The Institut Pasteur Institutional Review Board (IRB) protects the rights and safety of participants in research carried out by the Institut Pasteur abroad. Since it was set up in 2009, it has monitored nearly 50 international research projects involving human subjects. The Board is currently chaired by Dr. Gilles Raguin, a physician specializing in infectious diseases. We asked him to tell us more.
More than 90,000 people to date have been involved in research carried out abroad by the Institut Pasteur. The Institut Pasteur's teams collect biological data and samples from these "participants" with the aim of advancing medical research, in addition to the research carried out at the Institut Pasteur in France. The Institut Pasteur Institutional Review Board (IRB), a research ethics committee set up in 2009 and accredited by the US Department of Health and Human Services, is primarily concerned with protecting the rights and safety of these participants. It has already evaluated nearly 50 international research projects involving human subjects. The Board is currently chaired by Dr. Gilles Raguin, a physician specializing in infectious diseases whose career has spanned a wide variety of roles in basic and clinical research, as well as more operational positions (in humanitarian organizations and at Expertise France, the French public agency for international technical assistance, etc.). He gives us a brief picture of the IRB: What are its tasks? Who are its members? How does it carry out its work?
At the Institut Pasteur, the IRB may examine any research sponsored by the Institut Pasteur that will be carried out abroad, as long as it involves human subjects and is not examined by an Ethical Research Committee (CPP)
Gilles Raguin President of the Institutional Review Board (IRB) at the Institut Pasteur
Picture : © Expertise France / Cecilia Nilsdotter.
You were recently elected as Chair of the Institutional Review Board (IRB). Could you tell us what role this body plays at the Institut Pasteur?
The IRB is an institutional ethics committee with the same legal basis as all IRBs around the world – which gives it clear legitimacy but also requires it to comply with strict, recognized rules. Its main task is to protect individuals participating in scientific research. At the Institut Pasteur, the IRB may examine any research sponsored by the Institut Pasteur that will be carried out abroad, as long as it involves human subjects and is not examined by an Ethical Research Committee (CPP). Its role does not apply to research projects involving human subjects carried out in France, since these are the responsibility of CPPs, which were introduced by French legislation in 2004. Both the IRB and CPPs may refuse to approve or authorize research protocols which contain shortcomings with regard to the protection of the rights and safety of human participants in research. At our monthly sessions, we examine any type of research which fits the criteria I just outlined, such as projects involving the use of human biological samples or personal health information, as well as anthropological studies and clinical trials.1
1. Research in which individuals undergo a specific procedure or are offered an experimental medication.
So the IRB plays an essential role in protecting participants in research?
That's right. The role of the IRB is to protect people involved in research – and also to protect the Institut Pasteur itself, by making sure that all projects submitted to the Board are compliant with international ethical standards. In late 2018, when a Chinese scientist announced that babies had been born with altered genomes, it sparked international outcry – and rightly so. This episode, which triggered a huge media backlash, shows just how vital it is to have a solid ethical framework in place if we are to protect citizens from sometimes "wildly reckless" behavior – to coin the phrase used by Charles Nicolle, a disciple of Louis Pasteur.
You mentioned the famous Institut Pasteur scientist Charles Nicolle, winner of the 1928 Nobel Prize in Medicine. Was this issue of providing a framework for research one that came up often in the history of science?
I wouldn't say often – it is more of a recent concern. Charles Nicolle believed that scientists could be driven by a "wild recklessness", and that this recklessness could get the better of their conscience. His words2 came in response to experiments carried out in the 19th century. Louis Pasteur envisaged testing rabies vaccine candidates on convicts facing the death penalty in Brazil, and before him Edward Jenner infected human subjects with cowpox from cattle to see whether it provided immunization against smallpox. Charles Nicolle did not judge them, but he saw in their behavior a failure to comply with ethical standards, and he pleaded for those carrying out scientific experiments to adopt a humane approach. His views were both accurate and foresighted: since Nuremberg, the Declaration of Helsinki and the major ethical debates of the 1970s, with the development of health democracy, citizens now see themselves as stakeholders with an informed part to play in decisions that may endanger their lives, their bodies and, more broadly, their rights. The role of IRBs is to make sure that research projects submitted to them contain the necessary ethical guarantees.
2. Experimentation in medicine, a lecture by Charles Nicolle (1934) at the Collège de France.
How does the IRB carry out its duties?
