By David N. Leff
Whom the Gods would destroy, they first make mad.
Brought up to date, this famous line by Longfellow might read today: "Whom the Gods would destroy * man or beast * they first send prions."
Prion infection * 'mad cow' disease * today is decimating several million cattle in British herds. (See BioWorld Today, Dec. 20 and April 8, 1996, p. 1.)
This bovine spongiform encephalopathy (BSE) may also have infected 14 young men and women in the U.K. with the human equivalent of BSE, Creutzfeldt-Jakob disease (CJD). In 13 of the 14, clinical onset occurred during 1994 or 1995; BSE surfaced in 1988 * a likely incubation interval for the human infection (see related article on this page).
But the transmission of BSE to CJD, though likely, is still speculative.
Twelve of the 14 have already died of this invariably fatal infection; the other two have not long to live.
But BSE has driven thousands, if not millions, of other British subjects mad with worry. They fear that those 14 victims acquired their death sentences by transmission from the infected cattle, and that they are merely the tip of an enormous CJD epidemic to come.
At a news conference in London on Wednesday, Jan. 15, medical statistician Simon Cousens, of the London School of Hygiene and Tropical Medicine, presented data to the press that addressed these public anxieties.
Cousens' appearance before the media coincided with publication of those data in the latest issue of Nature, dated the same day, Jan. 15, 1996. His paper's title: "Predicting the CJD epidemic in humans."
It's based on the probable but unproven premise that the new clinical variant of CJD arises from exposure to the infectious prion agent that causes BSE.
"So few cases, only 14, over a reasonably long period of extended time," Cousens told the gathered journalists, "helped us to rule out the more catastrophic scenarios that were causing such public concern."
After summarizing the "dense" statistical-mathematical epidemiological estimates in his Nature article, Cousens addressed the question: "Having observed at this point in time a very small number of cases, can we say that there will not be a lot of cases in the future?
"The clear answer coming out of our statistical models," he answered, "is no, we can't say now."
Explaining this bottomless bottom line, Cousens pointed out: "There's an enormous range of possibilities, from hundreds to thousands of new cases, compatible with our observations so far."
Those observations extrapolate from the 14 individuals stricken to date, backward in time to the emergence of 'mad cow' disease in 1988, and forward in time to an array of alternative predictions, based on a spectrum of highly uncertain but plausible assumptions.
"If we were to continue observing a small number of cases each year," Cousens told BioWorld Today, "and there were evidence of a sharp increase in CJD incidence, we might predict 25 to 50 to 100 cases over several years ahead.
"On the other hand," he added, "if we see a sharp acceleration over the next few years, we're looking at the possibility of thousands and thousands of cases."
Between those two extremes, Cousens painted "a number of scenarios, where we see a less dramatic year-upon-year increase. In one case, it's about 1,600."
"These alternatives," he continued, "illustrate that even in several years' time, the message of the Nature paper, in response to that question, is: No, we can't rule out the possibility of a large epidemic."
He observed: "At the present time there is enormous uncertainty, which makes people very uncomfortable. But I'm afraid it's what the message is." *