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
Today I can recommend this interview with Sir James Black, discoverer of propranolol, cimetidine, and more. He's 83 and has a lot to say about the current state of the drug industry:
He becomes agitated when discussing a Harvard Business Review article from 2008 by Jean-Pierre Garnier, the former chief executive of GlaxoSmithKline, on the future of drug development. He agrees with the prognosis, but is fundamentally at odds over the prescription for change. . . He has no time for classic industry clichés such as "blockbuster" medicines; no truck with the modern approach to peer review; and no patience with any re-writing of history to suggest a more complex contemporary era of drug discovery has replaced one of "lowhanging fruit" in the past. . .He raises his eyes skywards when he discusses last week's $68bn (£48bn) takeover by Pfizer, the world's largest pharmaceutical group, of Wyeth, and says the restructuring to come will sap both teams. "Will they never learn? They will completely exhaust each others' energies for two years."
A lot of people sent that Gautier article along to me, and I meant to blog about it all last fall, but I just couldn't put myself into its worldview enough to do it. And all the talk about Sanofi-Aventis looking to get bigger, Merck saying that they can't rule anything out (Merck! Doing a big merger? Say it isn't true. . .) Well, let's just say that this doesn't look like the kind of future I really want to experience.
So Sir James's viewpoint is refereshing, in a way. He goes on to talk about the general uselessness of marketing forecasts, why you shouldn't let yourself be pulled out of R&D into bureaucratic shuffling, and many other useful things. Read the whole thing, as the blogging phrase goes. . .
I was priveleged to work with individuals who were a part SKF when Sir James was running the program that resulted in Cimetidine. They were supposedly told by the financial types that there was little interest in a therapy for a condition that could be "cured" by surgical removal of part of the stomach; therefore the program should be stopped. Sir James and his coworkers wisely ignored this advice.
At one point in time Sir James was slated to become head of R&D for SK&F in Philadelphia; he withdrew for personal reasons. It is intersting to speculate how things would have turned for that organization if he had taken leadership.
Black should know; he worked in a golden age where small groups were given a lot of freedom to pursue their own interests. As long as pharma snubs free-thinking, open-minded basic R & D, it will continue to slide downhill and finally extinguish itself. If there's anything we have learnt from the software hacker culture, it's that free-thinking not stifled by bureaucracy and management is the only way to encourage true innovation.
Human beings, as a group, are incapable of perceiving reality through means other than abject failure. Unless and until the actions of these financial types wreck the world and everything productive in it, people will not wake up.
It took an epidemic ('black death') to start the destruction of the hold of religion over people. It took WW2 to destroy colonial empires. It takes a lot of damage to convince groups of people that they were wrong. But they eventually learn.. well.. at least the survivors do.
"Black should know; he worked in a golden age where small groups were given a lot of freedom to pursue their own interests. As long as pharma snubs free-thinking, open-minded basic R & D, it will continue to slide downhill and finally extinguish itself. If there's anything we have learnt from the software hacker culture, it's that free-thinking not stifled by bureaucracy and management is the only way to encourage true innovation."
[James Black doesn't exactly present a convincing case for scientists being left alone does he:]
"We have moved away from studying the complexity of the organism; from processes and organisation to composition."
[I have no idea what he means by that statement]
"He rejects any suggestion that drug discovery was easier in the past. "I never found it easy. People say I was lucky twice but I resent that. We stuck with [cimetidine] for four years with no progress until we eventually succeeded. It was not luck, it was bloody hard work.""
[How is the notion of hard work independent of luck?]
"Sir James was not able to repeat his own blockbuster success a third time, either at Wellcome, at subsequent academic posts, in the James Black Foundation that he founded after retirement, or in his continuing research today."
[So he follows the familiar pattern: argues biology is hard (duh), success was achieved through bloody hard work, and his latest efforts have been for not.]
Bottom line: Black can't find drugs NOW either and has no idea what to do.
