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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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In the Pipeline

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August 9, 2013

An Interview With A GSK Shanghai Scientist

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Posted by Derek

Here's an interview with Liu Xeubin, formerly of GlaxoSmithKline in China. That prospect should perk up the ears of anyone who's been following the company's various problems and scandals in that country.

Liu Xuebin recalls working 12-hour shifts and most weekends for months, under pressure to announce research results that would distinguish his GlaxoSmithKline Plc (GSK) lab in China as a force in multiple sclerosis research.
It paid off -- for a while. Nature Medicine published findings about a potential new MS treatment approach in January 2010 and months later Liu was promoted to associate director of Glaxo’s global center for neuro-inflammation research in Shanghai. Two months ago, his career unraveled. An internal review found data in the paper was misrepresented. Liu, 45, who stands by the study, was suspended from duty on June 8 and quit two days later.

Liu was the first author on the disputed paper, but he says that he stands by it, and opposed a retraction (only he and one other author, out of 18, did so). He had been at the NIH for several years before being hired back to Shanghai by Glaxo, which turned out to be something of a change:

“This was my first job in industry and there was a very different culture,” Liu said behind thick, rimless glasses and dressed in a short-sleeve checked shirt tucked neatly into his belted trousers. “I was also not experienced with compliance back then, and we didn’t pay enough attention to things such as recording of reports from our collaborators.”

There was also a culture in which Glaxo scientists were grouped into competitive teams, known as discovery performance units, which vied internally for funds every three years, he said. Those who failed to meet certain targets risked being disbanded.

What I find odd is Liu's emphasis on publishing, and publishing first. That seems like a very academic mindset - I have to tell you, over my time in industry, rarely have I ever felt a sense of urgency to publish my results in a journal. And even those exceptions have been for other reasons, usually the "If we're going to write this stuff up, now's the time" sort. Never have I felt that we were racing to get something into, say, Nature Medicine before someone else did. Getting something patented before someone else, into the clinic before someone else? Oh, yes indeed. But not into some journal.

But neither have I been part of a far-flung research site, on which a lot of money had been spent, trying to show that it was all worthwhile. Maybe that's the difference. Even so, if the results that the Shanghai group got were really important for an approach to multiple sclerosis therapy, that's all the more reason why the findings should have spoken for themselves inside the company (and been the subject of immediate further development, too). We don't have to get Nature Medicine (or whoever) to validate things for us: "Oh, wow, that stuff must be real, the journal accepted our paper". A company doesn't demonstrate that it finds something valuable by sending it out to a big-name journal, at least not at first: it does that by spending more time and money on the idea.

But Liu doesn't talk the way that I would expect in this article, and I feel sure that the Bloomberg reporter on this piece didn't pick up on it. There's no "We delivered a new MS program, we validated a whole new group of drug targets, we identified a high-profile clinical candidate that went immediately into development". That's how someone in drug R&D would put it. Not "We were racing to publish our results". It's all quite odd.

Comments (18) + TrackBacks (0) | Category: Drug Development | The Dark Side


COMMENTS

1. grounded on August 9, 2013 8:39 AM writes...

Yes, it is odd, but GSK China has had a reputation for having a very competitive attitude towards all other research groups in GSK, for not collaborating, and for not sharing data. I hope that will change now. I always thought it was strange behaviour in a company (seemed more academic), but after reading the interview with Liu Xeubin, I better understand the internal pressures they were under to perform and publish. The rest of GSK R&D in my experience is not under that much pressure to publish in journals, but rather to go after the patents, the best molecules, the new targets, and the medicines. The DPU format cannot be blamed for driving people to play fast and loose with data, not pay attention to compliance, and mis-represent results. That is the fault of a dysfunctional local corporate culture.

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2. ScientistSailor on August 9, 2013 9:18 AM writes...

Derek,
There are companies with huge pressure to publish. They are the ones that like to think of themselves as academic institutions. Take a look at the current issue of Bioorg Med Chem Lett, you'll see three papers on three different targets from one department. That's a result of that pressure. Biology Scientists from the same company have to have a certain number of CSN (Cell, Science, Nature) papers to get promoted.

