Friday, September 28, 2007

The value of failure

It is an interesting life being a postdoc. One big difference from being a graduate student is that you do start to look at life in science a little differently. Contrary to what many people accuse me of having, life as a postdoc isn’t all fun and games, and there are plenty of stresses to cope with. Sure, you have a PhD and aren’t worried about graduation, but there are plenty of other things to worry about. The postdoc time is supposed to be that transition towards a “real job”, and while it used to be a road taken only for people interested in a future in academia, it no longer is so. The past two decades have seen a surge in science spending and growth in departments across universities, but more recent numbers are depressing. While the numbers of postdocs have increased many fold, the number of faculty positions haven’t. So, there are far fewer jobs that a postdoc has to compete for in universities. This leaves industry and startups (small biotech companies) as options for many of us.

Which brings us to the point of this post. Now, particularly in these ultra competitive times, a postdoc requires a substantial amount of high profile work in order to get that coveted faculty appointment. “High profile” can mean a couple of things; the first is work in an extremely “hot” field of research. Something like stem cells (and if you can throw in some more hot topics there, like micro RNA expression regulating ubiquitination that in turn controls histone methylases, all of which controls cell fate, then you are golden). But these areas are obviously ultracompetitive, and often become “hot” when the field has matured a little bit. So, if you enter it at the top of the wave, you are most likely to have to compete with too many people in the field, and may not be able to carve out a successful academic career. However, working in “hot” fields do sometimes give the postdoc the (illusionary) security of believing that even if her work isn’t pathbreaking, a couple of solid publications and mastering of some techniques will be sufficient to land a job in industry.

But there is a second road some postdocs choose to take (and I like to think of myself as one of them), to work on extremely challenging projects that ask questions that aren’t in the mainstream. In this case, all the experimental tools needed may not exist (or may exist but will have to be adapted from something else), but more importantly, the “field” itself does not really exist. The hope is that the hypothesis turns out to be correct, and you will make a discovery that will open up new areas of science. Perhaps this could be described as vertical as opposed to horizontal or incremental research. The problem lies in the possibility that the hypothesis could be completely wrong. Sometimes even if the hypothesis doesn’t hold up, the findings are modest and incremental enough to be publishable. Other times, it is all or nothing, and you could be left with absolutely nothing.

It is sometimes interesting to see how things work in industry. Sometimes with (say) startup companies, the people starting it up have a good idea(s), are extremely competent and take up significant challenges, but for various reasons the company does not take off, and eventually folds. Failure to make the company take off isn’t necessarily viewed negatively. Many people have failed in their attempts to start up companies, but are still highly valued by the industry for their experience and knowledge (of the process of building a company). They remain eminently employable and sometimes also desirable.

Unfortunately, I think life in academia may be a less rewarding for similar situations. Sometimes postdocs (or principal investigators) work incredibly hard on a potentially breakthrough hypothesis for years, only for the results to be unremarkable, or even go against the hypothesis (that could have resulted in a major breakthrough). Usually, you can predict that the person is in store for more hard times in the future, since the lack of any substantial publications means that there’s no chance of being offered a faculty position (or perhaps being denied tenure for a young investigator). It is also unlikely that this person would easily find an industry job, since jobs are relatively few, and industry itself has no clear metrics to measure you by (unlike failing in a biotech startup venture). The way things are set up presently, it is hard to impress someone by showing that you disproved a hypothesis. Most of the postdocs who decide to go down this road are pretty smart, technically competent, and think they can handle hard projects, hope they have some vision (in addition to the vision of their bosses), and are usually aware of the risks. But they are willing to spend the 3-4 years trying. If they fail, then they spend two more years doing something “safe”, which they usually are quite successful in doing, and so manage to get a job in industry after a painfully long postdoc.

