As British blood donations are banned by anxious countries, a team believes it may have found a simple test for vCJD. Emma Baines reports
Last year, when the European authorities were advised by scientists to ban British blood donors throughout the European Union, they refused on the not very scientific grounds that blood is "a national issue".
It was to have been the latest in a string of international bans on British blood put in place to guard against the possibility of spreading variant Creutzfeld-Jakob disease through blood transfusion.
The United States, Japan, Canada, New Zealand, Australia and Hong Kong were already refusing donors who had spent a total of six months in the United Kingdom between 1980 and 1996. Since then, France, Belgium, Austria, Switzerland and Spain have independently decided to ban British blood donors.
The argument in favour of banning British blood is that anyone resident in the UK during the past 20 years is more likely to have eaten beef infected with BSE, and therefore more at risk of developing the human form of mad cow disease. Some 102 of the 105 reported cases of vCJD have been in the UK. The others, two in France and one in Ireland, were people who had lived in the UK.
There is no known case of CJD being passed on through blood transfusion. But governments do not want to risk the kind of outcry that arose in France several years ago when ministers were accused of causing the deaths of 300 patients who had received blood contaminated with HIV.
The UK must tackle the problem another way because, though it buys plasma worth £25 million a year from the US, it cannot import all the blood the country requires. The National Blood Service treats whole blood with a process that removes 95 per cent of the white blood cells, believed to be the most likely source of vCJD infection.
These precautions are costly, and there is no way of knowing whether they are working without a simple and reliable test for vCJD. Currently, the vCJD agent can be reliably detected only in a postmortem examination of brain tissue.
Universities, research institutes and pharmaceuticals companies all over the world are racing to develop a simple test that can be performed on live humans. But according to Liz Love of the National Blood Service, the diagnostic tests in development have "some way to go before they can be adapted for mass screening of apparently healthy humans".
Tests have to be extremely sensitive because, in theory, a single abnormal protein molecule (prion) could pass on the infection.
In July, Serono Biotech, a pharmaceutical research institute based in Geneva, announced that it could soon have a suitable blood test on the market. The previous month Serono researchers, led by Claudio Soto, had published a paper in Nature , in which they described a method for speeding up prion replication.
Infectious prions multiply by slowly converting normal healthy protein molecules into new prions. In an infected patient, this goes on for years. Soto's team found that it could compress the process into a few hours by blasting the sample with ultrasound.
Soto believes that this method would make tests for BSE and vCJD several hundred thousand times more sensitive.
"Even if it is no more than a single molecule, theoretically we should be able to make it grow," Soto said.
The company is confident that it can produce a blood test for vCJD within 12 months. Soto himself doubts that the test will be ready so soon. It will have to undergo extensive trials to make sure that it is as accurate as possible before it is released onto the market, because anyone receiving a false positive result could spend years in suspense, waiting for the onset of a fatal, incurable disease. For the same reason, Soto foresees ethical problems in using human subjects in the trials. All this could turn into "a very lengthy process", he said.
Even if a test were developed, the case for routine testing of blood remains to be established. It may turn out that the infectious prions that cause vCJD might not be present in human blood.
Classic CJD is considered unlikely to be transmitted through blood transfusion since only the tissues of the central nervous system are infectious. The same is true of BSE in cattle and scrapie in sheep.
However, there is good reason to believe that vCJD is not restricted in the same way. Scientists have observed before that when a naturally occurring transmissible spongiform encephalopathy (TSE) moves to a new species, it can change its pattern of infection. Infectious prions have been found in the tonsils and spleen of several cases of vCJD indicating that, in humans, the disease is no longer confined to nervous tissue, but has infiltrated the lymphatic system. It is because of this that fears were first raised over the infectivity of blood, particularly white blood cells.
Because there is so little data from humans with the disease, all the models of blood infectivity that scientists are using to develop blood tests for vCJD are based on observations of animals infected with BSE, scrapie or another type of TSE. But since TSEs can change their properties every time they cross a species barrier, it is difficult to know whether the path the disease takes in these cases is the same as the path takes in people.
Most of the animal studies that have found that blood can transmit TSEs are not good models for blood transfusion between people. Usually they involve taking blood from an infected hamster or mouse and injecting it into the brain of a healthy animal. However, in September 2000 The Lancet published evidence that BSE could be passed on by whole blood transfusion between sheep.
Chris Bostock, director of the Institute for Animal Health in Newbury, led the team that carried out the research: "Sheep are a better model for humans than other animals. They have similar volumes of blood and the disease follows a similar pathogenesis in sheep and humans. That is, while in cattle the abnormal prions that are the infectious agent for BSE are found only in the central nervous system, in both sheep and humans they are also found in some parts of the immune system."
The paper in The Lancet reported that one sheep out of 19 that had received blood from an animal incubating BSE had come down with the disease. The study is still under way, but no more sheep have contracted BSE so far.
Even so, the implications for human blood transfusion are grim. As Bostock points out: "If none of the other sheep go down with BSE, and sheep are a good model for humans, then there is a 5 per cent probability of infection with blood taken from someone who is incubating vCJD."
Anxious not to be accused of a cover-up, Bostock's team decided to publish its finding, even though its study was nowhere near complete. Its paper may not have affected UK policy, but it was cited by the American Transmissible Spongiform Advisory Committee on June 28 in support of the committee's recommendation that the US extend its blood donor ban to the whole of Europe.