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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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December 7, 2012

Whitesides on Discovery and Development

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Posted by Derek

George Whitesides of Harvard has a good editorial in the journal Lab on a Chip. He's talking about the development of microassays, but goes on to generalize about the new technologies - how they're found, and how they're taken up (or not) by a wider audience (emphasis mine below):

Lab-on-a-chip (LoC) devices were originally conceived to be useful–that is, to solve problems. For problems in analysis or synthesis (or for other applications, such as growing cells or little animals) they would be tiny – the “microcircuits of the fluidic world.” They would manipulate small volumes of scarce samples, with low requirements for expensive space, reagents and waste. They would save cost and time. They would allow parallel operation. Sensible people would flock to use such devices.

Sensible and imaginative scientists have, in fact, flocked to develop such devices, or what were imagined to be such devices, but users have not yet flocked to solve problems with them. “Build it, and they will come” has not yet worked as a strategy in LoC technology, as it has, say, with microprocessors, organic polymers and gene sequencers. Why not? One answer might seem circular, but probably is not. It is that the devices that have been developed have been elegantly imagined, immensely stimulating in their requirements for new methods of fabrication, and remarkable in their demonstrations of microtechnology and fluid physics, but they have not solved problems that are otherwise insoluble. Although they may have helped the academic scientist to produce papers, they have not yet changed the world of those with practical problems in microscale analysis or manipulation.

Where is the disconnect? One underlying problem has been remarked upon by many people interested in new technology. Users of technology are fundamentally not interested in technology—they are interested in solving their own problems. They want technology to be simple and cheap and invisible. Developers of technology, especially in universities, are often fundamentally not interested in solving real problems—they are interested in the endlessly engaging activity of building and exercising new widgets. They want technology to be technically very cool. “Simple/cheap/invisible” and “technically cool” are not exclusive categories, but they are certainly not synonymous.

That is a constant and widespread phenomenon. There are people who want to be able to do things with stuff, and people who want stuff to do things for them, and the overlap between those two is not always apparent. What happens over time, though, in the best cases, is that the tinkerers come up with things that can be used by a wider audience to solve their own problems. Look no further than the personal computer industry for one of the biggest examples ever. If you didn't live through it, you might not realize how things went from "weird hobbyist thingies" to "neat gizmos if you have the money" to "essential parts of everyday life". Here's Whitesides again:

Here are three useful, homely, rules of thumb to remember in developing products.

• The ratio of money spent to invent something, to make the invention into a prototype product, to develop the prototype to the point where it can be manufactured, and to manufacture and sell it at a large scale is, very qualitatively, 1:10:100:1000. We university folks—the inventors at the beginning of the path leading to products—are cheap dates.

• You don't really know you have solved the problem for someone until they like your solution so much they're willing to pay you to use it. Writing a check is a very meaningful human interaction.

• If the science of something is still interesting, the “something” is probably not ready to be a product.

His second rule reminds me of Stephen King's statement on whether someone has any writing talent or not: "If you wrote something for which someone sent you a check, if you cashed the check and it didn't bounce, and if you then paid the light bill with the money, I consider you talented". It's also the measure of success in the drug industry - we are, after all, trying to make things that are useful enough that people will pay us money for them. If we don't come up with enough of those things, or if they don't bring in enough money to cover what it took to find them, then we are in trouble indeed.

More comments on the Whitesides piece here. For scientists (like me, and many readers of the blog), these points are all worth keeping in mind. Some of our biggest successes are things where our contributions are invisible to the end users. . .

Comments (24) + TrackBacks (0) | Category: Business and Markets | Who Discovers and Why


COMMENTS

1. David Formerly Known as a Chemist on December 7, 2012 12:39 PM writes...

Alas, the fundamental gulf between the academic mindset and the commercial marketplace! Whitesides is one man that definitely "gets it".

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2. Stu West on December 7, 2012 12:53 PM writes...

The comparison to microprocessors is well-taken. It took, what, three, four decades of deficit financing between the invention of the transistor and the computing business becoming a profitable commercial enterprise. And then maybe another ten to fifteen years before computers fundamentally changed the way we work.

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3. IO on December 7, 2012 1:02 PM writes...

In other words one needs a killer app.

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4. DrugA on December 7, 2012 2:26 PM writes...

I spent part of this week at a large conference on mobile health technologies (mHealth), to which the same caveats apply. There were lots of neat ideas, but a real resistance in some quarters to conducting well-designed studies that will assess actual health outcomes.

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5. John Spevacek on December 7, 2012 3:03 PM writes...

Derek,

Thanks for the mention.

JOhn

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6. jonas on December 7, 2012 3:23 PM writes...

