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About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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April 17, 2014

Changing A Broken Science System

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Posted by Derek

Here's a suggestion for a total reform of the graduate student/postdoc system of scientific labor and training. It's from a distinguished list of authors, and appears in a high-profile journal, and it says without any equivocation that the system we have is in major trouble:

In the context of such progress, it is remarkable that even the most successful scientists and most promising trainees are increasingly pessimistic about the future of their chosen career. Based on extensive observations and discussions, we believe that these concerns are justified and that the biomedical research enterprise in the United States is on an unsustainable path. . .We believe that the root cause of the widespread malaise is a longstanding assumption that the biomedical research system in the United States will expand indefinitely at a substantial rate. We are now faced with the stark realization that this is not the case. Over the last decade, the expansion has stalled and even reversed.

They trace the problem back to the post-World War II funding boom (Vannevar Bush's "Endless Frontier"). I have to say, the paper gives the impression (no doubt for lack of space) that the progress of funding in the biomedical sciences was smoothly upwards up until about 1990 or so, but as I understand it, the real kick was the post-Sputnik expansion. The 1960s were the real golden years for federal science and education spending, I think, as witness the profusion of buildings from that era to be found at many public universities. You can spot them from a hundred yards away, and boy, are there are lot of them. The authors lump that era in with the 1970s, but that latter decade, at least post-1973 or so, was hardly a period of a "vibrant US economy", as stated.

The doubling of the NIH's budget is also dealt with like a matador deals with a bull - a flick of the cape. But there's no doubt that the situation now isn't good:

However, eventually, beginning around 1990 and worsening after 2003, when a rapid doubling of the NIH budget ended, the demands for research dollars grew much faster than the supply. The demands were fueled in large part by incentives for institutional expansion, by the rapid growth of the scientific workforce, and by rising costs of research. Further slowdowns in federal funding, caused by the Great Recession of 2008 and by the budget sequestration that followed in 2013, have significantly exacerbated the problem. (Today, the resources available to the NIH are estimated to be at least 25% less in constant dollars than they were in 2003.)

The problem has been the same one faced by highway engineers: double the lanes on the highway, and new traffic fills up it again. Extra NIH money has been soaked up, and more, by an expansion in the customers for it. Even if their history is a bit off, the authors' analysis of the current situation seems to me to be right on target. :

The mismatch between supply and demand can be partly laid at the feet of the discipline’s Malthusian traditions. The great majority of biomedical research is conducted by aspiring trainees: by graduate students and postdoctoral fellows. As a result, most successful biomedical scientists train far more scientists than are needed to replace him- or herself; in the aggregate, the training pipeline produces more scientists than relevant positions in academia, government, and the private sector are capable of absorbing.

The result, they say, has also been Malthusian: an increasingly nasty competition for resources, which is taking up more and more of everyone's time. It's creating selection pressure favoring the most ruthless elbow-throwers and body-slammers in the bunch, and at the same time making them scientifically timid, because the chances of getting something unusual funded are too low. (Paula Stephan's thoughts on all this are referenced, as well they should be). You may now see the birth of the "translational research" bandwagon:

One manifestation of this shift to short-term thinking is the inflated value that is now accorded to studies that claim a close link to medical practice. Human biology has always been a central part of the US biomedical effort. However, only recently has the term “translational research” been widely, if un- officially, used as a criterion for evaluation. Overvaluing translational research is detracting from an equivalent appreciation of fundamental research of broad applicability, without obvious connections to medicine.

I'm not quite so sure about the evocations of the golden age, when great scientists were happy to serve on grant review committees and there was plenty of time for scientific reflection and long-term thinking. I would place those further back in history than the authors seem to, if they existed at all. But there's no need to compare things today to some sort of ideal past - they're crappy on the absolute scale, prima facie.

From the early 1990s, every labor economist who has studied the pipeline for the biomedical workforce has proclaimed it to be broken. However, little has been done to reform the system, primarily because it continues to benefit more established and hence more influential scientists and because it has undoubtedly produced great science. Economists point out that many labor markets experience expansions and contractions, but biomedical science does not respond to classic market forces. As the demographer Michael Teitelbaum has observed, lower employment prospects for future scientists would normally be expected to lead to a de- cline in graduate school applicants, as well as to a contraction in the system.
In biomedical research, this does not happen, in part because of a large influx of foreign applicants for whom the prospects in the United States are more attractive than what they face in their own countries, but also because the opportunities for discovering new knowledge and improving human health are inherently so appealing.

Too many players have an incentive to act as if things are supposed to go on the way that they have - universities get overhead out of grant money, so why not hire as many grant-bringers as possible? And pay salaries, as much as possible, out of those grants instead of from university funds? Why not take in as many graduate students as the labs can hold? The Devil is (as usual) on hand to take the hindmost.

The rest of the paper is an outline of what might be done about all this. The authors propose that these steps be phased in over a multiyear period, with a goal of making funding more sensible (and predictable), and altering the way that the academic research workforce is recruited and handled. Here are the steps, in order:

1. Require longer-term budgeting for federal research funding.

2. Gradually reduce the number of PhD students in the biomedical sciences. Support them on training grants and fellowships rather than out of research grants. The rules barring the funding of non-US citizens through these routes need to be changed, because these should become the only routes.

3. Make more funding opportunities available between science career paths and allied fields, so that there are more possible off-ramps for people with science training.

4. Gradually increase the salaries offered federally-funded post-docs, so the system doesn't overload with cheap labor. Limit the number of years that any postdoctoral fellow can be supported by federal research grants, and require salaries to be at staff scientist level if the person continues after this point.

5. Increase the proportion of staff scientists. Universities and granting institutions need to be given incentives to value these positions more.

6. Change at least some of the NIH granting mechanism to a system more like the Howard Hughes fellowships - that is, award longer-term money to outstanding people and labs, rather than to individual proposals. There should be several separate programs like this for different career stages.

7. Set aside a higher proportion of grants for "high-risk, high-reward" ideas.

8. At the same time, consider capping the total amount of money going to any one group, because of the diminishing-returns problem that seems to set in past a certain level.

9. Make grant evaluations less quantitative (number of publication, impact factors) and more qualitative. Novelty and long-term objectives should count more than technical details.

10. Broaden the reviewing groups (in age, geographical representation, and fields of expertise) to keep things from getting too inbred.

11. Start revising the whole "indirect cost recovery" system for grants, which has provided perverse incentives for institutions, with special attention to paying faculty salaries out of grant money.

The authors note that all these changes will tend to increase the unit cost of academic research and shrink research group sizes, but they regard these costs as worthwhile, because (1) the current system is artificially propped up in both regards, and (2) the changes should lead to higher-quality research overall. A lot of these idea seem sound to me, but then, I've never had to deal with the academic research environment. There will, I'm sure, be many people who look on one or more of these proposals with dismay, for various reasons. It will be quite interesting to see if this gets any traction. . .

Comments (42) + TrackBacks (0) | Category: Academia (vs. Industry) | Graduate School

July 8, 2013

Suing Your Grad School, And Your Professor

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Posted by Derek

As anyone who's negotiated with them knows, Harvard plays hardball when it comes to patent rights. But so do the university's students, apparently. C&E News has a report on Mark Charest, a former graduate student in the Myers lab, who is suing the university over patent royalties.

Myers, Charest, and others reported a new synthetic route into the tetracycline antibiotics, and this led to a new company (Tetraphase), which is developing these in the clinic. The dispute is over how the royalties are divided up: Charest, in his legal complaint, claims that the university forced him in 2006 to take a lower share than he considered his due, and he further claims that the university reduced his share even further in 2009.

Note that all of these disputes are over the scraps: Harvard is taking 65% of the royalties right off the top, and no one's going to be reducing that. And I'm not sure how far Charest is going to get with this lawsuit: the article says that an independent panel was called on at one point to review his contributions, so whether he liked the terms he was given or not, they've been scrutinized and he is presumably on record as having agreed to them.

