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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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In the Pipeline

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April 15, 2008

Walk Around Some

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Posted by Derek

Not many chemists come into the drug industry knowing very much about biology. I certainly didn’t, not on the level that was needed. It’s not surprising, but it’s also not as much of a handicap as you’d think, at least not at first.

That’s because the first job of a new hire in the med-chem department is to crank out compounds, and that goes for both the PhD and Master’s levels. (Those roles diverge as time goes on, though). But with a few obvious rules in hand (no hot reactive functional groups, no huge greasy monster molecules, etc.), a person can contribute reasonable-looking compounds pretty quickly. No biological knowledge needed.

But if you’re going to be more valuable than a new hire (and as time goes on, you’d better be), then you have to start picking up some more of the broader science of drug discovery. That turns out to involve a lot more than chemistry, which is one of the things that chemists have to get adjusted to. If you’re going to move up to the point of being considered to lead a new project, you’re going to have to show that you can converse with the folks who know protein expression, assay development, molecular biology, PK, toxicology, and so on. You’re not going to be expected to come in and solve their problems (although if you do manage to solve one once in a while, it’ll do both you and them some good). But you are expected to understand what they’re talking about.

So that’s a piece of advice I can give to new chemistry hires in this business: get ready to learn everyone else’s business, too. Listen up when the people from the other departments talk about what they’re up to, and especially when they complain about their problems. Try to understand why they’re complaining, and ask them (especially one on one) about what they usually try when this sort of thing happens. The occasional paranoid might think at first that you’re compiling info in order to mess with them later, but you shouldn’t be the sort of person around whom that suspicion credibly lingers. In general, if the people in those other groups are any good at all, they’ll be glad to tell you what’s going on, and you’ll pick up a lot of practical knowledge.

The consequences of not doing this sort of thing become more severe as time goes on. At one of my former companies, we once brought in a job candidate from BNP (Big Name Pharmaceuticals). He’d been around seven or eight years, enough time to be considered fairly experienced. But people at that level vary a lot, and he was (as it turned out) on the low end. When we’d ask him about, for example, any formulation problems he’d had to deal with on his project compounds, he told us that well, he didn’t usually go to those meetings, his boss did. And when we asked him about how he got along with the PK group – well, they were over in another building, and he hardly ever saw them. And so on, and so on.

He was well along to being crippled by the way things were done at BNP. Actually, it may have been more the way he was doing things. From talking with other people from that shop over the years, it’s clear that it didn’t have to be that way – if you made the effort, you could go to those meetings, and if you took the time, you could go over to those other buildings and show your face. But you didn’t have to, and this guy (since he didn’t have to) didn’t bother to. And by keeping to his burrow, he hadn’t learned nearly as much as he could have. We didn’t make him an offer. So talk to people, talk to people outside your field. If you’re any good at all, they’ll learn something from you, too.

Comments (14) + TrackBacks (0) | Category: How To Get a Pharma Job | Life in the Drug Labs


COMMENTS

1. Mark M on April 15, 2008 11:25 AM writes...

Derek writes: "Not many chemists come into the drug industry knowing very much about biology."

It's not that chemists with this knowledge arent applying. Rather it is the ridiculous bias against medicinal chemists who apply for positions as medicinal chemists within pharma as perpetrated by total synthesis snobs.

And spare me the "but they arent good synthetic chemists" crap.

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2. weirdo on April 15, 2008 11:47 AM writes...

Mark M;

It ain't crap.

If an individual with a medicinal chemistry Ph.D. displayed excellent synthetic skills, they would be a fairly hot commodity. Or, did some really nice medchem (not the typical crap academic medchem you see published all the time). Or, did a nice post-doc in a good synthetic lab.

But, typically, they do not. They blame "bias" and "snobs".

There may be bias and snobbery in some big pharma labs, but in my experience that is the exception rather than the rule.

Your mileage may vary.

