COULD a dose of antimatter cure cancer? Outlandish as it seems, a small Californian company has managed to persuade sceptical physicists at CERN, Europe’s leading particle physics lab, to put it to the test. Most of the schemes dreamed up to put antimatter to work don’t even make it though CERN’s front gate, so what’s special about this one?
“We are trying very hard to distance ourselves from some of the less feasible ideas about antimatter that have been bartered about,” says Carl Maggiore, lead scientist at PBar Medical in Newport Beach, California. Two years ago, the “business angels” who invested in PBar were casting around for a cutting-edge project in which to sink their money. PBar’s researchers had stumbled across a paper on antiprotons from the mid-1980s by Greek physicist Theodore Kalogeropoulos, who had suggested using a beam of this antimatter as a new form of radiotherapy to treat cancer. Though the one experiment that had been carried out did not even use living cells, the angels were sufficiently impressed to fund the research.
Radiotherapy works by blasting tumours with a beam of high-energy particles or radiation. The energy pumped into the tumour cells damages their DNA, causing faults to accumulate that make them sicken and die. The tricky part is killing off the tumour cells without wreaking too much havoc in healthy tissues nearby.
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X-rays have traditionally been used for this task, as they are cheap and easy to generate. But while X-rays can be focused into a tight beam, they dump their energy indiscriminately along its path, in front of and behind the target tumour, as well as within it (see Graph). The treatment only works because the cancer cells are less efficient than healthy cells at repairing damage to their DNA. But healthy cells still die in large numbers, leading to serious side effects that range from skin irritation to exhaustion.
Recently, 20 centres worldwide have started to provide radiotherapy that uses beams of protons instead of X-rays. Protons can be targeted far more precisely than X-rays because they do not scatter as much from tissue and bone. Also, the distance protons penetrate depends on the energy of the beam. This is because a proton passing through tissue gives up some of its energy by ionising nearby atoms, causing it to slow down. The ionisation increases as the particle loses speed, so the energy delivered by a proton peaks sharply where the particle comes to rest. Simply tune the energy of a proton beam until the peak lies within the tumour and you can hit the cancerous cells much harder than their healthy neighbours.
Maggiore’s team reasoned that antiprotons could be even more effective. As an antiproton passes through tissue it should behave just like a proton, but when it comes to a stop it will snatch a proton from a nearby atom, and the pair will annihilate each other in a burst of gamma rays and particles such as pions and muons. If this can be arranged to happen inside the tumour, it will give the cancer cells an extra zap that should help to kill them off (see Diagram).
PBar’s researchers adapted computer simulations used by particle physicists to model how high-energy particles interact in materials. Their results suggest that the gamma rays and pions will pass through the patient’s tissue without having any effect whatsoever. However, around 2 per cent of the mass-energy released as the antiproton-proton pair annihilates is soaked up by the atomic nucleus that sacrificed its proton. It is enough to make the nucleus unstable and decay into heavy fragments made up of protons and neutrons. These nuclear fragments make all the difference: because they are charged and travel so slowly, they dump all their energy into the surrounding cancer cells. Antiprotons, Maggiore’s team calculated, should hit the tumour even harder than protons.
On paper, at least, the prospects for antiproton radiotherapy were looking good, and the company began assembling a team of advisers. Cancer specialists, nuclear physicists and radiobiologists joined the collaboration, and in November 2002 PBar made a formal approach to CERN to plead for antiprotons to test its idea. CERN, which straddles the Swiss-French border near Geneva, is one of only two places in the world that can supply a beam of antiprotons. The other is Fermilab in Batavia, Illinois, but there the antiprotons are too energetic. CERN has a special “antiproton decelerator” which slows down the particles created when a beam of protons collides with the metal iridium. Though the antiprotons are ejected close to the speed of light, the decelerator slows them to around 10 per cent of that, which is about right for radiotherapy.
CERN has to turn off its power-hungry antiproton beam periodically to make sure that the lights keep burning in Geneva. At the end of last year’s season, there were three projects sharing the antiproton beam: two studying antihydrogen, while the third was investigating collisions with helium. PBar asked for only 10 shifts of 8 hours each when the accelerator restarts next month. The other projects agreed they could spare those few antiprotons but the final decision rested with a committee of 12 CERN scientists and two radiotherapists who had been brought in as advisers. Maggiore and his colleagues even made a special trip to CERN. “We talked to people directly to convince them that we are serious scientists, not wild-eyed lunatics…and we are trying to answer a serious scientific question,” he says.
But even at CERN, antimatter is in short supply. In the past 10 years, the centre has spent hundreds of millions of Swiss francs generating antiprotons, yet has produced less than a billionth of a gram of them. The reviewers were not convinced that Maggiore’s proposal justified using this precious resource, and they sent the PBar team away with a list of questions: they wanted proof that the experimental method worked, and data for proton therapy against which the antiproton results could be compared. To help it present its case, PBar then contacted Lloyd Skarsgard, a biophysicist at the British Columbia Cancer Research Centre in Vancouver, Canada. “When I was first asked if I would help them, my answer was no,” recalls Skarsgard. “But we had a long meeting, and by the end of the day I got sucked into it. I was intrigued. No one has ever measured the biological effect of antiprotons.”
To assess how well the experiments would work, Skarsgard adapted a technique he had invented several years ago, in which he simulates human tissue by embedding cells from a Chinese hamster in gelatin and packing it into a long tube. After firing a beam of protons lengthwise down the tube, he carves the gel into millimetre-thick slices, counts the number of cells in each slice, and cultures them to work out how many are still alive. The fraction of cells that die give a measure of the lethality of the beam, which can be plotted against depth in the tissue. This gives a characteristic “death curve” that is similar to the pattern of energy deposition for a proton.
The ratio of the fraction that die in the peak of the death curve to the fraction in the region in front of it is known as the relative biological effectiveness (RBE). X-rays typically have an RBE only a shade greater than 1, while protons have an RBE of 1.2 to 1.5, reflecting the fact that they target the tumour more precisely. Skarsgard estimates that antiprotons will have an RBE somewhere between 1.5 and 2.5 because of the extra zap of energy they give the tumour. But even a small improvement could make a big difference to the side effects suffered by patients. With a larger RBE, fewer healthy cells die for the same dose of radiation to the tumour. “A 20 per cent improvement would be pretty significant,” says Daniel Miller, an expert in proton therapy at the Loma Linda University Medical Center in California. “I would say that would be a breakthrough.”
In January, PBar’s scientists went back to CERN with their new data and a few more experts on their team. Among them was Rolf Landua, who leads one of the antihydrogen experiments at CERN and helped to guide the company through the lab’s application procedure. The team’s know-how finally convinced the reviewers that it was worth giving the experiment the go-ahead. Hans Taureg, scientific secretary of the committee explains: “For the moment, this exploratory experiment will not need a lot of time so one should do it.”
Maggiore and his team start their experiments in June, and over the next few months they will put tubes of gel in the antiproton beam. Skarsgard will take the gel tubes back to Vancouver for analysis and measure the death curve for antiprotons. The first results should be available towards the end of the year. Then the PBar team will have to decide on its next step: “If the first experiment is very promising and it looks like it’s worth pursuing, there are enough obvious follow-up experiments to keep an army of researchers busy for the next 20 years,” says Maggiore.
But even the most positive findings are unlikely to see cancer patients admitted to the echoing experimental halls at CERN. Instead, someone will have to build a dedicated antiproton factory, at a cost of about $200 million. PBar Medical may have convinced CERN’s physicists that its science is serious, but the hardest task could still be ahead of it: finding serious amounts of money.