It looks like he's going to claim that this agreement was made under duress and/or under false pretences, though. ChemBark has more details, including statements by Charest in his complaint (link via Paul at ChemBark) that he felt threatened both by Prof. Myers and by Harvard's technology transfer office, and is also alleging fraud (Halvorsen, below, is with Harvard's Office of Technology Development):

74. Dr. Halvorsen threatened that he would award all the inventors an equal 20% share, but that he would allocate 50% of the Inventor Royalties to a wholly separate, undisclosed patent application on which Dr. Charest was not an inventor (the “undisclosed patent application”).
75. Dr. Charest understood Dr. Halvorsen to be threatening him; he wrote to Dr. Halvorsen that “[i]n your previous email you issued the written warning that my portion of the inventor allocation would be reduced if I proceed forward.”
76. Dr. Halvorsen used this separate, undisclosed patent application to force Dr. Charest to take OTD’s offer.
77. The undisclosed patent application, however, was, on information and belief, filed after financial terms were agreed to between Harvard and Tetraphase and added to the license between Harvard and Tetraphase just prior to finalization of their license agreement.
78. Dr. Charest only later learned that this separate, undisclosed patent application was only a ruse to force Dr. Charest to sign OTD’s offer.

No such patent application ever published, the document says. Much of the complaint also focuses on Harvard's decision to give 50% of the inventor royalties to Myers, dividing up the rest between the students and/or postdocs on the patent, and claims that this is a violation of the university's stated policies. So there's no way that this cannot get ugly - it's gotten ugly already. My guess is that Harvard will do whatever it can to get this thrown out (naturally), but if they're unsuccessful in that, that there will be some sort of out-of-court settlement. I really don't see them signing up to have all this dragged though the courts (and the public record) - even if the university did nothing wrong (and I'm agnostic about that), there's still no upside for them.

So for anyone out there whose grad school experience was a bit on the rough side, take heart: at least it didn't end up in court. Updates on this case as it slowly drags itself through the legal system.

Comments (36) + TrackBacks (0) | Category: Graduate School | Patents and IP

January 24, 2013

Too Many Scientists: A "Pyramid Scheme"

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Posted by Derek

Chemistry World has really touched a lot of nerves with this editorial by economics professor Paula Stephan. It starts off with a look back to the beginnings of the NIH and NSF, Vannevar Bush's "Endless Frontier":

. . .a goal of government and, indirectly, universities and medical schools, was to build research capacity by training new researchers. It was also to conduct research. However, it was never Bush’s vision that training be married to research. . .

. . .It did not take long, however, for this to change. Faculty quickly learned to include graduate students and postdocs on grant proposals, and by the late 1960s PhD training, at least in certain fields, had become less about capacity building and more about the need to staff labs.

Staff them we have, and as Prof. Stephen points out, the resemblence to a pyramid scheme is uncomfortable. The whole thing can keep going as long as enough jobs exist, but if that ever tightens up, well. . .have a look around. Why do chemists-in-training (and other scientists) put up with the state of affairs?

Are students blind or ignorant to what awaits them? Several factors allow the system to continue. First, there has, at least until recently, been a ready supply of funds to support graduate students as research assistants. Second, factors other than money play a role in determining who chooses to become a scientist, and one factor in particular is a taste for science, an interest in finding things out. So dangle stipends and the prospect of a research career in front of star students who enjoy solving puzzles and it is not surprising that some keep right on coming, discounting the all-too-muted signals that all is not well on the job front. Overconfidence also plays a role: students in science persistently see themselves as better than the average student in their program – something that is statistically impossible.

I don't think the job signals are particularly muted, myself. What we do have are a lot of people who are interested in scientific research, would like to make careers of it, and find themselves having to go through the system as it is because there's no other one to go through.

Stephan's biggest recommendation is to try to decouple research from training: the best training is to do research, but you can do research without training new people all the time. This would require more permanent staff, as opposed to a steady stream of new students, and that's a proposal that's come up before. But even if we decide that this is what's needed, where are the incentives to do it? You'd have to go back to the source of the money, naturally, and fund people differently. Until something's done at that level, I don't see much change coming, in any direction.

Comments (32) + TrackBacks (0) | Category: Academia (vs. Industry) | Business and Markets | Graduate School

January 8, 2013

More on Grad School Pressures

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Posted by Derek

The next entry in the discussion on grad school and mental heath is up here, at Not the Lab. It's a very realistic look at what the pressures are; I think that most organic chemists will nod in recognition.

And I particularly enjoyed the first comment on the post, from a reader outside the US: "Dear Americans: a lot of your professors appear to be totally f*ing mental.". There's a lot of empirical support for that position, I'm afraid.

Comments (10) + TrackBacks (0) | Category: Graduate School

January 7, 2013

Grad School in Chemistry - The Mental Health Aspects

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Posted by Derek

ChemJobber is starting a series of posts today on grad school and its effects on the mental health of grad students. I have to say, the story he relates sounds very similar to some of my own experiences during my third year or so. I didn't break any household items, but I recall (for example) several instances of leaving the lab and getting back into my car late at night, but first pausing to shout a lot of foul language at the top of my lungs while beating on the steering wheel.

I really did have some moments where I wondered if I had made the mistake of my life, whether I was any good at all in my chosen field, and so on. Another big worry was that I was, from what I could see, losing my ability to enjoy what I was doing, and I had a great deal of worry about whether it would ever come back. (It did, by the way, but I had no way of being sure about that at the time). One of the biggest factors, I think, was the day-night-weekend-holiday nature of the work. My brain has a lot of things it enjoys doing, and being chained to the same wheel for an extended period doesn't help it any. Being persistent on my own motivation is one thing, but forced persistence is another thing entirely. I ended up (as do many grad students) worrying about every break I took from the lab. I'd go see a movie on Saturday night, and come out thinking "Well, there's another two hours added to my PhD"), which isn't a recipe for fun.

There were other stress factors, and looking back, it's a good thing that I started being able to deal with things when I did. The push I made in my fourth year to get things finished up was not without its problems - there's one story that I was sure I had told here before, where I inadvertently destroyed the largest amount of starting material I'd ever made, but I can't seem to find it in the archives. If I'd done that during one of my lowest points, I'm not sure what I would have done. But by that time, I could see the finish line, and I was devoting all my effort to getting out as soon as possible, having decided (correctly, I've always thought since) that doing so was the single biggest thing I could do for my career and for my sanity.

Having that as a goal was important. I saw several examples of grad students who got trapped at some point in their work or their writing-up phase, and were having a lot of trouble actually moving on to something else. Staying where they were was causing them damage, but they seemed to feel even worse when they tried to do something about it. Some of these people eventually pulled themselves up, but not all of them, by any means. I think that everyone who's been in a graduate program in the sciences will have seen similar cases. I became determined not to end up as one of them.

Comments (53) + TrackBacks (0) | Category: Graduate School

November 9, 2012

The Supply of PhDs

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Posted by Derek

Check out this graph from a recent ACS Webinar, as reprinted by Chemjobber. It shows PhDs awarded in the US over a forty-year period. And while chemistry degrees have been running a bit high for a few years, which surely hasn't helped the employment situation, they're still in the same rough 2000 to 2400 per year range that they've been in since I got my own PhD in 1988. The bigger employment problem for chemists is surely demand; that's slumped much harder than any supply increase.

But will you look at the "Biomedical PhD" line! It had a mighty climb in the late 1980s and early 1990s, then leveled off for a few years. But starting in 2004, it has been making another strong, powerful ascent, and into a vicious job market, too. . .what's driving this? Any thoughts?

Comments (37) + TrackBacks (0) | Category: Business and Markets | Graduate School

October 26, 2012

Accident Report, or One Damn Thing After Another

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Posted by Derek

I have this from a lab-accidents-I-have-known discussion over on Reddit. It is, of course, unverified, but it's depressingly plausible. As a chemist, this one is guaranteed to make you bury your head in your hands - it's the second law of thermodynamics come to take vengeance, with the entropy increasing as you go along:

"A graduate student was constructing three solvent stills (dichloromethane, THF and toluene) inside a hood in Room XXXX. As a final step in this process, the student was cutting pieces of sodium metal to add to the stills. Once the sodium had been added, the student began to clean the knife used to cut the sodium. During the cleaning, a small particle of sodium was apparently brushed off the knife. The sodium landed in a drop of water/wet spot on the floor of the hood and reacted immediately making a popping sound. The graduate student was startled by this sound and moved away quickly.

