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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: Twitter: Dereklowe

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October 15, 2009

Fall From Grace

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Posted by Derek

A couple of articles have come together and gotten me to thinking. Back during the summer, long-time medicinal chemist Mark Murcko published a short editorial in Drug Discovery Today comemmerating the Apollo 11 moon landing's 40th anniversary:

"People like me, who are old enough to actually remember the events of July 1969, are instantly assailed with powerful and reflexive emotions when we think back to the effect Apollo had on us: the excitement, awe and wonder. My family, like so many others, was obsessed with space exploration. The walls of our den were covered with NASA photos, diagrams and technical bulletins – anything we could get them to send us. Models of rockets hung from the ceiling by fishing line. . .We soaked it all in, and the events of that day remain a seminal memory of my childhood. It was glorious; nothing could possibly be more exhilarating.

And yet...there are some interesting parallels to what all of us, engaged in the roiling tumult of biomedical research, do here and now. Our mission – to invent new therapies that transform human health and alleviate suffering – captures the imagination as profoundly as did Apollo. Our efforts once were regarded with the same admiration as the NASA breakthroughs (and while public perceptions may be different today, our mission has not wavered). We are attempting, one could argue, even more complex technical achievements. . . ."

And just the other day I came across this piece in The New Atlantis entitled "The Lost Prestige of Nuclear Physics". (Via Arts and Letters Daily). Its thesis, which I think is accurate:

"The story of nuclear physics is one of the most remarkable marketing disasters in intellectual history. In the space of a few decades, the public perception of the atom’s promise to serve humanity, and the international admiration that surrounded the many brilliant people who unraveled the mysteries of matter, had collapsed. So pronounced was the erosion of attitudes toward nuclear physics that, by the late 1990s, several European physicists felt it necessary to establish an organization called Public Awareness of Nuclear Science for the explicit purpose of improving the public image of their discipline."

Of course, in that case, there was that little matter of the atomic bomb and the subsequent arms race) to contrast against the excitement of the scientific discoveries and their peaceful uses. One might argue that for the general public, it was all very admirable to be able to figure out the forces that kept atoms together, but when these forces turned out to have such alarming and immediate real-world consequences, the backlash was profound. And while I sympathize with the nuclear physicists, I have to only wish them luck in their attempts to regain a good public image. That's because those consequences are still very much with us, as a glance at the news will show.

But the fall from grace of drug research has been almost as profound, and we've never developed an equivalent of nuclear weapons, have we? In our case, I think the problem has been that we're a business. We bill people for our discoveries when they work. And as I've argued here, people will always have a much more emotional response to any issue that affects their physical health, and can quickly come to resent anyone that charges them money to maintain it. (Doctors, though, benefit from the one-on-one patient relationship. People hate hospitals, hate health insurance companies, and hate drug companies, but still respect their own physicians). This, as manifested by complaints about drug prices, uneasiness about hard-sell advertising, and suspicion about our motivations and our methods, seems to be what's sent public opinion of us into the dumper.

But in the end, Murcko has a point. We really are doing something good for humanity by working on understanding diseases and trying to find treatments for them. Not everything about the process is optimal, for sure, but can anyone argue that the broad effort of pharmaceutical research has been a bad thing? The problem is, it's easy to look around, and slide from there into self-pity. But moaning about how no one appreciates us is a waste of time. The best cure is, as far as I can see, to give people reasons to realize what we're worth.

People who've been pulled back from the brink of death from infectious disease or cancer already have those reasons. But there are so many terrible unmet medical needs still out there, which means that there's plenty of room for us both to do good and to show that we can do good. Yes, it will cost a lot of money to do that, which means that what cures will come will also cost money. But with the partial exception of air to breath, most of the necessities of life tend to involve money changing hands. That's not a disqualification.

So to the readers out there in the industry - go do some good work today. Don't spend too much time in your more useless meetings. Stand up in front of your fume hood or sit down in front of your keyboard and do something worthwhile. It's a worthwhile job, even if some people don't realize that yet.

