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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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August 18, 2014

ChemDraw Days

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Posted by Derek

Here's a look back at the beginnings of ChemDraw, and you won't be surprised to hear that its origins go back to someone (Dave Evans' wife!) who'd had way too much of the old-fashioned style of structure drawing.

As I've mentioned here before, my grad school experience ended up being timed to experience both worlds. For my second-year continuation exam, I had to do the structures the classic way: green plastic template to make the chair and boat cyclohexanes all come out the same, rub-on letters for the atoms. If you wanted to copy a structure, well, you went down to the copier and you copied that structure. And you Frankensteined each scheme together with tape (matte, not shiny) or glue stick to make The Final Copy, rolling it into the typewriter to put in the captions and the text over the arrows. As I've always said, it was, in retrospect, not too far off from incising a buffalo-dung tablet with a sharpened stick and leaving it in the sun to dry.

It was a lot closer to that then it was to ChemDraw, that's for sure. (The sharpened stick would have worked pretty well with those rub-on letter transfers). And this is exactly what happened every time an organic chemist saw it in action:

The program developed little by little in this manner, with Sally channeling the needs of chemists and Rubenstein doing the programming. In July of 1985, ChemDraw premiered at the Gordon Research Conference on Reactions & Processes in New Hampshire. Rubenstein and the Evanses demonstrated it during a break in the conference. Bad weather kept the conferees indoors, so attendance was high.

Stuart L. Schreiber, then a chemistry professor at Yale University, saw the demo and recalls “knowing instantly that my prized drafting board and my obsessive drafting of chemical formulas were over.”

Schreiber holds the distinction of being the first person to purchase ChemDraw. “The impact of seeing ChemDraw on a Macintosh computer was dramatic and immediate,” he says. “There was no doubt that this was going to change the way chemists interact with each other and the rest of the scientific community,” he says. At the time Schreiber was proudly using his Xerox Memorywriter electronic typewriter with two lines of editable text. “The combination of the Macintosh computer and ChemDraw clearly demanded next-day adoption.” He rushed home to New Haven and placed his order.

That's just how it went. Every organic chemist who saw the program in action immediately wanted it; the superiority of the program to any of the manual methods was immediately and overwhelmingly obvious. You hear similar stories about people's reactions to the first spreadsheet program (VisiCalc) in the late 1970s, and for exactly the same reasons. Advances like these need no sales pitch at all - you could demo such things in complete silence for five minutes and people would line up with their money. I can remember seeing ChemDraw for the first time when I was at Duke, and being stunned by the idea of copying and pasting structures, resizing them, rotating them, joining them together, and (especially) saving the damned things for later.

So for my dissertation, which I started writing in late 1987, it was Word (3.02!) and ChemDraw all the way, and I was the first person in Duke's chemistry department to solo with those two for the PhD writeup. I did some of it on a Mac Plus and a lot of it on Mac SEs, switching floppy disks in and out. There was a Mac II down the hall, with a color screen and a 20 MB hard drive, and I really felt like I was on the cutting edge when I used that one. My lone disk with the manuscript in progress went unreadable and unrecoverable after two weeks of intermittent work, which taught me a lifelong lesson about making backups. Although it was a major pain to keep it up, I ended (with not-so-unusual grad student paranoia) by keeping five copies at all times: the current working copy, an extra one in the desk drawer in my lab, one back by my bench, one over in my apartment, and one in the glove compartment of my car.

My PhD advisor was not a computer user himself at the time, though, which led to an interesting scene when I did hand the manuscript over to him some months later (which process was an interesting story in itself, for another time). He got it back to me with a large number of hand-marked corrections, but as I flipped through the pages I realized that almost all of them were the same corrections, flagged every time that they appeared. I saw him that afternoon, and he asked if I'd seen his changes. I had, I told him, and I'd made al the corrections. He looked at me, puzzled, so I told him about the "Find and Replace" command, and he raised his eyebrows and said "That's very. . .convenient, isn't it?" "Sure is," I badly wanted to say. "Welcome to the fun-filled late 20th century, boss. Let's see, what else. . .we landed on the moon in '69. Oh, the Beatles broke up. And. . ."

But I didn't say any of that, of course. You don't go around saying things like that to your professor, especially when you're in the final stages of writing up, not unless you want to face the choice of going back to the lab for a couple more years or asking people if they'd like the Value Meal. No, facing your committee is preferable in every way.

Comments (35) + TrackBacks (0) | Category: Graduate School

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 (58) + 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 (55) + 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. . .

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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.

Comments (40) + TrackBacks (0) | Category: Graduate School | Safety Warnings

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.

Comments (41) + TrackBacks (0) | Category: Graduate School | Safety Warnings

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. . .

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

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 taking classes and working in the lab part time. I was presented with a route to a tetrahydropyran compound that we needed, a four-or-five stepper that involved an aluminum alkyne opening an epoxide, a Lindlar hydrogenation, a ring closure. . .I can still draw the damn thing on the board, now that I think about it, and it's been twenty-five years ago this spring. Being a first-year grad student, I hopped to it - and hopped right into the mud, since the route bogged down (and how) at the ring closure stage). I kept at it for a while, and then one evening I decided to look up my target compound in Chemical Abstracts.

That wasn't so easy in those stone ax and bearskin days - command-line access to CAS via a rockin' 1200 baud modem and a terminal was still a few months away. I paged through the five-year indices, and found. . .my compound. In a Tetrahedron paper. Two steps, from stuff you could buy from Aldrich, and you form the ring in the first step through a Prins reaction. I was shocked. Surely this couldn't be a known compound. Surely someone must have looked the structure up before coming up with that route I'd been given.

Surely not. And thus did my lab education begin. So you know, when I think about it, even though those first couple of months were a waste of chemicals and effort, perhaps they weren't as much a waste of time as I thought. . .

Comments (19) + TrackBacks (0) | Category: Graduate School | Life in the Drug Labs

January 23, 2009

The Real Hazards of the Lab

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Posted by Derek

A run of bad accident news today, and all of the same kind. The Chemistry Blog has the story of a fatality in the labs at UCLA. The short and painful details are: inexperienced student, t-butyllithium, flammable clothing, and panic (as in not running toward the safety shower).

This is very sad to hear about, and as with so many lab accidents, one of the saddest parts is how easily it could have been prevented. t-BuLi is, of course, a well-known fire starter, and the student did know about that problem. But one of the keys to working with dangerous substances is to think through what you’ll do if something goes wrong. For a pyrophoric compound, that means knowing where the nearest fire extinguisher and safety shower are. It’s very easy to panic when something goes wrong, but if you’ve rehearsed what to do beforehand, you have a much better chance of doing the right thing in tough circumstances.

I pass this along to the students who read this site, and I’m sure the other experienced lab workers here will agree: always think “OK, what’s the worst thing that can go wrong with this reaction?”, and think about what you’ll do if that happens. Fire? Explosion? Sudden leak of nasty toxic stuff? Think it over. Anyone working in a laboratory should always know where the nearest fire extinguisher is. That is, the nearest appropriate one – if you’ve got a separate Class D model for metal fires, or even just a sand bucket, then when you need it you’re really going to need it. And everyone should know where the nearest safety shower is, because no one ever just sort of needs to use one of those. I’ve had to run and pull one once in my career, and let me tell you, it was a damned good thing that I knew where to go when the chips were down.

The other news I have was communicated to me privately, so I won’t go into details other than to say that it appears to be another fatality, this time involving inhalation exposure to trimethylsilyl diazomethane. The problem with these sorts of reagents is that you might think that they’d cause breathing trouble immediately, but you’d be wrong. Diazomethane, phosgene, methyl bromide and others can actually take hours to kill a person, and for a good part of that time, the only symptoms might be a slight cough. But serious lung damage can be coming on slowly during that period, and by the time it’s clear that there’s a problem it’s usually too late to do very much about it. Unfortunately, in some cases, it’s too late right from the start, but that takes quite a bit of exposure, and indicates a serious mistake somewhere along the line.

Anyone who works with such volatile and damaging reagents needs to be completely aware of what they’re doing, and to only handle them under good ventilation. I’ve used such things many, many times in my career, without incident, and so have most working organic chemists. But we should never lose respect for what we’re holding in our hands.

I’m not trying to scare beginning chemists out of doing lab work. It has it hazards, but so does driving to work in the morning or cutting up food for dinner. (When I was in graduate school, my mother once expressed her worries about my lab work, but I told her that the most dangerous thing I did was to drive 650 miles back home on holidays). But every well-appointed chemistry lab is full of death in screw-capped bottles, and that bears thinking about. Random, unforeseeable accidents are, fortunately, very rare. But that means that the others didn’t have to happen, and that’s painful to contemplate.

Comments (65) + TrackBacks (0) | Category: Chemical News | Graduate School | Life in the Drug Labs

October 28, 2008

Out the Door and Down the Stairs

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Posted by Derek

I’ve noticed over the years that my patience in seminars and talks has been eroding. This started in graduate school – I certainly sat through my share of lousy talks back then, but I was starting to skip out on the occasional one, after a certain level of grimness was reached.

For example, I remember walking down the hall with a new post-doc, when the building’s speakers came to life. “May I have your attention, please. . . “ We stopped to listen. “There will be a seminar in the main auditorium in ten minutes, entitled “Raman Spectroscopy of Synthetic Asphalt Roofing Materials” (I swear that this is a real title, or something very close; it was appalling). The new guy asked, in a slightly worried tone “Do you guys in the group usually go to these things?”

And at that point, one of my fellow group members came lurching out into the hallway, pantomiming elaborate choking gestures as he pointed desperately at the speaker up on the wall, slumping against the wall as the horror of the seminar’s title overcame him completely. We watched him slide to the floor, still gesturing at the intercom, and I said calmly: “No, we skip a few of them now and then”.

