France

French stem cell research strengths and significant recent results include:

• Developmental biology: the Institut Pasteur recently reported major progress in establishing mechanisms by which ESCs differentiate to muscle cells.
• Neural stem cells and cell therapies for neuroscience applications; Marc Peschanski's INSERM group was the first to use foetal neurones in treatment of Huntingdon's disease and is now hoping to improve the technique using ESCs.
• Skin stem cells; An INSERM group in Nice holds patents on growing new skin from ESCs.
• Gene therapy; Alain Fischer's INSERM group at the Hopital Necker carried out the world's first gene therapy trial for children with immune deficiency disorders. Although the trial was subsequently halted when 2 of the 11 children developed leukaemia the technique is still viewed as enormously promising.
• Haematopoietic stem cells

France has traditionally been more conservative than the UK on bioethics issues relating to the embryo. However a major change occurred last summer, when a new Bioethics Act permitted research on the embryo for the first time. Following an uneasy political compromise the Act declares that "research on the embryo is forbidden", before going on to introduce an exception to this ban for a trial period of 5 years. During this period research will be permitted on surplus embryos from IVF treatment, provided that

• the research could lead to "major therapeutic advances" ;
• the research could not be achieved by any other means;
• the couple concerned give their permission.

Both therapeutic and reproductive cloning are banned under the Act, as is the creation of embryos for research purposes.

Licensing of embryo research will be the responsibility of a new Agence de Biomedecine (Biomedical Agency). The Agency was established in May 2005 but the secondary legislation establishing its full licensing powers is still being prepared. In the interim a temporary decree published last October establishes an ad hoc committee to consider applications to import, store and carry out research on ESCs. The final secondary legislation, due to be passed by the end of 2005, is expected to:

• Establish the Biomedical Agency as licensing authority for applications to import, store and carry out research on embryonic stem cell lines;
• Enable the Agency to authorise research on surplus embryos from IVF and creation of new ESC lines;
• Enable the agency to authorise export of embryonic stem cell lines to countries whose bioethics legislation is consistent with that of France;
• Require creators of embryonic stem cell lines to register these with the Biomedical Agency.

Note that, unlike in the UK, these provisions will also apply to new research on existing ESC lines.

The French scientific community has been quick to take up the opportunities offered by the change in bioethics legislation; the ad hoc committee has already received 10 applications for import and research on ESCs, with 8 licences granted to date. Although the licensing procedures are viewed as lengthy and administratively heavy by the scientific community, researchers have been pleased by the authorities' flexible approach. There was some concern after the Act was passed that the requirement that research on the embryo be "capable of enabling major therapeutic advances" would be interpreted strictly, resulting in few successful licence applications. However licences awarded to date include basic research which can be shown to be relevant to treatment or understanding of particular conditions, such as studies of differentiation and autorenewal processes.

Despite the spate of recent authorisations, the community still feels handicapped with respect to overseas competitors. Since creation of embryos for research purposes is forbidden, creating stem cell lines with specific characteristics is difficult. Imported cell lines will therefore continue to be very important to the French stem cell research community.

Therapeutic cloning is hotly contested in France. Most scientists working in the field favour permitting the technique, although with some high profile exceptions. The French Academie des Sciences and Académie de Médecine both favour authorisation of therapeutic cloning due to its potential in finding treatments for new diseases. The statutory National Ethics Consultative Committee was unable to come to a consensus view on the topic, with a majority in favour of permitting such work but a minority including the chair against. The Government is publicly opposed, arguing that the scientific case for therapeutic cloning is not clear and pointing out that creating embryos for research purposes would require a major shift in the ethical approach to the embryo in French law. Although a citizen's panel of patients and patients' relatives convened by medical charities in 2003 ruled in favour of permitting therapeutic cloning, this received little press or parliamentary attention. No patient groups were invited to give evidence to either of the parliamentary committees reporting on the Bioethics Bill, a consequence of the weakness of the charitable sector in France.

Nevertheless, there are signs of increasing openness to discuss the issue and growing political support for authorisation of therapeutic cloning. Although President Chirac is known to be conservative on bioethics issues, former Health minister Douste-Blazy declared in introducing the Bioethics Act that "We must keep an open mind on this topic", and promised to commission a report on ethical implications of therapeutic cloning from the Agence de Biomedecine. The research ministry has long been keen for a more open attitude to therapeutic cloning. Following the May 2005 Korean announcement on derivation of human embryonic stem cellC lines following cell nuclear transfer, former socialist research minister Roger-Gerard Schwartzenberg proposed to Parliament a draft Bill authorising therapeutic cloning. Although there is little chance of it becoming law the draft Bill will give this issue a higher Parliamentary profile. Of the political parties only the communist party have openly declared their support for strictly regulated therapeutic cloning to date. The evolving consensus seems that it is too soon to justify permitting therapeutic cloning in a French context, rather than an outright "no".

As things stand and unless the new government that will take over in 2007 adopts a radically different approach, the earliest any change in the law could realistically take place is 2009, when an evaluation will compare the results of research in adults and embryonic stem cells preparatory to a review of the 2004 Bioethics Act. Whether or not a change does occur will depend strongly on progress internationally using both therapeutic cloning and adult stem cells, and whether the scientific case for the necessity of therapeutic cloning is clear. However there is a reasonable likelihood that therapeutic cloning will be permitted in future, particularly if there is a change of Government.

The vast majority of stem cell research in France is carried out either by medical research agency INSERM or in the life sciences department of fundamental research agency CNRS, both quasi-autonomous research organisations with their own laboratories and staff. INSERM and CNRS research groups may be associated with universities, and many INSERM groups are based in or associated with hospitals. Research groups in both organisations generally receive funding on a recurrent year on year basis, making it difficult to impose top-down priorities, and as a result there is no national strategy for stem cell research. The main vehicle for the Government to impose research strategy or priorities is via the National Research Agency, which manages both "programmed mode" and "response mode" research programmes across all areas of science. The agency is likely to launch a "regenerative medicine" initiative next year.

