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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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June 2, 2008

A Breath of Fresh Air from Fuji

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Posted by Derek

A longtime reader pointed me to this article from Business Week. Fuji Film of Japan, facing all kinds of problems like the other film makers of the world, has decided to put some of its money into a more exciting, profitable, high-margin business: pharmaceuticals! Back in February they made an offer for small-to-medium sized Toyama.

Readers who have been around the industry for a few years may shudder, remembering Kodak's disastrous experience with Sterling-Winthrop. (You couldn't have paid a gang of saboteurs to do a better - well, worse - job on Sterling and its employees; this PDF will give you some of the story). The details of the interview, which gets crazier as it goes on, do not inspire happy feelings. Well, unless schadenfreude counts as "happy", that is. Feast on this, for example, from Yuzo Toda, the company's VP for Life Sciences:

"The film in your camera is about 15 microns (one-thousandth of a millimeter) thick. Our color film has 17 different layers, each with a different function, and it contains nearly 100 different chemicals. Controlling the chemical reaction to develop these photos is extremely difficult. You have to start and stop the various chemicals at exactly the right time to make it all work. The trick is all in the conversion of chemicals. Drugs targeting a specific [organ or receptor in the body] work the same way. We have a chemical library of 200,000 compounds, which we think will help us with creating new compounds, and we have an expertise in nanotechnology. From our viewpoint, it's more a question of why not pharmaceuticals?"

Well, with a library of two hundred thousand compounds (cue Mike Myers as Dr. Evil, demanding his million dollars), I don't see what's going to hold them back. Considering the sorts of wonderfully druglike photosensitive absorbers and dye-coupling agents they're stocked up with, I'm sure the screening hit rates will be exciting, too. And yes, I am considering making "The trick is all in the conversion of chemicals" the new slogan of this blog, and I urge Fuji to make it the advertising tag line for their whole drug business.

But let's not pick on just one guy. Here's Toshio Takahashi, the company's CFO:

"Many drugs are made in higher dosages than we need. That's because they can't be fully absorbed by our bodies. It's a waste of resources, and it can have an adverse effect on organs such as the stomach and liver. We're researching compounds that will work in smaller doses because they will target a specific part of the body."

Now there's a thought. I wish Fuji luck with these innovative ideas, although I don't think I'm capable of delivering the quantities of luck that it appears they'll need. I assume that the people at Toyama don't talk this way, i.e., as if they'd just been beamed in from Neptune and then hit over the head, and for all I know they're burying their heads in their hands as they read this stuff, too. Who knows, maybe if Fuji can keep their hands off of them and not impart too many lessons from the film business, the deal could work.

But for now, check out the interview, and be glad it's not you. Sheesh.

Comments (21) + TrackBacks (0) | Category: Business and Markets | Drug Industry History


COMMENTS

1. milkshake on June 2, 2008 8:45 AM writes...

why dont they work on medical devices, or the advanced drug delivery systems, this sounds more like the area where they can have edge.

This reminds me Phamazia merging with Monsanto, only to find later that the agrobusiness synergies, uh, weren't there. We in Sugen had our targets in HTS done both on Kalamazoo compound collections and the Monsanto stuff. Guess which collection produced great medchem hits - and which one yielded only the highly-reactive electrophillic crap?

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2. CMC guy on June 2, 2008 10:25 AM writes...

I literally did shudder after reading the first paragraph and thinking back to Sterling-Kodak. I knew people who worked at Sterling and always thought was highly focused with good mix and innovative targets/approaches and was sad when that got co-opted by people who where great at chemical/photo business but did not understand how different pharmaceuticals are. Trust Fuji can do better, and being Japanese probably helpful in taking a long-term view, but if they get any leads from their libraries still likely will need solid med chem and other R&D to get to drugs.

In general since the Sterling-Kodak time pharma has changed a great deal and the current weakness of innovation way be a by-product. Mergers and mega-mergers with more and more emphasis on block bluster programs rather than more smaller projects. Biotech/Biopharma has taken on much of the front end discovery once exclusive to Big Pharma but often stumble when projects get into clinical stages. Although small sized Sterling knew the entire business and thus could foresee and integrate critical decisions and functions that do not see as common in the Biotech culture today.

