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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 (34) + 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 (54) + 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