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3. CMC guy on April 15, 2008 12:57 PM writes...

weirdo my mileage reflects more towards the Mark M view (and my background is as a traditional synthesis PhD). Often I have seen med chem groups (and process too) act as self perpetuating clones in hiring practices of only syn lab jocks. A Dept Head once offered was easier to teach a syn chemist to do med chemistry than a med chemist how to do syn when refusing to even bring in certain candidates. There is a corollary to somewhat common approach of only looking at people from Big Name Schools/Groups in that while has advantages (in general exposure to more high level science/seminars for one) does not necessary predict success/contributions. Like all stereotypes and prejudices these attitudes overlook the individual and what they may be capable of if given a chance. Creating a good environment that intertwines varied expertise and backgrounds is essential to achievements. Although can be taken to political correct extremes there is usually greater strength in diversity that brings together disparate perspectives and skills.

Derek righty points out that observation and communication with other functions are a key, including making sure that recognize same terms may mean different things in other fields which can be very subtle to the contexts. Discovery and Development does demand multidisciplinary interactions and probably the biggest adjustment for most PhD is learning to work in Project teams since majority of academic pursuits encourage an independent lone wolf methodology.

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4. milkshake on April 15, 2008 4:03 PM writes...

The real problem is that many academic medchem programs are not very good because their PIs have no clue what the actual drug development looks like - and they dont teach good chemistry and they dont teach good understanding of medicinal chemistry either. You need to have a broad exposure to synthetic methods, know purification tricks aand know how ho bring material through multistep sequence. Tot. synthesis is quite useful excersize.

As for the famous group bias, it is just like with a brand - some people would pay extra to buy Sony TV set. I agree it is unfar. The thinking goes like since the job applicant managed to get into a good school and good group, he cannot be completely bad.

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5. The stranger on April 15, 2008 6:21 PM writes...

I apologize for the thread hijack, and, if this is inappropriate, feel free to delete this, Derek. However, I had a question regarding this very topic that I would like to discuss with you, Milkshake. Would it be possible that I could email you?

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6. Sili on April 15, 2008 6:21 PM writes...

Burrowing is definitely bad. I just stuck to small molecule crystallography because it was fun and easy - right up till it wasn't anymore.

Now I wish I'd picked up some good lab skills. And just a bit of knowledge about proteins and protein chrystallography.

Silly me.

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7. Anonymous BMS Researcher on April 15, 2008 6:49 PM writes...

Derek, I must say, coming from the Biology side myself, I have long been impressed with how well you understand our side of drug discovery!

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8. Jiimmy D on April 15, 2008 8:51 PM writes...

"If an individual with a medicinal chemistry Ph.D. displayed excellent synthetic skills, they would be a fairly hot commodity."


Please identify the companies where chemists are valued 'hot commodities' and not considered disposable parts.

Jesus, haven't you noticed EVERYBODY is laying off and firing?

What kind of world do you folks live in? Is everybody posting here in Academia?

-perplexed

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9. drug_hunter on April 15, 2008 8:51 PM writes...

I'd add two other pieces of related advice:

(1) On your walks, be sure to include talking to clinical and marketing people. It can be quite an eye-opener.

(2) Occasionally, go to scientific meetings outside of your core area. For example, I'm not a peptide chemist but I attended the peptides Gordon Conference one year and learned a ton. I've had similar experiences over the years at conferences on bio-organic, cell biology, biomarkers, tox, structural biology, etc.

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10. Anonymous BMS Researcher on April 16, 2008 6:18 AM writes...

Jimmy D says:

>Please identify the companies where chemists are valued 'hot commodities' and not considered disposable parts.

Indeed, anybody who has been in this industry for a while (in my case, 10 years as of this summer) has done so by demonstrating capabilities beyond the merely technical. As one former boss put it, "throw a rock at any college campus and you'll hit a scientist, I need more than that."

As Derek and many others who have been around the block a few times can tell you, when a site closes the folks who work there had better be able to tell convincing stories about how they collaborated with other departments to advance programs.

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11. RTW on April 16, 2008 5:24 PM writes...

Well - I for one have a problem with Dereks second paragraph. What about those of us with BS degrees in chemistry. I have 11 patents in my 20 years in Pharma for which I made significant contributions. I had a published paper as an undergraduate, which I did almost all the work towards and a chunk of the writing. However as time went on I found that the BS degree was devalued more and more from when I entered the ranks of Big Pharma. As time went on you couldn't advance any further despite how good your ideas in medchem because they sure as hell were not going to give you an MS or PhD to supervise no matter your relative experence and capability next to them. Thats all they where hiring at that point in time.

