The rise of the male nerd and the decline of female computer scientists

From NPR comes a very interesting graph and hypothesis. The graph shows that the percentage of women who received degrees in computer science was actually rising until the 1980s and then started dropping. 

Why would that be the case?

The highly intriguing hypothesis is that the personal computer revolution during the 1980s mainly featured very simple applications like games that were primarily aimed at men. In fact it was this revolution that gave rise to the stereotype of the geek, tech-savvy, socially awkward male, a stereotype that is now nauseatingly on display in the nooks and crannies of Silicon Valley.

This trend would be consistent with some of the other things we know about the field: We know that the tech industry is male dominated, we know that women who try to get into computer science face all kinds of social and cultural barriers, and as demonstrated recently by the fiasco of 'Gamergate' we know how appallingly unfriendly certain extensions of computer technology can be to women. 

Interestingly the previous healthy presence of women in the field reminds me of something that I have been reading in Walter Isaacson's engaging new book "The Innovators". Isaacson documents that the percentage of women with degrees in math was actually higher in the 1930s than in the 1950s. I wonder if similar factors - perhaps the extensive application of math and physics to war-related problems, an activity that might have been viewed as predominantly "male" - were responsible for women dropping out of the mathematical professions then.

In any case, while correlation is not causation, these findings would certainly be consistent with the cultural factors that make it harder for women to enter the field. Which is something that we can always ponder and remedy.

"A Fred Sanger would not survive today's world of science."

Somehow I missed last year's obituary for double Nobel laureate and bench scientist extraordinaire Fred Sanger by Sydney Brenner in Science. The characteristically provocative Brenner has this to say about a (thankfully) fictional twenty-first century Sanger:

A Fred Sanger would not survive today's world of science. With continuous reporting and appraisals, some committee would note that he published little of import between insulin in 1952 and his first paper on RNA sequencing in 1967 with another long gap until DNA sequencing in 1977. He would be labeled as unproductive, and his modest personal support would be denied. We no longer have a culture that allows individuals to embark on long-term—and what would be considered today extremely risky—projects.

Depressing.

MIT and chemistry: What gives?

A reference to pioneering physical organic chemist Jack Roberts in a C&EN article again brought the following question to my mind: Why has MIT, over several decades, managed to lose some of the best chemists in the world to other departments? This question has been nagging at me for several years and resurfaced recently when Dan Nocera moved to Harvard from MIT.

I understand that my information is largely anecdotal, but it seems to me that the school has lost more highly accomplished chemists to other departments than pretty much any other top school. 

Of course, since these chemists were attracted to MIT in the first place that says something about the caliber of the department, but why lose them then?

Here's a tentative list of MIT chemists who have been successfully lured away. What is striking about the list is that it spans at least four decades and includes some of the most distinguished scientists of those four decades. Also interesting to note that most of these are organic/bioorganic guys so that could say something about what areas the department is focused on.

Jack Roberts (Caltech)
George Whitesides (Harvard)
Chris Walsh (Harvard)
Barry Sharpless (Scripps)
Peter Seeberger (Max Planck)
Greg Fu (Caltech)
Dan Nocera (Harvard)

Who else am I leaving out? I don't want to speculate on the reasons; a simple one could be that not every school focuses equally on all its disciplines. And nobody can deny that MIT chemistry has still been top notch over the decades; as I indicated before, the very fact that all these people launched their careers there vouches for the quality of the department. But the track record seems to indicate that MIT is much better at attracting people than retaining them. And there's got to be a reason for that.

First they came for the bloggers and I didn't speak up because...

Here's a breath of fresh air. I keep on thinking about Planck's quote about scientific revolutions not occurring until old generations die and new ones take their place and here's something of that sort happening, even if in a minor way. 

Prof. Phil Baran has started his own blog. It's easy to see this as a response to the commendable IBX oxidation experiment carried out by Blog Syn. That, by the way, was a great illustration of how science should work; research is published, it is then scrutinized, a few discrepancies are found, the original author responds and confirms the original results, and the new authors discover something new that had not been realized before.

But it's clear that the Blog Syn incident was only a seed for a realization that undoubtedly must have been crystallized in Phil's mind for a while. We have all seen how the old guard has often dismissed and scorned bloggers and their pesky, amateur blogs. Now here's someone from the new guard who clearly recognizes which way the winds are blowing:

Over the years I have vaguely followed some of them, mostly through my students or through being occasionally contacted by someone that runs a blog. Practically all of my colleagues roll their eyes the minute the word "blog" is uttered for a variety of largely justified reasons.  