"Users of technology are fundamentally not interested in technology—they are interested in solving their own problems. They want technology to be simple and cheap and invisible. Developers of technology, especially in universities, are often fundamentally not interested in solving real problems—they are interested in the endlessly engaging activity of building and exercising new widgets. "

This is definitely true in the imaging field!

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7. Alastair on December 7, 2012 3:42 PM writes...

My prematurely born daughter has spent the past 14 weeks in intensive care and I can tell you that any progress towards miniaturising blood assays of red blood cell count, CRP would be lapped up by the medical community - a heel prick test for these things would be great!

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8. MoMo on December 7, 2012 4:04 PM writes...

Thank You Professor Whitesides! You restore my faith that there are decent and honest and respectable Academics still out there, able to cut through the self-indulgent and self-serving financially-based propaganda and deliver real opinions!

Now how much money has been wasted by the American Taxpayer on this field alone to subsidize Lab-on-a Chippers?

And @7 Alastair, sorry to hear about your daughter and I hereby apologize for all the academics that diverted real money from the issues you face to technology that serves none.

Not that I am one of them, but they are usually too weak and arrogant to admit that they basically steal chances of real progress in science and medicine.

Professor Whitesides is not one of them, however.

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9. leftscienceahwileago on December 7, 2012 5:33 PM writes...

How many actual products as Whitesides delivered to a market?

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10. Algirdas on December 7, 2012 6:16 PM writes...

"How many actual products as Whitesides delivered to a market?"


This quip is a ridiculous ad hominem. How is the number of products that Whitesides delivered relevant? Either what he wrote is true or not. Whitesides is invited to write editorials because he is famous, but the quality if the arguments stands on its own. A Joe nobody (like me!) could make same arguments, and they would be just as valid. Ditto if the argument came from someone famous for actually creating innovative products for the market, like Steve Wozniak.

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11. Nick K on December 7, 2012 11:00 PM writes...

Astute observations by Whitesides.

#9 leftscienceahwileago(sic): You really believe that an academic's role is to produce devices commercially?

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12. leftscienceawhileago on December 8, 2012 2:00 AM writes...

10,11
Yeep, and ad hominem?

GW did start Genzyme, and I guess that was a successful venture (though I don't know any details about what work went on when it was founded and when it was acquired by Sanofi). But I think the narrative of the academic startup (especially in the bio/chemical sciences) does need a bit of a critical look.

We've all seen startup from labs (not so much these days, but it was more common during the early 2000s), more often than not many people could tell they would be complete failures...yet VCs continued to attract investor money. A good example would be the recent (laudatory) NY Times Langer article, who is described to have started many companies. The article makes it sound like all of these companies have delivered products to the market, I am only aware of Giladel...all of the other companies seem to have expired or be in a stage of venture funding.

One successful product is indeed enough to be able to dish out advice in an article, but need to remember the failure rates involved. The acquisition of worthless companies spun out of academic labs by big pharma is a commonly cited inefficiency here.

Furthermore, many of these articles fail to mention that some of these founders have access to subsidized, highly skilled laborers who, in my experience, rarely benefit from venture activity. Senior company members seem to make out just fine, even if the company is clearly doomed from the start.

Just worth thinking about.

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13. Beentheredonethat on December 8, 2012 4:39 AM writes...

I am affiliated with an university based in the heartland of USA. My prior experiences in the big pharma has turned me and the rest of us into more "goal oriented" individuals. In industry where it does not make sense, we move on to different ideas quickly until the goals are met. I find that spirit totally lacking in academia. Period. I am running into a brick wall. My impression is that the mentality " publisg first and patent or develop later " is a prevailing mentality in the academia. Your sagely advice on many issues that is plaguing the development of drug are simply ignored.

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14. Kevin on December 8, 2012 9:25 AM writes...

Working for an instrument manufacturer, Whitesides is dead on. Users don't want technology - that has been true for a long while even in academia when its not their research. - they want an answer to their problem. I can't count the number of offers we get from academics or small companies with a great concept or even a breadboard that "just needs development." Making a new device commercial costs millions - the prototype is the easy part.

I heard him speak in graduate school and later visited him professionally: his comment on the important of doubt has stuck with me since.

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15. newnickname on December 8, 2012 10:02 AM writes...

“Build it, and they will come” didn't work for MANY (perhaps most?) innovations. It took decades for electrification to become an invisible ubiquity. Likewise, telephony. The Wright Brothers were successful inventors but it took decades for airplane apps (US Mail, warfare, passengers) to become routine. [The list is quite long.]

Sometimes, it takes a Black Swan event (or a war or a famine) to catapult an available technology or academic curiosity to the point of being useful, applicable and invisible. (The story of electrospray ionization might fit that: an available solution waiting for the right problem.)