Well, over the years I’ve continued to skip a few of them now and then, and my threshold has been steadily creeping up. I realize that many of the topics that keep me glued to my seat are, by any objective standard, rather dry. Give a detailed talk about enantioselective hydrogenation, the thermodynamics of multivalent binding, or even the latest thinking about the patent office’s requirements for obviousness rejections, and I’ll be right there, practically munching popcorn. To me, those things are interesting. But plenty of things aren’t.

It’s to the point now where there are single phrases that give me that “late for the door” feeling. After that hits, it’s a major effort for me to stay in my seat. So, speakers, if you see me out in the audience and think that the ambience would be improved without me, it isn’t hard. Just spend a few minutes going on about “cross-functional goal setting” or the wonders of ISO nine-thousand-whatever. I’ll spray gravel on my way out. One day I’ll probably end up dangling from a bunch of knotted tablecloths, having rappelled down the side of my building from an upper-floor conference room. “Vision statement”, I’ll gasp to the passers-by as I drop to the sidewalk in relief. “They invited me to work on a new vision statement. . .”

Comments (11) + TrackBacks (0) | Category: Graduate School | Life in the Drug Labs

September 22, 2008

More Than This

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Posted by Derek

Science is taking a look at the 1991 members of Yale’s Molecular Biology and Biophysics PhD program. The ostensible focus of the article is to see what the effect of flat federal research funding has been on young potential faculty members, but there’s a lot more to pick up on than that.

The first thing to note is that out of 26 PhDs from that year’s class, only one of them currently has a tenured position in academia. Five others are doing science in some sort of academic setting, but only one of those is tenure-track. And you can tell that for at least a few observers, the response to those numbers is “What went wrong?”

Well, nothing did. As it turned out, the students didn’t necessarily come out of the program on a mission to go out and get tenure. But there was no particular way to blame the research funding environment for the numbers, because almost no one that Science interviewed mentioned that as a factor at all. Instead, many of them decided that there might be something more (or at least something else) to life than going from being a grad student and post-doc directly to. . .supervising more grad students and post-docs:

For some MB&Bers, academia was never really an option. "Even as an undergraduate in college, I never bought into the concept of being a professor," says Deborah Kinch, associate director for regulatory affairs at Biogen Idec in Cambridge. "Being a grad student is the last bastion of indentured servitude, and being a faculty member is pretty much the same thing, at least until you get tenure. Earning the same low salary and fighting for every grant--that was the last thing I wanted to do. . .

. . . Midway through their graduate training, a few MB&Bers hatched the idea of a seminar series to hear from former graduates working outside the academic fold. (Athena) Nagi said the group wrestled with the definition of an alternative career and decided that the answer was, in essence, "anything that didn't involve teaching at a major research university”. . .what (Tammy) Spain remembers most were their reasons for branching out. "They all said they didn't want to go into academia. None of them said, 'I failed.' None had even tried to find an academic job. It was the first time I got the sense that there was no shame in not going into academia."

That heightened sense of empowerment reinforced what some class members were already feeling. "At first, you think that academia makes sense," says Nagi. "But by your 3rd or 4th year, you start to get the lay of the land and look at the options. You realize that a postdoc isn't just for 1 year and that there are multiple postdocs."

I particularly like the way that a third-year graduate student had never realized until then that there was no shame in not going into academia. This is a major problem in academic science – the amount of this attitude varies from department to department, but there’s always some of it floating around. It’s no wonder that some of these people were baffled by the prospect of what they were going to do with their lives, because a large, important range of choices was being minimized or ignored.

But I have no room to talk – by that point in my graduate career, I wasn’t clear about what I was going to do, either. I was getting pretty sure, though, that going off and fighting for tenure at a major university was not in the running. I’d seen what the younger faculty put up with in my department, and it didn’t look much better than the life I was leading as a grad student. In many ways, actually, it was worse. Why would I want to do that?

As it turns out, a good number of the 1991 Yale people ended up at various small biotech companies. Some of them have made a success of it, and naturally enough, some of them are out of science altogether. But the rarest, least likely thing for them to do was to get tenure – or even to try. When I think back on the folks I went to grad school with in the mid-1980s, the picture is very similar. You just wish that there were a way to make this sorting-out process less painful. . .

Comments (50) + TrackBacks (0) | Category: Academia (vs. Industry) | Graduate School

August 25, 2008

How Not To Do It: Water Aspirators

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Posted by Derek

You need access to vacuum if you’re going to work at the bench in chemistry. In fact, you need more than one kind. Reasonably hard vacuum (well, by our standards, which is laughable by the standards of the physicists) is down in the single Torr or below – that is, less than about 1% of normal air pressure. We use that for pulling out residues of water or organic solvents from our compounds. You can’t usually see it happening from the solid ones, but the syrupy liquids will foam up or blow a long series of thick bubbles when the vacuum is applied. The foam can be an irritating problem at times; some things will fill your flask with sticky bubbles and go right on up into the vacuum line if you’re not watching them.

The lesser vacuum lines are used for bulk evaporation of solvent (on your rotavap) and for filtering things off. We do an awful lot of both of those, too, and a full vacuum-pump pull is too vigorous for them in most cases. Evaporating down reactions is a constant task in an organic chemistry lab; I’d rather not think about how much of it I’ve done over the years. As for filtration, there are many cases where a solid product can be filtered out of the bulk liquid (which is good) or where some undesired solid by-product has to be filtered out before you can go on (not as good).

The low-tech way to get the sort of pull-it-though vacuum you need for these things is a water aspirator. You don’t see these as much any more, and you don’t see them at all in industry, since they necessarily pull solvent vapors into the water stream. But they work. An aspirator is basically a narrowing tube that hooks up to a hard-spraying water tap and has a sidearm fitting. The accelerating blast of water pulls the air in the tube along with it as it goes, creating a useful vacuum. If you wanted to make one rather more environmentally friendly, you’d keep a well-stocked dry ice condenser in line with it to trap out the solvent vapors before they go down the drain (which is what your rota-vap should have on it, anyway), but even with that, you’re always going to be turning the water flow into a waste stream. As I say, you don’t see them as much these days.

But we used them back when I was in grad school, that’s for sure, mostly for the rotavaps. If you wanted to keep things from splashing around back in your hood, you attached some rubber tubing to the other end of the thing and ran it further down the drain a bit.

Well, one day, one of the guys in the lab next door to me was shocked to see water blasting around in his hood. It was a real fountain, just geysering out full blast from what must have been a cracked water line or something in the back. He ran over and immediately shut off every tap – but to no avail. Roaring, showering water everywhere. Getting a look at the source, he realized, to his consternation, that the water was coming up out of the drain in the back of his hood. I remember standing there with him, staring at this in disbelief. It looked like a special effect. How on earth could you get water blasting up out of a drain pipe?

Suddenly it hit me. I ran around to the other side of the lab, where a new Japanese post-doc had taken up residence. “Masa”, I asked him, “Did you just put that rota-vap in your hood today?” “Yes, yes, just started it today”. There was a water aspirator flooshing away back in the back of his hood. “Did you put some rubber tubing on that thing?” “Tubing? Oh, yes” “How much?!” “Whoaaa. . .” He spread his arms to indicate the mighty extent of the rubber tubing he’d added.

Mighty, indeed. He’d run the stuff down his drain, through a horizontal pipe and right through a T joint, and back up out of the drain of the other guy’s hood, which backed on to his. So when he turned his water on full throttle, he immediately started irrigating his labmate’s space. We finally go thing turned off, and trimmed back the rubber tubing to a more reasonable length (like, not seven feet), and order was restored. For a while.

Note: if you want to see How Not To Do It to a really expensive vacuum rig, try here.

Comments (25) + TrackBacks (0) | Category: Graduate School | How Not to Do It | Life in the Drug Labs

December 19, 2007

Scrape Off Some Attitude

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Posted by Derek

There is a pecking order in chemistry. That’s because there’s one everywhere. If it’s a human endeavor, staffed by humans, you’re going to have hierarchies, real and perceived - who you did a post-doc with, what huge company you're a big wheel in. But that doesn’t mean that we have to bow down to them, and it doesn’t excuse this sort of thing, from The Chem Blog:

” Waaaaaayyy back at the ACS in San Fran at the poster session, we were walking around and introduced ourselves to this guy standing in front of his poster. Now… old boy (a graduate student) engaged us in some dialog about his poster and we were getting along famously, my friend asking most of the intelligent questions (I was still recovering from giving blood a few hours before and drinking multiple beers immediately after.) As conversations normally flow, he asked us where we were from. I told him my fine institution and my buddy told him his. I assume he wasn’t put off my by school, but the look on his face when my buddy told him where he was from was at first a “are you serious” chuckle, which melted into one of those “do they have a department” and finally to a resound(ing), “I’m done with you.”

I stood there and watched it the whole time. So, my buddy being naive to the ways of the world, kept asking questions but the answers weren’t forthcoming any more. In fact, in the midst of a question my buddy was asking, the guy actually walked away from his poster and started talking to his friends. . .”

Read the rest of the post for the rest of the story, which goes off in a different (and still interesting) direction. But as for this behavior, there’s just no call for it. As far as I’m concerned, if a person is asking intelligent questions, they’ve already provided all the credentials they need to show. Likewise, I reserve the right to discriminate against time-wasting bozos (just as I reserve the right to define that class, although I’ll bet that most of my picks would easily pass a show of hands). But if you’re presenting a poster, you have, whether you realize it or not, entered into an agreement to take on the broad unwashed masses.

