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August 27, 2008

Biden on bird flu

The world is watching US SenatorJoe Biden today. The the new hopeful for vice president will speak tonight at the Democratic National Convention in Denver. Through his previous legislative proposals, though, he has already said volumes about what global health issues he views as important.

Last summer, Senator Biden introduced the Global Pathogen Surveillance Act of 2007 (S. 1687), which would expand overseas infectious disease laboratories run by the Centers for Disease Control and Prevention (CDC). Experts say the risk of an avian flu pandemic is as great as ever. But according to Biden, the US government is only "one-third" prepared for an outbreak.

A report submitted by Biden urging passage of the Global Pathogen Surveillance Act calls developing nations the “weak links in a comprehensive global surveillance and monitoring network” and cites research suggesting that about one-third of countries may not even have the tools required to diagnose avian flu in humans. It's no surprise then that the proposed legislation would also provide assistance to developing nations that need better tools for recognizing and containing infectious disease outbreaks.

Forgive the pun, but in my opinion this legislation kills two birds with one stone. In addition to offering increased protection from natural pandemics, it would help prepare the global community for launching a coordinated response against a biowarfare attack; biological agents, manmade or natural, are likely to spread through human populations in similar ways. If passed, the act would cost each American family about $1—a small sum compared with the approximate per-family cost of $300 for the United States Global Leadership Against HIV/AIDS, Tuberculosis and Malaria Reauthorization Act of 2008 (also known as PEPFAR), recently signed by US President George W. Bush.

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Photo by Just chaos

August 06, 2008

The best defense against biowarfare

The recent suicide of vaccine researcher Bruce Ivins, the FBI’s prime suspect in the fatal anthrax mailings following the 9/11 attacks, has brought bioterrorism back to the forefront of the national consciousness. Many people are pondering out loud: Is the US prepared to respond to a bioweapons attack? Probably not, according to recent media reports. The government has invested some $50 billion in biowarfare research since 2001, which has gone into creating new labs, building up stockpiles of antibiotics and smallpox vaccines, and devising strategies for large-scale distribution of these medicines. Yet despite considerable progress, there is still work to be done; we still don't have a suitable anthrax vaccine, for example.

Congressional investigators have expressed concern that the recent proliferation of biowarfare research facilities might actually increase US vulnerability because more people have access to dangerous materials, which generates more opportunities for accidents and abuse. There are currently some 14,000 people working at about 400 laboratories authorized to study certain 'select agents' — dangerous viruses, bacteria and toxins, some of which could be weaponized, The New York Times has reported.

But I think the more people conducting research in this area, the better. Chemical and biowarfare attacks are likely to happen regardless of how hard we try to thwart them. Much of the scientific information required to make bioweapons is freely available on the Internet; synthetic DNA can be mail-ordered with the click of a mouse. Our best defense against biowarfare is to cultivate a vibrant biomedical research community with agile response capabilities. We need biosensing systems that can rapidly detect dangerous particles in the environment, fast tests for identifying pathogens, along with new vaccines, antibiotics and antivirals.

Stockpiling medications is not sufficient; we need better techniques for designing and manufacturing the medicines, as it is impossible to anticipate every potential biowarfare scenario. (To get an idea of the number of potential agents we are dealing with, check out the select agents list compiled by the feds and you find everything from the familiar botulinum neurotoxin to the mysterious “Lumpy skin disease virus.”)

The best step the US government can take to prevent abuses and accidents is to cooperate with its international partners to create an effective oversight framework under which this type of research can flourish safely. This, unfortunately, has not yet happened.

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Image by canardo

The end of the middle class

Another long blogging hiatus. I can offer the same excuses as last time, plus a new one: I was told off after the last entry. Oh well! You live and learn, I guess.

This time, it's this article in Science that captured my imagination. In it, James Evans analyzed a database of 34 million articles to show that, as more journal issues have gone online, the articles currently cited tend to be more recent, fewer, and come from fewer journals.

Evans argues that print journals forced scientists to do more browsing, perhaps stretching scientists to anchor findings more deeply into past advances. He also argues that, sure, searching online is a more efficient way of putting you in touch with the prevailing views in your field. The price we pay, though, is that such "narrowing of science and scholarship" (borrowing from Evans' title) may accelerate consensus and impose limits on the range of ideas upon which we build scientific progress.

This is a fascinating contribution that, needless to say, I would find very difficult to formally evaluate. Yet, an intriguing question formed in my mind: is there a strict causal relationship between journals going online and this narrowing of scholarship, or are there other factors that explain that fewer, newer papers that come from fewer journals are being cited? In all fairness to Evans, he didn't make any claims regarding a strict causal relationship, and he didn't say that his observations fully accounted for the current citation pattern. Still, a provocative exercise is to think about other factors that may explain the trends he identified.