Comments (45) + TrackBacks (0) | Category: Drug Industry History | Drug Prices | Why Everyone Loves Us


1. pfizered on October 15, 2009 8:26 AM writes...

"Don't spend too much time in your more useless meetings" - if only I could! Today is a videoconference 'celebrating the end of Wyeth'. Tomorrow and videoconference with Pfizer ceo. Monday videoconference with Pfizer R&D. Tuesday videoconference with ...

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2. Wavefunction on October 15, 2009 8:27 AM writes...

Well said! I am actually in a pretty useful meeting right now so I think I can be excused. And technically Murcko is not a medicinal chemist since I think his background is in computational chemistry.

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3. T on October 15, 2009 8:50 AM writes...

Wow, Derek you seem to be in a very reflective mood today!

Great post - I shall try and follow your advice

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4. Ty on October 15, 2009 8:51 AM writes...

Drug industry's fall from grace coincides with the dominance of Pfizer. Coincidence? Not saying it's the cause, but it must have been an effect. The industry's success in the 80s draw a lot of people who specialize in making the most (money) out of it (well, generically called MBA types), kinda formed bubbles in the 90s, let go of the public appeal in the process, and heading toward a crash landing now. A typical life cycle of modern American industries; you focus on making money rather than creating value from what you do, you make a short-term fortune while eating up your own long-term growth potential and destroying public support at the same time. The way the course in unchanging (the money-counting became too a powerful presence), it won't be unlike auto industry in the end.

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5. CMCguy on October 15, 2009 9:52 AM writes...

Excellent and indeed reflect post. At its core I see industry stocked with dedicated and skilled people that are chasing extremely challenging problems. The dominate profit drivers, merger mania, lack of/MBA leadership, heavy bureaucratization and inefficiency/low success rates have contributed to changes in the industry/focus. Although I think much decline has been due to self-inflicted wounds the general lack of public science awareness plus poor/sensationalistic media add to negative impression.

Good "every day" advice in final sentences however I bet most will find difficult to implement.

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6. Vader on October 15, 2009 9:59 AM writes...

I remember a cartoon in the Christian Science Monitor purporting to show an Ivy League business school class. The professor has written on the board: "Production." He tells the class: "Today, we are going to talk about making ... things. Actual things."

A trio of students at the back of the class are very angry. "I don't want to learn how to make things! I want to learn how to make money!" Another suggests, "Maybe we could sue the business school. We could make some money that way."

I despise MBAs.

And yet, the MBA is supposed to be the great rationalizer of our economy, who comes into a business and streamlines everything for maximum efficiency.

I suggest that the record of MBAs at doing so is not very good. I think this lies in the distinction between "management" and "leadership."

And government isn't the answer. It's part of the problem. MBAs are highly trained in the bureaucratic methods of government.


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7. Hap on October 15, 2009 10:41 AM writes...

Well, I'll think I coat myself in napalm again.

I think the "MBA culture" thrives because it tells us (as a country) what we want to hear. There are legitimate issues with how much medical care ought to cost and how to provide it well, but I don't think we want to deal with those issues - we want health care, and we don't really care how it's paid for, as long as it's not by us. Our unwillingness as a society to pay the costs of what we want, and resultant willful unconsciousness of those costs, allows people who promise the sky and the moon (and whose business depends precisely on people not asking too many questions about how those heavenly bodies might be obtained) to be inordinately successful. I think that the government is likely to be the best tool for scoiety as a whole to decide how to pay for those costs, but we first have to be willing to acknowledge the costs of what we want and decide how everyone (and not just everyone else) ought to pay them. The dishonesty of the people selling drugs (and of insurers, etc.) only makes it easier for us to blame them for the cost issues we won't deal with. On the other hand, doctors provide what we want, and our doctor is an individual, rather than a class we can depersonalize, so it's a lot harder for people to to blame them.

Nuclear physics has probably been hosed more because of the dishonesty of the people managing nuclear energy (and the people in government, who forgot that their job was not to safeguard the nuclear industry but to protect their citizens) than by our desire for power without consequence, though that desire is a factor (we want electricity, but nobody wants a nuclear power plant or the waste near them).