Tactfully dealing with the clueless is a learned skill, but no such skill seems to have been called on here. This is tactfully dealing with the intelligent and informed, and if you can’t do that, you have some serious problems. It takes an awful lot of red-hot results to make up for a really obnoxious attitude, and a degree from Big Name U is only partially going to offset one as thick as this. Now, it's true that there are certainly some pretty abrasive folks from BNU, but the ones with the proven big-time track records can at least get away with it. Too many other morons take the shortcut, deciding that the nasty attitude is some sort of essential first step – in some cases, deciding that it and the Big Name is all they need.

Out here in the real world, where Poster Boy has yet to tread, it becomes clear that the wonderfulness of a marquee school background eventually goes stale. There are places in the drug industry where working for particular academic bosses will give you a leg up – for a while. It’s a real advantage to be able to get in the door that way, no doubt, but once you’re through the door you generally have to produce something. (And it’s good to keep in mind that even these advantages don’t necessarily last forever. A rollicking management purge can destabilize an old-boy network very quickly).

No, doing lots of work and doing it really well is a better long-term strategy. (Another part of that strategy is to make sure that people know who’s doing it, but that's a topic for another day). And having a personality that makes people grit their teeth and wait for you to leave is not such a good long-term plan. I wish Poster Boy well, but I hope that he has a lot to talk about. This isn't one of those businesses where you can get by on looks.

Comments (38) + TrackBacks (0) | Category: Academia (vs. Industry) | Graduate School | Life in the Drug Labs

November 20, 2007

And It Goes Like This!

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Posted by Derek

I had a hard drive failure the other day, which naturally got me to thinking about backing up data, and about the times I’ve been more paranoid about it. I wrote my PhD dissertation back in those far-off days (1988) when you could put Mac versions of Word and Chem-Draw on one 3.5-inch disk (yes, that was possible, and I still have the disk to prove it). But I went to the disk-swapping trouble of putting my dissertation-in-progress on a separate floppy.

So there I was, with a couple of week’s worth of dissertation draft on my floppy disk, when one fine day I insert the thing into the slot, and. . .it can’t be read. Hrm. I try other machines. I try them all. None of them can read the disk, under any conditions. It slowly dawns on me that my two weeks of work have evaporated, and a little later it dawns on me that things could have been much, much worse. I converted to the Backup Religion.

Grad students writing up tend to get a bit paranoid under the best conditions. Once I made my backup copy, I realized that I might run into a problem with the floppy drive – what if it subtly ruined my disk? Then one floppy would apparently be bad, so I’d feed the next one in, and the evil drive would chew that one up too. Hmm – better have three copies. I decided to keep one in my lab dsek, one at home, and one in my car. But then I started thinking of the unlikely – but still possible! – combinations of drive failures, fires, accidents, etc. that could still wipe me out. In the end, I had, I think, five separate copies of the dissertation in progress: one back at my apartment, one in the car, one in the lab desk, one back in a drawer by my hood, and one in my coat. I never needed any of the backups at all.

But it was a comfort to know that they were there, and mentally I needed all the backup capacity I could get in those days. Late one night I was awakened by a host of fire trucks roaring down the street. I lived only a quarter-mile from the chemistry building, and I found myself wondering, there at three in the morning, if that’s where they were headed. Ah, but I had my latest dissertation disks. But. . .I also had all the hard copies of my NMRs there in my lab. Aargh. (I should note that digital backups of NMR data were quite rare back in that era, at least in much of academia). What if the building caught on fire?

Worse, what if I’d been the cause? Had I really turned off that heating mantle when I left at midnight? Or did I just think that I had? Wasn’t there a bottle of hexane in my hood? (I did mention that this was three in the morning, right? Why the brain gets into these loops at that hour is a mystery, because that kind of thinking is normally alien to me, as my wife, to whom it’s second nature, will tell you). So I sat there, wondering if my lab and my data were at that moment going up in flames, until I finally rolled out of bed and called the lab. Ring. Ring. Ring. “Hello?” I recognized the voice – it was Randy, down the hall – but I suddenly realized that I didn’t know what to say to him. “So the lab’s not on fire?” didn’t seem like a good conversation starter, so I just hung up, and went back to sleep.

The next day I made my late-morning entrance into the lab, and ran into Randy. “How late were you here last night?” I asked him. “Oh, really late”, he said, and looked at me. “How did you know?”, he asked, and I looked embarrassed. “Hold it,” he said, “that was you, wasn’t it? You must have heard all those fire trucks going past! Thought the lab was on fire, didn’t you?” All I could do was turn red, because he had me.

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October 25, 2007

Looking Backwards

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Posted by Derek

A colleague reminded me the other day of a project that he and I had worked on back at the Wonder Drug Factory seven years ago. "Seven years ago", I thought. . .I was the project leader on that one, trying to keep things alive as weird toxicology kept torpedoing everything. In the end, we held it together long enough to get four compounds into two-week tox testing, whereupon every one of them wiped out for yet another set of ugly reasons. Ah, yes. No one's going to have to work on that stuff again, that's for sure.

Hmm, I thought. What was I doing seven years before that? Well, I was back at my first drug industry job in New Jersey. The company had just moved into a new building the year before, and the old site was on its way to becoming a Home Depot. I was spending my days cranking out molecules hand over fist. Boy, did I run a lot of reductive aminations. It's safe to say that during those years I ran the majority of all the reductive aminations that I'll ever run in my life, unless something rather unforeseen crops up. We made thousands of compounds on that project, and I remember pointing out in a talk that nobody makes that many compounds if they really understand what they're doing. This was not a popular line of reasoning, but it's hard to refute, unless saying how much you don't like something counts as a refutation.

And seven years before that? Still in the lab. I was midway through grad school, wrestling with the middle of what turned into twenty-seven linear steps by the time I pulled the plug. (At this point, I began to reflect that I've been doing chemistry for quite some time now). In 1986 I didn't know that I wasn't going to end up finishing the molecule, and I was still hauling buckets of intermediates up the mountainside, only to find them alwyas mysteriously lighter and smaller by the time I got to the top. My response, naturally enough, was to start with larger buckets - what else was there to do?

And seven years before that? That finally takes me over the chemistry horizon, back to my senior year of high school in Arkansas, and to what might as well be a different planet entirely. Although I was interested in chemistry - as I was in most all the sciences, something I've never lost - I'd never heard of a Grignard reagent, and I didn't know what a nucleophile was. Counting up, I see that some time next year will mark the point at which I will have spent a slim majority of my lifetime doing organic chemistry, which is an odd thought. And it makes me wonder what I'll be up to seven years from now. . .

Comments (11) + TrackBacks (0) | Category: Graduate School | Life in the Drug Labs

October 18, 2007

Understanding Dawns

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Posted by Derek

My graduate school lab, like most of them, had an assortment of people from different countries. That kept things at all sorts of hours, since we’d get the occasional Japanese post-doc who never really seemed to get off JST and worked the zombie schedule. It also made for some adventures in communication. English was the lingua franca of the lab, naturally, but there were a lot of varieties spoken (and attempted).

And although it’s risky to generalize, I think that the ones with the biggest language gap were the aforementioned Japanese. Friends of mine from the country have blamed the problem on the traditional state of English teaching there, and the way that too many students are taught the language as if its phonics really did conform to what’s available in Katakana.

That’s the writing system used in Japan to render words phonetically. Reading fancy Japanese (Kanji) takes some real practice, but any hack (like me) can plow through Katakana with a chart and a little practice. I’ve been asked many times, in wondering tones, if I read Japanese after I pulled out a useful reagent name from a Japanese patent, but I wasn’t reading Japanese – I was reading English. Sort of.

Sounding out the words makes you sound like the most unfortunate expatriate Japanese post-doc you’ve ever heard. “Cyclohexyl”, for example, comes out as “Sa-ki-ru-he-ki-sa-ru”, and “chloro” is “ko-ru-ru”. I’d probably sound even worse than that if I had to speak Japanese, but it does give you some insight as to where the stronger features of the accent come from.

One way or another, we all did communicate in the end. I remember talking with one of our post-docs, trying to learn some Japanese profanity (a well-known gateway into a foreign language, of course). But I couldn’t get the concept across. “Bad word?” he asked, puzzled. “Curse word?”

An idea hit me. “OK”, I said, pointing at his rota-vap where a 1 mL flask was spinning. “How long did it take you to make that stuff?” That stuff, he informed me, was step 17 of his synthesis, and had taken weeks and weeks of work. “Fine,” I said, “what happens if it falls into the water bath?” “Ah! Terrible!” he said, looking fearful at the very thought. “Right”, I told him: “If that happens, what do you say?”

Enlightenment! “Oh! Yes! Those words! Bad word, yes, now I understand!” A great moment in international understanding. We went on to explore the sorts of phrases that are absolutely guaranteed to come in handy in any research lab, no matter where.

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August 26, 2007

Cheer Up

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Posted by Derek

This is the first post from the new Blogging Room of Stately Lowe Manor here in Massachusetts. The internet is hooked up, the lights are on, and I'm surrounded by boxes no matter where I turn.

I had a few requests to do more posts on graduate school and what goes on there. Problem is, it's becoming an increasingly distant event for me (which in most other ways is not much of a problem at all!) There's one immediate thing I can think of to say to people who are still in the middle of it, though: Don't worry. You're not going to be stuck like this forever.

I'm thinking of what a generally foul mood I was in throughout my PhD work, compared to my overall sunnier disposition since. I didn't like having to work on the exact same molecule for years, and I didn't like having to do it days, nights, weekends, and holidays. I especially didn't like that little voice in the back of my head that took up residence there, telling me - every moment that I wasn't in front of my fume hood - that I should stop goofing off and get back to work.