In his haste to get away from the reacting sodium, he discarded the knife into a sink on the bench opposite the hood in which he was working.. Apparently, there was another piece of sodium still adhering to the knife since upon being tossed into the sink, a fire ignited in the sink, catching the attention of another student in the lab. As the flames erupted, the student noticed a wash bottle of acetone sitting on the sink ledge nearby. He immediately grabbed it to get it away from the flames, but in the process, squeezed the bottle, which squirted out some acetone which immediately ignited. The student immediately dropped the bottle and began to evacuate the lab. As he turned to leave, he knocked over a five gallon bucket containing an isopropanol/potassium hydroxide bath which also began to burn. This additional fire caused the sprinklers to activate and the fire alarm to sound which in turn resulted in the evacuation of the building.

When the sprinklers activated, water poured into the bulk sodium-under-mineral-oil storage bottle which had been left uncapped in the hood resulting in a violent reaction which shattered the bottle sending more sodium and mineral oil into the sprinkler water stream. This explosion also cracked the hood safety glass into numerous little pieces although it remained structurally intact. By the time the first-responders arrived on the scene, the fire had been extinguished by the sprinklers, but numerous violent popping sounds were still occurring. The first-responders unplugged the electrical cords feeding the heating mantles, shut off the electricity to the room at the breaker panel and waited until the Fire Department arrived. Eventually the popping noises stopped and sprinklers were turned off. The front part of the lab sustained a moderate amount of water damage The hood where the incident began also suffered moderate damage and two of the three still flasks were destroyed. The student, who was wearing shorts at the time of this accident, sustained second and third-degree burns on his leg as a result of the fire involving the isopropanol base bath.

There were some additional injuries incurred by the first-responders who unexpectedly slipped and fell due to the presence of KOH from the bath in the sprinkler water. These injuries were not serious but they do illustrate the need to communicate hazards to first-responders to protect them from unnecessary injury."

I doubt if the sodium was being added to the dichloromethane still; I've always heard that that's asking for carbene trouble. (Back in my solvent-still days, we used calcium hydride for that one). And it would take a good kick to knock over a KOH/isopropanol bath, but no doubt there was some adrenaline involved. I'm also sorry to hear about the burns sustained by the graduate student involved, but this person should really, really have not been wearing shorts, just as no one should in any sort of organic chemistry lab.

But holy cow. The mental picture I have is of Leslie Neilsen in a lab coat, rehearsing a scene for another "Naked Gun" sequel. This is what happens, though, when things go bad in the lab: we've all got enough trouble on our benches and under our fume hoods to send things down the chute very, very quickly under the wrong conditions. And were these ever the wrong conditions.

Comments (52) + TrackBacks (0) | Category: Graduate School | How Not to Do It | Safety Warnings

October 24, 2012

Chem Coach Carnival: A Few Questions

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Posted by Derek

Over at Just Like Cooking, See Arr Oh has been organizing a "Chem Coach Carnival". He's asking chemists (blogging and otherwise) some questions about their work, especially for the benefit of people who don't do it (or not yet), and I'm glad to throw an entry into the pile:

Describe your current job
My current job is titled "Research Fellow", but titles like this are notoriously slippery in biotech/pharma. What I really do is work in very early-stage research, pretty much the earliest that a medicinal chemist can get involved in. I help to think up new targets and work with the biologists to get them screened, then work to evaluate what comes out of the screening. Is it real? Is it useful? Can it be advanced? If not, what other options do we have to find chemical matter for the target?

What do you do in a standard "work day?"
My work day divides between my office and my lab. In the office, I'm digging around in the new literature for interesting things that my company might be able to use (new targets, new chemistry, new technologies). And I'm also searching for more information on the early projects that we're prosecuting now: has anyone else reported work on these, or something like them? And there are the actual compound series that we're working on - what's known about things of those types (if anything?) Have they ever been reported as hits for other targets? Any interesting reactions known for them that we could tap into? There are broad project-specific issues to research as well - let's say that we're hoping to pick up some activity or selectivity in a current series by targeting a particular region of our target protein. So, how well has that worked out for other proteins with similar binding pockets? What sorts of structures have tended to hit?

In the lab, I actually make some of the new compounds for testing on these ongoing projects. At this stage in my career (I've been in the industry since 1989), my main purpose is not cranking out compounds at the bench. But I can certainly contribute, and I've always enjoyed the physical experience of making new compounds and trying new reactions. It's a good break from the office, and the office is a good break from the lab when I have a run of discovering new ways to produce sticky maroon gunk. (Happens to everyone).

This being industry, there are also meetings. But I try to keep those down to a minimum - when my calendar shows a day full of them, I despair a bit. Most of the time, my feelings when leaving a meeting are those of Samuel Johnson on Paradise Lost: "None ever wished it longer".

Note: I've already described what happens downstream of me - here's one overview.

What kind of schooling / training / experience helped you get there?
I have a B.A. and a Ph.D., along with a post-doc. But by now, those are getting alarmingly far back in the past. What really counts these days is my industrial experience, which is now up to 23 years, at several different companies. Over that time, I don't think I've missed out on a single large therapeutic area or class of targets. And I've seen projects fail in all sorts of ways (and succeed in a few as well) - my worth largely depends on what I've learned from all of them, and applying it to the new stuff that's coming down the chute.

That can be tricky. The failings of inexperience are well known, but experience has its problems, too. There can be a tendency to assume that you really have seen everything before, and that you know how things are going to turn out. This isn't true. You can help to avoid some of the pitfalls you've tumbled into in the past, but drug research is big enough and varied enough that new ones are always out there. And things can work out, too, for reasons that are not clear and not predictable. My experience is worth a lot - it had better be - but that value has limits, and I need to be the first person to keep that in mind.

How does chemistry inform your work?
It's the absolute foundation of it. I approach biology thinking like a chemist; I approach physics thinking like a chemist. One trait that's very strong in my research personality is empiricism: I am congenitally suspicious of model systems, and I'd far rather have the data from the real experiment. And those real experiments need to be as real as possible, too. If you say enzyme assay, I'll ask for cells. If you have cell data, I'll ask about mice. Mice lead to dogs, and dogs lead to humans, and there's where we really find out if we have a drug, and not one minute before.

In general, if you say that something's not going to work, I'll ask if you've tried it. Not every experiment is feasible, or even wise, but a surprising amount of data gets left, ungathered, because someone didn't bother to check. Never talk yourself out of an easy experiment.

Finally, a unique, interesting, or funny anecdote about your career
People who know me, from my wife and kids to my labmates, will now groan and roll their eyes, because I am a walking collection of such things. Part of it's my Southern heritage; we love a good story well told. I think I'll go back to grad school for this one; I'm not sure if I've ever told it here on the blog:

When I first got to Duke, I was planning on working for Prof. Bert Fraser-Reid, who was doing chiral synthesis of natural products using carbohydrate starting materials. In most graduate departments, there's a period where the new students attend presentations by faculty members and then associate themselves with someone that they'd like to work for. During this process, I wanted to set up an interview with Fraser-Reid, so I left a note for him to that effect, with my phone number. His grad students told me, though, that he was out of town (which was not hard to believe; he traveled a great deal).

That night I was back in my ratty shared house off of Duke's East Campus, which my housemates and I were soon to find out we could not afford to actually heat for the winter (save for a coal stove in the front room). And at 9 PM, I was expecting a call from a friend of mine at Vanderbilt, a chemistry=major classmate of mine from my undergraduate school (Hendrix) who knew that I was trying to sign up with Fraser-Reid's group. So at 9 PM sharp, the phone rings, and I pick it up to hear my friend's voice, as if through a towel held over the phone, saying that he was Dr. Fraser-Reid, at Duke.