7. HOMO-LUMO on February 5, 2009 2:10 PM writes...
Another outstanding scot, why all the great scots are holding positions abroad, and almost none are in that small country, is a point that always bessoted me...Fraser and Macmillan just two examples
Skeptic: I think he's beyond having to find drugs. (I assume at 83, he's probably retired.) If you assume that it's not his ability that enabled he and his coworkers to find those drugs, then it had to be something else, something which has changed between then and now. Management style seems like a good place to start.
If I have to ask someone how to find drugs, should I ask someone who was helped find some or someone who knows money but little about drugs? The answers might have something to do with pharma's recent lack of success.
Anyone who utters this statement should have been closely involved in discovering a blockbuster or two. If not.. just shut up!
//Sir James was not able to repeat his own blockbuster success a third time, either at Wellcome, at subsequent academic posts, in the James Black Foundation that he founded after retirement, or in his continuing research today//
There is your problem! Drugs are not found by 'knowing the answer' or 'I am always lucky'. It is a combination of chance, ideal working conditions, competence, hard work, vision and whimsical decisions. It is not a method, it is a semi-random process driven by hunches and fortunate mistakes.
//Bottom line: Black can't find drugs NOW either and has no idea what to do.//
I have an idea to improve productivity in pharma. We should get rid of-
1] all MBA types
2] all 'pedigreed' scientists (especially the well funded bozos) who have ever uttered the words - "I am certain that..."
I seconds Hap's comments wholeheartedly. GOOD executives know how to "butt out" when required and when to provide direction. Good executives seem to be scarce these days.
11. S Silverstein on February 5, 2009 9:46 PM writes...
Sir James Black sounds a lot like Maurice Hilleman, PhD, who in his 80's as Merck emeritus was one of the most voracious users of the MRL science research library I ran at WP from 2000-2003. Dr. Hilleman was the inventor of many major vaccines.
Dr Hilleman wrote review papers on vaccines, and used to chat with me in my office about his take on "modern" R&D.
He echoed some of the same sentiments as Black, in the sometimes colorful language Dr. Hilleman was known for. He did not take kindly to incompetents and bureaucrats and the sterile formalisms and unproductive rituals of the latter.
Interestingly, regarding R&D support he also defended keeping traditional information assets as opposed to a move entirely away from paper. He wrote me a supportive memo to that effect which you can see here.
One problem in all this is a cultural trend. We want everyone to be more "accountable" and we want to show that good processes are being used. Those are laudable goals in the right context, but basic discovery-oriented research is probably not one of those contexts. They are part of a secular trend toward increasing layers of red tape and review carried out for seemingly ritualistic purposes. "Can-do" informality has become a kind of sin.
For that matter, the "accountability" overheads in areas such as defense procurement, science funding, public-sector personnel decisions, financial reporting of companies, and environmental impact statements have probably gone well past the point of zero marginal returns into negative territory. But there are now huge vested interests that benefit from all the red tape, individuals and organizations that have specialized in participating in these rituals. The day we can get back to funding and building something like Brookhaven National Labs based on a five-page memorandum from its founder will be the day many of these problems will diminish.
Accountability: A pharma company that "measures success" and minutely flow-charts its research projects (with go/no go decision-making points) is managed by phony accountants with no accountability.
14. Jack Curtis on February 6, 2009 11:29 AM writes...
"One problem in all this is a cultural trend. We want everyone to be more "accountable" and we want to show that good processes are being used. Those are laudable goals in the right context, but basic discovery-oriented research is probably not one of those contexts. They are part of a secular trend toward increasing layers of red tape and review carried out for seemingly ritualistic purposes. "Can-do" informality has become a kind of sin."
I would interpret what is going on somewhat differently. Corporations like one thing in particular: predictable results. Pharma's approach to drug discovery strikes me as throwing money, machinery, and intellectual talent at a difficult problem with extensive controls in an effort to achieve predictability of results. This works fine for engineering computers (my current field) and designing, say, aircraft, but drugs are not engineered systems and organisms are extraordinarily complex. Talent + Money + Serendipity + Informed Luck are probably all neccessary and cannot be captured within the desired business model. Ten years of hard work plus an intuitive flash in the shower one morning followed by four years of concentrated work is a darned hard thing to replicate.
