Epo may be out in the open but now a new doping controversy is brewing. Pfc — Artificial blood — can carry 50 times more oxygen than real blood and It's undetectable. but for cyclists, it may be lethal.

story: ian austen.

The post-EPO era in cycling began late in spring last year, on a back road in the Swiss canton of Ticino, when Mauro Gianetti slipped out of the back of the bunch in the Tour of Romandie and waved for the race ambulance. Gianetti was to spend the next fortnight fighting for his life in intensive care in hospital in Lausanne.

This was the event that brought perfluoro-carbon (PFC) to the notice of the cycling authorities. Gianetti is currently suing a Swiss doctor who treated him in the Lausanne hospital to which he was taken, over allegations that the drug was responsible for his illness. Gianetti himself blames a combination of stomach trouble and dehydration.

Whatever the truth of those particular allegations, the fact is that only a few days later, at the start of the Giro d'Italia in Nice, the Union Cycliste Internationale issued a letter to all the teams taking part warning them of the dangers of using PFC.

The Gianetti controversy was largely forgotten for the next couple of months, only to resurface in the Tour de France. It was then that the French press began talking to the men who had treated the Swiss rider – and they remained adamant, despite Gianetti's denials, that his illness was due to the use of the new drug.

Others maintained that Johan Museeuw's illness after his crash in Paris-Roubaix last year was due to use of PFC. The 1996 world champion was adamant in his denial.

So no-one knows for sure whether PFC is being used by professional cyclists. There was, though, the same kind of uncertainty with EPO until last July: that episode proved once again that in the fight against drugs in sport, the cheats are always one step ahead of the authorities.

Just as the 1998 Tour de France doping scandal is finally forcing the development of effective measures against EPO and other cloned hormones, PFC is just one of a whole new range of products that may soon make EPO and its ilk passé.

The new drugs, known as 'artificial blood', offer those seeking an illicit edge all the performance enhancement of EPO without the lag time, and at lower cost. Unfortunately, the potential for health problems among top athletes is equally dramatic.

Human experiments for legitimate uses of one blood substitute, made by the American drug giant Baxter, resulted in an unexpected number of unexplained deaths – despite careful supervision and supporting research.

The recent scares over blood tainted by HIV, CJD and other potentially devastating diseases have sparked a rush by drug companies to create a new form of the most vital of bodily fluids.

Without exception, all the substitutes so far in production perform the one task that is vital for performance enhancement – they deliver oxygen quickly to oxygen-starved muscles. None of them, though, are ambitious or inventive enough to attempt to recreate all the other vital functions of blood, including disease suppression and clotting.

Whatever the performance benefits, squirting fake blood into the veins of cyclists whose bodies are already under enormous stress would seem to be irresponsible in the extreme.

To date, only one blood substitute – PFC, the substance Gianetti is accused of using – has attracted any substantial notice in the cycling world. Gianetti spent the best part of a month in hospital after his initial scare, and only came back to racing late in the season. PFC is also the only fake blood that has so far received full approval for use on humans. Even so Dr Laurent Rivier, head of the Institute of Legal Medicine at the University of Lausanne, Switzerland's IOC-approved anti-doping lab, thinks PFC might be a waste of time and money for its illicit users. "The riders will not tell us why they use it," says Dr Rivier. "I am very doubtful of its value."

At first glance, PFC looks like a doper's dream. To start with, it can carry 50 times more oxygen than real blood in some circumstances. Mind-bogglingly, that means you can fill a beaker with oxygenated PFC, drop a mouse in it, and the mouse will stay alive even after its lungs have filled with the liquid.

Detection of PFC using current anti-doping controls is also impossible. It's expelled from the body by breathing rather than being passed in urine, and its use has no impact on red blood cell or haematocrit levels – the current, unsatisfactory, indicator used by the UCI to monitor EPO use.

But there is, of course, a catch. PFC is a chemical cousin of Teflon, that slippery substance used in non-stick frying pans and chain lubricants. So while that swimming mouse may not drown while paddling in the beaker, it might not come out in the best of health.

PFC has been transformed into synthetic blood to try to get around that problem, through some chemical manipulations and a degree of control over the level of exposure that users are subject to.

Generally, PFC can only be safely used for a couple of hours in relatively small quantities, usually between 500ml and one litre. Yet that strips away much of its dramatic oxygen-carrying power.

Patients using Fluosol, a brand of PFC approved for use during heart surgery, must also breath pure oxygen during surgery. Most doctors found that process so awkward that the product was pulled from the market because of poor sales in 1994.