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3. processchemist on June 2, 2008 11:02 AM writes...

Japaneses know something I dont ?
Big Pharma is divesting and relocating research or production in Asia, and japan companies are out for shopping both in US and Europe...
What is that makes investment in pharma so attractive to them? the amount of money needed to run Phase III and reach an NDA? Around me small-medium pharma is completely dropping the idea to get on the market on their own with also the most promising NCEs... not a tragedy, because a successful Phase II has all the attention of the buyers of licenses from the Big Ones.... Japaneses are thinking about this kind of business model?

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4. burt on June 2, 2008 11:33 AM writes...

"Japaneses know something I dont ?"

The Japanese know you get what you pay for. There are many truly excellent Chinese and Indian chemists. Guess what? The vast majority don't live in China or India. This will likely change over the next few decades, but let's deal with today's reality rather than hypotheses about the future.

"What is that makes investment in pharma so attractive to them? the amount of money needed to run Phase III and reach an NDA?"

The FDA needs to improve it's approval efficiency and, inexplicably, seems to be headed in the opposite direction.

Also, the Gov't could stimulate the drug industry
AT NO COST by banning direct-to-consumer ads which, at least to SOME degree, waste money that could be used on research.

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5. Jose on June 2, 2008 11:55 AM writes...

When a VP of Science is making statements like "Our films are made in a complex seven- or eight-step process. We want to apply the same principles we have used in making film to making drugs. It's not easy. With each step your yield goes down. Let's say your yield from the first of seven steps is 90%. By the time you're finished with all seven steps it's probably 10%. But we have decades of experience in maintaining high yields."

It is time to run for the bunkers.... scary stuff indeed. I heard horror stories from Sterling-Winthrop folks about all the hits they got from Kodak compounds, as everything was dosed with Ag salts....

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6. Colby Cosh on June 2, 2008 12:10 PM writes...

It's all fun and games until your cutting-edge arthritis pill starts turning your skin blue.

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7. SRC on June 2, 2008 12:16 PM writes...

Kinda reminds me of a business guy, who on hearing that we had to protect two positions to derivatize a third, rolled his eyes at our stupidity and told us just to put in two-thirds as much reagent.

He really didn't give us much credit.

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8. processchemist on June 2, 2008 1:05 PM writes...

>There are many truly excellent Chinese and Indian >chemists. Guess what? The vast majority don't live >in China or India. This will likely change over the >next few decades, but let's deal with today's >reality rather than hypotheses about the future.

No doubt. The matter it's all about money. In the western world excellent chinese an indian scientist have salaries five times greater than the ones of excellent chinese and indian scientists working in their home countries. So: what's driving money in
US or europe, and not in another smart(?)-but-extremely-low-cost chinese R&D company located near Shangai?

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9. milkshake on June 2, 2008 2:14 PM writes...

Its not the quality of chemists - you can actually have quite average chemists in medchem and if they are hardworking and motivated and have a good boss, they will stil crank out triazoles, indoles and what not in sufficient quantities to support the biology. (And if they get lousy 15% yield they just purify it on prep HPLC and submit the stuff in 80% purity for testing. This kind of approach would not work in process chemistry of course). You can definitely find enough bright chemists in China, Russia or India who could do this kind of work for you - the problem is the biology, you need a fast compound design->screening->re-design cycle and this takes a close, personal interaction between chemistry and the biology so shipping compounds overseas for screening does not work too great. (And there may be IP issues with it also). I think in fact its the lack of drug-discovery trained biologists and DMPK people in south-east Asia and Russia that keep medchem from being subconbtrated out of US. For the time being - I am not sure how long this advantage will last, with Singapore and Chinese government active support of biology research. The main factor that brought people from China, India, Russia to US were excellent university programs here and fairly easy access to scholarships and the economic advantage to stay and work in US - but now Chinese give great career incentives and even perks for people who want to return and work in atractive mainland locations like Shanghai.

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10. Wavefunction on June 2, 2008 3:23 PM writes...

The Chinese are indeed aggressively pursuing incentives to lure back good people from the US ("reverse brain drain"). Just in the last two years four of my friends went back to China from reputed US universities right after their PhD. with lucrative faculty and industrial (Novartis) positions in hand.
Unfortunately I don't think you can say the same about Russia or India.