But times are clearly changing...Last year I was at a dinner symposium where EJ Corey gave a brilliant impromptu talk before a toast. It was a captivating speech all about how things have rapidly changed over the span of his 80+ years. The take home message was that change is natural and you can either embrace it and adapt or be left behind. I'm no fortune teller but it is clear to me that blogging is here to stay and is gathering momentum.

There is something ironic about the fact that the words of the great E. J. Corey - an exemplar of the old guard who almost certainly is not going to start blogging anytime soon - should serve as an invitation to blog for the man who is widely regarded as one of the most creative synthetic organic chemists of his generation. 

Thank you Prof. Baran. Now, the next time they come for us, we know you will speak up because you are are a blogger.

Other reactions: Chembark

Introverts, extroverts and modern science

Over at "In the Pipeline", Derek has a post that indirectly asks the following question; all other factors being the same, is modern scientific research more conducive toward introverts or extroverts?

The post was inspired by an Op-Ed in today's New York Times by Susan Cain, a social scientist who has an interesting book arguing that modern professional life's bias toward extroverted behavior may be stifling the kind of creativity engendered by introverts. Whether at home or at work, we are expected to constantly collaborate, interact, email and reach out and perhaps all this is turning a little obsessive. I haven't read the book yet but the author is suggesting that much of the modern workplace not only encourages but often demands constant collaborations, meetings (both offline and online) and social networking in ways that are stacked against quiet introverts whose valuable skills may be lost in the din.

It may be worth noting first that both introverts and extroverts have made monumental contributions to scientific research, although there could be an argument for certain types of research favoring one or the other kind of personality. If most of your research involves working out dense mathematical theorems or tracing the life histories of ants in the Amazonian rainforest for that matter, an introverted personality that isn't too fond of social interaction may be best for you. On the other hand, if your research involves tracking consumer behavior in supermarkets or evaluating the effects of political bias on brains using fMRI, you may be best off being an extrovert who likes to interact with other social creatures.

Notwithstanding this tailoring of certain kinds of personalities for certain kinds of research, it's pretty clear that there are lots of exceptions and that people with diverse temperaments have flourished in scientific research. Henry Cavendish who would probably have received two or three Nobel Prizes had his discoveries been made in recent times was pathologically shy and would fire his maid if she stepped in the same room with him. As a contrast, among modern scientists, Niels Bohr was famous for being someone who thought best by talking to people. In the words of his protege, the physicist John Wheeler, talking physics with Bohr was like playing a one-man tennis match, with the other person serving as a wall to relentlessly bounce off ideas. Bohr would often take his students and collaborators for long walks, sometimes for circular walks around the building with the intent of hammering out his thoughts. The mumbling and the perpetual refinements and revisions of his sentence constructions made the experience a little harrowing for the listener. As Bohr and his victim went round and round, ideas would spin off. In sharp contrast to Bohr, Paul Dirac was equally famous for being taciturn to an almost pathological degree, mostly remaining silent even when questions were asked. Another example is Fred Sanger, the two-time Nobel Prize winner who is one of the most self-effacing and introverted scientists that you can find. In his case his inward-looking personality led to a career-long life in the lab doing technical work with scant regard for interviews, publicity or even scientific writing. Sanger who faithfully retired at the relevant age and now tends roses in his garden says that he has always been good at doing, listening and talking, in that order.

But as far as the trend of modern research and the current emphasis on open science goes, James Watson and Francis Crick's collaboration may be a better role model than Bohr's peripatetic thinking-out-loud style. The two hit it off almost instantly at the Cavendish Laboratories. Watson was irreverent and not afraid to walk up to anyone and ask any question that came to him. Crick was notoriously talkative and loud to the point of being irritating. The two were ideally suited to constantly bounce ideas off each other and rattle off their latest brainwave without any thought of politeness or social etiquette. But the real reason their collaboration serves as an inspiration for modern research is because of their completely open style of approaching the DNA problem. The two would ask anybody, learn any technique, build any model, perform any calculation, read any textbook and consult any reference, all without abandon. Any person, printed source, experimental or theoretical technique was meat and drink to them, even if in one infamous case Watson used Rosalind Franklin's x-ray data without her knowledge. This practice of doing whatever it takes to solve a problem is cardinal to today's multidisciplinary scientific research and it will continue to serve us well.

