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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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January 14, 2007

Problems and Solutions

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Posted by Derek

I had some e-mail from a graduate student in a good lab the other day, and I thought the questions raised were worth a blog post. He wrote:

One thing which stands out to me is your enthusiasm for chemistry,
after having been in pharma for a while. This is something which I am
afraid I might lose getting out of academics. I actually was strongly
leaning academically until recently. It just seems the chemical problems you
would be presented in industry are very vanilla....the problem is I
really don't have a good grasp on what these are (especially in drug
discovery).

Then I imagined in drug discovery, you can use any chemistry you want,
so the "cutting edge" (i.e. new organometallic transformations with way
too much expensive catalyst) is still very relevant. I guess I'm just
curious how you stay as passionate about the science as you are. Do you
see this/has this changed since you started in industry? As you move up
the ranks and further from the bench does chemistry get less and less
important?

These are definitely worth asking. My reply was:

?As for the enthusiasm part, I may be a little bit odd, but not all that much. There are still plenty of people who enjoy what they're doing.

But part of it is realizing that chemistry is a means to an end in the drug business, not an end in itself. People are enthusiastic about finding something that works as a drug - that's why we don't mind mundane reactions as much, because those give you a lot more shots at making a drug than something that needs 2 days to set up. Of course, if you do nothing but (say) make sulfonamides all day, every day, you'll go nuts. But things vary too much for that to be a problem (most of the time). There's always another new structure idea that you have to figure out how to realize, another new core to work on, etc.

And the chemistry problems are just as knotty as you'd get in academia - how do I set these stereocenters, how do I do this reaction selectively so I can avoid a protecting group, etc. Sometimes they're on a different wavelength as well: How can I make this stuff in fewer steps? How can I avoid that evil mercury reagent? How do I get this stuff to form the right polymorph? How can I get to an intermediate that'll let me sit back and crank out a few analogs, instead of making everything from the ground up?

But, as I said, chemistry is means to an end. And the non-chemical problems are a lot harder: how do I get these compounds to have higher blood levels? (Next question - why are they so low now? Do they not get in through the gut, or are they getting whacked by the liver, or are they partitioning into some other tissue, or getting hosed out extra fast by the kidneys?) Why does this compound work, but the one without a methyl group kill the rats? (I've had that exact situation - truth be told, we never did completely figure out what was going on. . .) Why does this thing work so much better in mice than rats, and which one is going to be more predictive of humans - if either? And so on.

So, in a way, the chemistry problems take up less of your time the further on you go. Biology and development problems pick up the slack, and then some."

I'd be interested in hearing other takes on these, and I'm sure my correspondent would, too. Any industrial readers care to add some details?

Comments (11) + TrackBacks (0) | Category: Academia (vs. Industry) | Life in the Drug Labs


COMMENTS

1. milkshake on January 14, 2007 11:08 PM writes...

Medicinal chemistry is like engineering - you don't try to invent new tools unless you are desperate and absolutely have to. You use existing and preferably fully-developed metodology to get to a molecule that works as drug - and the simplier the solution is the better. The medchem elegance is in simplicity but if you do something clever in your chemistry along the way that is just as well and you will have some extra bragging rights years later, when your company eventualy lets you to present it.

Medicinal chemists like cyclizations and stereoselective reactions too - but only if these reactions are robust enough to work outside the glove box and if one could buy the precursors. Making the precursor in 12 step sequence before the final step isn't the most practical thing in industry. As allways one has to prioritize - am I going to try chemistry which allows me to make 6 compounds a week - or another chemistry that would take 6 weeks for one compound?

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2. Kay on January 15, 2007 7:29 AM writes...

Academia wants to compete in drug development (Scripps, Burnham, etc) in a more serious way. Perhaps they can find the right mix of freedom and intent. At this point in time, it looks like smoke and mirrors. These academic drug development efforts might succeed over the long term, however, because the largeco model is so out of favor with investors.

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3. Harold Kluender on January 15, 2007 3:38 PM writes...

Hi Derek, If a young chemist wants to continue to work in a lab, he/she would have a greater chance of doing that by going to work in big pharma rather than at big U. While a junior professor may work in a lab himself a bit, if he is succesfull, he will soon be directing grad students as they do the grunt (interesting) work. And then it's the prof's job to get the grunts to think for themselves so, even the most interesting discoveries may come from them, not the Pappa Dog. Of course, he takes all the credit, but we know who deserves it. I worked 32 years in big pharma and a year did not go by that I did not get an opportunity to drop a flask or two, with my my final product of course, into the Rotovap. It was all great fun that I thoroughly enjoyed.

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4. Tom on January 15, 2007 10:37 PM writes...

