“AM” thought she was dying. Moments after taking a deep breath through the mask that had been voluntarily placed over her nose and mouth she lifted her arms in panic and clenched her hand into a fist. She was 37 years old and it was the first time in her life she had felt fear.

This came as quite a shock to , now at the California Institute of Technology in Pasadena, who carried out the experiment. That’s because AM has a rare genetic condition called Urbach–Wiethe disease that has, until now, made her fearless due to the destruction of a region of her brain called the amygdala. Her experience challenges the widely held belief that the amygdala is essential for fear.

Feinstein managed to scare AM by exposing her to carbon dioxide levels of 35 per cent via the mask, a protocol that can produce breathlessness, a rapid heartbeat and dizziness lasting about 30 seconds. It usually induces a sense of fear in about 25 per cent of people who try it.

The technique also provoked intense fear in two other volunteers with the genetic disorder. Feinstein had previously subjected one of them to every other scare tactic imaginable – snakes, scary films, haunted houses – but couldn’t frighten her.

Anticipating fear

Interestingly, the amygdala-impaired volunteers still didn’t react in the same way as healthy volunteers. Unlike most people, whose heart and perspiration rates rise immediately prior to a repeat of the carbon dioxide experiment, AM and her cohorts never developed an anticipatory response. They could feel fear, but they couldn’t anticipate it.

Carbon dioxide changes blood acidity, activating acid-activated chemo receptors in the brain. This study hints that internal threats, like carbon dioxide, are processed differently by the brain than external ones, says Feinstein.

“This study shows there are other ways to get fear besides through the amygdala,” says , a molecular biologist at the European Molecular Biology Laboratory in Monterotondo, Italy. He hypothesises that the hypothalamus might be involved, since it can mediate fear response in healthy people.

Journal reference: Nature Neuroscience, DOI: 10.1038/nn.3323

That is the message sports officials are promoting after US cyclist Tyler Hamilton was nailed by a surprise test for a previously untraceable method of blood doping during the Tour of Spain race last week.

Hamilton, who won a gold medal at the Athens Olympics in August, denies any wrongdoing, and his backers are questioning the validity of the new test. But experts contacted by żěè¶ĚĘÓƵ believe the science is watertight.

In endurance sports like cycling, ways of boosting the blood’s oxygen-carrying capacity can enhance performance by 20 per cent or more. The first tactic cheaters adopted was to give themselves blood transfusions, which pack the blood with extra oxygen-carrying red blood cells.

But transfusions carry significant risks, such as contracting bacterial and virus infections and life-threatening immune reactions. So when a natural hormone called erythropoietin (EPO) that boosts red blood cell production was turned into an anaemia drug in the 1980s, a black market for it developed among athletes.

Foreign cells

It was not until four years ago that a test for EPO became available. Since then old-fashioned blood transfusions have been making a comeback, despite the health risks. But now transfusions can be detected too.

The antibody-based test works by detecting foreign cells within an athlete’s blood sample. Every red blood cell from a particular individual has the same set of proteins or antigens on its cell surface.

The A/B/O blood group system involves major antigens that must be cross-matched for transfusion otherwise recipients could suffer serious immune reactions. But it is not essential to match the many minor antigens.

The new test looks for 15 different minor antigens and can detect the presence of just one unit (about 500 millilitres) of transfused blood. “If you find several sets of antigens, it means that you have blood from two different people,” says Ann-Muriel Steff, research manager at the World Anti-Doping Agency (WADA) in Montreal, Canada.

Hamilton’s professional team, Phonak, announced last week that both the cyclist’s A and B test during the Tour of Spain race had been positive, as was his A test from Athens. The cyclist looks likely to keep his gold medal, as the B test from Athens had been incorrectly stored.

Hamilton said last week he was “100 per cent” innocent of the charges against him. And Phonak has since announced it will set up a panel of independent scientists to examine the validity of the test.

Second set

But its developer, Michael Ashenden, a sport scientist at Science and Industry Against Blood Doping in Australia, is adamant: “The test doesn’t make mistakes. You either have someone else’s blood in your circulation or not.”

Only three other situations could account for a second set of antigens, all of which could easily be checked for.

The first is a recent bone marrow or stem cell transplant. The second could happen if the athlete had a non-identical twin, as sometimes twins exchange cells in the womb. The third scenario would occur if two embryos fused together early in development, creating a single chimeric person (żěè¶ĚĘÓƵ print edition, 15 November).

What the new test cannot pick up, however, is someone who has given themselves a transfusion of their own blood, donated beforehand and stored until just before a race.

Ashenden is now trying to develop ways of detecting the dip this would cause in a person’s natural EPO levels. “We won’t be announcing when the tests will be used, and we’re saving samples so we can go back and test them,” he says.

Some athletes are also thought to be using artificial forms of haemoglobin which are being tested as potential blood substitutes in clinical trials. WADA says it already has tests that can detect these, although the agency has not released details.