Jim is also an exceedingly nice chap. After a meeting dinenr in Dublin he was happy to come to the pub (bar) with a group of us and just sat round the table chatting to all
1. bobalbrght on February 5, 2009 9:16 AM writes...
Hey Derek,
Can you drop the link into your comments?
or am i missing it?
Permalink to Comment2. bobalbrght on February 5, 2009 9:16 AM writes...
Hey Derek,
Can you drop the link into your comments?
or am i missing it?
Permalink to Comment3. Russ on February 5, 2009 10:49 AM writes...
I was priveleged to work with individuals who were a part SKF when Sir James was running the program that resulted in Cimetidine. They were supposedly told by the financial types that there was little interest in a therapy for a condition that could be "cured" by surgical removal of part of the stomach; therefore the program should be stopped. Sir James and his coworkers wisely ignored this advice.
At one point in time Sir James was slated to become head of R&D for SK&F in Philadelphia; he withdrew for personal reasons. It is intersting to speculate how things would have turned for that organization if he had taken leadership.
Permalink to Comment4. BACE on February 5, 2009 12:14 PM writes...
Black should know; he worked in a golden age where small groups were given a lot of freedom to pursue their own interests. As long as pharma snubs free-thinking, open-minded basic R & D, it will continue to slide downhill and finally extinguish itself. If there's anything we have learnt from the software hacker culture, it's that free-thinking not stifled by bureaucracy and management is the only way to encourage true innovation.
Permalink to Comment5. lucifer on February 5, 2009 1:08 PM writes...
Human beings, as a group, are incapable of perceiving reality through means other than abject failure. Unless and until the actions of these financial types wreck the world and everything productive in it, people will not wake up.
It took an epidemic ('black death') to start the destruction of the hold of religion over people. It took WW2 to destroy colonial empires. It takes a lot of damage to convince groups of people that they were wrong. But they eventually learn.. well.. at least the survivors do.
"Black should know; he worked in a golden age where small groups were given a lot of freedom to pursue their own interests. As long as pharma snubs free-thinking, open-minded basic R & D, it will continue to slide downhill and finally extinguish itself. If there's anything we have learnt from the software hacker culture, it's that free-thinking not stifled by bureaucracy and management is the only way to encourage true innovation."
Permalink to Comment6. Skeptic on February 5, 2009 1:31 PM writes...
[James Black doesn't exactly present a convincing case for scientists being left alone does he:]
"We have moved away from studying the complexity of the organism; from processes and organisation to composition."
[I have no idea what he means by that statement]
"He rejects any suggestion that drug discovery was easier in the past. "I never found it easy. People say I was lucky twice but I resent that. We stuck with [cimetidine] for four years with no progress until we eventually succeeded. It was not luck, it was bloody hard work.""
[How is the notion of hard work independent of luck?]
"Sir James was not able to repeat his own blockbuster success a third time, either at Wellcome, at subsequent academic posts, in the James Black Foundation that he founded after retirement, or in his continuing research today."
[So he follows the familiar pattern: argues biology is hard (duh), success was achieved through bloody hard work, and his latest efforts have been for not.]
Bottom line: Black can't find drugs NOW either and has no idea what to do.
Permalink to Comment7. HOMO-LUMO on February 5, 2009 2:10 PM writes...
Another outstanding scot, why all the great scots are holding positions abroad, and almost none are in that small country, is a point that always bessoted me...Fraser and Macmillan just two examples
Permalink to Comment8. Hap on February 5, 2009 2:56 PM writes...
Skeptic: I think he's beyond having to find drugs. (I assume at 83, he's probably retired.) If you assume that it's not his ability that enabled he and his coworkers to find those drugs, then it had to be something else, something which has changed between then and now. Management style seems like a good place to start.
If I have to ask someone how to find drugs, should I ask someone who was helped find some or someone who knows money but little about drugs? The answers might have something to do with pharma's recent lack of success.
Permalink to Comment9. lucifer on February 5, 2009 5:51 PM writes...
Anyone who utters this statement should have been closely involved in discovering a blockbuster or two. If not.. just shut up!