Open science will indeed bring us enormous benefits but it may also inevitably cast out the valuable outliers. The book by Cain seems to argue that there can be such a thing as too much collaboration if it becomes enshrined in scientific practice as an inviolable rule, leading to those who don't fit the mold being ignored or even ostracized. The real problem is with implicitly or explicitly penalizing introverts who would rather work by themselves. I myself am someone who prefers a balance; I don't like to be secluded in a private office (as I was in a previous job) and certainly prefer an open work space with desks and cubicles. But I would also like to work on ideas in solitude both before and after I discuss them with others. If I were to criticize modern collaborative science, it would be in its tendency to convene meetings or telephone conferences to sometimes discuss even trivial matters. It would be in emphasizing a talent for teamwork so much that not perceiving someone as an extroverted team player almost automatically ejects him from the pool of job applicants in an interview. And it would be in criticizing or even bullying up on someone who does not instantly subscribe to the latest technological breakthrough in online collaboration and data sharing.

There's one more drawback which I think is inherent in this era of constantly collaborative science. It offers little opportunity to work for some time without preconceived notions. Sometimes the best ideas come from people who can think outside the box precisely because they are not already exposed to the conventional wisdom in the field. In some ways, the first few days in a new position offer the best chance to do independent thinking that is unencumbered by groupthink. Bringing a new researcher in your organization or group up to speed by instantly steeping him or her in the group's research philosophy may seem like a good idea, but it may deny you the chance to tap into fresh and original insight. It is important in my opinion to let a newcomer in a research organization take some time and offer his own way of thinking to others rather than have him fall in line with your preferred mindset right away. And then there's the currently unanswered question of how much a world full of distractions that include the internet, phones, email and co-workers is affecting productivity.

Part of the reason why Cain's outlook strikes a chord with me is because of the realization that scientific research has always benefited from personalities, working styles and mindsets that are as diverse as the discoveries they make. Science has had room for all of them; the introverts, the extroverts, the evangelists, the prophets, the quiet lab technicians, the soap box enthusiasts and the madmen. All of these have made modern science, and all of them deserve a place at the table, no matter how eager its inexorable march.

On chemistry's multiple cultures

As an organic-turned-computational chemist, I once went to a drug discovery conference where conversation during the coffee break turned to our respective backgrounds in chemistry. Computational chemists traditionally fill a niche in drug discovery and hence are not as abundant as traditional organic chemists. When I mentioned I was a modeler, the medicinal chemist I was talking to said in mock disapproval, "Oh, you are one of those chemists!". It reminded me a little of a moment in the 2008 presidential debate when, in reference to an apparently wasteful spending bill, John McCain dismissively referred to Barack Obama as "That one".

While the remark was made in jest, it was not the first time I had encountered such a reaction. The remark is unfair not only because many computational chemists have a sound background in and appreciation for organic, physical or biological chemistry but because computational chemistry as a field is a much newer endeavor than synthesis; virgin territory where the real peaks are yet to be scaled. The general problem of synthesizing an arbitrary complex molecule has been largely solved but the general problem of calculating the free energy of binding for an arbitrary protein-ligand complex is one that we are far from surmounting. Computational chemistry has yet to see its full share of its Woodwards, Coreys, Fischers and Robinsons.

But I digress.

Much has been made of C P Snow's famous "two cultures" signifying a fundamental divide between science and the humanities. It is undoubtedly important that we remedy this rift since humanity as a whole needs both. But what is less discussed is the proliferation of multiple cultures within a field. These cultures can sometimes be as divisive as the overarching cultures of science and the humanities.

This phenomenon is as true in chemistry as it is anywhere else. If we as a community want to pitch the merits of our discipline to the public, we must first make sure that our own house is in order. Sadly I don't find this to be the case, especially within academic chemistry. Computational chemistry is considered flippant by experimentalists, biochemistry is considered too hyped by materials chemists and inorganic chemistry is just plain boring for many biochemists.

