Uncertainty and research

A dispute about the effects of a hormone illustrates the uncertainty and controversy that surrounds scientific research.

Many groups are searching for molecules involved in metabolic processes affecting body weight, with a view to developing new therapeutics.

In 2002, a London lab headed by Professor Steve Bloom caused much excitement when they reported in the journal 'Nature' that a molecule called PYY3-36 made rats less hungry; they ate less and got thinner. The molecule even seemed to work on people, in a small clinical trial.

Unfortunately, other labs said they couldn't get the same results. For any scientific study to be widely accepted, it needs to be reviewed by experts, published in a scientific journal, and the results confirmed by different labs. Yet several labs around the world found they couldn't replicate the findings.

What was going on? Two labs may get different results for a variety of reasons. For instance, like following a recipe from two slightly different cookbooks, the labs may follow slightly different methods. Or like two different chefs, some scientists will be better at certain experiments than others. Or lab conditions might be slightly different, or the 'ingredients' (the reagents) might differ. Very occasionally – and there is not the slightest suspicion that this is the case here – the lack of replicability is evidence of scientific fraud.

Things reached a head when a scientist called Matthias Tschöp got together with other labs to say publicly that they couldn’t repeat Bloom’s results. Tschöp and the others had used the same rats, the same rat food given at the same time of day, and the same PYY3-36, but still couldn't get the same results.

Bloom suggested the other groups were not doing the experiments properly, handling the rats in a different way. Things got more complicated when the drug company that planned to sell a drug based on PYY3-36 said they could repeat Bloom's results. And in November 2004, two groups announced they could get PYY3-36 to affect appetite, in rats and rhesus monkeys.

The episode illustrates that science is not cut and dried. At its leading edge, there is controversy and disagreement, different theories and models. Over time, as more experiments are carried out, published and scrutinised, a consensus emerges and (usually) everyone moves on.