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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 30, 2009

10,000 Hours To Drug Discovery?

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Posted by Derek

I see a fair number of people reading Malcolm Gladwell’s Outliers while I’m commuting. I haven’t read it myself yet, but it seems that a key feature of his case is the “10,000 hour rule”, the idea that many people who are extremely good at a given task have spent at least that long perfecting their skills. (This derives from the work of Anders Ericsson and Herb Simon over the last thirty or forty years).

One of the more perceptive reviews of Gladwell’s book I’ve read is by Michael Nielsen. He brings up the problems that many scientists have had with some of Gladwell’s past work, and according to him, if you weren’t happy with Blink or The Tipping Point, you may well not be happy with this one. (Of course, if you didn’t like those, you probably won’t read this one!) Of course, as a scientist, when you read about something like the ten-thousand-hour rule, the first thing you ask yourself is “Hmm. I wonder if that’s true?” But as Nielsen points out:

There are, of course, many provisos to the 10,000 hour rule. As just one example, to acquire mastery in an area, it’s not enough to just practice for 10,000 hours; the person practicing must constantly strive to get better. Someone who practices without pushing themselves will plateau, no matter how many hours they practice. I suspect many scientists fall afoul of this proviso, putting in enormous hours, but mostly doing administrative or drudge work which doesn’t extend their abilities.

But that said, Nielsen goes on to talk about some scientists who have done great work well before their 10,000 hour mark. These people were working at discontinuities, sudden discoveries that didn’t necessarily build on the past, so they didn’t have as much of a tradition or art to master. A thorough grasp of 19th-century physics didn’t help people much when it came time for quantum mechanics. It wouldn’t be surprising, Nielsen says, if a disproportionate number of great discoveries in science fell into this category.

Now, which category does drug discovery fall into? We have a fair amount of art to be learned and experience to be gained, true. But there’s another factor that confounds things: sheer luck. I think that the fundamental issues of drug design are still so poorly understood that no amount of skill can compensate for them. I’m thinking of difficulties like designing compounds that have good oral absorption or blood-brain barrier penetration – sure, there are guidelines, and there are things that you learn to avoid, but once past those it’s a crap shoot. And then there’s toxicity – you learn pretty quickly not to put known landmine groups into your molecules, but after that, you just have to cross your fingers and hope for the best.

These things also mean that there’s a good amount of work to be done that doesn’t extend a person’s abilities, as the quote above has it. The worst of it is being outsourced these days, the well-known “methyl ethyl butyl futile” stuff, but there’s still a lot of pickaxe work that has to be done in any drug project. It would be a fine thing if ten thousand hours of hard work and practice allowed someone to come in and make nontoxic molecules, but they often have to be discovered by trial and error, and more of the latter.

That said, I take Nielsen’s point about putting in good hours rather than empty ones. As much as possible, I think that we should try to do things that we haven’t done before, learn new skills, and move into untried areas. Try not to get butyl-futiled if you can possibly avoid it; it’s not going to do you much good, personally, to set up another six or eight EDC couplings. There are times that that’s exactly what needs to be done, but don’t set them up just because you can’t think of anything else. This gets back to the point I’ve made about making yourself valuable; anyone can set up amide reactions, unfortunately. Maybe some of the time we spend learning our trade is spent learning how to avoid falling into all the tar pits and time-wasting sinkholes we have.

Comments (23) + TrackBacks (0) | Category: Who Discovers and Why


COMMENTS

1. john.spevacek@aspenresearch.com on January 30, 2009 9:07 AM writes...

I thought the 10,000 hours was about right. That's about 5 years of work. If you figure that half that time is spent in the non-productive paperwork, meetings, methyl-ethyl-propyl... work, then it takes 10 years. It's always seemed to me that people hit their stride (if they are going to at all) in about 10 years.

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2. Doug on January 30, 2009 9:10 AM writes...

I like your point about productive experience versus unproductive experience. To think of it another way, sometimes it is not the nature of what you do but the amount of thought you put into it. It's bad enough when you burn through a project just going through the motions but the real killer is when you get to the end of the project and rather than taken the time to analyze the results and think about what happened and what lessons can be learned, instead, rush headlong into the next project.

Institutions are guilty of this as well as individuals, and it is a good argument for a system which inludes formal peer reviewed papers, even when these papers don't ever see the light of day for proprietary reasons.

Incidentally there's a saying among poker players that fits this situation. Sometimes you'll hear a grizzled poker player proclaim that they've got 30 years of experience at the game. The answer to that is "He doesn't have 30 years of experience. He has 1 year of experience repeated 30 times."