Hah! Nice try. "You fool, he's out of town!" I said gleefully. There was a pause at the other end of the line. "Ah, is this Derek Lowe? This is Dr. Fraser-Reid, at Duke." And that's when it dawned on me: this was Dr. Fraser-Reid. At Duke. One of my housemates was in the room while this was going on, and he told me that he'd thought until then that watching someone go suddenly pale was just a figure of speech. The blood drained from my brain as I stammered out something to the effect that, whoops, uh, sorry, I thought that he was someone else, arrgh, expecting another call, ho-ho, and so on. We did set up an appointment, and I actually ended up in his group, although he should have known better after that auspicious start. This particular mistake I have not repeated, I should add. Ever restless and exploring, I have moved on to other mistakes since then.

Comments (7) + TrackBacks (0) | Category: General Scientific News | Graduate School | Life in the Drug Labs

September 5, 2012

More on Getting a Science PhD

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Posted by Derek

An article in Slate on science PhDs and scientific employment has been creating a stir among people who think about such issues. (This topic has come up around here a few times, naturally). It's titled "Is a Science PhD a Waste of Time?", and I'll spare you any suspense and tell you that the author's answer is "No". Scientific unemployment has been exaggerated, says the article, and the degree is pretty much totally worth it.

Chemjobber has his own response to all this, and he brings numbers and citations (rather than anecdotes of unnamed people) to the discussion. But it's the whole thrust of the article that he finds hardest to deal with:

I find Mr. Lametti's essay very frustrating. It is suffused with youthful optimism, which is no substitute for a cold look at the facts. I am surprised at the apparent non-existence of the unemployed scientist, and that there doesn't appear to be anybody older than 35 or so in his essay. Wrestling with the damage caused by layoffs or outsourcing don't seem to be worth his time; you got your Ph.D.! Isn't that wonderful? (You should be able to find another job in a snap!)

Nothing against youthful optimism - I keep some (well-insulated) for use in times of need myself. And if someone really does feel like a career in research is right for them, even after getting well into grad school, they're probably right. If you're a fit with this sort of thing, there may well be no good substitute for it. But anyone who's pursuing that career needs to be as clear-eyed as possible about it and about what's going on in the real world. Optimism and lack of information (willed or not) - that's a recipe for trouble.

Comments (56) + TrackBacks (0) | Category: Graduate School

June 14, 2012

Organic Synthesis: A Dead End For Graduate Students?

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Posted by Derek

Via ChemJobber, here's a quote from the National Research Council's Committee on Challenges in Chemistry Graduate Education. Their report has just come out, and I agree that this should be a key point for people to ponder:

Whitesides believes that the question should be asked whether PhD theses are narrow technical presentations for jobs that no longer exist. Should U.S. graduate students be doing organic synthesis if most organic synthesis is being done in China? “That’s not to say that these aren’t really important activities, but we need to connect our investment in graduate school with what’s actually needed to give jobs to students.”

It's worth remembering that Whitesides hasn't exactly been the biggest booster of traditional organic synthesis over the years, he does have a point. This may not be the right way to look at the situation, but if it hasn't crossed your mind, you haven't thought hard enough about the issues yet. I have a couple of quick responses:

1. There are all kinds of organic synthesis. I don't think that there's much point to the human-wave-attack style of making gigantic natural products, as I've said here several times. And if there's not much point to what's considered the highest level of total synthesis, then there must really not be much to the low levels of the field. Those are the papers I'd characterize as "Here's a molecule that no one much cares about, made in a way that you'd figure would probably work, using reactions everyone already knows". But there's more to the field than that; at least, there'd better be.

2. Prof. Whitesides is exaggerating to make a point. It's not like there's no organic synthesis being done in the U.S. A lot of the stuff that's moved to China (and India) is routine chemistry that's being outsourced because it's cheap (or has been cheap, anyway). As that changes, the costs go up, and we head towards a new equilibrium. It seems beyond doubt that there are fewer people doing industrial organic chemistry than there used to be in this country, but it's not like it's only found in China (or will be).

3. That said, he's absolutely right that people need to think about where the jobs are, lest chemistry (and some other sciences) go the way of some of the humanities graduate programs. If you go off and get a doctorate in English with a dissertation on minor 18th-century poets, you're mostly qualified to teach other people about minor 18th-century poets so they can go off and write dissertations of their own. (Actually, your own work would probably have concentrated on the relation of said poets to prevailing gender norms or something, in which case I really don't see the point). We do not want to teach people to do organic chemistry if the majority of them are going to have to seek jobs teaching other people to do organic chemistry.

4. Doing that - thinking about the larger economic and scientific context - is hard. The time it takes to get a degree means that the situation could well have changed by the time a person gets out of grad school, compared with the way things looked when they made the decision to go. But this has always been the case; that's life as we know it. People have to keep their eyes open and be intelligent and flexible, because there are potential dead ends everywhere. As hard as that advice is to follow, though, I still think it's better than any sort of scheme to allocate/ration people among different fields of study. My bias against central planning isn't just philosophical; I don't see how it can possibly work, and it is very, very likely to make the situation even worse.

I'm on the train, and can't download a 120-page PDF at the moment, but I'll have a look at the report and add more thoughts as they come up.

Comments (66) + TrackBacks (0) | Category: Business and Markets | Graduate School | Natural Products

May 9, 2012

PhDs On Food Stamps?

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Posted by Derek

A number of people have sent me this article about the number of people with Master's and PhD degrees who are receiving food stamps. And while it's undeniable that the numbers have grown, I'd ask for everyone to keep their statistical glasses on. According to the chart at the end of the piece, the percentage of doctorate holders receiving assistance went from 0.05% in 2007 to 0.15% in 2010. (For MS/MA degree holders, it went from 0.5% to 1.3% over that same time).

So it can't be said that this is a widespread phenomenon. One would also want to see the numbers broken down by age cohort, and (especially) by field of study. The examples in the article are all history and English types. Also, if those figures are correct, the headline could have just as easily read "Master's Degree Holders Ten Times More Likely To Be On Food Stamps".

Honestly, the number I find most alarming in that chart is the total number of advanced degree holders. We went from 20 million in 2007 to 22 million in 2010 - two million more in only three years? The population of the country went from 301 million to 313 million during that time, so that's a pretty good crop of degree holders. Given what the economy has been like during that period, I'm surprised the food stamp figures aren't even higher.

Looking at advanced degrees as a percentage of the population, we have 4.3% in 1970, 7.2% in 1980, 8.8% in 1990, 8.6% in 2000 (a decrease I'm at a loss to explain), and 10.6% in 2009. Those figures don't quite add up with the ones in the food stamp article, but the trend certainly is in the same direction. We have figures in the growth in bachelor's degree or higher going back to 1940, and they show the relentless uptrend you'd expect.

So it shouldn't come as a surprise that well-educated people are participating more in some of the downsides that hit the rest of the population. Well-educated people are becoming more and more of the population.

Comments (20) + TrackBacks (0) | Category: Business and Markets | General Scientific News | Graduate School

March 30, 2012

Grad School Opportunity Costs? Not to Worry!

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Posted by Derek

Some of you may have seen this graduate student's comment in the Chronicle of Higher Education on his neuroscience PhD. He's worried about the job market, but takes the attitude that he can, in the end, do all sorts of things with his PhD. But what makes him so laid-back, I fear, is that he's not trying to make a career in the sciences:

To some people, this state of affairs has all the trappings of a pyramid scheme. Graduate schools and principal investigators take on too many students because they are inexpensive, work hard, and help to get papers published. At the same time, the graduate schools and investigators know full well that not all the students can move up the pyramid. In this view, the university is not an educator so much as a scientific sweatshop.

This all sounds like a horror story: Toil for years in obscurity, only to emerge from that dark tunnel onto a bridge to nowhere. But as I plan to leave academe to return to a full-time writing career, it is clear to me that this seductive explanation of supply and demand does not jibe with my experience as a doctoral student in the sciences, which has been full of teachable moments that I know will benefit me regardless of the specific work I pursue.

Chemjobber has a very good post on all this, to the effect that (1) getting that degree was not without its costs, in money and (especially) time, and (2) for many of those alternative careers, a science PhD would not have been the most efficient path, to put it mildly. Check out his take and the comments he's attracted, and see what you think.