And I wondered if the experience had permanently damaged me. I really worried about that. When you're younger, these thoughts occur to you if you've got any introspective tendencies at all, and my working hours gave me plenty of time for thinking about such things. Was I ever going to wake up and feel enthusiastic about going to work in the lab? If not - and there seemed a real chance that the answer was, in fact, "Never again" - how was I going to make any sort of worthwhile life for myself? After all, here I was committing a good slice of my 20s to getting an advanced degree in a field whose same advanced degree might be ruining my chances of ever using it.

No wonder I was surly. I wasn't sure I was doing the right thing, and I wasn't sure what shape I'd be in if I stopped or if I kept going. Admittedly, I never seriously considered the first option. The going didn't get really rough until I was in far enough that the shortest way out was at the other end. I knew that I could hang in long enough to get the degree; what I didn't know was what kind of shape I'd be in after I got it.

Well, as it turned out, I was fine. My worries, though real, were overblown. It took a while on my post-doc in Germany, but my brain proved to be more resilient than I'd feared, and it soon bent back to its usual shape. I stopped feeling as if the dogs were chasing me when I wasn't in the lab on, say, Sunday nights or the day after Christmas. And I started enjoying the times that I did go in. Not being up to my elbows in lab work all the time made it fun when I did it out of choice. No permanent damage seemed to have occurred.

Actually, I came out of the experience stronger than when I went in, for having gone through it without breaking. So, if you're trying to finish up your last year or two of a degree, and you feel as if it's never going to end, take it from me: it does. And if you think that you can't stand the time remaining, prepare to surprise yourself, because odds are very good that you can. And no, you won't always feel like you do on your worst days in your grad school lab. That's not the real world; it's just pretending to be.

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August 23, 2007

". . . Jobs That Don't Exist"

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Posted by Derek

The FASEB folks have collected a large amount of data on training and employment in the life sciences (start here), and see the discussions over here at the AAAS).

Many of the conclusions are not going to surprise people, but it's good to have some data to back up everyone's impressions. I can sum the whole presentation up in a sentence: academic life science is a hard place to make a living, and getting harder every year. For example, the average age of first-time R01 grantees has been going up for the past thirty-seven years. And over the past twenty years, the number of doctorates awarded has roughly doubled, while the number of people employed in tenured (or tenure-track) positions has stayed exactly the same.

So where is everyone going? Well, down the hall from me - industry is where the job growth is. I know that my pharma/biotech readers might be startled by that statement, but compared to academia, we're a boom town. (I mean, look at it, no head count increase since 1987?) The problem is, as far as I can see, many PhD candidates and post-docs have been trained in environments where an tenure-track academic position is seen as the natural and desirable goal, and industry is just the fallback for the also-rans. If this ever was congruent with reality, it isn't now. As a commentary in the latest Nature put it:

More effort is needed to ensure that recruitment interviews include realistic assessments of prospective students' expectations and potential in the academic workplace. And training should address broader career options from day one rather than focusing unrealistically on jobs that don't exist.

Chemistry doesn't have this mindset problem to the same extent. There do seem to be some research groups who don't so much look down on industry as over-exalt academia, but there are plenty of strong people from the top-ranking groups all over the pharma landscape. But the hiring problems, well, I'm sure those track pretty close to the FASEB story.

And that gets us back to the ever-popular topics of medicinal chemistry employment, outsourcing, restructuring, and so on. For now, I'll reiterate my strongest opinion on these subjects, which is that this is not a good time to be an ordinary medicinal chemist in the US. You need skills, you need to keep them sharp, and you need to be ready and able to move into new research areas as they get interesting. It's not easy. But at least it's easier than trying to make it as a professor. . .

Comments (19) + TrackBacks (0) | Category: Graduate School | How To Get a Pharma Job

August 13, 2007

Pilferage

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Posted by Derek

One of the comments to my brief post earlier today brought back some memories. Back in graduate school, we were a comparatively well-off group. That is, we graduate students lived off grant money after our first year - no more teaching assistant duties. Compared to some of the other professors, whose students were TAing in their fourth years and beyond, this was luxury.

But luxury went only so far. We still had to watch our expenditures in the lab, and ordering of reagents and supplies was kept under tight control. We didn't go as far as recycling our wash acetone (well, most of us didn't - see here for what happened to the fellow who did), but If you wanted a fresh bottle of something, you had to justify it: what's wrong with the one we've got, heh?

I was pushing a big pile of material through the early stages of a long synthesis, so I (and the people like me) needed larger amounts of things. I remember getting in a fresh 800 mL bottle of borane/THF, of which I was going to use about 700 mL in one big ol' hydroboration reaction. Ready to go! Got my starting material on the pump, got my freshly distilled solvent, got my untouched bottle of. . .wait a minute. That's not on the shelf where I left it. And it's. . .it's. . .

What it was, was about half empty. Yes, one day in the lab was all it took for my pristine stockpile of borane to be raided. To add that extra emotional touch, when I unscrewed the cap and looked at the seal, the person who'd pirated the stuff had apparently used something the size of a knitting needle to remove it. The "Sure-Seal" was surely hollowed out, to the point that I could see the borane solution sloshing down there in the distance.

I didn't take it well - it was grad school, so I didn't anything too well. I went stomping through the labs, beard bristling out, hands making involuntary strangling motions in the air, asking who, just who, had helped themselves to half a liter of borane/THF in the last day? Eh? Well, as you'd guess, no one had. Nope, nobody at all had used that there borane, no-sir-ree, didn't even know it was there. Some of my colleagues assured me that they'd never used borane in their lives, and a couple of them seemed surprised to find that there was a chemical with such an odd and catchy name. What you say, boh-rain?

I never did find the culprit. Most of the time, you never do. I gritted my teeth, used some more foul language, ordered another bottle of reagent - and used it right out of the box this time, trailing little flecks of vermiculite packing material behind me.

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April 17, 2007

The Doctorate and Its Discontents

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Posted by Derek

The doctorate-or-not discussion is roaring along in the comments to the last post, and they're well worth reading. I have a few more thoughts on the subject myself, but I'm going to turn off comments to this post and ask people to continue to add to the previous ones.

One thing that seems clear to a lot of people is that too many chemists get PhD degrees. I'm not talking about the effect of this on the job market (more on that in a bit) so much as its effect on what a PhD is supposed to represent. So, here's my take on what a PhD scientist is supposed to be, and what it actually is in the real world. I'm going to be speaking from an industrial perspective here, rather than an academic one, although many of the points are the same.

Ideally, someone with a doctorate in chemistry is supposed to be able to do competent independent research, with enough discipline, motivation, and creativity to see such projects through. In an industrial applied-research setting, a PhD may initiate fewer projects strictly from their own ideas, but they should (1) always be on the lookout for the chance to do so, (2) be willing and able to when the opportunity arises, and (3) add substantial value even to those projects that they themselves didn't start.

That value is both creative and managerial - they're supposed to provide ideas and insights, and they're supposed to be able to use and build on those of others. They should be able to converse productively with their colleagues from other disciplines, which means both understanding what they're talking about and being able to communicate their own issues to them. Many of these qualities are shared with higher-performing associate researchers, who will typically have a more limited scope of action but can (and should) be creative in their own areas. Every research program is full of problems, and every scientist involved should take on the ones appropriate to their abilities.

So much for the ideal. In reality, many PhD degrees are (as a comment to the previous post said) a reward for perseverence. If you hang around most chemistry departments long enough as a graduate student, you will eventually be given a PhD and moved out the door. I've seen this happen in front of my eyes, and I've seen (and worked with) some of the end results of the system. The quality of the people that emerge is highly variable, consistent with the variation in the quality of the departments and the professors. Unfortunately, it's also consistent with the quality of the students. But it shouldn't be. The range of that variable shouldn't be as wide as it is.

There are huge numbers of chemistry PhDs who really don't meet the qualifications of the degree. Everyone with any experience in the field knows this, from personal observation. You will, I think, find proportionally more of these people coming out of the lower-quality departments, but a degree from a big-name one is still far from a guarantee. The lesser PhD candidates should have been encouraged to go forth and get a Master's, or simply to go forth and do something else with their lives. They aren't, though. They're turned loose on the job market, where many of them gradually and painfully find that they've been swindled.

Over time, the lowest end of the PhD cohort tends to wash out of the field entirely. There are, to be sure, many holders of doctoral degrees in chemistry who go into other areas because of their own interests and abilities. But there are also many jobs that make an outside observer wonder why someone with a PhD is doing them, and that's where many people end up who shouldn't have a doctorate in the first place. Others, somewhat more competent, hold on to positions because they're able to do enough to survive in them, if no more. While there are plenty of bad or irrelevent reasons for people not to be promoted over the years, some cases aren't so hard to figure out.

Those, then, are my thoughts on the doctoral degree. What can be done about this situation, if anything, will be the subject of a future post. I have another set of opinions on the Master's degree and its holders, which I'll unburden myself of a bit later on. Comments, as mentioned, should go into the discussion here.

Comments (0) + TrackBacks (0) | Category: Academia (vs. Industry) | Graduate School | Life in the Drug Labs | Who Discovers and Why

April 15, 2007

Doctorate or Not?

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Posted by Derek

There's been a lively discussion in the comments thread to this post about the differences between hiring PhD and associate-level chemists. Anyone who's interested in the topic should have a look, because there are a number of issues in play: chemical knowledge, ability to manage direct reports, adaptability, and more.

There's little doubt that non-Phds have an easier time getting hired. There's almost always a ceiling over their heads, rarely one as transparent as glass, but finding a place under it isn't as hard as finding one off to its side. One question that's come up is whether chemists with doctorates could (or should) apply for associate-level positions.

