Contracting away our credibility?

The deep reach of the pharmaceutical industry into academic and clinical medicine sets up ample opportunity for conflicts of interest on the part of biomedical researchers. To minimize the risks that such conflicts could introduce bias into the scientific literature, most publications impose reporting regulations that make transparent any financial stake that an individual researcher may have in the subject of his or her publications. Similarly, most institutions regulate the nature and scope of such financial agreements.

However, there appears to be significantly less oversight when it comes to an individual researcher’s ability sign away freedom of inquiry and publication. In a commentary in this week’s Chronicle of Higher Education, Harvard School of Public Health professor Marc Lipsitch points out that few universities have explicit regulations to prohibit researchers from signing consultation agreements that severely curtail their freedom to express their opinions or choose the direction of their research. And in the absence of such regulations, Big Pharma are starting to ask for precisely these types of contractual restrictions. Lipsitch reports his own experience: (more…)

Do we expect the body to be a “One Hoss Shay”?

In an 1858 humorous poem The Deacon’s Masterpiece, or the Wondeful One Hoss Shay, Oliver Wendell Holmes Sr. described a carriage so artfully constructed as to have no weakest link. The carriage ran smoothly for exactly a hundred years, and then one day

it went to pieces all at once, –
All at once, and nothing first, –
Just as bubbles do when they burst,

leaving its driver sitting atop a pile of rubble and dust.

(more…)

Hedging against Antiviral Resistance During the Current Influenza Pandemic

Hedging against Antiviral Resistance During the Next Current Influenza Pandemic

Commentary on: J.T. Wu, G.M. Leung, M. Lipsitch, B. S. Cooper, and S. Riley  2009. Hedging against Antiviral Resistance during the Next Influenza Pandemic Using Small Stockpiles of an Alternative Chemotherapy. PloS Medicine. Online ahead of print 4/30/09. http://www.plos.org/press/plme-06-05-wu.pdf

Eight days ago we received the first reports of a half-dozen infections in Texas and California patients by a swine-derived strain of influenza A H1N1; these reports were accompanied by speculation that these case might be related to a cluster of atypical pneumonia cases in Mexico City. Only eight days later, we now are looking at hundreds of confirmed cases, and presumably thousands of total cases, distributed throughout the US and Mexico, with additional confirmed cases in multiple regions of Europe, Asia, and Oceana. The World Health Organization has raised the pandemic alert level from phase 3 to phase 5 (widespread human infection), and pandemic plans are being put into operation around the globe.

The point is that things move extremely fast in the early phases of an epidemic – and at the same, early decisions about plans to control or mitigate the epidemic can cast a very long shadow with respect to the ultimate trajectory that the epidemic takes. Yesterday, PloS Medicine released an advance copy of a paper by Wu et al., written prior to the current situation but uncannily relevant to the current pandemic control process.

Using a set of simulation models, the authors show that the choice of which antivirals to use early in an influenza pandemic can have dramatic consequences for the evolution and spread of antiviral resistance (more…)

Avoiding resistance by disrupting cooperation

As most readers of this website are well aware, antibiotic resistance poses a considerable problem for public health, and we are in serious need of new approaches for dealing with this threat. One possible direction could be to use drugs such as quorum-sensing disruptors (e.g. Dong et al. 2001 Nature) that target disrupt bacterial cooperation, since coordinated cooperative behavior is necessary for many forms of pathogenesis. At the conclusion of my previous commentary, I briefly mentioned a paper in Ecology Letters by André and Godelle 2005 about the possible evolutionary benefits this approach. There, André and Godelle ask the question “How quickly will resistance evolve to drugs that target group-level cooperative traits of bacteria?”

Prior to reading this paper, I had always been somewhat pessimistic about the prospects for drugs that disrupt quorum signals, for the simple reason that I expected that  bacteria could quickly evolve resistance to such compounds. All it would take to get resistance, after all, is a point mutation to constitutively express the genes that were previously regulated by the quorum sensing signals.

But that reasoning of mine may be flawed: (more…)

Phenotypic noise and the evolution of virulence

Commentary on: M. Ackermann, B. Stecher, N. E. Freed, P. Songhet, W.-D. Hardt, and M. Doebeli (2008) Self-destructive cooperation mediated by phenotype noise. Nature 454:987-9

One of the most exciting developments in microbial population biology over the past few years is the recognition that high levels of phenotypic noise – in which genetically identical microbes express different genes and manifest different phenotypes despite a common environment – is widespread in bacterial populations and that this noise plays an important role in bacterial evolutionary ecology (e.g. Elowitz et al. 2002, Balaban et al. 2004, Rosenfeld et al. 2005, Acar et al. 2008, Veening et al. 2008). I have always thought that the best explanations for this phenomenon involve bet hedging in uncertain environments (Seger and Brockmann 1987), and indeed this bet-hedging perspective has been well supported by mathematical modeling (e.g. Thattai and van Oudenaarden 2004, Kussell et al. 2005).

But in this week’s issue of Nature, Martin Ackermann and colleagues propose an alternative explanation (more…)