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Derek Lowe The 2002 Model

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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: Twitter: Dereklowe

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« Microwave Synthesis | Main | The Reproducibility Initiative is Open »

October 16, 2013

Holding Back Experimental Details, With Reason

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Posted by Derek

There's a lot of worry these days about the reproducibility of scientific papers (a topic that's come up here many times). And there's reason to believe that the sharing of data, protocols, and materials is not going so well, either.

. . . authors seem less willing to share these additional details about their study protocols than they have been in the past, according to a survey of 389 authors who published studies in the Annals of Internal Medicine. The findings, presented on 9 September at the International Congress on Peer Review and Biomedical Publication in Chicago, found that over the five years studied the percentage saying they would be willing to do so has dropped from almost 80% to only 60%.

A lack of incentives for sharing might be partly to blame. “There's no recognition, no promotion and no profit for scientists who share more information,” says Steven Goodman, a clinical research expert at Stanford University School of Medicine in California, who was part of the team that evaluated the survey results.

But there are two new papers out that deliberately does not share all the details, and it's not hard to see why. This NPR report has the background, but the abstract from the first paper will be enough for anyone in the field:

Clostridium botulinum strain IBCA10-7060, isolated from a patient with infant botulism, produced botulinum neurotoxin type B (BoNT/B) and another BoNT that, by use of the standard mouse bioassay, could not be neutralized by any of the Centers for Disease Control and Prevention–provided monovalent polyclonal botulinum antitoxins raised against BoNT types A–G.

That's not good. Until an antitoxin is available, the sequence of this new neurotoxin will not be published, although the fact of its existence is certainly worth knowing. The Journal of Infectious Diseases has two editorial articles on the issues that this work raises:

(The) identification of a novel, eighth botulinum neurotoxin (BoNT) from a patient with botulism expands our understanding of Clostridium botulinum and BoNT diversity, C. botulinum evolution, and the pathogenesis of botulism, but it also reveals a significant public health vulnerability. This new toxin, BoNT/H, cannot be neutralized by any of the currently available antibotulinum antisera, which means that we have no effective treatment for this form of botulism. Until anti-BoNT/H antitoxin can be created, shown to be effective, and deployed, both the strain itself and the sequence of this toxin (with which recombinant protein can be easily made) pose serious risks to public health because of the unusually severe, widespread harm that could result from misuse of either [3]. Thus, the dilemma faced by these authors, and by society, revolves around the question, should all of the information from this and similar studies be fully disseminated, motivated by the desire to realize all possible benefits from the discovery, or should dissemination of some or all of the information be restricted, with the goal of diminishing the probability of misuse?

I think they've made the right call here. (Last year's disputes about publishing work on a new strain of influenza are in just the same category.) Those studying botulin toxins need to know about this discovery, but given the molecular biology tools available to people, publishing the sequence (or making samples of the organism available) would be asking for potentially major trouble. This, unfortunately, seems to me to be an accurate reading of the world that we find ourselves in. There is a point where the value of having the knowledge out there is outweighed by the danger of. . .having the knowledge out there. This is going to be a case-by-case thing, but we should all be ready for some things to land on this side of the line.

Comments (14) + TrackBacks (0) | Category: Infectious Diseases | The Dark Side | The Scientific Literature


1. annon on October 16, 2013 11:24 AM writes...

So, why publish it at all?

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2. Tuck on October 16, 2013 11:36 AM writes...

Good case, but what about the other 39.999% of researchers who don't want to publish their data? :)

"So, why publish it at all?"

Because medical professionals need to know about it, and if it's becoming common, the only way to know that is if doctors are aware and can report it.

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3. Hap on October 16, 2013 1:42 PM writes...

Why do I have the feeling that the infection didn't turn out well for the baby who had it?

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4. PharmaHeretic on October 16, 2013 2:22 PM writes...

Here is an interesting and possibly significant development in treating MS. Benztropine appears to be effective at stimulating remyelination in animal models at concentrations that are clinically doable in human beings. Best of all, it is an already approved drug for treating some symptoms of Parkinsonism.

A regenerative approach to the treatment of multiple sclerosis

"Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis."

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5. Thomas on October 16, 2013 3:02 PM writes...