In several ways. Firstly, the IRB evaluates research protocols before they are put into practice. It may approve these protocols, refuse to allow them to be implemented and/or request adjustments. Its opinions are delivered independently and on its own initiative. Apart from a few specific cases linked to applicable legislation, all approved projects are reviewed once a year until they are completed. In practice, this means that the IRB provides guidance for research projects throughout their life cycle, verifying their "ethical balance" (the safety and well-being of research participants) on a regular basis.
I would add that it is the wealth of expertise and the spirit of cooperation at the IRB that enable us to deliver relevant, informed opinions. We always strive for consensus, only holding a vote if we are unable to reach agreement. The IRB is composed of people from a variety of horizons with different sensibilities, including doctors, experts in social science, law and ethics, scientists, philosophers, anthropologists and representatives of patient associations. And even though the IRB is an institutional committee, 5 of its 13 members are from outside the Institut Pasteur, which broadens its expertise and strengthens its independence.
You mentioned ethical frameworks in other institutions around the world. Are there other IRBs?
Yes, there have been IRBs (in the standard format that we know today) since the early 1980s in the United States. The Americans led the way in this area. IRBs are a standard type of ethical research committee that was developed on the basis of work carried out following the publication of the Belmont Report (see inset). The Institut Pasteur set up its own IRB in 2009 to provide a framework for international research projects. It is an independent body and its opinions are binding, meaning that they must be observed. Since it was set up by the Institut Pasteur, the IRB has helped protect the safety and rights of 90,000 people, half of them vulnerable individuals such as pregnant women or children. It has monitored or continues to monitor 47 research projects.
What does being Chair of the Institut Pasteur IRB represent for you?
It is an honor to be given a role whose aim is to protect people and ensure the smooth functioning of research. Moreover, in an era seemingly dominated by fake news, in which many people are beginning to doubt science, it is vital to restore trust between scientists and civil society. The work of ethics committees can lend credibility in the eyes of the public to scientists' efforts to improve human health, provide citizens with accurate information and make sure their rights are respected. And it should never be doubted that the scientific community is firmly committed to ethical issues, even as they give rise to ever more heated debates among scientists and citizens in an era of major technological and scientific progress.
On a more anecdotal note, I am particularly touched to have been entrusted with this role because my paternal grandmother's grandfather was Joseph Bertrand, Permanent Secretary of the French Academy of Sciences and Chairman of the Institut Pasteur Committee when it was first set up. He was the first speaker at the inauguration ceremony for the Institut Pasteur on November 14, 1888. I myself was a student of the Institut Pasteur course in the 1980s, then a research intern in the Lentiviruses Unit. So I am well acquainted with the Institut Pasteur, its professionalism, its interest in human health and its passion for passing on knowledge. All these aspects and dimensions are vital when it comes to questions of transparency and ethics.
From the Belmont Report to IRBs
In 1979, the Belmont Report was published by the United States Department of Health, Education, and Welfare (subsequently renamed the United States Department of Health and Human Services). The report is entitled Ethical Principles and Guidelines for the Protection of Human Subjects of Research. It was not the first important document to be published on the topic of research ethics (there had already been the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964), but it left a lasting impression on the English-speaking world.
The Belmont Report followed on from the 1974 National Research Act, which itself was a response to the public outcry among American citizens when they found out about the Tuskegee Study. This study on syphilis, which lasted for more than 40 years (1932-1972), was carried out in Alabama by US physicians on poor black populations.
Although the Tuskegee Study began before the discovery of antibiotics to treat syphilis, it continued unchanged even when medication to treat the disease became available. For the sake of the study, participants were deliberately left in the dark as to the therapeutic possibilities available, and several died and/or contaminated family members.
Following the scandal (which was revealed by the press), a specific commission was set up to identify the ethical principles that should be respected with regard to human participants in research. The Belmont Report lays down three fundamental ethical principles:
- Respect for the autonomy of people, which implies the need to obtain free and informed consent from anyone participating in research
- "Beneficence", which means that the risks of research may not outweigh its benefits
- Justice, which implies in particular that research subjects should be selected fairly and in a non-discriminatory fashion
In the years following the Belmont Report, IRBs were given a legal basis (and no longer merely set up as ad hoc committees by individual institutions) and became widespread, not just in the United States but worldwide.