Wednesday, September 01, 2010

The prospect for September


Bit of overmatter from my Prospect Lab Report this month, as the top story below blew up shortly before it went to press, so the last two stories below were shelved. Here, as ever, is the unexpurgated version.


It would be nice to be able to report that the much trumpeted ‘end of antibiotics’ is just a slice of media alarmism. But it isn’t. The danger that just about all our existing antibiotics will soon be powerless against resistant bacteria, as claimed in Lancet Infectious Diseases, is all too real. A paper in the journal reports the emergence and spread of strains of common pathogens, such as E. coli and the pneumonia bug K. pneumoniae, containing a gene that confers resistance against even current last-resort antibiotics called carbapenems. Such bacteria, Chris Walsh of Harvard Medical School confirms, “are on the brink of being impossible to treat with existing antibiotics.” “This is a very serious problem”, agrees Gerry Wright, a specialist in antibiotic resistance and discovery at McMaster University in Ontario. Without antibiotics, even routine surgery could cause fatal infections.

Antibiotic resistance has been with us ever since penicillin revolutionized medicine. So why the problem now? Partly, it’s simply becoming harder to find new drugs to expand the arsenal. But the difficulties also stem from practices within the pharmaceutical industry. “This is a very grim time in antibacterial drug development”, says Wright. “The reasons are complex, but the fact that many pharmaceutical companies have moved to a focus on chronic diseases is one.”

Wright is one of several specialists who have been clamouring for years about the danger. In 2004, Carl Nathan of Cornell University’s Weill Medical College decried the way companies look for profitable blockbuster antibiotics. These are general-purpose drugs for chronic infections, and their widespread use quickly elicits resistance. But if their use is restrained, profits fall and funding and expertise leaches away. This, along with regulatory hurdles, the debilitating effects of a spate of big pharma mergers, and myopic focus on hitting tried-and-tested biochemical targets in the pathogens, has now almost dried up the antibiotic development pipeline. Nathan called for an overhaul in the way new antibiotics are sought and brought to market, including a vigorous not-for-profit pharmaceutical sector.

Something certainly needs to change: this is a global problem for which the market may not offer any solution. “Multidrug resistant bacteria will only continue to spread”, says Wright. “There is no chance that the problem will go away.”

*****

The UK coalition government’s plan to dismantle the Human Fertility and Embryology Authority in its cull of ‘health quangos’ is nothing short of vandalism.

The Health Protection Agency, also on the hit list, supplies vital advice about infectious diseases to the government, public and medical profession. But that demands rather specific expertise which could at least conceivably be transferred intact within the civil service. The HFEA is different.

Set up in 1991 after much governmental procrastination in the wake of the first IVF birth (1978) and the subsequent Warnock Report (1984) on embryo research, its responsibilities ballooned as developments in embryology and assisted conception accelerated. The authority’s recent wrestling with the ethics of human-animal hybrid embryos and stem-cell research seems a long way from treatments for infertility, but there is an inextricable link between them, historically and scientifically. This is one reason why the possible plan floated by Health Secretary Andrew Lansley to parcel out the HFEA’s work to three other bodies is naïve and potentially dangerous. Decisions about these delicate matters at the forefront of reproductive and biomedical technology require a comprehensive overview of the context, and ever more so as time goes by.

The real tragedy is that the HFEA did its job so well, as attested by the fact that it managed to upset both religious (and secular) conservatives, for perceived liberalism, and scientists, for alleged restrictiveness (despite the UK having one of the most permissive embryo research frameworks in the world). The HFEA was genuinely independent, refusing to kowtow to government, scientists, IVF clinics, religious groups, or public opinion. Doubtless some of its decisions could be criticized, but they were always taken with sober, informed consideration. It was a bulwark against the hazards of both a laissez-faire free market in infertility treatment and knee-jerk reactionary prohibition. It will be a miracle if the same acumen can be assembled from the scattered remains.  

*****

The announcement of an antiviral vaginal gel that can reduce HIV infection by around 50 percent is good news, however qualified. The current clinical trial, conducted by the Durban-based Centre for the AIDS Program of Research in South Africa, is modest in scale and awaits replication, along with more data on safety and a better understanding of why it doesn’t always succeed. But the great virtue of this strategy is that it gives some autonomy to women, who can reduce their chance of contracting the virus when male sexual partners refuse to use a condom. In South Africa, a third of all women between 20 and 34 are thought to be HIV-positive, and they account for around 60% of all new infections.

The gel contains an antiviral drug which interferes with a key enzyme involved in viral replication, unlike previous efforts which have sought either to inhibit the entry of viruses into cells or to kill the viruses (or infected cells) directly. Testing on 889 HIV-negative women over two years showed that regular use could reduce the chance of infection by 54%. The gel should be very cheap per dose and has few side-effects. The question now is how to balance the urgency of need against time-consuming confirmation and in-depth clinical testing.

There was more promising news with the announcement that two ‘therapeutic vaccines’ for HIV – which aim to prevent transmission from infected people rather than preventing infection in the first place – have at last shown some success in boosting immune systems debilitated by HIV. The vaccines use pieces of RNA from the virus to stimulate an immune response.

Many AIDS researchers had concluded that therapeutic vaccines would not work, and even now the response to the new trials, which report only a modest suppression of the virus, is somewhat muted. Some fear the strategy might backfire by boosting evasive viral mutations.

*****

It’s a good time to be an oil specialist: lucrative contracts beckon both from BP and from the US government as they prepare for the obligatory Natural Resource Damage Assessment. But there are strings attached in either case: you probably won’t be able to publish your research for confidentiality reasons. Some academics have already declined offers for this reason. There is of course nothing very usual about gag rules for work contracted by a private company or for government-backed research with legal implications. But it could mean that, in the absence of significant independent funding for such research, a detailed understanding of the effects of the Deepwater Horizon spill will never be made public.

On the other hand, oil clean-up technology could be improved by the carrot of a $1.4 million prize dangled by the X Prize Foundation, a Californian organization that aims to stimulate “radical breakthroughs for the benefit of humanity”. The company has previously offered a $10 million award for the development of a privately funded, manned spacecraft, which was claimed by the company Scaled Composites now working on Richard Branson’s Virgin Galactic commercial spaceflight programme. Entries for the oil prize are already being prepared. It’s good that the Foundation has noticed there are better ways to spend its money.

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