Lab report

What lessons can we draw from the Northwick drug trial catastrophe? Plus new data provides evidence for cosmic inflation theory. Or does it?
May 19, 2006
Lessons from Northwick drug trial

Perhaps the most important lesson from the catastrophic human trial of TeGenero's TGN1412 drug at Northwick Park hospital is that it is dangerous to generalise. Dangerous for drug companies, which in this instance assumed, reasonably but nearly fatally, that the immune system of monkeys was all but identical to that of humans. Dangerous for opponents of animal experiments, who cannot credibly argue that this episode undermines the entire concept of animal models. (If that were so, the events at Northwick would be routine.) And perhaps dangerous for the immunologists pursuing this strategy of recruiting the body's immune response to combat leukaemia and auto-immune diseases, such as rheumatoid arthritis.

While details have yet to emerge, it seems that the aim of the drug was to stick to a molecule called CD28 on the surface of so-called T-cells involved in the immune system, kicking these cells into action. While some T-cells help combat disease by provoking an inflammatory response, TGN1412 was supposed to turn them into "regulatory" T-cells that suppress inflammation. But it may instead have aroused an unspecific militancy in T-cells, making the immune system of the volunteers attack itself or churn out toxic molecules. If so, minute differences between monkey and human CD28 could explain the lack of response in animal tests. Alternatively, the drug may have pressed the wrong buttons by activating CD28 on the surface of entirely different cells.

In any event, some immunologists think the trial shows that activation of T-cells via CD28 is too risky an approach, at least until more is known about this biomolecule and its involvement in the immune response.

Cosmic inflation—latest news

The picture of the universe revealed by Nasa's Wilkinson Microwave Anisotropy Probe (WMAP) satellite is far stranger than any science fiction novelist could have dared imagine. Three years ago, the first batch of WMAP data showed a cosmos almost entirely composed of varieties of energy and matter that we cannot see and about which we know nothing.

The latest measurements now provide strong evidence for an unimaginably rapid growth spurt at the start of cosmic history. In less time than it takes for light to cross the face of an atom, the universe appears to have grown from smaller than an atomic nucleus to something approaching its current size.

Known as "inflation," this sudden expansion was proposed two decades ago to explain some puzzling features of the universe today, such as why its temperature is so even from one side to another, and why it is so "flat," seemingly perfectly poised between eventual collapse and perpetual expansion. The period of inflation is thought to have happened less than 10-20 seconds after the big bang, when the universe grew much faster than the speed of light. Once inflated, the universe continued expanding at a much more leisurely pace.

Evidence for inflation is imprinted in the afterglow of the big bang, spread across the sky as a faint buzz of microwaves. This tell-tale pattern is the weakest cosmological signal ever detected, requiring three years of painstaking analysis that even the WMAP project leader Charles Bennett described to Nature as "gruesome detail day after day."

The cosmic temperature map produced by WMAP in 2003 showed minute variations throughout the universe. Although the pattern of this patchiness fitted the predictions of inflationary theory, it could have been an artefact caused by the way the cosmic microwave radiation has bounced off interstellar gas. The WMAP team has now ruled out that possibility by looking at a property of the microwaves called polarisation, which allows them to subtract such distorting effects from the primordial fingerprint.

But inflation is not so much a theory as a class of theories, each of which posits a different cause for the rapid expansion. The new data can rule out some of these ideas. But the WMAP results also hint at conflicts with the surviving inflationary models, while they remain consistent with some non-inflationary scenarios, such as the cyclic growth and collapse of the universe. Such puzzles only serve to underline, however, that this is indeed a golden age for cosmology.

When chemistry is fatal

Chemistry's reputation for stinks and bangs used to be a major selling point. Today's students are so assiduously protected from such hazards that lecturers complain they arrive at university with no practical skills and a terror of "chemicals." But a recent fatal explosion in a lab in France shows real perils remain in chemical research. Professor Dominique Burget of the École Nationale Supérieure de Chimie de Mulhouse was killed, and a student seriously injured, in a blast of unknown origin that wrecked the entire building of a laboratory dedicated, ironically, to industrial safety.

Such things were a regular feature of 19th-century chemistry—Davy and Faraday were regularly picking glass splinters out of their flesh, while studies on nitroglycerine killed Alfred Nobel's brother Emil. Whatever its cause, the latest display of the potential violence of chemical reactions is a reminder that such research cannot be risk-free, and that sanitising the learning lab is no way to instil appropriate caution in tomorrow's chemists.