In terms of citing newer papers, I suspect that technical advances have a lot to do with that. For example, the advent of transgenic and knockout mice represented a turning point for biology. You can now obtain much more definitive answers about the function of a molecule if you have a knockout than before, when all you could hope for was having a more or less specific antagonist. It wouldn't be surprising if advances of this sort have modified the citing behavior of a scientist writing a paper.

Regarding the citation of fewer papers, some studies have shown that many people tend not to read the references they cite, but simply copy them from other papers that have cited them—a behavior that one could refer to as "meta-referencing". Also, I have anecdotal evidence of people who don't cite anything that isn't in PubMed. For example, when a referee asks an author to cite the classic papers from Dr. Smith from the 1950s, it's not that uncommon to hear that they "couldn't cite them because the abstract wasn't in PubMed".

So, the whole universe of citable papers does not extend beyond the 1970s, and many of us cite papers even though we haven't read them, just because someone else did. And we haven't even talked about the proliferation of review articles, in which you often find the authors citing other reviews on the same topic—a behavior one could refer to as "meta-reviewing". No wonder few papers get the benefit of a citation.

The last point has to do with the observation that we now tend to cite papers from fewer journals. A first corollary of this fact is that the journals that publish the papers that garner those highly coveted citations will have the highest impact factors. A second corollary is that, if fewer journals have most of the citations, this would predict that we will see an ever increasing gap between the impact factors of the high-profile and the more specialized journals. In socioeconomic terms, we will see a widening gap between the wealthy and the poor at the expense of the middle class.

From where I sit, this prediction seems to be proving right. Back in the 1980s, when I started in research, publishing your work in any international journal truly represented the crystallization of a lot of work. So, even though you didn't get your paper in Science or Nature, it didn't matter so much because your small contribution, however humble, still counted for something to those working in the same field as you. These days, some journals in which I published my work are largely ignored by the community, which tends to think about them as "places in which you publish your work after everything else fails". In fact, some people prefer to store the paper in the filing cabinet before publishing in some journals that have come to be too specialized for their taste.

As for the current middle class, the journals that aren't regarded as high profile but are very solid publications that demand a lot from authors -- those journals where you immediately send your paper after the "vanity" journals turned you down -- are constantly trying to improve their image and position themselves in such a way that they are also perceived as high profile, quite often with great success. This is, of course, a very smart thing to be doing because, as the gap between rich and poor widens, you don't want to be caught on the wrong side of the divide.

To end, I thought I'd paste Evans' last paragraph, which also fed my imagination, triggering associations that I may share in a future post:

"The move to online science appears to represent one more step on the path initiated by the much earlier shift from the contextualized monograph, like Newton’s Principia or Darwin’s Origin of Species, to the modern research article. The Principia and Origin, each produced over the course of more than a decade, not only were engaged in current debates, but wove their propositions into conversation with astronomers, geometers, and naturalists from centuries past. As 21st-century scientists and scholars use online searching and hyperlinking to frame and publish their arguments more efficiently, they weave them into a more focused—and more narrow—past and present."

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Photo of Newton @ Madame Tussauds by _Colaco_. Scan of Darwin portrait by cpurrin1.

August 01, 2008

United we disclose

The relationship between pharmaceutical makers and physicians has come under close scrutiny lately. In recent weeks Congressional leaders have accused Harvard physicians of failing to properly disclose large payments from drug companies; meanwhile, other reports have highlighted the industry ties of certain experts who helped write the American Society of Pediatrics’ new recommendations for managing childhood cholesterol.

One way to facilitate greater transparency in biomedical research is to adopt a universal policy for reporting conflicts of interest in the scientific literature, according to the Center for Science in the Public Interest, a nonprofit health advocacy group based in Washington, DC.

The group has released a model disclosure policy, which requires authors to tell editors about all potentially relevant financial relationships from the past three years. This means all types of employment, consulting gigs, patents and patent applications for products related to the research, travel grants, speaking fees, writing fees, membership to science advisory boards, stock ownership (including investments by immediate family members) in funding by firms that have anything at stake in the research, and perhaps even strong personal, intellectual or political convictions relating to the study. The authors would also submit formal conflict-of-interest statements to be published along with the paper, which editors would evaluate against the scientists’ private declarations.

Transparency always seems to be the best policy, but will everyone agree upon what constitutes a potentially relevant conflict of interest? Some people are exceptionally good at convincing themselves that they are immune to bias, and since the policy relies on an honor system it will be hard to keep track of those who defy it. The other question is whether a uniform policy is better than having each journal frame its own policy, one that is tailored to the particular set of issues affecting its field. For example, patent issues seem to be particularly germane to biotechnology but not so much to geoscience, and pharmaceutical consulting fees are intensely to relevant to medicine but much less so to the physical sciences. Would a universal policy even be practical?

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Photo by Mike Licht, NotionsCapital.com