So, just using this comparison with industry, can there be any ways to measure the value of a postdoc who has worked on some extremely risky projects which have failed? Is a postdoc who has worked on some extremely challenging projects (which haven’t worked) more or less valuable than a postdoc who has managed a couple of publications, but done so using well established methods and a well established system? Can risk takers become valuable in academia? After all, they’re extremely valuable to investigators who need postdocs willing to go after the most challenging ideas the investigator has, but how can that value carry over to the job market?

Wednesday, September 26, 2007

Sleep, the final frontier

Sleep is something (most of us) spend a third of our lives doing, though we hardly give it a second thought. Yet sleep is absolutely essential for all vertebrates, and if an animal is completely deprived of sleep, it will die. Rats that are sleep deprived die in a matter of days, and in the past, when it was still possible to do crazy human experiments, humans have been kept awake for as long as 72 hours, within which time they would descend into psychosis. The few human sleepless anomalies who exist remain with numerous mental and metabolic problems, and the reason why they remain alive are unanswered (warning: do not try to avoid sleeping completely for days on end in order to discover that you are a natural anomaly. You WILL die).

One of the most fascinating questions that still remains somewhat unanswered is “why did sleep evolve in animals”? Now, single celled organisms (like bacteria or yeast) don’t sleep. They continue to grow, and constantly divide at a certain rate. More interestingly, our own cells, when isolated and grown independently in culture, don’t “sleep”, but continue to divide and grow constantly. Sleep itself is a complex phenomenon with distinct physiological, neurological and psychological features. Evolutionarily, one could reason that it could even be advantageous for an animal to evolve to avoid sleeping completely. This would give that animal twice the amount of time needed to forage for food, or reproduce (compared to other competitors), and could even be considered a huge survival advantage. But that has not happened, suggesting that the evolutionary need for sleep is far greater than any benefit a lack of sleep could allow.

Sleep remains essential for all animals, and there remain a number of reasons why that could be so. One reason is that as organisms became more complex (and evolved into multicellular organisms from single celled ones), the need to adapt to a day-night cycle on earth became stronger. This is what’s known as the circadian clock. Much progress has been made in understanding the molecular mechanisms of the circadian clocks, and identifying master-regulators of this clock (like the clock, period and BMAL genes). The subsequent consequences on the cell cycle and metabolism are slowly being unraveled. Yet, the circadian clock does not answer the need for sleep (though understanding the clock allows us to understand many aspects of basic metabolism and growth), since some single cellular organisms that don’t “sleep”, like cyanobacteria, exhibit a robust circadian clock.

Other researchers look at sleep and the circadian clock itself from a metabolic perspective, and from the basic metabolic needs of the body. During sleep, some dramatic processes occur, starting with the basic metabolism of the animal, which shifts from catabolism (or breakdown of molecules, and the release of energy) to anabolism (the active consumption of energy, and subsequent growth and building). So, sleep is in some ways the opposite of a “resting state”, as energy is being consumed, in order to let the body grow or build or recover.

All these details are slowly being unraveled. Yet understanding the very fundamental question of “why we sleep, and how sleep evolved” remains one of the great unanswered questions of science. In a recent post, I described Dan Koshland’s concept of discovery; Charge, challenge and chance. Understanding the fundamental need for sleep, and the evolutionary reasons for it will remain one of the great science questions which will perhaps be answered by “charge”, or “challenge”.

Wednesday, September 19, 2007

Oh what a good time for miracles

I had spent a lifetime thinking the wonderfully superstitious and gullible folks back home in India held a monopoly on natural “miracles” in these modern times. What with people drinking sewage filled seawater that had turned sweet or wasting perfectly good and nutritious milk on Ganesha idols which lapped the milk up (and that is just a select sampling of wonderful “miracles” to pick from).

But nooooooooo, I couldn’t be more wrong. There are no geographical boundaries for gullible folks searching for that next miracle to happen, so that they can reinforce their irrationality and allow their ability to think to atrophy. I discovered that the land of free thinkers, the United States, has a long and proud tradition of miracles as well. In fact there is a veritable cornucopia of miracles here, happening all the time. From the virgin Mary on tortillas to the NunBun in Nashville, there’s a fine collection of miracles all around.