Comments (45) + TrackBacks (0) | Category: Graduate School

January 13, 2012

Dealing With Dishonesty

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Posted by Derek

So, we've been talking here since yesterday about what looks like large-scale fraud, but there's small-scale stuff that goes on inside various labs (often in academia, which is where people like this are supposed to wash out). Many readers will have encountered, in their grad school days, the person whose reactions won't quite reproduce, who comes in while you're not around and "borrows" your reagents, and who can't quite locate that key procedure when it's time to look at it closely. (And yes, I've had dealings with members of this tribe before, and they're no fun at all).

Here's a reminiscence from a professor at Nebraska of how he dealt with someone like this, and his technique may be something that others have tried (or been tempted to). It worked, though. This is the flip side of the laboratory sabotage discussed here and here, used for good instead of for evil. Are such methods justified? Used carefully, and in extreme cases, I'd say yes. Thoughts?

Comments (32) + TrackBacks (0) | Category: Graduate School | The Dark Side

December 28, 2011

The UCLA Lab Fatality: Criminal Charges Filed

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Posted by Derek

Most readers here will remember the fatal lab accident at UCLA in 2009 involving t-butyllithium, which took the life of graduate student Sheri Sangji. Well, there's a new sequel to that: the professor involved, Patrick Harran, has been charged along with UCLA with a felony: "willfully violating occupational health and safety standards". A warrant has been issued for his arrest; he plans to turn himself in when he returns from out of town this season. The University could face fines of up to $1.5 million per charge; Harran faces possible jail time.

This is the first time I've heard of such a case going to criminal prosecution, and I'm still not sure what I think about it. It's true that the lab was found to have several safety violations in an inspection before the accident - but, on the other hand, many working labs do, depending on what sort of standards are being applied. But it would also appear that Sangji herself was not properly prepared for handing t-butyllithium, which (as all organic chemists should know) bursts into flames spontaneously on exposure to air. She was wearing flammable clothing and no lab coat; no one should be allowed to start working with t-BuLi under those conditions. Being inexperienced, she should have been warned much more thoroughly than she appears to have been.

So something most definitely went wrong here, and the LA County DA's office has decided to treat it as a criminal matter. Well, negligence can rise to that level, under the law, so perhaps they have a point. Thoughts?

Update: here's a post that rounds up the responses to this across the blogging world.

Comments (97) + TrackBacks (0) | Category: Chemical News | Graduate School | Safety Warnings

August 18, 2011

The NIH Wonders About the Future of Biomedical Workers

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Posted by Derek

A reader passes along this request for comment by the NIH. The "Advisory Committee to the NIH Director Working Group on the Future Biomedical Research Workforce" is asking for thoughts on issues such as the length of time it takes to get a PhD, the balance between non-US and US workers, length of post-doctoral training, the prospects for employment after such is completed, general issues relating to whether people choose biomedical research as a career at all, and so on.

These are, of course, issues that have come up here repeatedly (as well they should), so if you want to have a shot at influencing some NIH thinking on them, they're asking for anyone's thoughts by October 7. (Use this form).

Comments (9) + TrackBacks (0) | Category: Business and Markets | General Scientific News | Graduate School

July 19, 2011

Sezen / Sames: What Does it Say About Grad School?

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Posted by Derek

If you haven't seen it, Chembark has Part III of the series on the Sezen/Sames research scandal. And it's another good one, focusing this time on Prof. Sames and his responsibilities in the whole affair. Everyone who's interested should go over to Paul's blog to read what he has to say about things. He's not keeping things bottled up:

Apparently, there is a double standard when it comes to judging students and professors. I guess that shouldn’t surprise anyone. Apparently, students should be fired for failure to replicate fictitious results, but professors are to be rewarded with tenure for being so grossly negligent as to oversee the greatest case of scientific misconduct in the history of organic chemistry.

But that quote shouldn't give you the idea that his post is all invective - there's a lot to back up those statements as well. I'll add that I'm not surprised by a double standard, either - after all, tenured professors are around for years. They bring in grant money (and overhead), while students. . .well, they're transient, and there are always more of them where the last bunch came from.

And while I think it would be a good thing if some of that were to change, I'm not optimistic about that happening. Unstacking that deck would be very, very hard. What would help a bit, though, would be for graduate students (and prospective graduate students) to realize that the deck is stacked, or in some of the more extreme cases of cluelessness, to realize that the deck exists in the first place. Forewarned is forearmed. You are in a very unequal and potentially precarious position as a graduate student, which is one the reasons my standard grad-school advice is to get a PhD as quickly as is consistent with honor and propriety. Don't hang around one day longer than you have to. My own university educated me in that regard: whenever it was more advantageous for them to consider us students, well, that's what we were. Did it then, five minutes later, cost them less money and trouble with respect to some other issue to consider us staff? Then we were staff. Whatever put the university in a better relative position or allowed them to save a nickel.

That's not to say the world beyond graduate school is fair, because it isn't, of course. Wide-ranging hopes in that line will not serve you well. Fred Schwed put it well, quoting what he called "the falsest text in the language" (from Sterne), to the effect that the Lord tempereth the wind to the shorn lamb. "He doesn't, you know,, said Schwed. "Look around you". But at least in some other spheres there are usually more options, more means of redress, than are available to any graduate student. Those problems with university administration are small compared to the potential for trouble with your own professor, and in many cases there's not a damn thing you can do about it - even being in the right may help least of all. The students dismissed from the Sames group over Sezen's work appear, from this vantage point, to have been quite correct about her conduct and the quality of her work. In vain.

Comments (68) + TrackBacks (0) | Category: Graduate School | The Dark Side

April 13, 2011

The Fox's Lament

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Posted by Derek

That hedgehog/fox distinction reminds me of my own graduate school experience. I'm a natural fox myself; I've always had a lot of interests (scientifically and otherwise). So a constant diet of my PhD project got to be a strain after a while. I was doing a total synthesis of a natural product, and for that last couple of years I was the only person on it. So it was me or nothing; if I didn't set up some reactions, no reactions got run.

And I don't mind admitting that I got thoroughly sick of my synthesis and my molecule by the time I was done with it. It really went against my nature to come in and beat on the same thing for that length of time, again and again. I kept starting unrelated things, all of which seemed much more interesting, and then having to kill them off because I knew that they were prolonging my time to the degree. Keep in mind that most of my time was, necessarily, spent making starting material and dragging it up the mountainside. I only spent comparatively brief intervals working up at the frontier of my synthesis, so (outside of any side projects) my time was divided between drudgery and fear.

My doubts about the utility of the whole effort didn't help, I'm sure. But since coming to industry, I've happily worked on many projects whose prospects I was none too sure of. At least in those cases, though, you know that it's being done in a good cause (Alzheimer's, cancer, etc.) - it's just that you may worry that your particular approach has a very low chance of working. In my total synthesis days, I wasn't too sanguine about the approach, and by the end, I wasn't so sure that it was in a good cause, either. Except the cause of getting a degree and getting the heck out of grad school, naturally. That one I could really put my back into. As I used to say, "The world does not need another synthesis of a macrolide antibiotic. But I do."

Comments (9) + TrackBacks (0) | Category: Graduate School | Who Discovers and Why

April 5, 2011

In Which I Reminisce About the Prins Reaction, Chemical Abstracts, and John Keats

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Posted by Derek

Well, this post needs updating. In it I mentioned never running a Prins reaction again since the 1980s, nor any photochemistry, and today what do I find myself doing? Both of them, although not at the same time.

I am, fortunately, not running the Prins this way. But even bringing it up at all recalls to me a key part of my education. When I first joined my graduate school research group, I was put to making some tetrahydropyran systems. I was handed a synthesis, drawn up before my arrival, of how to make the first one, and like most first-year grad students, I gamely dug and and started to work on it.

I should have devoted a bit more thought to it. I won't go into the details, but it was a steppy route that relied, in the final ring-closure step, on getting the cyclic ether to form where one of the partners was a neopentyl center. The organic chemists in the audience will immediately be able to guess just how well that went.