This has been done - but it usually involves deception. If you have a PhD on your CV, most places just aren't going to consider you for an associate job - thinking (probably correctly) that you're going to be more trouble than you're worth. The feeling is also, even in down job markets, that you're selling yourself short by going for these jobs, and that there must be some good reason why you're doing so. . .

I have personally seen a case that bears on this. Karl (as I'll call him) was a pretty good associate. Not (I'd say) the absolute best we had at the time, but definitely above average. A vacancy appeared in the PhD ranks in the group, and Karl stunned the group leader involved by marching in to his office and revealing that he actually had his doctorate, and that he was interested in applying for the position.

What happened to him? Well, he was fired. He was fired reluctantly, and people in the organization found him a position with a small company in the area, but he was fired. He'd lied on his job application materials, and the company's legal department had only to hear that before they ruled that there was no other choice. How could we deal with people who lied about other things on their applications if we kept him on?

The problem was that as things stood, Karl would have moved from being one of the best associates to being one of the lesser PhDs. His strengths and weaknesses at the time fit better for an associate position than as a lab head. And that brings up another question from the comment thread: are too many people going on to get doctorates? I have no idea myself, but I have to say, it's not an unreasonable thought. . .

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March 7, 2007

Fish Nor Fowl?

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Posted by Derek

The grad-school advice topic from the other day got me to thinking about another issue in that line. Everyone knows about how hot all the mixed chemistry-biology stuff is (and has been). Chemical biology, biological chemistry - call it what you like, a lot of people are doing it (and a lot of people are getting funded for it).

That's fine with me. I find a lot of the work very interesting (though not invariably), and some of it looks like it could lead to useful and important things. My worry, though, is: what happens to the grad students who do this stuff? They run the risk of spending too much time on biology to be completely competent chemists, and vice versa. Instead of being seen as well-rounded modern scientists, ready to take on the blurred boundaries of the new research, they might end up unacceptable to their potential colleagues in any given discipline.

I'm sure these fears have come up every time a new field of research opens up. ("Organometallics, you say? So, are you an organic chemist or an inorganic one, hey?") They've taken care of themselves in the past, and they probably will this time, too - eventually. But I'd have to think that there's going to be a lag time, which we're surely still in, during which the people who've done hybrid projects are going to have a hard time proving themselves in the traditional categories.

I should qualify that to the traditional industrial categories. Academia, following the hot topics and following the grant money, is surely more more hospitable to the new breed. But many of the tools of chemical biology are still a bit blue-sky for use in the drug industry (or are seen to be), and even the ones that are already in use tend to be used by people who are more easily classified. Probably the smaller companies are out in front on this, having less invested in the standard organizational charts and often being closer to the academic worldview anyway. Thoughts?

Comments (17) + TrackBacks (0) | Category: Graduate School | How To Get a Pharma Job

March 6, 2007

Decisions, Decisions

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Posted by Derek

I've had an e-mail from someone going off to grad school in chemistry. He wants to eventually do drug discovery work, and is wondering which way to go:

I have it narrowed down to two departments. One is a large, well funded and well respected university with a specific research advisor that is actively recruiting me for his lab. He is a leader in his field and my place in the lab would be in the capacity of synthetic chemist (making various inhibitors). Although his lab is in the chemistry dept it is more on the bio-organic side. My other choice is a smaller less well respected school with fewer resources (lots of TAing) but I could do total synthesis. I would like to join the first group but obviously I want to be able to get a job. If I joined the first group, would I be unemployable in pharma? With a post doc heavy in synthesis would I be able to get a job?

My answer to him was that I'd go with the first lab. A larger school with a more well-known advisor is worth more than the chance to do total synthesis for a PhD - and just as he mentioned, he can do a synthesis-heavy postdoc if need be. Connections mean a lot - ask someone who's job hunting! - and a PhD advisor is generally the first major source of them at the start of a career. The work described is definitely not so far afield that it's going to mess up later job-hunting.

I told him, though, to be sure to get a varied chemistry background in whichever group he joins. You don't want to get too specialized - for future med-chem employment, that can be a killer. A seminar full of same reaction (or class of reactions) over and over isn't going to impress anyone later on - you need to show that you can pick up new chemistry and get it to work, and that you've had to deal with the things that didn't.

One of the reasons that we like total synthesis people is because they've had a wide range of experience, as well as practice with overcoming difficulties. Total synthesis is probably the most efficient way of getting a wide background in synthetic problem-solving in the shortest amount of time. Admittedly, it doesn't always seem like the shortest amount of time while you're doing it, but you can't have everything.

Comments (49) + TrackBacks (0) | Category: Graduate School | How To Get a Pharma Job

February 8, 2007

Depraved and Deprived

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Posted by Derek

Here's another one of those topics that is a bigger concern in academic labs than in industrial ones: stealing supplies from each other. The difference is easy to understand, and can be summed up (as a terrifying number of things can) by the word "money". Industrial labs generally are the Land of Research Plenty, so people don't spend much time looting and pillaging.

But boy, do they have to unlearn those habits. Most academic labs run on tight budgets, so valuable reagents and pieces of equipment get hoarded. People would practically steal things out of my lab coat pockets. I remember going on vacation in graduate school and leaving notes in the drawers in my lab: "Please don't take this. It's the only one I have" or "Go steal one of these from So-and-So. He has more of them than I do". When I came back, people told me how much they liked the notes.

Deprivation leads people to all sorts of money-saving (but time-wasting) attempts to economize. I mentioned a disastrous attempt to recycle lumpy, brown waste acetone here, and there are more stories like that to be found whenever chemists gather. Graduate student time is the one cheap commodity in academia, so you see people redistilling used solvents or washing and re-using silica gel, both of which are (to me) roughly the same as trying to dry out uneaten pasta so it can be boiled again later.

A group down the hall from me in those days used all sorts of exotic mixtures, and whoever made up decent quantities of them was sure to see pilferage. A friend of mine got tired of making things for his colleagues to steal, so he started labeling his bottles with the names of freshwater fish. A midnight raid on his cabinet would present the would-be shortcutter with a row of jugs labeled "Rainbow Trout" and "1:1 Catfish / Smallmouth Bass". That slowed things down for a while, anyway.

Comments (20) + TrackBacks (0) | Category: Graduate School

October 19, 2006

Levoglucosan

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Posted by Derek

Three days before: go to the local supermarket and ask to buy a case of corn starch. Ignore the puzzled looks, which come your way since you don't look like you own a Chinese restaurant. Pay for the stuff out of your own pocket (this is grad school, y'know) and head back to the lab. Ignore the puzzled looks of colleagues who haven't seen you walking around with boxes of corn starch before.

Two days before: mix up a kilo or two of the starch with some dilute acetic acid into a weirdly dilatant fluid. Hold on to the memory of it, unknowingly, for fifteen years or so until you have kids of nursery school age. In the meantime, pour the stuff into a cheap baking pan and put it into a drying oven that no one, since you started in on it, will use for anything else.
One day before: take the baking pan out of the oven, wheezing into the waiting faceful of acetic acid fumes if you try to rush the process. Break the cracked, slightly shrunken white cake into chunks small enough to be loaded into your apparatus. Wonder to yourself if this is how other famous scientists started during their doctoral work, and if it is, how come you never read about it.

Day of prep: load up the reactor, a metal box with a glass tube and ball joint poking out of it, with the chunklets of corn starch. Hook up to a connecting adaptor, with a vacuum take-off on it, which you're going to need, big-time, and a large round-bottom flask at the bottom, ditto. Pour plenty of liquid nitrogen into the dual traps on the vacuum pump, regretting the day that you ever told your summer undergrad, who isn't around, of the potential dangers of LN2 traps, because now he won't get near one.

Hook up the vacuum line and pump down the system, and break out a Fisher burner, without realizing (naturally enough) that you won't use one again for at least twenty years. (Not using corn starch as a starting synthetic reagent for at least twenty years, on the other hand, is something you actively yearn for). Take a deep breath and begin flaming the bottom of the metal box with the burner, making sure to get the whole surface and not to linger too long on any one spot. Moderation, moderation in all things.

Note the wisps of vapor flashing through the glass part of the apparatus, accompanied by a throatier note from the vacuum pump. As the heating continues, look for the appearance of an ever-darker flow of thick heterogeneous syrup. This sticky ooze with black flecks in it is your desired product, damn it all. Continue heating until the lava flow dwindles and its color becomes darker than you think you can ever lighten.

Cool down the apparatus, bleed in some air, pull the vacuum line and kill the pump - in that order, unless you really want to suck oil back into the traps, and you really don't. Now would be a good time to lift those traps out of their liquid nitrogen Dewars, to guard against just that oxygen-condensing explosion risk you foolishly warned your undergraduate student about. Make sure that the pump system is open, though, and that the hose is draped into a fume hood, because some of that odd stuff that's condensed in there is probably carbon monoxide and it will be evaporating shortly.

Turn your attention to your product, which has now cooled into a tarry reddish-brown glass. Dissolve it in water and transfer it to the three-foot-tall liquid-liquid extractor, which you will eventually describe to people who will look at you as if you are describing how you used to hunt mammoths. Start heating up a three-liter pot of ethyl acetate, make sure that all the hose fittings to the water condensor are tight (about three times should be enough to relieve your paranoia), and go to what passes, for now, for home. Your product will be ready for the next phase of its purification, which involves the irreversible blackening of a thick column of ion-exchange resin, in just under a week.