For all of that, I probably agree with GW to a large extent.

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16. Cellbio on December 8, 2012 10:06 AM writes...

Wow is that ever a refreshing view from the trenches of academia. I have advised several of these academic entrepreneurs in the LoC space. The story is always the same, namely, the ability to use extremely small volumes to measure analytes at exquisite sensitivity with increased speed and the ability to multiplex, providing a POC platform with real time results.

So I ask, what assay, today, is limited in use or stalled in development by sensitivity? What clinical sample is limited in volume (perhaps NICU as stated above)? What office visit or hospital setting would benefit from getting test results in 5-10 minutes instead of hours to days? What practitioner would be able to digest the test results, especially if multiplexed, in real time to make decisions? What treatment decision would be made that could not wait the additional time? What payer would see added value in multiplexed assays? What will it take to convince conservative managers of clinical labs that they should provide bench space for your new, untested instrument?

As great as these LoC guys have been, sadly, they come from far afield and the answers to these questions are lacking. They also often start out without an appreciation for the regulatory aspects of Dx development. For one company, the original plan was to develop a novel technology along with novel tests, doubling the risk. We went away from Dx to first work towards developing lab instruments so the technology development was not concurrent with Dx development and the challenges LoC systems have with biological fluids. And those challenges are significant.

Don't you think parallel problems in testing whether there is a practical application to a real problem is wide spread in nanoparticles as well? Neat cages, wonderful theoretical application, just a tiny problem of playing well with living systems.

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17. Anon on December 8, 2012 3:42 PM writes...

#9: Basically you are implying that no one who has actually brought a drug to the market has a right to have a useful opinion on the topic. I guess that probably means Derek should stop talking about drug development.

I think we can understand why you "leftscienceawhileago"

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18. Algirdas on December 8, 2012 3:46 PM writes...

@12 "Yeep, and ad hominem?"

Well, yes. An ad hominem is a type of a logical fallacy. To quote the definition from m-w.com, it is "marked by or being an attack on an opponent's character rather than by an answer to the contentions made". You did not write "Oh, no, Whitesides's argument is dead wrong, it is the stupid users that do not appreciate the brilliant ingenuity of academic LoC inventions." Or some such. No, instead your comment #9 goes along the lines "Whitesides has not invented anything, ergo he can not possibly have anything useful to say on this topic."

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19. Anonymous BMS Researcher on December 8, 2012 4:00 PM writes...

New technologies are easier to sell if they are drop-in replacements for an existing technology. The current boom in solid-state disk drives is an example: it works much faster than a hard drive, but the customer does not have to change anything else to benefit from solid-state storage.

But most truly disruptive technologies only deliver their full potential when the rest of the world changes around them, which means their benefits must be pretty compelling to gain wide adoption. For many years in the late 20th century, economists spoke of the "IT Productivity Paradox," that despite substantial investment in computers they could not find evidence of much return on that investment. Then we had the longest economic boom on record after companies began changing how they operated in ways made possible by all those computer networks.

Google Carlota Perez for an economist who has studied the history of technological innovation. There are fascinating analogies between the Railway boom of the 1800s and the Tech Bubble around 2000, for instance.

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20. hn on December 9, 2012 1:07 AM writes...

@16,

Good points about not addressing key needs in medicine in your typical setting. There are potential unmet needs that lap chips could address in military applications or undeveloped rural areas.

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21. Anonymous on December 9, 2012 9:42 AM writes...

What is LoC, please?

See the Whitesides quote back at the top of the page.

("Lab-on-a-chip")

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22. sepisp on December 10, 2012 5:54 AM writes...

The problem with devices like this is inflexibility. We had a screening task where we needed an array of mixtures and their spectra. We found a high-throughput machine at another department, but it was designed exclusively for their task, and could not be used for anything else. This meant we had to settle for measuring the spectra traditionally one-by-one.

The same with the flow reactors. The pressure ratings are never high enough, and the right catalyst cassettes are never available from the manufacturer. I could easily name at least ten other analyses that I do by hand, because the cost of miniaturizing and automating them is higher than the cost of just doing them by hand.

I can't see this improving. Maybe you'll get a couple of individual medical testing applications, but that's going to be it.

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23. Thomas McEntee on December 10, 2012 8:07 AM writes...

George has one of the most incisive minds I've ever encountered. His ability to cut through BS is welcomed...unless you're on the receiving end. I can imagine that he might come across as 'severe' to grad students but academia, and US S&T in general, would be in far better shape if we had more people who think like he does. Along a similar vein, the Heilmeier Questions, attributed to George H. Heilmeier, push you towards the same end that George is talking about.

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24. Anonymous on December 17, 2012 4:33 PM writes...

23
His ability to generate BS is also impressive.

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