So I beat on it and whacked at it, getting nowhere as I used up my starting material, until I was finally driven to the library. In the spring of 1984, that was a different exercise than it is now, involving the 5-year Chemical Abstracts indices and an awful lot of page flipping. (I haven't so much as touched a bound volume of CA in I don't know how many years now). If you were a nomenclature whiz, you could try looking up your compound, or something like it, in the name index, but a higher-percentage move was often to look up the empirical formula. That gave you a better shot, because (if it was there at all) you could see how CA named your system and work from there.

To my great surprise, the second set of collective indices I checked (the good ol' 9th), yielded a direct hit on an empirical formula, and the name looked like exactly what I had been trying to make. The reference was in Tetrahedron, which we most certainly had on the shelf, and I zipped over to see if there was any detail on how to make the stuff.

There was indeed. A one-stepper Prins cyclization gave just the ring system I'd been trying to make, and that was one step from the intermediate I needed. I just stared at the page, though. I honestly couldn't believe that this was real (as I mentioned, I was in about my second month of grad school lab work). Surely the synthesis I'd been given was the way to make this stuff? Surely the people responsible for it had checked the literature before drawing it up? (After all, it had only taken my a few minutes to find the stuff myself). Surely I couldn't just make the ring in one afternoon using two starting materials I could buy cheaply from Aldrich?

Well, surely I could. And that's just what I did, and got my project moving along until the next interesting difficulty came up a couple of months later. But I still recall standing there in the Duke chemistry library, looking at that journal article "with a wild surmise" that perhaps I should check things out for myself next time instead of just taking everyone else's word. It took a couple more lessons for me to really grasp that principle (Nullius in verba!, but it's helped me out a great deal over the years. I have the 27-year-old photocopy I made that afternoon in front of me now. It's a good reminder.

Comments (15) + TrackBacks (0) | Category: Graduate School | Life in the Drug Labs | The Scientific Literature

January 7, 2011

The PhD Problem

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Posted by Derek

We've had the too-many-doctorates discussion around here a few times, from different angles. The Economist has a good overview of the problem - short on solutions, naturally, but an excellent statement of where things are:

Whining PhD students are nothing new, but there seem to be genuine problems with the system that produces research doctorates (the practical “professional doctorates” in fields such as law, business and medicine have a more obvious value). There is an oversupply of PhDs. Although a doctorate is designed as training for a job in academia, the number of PhD positions is unrelated to the number of job openings. Meanwhile, business leaders complain about shortages of high-level skills, suggesting PhDs are not teaching the right things. The fiercest critics compare research doctorates to Ponzi or pyramid schemes.

One thing for those of us in the sciences to keep in mind is that we still have it better than people studying the humanities. Industrial jobs are in short supply right now, that's for sure - but at least the concept of "industrial job" is a valid one. What happens when you take a degree whose main use is teaching other people who are taking degrees?

roponents of the PhD argue that it is worthwhile even if it does not lead to permanent academic employment. Not every student embarks on a PhD wanting a university career and many move successfully into private-sector jobs in, for instance, industrial research. That is true; but drop-out rates suggest that many students become dispirited. In America only 57% of doctoral students will have a PhD ten years after their first date of enrolment. In the humanities, where most students pay for their own PhDs, the figure is 49%. Worse still, whereas in other subject areas students tend to jump ship in the early years, in the humanities they cling like limpets before eventually falling off.

(See this post for more on that topic. And this inevitably leads to the should-you-get-a-doctorate-at-all discussion, on which more can be found here and here). In the end, what we seem to have is a misalignment of interests and incentives:

Academics tend to regard asking whether a PhD is worthwhile as analogous to wondering whether there is too much art or culture in the world. They believe that knowledge spills from universities into society, making it more productive and healthier. That may well be true; but doing a PhD may still be a bad choice for an individual.

The interests of academics and universities on the one hand and PhD students on the other are not well aligned. The more bright students stay at universities, the better it is for academics. Postgraduate students bring in grants and beef up their supervisors’ publication records. Academics pick bright undergraduate students and groom them as potential graduate students. It isn’t in their interests to turn the smart kids away, at least at the beginning. . .

And I'm not sure how to fix that. Talk of a "higher education bubble" may not be idle chatter. . .

Update: more on the topic this week from the Chronicle of Higher Education.

Comments (89) + TrackBacks (0) | Category: Business and Markets | Graduate School

September 30, 2010

The Hours You Put In

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Posted by Derek

Several people have brought this editorial (PDF) to my attention: "Where is the Passion?" It's from a professor at the Sidney Kimmel Center at Johns Hopkins, and its substance will be familiar to many people who've been in graduate school. Actually, the author's case can be summed up in a sentence: he walks the halls on nights and weekends; there aren't enough people in the labs. Maybe "kids these days!" would do the job even faster.

I'm not completely unsympathetic to this argument - but at the same time, I'm not completely unsympathetic to the people who've expressed a desire to punch the guy, either. The editorial goes on for quite a bit longer than it needs to to make its point, and I speak as someone who gets paid by the word for printed opinion pieces. It's written in what is probably a deliberately irritating style. But one of the lessons of the world is that annoying people whom you don't like are not necessarily wrong. What about this one?

One of the arguments here could be summed up as "Look, you people are trying to cure cancer here - don't you owe it to the patients (and the people who provided the money) to be up here working as hard as possible?" There's no way to argue with that, on its face - that's probably correct. But now we move on to the definition of "as hard as possible".

He's using hours worked as a proxy for scientific passion - an imperfect measure, to be sure. At the two extremes, there are people who are not in the lab who are thinking hard about their work, and there are people in the lab who are just hamster-wheeling and doing everything in the most brutal and stupid ways possible. But there is a correlation, especially in academia. (In many industrial settings, people are actively discouraged from doing too much lab work when they might be alone). If you're excited about your work, you're more likely to do more of it.

Unfortunately, it's hard to instill scientific excitement. And if anyone's going to do it at all, you'd think it would be the PIs of all these grad students. What surprises me is that more of them aren't falling back on the traditional grad-school substitute for passion, which is fear. The author does mention a few labs at his institute that have the all-the-time work ethic, and I'm willing to bet that good ol' anxiety and pressure have as much or more to do with their habits. And a little of that mixture is fine, actually, as long as you don't lay it on with a trowel.

So yes, I wish that there were more excited, passionate researchers around. But where I part company with this editorial is when it goes into get-off-my-lawn mode. The "You have to earn your way to a life outside the lab" attitude has always rubbed me the wrong way, and I've always thought that it probably demotivates ten people for every one that it manages to encourage. The author also spends too much time talking about the Good Old Days when people worked hard, with lousy equipment. In the dark! In the snow! And without all these newfangled kits and time-saving reagents! That makes me worry that he's confusing some issues. An idiot frantically digging a ditch with a spoon looks like a more passionate worker than someone who came through with a backhoe three hours ago, and is now doing something else.

Still, the point of all those time-saving kits is indeed to keep moving and do something else. Are people doing that? I'd rather judge the Sidney Kimmel Center by what comes out of it, rather than how late the lights burn at night. Is that the real "elephant in the room" that the editorial winds up invoking? That what the patients and donors would really be upset about is that not enough is coming out the other end of the chute? Now that's another problem entirely. . .

Update: Chemjobber has some questions.

Comments (138) + TrackBacks (0) | Category: Graduate School | Who Discovers and Why

September 2, 2010

Posters and Pickiness

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Posted by Derek

Blogging time is short today, since I'm on a deadline to produce a couple of posters for presentation. These are for an internal hoe-down, unfortunately, so I won't be able to share the fruits of my labors with everyone out there in the readership. With any luck, though, they'll turn into public presentations/publications eventually, though.

As far as I'm concerned, posters are quite a bit harder to work up than a talk. They really should stand by themselves, for one thing, so you can't fill in any holes verbally. And narrative flow is harder: there's no chance to go back and re-emphasize or contrast with later slides, because the whole thing is sitting out there, with no guarantee of what order people will use to see its parts. (I find that narrative is one of my main weapons in a presentation, so going without it is always tough).