After that and all the rest of it (the evaporation, the decolorizing charcoal, the methanol, the crystallization), take a small sample of your product and put it in a glass vial, hanging a paper label around its neck. Pack it and take it with you on your every move over the next twenty years so that you have it, with its now-yellowed label with the faded ink structure on it, as you sit down at your computer.

Comments (7) + TrackBacks (0) | Category: Graduate School

October 15, 2006

German, Anyone?

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Posted by Derek

Back when I was a first-year graduate student, I had to do something that I'm not sure that folks today have to worry about: pass a German test. Mind you, it wasn't much of a test - you got a passage from a journal article, and could use a dictionary, and you had a couple of hours. Fast page-flipping would get you through it, which is basically how I did it, since I'd only had one semester of the language as an undergrad (and not much of it took). Little did I know that I'd have a year coming up when I'd have to speak the language in order to eat.

You couldn't substitute another language, either, because German is a uniquely important one in chemistry. A lot of the older physical and inorganic (and a huge amount of the early organic) work was done in Germany, which also produced huge reference works like Beilstein, Gmelin, and Houben-Weyl. But perhaps all the verbs in those sentences should be in the past tense, because both of those references are now appearing in English.

Beilstein switched over with the 5th printed supplement, which appeared only after massive delays which led many scientific libraries to give up on their subscriptions. At one point, the print edition was a good thirty years out of date. Organic grad students had regarded Beilstein with awe back in the 1950s and before, but by the 1980s many of them had never used it. The switch to electronic database searching, which was done in English right from the start, brought them back to relevence. Now libraries are having to remind people that the computer-based service used to be part of a printed handbook.

Houben-Weyl, for its part, switched to English in 1990 or so, but that doesn't seem to have raised its profile in the non-German-speaking world. I recall a Dylan Stiles post where he didn't seem to have heard of the work, for example. The publishers finally caught on to the fact that printed reference works are in trouble, and have moved into the electronic age.

So, here's a question for the grad-student readers: does anyone have to take a German exam any more? The importance of the language in chemistry has been in steady decline for decades, and (if anything) accelerated decline for the last fifteen years. And if you do have to take a test, does anyone at your department still know why?

Comments (33) + TrackBacks (0) | Category: Graduate School | The Scientific Literature

September 18, 2006

Tenderbutton Calls It Quits

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Posted by Derek

So I see that Dylan Stiles is going to close down his blog next month. I'll miss it, but I can't say that I'm completely surprised by his decision. He's in the home stretch of his PhD work in a demanding group, and there will doubless be some stretches in the next few months where he'll be lucky to have time to go to the john, much less update a blog. I wish him luck, and hope that his eventual transition to Dr. Stiles is as quick and painless as possible.

And yes, that's my theory as to why he's calling a halt. I'm sure that questions of future employment and so on have crossed his mind, but his kind of site definitely won't hurt his prospects, should he decide to go into industry. Dylan obviously knows his synthetic chemistry, enjoys doing it, and can pick up new material quickly - those are some of the key things that you look for when you're hiring. I second the suggestion made by one of the commenters on his site that anyone who's offended by the blog is someone you wouldn't want to work for, anyway.

When I first linked to him, I wrote that it was a good thing that the internet didn't exist when I was a grad student. I meant that two ways - first off, I'd have wasted huge amounts of time rooting around on the web, naturally, not that I didn't make do with what was at hand. But the second problem would have been that I would have probably been tempted to start a blog myself, which would have taken up even more time that I couldn't have afforded. As I've written here before, the purpose of graduate school is to prove that you can get out of graduate school. After allowing for a certain amount of down time needed to maintain your sanity, things that distract you from that main purpose are not your friends.

If I'd had a blog, I'd have spent a good amount of time venting. That surely would have gotten me in trouble sooner or later, given the amount of steam that I had available. I'm pretty sure that I wouldn't have wanted future employers reading what I had to say after I messed up some reaction at 3 AM, what I wanted to do to my summer undergrad student after he blew us all up, or after one of my ever-helpful labmates had stolen a lab jack out from under a distillation of mine while it was still going. No one knowingly hires someone who sounds like a cranky, hyperverbal maniac, which is what I sounded like much of the time back then. (My current co-workers who read this site can, I hope, restrain themselves from further comment).

As for my situation now, well, I blog mostly at night, and I post from home. That's because "night" and "home" are real times and real places now, as opposed to graduate school, when they were crammed over into that little area on the left-hand side of the dial marked "Not in the lab, for some reason". Life's extras fit into place better after you've had the time to get a life to fit them into.

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September 13, 2006

Spectroscopic Days

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Posted by Derek

Talking about my old optical spectroscopy class brought a couple of other things to mind. One of them is that I have never used a good solid 95% of the material I learned there, ever again. Not even once. I worked on a big ol' honking normal coordinate analysis for a class project during that time, and looking back at it, I'm shocked to see the stuff in my handwriting. I supposed there must have been some benefit to learning all of this material, but it is a benefit that time has managed to obscure.

The main thing I took out of the class was the incident I spoke of earlier in the week - hitting the wall of what I had already learned or could pick up on the fly. I'd been warned for years, while growing up, that I was going to have to buckle down and study someday, which news I absorbed in an abstract sort of way. I thought that the prediction had come true in college, but in those courses I could still show up unprepared and understand what was going on. This spectroscopy class was a different order of experience, and a useful one. Fortunately, I left academia before running into the experience of a subject that not only could not be understood in real time, but couldn't be understood after long and careful thought, either. I am reliably informed that they're out there.

The other result of the class was the following work of art, which I composed one day in lieu of doing the assignment. I posted some of this a few years ago, but many readers will not have seen it. It is, of course, a parody of Lewis Carroll's White Knight's song from Through the Looking Glass, which is in turn a parody of Wordsworth, who seems to have tuned up many parodists to concert pitch.


He waved his hands and asked me why
Some peak would polarize
But I was thinking of my lunch
And looked up in surprise.

He then showed me a diagram
And I found to my shame
I didn't know what good it was,
And couldn't say its name.

And if now I chance to put
My tongue in super-glue
Or madly cram my chiral foot
In its enantiomeric shoe,
I weep, for it reminds me so
Of that old class I used to know,
Of ligand fields and planar nodes
And symmetries of normal modes.

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September 10, 2006

If You Want Your Explanations Overnight, It'll Cost You

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Posted by Derek

OK, the votes in the comments to the Explain This! post came out with NMR/MRI as the clear winner, with a strong plurality wanting to make sure that Fourier transforms are part of the explanation. So that's what I'll take on, but it's not going to appear this week. I'm going to try to pitch the explanation to an intelligent lay reader who doesn't have any particular physics, chemistry, or math skills. I'm out of my mind.

In second place were various suggestions about X-ray crystallography, and perhaps that'll be topic number two. Chirality would be tied with that, except there were actually more votes against it than for it, with people finding it not all that hard to explain. (They've clearly never tried to explain to someone whose specialty is running a Morris water maze assay why all the compounds flipped from R to S just because a group changed out on the far end of the molecule). Other multiple-vote getters were Woodward-Hoffman/FMO, structure determination in general, and antibiotic resistance.

Many of the single-vote topics would be good as well, and some of them would be quite tricky. The person who suggested point group symmetry, though, brought back some memories. I'd never covered anything in that area as an undergraduate, for one reason or another. So there I am in my first year, taking an optical spectroscopy class, and on about the second day the professor launches into a discussion of symmetry operations and their relevance to infrared absorption bands (which is considerable).

And this was the first lecture I had ever heard where I understood nothing but the common verbs and the minor parts of speech. I listened to the whole thing with mounting alarm. It had taken me all the way to graduate school to come definitively to the limits of my knowledge, but the pavement ran out right there. I was so stunned I couldn't even take notes - I'd never tried to take notes on something that I wasn't comprehending at all, so I didn't know how.

That evening, I stalked over to the chemistry library and checked out, among other things, Harry Gray's book on group theory, renowned as the first one on the subject "that you could read in bed without a pencil in your hand". And I didn't go to bed myself until I understood just what I'd been listening to that morning, because I didn't enjoy the experience one bit, and wanted to make sure that it never happened again.

Comments (3) + TrackBacks (0) | Category: General Scientific News | Graduate School

July 31, 2006

Hobson's Choice

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Posted by Derek

One of the things I've noticed over the years is that I rarely stay on a project long enough to have the kind of familiarity with the molecules that I had with the ones I worked with in graduate school. I'm not complaining. I knew my PhD project molecules like an infantryman knows the hundred-pound pack on his back - that is, much more than I ever wanted to or believed possible. I knew tiny details in their NMR spectra, things like long-range coupling constants and NOE enhancements, and the moment something changed I would point like a hunting dog.

But now, my lab stays on a project for a few months, maybe a year at the outside. And during that time, we'll work on several varied groups of molecules - usually with the same core, but with all sorts of things coming off of it. We get a working knowledge of them, but we're always being surprised by little details that would have been second nature after a good solid three years of the same series. Of course, after that good solid three years we'd all be good and solidly sick of the chemistry, too, but that's the price tag.

I used to tell people in grad school, while I hauled yet another load of synthetic intermediates up the mountainside, that the grunt work left me a choice of two moods: bored, or angry. If everything was working just the way it always had, I was bored. And if a reaction decided to unexpectedly fail, then. . .not much of an emotional range, is it? No, I'll take what I have now, where boredom doesn't have as much of a shot at me, and I don't have the chance to stay angry about any one thing for long. Variety, the spice of chemistry. (One of my "Laws of the Lab" covers this topic - I'll get to that later in the week).

