Reactor sideline sheds light on possible cancer cure

March 20, 1998

Tony Tysome and Martin Ince (bottom) report on the work of the 'laboratory of Europe'

ASKED to justify the cash that goes into the Joint Research Centre, its managers would probably point to the Boron Neutron Capture Therapy facility that has just opened at its centre at Petten in the Netherlands. It involves international collaboration from many EU countries: it makes use of advanced technology, including a nuclear reactor, that researchers are unlikely to have available in their own institution: and it cures cancer, or may do so in the near future.

The Petten site is one of two, along with Ispra in Italy, making up the JRC's Institute for Advanced Materials. The high-flux beam of neutrons which emerges from its reactor was never meant to be turned on humans. And work on atomic structures and materials science still uses up most of its time. But it turns out to be ideal for a new technique in which medicine, biochemistry and atomic physics join forces.

While the JRC costs more than Ecu 1,140 million a year, the BNCT facility is a highly visible operation whose costs are barely in the millions. The objective is to provide a more effective and kinder alternative to the massive doses of radiotherapy now used to attack extremely malignant brain cancers called glioblastoma, which affect 15,000 people a year in the European Union. They almost all die.

The Petten centre has just treated its first few patients, although the scientists stress that they do not yet have a cure for the disease and the people treated in the experiments so far will die. Wolfgang Sauerwein, director of the BNCT medical programme, stresses: "We do not want to give the impression that we have found a cure for these cancers yet."

The new treatment starts with a new drug called BSH, which contains the light metal boron. Boron does not normally leave the bloodstream. but it concentrates in brain tumours because of the thinning of blood vessel walls where the tumours occur. When neutrons such as those produced at the Petten reactor hit the nucleus of a boron atom, it decomposes and produces a heavy alpha particle which can kill cancerous cells. Because the boron does not get into healthy parts of the body there are none of the grim side-effects of radiotherapy.

The European Commissioner for research, Edith Cresson, said in Petten recently that: "Although health is a national rather than European responsibility, this technique requires big financial and scientific resources so we decided that the Commission should become involved." Researchers from 14 countries, as well as the JRC's staff, are involved, especially German, French and Dutch scientists and doctors, with clinical responsibility based at Dr Sauerwein's department at the University of Essen. The project, which is bound to figure in many case-studies of European collaboration, is managed overall at the University of Bremen and also involves the Amsterdam Free University hospital, the source of many of the patients.

The Petten reactor is already Europe's principal producer of radioisotopes for medical use, which are made commercially by a company, Mallinckrodt Medical. (The UK left this business with the closure of reactors at Harwell in the 1980s.) The hope is that BNCT will turn into another element in a "medicine valley" which could create jobs to make up for some of the many lost in north Holland in recent years.

Detlef Gabel from Bremen says that the BNCT development at Petten began in 1985 as a "concerted action" across the EU, including participants in Edinburgh, Glasgow and London. In 1985 the reactor was shut for rebuilding, and a new reactor vessel was installed to allow new experiments such as BNCT to be tried. "We needed to know about the drugs as well as the neutron therapy. Previous attempts to use BNCT had failed because the drugs used damaged healthy tissue. Our research suggests that we are now solving this problem," says Gabel.

According to Sauerwein, the international ramifications of the project have created a legal structure "as complex as a diagram of the human body," not least because of the need to satisfy medical ethics requirements of different EU countries. "The time we have spent on these issues has damaged the lead Europe had in this method, and we now need more clinical trials to take things forward."

Ray Moss, leader of the high flux reactor group at Petten, says: "We need to have more trials to build confidence in the technique, which is distrusted by people in the radiotherapy community. At the moment there are two places in the US and a few in Japan which are also treating patients. The details differ but they all rely on the same principle - to hit DNA in tumour cells and stop them dividing and reproducing." He says that the Petten neutron beam has a good parallel shape, so that it can be used more precisely than those from other reactors, which ought to make it easier to treat tumours deep in the brain.

Hugh Richardson, deputy director of the JRC, adds that Petten is not the JRC's only outpost of high-technology medicine. At Karlsruhe in Germany, the JRC's centre for work on transuranic elements is developing the use of the metal bismuth 213, which decomposes to produce alpha particles. It can be attached to an antibody which seeks out target areas in the bone marrow, liver and spleen for treatment. Like the BNCT work, this involves biology and medicine as well as physics, and there are partners in medical institutions in Germany, France and the United States.

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