//Sir James was not able to repeat his own blockbuster success a third time, either at Wellcome, at subsequent academic posts, in the James Black Foundation that he founded after retirement, or in his continuing research today//
There is your problem! Drugs are not found by 'knowing the answer' or 'I am always lucky'. It is a combination of chance, ideal working conditions, competence, hard work, vision and whimsical decisions. It is not a method, it is a semi-random process driven by hunches and fortunate mistakes.
//Bottom line: Black can't find drugs NOW either and has no idea what to do.//
I have an idea to improve productivity in pharma. We should get rid of-
1] all MBA types
2] all 'pedigreed' scientists (especially the well funded bozos) who have ever uttered the words - "I am certain that..."
Permalink to Comment10. burt on February 5, 2009 5:51 PM writes...
I seconds Hap's comments wholeheartedly. GOOD executives know how to "butt out" when required and when to provide direction. Good executives seem to be scarce these days.
Permalink to Comment11. S Silverstein on February 5, 2009 9:46 PM writes...
Sir James Black sounds a lot like Maurice Hilleman, PhD, who in his 80's as Merck emeritus was one of the most voracious users of the MRL science research library I ran at WP from 2000-2003. Dr. Hilleman was the inventor of many major vaccines.
Dr Hilleman wrote review papers on vaccines, and used to chat with me in my office about his take on "modern" R&D.
He echoed some of the same sentiments as Black, in the sometimes colorful language Dr. Hilleman was known for. He did not take kindly to incompetents and bureaucrats and the sterile formalisms and unproductive rituals of the latter.
Interestingly, regarding R&D support he also defended keeping traditional information assets as opposed to a move entirely away from paper. He wrote me a supportive memo to that effect which you can see here.
Permalink to Comment12. srp on February 6, 2009 3:47 AM writes...
One problem in all this is a cultural trend. We want everyone to be more "accountable" and we want to show that good processes are being used. Those are laudable goals in the right context, but basic discovery-oriented research is probably not one of those contexts. They are part of a secular trend toward increasing layers of red tape and review carried out for seemingly ritualistic purposes. "Can-do" informality has become a kind of sin.
For that matter, the "accountability" overheads in areas such as defense procurement, science funding, public-sector personnel decisions, financial reporting of companies, and environmental impact statements have probably gone well past the point of zero marginal returns into negative territory. But there are now huge vested interests that benefit from all the red tape, individuals and organizations that have specialized in participating in these rituals. The day we can get back to funding and building something like Brookhaven National Labs based on a five-page memorandum from its founder will be the day many of these problems will diminish.
Permalink to Comment13. milkshake on February 6, 2009 9:33 AM writes...
Accountability: A pharma company that "measures success" and minutely flow-charts its research projects (with go/no go decision-making points) is managed by phony accountants with no accountability.
Permalink to Comment14. Jack Curtis on February 6, 2009 11:29 AM writes...
"One problem in all this is a cultural trend. We want everyone to be more "accountable" and we want to show that good processes are being used. Those are laudable goals in the right context, but basic discovery-oriented research is probably not one of those contexts. They are part of a secular trend toward increasing layers of red tape and review carried out for seemingly ritualistic purposes. "Can-do" informality has become a kind of sin."
I would interpret what is going on somewhat differently. Corporations like one thing in particular: predictable results. Pharma's approach to drug discovery strikes me as throwing money, machinery, and intellectual talent at a difficult problem with extensive controls in an effort to achieve predictability of results. This works fine for engineering computers (my current field) and designing, say, aircraft, but drugs are not engineered systems and organisms are extraordinarily complex. Talent + Money + Serendipity + Informed Luck are probably all neccessary and cannot be captured within the desired business model. Ten years of hard work plus an intuitive flash in the shower one morning followed by four years of concentrated work is a darned hard thing to replicate.
Permalink to Comment15. petros on February 6, 2009 12:55 PM writes...
Jim is also an exceedingly nice chap. After a meeting dinenr in Dublin he was happy to come to the pub (bar) with a group of us and just sat round the table chatting to all
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