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11. Petros on June 2, 2008 4:09 PM writes...

Ah yes Kodak got Sterling before BAyer could buy it, or at least the Aspirin trademark,back

And as for screening colelctiosn fulll of crud some of teh early WDF collectons had some strange dyes and photochemicls in, but then Agfa was a subsidiary company!

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12. CMC guy on June 2, 2008 5:06 PM writes...

burt I don't like DTC but my understanding is that it works well at bringing in more revenue, some of which goes toward R%D. Its doubtful that even if made to go away the money "saved" would get back to R&D.

I have seen trends to what Wavefunction indicates for both Chinese and Indian scientists in past several years. Opportunties (lack of) to return home and relative differrentials that once existed in salary/freedom/modern access (or is it excesses) are no longer as big of factors. Likewise there are ofetn less barriers for starting new enterprises that take advantage of global economy.

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13. srp on June 2, 2008 5:07 PM writes...

Weren't some of the first useful drugs based on dyes? I seem to recall reading that in my youth--de Kruif's Microbe Hunters, I think.

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14. Axicon on June 2, 2008 8:17 PM writes...

The article seems too vague to pan Fuji like this. Perhaps they have a niche in mind for their expertise. If I am to read this critique correctly, then you all must think very poorly of startup companies. How dare they play with the big dogs!

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15. Derek Lowe on June 2, 2008 9:24 PM writes...

Axicon, a lot of start-ups are founded by people with experience who have a good idea of what they're getting into. I wish 'em luck! But the Fuji quotes, for anyone in drug discovery, are hilariously clueless. And what really puts them over the top is that they don't seem to realize how little they know. That's a dangerous combination.

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16. Jose on June 3, 2008 1:07 AM writes...

Axion- just to echo Derek's response, the quotes from Fuji show a true, actual, and fundamental lack of understand of biology, med chem, and the simple realities of the entire industry. It isn't a matter of belittling a smaller player, but the fact that they really seem to have *not a clue* what they are talking about or getting into. Could be a translation issue, but aside from that, it is just staggering ill informed.

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17. Cellbio on June 3, 2008 10:52 AM writes...

I agree with milkshake about the value of the 'close personal interaction' between chemists and the biologist testing the compounds, though I am biased, having built a biology group for this purpose. As my favorite chemist said, "the activity of a compound is fixed the moment it is made, it is up to screening to reveal the merits and liabilities'. But to add a fine distinction, the quality of the chemist is key also. Perhaps they can be average in synthetic ability, but they need to be top notch in digesting the various forms of screening data that come back to properly direct the next rounds of synthesis. The mediocre ones I have worked with appear to design analogues with a heavy influence from what is doable (available intermediates, ease) rather than using screening data. My favorite chemist has stepped into the resulting screening quagmire, often refered to as SAR, though I wondered what the R part was, and looked all available data and made one compound that became the program lead, in one case a clincal candidate.

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18. Skeptic on June 4, 2008 5:50 AM writes...

"But the Fuji quotes, for anyone in drug discovery, are hilariously clueless"

And the systems biology crowd says the medicinal chemists are clueless. So there you go.

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19. Nick K on June 4, 2008 9:05 AM writes...

Skeptic: Perhaps you could give us evidence to support your allegation. It strikes me as idiotic, like most of your contributions.

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20. Morten on June 4, 2008 3:28 PM writes...

srp:

Paul Erhlich (sp?) who did the first drug program in the world hypothesized that since different tissue was dyed by different dyes then there would also be a toxicity difference between tissues. And some compounds which were toxic for infectious agents would be harmless for humans.
And he was right. Which became Salvarsan. It should be mentioned that Erhlich did HTS with all the compounds he could get his hands on (~1000). And his assay was curing rabbits of syphilis.

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21. Axicon on June 7, 2008 9:43 PM writes...

Derek and Jose: I get your point(s). And I recently noticed that Wyeth got into the coffee business through an acquisition in the 1940's, and it didn't seem to work out for them.

Regardless of what the garbage MBAs say, I find Fuji's interest in pharmaceuticals intriguing. Especially since it isn't my money.


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