I would be curious to know what kind of experience you guys in industry has as an undergraduate? I am currently an undergrad who is involved in some med chem myself. I am currently working on a 12 step synthesis of a combretestatin-like drug which I more or less designed myself. I more or less run all my own reactions and I am responsible for decoding my NMR's... It can be a really huge frustration sometimes, because my prof won't ever really tell me how to do things. He just spends most of the time staring at me blankly and tells me to go look it up.

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5. Srikanth on January 16, 2007 2:36 PM writes...

I tell young people chemistry ok career if you know 'the way'. Make sure always please big brain boss and maybe you will be ok. Do not create ideas, use his ideas and prosper you will. You are paid to work, not dream of being moviestar.

Also you must know that you must have retirement money by 35 years. Some on this posting site say old guy better than young which is not true for chemistry. Everyone know chemistry is young persons game. Just move back to whereever you came from when done so can live cheaply as US up north is very expensive. Mexico looks cheap but not as cheap as China.

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6. Derek Lowe on January 16, 2007 5:29 PM writes...

Sounding more like Yoda every day you are, Srikanth.

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7. weirdo on January 16, 2007 7:07 PM writes...

Ah, Derek, don't feed the troll!

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8. Srikanth on January 17, 2007 2:58 PM writes...

Ha! Srikanth know the force is strong within him. Teach you he will.

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9. David Eaton on January 27, 2007 10:14 AM writes...

Hi, y'all-

I'm a PhD research chemist in industry, but far from pharma. The world I work in is dominated by electrical engineers, and I have found that the path to happiness involves learning to speak the language, and appreciate the worries, of those guys. Our chemistry department, split between synthetic/materials chem and analytical make up about 10% of the firm, and our business is dependent on our work, so we get respect and support.

We are not a chemo-centric business, but we work hard to reduce costs and solve manufacturing problems, which ends up buying us a lot of leeway to do pretty speculative research. We always seek to understand what problems the company is having, enforcing a scientific discipline that was new to even other technical people, but that they have learned to appreciate, because it solves and anticipates problems.

We are several hours from a big U, but several of us maintain contacts and intitiate small projects at colleges and universities where we have friends. There is often tension about what we must do vs what we would like to find out- this is probably true even in academia, but it is constant in industry- but I have found ways to get to what I want. The problems I encounter are plenty challenging, and the economic constraints require a second level of creativity and finesse. It can be aggravating, but it is never dull, and it's generally rewarding, even fun.

Like Derek said, chemistry is a means to an end. We have a great crew, good leadership, and management that is technical enough to appreciate what we do, so we are taken care of pretty well. I spend far more time in meetings than I want to, and less time at the bench or doing background research, but that's the price of admission. I think all the people I work with (1/5 are PhDs, the balance BS in science or tech degree, with one chemical engineer for fun) are still excited by the business and the science. People who have been with us nearly 20 years haven't lost the bug for attacking scientific problems. I get up every morning excited by my experiments and by the prospect of solving problems, chemical and otherwise. Speaking to a student, I would say that I did not envision this, exactly, but the reality is better than what I imagined, and I have not one regret for having chosen this path.

Permalink to Comment

10. eugene on January 27, 2007 1:34 PM writes...

David, that's great. It's good to know that there are good jobs (and apparently long lasting) that are still available.

However, most of the chemistry propaganda to get young people to join focuses on finding novel cures to diseases such as cancer or Alzheimers. That's the promise of a biochemistry career as well. Of course, once many do start doing research in the lab, they get lost along the way in materials science, analytical, etc... But I still think that the promise of being able to put your chemistry degree towards curing diseases is what gets many freshmen to go into chemistry in the first place.

And that's why there are so many frustrated biochemists and chemists at the end of the line as well. What they see are the high turnover rate, the doom and gloom, the mergers, and the idiocy that is management of most Pharma companies today.

Maybe drug discover, something that does not follow model business trends, but is so important for well-being, is better off being a government agency (that is not worried about election terms), as well as solely a private sector entity.

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11. David Eaton on January 27, 2007 5:14 PM writes...

Eugene-

To be able to do good while doing something compelling and interesting is a charm of chemistry that drew me to it. I heard the propaganda too, and I have nothing but respect for people who do the hard work in drug discovery and development. 3/4 of the people I worked with as a graduate student went to pharma companies; about half have either been laid off or left for greener pastures, so I guess it's a rocky career path. I thought it looked interesting, too, but my choice of post doc ended up redirecting me.

Frankly, I did not know that the industry where I work now even existed when I was a student. I think it would be good if more chemistry graduate students had some background in business and developed some entrepreneurial skills. Many will end up where these would be invaluable.

I guess another thing I'd tell a student is that the lens though which academics see tends to filter out everything that doesn't fit with the things they have to worry about. So does everyone else, I guess, but it is pretty easy for a student to mistake the opinions of professors for gospel, as isolated as they are. It is good to get a lot of opinions, and talking to people working in industry (e.g. at ACS meetings) long before you are looking for a job will improve your understanding of what is out there.

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