So I was hardly surprised when I read today’s Dallas Morning News, which proudly reported the story of the holy “weeping tree”, which is loaded with “supernatural ice”. Here’s the deal; an old woman dies, and is buried. Soon, a tree that belonged to her starts to collect yellowish-white froth, and bits of liquid started accumulating under the tree.

Family members said they noticed the yellow-tinted froth and the puddles of liquid around the trunk a day after they buried the 92-year-old matriarch…The tree has been "weeping" ever since, they say.

Here’s more; “her daughter, Mary Lou Sanders, said. "Where it's coming from, I do not know. It is something I cannot explain."

Sure, you can’t explain it, therefore it must be a bonafide miracle. And so the faithful flock towards it, in docile submission and hope for more miracles, like restoring the health of a wheelchair ridden child.

If it wasn't true, it would be so funny.

They kneel before it and pray. They stand, patiently extending their open palms or clutching Styrofoam cups with hopes of getting some of the "holy water" drops.

I’m sure that holy water tasted good. After all, it has a wonderfully miraculous source.

Insect spit.

Yup, bonafide insect drool produced by the infamous spittle bug. Or, to quote the Dallas morning news article:

“Not likely, say insect and tree experts who viewed photographs of the substance. They said the "miracle ice" is probably nothing more than a spittlebug nest.” link

Oh well, at least they weren’t drinking sea water. Not much seems to have changed since the dark ages, or so it seems.

(I might as well point towards a guest essay I had written for The Scian, titled The joy of questioning, for those of you who missed reading it earlier. It’s my futile effort to resist the relentless forces of ignorance).

Saturday, September 15, 2007

Charge, challenge, and chance

A few weeks ago, a giant in the world of science passed away. Daniel Koshland left behind a legacy in science. Daniel Koshland left his mark on many aspects of science. As a pioneering enzymologist, he proposed the “induced fit” model of protein-ligand interactions, which now forms one of the foundations of enzymology and most protein-ligand interaction studies. He also had a number of other outstanding discoveries in a long career as a pioneering biochemist, which won him many awards and honors.

In addition, he was perhaps the best known editor of the premier scientific journal Science, which he transformed from “a good journal” to one of the highest impact journals out there. Most scientists strive to publish their best work in Cell, Science or Nature.

Of course, I never knew Dr. Koshland, but my present boss did, and he had the greatest respect and regard for him. He once told us about one of his own major scientific breakthroughs in the late eighties/early nineties, which he had sent to Science and which the reviewers had rejected (the findings seemed too speculative and out of the mainstream for the time). Dan, who was the editor then, overruled the reviewers, published the paper anyway, and the reported findings were proven to be absolutely right, and my boss went on to do many wonderful things in his scientific life.

Anyway, just a couple of weeks before he died, he wrote a perspective in Science called The Cha-Cha-Cha Theory of Scientific Discovery (subscription may be required). In this, he insightfully categorizes scientific discoveries into three groups; charge, challenge and chance, that he calls the “cha-cha-cha” theory. He describes “charge” discoveries as those where the discovery itself is obvious (the movement of stars and gravity, the laws of heredity, causes of heart attacks), but the way to solve to problem, or describe how it happens, is not clear. Everyone has seen it, but the discovery is in thinking of something no one else has thought about. Challenge is where there is a slow accumulation of facts or concepts that don’t quite fit with the existing scientific ideas of the time. The classic example of this would be quantum mechanics, which went beyond classical Newtonian mechanics. Finally, chance discoveries are those that the “prepared mind” encounters. The classic examples here are X-rays or Penicillin.