Extra oxygen is also likely to be required for users of Oxycyte, an improved version of PFC that's likely to undergo human tests this year. Obviously, riders are unlikely to strap on cylinders of oxygen before heading out to sign on. And that's why Dr Rivier is sceptical about the value of PFC for abuse in sport. Either its abusers are taking dangerous doses or they're wasting their money.

"If this is something that is being used," says Dr Rivier, "it is still very rare." Nevertheless, Dr Rivier's lab, as well as the IOC's approved facility in Montreal, are developing methods to detect PFC.

Looking for a pure synthetic like PFC should be far easier than detecting cloned EPO, which is largely indistinguishable from that produced naturally by the body. By contrast, says Dr Rivier, "the body does not produce PFC, so far as we know."

Instead, his chief frustration is the agreement between riders and the UCI, preventing his lab from testing riders' blood for anything other than haematocrit levels and other EPO-related indicators – the infamous 50 per cent test. "We need to get access," says Dr Rivier pointedly. That may be coming. But it might, in any case, ultimately be irrelevant. The other major approach to artificial blood, which is nearing the market, may make PFC obsolete even before it catches on.

At least four companies are chasing a new plan that's compellingly simple: purified haemoglobin.

Haemoglobin molecules within red blood cells deliver oxygen throughout the body. As long ago as the early '80s, a US military project managed to remove pure haemoglobin from the red cells. But only now has a way of safely reintroducing modified haemoglobin into the bloodstream been devised.

The new development has given rise to several new products; three are currently undergoing tests on humans. They are packed into the same kind of intravenous bags now used for regular blood, and are administered in much the same way.

Best of all for both legitimate and illegitimate users, they are the height of convenience. A rider with a low haematocrit count could raise it instantly with an infusion – like adding oil to a car engine.

By comparison, EPO abuse is an extremely long and complicated process. Because the hormone only stimulates natural red cell production, it must be injected up to two weeks before competition. And, if deadly blood thickening is to be avoided, dosages have to be calculated using a formula based on body weight and a rider's programme.

As with any new product that has doping-abuse potential, the big question on modified haemoglobin is whether top athletes are actually using it. Privately, a top executive at one of the modified haematocrit makers acknowledges that there's great potential for abuse of his product by athletes. But Dr Rivier simply doesn't know what, if anything, is happening.

The only modified haematocrit approved for sale right now is made by BioPure in Cambridge, Massachusetts, and intended for animals – although, in theory, it could be used by illegally by humans. But even using the human product illicitly is something that should require serious thought – for safety reasons alone, if not for moral ones. At one time it looked as if Baxter's product, HemAssist, would be available for sale for human use by now. The company had, in fact, already built a factory in Switzerland to manufacture it.

Human trials on elective surgery patients went without a hitch. But when the company tried the product in hospital emergency rooms on trauma patients, such as cyclists who had been knocked down by motorists, they started to run into problems. Three patients using the product died to every control patient who didn't receive it. Baxter quickly junked HemAssist, restarted their programme by buying another company working on a similar product, and are now figuring out what to do with that $110 million factory.

The source of the trouble is still unclear. But the leading theory is that the products aren't suitable for patients in shock and under severe stress. Professional bike riders aren't in shock, but no one would argue that their bodies are in anything approaching a normal state during the middle of, say, a mountain stage in the Tour de France.

Whatever the potential danger, though, it still seems likely that the modified haemoglobin products' ability to boost the blood oxygen with little fuss and at relatively low cost will attract some illicit users. But, as yet, it doesn't appear that any IOC lab is attempting to develop a test. Of course, this is another doping abuse that only blood testing will establish.

But beyond that, the big problem is simply money. Despite all the post-Tour fuss, work in Canada on a test for EPO – for which Dr Rivier's lab conducted field tests of riders – remains stalled because funding is scarce for further large-scale tests on athletes. And Dr Rivier is already struggling to fund his other projects. "We have enough difficulties already with the PFCs," he says, and is consequently reluctant to take anything else on.

Dr Christiane Ayotte, head of the Institut de la Récherche Scientifique-Santé – an IOC-approved anti-doping lab near Montreal – believes athletes using PFC are either wasting their money or seriously risking their health.

"It's toxic," she says. "We are really surprised at some substances we find in athletes. It's just because it's an oxygen-carrying substance that some guru or trainer has thought about injecting it."

While its illicit use has not been studied, Dr Ayotte says papers on its legitimate use suggest that non-toxic doses of PFC offer little in the way of performance enhancement: in other words, it's of no use to athletes or cyclists unless they are prepared to use health-endangering quantities.

