Of the six volunteers who became seriously ill during a drug trial last week, four, mercifully, seem to be beginning to recover, while two are still critical, according to the most recent BBC news story. It’s still too early to be sure what went so tragically wrong; there are informative articles, with some informed comment, on the websites both of New Scientist and Nature. What we should learn from this is that even as medicine gets more sophisticated and molecularly specific, many things can go wrong in the introduction of new therapies. The length of time it takes new treatments to get regulatory approval can be frustratingly, agonisingly long, but we need to be very careful about the calls we sometimes hear to speed these processes up. The delays are not just gratuitous red tape.
The drug behind this news story was developed by a small, German company, TeGenero immunotherapeutics. It’s a monoclonal antibody, code-named TGN1412; a protein molecule which specifically binds to a receptor molecule on T-cells, a type of white blood cell which is central to the body’s immune response. The binding site – code-named CD28 – is a glyco-protein – a combination of a protein with a carbohydrate segment – which provides the signal to activate the T-cells. What’s special about TGN1412 is that the action of this drug alone is sufficient to activate the T-cells; normally simultaneous binding to two different receptors is required. It’s as if TGN1412 overrides the safety catch, allowing the T-cells to be activated by a single trigger. It’s these activated T-cells that then carry out the therapeutic purpose, killing cancer cells, for example.
Few people have connected these events with bionanotechnology (an exception is the science journalist Niels Boeing in this piece on the German Technology Review blog). There are now a number of monoclonal antibody based drugs in clinical use, and they are not normally considered to be the product of nanomedicine. But they do illustrate some of the strategies that underlie developments in nanomedicine – they are exquisitely targeted to particular cells, they exploit the chemical communication strategies that cells use, and they increasingly co-opt biology’s own mechanisms for clinical purposes. Biology is so complex that it’s always going to spring surprises, and the worry must be that as our interventions in complex biological systems become more targeted, so the potential for unpleasant surprises may increase. Whenever one hears blithe assurances that nanotechnology will soon cure cancer or arrest ageing if only those bureaucratic regulators would allow it, one needs to think of those two men struggling for their lives in a North London hospital. There may be good reasons why the pace of innovation in medicine can sometimes be slow.
I’m not sure we should be so quick to accept the ethical balance presented here. There are a lot more than two people struggling for their lives due to cancer or ageing. Why exactly do the two people in North London outweigh the billions who will suffer from these other conditions?
Well, of course this particular treatment was not going to cure cancer or ageing. But if someone came up with something that had a good chance of working, wouldn’t it make sense to accept an expedited path through clinical trials, even if it did increase the risk to experimental subjects?
An ethical principal that we cannot risk even one person’s life in pursuit of a treatment that could save billions seems far too conservative to me.
Hal, there’s a great deal that can be written about the ethics of clinical trials, but that wasn’t really my main point here. The point is that the people who developed this drug undoubtedly did think it had a good chance of working, and they did have a lot of good scientific reasons to think that it might be a cure for cancer (at least some types, in some circumstances). We will undoubtedly learn from the inquiries that will follow whether they were too hasty in taking the drug to human trials, but the bottom line is that when confronted with the complexities of a real human, their scientific assumptions proved to be very fallible. It’s assumptions of precisely this kind that underlie judgements of the kind you imply in the phrase “something that had a good chance of working” so we’d better be very clear about how reliable these assumptions are likely to be.
I totally agree with Richard. Hal didn’t get the point at all.
well said. I wonder how many others in the medical community think so too? I fear that the majority grab the same end of the stick as Hal
I apologise for missing the point of the article. I thought Richard was saying that the suffering of these two unfortunate experimental subjects outweighed the potential good of even a cure for cancer. The Hippocratic Oath says, first, do no harm; and it seemed that Richard was advocating such a standard for scientific research. He would not be alone in doing so: the so-called Precautionary Principle extends this concept into a larger arena, and is widely supported. It is this direction of thought that I think is fundamentally misguided and which I thought was important to take issue with.
However, on reading Richard’s comment and re-reading his essay, I now think that I misinterpreted his point, and that in fact he was saying that biology is complicated, medicine is complicated, and even interventions that seem likely to be safe and effective may not work the way we expect. Hence, progress in medicine, nanomedicine, and biology will continue to be slower than we might wish.
I find this unarguable, and I assume most other people would, too.
Hal, I appreciate your gracious clarification.
These kinds of incidents can happen in any of the clinical trial irrespective of nature of product under investigation. All clinical scientist has to follow guidelines and cGCP to conduct study and generate data for submission to the regulatory authorities like FDA or MCA. No one will be dare enough to put their molecule under clinical test if they get a slightest hit of possible acute or chronic toxicity. However, nanotechnology based products has to be handled with extra care as by the virtue of their size they might pose a total different clinical manifestations. Recently a consumer product based on nanotechnology was recalled from the market in Germany. FDA will be more coutisious in dealing with application of (IND/NDA) nanopharmaceuticals.
Some links for more information
http://www.nanopharmaceuticals.org
http://www.nanopharmaceuticals.org/news_2006/First_nanoproduct_recall.html
I am currently particpating in a clinical drug trial in Japan. The money is definitely an incentive, but as long as adequate information is provided about the drug prior to consent, then I feel these studies have some altruistic merit. In anycase, the experience is very interesting and I am publishing an online diary about it at http://whitemice.wordpress.com/
That looks an interesting blog, but I’m probably too squeamish to follow it! Good luck, anyhow, and I agree with you that this is something with a real benefit to society.