This succinct group pretty much describes how almost all major discoveries are made. I thought this was a tremendous little article particularly for young scientists. From these examples, it is obvious that waiting around for chance discoveries is unlikely to lead to a great career in science. For that you need to be at the right place at the right time, and most times are not those times. But “charge” could define a majority of everyday science. Even for small findings, the scientist takes charge and attempts to find a solution to an already existing problem (however small it might be). So, the key is to keep working on problems that exist, and to constantly work towards new solutions or explanations for them. Along the way, there may be times when solutions to “challenge” problems might arise.

So far, some of my most enriching moments in science have come from reading or listening to thinkers like Koshland, who help put things in perspective, while simultaneously inspiring scores of scientists around them.

Some further reading/resources:
The nine lives of Daniel E. Koshland (Randy Schekman, subscription may be required).
Interviews with Daniel Koshland (audio).
Lasker award.
A retrospective of Koshland’s life in Science magazine.

Sunday, September 09, 2007

Mendel's garden at Balancing life

Welcome to the September 10, 2007 edition of Mendel's garden, and apologies for the late posting. Mendel's garden #18, hosted here at Balancing life. Mendel's garden is a blog carnival devoted to genetics, featuring some of the best science blogging focused on genetics, from the past month.

Speaking of Mendel, one of the "founding fathers" of modern genetics, too many people think Mendel was just a simple monk pottering about in his garden, where he accidentally observed the inheritance of traits in peas, from which the laws of inheritance (classical Mendelian genetics) were formed. Little could be farther from the truth. Mendel was a very well trained scientist, and systematically applied statistical methods (more typical of the physical science then) to biology. After his schooling (gymnasium) he went on to study for two years at the Philosophical Institute in Olmutz, as preparation for University. Since he was too poor to go on to University, he joined the monastry of St. Thomas in Brunn, and the abbot, an enlightened man who wanted to create an intellectual center at Brunn, strongly supported Mendel's research and education. He even sent Mendel to the University of Vienna to study for two years, where Mendel studied as much physics, statistics, probability, chemistry and biology as he could. His subsequent work with peas, which laid the foundations for the understanding of how attributes of parents are inherited by their offspring, took over seven years of meticulous research.

Anyway, that was a little aside. One with the carnival!

Larry Moran has an excellent post titled Identity of the Product of Mendel's Green Cotyledon Gene posted at Sandwalk.

Hsien-Hsien Lei, PhD takes some time off to visit the Wellcome collection exhibits, and writes about Genomes at the Wellcome Collection at Eye on DNA. This looks like a must see exhibit, if you are in the neighborhood.


I had a running joke with some of my friends in grad school (who used to study the wnt signaling pathway) that wnts were responsible for everything. Chris Patil now writes A hazy shade of Wnt over at Ouroboros.

Evolutionary genetics

CAD writes about Evolutionary Solutions to the Hairy Back Problem posted at VWXYNot?, mostly describing primarily evolutionary genetics, with a touch of development and gene expression! This post summarizes recent research that explicity links multiple microevolutionary changes to a novel morphology in the larvae of a Drosophila species."

Luigi Guarino has a few posts on iron, and writes a little more on iron at Agricultural Biodiversity Weblog> at the Agricultural Biodiversity Weblog, saying, "We've had a couple of posts on the human genetics of iron metabolism and the role of agricultural biodiversity in fighting iron malnutrition"

RPM has an excellent post titled "Promoting Intelligence" over at evolgen, describing promoter differences between humans and chimps which reveal that brain genes and nutrition genes may have changes in expression.

Gene expression

Eric Michael Johnson has a well written post called Shamanic Visions of Selective Sweep at The Primate Diaries where he discusses the evolution of schizophrenia and the nature of contingency.

Fun stuff

Sandra Porter has a little DNA puzzle for us to solve over at Discovering Biology in a Digital World, and it should be quick, enjoyable and entertaining for most biochemists to figure out.

More fun stuff

Andrew Fox has some DNA you can wear! posted at Sexy Secularist!, blogging about a jewelry maker who is fashioning custom Double Helix bracelets with messages spelled out in genetic code.