Dr Ayotte's lab is currently developing a testing programme for PFC, although it has encountered some bureaucratic delay in obtaining samples. Not wishing to scaremonger, she does admit that, at the moment no-one really has any idea about the extent of its illicit use. "It's difficult to know if it's used or not. There may be only one case."

She is certainly worried, though, about the potential for abuse offered by the modified haemoglobin drugs: "I may be getting cynical but this seems to be the way sport is going." Her fear is of a possible series of deaths from blood clots in otherwise healthy athletes.

As usual, the acid test of whether cycling and other sports are serious about controlling the escalation of doping will come down to putting hard cash behind the hand-wringing and pious promises.

Artificial blood is just one example of a medicine that has been abused by sportsmen to enhance performance – with potentially disastrous side-effects. But there are many others…

DHEA
Used medically to slow down the effects of ageing.
Used by sportsmen to enhance muscular development.
Side-effects: the same as other anabolic steroids – acne, migraines, nosebleeds, tendinitis, prostate cancer and, in the long term, death.
Creatine
Used medically to treat cardiac problems. Not banned, but the topic of intense debate.
In sportsmen, increases muscle strength, often in conjunction with anabolic steroids.
Side-effects can include liver and kidney problems.
Anticoagulants
Used medically to prevent blood clotting.
Used by sportsmen in conjunction with EPO to thin the blood. Not banned, because on their own they do not enhance performance.

Bronchiodilators

Used widely to treat and prevent asthma. Banned if found in large amounts.

Used by sportsmen as a stimulant because the main ingredient, salbutamol, is similar to adrenalin, and to increase respiratory powers.

Side-effects include headaches and digestive problems if taken to excess.
Testosterone
Administered medically to men whose testicles do not produce enough of the hormone.

Used by sportsmen as an anabolic steroid, to increase muscular mass. Weightlifters have been rumoured to take up to 250 times the normal medical dose.

Side-effects include acne and low sperm count.
Trinitrin
Medical use is as a blood vessel dilator and heart stimulant to treat and prevent angina.
Sportsmen apparently use it for explosive events as it reduces warm-up time.
Side-effects include headaches, nausea and high blood pressure.

For an athlete, it's a naturally occurring hormone with an undeniably alluring promise: more muscle, less fat. In short, it's a substitute for steroids that's completely undetectable with any current anti-doping test. But Insulin Growth Factor 1, or IGF-1, has so far attracted little of the scrutiny heaped upon EPO since the Tour scandal.

Despite IGF-1's low profile, no-one doubts that it's being used in sport. Last autumn, the doctor for the Australian national track team acknowledged that his riders were receiving a milk product containing the banned substance – a situation that the team insists doesn't violate the IOC ban on the hormone. And there's no coyness about IGF-1 in the bodybuilding world – it's openly touted in magazines and on the Internet as the next wonderdrug and a 'natural' alternative to steroids.

IGF-1 is a hormonal cousin of the better-known Human Growth Hormone. In fact, in natural circumstances HGH stimulates its production within the body. In the medical world, cloned IGF-1 is used, or being studied, for treating dwarfism in children, some forms of diabetes, wasting in AIDS patients and physical degeneration of people with non-functioning pituitary glands.

Like EPO, IGF-1 evades all current anti-doping measures because it is a clone of a naturally occurring human hormone and its levels vary wildly even over the course of a single day.

Legality aside, does it fulfil its promise for athletes interested in a needle-induced performance boost? Despite all the hype in the bodybuilding world, no-one really knows for sure. Dr Christiane Ayotte, head of the IOC-approved anti-doping lab in Canada, says the lack of recognised research about IGF-1's effects on athletes could mean that, as with many drugs, its power may be grossly exaggerated.

"Sure, you can probably find some paper published in Bulgaria. But is that a reason to inject it in athletes?" What's more, much of what is being sold as IGF-1 in the United States does not appear to be a clone of the human hormone. Exactly what those products are is a mystery, as US law excludes so-called dietary supplements from any kind of government testing or regulatory scrutiny.

But even if it's pure, IGF-1 has some frightening potential problems. It can cause brain swelling, coronary artery disease and enlarged hearts, and induce diabetic comas. There are unproven fears that prolonged use could lead to cancers of the soft body tissues. The real stuff is also hugely expensive, even without black market mark-ups. Medical patients in the United States can spend up to $20,000 a year on the drug.

Don't despair if you're short of cash and not interested in an early death. There is a cheap and risk-free way to boost your IGF-1 levels: training.