This is similar to not publishing computer viruses in a library. Warn about the risk, the effect, and the differences with previously discovered strains.

There is very little use to publishing a complete ready to use computer virus if there is a description about how it works. Same applies to this DNA sequence, I'd suppose. Knowing it is available should be enough; the authors are likely available for collaborative efforts.

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6. azetidine on October 16, 2013 7:59 PM writes...

Without the ability to reproduce their work, we cannot verify that the authors are telling the truth.

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7. Insilicoconsulting on October 16, 2013 10:19 PM writes...

The only places where such research could be exploited for military bioweapons use would be the West. Anthrax anyone? Like the nuclear non-proliferation treaty and pressure on syria the west would not allow biological weapons to be developed /bought by others, regardless of the fact that they may already have stocks of the same.

If its a public health problem, its better to release the data and CDC and other institutions can collaborate before anything more serious happens. Just a ruse, probability of misuse indeed.

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8. Kaleberg on October 16, 2013 11:42 PM writes...

This is a strikingly similar approach to that taken by the computer security community when new exploits are discovered. If you want to keep your white hat you can loosely describe the exploit to the public, but make sure that the target has some time to put out a bug fix first.

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9. Lars on October 16, 2013 11:49 PM writes...

This is a long-standing discussion. The locksmiths had it in the 18th
century, Kerckhoff published his 'La cryptographie militaire' in the
latter half of the 19th. We have it in the IT sector, in software
vulnerability analysis. A couple of years ago, a Danish chemistry mag
withheld some details in an article on TATP. I'm sure this has
occurred in the field of virology before.

In my field (IT), there is a need to create incentives for the
developer of a piece of software to fix his stuff. Since the cost of
re-releasing a piece of software can be high, we have developed a
model called responsible disclosure, which ensures that sufficient
information is released to ensure that users know there is a problem,
and the rough details. The model then calls for the security
researcher and the software developer to cooperate, and to ensure that
full details are published either when a fix is available or when it
becomes clear that cooperation is not going to happen. The details can
vary, of course. The vulnerability is then typically added to programs
like Metasploit which allow for so-called automated penetration testing of
company IT facilities as an ongoing proactive measure.

So I guess my question is, how long is this going to take? And what is
going to happen if antiserum cannot be made for whatever reason - will
they put a lid on it until the next case report comes in or are there
guarantees in place?

Lars (computer scientist, working in IT security)

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10. petros on October 17, 2013 6:35 AM writes...

Remember that some patent filings may be kept closed on national security grounds. This is certainly the case in the UK and I assume elsewhere

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11. Paul on October 17, 2013 10:05 AM writes...

In my field (IT), there is a need to create incentives for the developer of a piece of software to fix his stuff.

There are other incentives. Security agencies (like No Such Agency) pay good money for zero-day exploits. So if I find an exploit, do I report it to the company, or do I sell it to the highest bidder?

This might even be seen as an incentive to insert problems into commercial code, so they can later be "discovered" and monetized.

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12. metaphysician on October 17, 2013 4:45 PM writes...


What would make you think that? Biological and chemical weapons design isn't anywhere near the same magnitude of difficulty as nuclear weapons design.

( for that matter, nuclear weapons design isn't *that* hard, either, the real challenge is producing enough high grade fissionables and miniaturizing it enough to fit on a practical missile )

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13. Cellar on October 19, 2013 7:33 AM writes...

Please do tell: How does this relate to something like half of recent biomedical research results turning out not to be reproducible, even without withholding details?

There may be good reasons, but there are also very good reasons for publishing everything. In fact, it's one of the things that have made science such a roaring success.

The reasons stated for publishing only a little bit is because knowing that much is valuable already. And so it is. But is the paper still science?

I think not. Intelligence, an interesting anecdote, but not data, and not science. And as long as you don't pretend it is science, that's fine. But we do need to know that. So no pretending.

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14. Spiny Norman on October 27, 2013 12:22 PM writes...

So by not publishing the sequence, the rather likely possibility that clinical labs might stumble across these strains in the wild thereby permitting surveillance is effectively precluded

In exchange, the wildly improbable manufacture of these toxins for bioterrorism is impeded.

This strikes me as yet another failure of risk/benefit analysis.

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