France plays drugs catch-up

Britain's success in exploiting academic research in biotechnology attracted envy across the Channel a few years ago, where the head of French chemical giant Rhone-Poulence decided it was time to make up the lost ground. Nina Hall reports

During the 1980s, scientists and policy-makers in the United Kingdom regularly agonised about the weakness of links between academic research and industrial exploitation, unfavourably comparing the British situation with that elsewhere. Consequently various government agencies dreamt up funding schemes to improve technology transfer, the latest and greatest being the Department of Trade and Industry's Technology Foresight initiative. Today, only those researchers undertaking the bluest of blue-skies research admit to having no connection with the commercial world. Virtually every major chemistry and life sciences university department must receive some kind of funding or equipment from the UK's highly successful chemical and pharmaceutical businesses. Even particle physicists and astronomers find that their sophisticated software is snapped up by IT companies, and that their state-of-the-art detectors eventually turn up in cameras sold in high-street shops.

But just across the Channel, economic forces have not driven the research culture down the same road, at least not in the biosciences. There has been little cooperation between French academic institutes and life-science based companies. The result has been that France has fallen behind in the world biotechnology stakes. While the United States has more than 1,300 biotechnology companies, France has only 20.

It was this widening gap in competitiveness that worried Philippe Desmarescaux, the group president of the French chemical giant Rhone-Poulenc, a few years ago. "We were behind because we were not spending enough on research and we were not open enough to the outside world, in particular academia," he said. In 1987, Desmarescaux decided to hire, on a part-time basis, two of France's top guns in academic chemistry,Nobel laureates Jean-Marie Lehn and Pierre de Gennes, to help him develop a strategy for encouraging cooperation between company and state-run laboratories. The result was a unique project of typical French grandeur - the Bio Avenir (Bio Future) programme. Its ambitious remit was "to reinforce collaboration and accelerate the transfer of knowledge between basic research and the life sciences industry". This mini Technology Foresight was launched at the end of 1991 for five years and brought together CNRS (Centre Nationale de la Recherche Scientifique), INSERM (Institut National de la Recherche Agronomique), INRA (Institut National de la Recherche Agronomique), CEA (Commissariat de l'Energie Atomique), the Institut Pasteur, university departments and Rhone-Poulenc's own research divisions. The total budget was Fr1.6 billion (Pounds 163 million) of which Fr1 billion came from Rhone-Poulenc. About 500 researchers in 100 laboratories took part in the programme.

Bio Avenir was divided into three main themes: health, agriculture and biochemistry, supported by a fourth, research into new methodologies, which covered analytical, chemical synthetic and biological screening techniques. One of the biggest projects in the health area has been on gene therapy, carried forward by a network of 19 laboratories under the name Gencell. They have been working on, for example, gene therapies to treat various cancers using the P53 tumour-suppressor gene. When introduced into cancer cells this induces apoptosis, or programmed cell death. According to Rhone-Poulenc, the programme has been extremely successful. Therapies for lung cancer and head and neck cancers are undergoing phase one and phase two clinical trials respectively. Gene therapies for disorders of the nervous system such as motor neurone syndrome and Parkinson's disease are also being developed, based on using an adenovirus (cold virus) to deliver certain "neurotropic factors" which prevent nerves from degenerating.

On the agricultural front, too, much of the research into plant protection and better sources of food has been based on genetics. Researchers have been developing new methods for inserting genes into plant cells to improve microbial resistance. They have also patented a process to create artificial seeds. The biochemistry area has been looking at the chemical mechanisms by which microbes produce useful chemicals such as antibiotics. It includes research into designing more environmentally friendly chemical reactions using microbial enzymes. Rhone-Poulenc has, for example, now developed an enzyme-based method for recycling nylon waste.

The Bio Avenir programme officially finished last November. How successful has it been? It is probably too early to assess the overall scientific impact on French biotechnology research. However, the programme has already generated almost 200 patents and 500 papers. According to Desmarescaux, Rhone-Poulenc has several products in the pipeline - eight new drugs and a new family of fungicides; and a new antibiotic, Synercid, for treating highly resistant hospital-acquired infections is seeking authorisation in Europe.

Desmarescaux believes that the programme has changed the research culture within Rhone-Poulenc. The company has become more flexible in taking advantage of academic results. Desmarescaux gives an example: "In the beginning, Rhone-Poulenc said that cardiovascular diseases was not its field, but when we found we had access to strong expertise, which was getting results, it became one of our priority therapeutic areas."

On the academic side, Michel Perricaudet who works on gene therapy in the Institut Gustave Roussy in Villejuif in the Paris suburbs found that Rhone-Poulenc was willing to support truly original research: "The possibility of gene therapy started appearing in 1985. My publications demonstrating the value of the adenovirus were, at that time, out of step with the general consensus of the scientific community, which was paying most attention to retroviruses. Rhone-Poulenc had the foresight to back our laboratory, allowing us to reinforce our resources." He also welcomed the constraints of working to deadlines imposed by the cooperation.

There will be no further government support, however - no Bio Avenir II. Claude Allegre, the French minister of national education, research and technology, announced at a recent conference marking the end of Bio Avenir that: "We do not intend to finance big companies. They must do it themselves." Instead, Allegre plans a radical new programme to help small and medium enterprises. Watchful of the high unemployment figures in France, he is keen to provide seedcorn money for PhDs wanting to start high-tech companies.

Desmarescaux agrees that biotechnology boutiques have an important place in the kind of technological culture that he thinks is necessary for economic success. To this end, Rhone-Poulenc wants to help set up small autonomous companies by offering finance and laboratory support. This is a rather unusual stance for a pharmaceutical multinational: they often eat up small companies whose expertise they need.

Although Bio Avenir has ended, the research projects it covered will continue in some form or another. The initiative has already trained more than 200 PhD students, allowing the firm to pick the best to work for Rhone-Poulenc afterwards. This is common practice in the UK where research students are often directly funded by drug companies or through the research councils' CASE award scheme. Glaxo Wellcome has academic collaborations with more than half the universities in the UK and spends more than Pounds 15 million per year to support PhD studentships and research projects. "We are re-inventing the British model within the French culture," admits Desmarescaux. Rhone-Poulenc has already seen the benefits of open collaboration. It remains to be seen whether other French companies follow suit.