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8. John Johnson on October 15, 2009 10:56 AM writes...

Thanks Derek, I needed that.

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9. PJ Hansen on October 15, 2009 10:59 AM writes...

Nice post, Derek! I'll try to do my best. Does that mean I have to stop reading here and get back to work? ;-)


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10. PJ Hansen on October 15, 2009 11:02 AM writes...

Nice post, Derek! I'll try to do my best. Does that mean I have to stop reading here and get back to work? ;-)


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11. Vader on October 15, 2009 11:02 AM writes...

"the dishonesty of the people managing nuclear energy"

Could you be more specific about who these people were, and what they were dishonest about?

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12. okemist on October 15, 2009 11:11 AM writes...

Thanks Derek, I just put 2 kg in the bottle to go into a Phase II. I hope it helps the patients who get it.

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13. retread on October 15, 2009 11:12 AM writes...

Well, since we're dealing in philosophy today, the decline in respect for all things technical (not just drugs and nuclear physics) is, in part, the result of an agenda by a variety of nontechnical types. Consider the Sokal hoax in "Social Text". Here were various postmodern types, using scientific lingo they didn't understand, attempting to set themselves up as judges of the whole scientific enterprise. If this isn't enough look at "Fashionable Nonsense" (ISBN 0-312- 20407-8)

It is necessary for some of them to chip away at the whole notion of progress, having made so little themselves in their respective fields. If Piss Christ or the paintings of de Kooning when he was dying of Alzheimer's represents artistic progress, or the 12 tone scale or John Cage represents musical progress, who can blame them? I'm sure the readership can provide more examples.

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14. Lucifer on October 15, 2009 11:19 AM writes...

When you drive out the innovative wierdos and recruit yes men- you will not get innovation.

When you drive out people who think beyond the next few quarters and replace them with MBAs- you will not get real growth.

When you drive out people who understand what they don't know and replace them them with 'know it alls'- you won't get knowledge.

When you replace job security, by the necessity to show productivity- you won't get calculated risk taking

Replace those who can admit mistakes, with those who won't- and you will never get progress.

Is that so hard to understand.

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15. Hap on October 15, 2009 11:23 AM writes...

Well, the behavior of the people running Three Mile Island might be an example - instead of admitting their problems, they blamed everyone else for talking about them. We've had chunks of safety problems here (the hole in Davis-Besse being an example). The NRC generally seems to act as an advocate for the nuclear industry rather than as a buffer or mediator between the public (its nominal employer) and the nuclear industry 9on whose existence it depends).

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16. Doug on October 15, 2009 11:43 AM writes...

No more good or bad than any other commercial venture. Take your own advice, go do something useful today, and get over the persecution/righteousness debate.

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17. Rogi on October 15, 2009 11:52 AM writes...

I, along with many of my former colleagues, would love to take your suggestion of "doing something useful. Unfortuantely, as many medicinal chemists will soon discover, it's difficult to effect this gracious suggestion when one does not have a job to put said talents to use.

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18. barry on October 15, 2009 11:58 AM writes...

The purveyors of nuclear energy are dishonest in the same ways that the rest of the energy sector (barring wind and solar) are dishonest. Economists call it "externalities". The cost of storing radioactive waste for a thousand year--or of dumping CO2 and mercury into the atmosphere, or of destroying a river's ecosystem--are simply discounted from the kilowatt's calculated cost.

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19. Hap on October 15, 2009 12:12 PM writes...

I don't consider that dishonest - it is a problem with the way economics deals with noneconomic values (and the inherent imprecision in such) and not with the people who sell things, and the job of the people who regulate markets to account for externalities and the costs imposed on others. I figured dishonesty was knowing something to be true and either trying to hide it from others or lying about it - active behavior to avoid unpleasnt facts rather than systemic constraints over which they have no control.

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20. Hap on October 15, 2009 12:16 PM writes...

Most commercial ventures can't save your life, or kill you if poorly executed. Most commercial ventures haven't significantly extended the life span of humans. If you think drugs are simply another commercial venture, then go without them and see how far that gets you.