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June 27, 2006

Academia in Summertime

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Posted by Derek

When I was in graduate school, I had a law student as a neighbor for a while. We were both pretty quiet, and got along fine in our respective dinky efficiency apartments, but we couldn't help but notice some differences between our studies. The biggest one became clear around this time of the year: he left, and I stayed. I still remember the look of surprise on his face when I told him that we didn't have any time off.

Well, I know that law students don't generally go off and laze around on the ol' hammock during the summer, but they at least get to go somewhere else for a while. But grad students just keep banging away, and if they're in the sciences, they're up there nights, weekends, and holidays.

Ah, those holidays. I still have in my files a memo from my old chemistry department, reminding everyone that the university (undergraduate) vacation schedule most definitely did not apply to us. Do not attempt to take these holidays was the very pointed message, because we will notice if you do. I sure didn't. I did take off some time at Thanksgiving and Christmas, and I didn't work every single July 4th, but otherwise it was a rare, rare day when I wasn't in the lab.

I've written before about my physical surroundings during that time, but things like this memo didn't add to the festive atmosphere very much, either. On the university level, it became clear pretty quickly that we weren't students, and we weren't staff - well, not all the time, anyway. We were whichever caused the least expense and inconvenience to the school at the time you asked the question.

But the biggest factor was the work. It was a strain. I like variety up here in my head, and this was the first time I'd ever had to do the same thing, think about the same thing, day after day (and night after night). It brought on, eventually, the mental equivalent of a leg cramp - I know for sure that I was in a much crabbier mood during my grad school years than I was afterwards, and I'm sure that it was largely because I was venting off some of the pressure. My project had the usual twists and turns, which during one point just about had me tearing my hair in frustration, but the real problem was that there was no escape from it.

Every hour I spend doing something else, besides necessities like eating and laundry, I found myself thinking about how I'd just added another hour to my graduate studies. When I could have, you know, been back in the lab trying to find a way out of the place. That is to say, doing something useful with my time. In the end, anything that didn't directly involve getting out was classified as a luxury, and I tried to ration such things. I remember going past a TV set at one point that had a golf tournament on, and I found myself amazed at these people - not the golfers, the spectators, these people who felt free enough to just wander off and spend the whole day in a sunny park watching a sporting event, without having to worry the whole time about what it was taking them away from.

All of which is why I reiterate my advice to my grad-school readers, who may be watching the summer weather out the windows of their labs (if they have windows, that is): get out. As far as it's compatible with taking a reasonably honorable and complete degree and not leaving any bad blood behind you, get out. The whole point of graduate school is proving that you can make it out of there.

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March 20, 2006

Grad School, Blogged

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Posted by Derek

I spent the day giving the Wonder Drug Company good value for their money - cranking out a load of intermediate for other folks on the project and getting analytical data on some other samples. And talking about that sort of thing reminds me to link to a chemistry blog that I wasn't aware of until recently: a grad student named Dylan Stiles, who's working for Barry Trost out at Stanford.

Stiles is running just the kind of blog that I would have if. . .well, if the Web had existed back in 1985 when I was a grad student. Actually, it was probably a good thing for my graduate career that it didn't, come to think of it. That's the era of the "old timey" NMR machine in this post of his, which makes me wish I could find a photo of what we considered an old-timey machine. Ah, here we go: scroll down to the middle of the page, to the picture under "1976-1977". I used one of those things, and no, you didn't have to load coal in the back of it and wait for the boiler to fire up. It just looks that way.

At any rate, Stiles talks about the reactions he's running, with drawings and schemes, and takes photos of the crystals he gets and other oddities around the lab. I really wish I could do something similar once in a while. I obviously can't talk much, though, about (for example) the heterocycle I finished up today, except to note that the reaction used an unseemly amount of straight hydrazine, like nearly half a liter, and I was very glad to see the back of it. And I'd like to show some photos, too, but the Wonder Drug Factory has a "no camera" policy, and I can see why, what with chemical structures drawn all over the place.

But there would be some things to show off: I dropped a big stirbar right through the side of a one-liter pear-shaped flask the other day, for example, producing a perfect Pyrex analog of a gourd birdhouse. All I need to do is flame-polish the hole and find a way to stick a stopper permanently into the ground glass joint, which is a task that I've always seemed to be pretty skilled at, and I'm in business. See what you're missing?

Anyway, give Stiles a look if you're a hard-core organic chemistry geek like me, and if anyone knows of some other chemistry grad student or post-doc blogs, please send them along. I need to differentiate my blogroll a bit more, and that would be a fine category to have.

Comments (5) + TrackBacks (0) | Category: Graduate School | Life in the Drug Labs

November 13, 2005

Arcadia's Furnishings

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Posted by Derek

I haven't worked in a US academic chemistry lab since 1988, so you'll have to take that into account as you read today's post. But I don't think that things have changed enough to invalidate this observation: many grad-school science labs are so depressing as to defy belief. This isn't universal, but I've seen enough examples to convince me. The atmosphere doesn't correlate well with the amount of money around, either, because I've seen some lower-level departments that weren't so bad, and a couple of Ivy League lab corridors that would pull the serotonin right out of your brain just to walk down them.

Many of the students and post-docs working at these places don't realize this, though, which is surely to their benefit. It's only after you've gone out into the Real World for a while and come back for a visit that it hits you. That's certainly how it dawned on me. I believe it says over there to the left that I went to Duke: maybe someone there could tell me if that second-floor "graduate student lounge" in the chemistry building is still there? I sure hope not.

This was one of the most cheerless rooms I've ever seen; it made laundromats seem warm and inviting. There was no ceiling as such, just the fluorescent lights hanging down from the industrial clutter above. Some scuffed paneling on the walls surrounded an assortment of worn, stained, mismatched thrift-store furniture. A small damaged table in the middle of a couple of sprung couches held an assortment of torn, dogeared cycling magazines, some of which had been there when I arrived and were still sitting there when I defended my PhD. A scarred counter held a 1970s-vintage microwave, which might as well have had "X-1 Prototype" stenciled on it. A bike frame without wheels, furry with dust, was chained to a rack in one corner. That was still there when I left, too.

You feel bad enough at 3 AM on a Sunday morning up in the lab, running a reaction for the twenty-third time. Taking a break by wandering down to a dingy room full of junk is not the recommended antidote. Why more people didn't just decide to end it all after a session in there is a real mystery.

Update: Reader LNT, in the comments to this post, passes on this news:

"I graduated from Duke in 2001 and the graduate student lounge hadn't changed from what you described. I don't know why university chemistry departments can't budget a couple thousand bucks a year to keep a decent communal area for their slave labor pool..."

Oh, dear.

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August 2, 2005

Never Came In Handy. Not Once.

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Posted by Derek

I was trying to think back to the least useful chemistry I ever learned in undergraduate and graduate school, and let me tell you, it's a tough league to play in.

I know, I know, many of you are thinking "Yeah, I hated quantum mechanics, too", but that's not what I'm talking about. Quantum stuff is actually interesting to me, although I am glad to not be obligated to finish any paragraph that begins with "Consider the Hamiltonian. . ." No, I'm thinking of things that were presented as techniques that I'd be using and had better understand and commit to memory.

How about. . .electron spin resonance? ESR was sold to us as a parallel world to NMR, full of its own utility, well worth getting to know. Sheep dip. ESR is interesting and useful to that subset of people who deal with reasonably stable free radicals, but to very few others indeed. I take that point that it's a fine technique for those people, but I'd like to point out that my chances of becoming one of them were never very high. The time and effort I put into learning it could have been spent much more profitably.

"But hold it," says my memory. "You didn't spend any time getting to learn ESR spectroscopy. You read the newspaper during the lectures. You didn't buy the textbook. You only exerted yourself during the hours leading up to the exams, and sometimes not even then. It's no wonder you don't know squat about it."

Er, well, I suppose there's something to that. I recall that the class was divided up into groups of three or four, and assigned regular problem sets to work out and hand in. My group of three became increasingly demotivated as things went on, and by the time of the last problem set, we spent our time complaining about how much we couldn't stand the stuff any more and never got around to solving any of the problems.

Come that Monday morning, I realized that I hadn't put anything together for us to hand in. So I just dug around and found a sheet or two where we'd taken a listless stab at working a problem. That seemed a bit lacking in heft, so I bulked it out with a random handful of paper from a disused notebook, put our names on it, stapled the pile up, and turned it in. There were blank sheets of paper in there; there was a paper towel. The sheets with writing on them often weren't even from the course in question, and many of them were upside down, anyway. What the hey.

Looking back, it's hard to believe I actually did that. My problem set partners found it a bit difficult, too, even at the time: "You did what?" I awaited our grade with interest. A few days later, the professor stopped me on my way out of the class and asked "Do I have your group's problem set?" "Sort of," I responded. "Oh, yes!" came his answer, "that was a messy one, wasn't it?"

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August 29, 2004

. . .It's a Wonder I Can Think At All

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Posted by Derek

When I think back on all the things I learned in grad school. . .well, let's say that not all of it has come in handy. Chemistry, like all the other sciences, long ago split into all kinds of sub-specialties, so it's no wonder that I haven't had to worry much about Tanabe-Sugano diagrams (to pick a representative example from inorganic chemistry.) Nor has normal coordinate analysis featured much in my work of the past twenty years, since I'm not some sort of theoretical spectroscopist. And, thank God, I haven't had to sit down and do any quantum mechanics since the day of my final exam in that well-known rite-of-passage course.

But I haven't had to use things that are nominally in my area of expertise, either. Electron spin resonance, for example - that's something that free radical chemists care about, but I did a whole post-doctoral year doing free radical chemistry, and never did the subject come up. Makes me glad that I didn't spend any more time learning it.

