Next month should see the conclusion of one of the most bizarre and intriguing legal challenges ever mounted by an athlete to a doping ban. Weeks after he won gold in the time trial at last summer's Athens Olympics, US cyclist Tyler Hamilton failed a new blood test. Hamilton has fought the findings of the test ever since. His appeal against the two-year ban imposed by the United States anti-doping agency is due to be heard in July.
Blood-doping has long been popular in extreme endurance sports. If an athlete can boost the number of red blood cells, this improves the efficiency of the oxygen transport system. In the 1990s, performance hikes of 10-20% were made possible by a drug originally developed for kidney dialysis patients, erythropoietin (EPO), which stimulates the bone marrow to produce more red cells.
By 2000, a test for EPO became available, seeming to close the door on this type of doping. It remained possible to have a transfusion either of an athlete's own stored blood or someone else's. The latter is what Hamilton is presumed to have done, since he fell foul of the new test designed to detect mixed blood.
Protestations of innocence by athletes caught cheating are common, but rarely is the scientific validity of a test challenged. Yet this is what Hamilton has set about, mounting a legal challenge to the doping agency which has already cost several hundred thousand dollars.
Hamilton lost the first round at an arbitration court and received a two-year ban (which would, at the age of 34, effectively end his career). But he was encouraged by the fact that the three-person panel was split. The dissenting member, a former wrestler named Christopher Campbell, issued a strongly-worded critique of the test.
Hamilton's key argument, highlighted by Campbell's statement, is that no rate of false positives has been determined for the new test.
"I think it's very unlikely they would be using a test without a known false positive rate," says Richard Budgett, chief medical officer of the British Olympic Association. Yet this is exactly what Hamilton's team says occurred.
But this raises the question of how, if not through transfusion, could someone have mixed blood populations?
There are other possible physiological causes, but two can be ruled out immediately for an elite athlete in peak condition: disease (some cancers can produce mixed blood populations) and bone marrow transplantation. That would leave two theoretical options: intra-uterine twin transfusion, and human chimerism.
Here we enter a twilight zone of biological oddity. The first theory relies on the notion of the "vanishing twin" syndrome - a twin pregnancy where one embryo fails to develop and is ultimately absorbed into the other, but leaves a phantom of its DNA in its surviving twin. It is impossible, however, to discover how often this results in the "microchimerism" of an adult still showing trace blood cells with a vanished twin's DNA.
The alternative proposal - that a person might be a human chimera, in effect naturally producing more than one person's blood groups - is essentially the same theory but without the long-lost sibling. According to a recently published paper, this is common in women who have had children.
Hamilton, of course, has never been pregnant, and chimerism is extremely rare. According to one source, only 45 cases have been recorded. This may be because no one has gone looking for it, although a 1996 Danish study found blood chimerism in 8% of fraternal twins (and 21% of fraternal triplets). According to the New York Times, Ann Reed, a research director at the Mayo Clinic in the US, has found that 50-70% of people exhibit chimerism, or "genetic mosaicism".
In the absence of definitive data, the chimerism hypothesis was not offered as part of Hamilton's defence. But its mere possibility did open a chink in the prosecution case, the theoretical chance that something other than a transfusion could be to blame. Blood chimerism could give a false positive result in a test devised to detect someone else's cells.
When establishing a new scientific test, two protocols are regarded as axiomatic - submission to peer review and determination of the rate of false positives. Validation of the test that snared Hamilton is central to his case.
"Very few tests are 100% sensitive and specific," says Roger Palfreeman, the doctor for the British cycling team. "In any validation study, you would mention and work out the rates for true and false positives and negatives. Ideally, to obtain a true value, it should be done on a large enough population. A small sample size will give only an estimate of what would occur in a population."
"Most of these tests are extremely reliable," says Budgett. "There are quite a few tests in the pipeline - there's one for human growth hormone, for instance - but one reason why they are delayed is so that it can be established that you don't get false positives or false positives in different populations."
By coincidence, Hamilton too notes (on his website) that the test for human growth hormone has been delayed precisely because of the difficulties of validation.
So was the blood test sufficiently trialled? Asked whether it may have been rushed to market prematurely, as Hamilton implies, one expert commentator who did not wish to be identified says: "Possibly it was hurried through in time for Athens."
Budgett remains sanguine. "People have long arguments about whether the standard of proof in these tests should be 'beyond reasonable doubt' or 'on the balance of probability'. The consensus is that it should lie somewhere between."
Hamilton's challenge may have revealed an element of reasonable doubt, but will he succeed in tipping the balance of probability? If he does, then the entire anti-doping establishment will be forced to admit that it gambled its credibility on a bad bet.