To: BSE-L@uni-karlsruhe.deThe Lancet Neurology
Volume 2, Number 1 01 January 2003
vCJD complacency—cause for alarm?
Maintaining a reasonable balance between alarmism and complacency is
important in many aspects of science and medicine. But perhaps nowhere
is this balance more important than for variant Creutzfeldt-Jakob
disease (vCJD), a fatal illness for which there is no known cure and
which some believe may yet claim thousands of lives. According to a
story in the Sunday Times newspaper (Dec 1, 2002), Nobel laureate
Stanley Prusiner believes that “every Briton should be tested [for CJD]
so that if they are developing the disease it can be spotted before
symptoms appear”. By contrast, 2 days later The Daily Telegraph ran a
story entitled “Cases of vCJD in decline”, which points out that there
have been 15 cases in the UK so far in 2002, compared with 20 last year
and 28 in 2000.
The main problem, of course, is that no one knows the true extent of
infection. This issue was thrown further into confusion on Nov 28 with
the publication of research done in mice suggesting that some cases of
sporadic CJD might also be caused by eating BSE-infected meat (EMBO J
2002; 21: 6358–66). In support of this hypothesis, there has been a
steady increase in the incidence of sporadic CJD in the UK over the past
decade; this trend has been mirrored in Switzerland, which had the most
cases of BSE of any continental European country, where incidence of
sporadic CJD increased two-fold in 2001 (Lancet 2002; 360: 139–141).
Both increases could be attributed to the transmission of a prion
zoonosis, though better detection procedures and iatrogenic transmission
cannot be ruled out. Which explanation is correct is still a matter for
debate.
The one thing that everyone agrees on, however, is that adequate
health-service planning will be impossible until the precise extent of
human infection becomes known. Prusiner's group recently claimed to have
developed a highly sensitive, automated test for detecting prions that
could be used for high-throughput testing of brain samples from cattle
with BSE (Nat Biotech 2002; 20: 1147–50). Clearly, brain biopsies are
not practical for widespread human diagnosis; what is really needed is a
reliable, preferably blood-based, test. But even if such a test was
available, widespread screening would probably be rejected by the UK
government for logistical, financial, and ethical reasons. Knowledge of
infection would undoubtedly cause immense distress among those found to
be incubating a disease that could take up to 40 years to develop. Would
you want to know you might develop an untreatable fatal condition?
Although there are many drugs currently under investigation, the small
numbers of patients with CJD will make it very difficult to test any of
these compounds in a systematic and statistically significant way. So
far, therapeutic compounds have been tested in only a few individuals.
In a well publicised case, Rachel Forber, a British patient with vCJD,
flew to Prusiner's Californian clinic in August 2001 to receive
quinacrine and chlorpromazine, which had been shown to be effective in
vitro. Although she was reported to have improved after treatment, she
died later that year; it has since been shown that quinacrine does not
prolong survival in a murine model of CJD. More recently, the families
of two young people with vCJD went to the UK High Court to persuade
their doctors to try an experimental treatment—pentosan
polysulphate—that would be injected directly into the brains of their
children; as The Lancet Neurology went to press, a decision had not been
made.
When vCJD first hit the headlines in 1996 there was a real cause for
alarm. The patients were young, previously healthy people, who developed
a fatal, rapid-onset dementia for which there was no known cure.
Thousands of cattle had developed BSE and it seemed possible that a
similar epidemic could hit the human population since millions had
consumed infected beef. Now, 6 years later, only 119 people have died of
vCJD in the UK and some scientists believe that a human epidemic will
never happen. Previously, alarmist news could have created panic. Now,
complacency is the real enemy. If vCJD does have a long incubation
period, as some people fear, thousands may yet develop the disease. In
this scenario, time is in our favour—we must ensure that we use it wisely.
The Lancet Neurology
http://neurology.thelancet.com/journal/vol2/iss1/full/lneu.2.1.the_leading_edge.23558.1
Volume 360, Number 9350 21 December 2002
Lifeline
Prion protein scrapie
lifeline
I started my career in spongiform encephalopathies with sheep. Rather a
desk job, scrapie. My breakthrough came in crashing the species barrier
into UK cattle and the exhilarating epidemic of bovine spongiform
encephalopathy (BSE). Better still was variant Creutzfeldt-Jakob disease
(vCJD)--a career high.
Which event has had most effect on your work, and why? The day in May,
1990 (6 years before the first cases of vCJD were reported in The
Lancet), when the UK agriculture minister, John Selwyn Gummer, was
photographed eating a hamburger with his young daughter to assure the
public of the "safety" of UK beef.
What alternative therapies have you tried? Did they work? None, but I've
had several tried on me; they did not work.
What is your favourite book, and why? No question: the 16 volumes of the
official UK BSE report; a laugh a page.
What is your greatest fear? Cure, of course, not that there's any
immediate prospect; pentosan polysulphate is hopeless.
Do you believe in capital punishment? As I'm invariably fatal when fully
underway, it'd be hypocritical to say "No".
Do you apply moral judgments in your work? No, I'm strictly an opportunist.
If you had not entered your current profession, what would you have
liked to do? Be something a little more flamboyant--a filovirus, perhaps.
Describe your ethical outlook. Predominantly deontological.
What is the least enjoyable job you've ever had? I did a research
fellowship in Edinburgh, UK, trying to deform prions of 171 Arg
homozygous Cheviot sheep; waste of time.
Do you believe in monogamy? Any sort of -gamy for a prion is a problem,
but as I bend straight prions so they can aggregate, I suppose that is
polygamy.
Do you believe there is an afterlife? As long as there are brains, there
will be prions.
http://www.thelancet.com/journal/journal.isa
TSS