I care about design, too, probably more than I should, so a poster also presents complications there. If visual cues wander a bit from slide to slide through a presentation, that's not good, but it's not fatal, either. But when everything's up there on one sheet, the messages really have to be consistent: same fonts, same colors, same rotations, views, and angles, etc.

But at these times I try to remind myself of what happened to a friend of mine many years ago. She was working on a poster for an ACS meeting, and took it to her PI to look over. "Yes, yes, that looks good", came the word, "but could you perhaps take this part over to here? And emphasize this a bit more? And. . ." So she went back and made the changes, and took the poster back for a re-check. "Much better! Yes. . .but I wonder if maybe this part should be bigger? And did you find a way to include those results where. . ." Back for another round.

After another iteration of this, she caught on. She started taking an unchanged version back to the PI, and after another couple of rounds of seeing the exact same poster, it was finally pronounced ready for viewing. Saves time, saves effort - try it when you can!

Comments (23) + TrackBacks (0) | Category: Graduate School | The Scientific Literature

September 1, 2010

How Long Would It Take - If Everything Worked?

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Posted by Derek

Over at BoingBoing, they're investigating the question: "How long would your PhD have taken if everything worked the first time?" I have to admit, it took me a few minutes to adjust my head to that idea, since God knows, nothing in my PhD ever looked like working the first time.

And it's a hard one to answer, because I had to do some backtracking, as so often happens in total synthesis. This was of the "Dang it all, turns out I can't install that carbon at that step, so I'm going to have to go back, put it in earlier, and hope the downstream stuff still works" variety. (Not all of it did, of course). So how do you account for tactical moves like that? There are several layers.

How long would it have taken if I'd chosen the right move each time, and each reaction worked on the first shot? Even then, that's a tricky one, because one typically runs things on a test scale and then on larger amounts as the ground firms up beneath you. So if things had worked every time, just fine, and I'd scaled up as soon as they did each time. . I'd say around a year. Maybe even nine months; it's hard to say, because the concept of everything working is so alien.

Then one could ask, how long would it take to run through the chemistry in your dissertation, straight through, knowing what there is to know about it? In that case, it would be shorter. Just flogging away at the procedures, nonstop, and having nothing go wrong along the way (hah!), I think you could beat through everything in mine in two or three months. Boy howdy, would I hate doing that.

What does that leave out, then, of a degree that took me four and a half years? (A flippin' short span, I might add, considering some of the other degrees coming out of my old group). Well, there are all those false starts down synthetic routes that ended up painting me into corners. Being carbohydrate-based synthesis, many of those were protecting group problems, but there were a couple of rip-the-whole-sequence-up episodes, too, when things just wouldn't go any further. And there were things like finding out that a base camp of material I'd stored in the freezer had gone to hell anyway, in the dark, under argon. And realizing that a TBDMS group had up and migrated on me, such annoyances as that, which also involve proving that it happened and making sure that I knew where everything was still attached.

And there's an awful lot of time spent just getting each reaction to work - six or eight or ten ways to bring in a methyl group. Four or five different reduction conditions. All those choices, every time: borane THF or borane-dimethylsulfide? Swern or PCC? Hydrogenation catalysts, Lewis acids, finding out that switching from BuLi to KHMDS when making methylene Wittig reagent changed the yield of alkene from 10% to 90%. Chip, chip, chip, at every step along the way. At the time, it seemed as if my legs were mired in not-so-fresh concrete, three feet deep across the lab. Looking back, though, I think I must have been flying. . .

Comments (28) + TrackBacks (0) | Category: Graduate School

August 27, 2010

How Much is the PI To Blame?

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Posted by Derek

Chemjobber has a post up on the responsibility of the professor in the Texas Tech explosion case. I have to agree with him: if you're going to get grant money to have your group work on energetic materials, you have to keep a close eye on things. And the C&E News piece on the whole affair doesn't make it sound like that was happening. It's easy for me to sit here, ex post facto, and say something like this, but I'll say it anyway: from what I can see, this research group wasn't being run the way it should be.

At the same time, there's no amount of training that will keep a real idiot from doing something stupid (thus the German quote that led off my previous post on the subject). Believers in seminars and checkboxes always have to come up against that fact, and against the people that exemplify it. But here's what you have to do with such people: get rid of them. Get them off the dangerous projects at the very least, and try to get them out of your group, out of the building, out of chemistry as a career. Anyone who would scale up a known sensitive, energetic material by a factor of 100 over the recommended amount and then put it in a mortar and pestle does not belong in a chemistry lab.

But that takes us back around to the professor again. Anyone running a research group should know when there's someone in it with a reputation as a wild-eyed cowboy. And when your group is concentrating on hazardous materials, well. . .

So sure, there should have been more training, and it sure sounds as if this lab could have used a better culture in general. But the first thing it could have used was this guy's rear end being kicked down the stairs. And Chemjobber's right: all of these are the responsibility of the PI.

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August 24, 2010

Gegen die Dummheit . . .Well, Guess Who Wins, Again

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Posted by Derek

If you haven't heard about the explosion at Texas Tech earlier this year, this piece is the place to learn about it. (More from Chemjobber and the newly re-blogging Paul Bracher). In short, two graduate students were preparing a nickel hydrazine perchlorate complex, on far more than the recommended scale, and one of them was severely injured while trying to break up the substance in a mortar and pestle.

This is, as any experienced chemist could tell you, not a surprise. Call me when something like that doesn't blow up. But these weren't experience chemists. They were grad students, and I'm just glad that they didn't pay an even higher price for not realizing what they were getting themselves into.

At the same time, I find myself lining up more with Bracher's post, although I won't express myself quite as vigorously. The entire point of this research program was to look at hazardous energetic materials. The professor involved specifically told the students not to make more than 100 mg of material; they made ten grams. The injured student then ground up this material - yep, I did say "mortar and pestle" for real back there - with no blast shield, and gave the stuff one last poke after having taken off his goggles. He now gets to learn to write with his other hand. I can't figure out how he's still alive.

It's cruel, but one thing I actually respect about the physical sciences is that they have no regard for humanity. No exceptions are made; they respect no laws save their own. In a chemistry lab, we are dealing with the world as it really is, not as we'd like it to be. And if you want to believe that you can scale up the synthesis of a violent explosive by a factor of 100, despite warnings, and poke at the material without protection - well, you'd be just as well off doing it to a tiger. Perchlorates don't care what you think you can get away with, or how invulnerable you think you are.

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January 8, 2010

Reasons Not to Go to Grad School?

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Posted by Derek

There's an article in the Chronicle of Higher Education that's been getting a lot of recent attention. It's titled "Grad School in the Humanities: Just Don't Go". The author, clearly (and to my mind, justifiably) embittered about what he sees happening, is an associate professor of English who sees no need to produce a huge surplus of people who want to go on to become associate professors of English.

Some of his warnings don't apply to the sciences. The biggest difference is that there have always been many more places to find work with a science degree other than academia, which is not so true if you've concentrated your graduate studies on the life of Rainer Maria Rilke. Another key factor is that we don't generally come out of grad school with academic debts. To be sure, a Rilke scholar would learn an awful lot about sponging money off wealthy people, but there's that pesky poetic talent problem to be dealt with before you can put those techniques into practice. . .

Of course, these days the jobs aren't exactly coming so readily for new science graduates, although we're still in better shape than anyone over in the humanities. A lot of people are rethinking grad school, though, if the mail I get is any indication. For what it's worth, I offer the Chronicle author's list of bad reasons why people take on graduate study in the humanities - let's take a look and see how many apply to the sciences. I'm going to number them for easy reference:

(1) They are excited by some subject and believe they have a deep, sustainable interest in it. (But ask follow-up questions and you find that it is only deep in relation to their undergraduate peers — not in relation to the kind of serious dedication you need in graduate programs.)
(2) They received high grades and a lot of praise from their professors, and they are not finding similar encouragement outside of an academic environment. They want to return to a context in which they feel validated.
(3) They are emerging from 16 years of institutional living: a clear, step-by-step process of advancement toward a goal, with measured outcomes, constant reinforcement and support, and clearly defined hierarchies. The world outside school seems so unstructured, ambiguous, difficult to navigate, and frightening.
(4) With the prospect of an unappealing, entry-level job on the horizon, life in college becomes increasingly idealized. They think graduate school will continue that romantic experience and enable them to stay in college forever as teacher-scholars.
(5) They can't find a position anywhere that uses the skills on which they most prided themselves in college. They are forced to learn about new things that don't interest them nearly as much. No one is impressed by their knowledge of Jane Austen. There are no mentors to guide and protect them, and they turn to former teachers for help.
(6) They think that graduate school is a good place to hide from the recession. They'll spend a few years studying literature, preferably on a fellowship, and then, if academe doesn't seem appealing or open to them, they will simply look for a job when the market has improved. And, you know, all those baby boomers have to retire someday, and when that happens, there will be jobs available in academe.