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21. processchemist on October 15, 2009 12:22 PM writes...

From my european point of view things are quite clear: we're living the initial phase of the decline of the "scientific/technical civilization".
The usual equations showing the global constant or growing level of sci/tech jobs is based on a gross misunderstanding of reality: 1 chinese researcher in a 5 years old chinese CRO company it's not equal to 1 western researcher in a 30 years old company with a 30 years record of faults and successes in drug discovery/development. Technical industrial culture is built on people. If you fire people, you destroy industrial culture. Thousands of freshly unenmployed scientists in the western world are a global loss. Easy to say where most of the responsibility lies. Much difficult to divine a way out from this situation.

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22. Jose on October 15, 2009 12:33 PM writes...

Doug, "No more good or bad than any other commercial venture."
Seriously? I can only imagine who you work for- AMRI, perhaps, or Covance?? Then, you are spot on!

"30 years old company" sad to realize how many companies there existed with an extensive pedigree, and how very, very few of them survive.

"Lucifer's List" above should be posted in every hood all over the industry- so damn true.

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23. Hap on October 15, 2009 12:43 PM writes...

Vader: I can't find the specific reference to TMI iI was looking for, let alone the systemic dishonesty I was referring to, so you can assume my third paragraphy may be wrong. Alternatively, if you have a pointer to better history, that would be OK.

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24. Anne on October 15, 2009 1:13 PM writes...

If the reason drug companies have lost our respect is because they seem to be holding our health hostage until we pay them money, doesn't that make it mostly an American problem? After all, in a country with socialized medicine, you get treated whether you personally can pay or not. The way you actually pay, through taxes, is so nebulously connected to what the drug companies charge, it shouldn't have the same effect at all. So do drug companies get more respect in, say, Canada? (Or, since Canada is strongly affected by American culture, European countries with socialized medicine?)

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25. Jorgensen on October 15, 2009 2:12 PM writes...

Murcko likens his endeavors to those of Apollo 11. But in my experience with Murcko and his lot, they are more akin to those of Nestle, who went to third world countries and convinced mothers to give up breast feeding for formula. That is to say: Self serving, and an attempt to replace something that works (traditional drug discover/design, breast feeding), with something that probably doesn't work much better, if at all, but which fattens a few pockets ("rational drug design", formula).

There have been some seeming successes in rational drug discovery. But as someone who has been in the field since the days of the dinosaur, I can tell you that if you lift the veil off most of these success cases, you will find a lot of puffery and mostly luck and traditional approaches.

There are a few superstars in the field who can honestly claim to have made real contributions based on rational discovery that stand up to scrutiny. But not many. And none of them are better known for talks and op-ed pieces than nose-in-trench work.

Probably enough said.

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26. Lu on October 15, 2009 2:18 PM writes...

24. Anne

I'm from one of the Europeans countries with socialized medicine.
Local drug companies are invisible there.
They just do their jobs, slowly but steadily, and their products are available for a pocket change.

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27. Anon on October 15, 2009 2:38 PM writes...

Well said - I'm off to make some compounds 

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28. milkshake on October 15, 2009 2:39 PM writes...

Though they be mad and dead as nails,
Heads of the characters hammer through daisies;
Break in the sun till the sun breaks down,
And death shall have no dominion

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29. Mark on October 15, 2009 2:48 PM writes...

My former employer would bring in patients that were helped by our drugs. It was always a powerful presentation. These were people, whose lives were stolen (or about to be ended) by disease.

Then they talk about talking a drug that your company made and having their lives transformed. About the closest you can come to the resurrection of the dead. And then they talk about everything that goes along with that: spending time with their children or such simple pleasures as being able to talk a walk on a nice spring day.

That's the kind of work that the public needs to know about.


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30. CMCguy on October 15, 2009 2:49 PM writes...

#14 Lucifer is magnificent summary although I do disagree with #22 Jose as posting on hoods would be like "preaching to the choir". If only could place this in industry Boardrooms to be read at each strategy meeting then it might have a chance to gain understanding.