This is in spite of the fact that every discipline of chemistry has its own strengths and uses and draws on all others. A biological chemist can gain little insight unless he or she knows the basics of organic chemistry. A synthetic organic chemist must know about metallic oxidation states to get the most out of the power of organometallic chemistry. Many fields of chemistry can be enriched by computational models that can constrain the choice of compounds to be made, pathways to be investigated, enzymes to be crystallized. You cannot study mechanisms in either inorganic, organic or biological chemistry without knowing about thermodynamics and kinetics, and a materials chemist without an understanding of solid-state chemistry and physics may just be limiting his or her chance to gain deep insight into organic electronics. Thus it's obvious that every field of chemistry feeds off every other. Especially in today's age when most important problems are complex and inherently interdisciplinary, one cannot afford to rely only on one's own speciality. A team of experts in different branches of chemistry approaching a complicated problem is piecewise no more competent to judge the whole than is the team of blind men who each approach one part of the famed elephant.

In spite of this obvious utility of every subfield of chemistry and its reliance on every other, chemistry departments are rife with turf wars. Sometimes the rivalry is healthy and the multiple cultures can foster a productive tension between different camps that leads to the rigorous testing and perfection of certain approaches. Often it is not. Sometimes it borders on the comical. I heard of a heterocyclic chemist who in his classes would eschew almost any structure that had more than two chiral centers, relegating the study of such unruly sp3-rich compounds to those lowly polyketide chemists. A total synthetic chemist was quick to condemn an elegant quantum chemical calculation on a particularly complex molecule, no matter that experiment actually supported the calculations. Medicinal chemists often put down the utility of computational models, in spite of the fact that prudent modelers themselves consider their models as more of constraining guidelines than accurate depictions of "reality". Now, in many cases the real problem is not the science but the scientists who have oversold the power of their approach, but that in no way forgives those who would condemn the discipline wholesale instead of rebuking its overenthusiastic practitioners.

If we are to make the most of a complex problem, we need to pick the strengths of each discipline and utilize it as well as we can. This fact is probably recognized more by scientists working in inherently multidisciplinary fields like energy, drug discovery and nanotechnology. These scientists know for a fact that the problems in their field are too complex to be addressed by only one approach, instrument, field or school of thought. Drug discovery scientists for instance recognize (or at least should recognize) the essential utility of synthesists, biologists, formulators, crystallographers and modelers in the discovery of a new drug. Yet you find turf wars even among such interdisciplinary scientists who are often convinced that their latest brainwave is the answer to life, the universe and everything else.

If multiple cultures are sporadic among more applied chemists, they are virtually endemic in academia. How many times have you come across a total synthesis chemist who believes that all of organic chemistry essentially exists to serve the science and art of total synthesis? The materials scientist who believes that organic electronics is the only field worth working in for the next fifty years? And how about that computational chemist who believes that the time when computation is so pitch-perfect that you don't even need to make the molecule is already here? Academic chemists who have dedicated their careers to one single technique, methodology, class of molecule or paradigm are unfortunately among the biggest contributors to the proliferation of multiple cultures. They are quicker to pick favorites and to condemn other modes of thinking, and their very strengths that make them unique experts in their area also constrain them into a local minimum of narrow thought.

This will not do. If we want to hold up the discipline of chemistry as a shining contributor to the welfare of society, we must first make sure that the infighting is kept to a minimum. On a practical level, this would mean giving greater publicity to interdisciplinary chemical fields that automatically feature the participation of a wide variety of chemical scientists. We cannot represent a united front if those from our own ranks remain squabbling and divisive. Ultimately there is one kind of chemistry, the one that applies itself to and solves society's most pressing problems. We need every kind of chemistry to make a contribution to this enormously challenging goal.

If we want to reform the culture of chemistry, we first need to ensure that there is a united culture in the first place.

"The Thexperiment Cafe": Bridging theory and experiment?

Discodermolide and dictyostatin are complex, flexible molecules that bind to the protein tubulin and promote the assembly of microtubules during cell division. This mechanism, similar to that of the bestselling drug Taxol, derails the precise timing of cell division and kills cells by causing apoptosis or cell death. Since cancer is quintessentially a disease of aberrant cell division, both molecules have emerged as potentially promising anticancer agents. Discodermolide and dictyostatin are of special interest not only because of their extraordinary potency, but especially because they seem to retain that potency against cells which have become resistant to taxol.

A year ago I co-authored a J. Med. Chem. paper that proposed a protein-bound conformation for discodermolide using a combination of NMR data and molecular modeling techniques. We followed up with a paper published last week in JACS in which we applied similar techniques to dictyostatin. In a nutshell, the two studies revealed surprising and unexpected dissimilarity in the solution and protein-bound 3D conformations of the molecules; similarity which is belied by their superficial 2D structures. While dictyostatin presents a diverse family of conformations, discodermolide sustains a remarkably constant conformation in very diverse environments (solid-state, solution, and in the protein binding site) that is enforced primarily by steric factors.