I was fortunate before management forced me out (became too expensive to keep for someone they wanted to just be a pair of hands and not think) to have a young very productive supervisor that actually told me he was learning many things in the lab from me! This was a guy that had no peers in the department. No one could touch his productivity and ability to get compound in a bottle. I and many others could not figure out how he was able to do it!

I take exception as well to MarkM's assertion as well. At the entry level in Big Pharma they expect you to put lots of compounds in a bottle to test. Most medchem programs don't do a good job providing those kinds of lab skills. Early in ones career cmpds in bottles equates to being more important that what you knoe about medchem.

That said - If you stick around in one Big Pharma company long enough you will see that quite a few departments members come from certain research groups. The majority of interviews from certain groups of schools. Big Pharma had their pick of the most promising people from the big names in chemistry. Too bad most of them only ever did carbocyclic chemistry. A lot had to spend time making the transition to heterocyclic chemistry. In my opinion its a whole other animal.

Lastly I have to agree with JimmyD. Chemists with a lot of experence are being let go in larger numbers than ever before to be replaced by cheaper offshore resources. When the Pfizer Ann Arbor facility was closed almost no one at all in their 40s to early 50's was retained if all they had as a BS or MS degree. On fact in the two years prior to the site closure I bet more of that group of scientists than any other where being pressured via many means they could to leave. In my case I got tired of the reaction counting. Didn't matter that my reactions where usually 2 to 3 times more productive leading to desired products put in a bottle...

Additionally be careful in todays big pharma. They hire you to do one thing you better not spend any time trying to learn about other aspects of the business on their nickel. I was very interested in Cheminformatics. They tried for many years to push me out of chemistry into IT, where every chemist I know that moved that way lost their job inside of two years.... Similar situation there. Well we can teach a CS major all about chemistry....

Enough said. Sorry about the seeming rant...

Permalink to Comment

12. Anon on April 16, 2008 11:50 PM writes...

Well we can teach a CS major all about chemistry....

That is pretty funny.

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13. Kay on April 17, 2008 8:42 AM writes...

Knowing the rule of five and that good PK in any two species equals success is enough biological and medical knowledge.

We are not up to speed in Chinese, however: in addition to the very best financial terms, licensors generally look for some special cultural sophistication as evidence that a civil business relationship is possible.

A basic level of conversational skills may sway the deal in your favor.

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14. zts on April 23, 2008 5:38 PM writes...

This is a comment regarding the value of a degree in total synthesis versus medicinal chemistry, for someone going into big pharma. I come from a total synthesis background, and am thusly biased, but I agree with the often-heard idea that it is easier for someone with a synthesis background to pick up the needed medicinal chemistry than vice-versa.

One of the principle differences is that nobody (at least at my company) really talks about synthesis in any depth at all. People talk about medicinal chemistry. They talk about what compounds to make and why. They discuss SAR. They talk about what they should try to do to get into the brain, or to increase solubility, or to improve metabolic stability, etc. It becomes much easier to pick these things up, because that is what you're immersing yourself in. In terms of synthesis, sure, sometimes people will make suggestions of routes, or different reagents to try, or things that might or might not work, but I rarely hear anyone explain *why*. Nobody discusses mechanism. Nobody discusses the strategy, the how to think about synthesis type things that people in synthesis groups spent so much time dwelling on.

One might say we don't really need to know the mechanisms, we just need to make the compounds. Or we don't really need to know the subtle details of the modern catalytic asymmetric variant of whatever is currently trendy in academia. But I think these things are important, in terms of being able to think about chemistry, to design and troubleshoot the routes, and have the hands to actually carry them out. Yes, you can get this kind of training in a med chem group, but in my experience it isn't quite the same level. And these are of course all broad generalizations. There are no doubt countless exceptions, and either kind of group can turn out great scientists. I just think that it is typically a little easier for someone from a total synthesis group.

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