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31. retread on October 15, 2009 3:07 PM writes...

#29 Mark: That's exactly why I found medicine much more personally satisfying then chemistry or math, despite its numerous frustrations and intellectual slovenliness. For an example of the latter see the Chemiotics II post of 5 October.

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32. Witty Brit on October 15, 2009 3:26 PM writes...

I wish I could be doing something that I found incredibly worthwhile in my Pfume hood. But since greedy Big Pfarma MBAs and lawyers outsourced my job to China and India to line their own pockets while I collect unemployment and struggle to pay my family's COBRA insurance, I can't. For those of you who can, run a TLC for me.

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33. Robert on October 15, 2009 3:41 PM writes...

I think there's a perception that drug companies, while developing treatments for diseases and afflictions, are not financially interested in developing cures for diseases because it's not long-term profitable; why give someone the opportunity to pay once and not have a problem anymore when they can continually pay out money to live/survive? The position is that there is a monetary value on life/illness that must be met or you will die without it, practically forcing the choice.

How much truth is there to this?

Obviously financial success of a company in this country (the US) is measured in continued growth and profit margins; how much does this importance of financial security take dominance over the vested human value of life?

That's what worries me the most.

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34. Sili on October 15, 2009 4:20 PM writes...

The problem seems to be that there's no way for a company to survive by doing good. It has to do well.

As long as there are shareholders, there is a need to keep those satisfied, which means turning a profit.

I'm not saying that making money is bad, but is there any way to make money while targeting say malaria or one of the other multitude of developing world diseases*.

Of course it's easy to point the finger at organisations (or at least an organisation) with more money than is good, but while they may on paper be committed to doing 'good', they're certainly not doing much of it. So I don't seeing them setting up non-profit pharma research.

*I've said elsewhere that I'm in favour of getting rid of people en masse, but I really do not want to do so through pain and suffering.

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35. Morten G on October 15, 2009 5:04 PM writes...

God, so self-centered! People hate bankers, insurance agents, lawyers, and politician right now. Pharma is way down the list right now.

/tongue in cheek

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36. Banana Fish on October 15, 2009 5:08 PM writes...

Thanks Derek, needed the inspiration during the lull time on my project. Cheers.

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37. Another CMC Guy on October 15, 2009 6:33 PM writes...

Derek, a thoughtful and well written post today. The first-person stories we hear at work of patients who have had their lives transformed or returned to them due to the important work of our industry are still the best reward of this business. Thanks for the reminder about what is ultimately important. Profits are a necessary means to a bigger end.

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38. LFreeh on October 15, 2009 11:05 PM writes...

Bring it on, promptly on Friday without fail, your ever so predictable diatribes against success. Don't let us down. Eh.

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39. TJ on October 16, 2009 7:29 AM writes...

The reason we were so enthralled with this "glorious" "exhilarating" achievement is because it was THE MOON! Come on, Man, drug discovery is not the moon landing. A six year old can't look at a pill in a bottle or shot in the rear and say wow, this must be like landing on the moon! And neither can many 50 year-olds. And if by some stretch of hyperbole and curving of the "parallels" that are described one claims the pharma industry is landing on the moon - I'd say the thrill is gone not because of the achievement but because of the repetitiveness ( and many others) or near misses that keep occurring. Bring on the drug equivalent of a Mars landing or that fossil of life on the moon and you'll see the image of pharma rise...and deservedly so. But another more powerful rocket to the moon by another country coming of age isn't going to do it. . . and now it's time to go work up that reaction.

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40. TMac on October 16, 2009 7:47 AM writes...

You're absolutely right Derek. While the process isn't perfect it sure turns out extraordinary product. I wouldn't be here typing this note if it wasn't for my BMS investigators who created Sprycel. Everyday I get up and look out the window, I get that incredible sense of awe which I hope is like landing on the moon. So anyone in the research community reading this -- bless you and keep up the fantastic work!


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41. Vader on October 16, 2009 9:55 AM writes...