I would like to describe the work in the latest paper separately, but for now I am intrigued by another aspect of the problem. In both cases we proposed protein-bound conformations of two medicinally relevant molecules, but in both cases our conformations were not unique. In case of dictyostatin there is at least one alternative proposed conformation while in case of discodermolide there are no less than two. Of course we think that our proposed conformation better satisfies the data (otherwise we wouldn't have published the papers!), but the fact is that we are now presented with a puzzle. Which of the proposed conformations is correct and what technique would best resolve the quandary? The answer is unambiguous: x-ray crystallography on dictyostatin and discodermolide bound to tubulin should tell us what the correct conformation is.

Max Perutz once said that one of the most attractive qualities of science is that there is usually only one right answer, unlike politics where the answer depends on the viewpoint. I think this example illustrates that quality. The question is well-defined. We now have several competing proposals for the protein-bound conformations of two important molecular targets, but we know that there must be only one bound conformation in the solid-state, one right answer. Which conformation among these is it? Or is it a totally different one which has slipped through the cracks? The question is important not only because it would reveal the mode of action of a potentially novel class of anticancer drugs, but also because it could be very useful to organic chemists who could then modify the structures of the drugs based on their bound conformations to improve their potency and other properties.

In case of discodermolide, one molecule, three proposed conformations. But only one true conformation to rule them all. Which is it? In one sense the gauntlet has been thrown in front of crystallographers and the goal should be tantalizing for them, especially because there is a single right answer. The task will undoubtedly be difficult. Until now only the tubulin-binding drug taxol has succumbed to x-ray crystallography while the drug epothilone has lent itself to electron diffraction. Both dictyostatin and discodermolide are flexible molecules that won't yield to protein co-crystallization easily. And yet the solution would almost certainly result in publication in a top journal and new directions for synthetic chemists. Most importantly, it would be the definitive validation of a scientific puzzle that is currently unresolved.

But this train of thought brings to my mind another idea. Wouldn't it be great if we could have an exclusive website where experimentalists post results that theorists have to explain and theorists post results that experimentalists have to validate? The interplay between theory and experiment has of course been the bedrock of science since antiquity. But all too often, the right kind of puzzle is not clearly communicated by one group to another. Sure, if you work in a particular field, you will probably be up to speed on the literature in your field. But the sheer deluge of information ensures occasional omission, and sometimes you may also be interested in potential challenges from other areas which cannot be easily communicated to you. For instance, the dictyostatin/discodermolide puzzle may be interesting to scientists who don't have anything to do with tubulin but who are simply eager to test a new structure determination method that can be applied to such complicated molecules. As we all know, solutions to scientific puzzles can emerge from unexpected corners, and scientists sometimes may find surprises from other fields that pique their curiosity. For example, the spectacular harnessing of physics-based methods in chemistry and biology is well-known.

Yet scientists in one field cannot possibly keep track of all other fields whose developments may be attractive to them. For instance a physicist who may be developing a promising new electron diffraction technique, potentially applicable to tubulin and discodermolide, is usually not going to be aware of literature in this area. In such cases, it would be tremendously useful to have a website whose express purpose is to serve as a bridge between theorists and experimentalists. The website would be divided into the traditional fields of science along with interdisciplinary sections. Every week, a theorist or experimentalist would pose a puzzle from his or her field whose unambiguous solution he or she believes would be amenable to experimental techniques. The puzzle would be tagged with the names of all possible fields to which it could be relevant. People could vote up or down a problem which they find particularly enticing and tractable. Experimentalists from different disciplines can then take a look at the problem. The right answer could come from left field, from quarters which were completely unexpected for the scientist who posed the question. There would still be some querying that would be necessary, but the specific nature of the website would necessitate far less wading through literature from other fields than what's usually required. Similarly, experimentalists could post curious, unexplained results that would tickle theorists' grey cells.

The website could perhaps be called "The Thexperiment Cafe" or something less obnoxious. It would be a place where theorists and experimentalists rendezvous and challenge each other with specific puzzles. It could bypass the usual exhaustive literature searching and serve as a rapid delivery vehicle for problems whose solutions are unambiguous (or even ambiguous!) and which could benefit members from each camp. Experimentalists and theorists could be one big, happy family. And science will always win.