How about chiral aldol chemistry? That's close to home. It's organic synthesis, my very own subfield, and it was the subject of the first question I was asked during my PhD orals. Have I ever done a chiral aldol reaction? Not a one, and I don't have any plans to. Was my time well spent learning all the various theories about how they work? Doubts have crept in.

Moving even closer to how I earn my living, how about all those med-chem graphs and equations they try to teach you? My first year in the business, they sent me (and a number of other folks) off to a well-known summer short course in medicinal chemistry, to teach us the ropes. Now, I can't pretend that I didn't learn anything useful there, although it was all material that I was going to learn anyway. But those equations, those fine equations for pharmacokinetic behavior, for clearance and absorption and distribution. . .I haven't had call for one of them since.

I mean, I think about those phenomena all the time, but not in mathematical terms. The real systems are just too messy for that, and most of the time we don't understand what's going on, anyway. I can just see myself back in that classroom, copying these things down. Did I have the suspicion right there that I'd never write them down again, or did that take a little while longer?

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June 2, 2004

Industry vs. Academia: The Mental Aspect

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Posted by Derek

It's been a while since I returned to this topic. Many differences remain for me to talk about, but I though that it was time to address the biggest one, which is psychological. Some of you probably thought that the biggest difference was money. Can't ignore that one - it probably contributes to some of the effects I'll be talking about. But there's a separate mental component to graduate school that never really recurs, which should be good news to my readers who are working on their degrees.

Some of this is due to age, naturally enough. The research cohort out in industry ranges from fresh-out-of-school to greybeards in their fifties and sixties. (I can say that, since I'm in my early forties, the color changes in my own short beard notwithstanding.) Everyone in graduate school is a transient of one sort of another, usually someone whose life is still just getting going. But in the workplace, most people are more settled in their lives and careers. There are still some unsettling waves that move through industry, mergers and layoffs and reorganizations. But people respond to them differently than they would in their 20s - often better, sometimes worse, but differently.

And not all your co-workers in grad school are actually stable individuals, either. Some of these people wash out of the field for very good reasons, and you don't see as many of the outer fringes later on in your career. It's not that we don't have some odd people in the industrial labs, believe me. But the variance isn't as high as it is in school. Some of those folks are off by so many standard deviations that they fall right off the edge of the table.

Another factor is something I've already spoken about, the way that most graduate careers come down to one make-or-break research project. The only industrial equivalents are in the most grad-school atmospheric edge of the field, small startup companies that have one shot to make it with an important project. But in most companies, no matter how big a project gets, there's always another one coming along. Clinical candidate went down in flames? Terrible news, but you're working on another one by then. There's a flow to the research environment that gives things more stability.

The finish-the-project-or-die environment of graduate study leads to the well-known working hours in many departments. Those will derange you after a while: days, nights, weekends, holidays, Saturday nights and Sunday mornings. I worked 'em all myself when I was trying to finish my PhD, but I don't now. If a project is very interesting or important, I'll stay late, or once in a while work during a weekend. But otherwise, I arrange my work so that I go home at night. For one thing, I have a wife and two small children who'd much rather have me there, but even when I was single I found many more things to do than work grad-school hours. It took me some months after defending my dissertation before I could decompress, but I did. Having a life outside the lab is valuable, but it's a net that graduate students often have to work without.

But beyond all these, there's one great big reason for why grad school feels so strange in retrospect, and I've saved it for last: your research advisor. There's no other time when you're so dependent on one person's opinion of your work. (At least, there had better not be!) If your advisor is competent and even-tempered, your graduate studies are going to be a lot smoother. If you pick one who turns out to have some psychological sinkholes, though, then you're in for a rough ride and there's not much that can be done about it. Everyone has a fund of horror stories and cautionary tales, and there's a reason for that: there are too damn many of these people around.

Naturally, there are bad bosses in the industrial world. But, for the most part, they don't get quite as crazy as the academic ones can (there's that variance at work again). And they generally aren't the only thing running (or ruining) your life, either. There's the much-maligned HR department, which can in fact help bail you out if things get really bad. Moving from group to group is a lot easier at most companies than it can ever be in graduate school, and it's not like you lose time off the big ticking clock when you do it.

I can see in retrospect that I was a lot harder to get along with when I was in grad school. I responded to the pressure by getting more ornery, and I think that many other personalities deformed similarly. When I've met up with my fellow grad students in the years since, we seem to be different people, and with good reason. It isn't just the years.

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March 18, 2004

Differences Between Industry and Academia, Pt. 1

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Posted by Derek

A reader's e-mail got me thinking about this topic. It's worth a number of posts, as you'd guess, since there are many substantial differences. Some are merely of degree (funding!), while others are of kind.

But the funding makes for larger changes than you'd think, so I'll get that one out of the way first. When I was in graduate school, my advisor's research group was actually pretty well-heeled. We had substantial grant money, and none of us had to be teaching assistants past our first year. But even so, we had to watch the expenditures. For example, we didn't order dry solvents, in their individual syringable bottles, from the chemical companies because those were too expensive. Instead, we had our solvent stills, which (to be fair) produced extremely good quality reagents at the price of the occasional fire.

Grad student labor is so cheap it's nearly free, so making expensive reagents was more cost-effective than buying them. (At least, it was if you weren't the person making them.) I had a starting material that's produced from pyrolysis of corn starch (levoglucosan, it's called, and I'd be happy to hear from anyone who's worked with the stuff.) At the time, it sold for $27 per 100 milligrams, and since I used it in fifty-gram batches, that was out of our price range for sure.

So I pyrolyzed away, producing tarry sludge that had to be laboriously cleaned up over about a week to give something that would crystallize. (I saved the first small batch that did that for me back in the summer of 1984, and it's sitting in the same vial right next to me as I write. The label looks rather distressingly yellowed around the edges, I have to say.) A kilo of corn starch would net you about fifty grams of starting material, if everything worked perfectly. And if it didn't, well, I just started burning up another batch, because it's not like I had anything to do that Sunday night, anyway.

When I got my first industrial job, it took me a while to get all this out of my system. I needed an expensive iron complex at one point, about six months into my work, and sat down to order the things I needed to make it. My boss came by and asked what I was up to, and when I told him, asked me how much the reagent itself would cost. "About 900 dollars", I told him, whereupon he told me to forget it and just order the darn stuff. He pointed out that the company would spend a good part of that price just on my salary in the time it would take me to make it, and he was right, even at 1989 rates.

So we throw the money around, by most academic standards. But there can be too much of a good thing. There's a famous research institute in Europe, which I'm not quite going to name, that was famously well-funded for many years. They had a very large, very steady stream of income, and it bought the finest facilities anyone could want. Year after year, only the best. And what was discovered there, in the palatial labs? Well, now and then something would emerge. But nothing particularly startling, frankly - and from some of the labs, nothing much at all. You'd have to have a generous and forgiving spirit to think that the results justified the expenditure. There are other examples, over which for now I will draw the veil of discretion.

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December 9, 2002

Sweet Maybe, But Trouble, Too

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Posted by Derek

As I mentioned in that last post, I did carbohydrate-based chemistry back in grad school. (I still break out the sugars once in a while, but there aren't as many opportunities in medicinal chemistry.) Back then, I was on a project that was using them as starting materials to try to synthesize a large antibiotic molecule from scratch. The idea's fairly sound - the antibiotic has a lot of chiral carbons in it, and sugars are a rich source of strings of chiral carbons.

But there were complications. There's no carbohydrate with just the sort of backbone you'd need (if there had been, the synthesis would have been pretty trivial.) So the project involved taking some of the available ones and tweaking them around - remove a hydroxy group here, flip one over down there, change this to a branching carbon over around this way. The synthetic steps really start to add up after a while, I can testify. A lot of the difficulties came from starting out with such highly functionalized molecules. You had to first protect all those hydroxy groups, and do it in such a way that you could take each protecting group off at just the time you needed it. Pretty soon, you run out of possible protecting groups!

I pulled the plug on the whole thing at about 27 linear steps, and it wasn't finished then. It really seemed to me that we had reached the point of diminishing returns, which opinion of mine time has completely confirmed. It would have taken me another year, at the rate things were going, and that would have been a really bad trade. Even as it was, I was spending most of my time making starting material (as my readers in the organic synthesis field can readily imagine.) And no matter how large a flask (flask? how large a bucket) I started the chemistry off in, I always seemed to get to the frontier of the synthesis with about 20 milligrams. I felt like the guys painting the bridge - as soon as I finished, it was time to start again.

Some time I'll tell the story about what my PhD advisor did when I shared the news with him that I wasn't going to finish the molecule. He wasn't taken with the idea.

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February 18, 2002

A Couple of Days Off

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Posted by Derek

I won't be posting for another day or two; I'm taking tomorrow off from the Wonder Drug Factory and heading out with the family. My chemistry can get along without me just fine, and the people that report to me will most likely be even more productive without me around.

Leaving the lab for a few days was much harder back in graduate school, of course. The main reason was psychological. It took at least six months after I got my PhD for that voice in the back of my head to stop telling me to get back in lab, that I was wasting time. Every hour that I wasn't trying to finish my project was an extra hour that I was going to spend in grad school. This mental nudging didn't just occur when it should have. No, I felt this way when I was doing frivolous stuff like buying food, or putting gas in the car.

The second problem with leaving the lab was that I had a lot of chemistry going on simultaneously. I persisted in thinking that I'd remember every tiny detail when I got back. So I'd return and find a bunch of flasks, helpfully labeled with things like "large batch," "other fraction," or "N." My first day back in the lab always involved a lot of staring up at the ceiling, trying to remember what the heck I was doing.

Of course, many of my days in the lab involved some staring up at the ceiling. The difference was, on those occasions, my lips were moving.

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