem that it took years to undo. Unless of course you went to an IIT. In that case you really believed you were special even if you flunked half your courses while you were there.

At least, I think it was mostly like that.

Anyway, when I came to America years ago for grad school, I learnt pretty quickly that things were quite different on this side of the pond. Most kids seem to have gone through school and college generally being told that they were wonderful and unique, or “gifted”. Grades in courses seemed hugely inflated, and students seemed particularly prone to what can only be described as whining. A’s seemed to be handed out like free seminar pizzas, and the rare professor who really spread his/her grades out over a median distribution was labeled a hardass. This extended to how you spoke to students as well. A lousy student could never be told that he/she sucked, and had chosen something he/she had no aptitude for. Extreme PC is the rule here. Early in grad school, we had to spend a couple of quarters being teaching assistants. Half my students did poorly in the quizzes I set (strictly from the material at hand). I didn’t give them any freebies. I got lousy ratings as a TA. That taught me a lesson. The next time I was a TA, I handed out soft quizzes, played “pharmacology jeopardy”, brought Halloween candy to class on Halloween, and told my class that they rocked. That won me rave reviews and an insanely high score of 4.6 out of 5 as a TA. While most undergrads would go away to get a real job, some of them would actually come to grad school. There some would discover that they were utterly incompetent, had no lab skills, couldn’t plan an experiment, and even if they did, couldn’t execute it. This would drive their mentor nuts. In my case, while supervising some particularly incompetent rotation students, I’ve learnt to just walk out of the room, take deep breaths, rip a sheet of paper, and come back and smile. And then a few of them might ask you for your “honest opinion of their abilities” at the end of their stint in the lab. “Honest opinion” means anything but that. You’re supposed to be smiley and polite and say how they really have great potential, and their flaws (if any) are so minute that they were practically perfect. If you say they sucked, they’re guaranteed to go about ensuring your reputation as an unreasonable a****le. After all, they came through college with straight A’s and no one had ever told them they sucked ever before.

The good in all of this is the great amount of self-confidence and ambition most students have. But the flip side is a serious confusion of ambition and ability. They aren’t the same. There aren’t any pretty gold stars for doing something, making a mess of it, not trying hard to get it right (or correcting your mistakes) and then whining about how tough it is.

So, having written down these thoughts, I’m still trying to figure it out. Is it better to go through a system without any mollycoddling, to come out of it diffident, overcautious, sometimes insecure, or entering the world full of ambition, but being sometimes incapable of facing reality?