"The purveyors of nuclear energy are dishonest in the same ways that the rest of the energy sector (barring wind and solar) are dishonest."

I would say that the purveyors of wind and solar are dishonest in a different way than other parts of the energy sector.

It's probably true that fossil energy gets away with writing off a lot of its externalities. In fairness, those externalities are very difficult to compute.

Hydro is remarkably low in externalities, primarily because water and land rights, which it most heavily impacts, are very closely tracked. Yet hydro gets a lot of criticism from people, who rarely own the land or water rights affected.

I'm not sure nuclear has that many externalities. Nuclear plants dump a lot of heat into their cooling reservoirs, but that's unavoidable thermodynamic reality. The nuclear emissions are tightly controlled and, frankly, negligible -- they were negligible even at Three Mile Island. Chernobyl is another matter, but that spectacular display of irresponsible engineering has no counterpart in the West. Nuclear waste is not an externality; the nuclear plant operators have to pay to have the waste disposed of. In fact, they've been required to pay to have their waste disposed of for decades now without the waste actually getting disposed of, which hardly makes them seem like the evil party here.

At risk of saying too much about myself (there's a reason I use an eponym) I've had some involvement in characterization of nuclear waste disposal schemes, and I've concluded the problems are mostly political rather than technical. Want to get rid of the waste for good? (I point out that that may not be the best goal.) Drop the waste in empty torpedo casings into an oceanic subduction zone. The torpedo will hit bottom with enough speed to penetrate deeply into the muck, and then there ain't anything going to get out -- any leakage will adsorb to all that highly reactive muck. Which will then be drawn deep into the mantle for a million years. But it's politically impossible to dump nuclear waste in the ocean, however technically sensible.

That the problems are primarily political doesn't mean they are imaginary, any more than love or hate are imaginary. If anything, it means the problems are more intractable than a pure technical problem.

Getting back to solar and wind -- The lie here is that these are economical alternatives to other energy sources. I see solar as a useful supplement to nuclear, no more. The capital costs are high even compared with a nuclear plant; the reliability is low; and the footprint is large, because you're tapping a low-density energy source. Wind is not even much of a supplement, because all the same factors are at work, squared. It's a boutique power source at best.

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42. Randy on October 16, 2009 10:07 AM writes...

#39 TJ: Drug discovery not as big as a moon shot? I'll grant you it lacked the thrill of watching live video from the Moon, but I would point to the arrival of polio vaccines in 1955 as a far greater good. They were simply a Gift From God. No TV show (even one from the Moon) can compare to knowing that your children are finally safe from polio. Personally, I'll take the grateful thanks of a billion parents over being spam-in-a-can, any day.

Old fears are soon forgotten. We have the great work of drug developers like Salk, Sabin, and Hilleman to thank for that.

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43. TJ on October 16, 2009 3:24 PM writes...

Of course the polio vaccine in 1955 was a far greater good. Murcko wasn't talking about a greater good for the lunar landing in his editorial, he was talking about "excitement, awe and wonder". I don't disagree that the arrival of the polio vaccine, and yes I am too young to recall the days prior, was equivalent to the events of the summer of '69. But to get back to that type of glory in the public eye, we need more than an image makeover and more than another ssri.

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44. doctorpat on October 18, 2009 10:34 PM writes...

"The purveyors of nuclear energy are dishonest in the same ways that the rest of the energy sector (barring wind and solar) are dishonest."

Ha! Those solar and wind guys have you wrapped around their little finger. I have to admire their brilliant snow job that people swallow without blinking.

(I work peripherally for both industries).

"I think there's a perception that drug companies, while developing treatments for diseases and afflictions, are not financially interested in developing cures for diseases because it's not long-term profitable; why give someone the opportunity to pay once and not have a problem anymore when they can continually pay out money to live/survive?"

That works if there is one or two drug companies. If there are several, then the company that DOESN'T make the long term treatment has every motivation to make the cure and steal the business.

Which is why we need a merger tax.

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45. Absurdist on October 19, 2009 2:57 PM writes...

Vader@41: Excellent analysis

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