Although in general France's life sciences research is less strong than that of the UK, until 1994 the influence of eminent scientists such as Nicole le Douarin and Nobel Prize winner François Jacob resulted in a strong niche activity in developmental biology, including the role of stem cells. One of these groups claims to have been on the point of establishing France's first human embryonic stem cellC line in the early 1990s. This activity was significantly slowed in 1994 when a new Bioethics Act forbid research on the human embryo or cells derived from the human embryo. Between 2000 and 2003 the research ministry and CNRS made an effort to maintain the health of the sector with a 14 M€ targeted programme in developmental biology, in which the role of stem cells in development was one of four main themes. In 2003 INSERM launched a one off targeted call for proposals in stem cell research jointly funded by the research ministry and two medical research charities in a further attempt to maintain capacity. This call focussed on stem cell characterization, techniques for maintenance of and inducing differentiation in stem cell lines, and applications in stem cell therapies.

Despite these measures the sector has inevitably suffered. A French Academy of Sciences report of December 2004 concluded that the stem cell area required additional funding and clarity of strategy. They were also concerned that the previous ban on embryo research had discouraged young French researchers from beginning careers in this area, and that the ambiguous formulation of the current Act would lead to continued difficulty in encouraging talented young scientists into the field and in keeping more experienced researchers in the country. These difficulties are compounded by the low salaries and bureaucratic difficulties in carrying out research in France. INSERM shares these concerns and is worried that skills shortages will prevent them making the most of the current 5 year window of opportunity to demonstrate the benefits of ESC research. Researchers are now desperately playing catch up, but are pessimistic about prospects for France becoming a major player in this area.

Since the change to the law in 2004 a number of these groups have rushed to put in place new human embryonic stem cellC research programmes in an attempt to make up for the lost time. While CNRS groups focus largely on developmental biology and mechanisms of stem cell differentiation, using mouse, chicken and quail models, INSERM groups are more therapeutically focussed. INSERM is also funding a new Biotherapy Research Institute associated with Montpellier hospital to bring together cell therapy research from fundamental science through to clinical applications, with stem cell research a particular priority.

Private sector stem cell research is extremely limited. Vivalis, a medium sized pharma company, have considerable expertise in avian ESCs for use in vaccine manufacture and have an agreement with Sanofi-Aventis for further research in this area. The start up Myosix is commercialising INSERM research on use of myoblasts (muscle stem cells) for treatment of heart disease. Urodelia specialise in bone reconstruction and have recently started research in adult stem cells. A handful of other start ups work with adult stem cell lines. Generally the financial and regulatory environment in France is less favourable towards spin-outs and start-ups than in Britain, and the biotechnology sector as a whole lags behind that of the UK.

France is clearly not a global player in stem cell research and is unlikely to become one as long as the current legislative ambiguity and lack of overall persists. However in niche areas such as cell therapy and developmental biology they may be able to "catch up" to an internationally prominent position.

There is huge respect for the British scientific system in France, with researchers looking enviously across the channel to what is perceived as a better funded, less bureaucratic and less political research system, although more competitive and pressured. French scientists are generally keen to collaborate with UK colleagues, although the very different organisational and funding structures can act as barriers in practice (1). Debate on bioethics issues in France often cites the UK as an example of best practice in licensing procedures, with a considerable respect for the HFEA. However the perception even among scientists is that the ethical framework behind our licensing system is "utilitarian" and influenced by a wish to promote the competitiveness of the UK bioscience sector. This Embassy organised a Franco-British bioethics seminar in March of this year both to combat this perception and promote the UK regulatory approach as a model of best practice. Feedback demonstrates that the event was successful on both counts, with interest in a follow up event.

There is considerable scope to attract young French scientists to the UK, both at PhD and postdoc level. There is a shortage of funded PhD places in France, and grants are around a third lower than in the UK (2). Similarly postdoc places in France are hard to come by and salaries are again lower than in the UK. The UK is already the leading EU country for French PhD students who wish to study overseas, attracting a third of this group. At postdoc level the US is a clear competitor nation, attracting around 3000 French postdocs a year. Attracting experienced researchers is likely to be harder. Although UK academic salaries are higher than in France, the security of tenure and research funding for CNRS and INSERM staff goes a considerable way to making up for this.

A number of areas could provide scope for collaboration for the benefit of the UK:

• The fact that new embryos cannot be created for research in France clearly hampers the ability to produce stem cell lines with specific characteristics. There is hence potential for UK firms or academic institutions to carry out drug screening or toxicity testing on behalf of French pharamceutical industry customers.
• French ESC research will continue to be highly dependent on imported ESC lines. To date imported lines have come from Cellartis in Sweden, the US, and Israel, suggesting that French scientists are already collaborating with these countries. The Agence de la Biomedecine is keen to publicise the UK stem cell bank among French researchers, and to encourage them to deposit ESC lines developed here in the UK bank. This might require some form of MoU to confirm that the bank's practices comply with French regulation on embryo and ESC export, but could provide a useful means to foster R&D collaborations between British and French groups working in similar areas or to initiate contacts leading to French researchers moving to the UK.
  

(1) e.g. French research organisations often require MoUs before putting in place international activity, but UK research councils cannot enter into such MoUs on behalf of the universities where research is actually carried out.

(2) UK PhD grant minimum is £12,000. French "allocation de recherche" is 1306 € gross/month, around 1100 € net i.e. French annual net PhD grant of ~ £9100.

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copyright: © | last updated 24 November 2005