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3. alig on August 9, 2013 9:18 AM writes...

Patrick Vallance has made it extremely important to publish to be successful at GSK. I think it is because he is an academic and not a drug researcher; even though he is head of Drug Discovery

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4. barry on August 9, 2013 9:59 AM writes...

I've never been pressured to justify my programs against those of other "Discovery Progress Units" every three years. I can imagine that a tally of publications might be part of the assessment that will get more Process resources. So it's five twelve-hour shifts to advance a class of molecules and weekends to get some publications.

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5. Biotechie on August 9, 2013 10:01 AM writes...

To add to ScientistSailor's point, smaller size companies/startups also often use publishing in a high profile journal as a means of validating their technology or assets to investors when looking to raise funds.

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6. annonie on August 9, 2013 10:35 AM writes...

First, it must be recognized that GSk China wanted unlimited independence, including a total absence of review & scrutiny, from upper management and from other GSK R&D. They were allowed a great amount of such separation, and did not report to Valance. That is one of the major problems with the set up from the get-go.

Second, there were statements from the beginning for new drugs to come from China for GSK within 5 years in the area of neuroscience, an area that the former UK group was sturggling to find new potential therapeutics & hence the group was shut down at the time that GSK China was set up. Locally, they were absolutely committed to get something within 5 years......and so......

Xuebin says that he worked many hours, including weekends. When I was a young investigator, working 10 hours was not uncommon, and weekend work was common too. What is his point? Did he do this voluntarily, or was he pressured to do it?

Finally, his excuse about not knowing about "compliance" is simply silly. What is compliance except for proper documentation of experimental methods, recording of data, and writing up results in a permanent place. This is not a problem with GSK, as they have ways to conduct and insist on proper documentation. Also there were / are non Chinese people in biology in GSK China who had worked in the US or UK sites with long time, many years experience, and they knew how experiments should be recorded, and how documentation should be reviewed by supervisors. If this was ignored, or not in place in China, then the problem is likely more wide spread than this single situation, and GSK has a much larger problem internally than is being admitted in public.

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7. anon-1 on August 9, 2013 12:08 PM writes...

a further to @6.

1. GSK was clearly trying to establish an alternative model for revenue and productivity in China.

2. GSK had taken the trouble to set up a solid "back-door network" to make up sales.

3. with a "back door network" you can pretty much sell a drug under any pretext. Cf - in India they have a similar system of selling "branded generics".

4. it is therefore no surprise that - GSK-China wanted total independence.

5. In india - one can get a drug approved with marginal efficacy data generated from a small 100 - 200 patient "phase-III" study for NCEs !! go figure.

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8. more on August 9, 2013 2:07 PM writes...

The push to publish in China is very widespread and definitely not due to a single company or even just the drug industry.

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9. cynical1 on August 9, 2013 2:31 PM writes...

Anon-1(#7): There's a big caveat to what you wrote. The work in question was targeting multiple sclerosis. MS is extremely rare in India and China. The disease is mostly restricted to North America, Europe and Australia. So developing an MS drug to sell mostly in China and/or India would be a waste of time and money. No patients.

I also used to work for GSK in the US. But I never interacted with the researchers in China so I'm not going to speculate about their culture over there. However, I will say that you got disbanded at GSK whether you or your group met their objectives or not. And there was definitely no group safer than the one in China. Everyone knew that. So I have not an ounce of pity whatsoever for this guy's whiney sad bear story either. I could care a less what his excuse is to be honest.

More than anything, what he did was stupid and he got busted. Tough. Cry me a river, dude. Besides, stupid should hurt. And why does anyone care about this loser anymore, anyway?

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10. TX raven on August 9, 2013 3:25 PM writes...

Derek,
For organizations that have decided to make collaborations with external academics part of their research strategy, publications are a way to self-reassure they are down the right path.