Reason #1 is probably common, to some degree, across all academic fields. Graduate school is, in fact, largely about finding out whether you have enough dedication to get through graduate school (and is used as a credentialing signal for that very reason). Reason #2 also probably happens to some extent everywhere, but in science research programs there often aren't any grades after the first year. You have to get your validation from getting good ideas and getting your research to work, with is the same situation that obtains in the real world of science.

Reasons #3 and #4 are actually some of the things that keep people in grad school too long. Though the environment can be odd and stressful, you come to feel at home in it, and worry about going to some new situation where you won't have a place that you've made for yourself. Everyone in the sciences has known people in grad school who've stalled out for just these reasons.

Reason #5 doesn't apply as much for the sciences, I'd say. The kinds of jobs available to someone with just an undergraduate degree are often much different than the ones open to people with graduate training. And the material that you learn in grad school is much like what you started to learn as an undergraduate, just more of it and in more detail. The biggest change is in actually applying it to real research, instead of just learning it and doing well on a written test about it. That's another transition that throws some people out of a scientific career.

But reason #6 would definitely seem to apply, both for academic and industrial jobs. I'd have to think that we have a lot of people who are taking a bit longer to finish their PhDs than they might have otherwise, and a lot of people looking for post-docs who might otherwise not have done one, while they wait for the job market to improve. . .

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November 18, 2009

I'll Get Right On That For You, Professor

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Posted by Derek

I was going over some thermodynamics the other day, and it hit me that this was just the sort of thing I always tried to avoid when I was actually taking chemistry courses in college and grad school. And here I was, looking it up voluntarily and even reading it with some pleasure. A couple of professors of mine would have been rather pleasantly surprised at the sight, though, since physical chemistry (especially) tended to exacerbate my often lazy approach to my course work.

When I look back on it, it's a very good thing that my graduate school curriculum only featured classes during the first year. Because I was trying to get away with more and more by doing less and less, and those two trend lines were heading toward an intersection. (Another example of that from my grad-school past can be found here). In the end, the chrome-plated jaws of destiny did not quite snap shut on my academic career, but it was a near thing. I can well recall being assigned problem sets in a course during my first year of grad school, with a strong probability of having to be called up to the board to work out a random one from the list in front of the professor and the class, and just not getting around to doing them.

So more than once, I'd be called upon to present a problem I hadn't actually bothered to look at. A classmate of mine, Bill, had a similar approach to his work, and he and I would sometimes end up side by side at the board, quietly saying things to each other like "You do any of these?" "Nope, me neither. This one look like the Eyring equation to you?" At the same time, I was ceasing to take notes in the class, finding that (for whatever reason) I wasn't getting much out of the lectures, and seemed to be doing OK by reading the material.

The professor involved noticed me sitting there without a notebook day after day, and called me in for a chat. "You seem to have ceased bringing any sort of writing implement to my lectures", he said. "I presume that there's some reason for that?" I stammered out some line about how I found that I was able to concentrate more on the material when I wasn't having to worry about getting it down on paper, and I could tell that he didn't buy that one for a minute. "I see. . ." he said slowly, and let me go. The next lecture (and you knew this sentence would start out that way), he was up at the board talking about More O'Ferrall plots or something of the sort, and in the middle of explaining one said ". . .then when you move into this quadrant the transition state is affected like so and does that look OK to you, Derek?"

Zzzzzip! Some home-security monitor circuit in my brain tripped, and I returned to reality with the unpleasant sensation of having been dropped into my seat from a helicopter. "Umm. . .no mistakes that I can see", I said, which was certainly true, and the professor gave me a narrow-eyed look. "Yes. . .no doubt".

So no, this couldn't have gone on in that style for too much longer, and it was with relief that I moved on to full-time lab work. But I still have little patience for lectures I find uninteresting. I'm just glad that no one's passing out exams afterwards. . .

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June 10, 2009

Random Questions, Answered Randomly

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Posted by Derek

I had some requests to answer my own "Random Questions" from the other day, so here goes:

1. Does it bother you, or by contrast make you a bit proud, when you tell someone that you're a chemist and (as happens in about seven out of ten cases) they say "Oh, that was my hardest/least favorite/most boring subject when I was in school"?

Well, whether it bothers me or not, this happens all the time. Like pretty much every chemist in the world, I get to hear all about how people couldn't stand my subject in school. I take the point that mathematicians have it even worse, but it's not like we miss many of them with chemistry, either.

When people ask me what I do, I tell them "drug discovery", and I mention the diseases that I'm working on. That never fails to get some interest, and only then I spring on my listener the (often unexpected) info that this involves chemistry. Coming at it from that angle almost always leads to a good conversation, while coming at it from the "I'm a chemist" angle often leads to "Hey, look at the time!" effects. It's worth doing it in the right order, though - I like the effect when of showing that this boring/hard/useless subject actually leads to what most people find is a really interesting job.


2. How many thousands (10s, 100s of thousands) of dollars of unused equipment is sitting in dusty, unused storerooms at your company, because someone ordered it years ago and either (1) never got it to work, (2) was the only person ever to get it to work, or (3) found that it worked, but what it did wasn't worth doing that way?

Disused equipment? What is this disused equipment you speak of? Never have I seen such a thing. Why, those elaborate combichem machines in the sub-basement, they're just down there because they're so valuable. That rotating split-and-mix thingamabob and the multichannel parallel doohickey, we guard those closely.

Hah! Actually, I remember a couple of labs where this stuff wasn't in the basement at all. No, it was out there in the hoods, taking up space and slowly gathering dust, a standing reproach to everyone who walked past it. It would have been better off out of sight, but no one quite had the heart. And besides, it would sometimes get turned on for visiting groups - there was that.

3. Have you ever set up a reaction and thought "Boy, I sure hope that this doesn't work"?

I suppose that this is somewhat shameful, but yes, I have set up reactions hoping that they would fail. Usually it's been when I've had to use a particularly distasteful reagent (sodium ethanethiolate, for example), and I don't want to end up using it on a larger scale. I remember a fellow grad student presenting his work while we were trying to get our PhDs, and he detailed a deoxygenation step which only worked when his intermediate was made using a hefty excess of thiophosgene. "As fate would have it", said his long-suffering labmate from the back of the room.

And I've had less honorable instances, dating back to grad school or early in my industry career, when I was more or less forced to run a reaction a particular way even though I felt there was no chance for it to work. So yeah, in those cases I did look forward to saying "Yes, I tried your idea. And no, it didn't work any better than mine."

4. For the drug discovery people out there, what per cent of compounds you've made over the years would you guess dissolve in plain water to any real extent? Is that figure going up, or down?

The figure is hard to estimate, but it sure isn't high. Things that dissolve in straight water are hard to work with, y'know - they tend not to extract so well into ethyl acetate or dichloromethane, and they don't run so great on silica when you try to clean them up. That's worth another blog post in itself - the way that our standard chemistry techniques tend to push us away from a lot of polar molecules that might be just what we need for med-chem.

5. What, off the top of your head, would you say in retrospect is the most time-wasting chemistry you've ever ended up doing?

Tough competition. I'm tempted to say vacuum pyrolysis of corn starch to make levoglucosan, but I needed that for my dissertation, so it can't be called useless.

The real winner, in retrospect, has to be a series of reactions I did in my first couple of months in my grad school group, when I was still taki