GrrlScientist says why Pretty Boys Have All the Chicks at Living the Scientific Life. She says "Everyone is familiar with sexual dichromatism in birds; you know, the gorgeous, colorful male who is paired with the drab female or two. It has been observed in birds that, when males and females differ dramatically in appearance, the females are preferentially mating with a few "pretty boys"; those that have elaborate plumage colors or ornamentation. As a direct result of female breeding preferences, these "pretty boys" sire more offspring than those males with less colorful plumage, thus driving the evolution of sexual dichromatism in the population. This behavior concurrently drives evolution of a polygynous breeding system in the population. But what about those birds that are monogamous yet still show strong sexual dichromatism? How did they get to be that way?"

Finally, in case you need some good reading material, and are looking for good general science history, I have a review of John Gribbin's "The Scientists", which I quite enjoyed reading.

That concludes this edition. Apologies if I missed any submissions, but do send that post over to the next Mendel's garden next month. Submit your blog article to the next edition of Mendel's garden using our carnival submission form. Past posts and future hosts can be found on our blog carnival index page.
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Wednesday, September 05, 2007

Some entertaining mind control

(This blog certainly has been neglected over the past week, and has been crying for some attention. So, even while weekdays leave little time for active blogging, here’s a little post saying I’m alive).

Most of the time, the SciFi channel on TV kills the mind with some awful movies or Star Trek reruns. But every once in a while there’s something really enjoyable. On top of that group must be Mind control with Derren Brown. In case you haven’t heard of Derren Brown, he’s a “psychological illusionist”, doing stage hypnosis and that kind of stuff. And he’s also a terrific entertainer, who sometimes reveals some secrets, just to keep all of us really intrigued, and wondering how he does it.

I particularly enjoyed a show where he had different groups of people in rooms, and asked them all to draw out an outline of their hands, and put a personal item in an envelope. He then went on to give them all detailed typed up accounts of their lives, and their inner desires. They all swore that the statements were 90% accurate, and most of them thought he had psychic abilities. He then showed them their typed documents. ALL of them were the same!

Anyway, for your entertainment, here are two videos of him, one of them where he plays chess with 9 opponents simultaneously (a bunch of British Grandmasters, International masters and FIDE masters), coming out on top, and a second one with the inimitable Stephen Fry.

Terrific entertainment, and while I don’t know how he does it all, he certainly keeps us lapping it up.

Saturday, September 01, 2007

What's with the accent?

Every once in a while, I switch off from NPR and tune into one of the Indian radio stations that you can catch here in Dallas. Just so that I can pretend to be up to date with the latest music in Bollywood, or listen to oldies (or occasionally even catch some Tamil songs that they air on weekends).

Anyway, while I have no complaint with the content, here's something that doesn't cease to puzzle and annoy me. What's with the language of the RJ's and hosts on these shows? I perfectly understand hosts speaking in English with an American twang. We're in America, and many of the hosts were raised here, so that's fine with me. I can also tolerate some hosts who speak English naturally with an Indian accent, but try to put on an American drawl (usually failing miserably, resulting in something that is neither here nor there, but mostly unintentionally funny). That's fine too, you're trying to assimilate or whatever.

But what I really, really cannot stand is hosts who try to speak Hindi (or Tamil or Telugu or whatever else) with a ridiculous anglicized accent, and a terrible vocabulary. What's the deal there? Why murder a language which you obviously are a native speaker of, by putting on a terrible accent, and killing all semblance of grammar, just to sound "cool"? If we're having a show in Hindi (or another language), why can't that show be in Hindi (or what ever language), with a reasonable diction and without an overuse of English?

I'm almost tempted to call some of those shows and tell the hosts what I think.

Or maybe I'll just go back to listening to NPR, and my cds and mp3s with Indian music on them. I'm probably just a fusspot, that's all.