Prion theory which defied the CJD orthodoxy

STANLEY Prusiner has been on the wrong side of scientific orthodoxy for almost his entire career, which mixes medicine and science.

Professor Prusiner developed the theory of "prions" - misshapen proteins which can cause infectious diseases such as Creutzfeldt-Jakob Disease (CJD) and BSE - in the 1980s as an extension of his medical work after one of his first patients died from a form of CJD.

Prion theory overthrows previously accepted ideas, which insisted that genetic components - DNA - are required to pass diseases. Professor Prusiner said that misshapen proteins could on their own cause diseases that eventually destroy the brain by causing similar proteins in the body to become misshapen as well. That, he argued, triggers an avalanche in which misshapen proteins increase until cells die. That his opponents - who hold to the DNA theory - are now in the minority testifies to his strength of will and the power of his idea.

But the theory is incomplete. It doesn't explain exactly how the misshapen proteins trigger the avalanche, or why the disease can take so long (sometimes decades) to appear. Even his supporters were surprised this year when Professor Prusiner received the Nobel Prize for Medicine; Nobels are usually awarded for work which has proved itself fully.

Yet his declaration yesterday that he does not think there was a link between BSE and "new variant" CJD (v-CJD), which has so far killed 26 Britons, seems to take unorthodoxy beyond even his extraordinary limits.

The link is not just a hypothesis. Two important scientific papers have used independent methods which show that the two diseases are closely linked. Late in 1996 John Collinge of St Mary's Medical School in London analysed the molecular weight of BSE prions, and of "normal" CJD, v-CJD and scrapie (the sheep form of BSE). He found that v-CJD and BSE prions have distinctive molecular characteristics.

Then last year Moira Bruce of the Neuropathogenesis Unit in Edinburgh compared mice injected with BSE, and other mice injected with v-CJD. Both developed the same sort of damage to the brain, different from mice given "normal" CJD or scrapie.

Finally, only Britain has had an epidemic of BSE in which huge numbers of infected cattle passed into our food. And only Britain has v-CJD, which is definitely a new disease - doctors the world over have checked.

The delay between the appearance of BSE and v-CJD also matches what is known about the incubation times of these diseases.

Comments