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11. oldnuke on August 9, 2013 4:27 PM writes...

@10

It might be self-reassuring, but from of the articles that have been pointed out recently, you can't depend on the reviewers to catch all of the flaws.

There should be a "funding death penalty" for folks caught fudging their results.

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12. Insilicoconsulting on August 10, 2013 9:11 AM writes...

Looks like a lame excuse to falsify. But still one "pressure point" that I am aware of is that of proving to western scientists that asian research is just as good western.

No amount of success in discovering novel targets or leads can convince otherwise skeptical scientists that outsourcing to chindia is worthwhile. Outsourcing R&D is blamed on bean-counters. Perhaps gsk china people thought publishing in high profile journals would bring more acceptability. No a wholly unreasonable hypothesis given the chinese nationalism. Remember the south koreans and japanese also trying to prove their scientific and technical prowess to their own governments , which can then tom tom those...

Problem is, falsification can neither overturn western biases nor bring confer true recognition they seek, from political masters, national populace or the west.

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13. TX raven on August 10, 2013 9:35 AM writes...

@10: agreed on the "funding death penalty" for falsifying data.

As for peer reviewing your results, it is certainly more likely to add diversity of thought comparing with just staying "in house", in my opinion.

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14. gyges on August 11, 2013 4:46 AM writes...

re: "There's no "We delivered a new MS program, we validated a whole new group of drug targets, we identified a high-profile clinical candidate that went immediately into development". That's how someone in drug R&D would put it. Not "We were racing to publish our results". It's all quite odd."

Take care with this analysis, Derek. Journalists tend to corrupt and pollute what their subjects say simply because they don't understand what is being said. Gonzo journalism at its worst.

I have other examples from other situations eg when ransom demands were being reported during Gulf War One they were invariably reported in US dollars in the US and GB pounds in the UK but were most probably in neither of these currencies.

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15. Chris on August 12, 2013 1:00 AM writes...

Great interview! But I would like for you to ask questions on different pointers. Western scientists are as good as Eastern scientists. I think that should be pointed out.

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16. Anonymous on August 12, 2013 3:52 AM writes...

*lol* @ #9!!

SNAP!! My dept at GSK was cut in favour of our similarly-sized foreign counterpart that delivered far fewer candidates and drugs than us.

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17. Validated Target on August 12, 2013 8:44 AM writes...

@5 Biotechie: "smaller size companies/startups also often use publishing in a high profile journal as a means of validating their technology or assets to investors when looking to raise funds."

I was in a biotech with this philosophy. We were also heavily staffed with H1B visa holders to the point that the State Dept asked us why we were requesting more exemptions. I constantly asked my colleagues why they didn't support my own criticisms of our programs (which hurt MY career) which were decidedly NOT working. Answer: "I am afraid [to speak up]. I want to get my green card." Some of these colleagues as well as grad school colleagues told of "funny" stories of corruption in order to survive or thrive in China ("the norm"); to get to leave China for US grad school; and so on.

Weirdly, although disappointed by their admissions, these are still my friends (I think). I did not have to 'walk a mile in their shoes' in China. Even so, I did not betray the science for personal gain; in fact, I suffered by it.

BTW ... the "publish garbage to boost investor confidence" approach failed and the biotech was wiped from the face of the earth, as it deserved to be. The scheming MBAs and a few top level scientists made out very well; the rest of us got shown the door.

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18. GSKZombie on August 27, 2013 4:56 PM writes...

GSK has now (August 1) taken action to fully integrate (GSK buzzword is "align") China R&D into the standard global R&D organization.

Up until recent scandal, China R&D was largely independent of rest of R&D. They were clearly trying to let 'China be China.'

Get faster throughput at lower costs.

A grand experiment that completely blew up.

I give GSK R&D mgt credit for now attempting to pull China into the routine business structure.

Of course, I also give GSK R&D mgt full blame for the failed experiment in China R&D.

Many of us in UK & US saw this coming and predicted it. We were ignored (as always) in favor of the mgt fad of the month.

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