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3. Jordan on January 30, 2009 9:38 AM writes...

My understanding was that the 10,000-hour "rule" was always more about the cultivation of particular skills (usually musical or athletic) than about abstract ideas or problem-solving. I'm actually a bit surprised to see people try to apply it to research.

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4. RB Woodweird on January 30, 2009 10:21 AM writes...

"A thorough grasp of 19th-century physics didn’t help people much when it came time for quantum mechanics."

Hypothetically, maybe not. But I'm willing to bet that anyone who ever had a grasp of quantum mechanics also had an equally deep knowledge of Newtonian physics. It reminds me of the Picasso exhibit a couple of years ago. One might think that he drew flatfish people because that was all he could do, but his early work was beautiful and traditional.

"My understanding was that the 10,000-hour "rule" was always more about the cultivation of particular skills (usually musical or athletic) than about abstract ideas or problem-solving. I'm actually a bit surprised to see people try to apply it to research."

You don't think organic synthesis is a collection of skills mastered over years of study and labor? Which level of management are you?

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5. Wavefunction on January 30, 2009 10:39 AM writes...

I think the deal about the 10,000 hour rule is that it could be seen as a necessary but certainly not sufficient condition. In fact it may not even be necessary; it's just the trivial observation that hard work is more likely to make you successful. It's just a matter of probability and a rather simple and effective instruction, not really some kind of 'rule'.

I think the trick that Gladwell uses to sell his books is to write about things that are usually more than obvious but then illustrate these with concrete examples and lots of details. To me he is a good journalist who can tell interesting stories, that's all; not some soothsayer or philosopher guru. All those who have criticized him for lack of profundity or new insight are looking at the wrong thing.

And luck, yes, that's something that Gladwell puts a very high premium on, as he illustrates with his stories about Bill Gates for instance.

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6. Matthew on January 30, 2009 2:14 PM writes...

"Now, which category does drug discovery fall into? We have a fair amount of art to be learned and experience to be gained, true. But there’s another factor that confounds things: sheer luck..."

Sure, luck pays into drug discovery. But, I think technical advancement plays a heavy hand in drug development. The "practice" is learning about what tools are available and how they might apply to your particular project or pipeline niche. Think about all the factors over the past decade that have fundamentally changed how we address the biology of a target. The genetics alone has really changed patient stratification for oncology, and I suspect SNP classifications will do the same for other disease areas.

What if gene therapy can be safely worked out? That would certainly open a floodgate of new possibilities.

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7. Jordan on January 30, 2009 3:01 PM writes...

"You don't think organic synthesis is a collection of skills mastered over years of study and labor? Which level of management are you?"

No need to come out swinging at me. I'm a working bench chemist, spent many years in grad school and a post-doc, and have never been in management.

My point is that it isn't necessarily valid to apply the 10,000-hour "rule" -- which is usually used to describe individual mastery of a specific physical skill, like playing a music instrument or sports -- to the process of R&D, which is a team-based problem solving effort.

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8. milkshake on January 30, 2009 3:04 PM writes...

There is an excellent nit-picking treatment of the book, in several installments, from Quantum Pontiff. On the 10,000 hour rule:

http://scienceblogs.com/pontiff/2009/01/a_curmudgeons_and_improvs_guid.php

Spoiler Alert: Dave Bacon aka Quantum Pontiff looks closely at these weighty matters and finds the book wanting. The examples given in the book do not quite support the books conclusions.

(I am sure the management types will soon make a good use of the Outliers and the 10,000 hour rule in their pep talk)

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9. Sili on January 30, 2009 3:20 PM writes...

Woodweird has a point about QM. The physicists of the early twentieth century very likely had a completely different, thorough comprehension because they had mastered far more classical physics than most people these days.

Einstein may seem to have come out of the blue, but Schrödinger could not have focused on the QM Hamiltonian had he not been intimately familar with the classical Ham. and Langrangian mechanics. All while younger than me.

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10. Eskimo on January 30, 2009 3:57 PM writes...

Wasn't it Niels Bohr who said that the expert is someone who has made all the possible mistakes in his/her field?

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11. Anonymous BMS Researcher on January 31, 2009 5:53 AM writes...

In the IT world there's a longstanding rule of thumb for estimates of how long a project will take: multiply the initial estimate by 20, then divide by the number of years the person making the estimate has been in charge of similar projects.

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12. Anon #3849211 on January 31, 2009 8:22 PM writes...

The idea of 10,000 hours of practice goes back at least to the late 1950s. Bob Richards, who won gold in the pole vault at the 1952 and 1956 Olympics, made 16mm movies of lectures in which he talked about success, stating that before he reached the Olympics, he had spent 10,000 hours practicing. My father saw one of these movies at a Lions Club meeting and borrowed it (along with the projector) to show it to us at home.

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13. Shannon Love on February 2, 2009 2:05 PM writes...

I think painstaking, tedious work in science doesn't get the credit it deserves. Yes, theorist with flashy insights get most of the credit but the real work of science is experimental. Theorist have been around for ever but science did not take off until the dull experimentalist showed up.

Especially in areas such as drug research where serendipity and luck play a large role, plodding carefulness pays off in the long run more than insight. I doubt that the 10,000 hour rule applies to all scientist as individuals but science is a team effort and every insightful theorist relies on thousands and thousands of hours of work by those who measure and experiment.

So, looking at just the amount of time it takes a particular individual to acquire the skills that led to their breakthrough doesn't capture the huge amount of time that the people supporting them put in to generate the high quality information the breakthrough required.

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14. Neo on February 2, 2009 2:19 PM writes...

I wonder just how the 10,000 hour rule works in a place like Silicon Valley where many companies have average employment times well below 10,000 hours.

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15. entretouf on February 2, 2009 2:34 PM writes...

The all-to-often emergence of brilliance early in scientific careers, followed by much less productive years trying to recapture past glory, belies the 10,000 hour "rule".

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16. Shannon Love on February 2, 2009 2:39 PM writes...

Neo,

I wonder just how the 10,000 hour rule works in a place like Silicon Valley where many companies have average employment times well below 10,000 hours.

I don't think the rule applies to just paid work hours but rather all the hours required to acquire a skill. I put in hundreds if not thousands of hours programming as a teenager and then double that in college before I ever got a paying job in computers.

The same is true of the sciences. An individual will have put in thousands of hours studying general science before they reach the graduate level and actually start doing experiments.

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17. ken in sc on February 2, 2009 2:53 PM writes...

In the military, we had a saying that seems to apply here. It goes, "Some people have 20 years experience; others have one year of experience 20 times."

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18. DensityDuck on February 2, 2009 2:57 PM writes...

RB Woodwierd:
"You don't think organic synthesis is a collection of skills mastered over years of study and labor? Which level of management are you?"

Effin' tell me about it. I'm dead sure there are a bunch of MBA Meatheads out there thinking "hmmm, 10,000 hours...so that's 50 guys spending 200 hours each..."

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19. medicinal_chemist on February 2, 2009 3:17 PM writes...

To complete a commenter's series (well known to chemists, perhaps not others): methyl, ethyl, propyl, butyl, futile (ie, don't go on forever). I first heard it stated by Paul Janssen in the 60's, but it was old then.

Ten thousand hours is about 2/3-3/4 of a typical PhD training program in chemistry, which may confer mastery in one area and knowledge of more.

And, yes, there's always some manager (usually a non-scientist) who thinks that if one cow can produce a calf in 9 months, with a little extra management and 9 cows you can have a calf in 1 month. This is why they are management.

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20. Austin on February 2, 2009 3:18 PM writes...

If one looks at those who worked on QM such as Feynman, you will find a very very long period doing math before they did QM. The same goes for Watson and Crick when it relates to DNA.

In general, if I want to understand how good someone is, I ask about their background, work history - there HAS to be a period where they worked 80 hour weeks on SOMETHING related to what they are being hired for. OR, they have to show a history of being totally immersed to learn something.

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21. srp on February 3, 2009 1:41 AM writes...

To Shannon's point: An undergraduate physics professor pointed out to us that Max Planck would never have been able to make his breakthrough if it hadn't been for zillions of hours of spectroscopists analyzing the flames of different substances and recording the results. That database of spectral lines (and the techniques developed to measure them) was the work of a lot of people over a lot of hours.

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22. DensityDuck on February 3, 2009 4:17 PM writes...

It's also worth pointing out that our current knowledge of orbital mechanics and celestial navigation started out with guys doing curve-fits to recorded data.

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23. Mat Todd on February 3, 2009 5:29 PM writes...

Yes, it's the immersion that's important. A PhD, which is more than 10,000 hours, does not confer genius/master standing on all graduands. I read a precis of the book that focussed on Mozart and Bill Gates. The line was that they were totally dedicated, and maintained that dedication over 10,000 hours. Like it or not it's a thesis, but obviously silly without the first part.

@Doug. I like the poker comment - that can be applied very widely...

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