Role Reversal: Science Should Be Leading Technology, Not The Inverse

Photo Françoise Barré-Sinoussi / Head of the unit of regulation of retroviral infections, Institut Pasteur / June 20th, 2011

Looking for balance between science and technology in modern research, we can observe it is the latter in the ascendant. Research is being dictated by the availability of technological resources but in the past, the reverse was true. Projects began by a review of the available data from which a scientific hypothesis was constructed, and finally a search for the best technological tools would begin. Françoise Barré-Sinoussi has suggested that in the rush to embrace technology, researchers may be missing the chance to learn from what worked so well in the past.

ParisTech Review: Numerous criticisms have been made over deficiencies in the French research environment. What criteria are used in evaluating the performances of individual researchers?
Françoise Barré-Sinoussi:
The review process is complex and often international in scope. The most important factor is the quality and quantity of published material as established by an “h-index”, based on an equation to measure a combination of published works and citations over time. The impact on the index that publication in a major peer reviewed journal can have makes those outlets especially prized in the eyes of the majority of researchers. Co-authorship also plays a role and an evaluation is made based on an individual’s position at the head of the list of signatories, at the end, or less desirably in the middle. A position at the base of the list indicates an individual’s role as the driving force in a particular project while placement at the head represents whomever was most active in the experimental research. Researchers are also judged on their capacity to obtain external funding for research and their success at transforming experimental research into concrete results, which is to say through the number of patent applications made. The standing of a team in the eyes of the global community also plays a role as it is through peers that invitations to international conferences arrive and publication opportunities are maximized. Receiving an invitation to speak on the opening or closing panel of a major conference naturally signals a – and translates into – greater recognition from the global scientific community.

Does peer review add more value to research?
If other sectors of the economy or corporations were subject to as much scrutiny as researchers, then perhaps wider society would better understand the demanding nature of our work. We spend our entire working lives under review. Obtaining funding requires the submission of proposals and, in light of the competition and a rigorous sifting process, only the best have any chance of receiving grants. Aside from financing primary research conducted at the laboratory, grants are required to support the work of an institution’s younger researchers. In any case, once a project is accepted, a timeline must be submitted, which is again subject to further review. Furthermore, if we are attached to an organization financed by a major research organization such as the Institut Pasteur, INSERM, or CNRS, we are nevertheless individually evaluated every two years by a review board that examines all the details of activity over the specified period. The result is a state of permanent evaluation to which is often added participation on various scientific review boards and at a certain point in my career all these activities alone consumed around 50% of my time!

What incentives exist to encourage the kind of risk taking so crucial to successful research?
On numerous occasions, I have questioned whether the review process is acting as a brake on innovation and creativity. The outline I just sketched of the current methods of evaluation in the international scientific community could certainly lead one to the conclusion that it stifles innovation and creativity. If a project appears risky, which is often the case for projects in their infancy because of a dearth of hard results, the chance of receiving funding is drastically reduced. Given the international nature of the environment in which we work, it should be expected that there is a certain hesitation to fund research in the absence of reliable data but with the bar raised so high researchers can find themselves trapped in a vicious circle. How does one generate reliable data without first obtaining the funding required to produce it?

In your view, what perspectives exist for the future of scientific research?
The current reality is somewhat disconcerting and I feel something is being lost in the contemporary “techno” obsessed climate that leads a number of researchers to ask: based on the technology to which I have access, which direction should my research take? I struggle to see how this sense of priorities can reap any benefits. For my generation, reasoning proceeds from the opposite direction. Based on the availability of data on a given subject, a conceptual or hypothetical framework is constructed, and at the end of the process questions on the technological aspects are considered. The entire spirit in which research is undertaken has been transformed and the role of technology has become the driver rather than the reverse as was previously the case. Technological advances have been remarkable and while they have certainly created some significant advantages, to confuse these with real science would be to risk allowing research to become increasingly inward and could lead to eventual stagnation. Blinkered by an obsession with cutting-edge technology, researchers are less alert to the arrival of new concepts on the marketplace of ideas. The demand for technological advances demands resources that need to be justified through publication in scientific journals which serve, as I noted earlier, as the primary platform for review by one’s peers creating some notable tensions. Because career advancement, tenured positions, and financial support depend so heavily on the peer review process, this never ending cycle of grant seeking and production of ever more scientific data could lead to a dead end and ultimately be harmful to long-term innovation.

Rewarding uniformity to a degree?
In the private sector, such as in a pharmaceuticals laboratory, the very foundation on which R&D rests is dictated by the logic of the market. Maximizing profits is the very reason it exists. In the public sector however, where the tradition of pure research and free exploration play a greater role, this rush toward the profit motive threatens to inflict significant damage.

In the context of global competition, is French research suffering from under-investment?
Yes, finances play a large role. A quick glance at the paucity of entry-level positions for recent graduates tells part of the story as does the salary researchers can expect to earn which remains inadequate. The gravity of the problem is serious, as research institutions depend on new inflows of talent to stave off decline and, in the worst cases, extinction. Younger members are vital to the health of research teams as they bring technological sophistication which acts as the perfect complement to the more sophisticated perspective of more senior members. They are eager to pose questions and possess the technological know-how to create solutions. Without this fresh energy, a laboratory loses its vitality. In fact, it is well known that young people are expressing less of an interest in science and when looking over the current terrain and acknowledging the number of obstacles lying in the path of a successful research career, their choice is somewhat understandable.

You were a primary participant in the work that led to the discovery of the human immunodeficiency virus (HIV) and received the Nobel Prize in 2008 for your role. Looking back over your experience would you say the arrival of AIDS marked a fundamental turning point in the way research is approached?
Without question. The response to the AIDS epidemic was unprecedented in the way it united a broad spectrum of concerned parties ranging from researchers and clinicians to other health professionals and patient advocacy groups. Previously, researchers were isolated in their labs and clinicians in their hospitals and contact between the two groups was the exception rather than the rule. The magnitude of the stakes involved, and the needs of the patients, required each group to leave their sequestered environments and cooperate with the result that research advanced at a pace that simply would not have been possible otherwise. Moreover, a virtuous circle was created through the interaction between the public and private sectors. Indeed, the response to HIV could never have evolved so rapidly were it not for the crucial participation France’s Sanofi Diagnostic Pasteur, who, as a private entity, possessed the capacity to quickly create screening equipment on a scale required to isolate and better understand the disease. Development teams were sent directly to the laboratories to deploy the new technology and by 1985, tests were commercialized to provide rapid detection of the virus in order to prevent its further spread through blood transfusions. What we have been fortunate to witness since the dawn of the eighties is the creation of a truly multi-disciplinary approach capable of rapidly transforming scientific advances into practical applications.

Could this research environment be defined as “translational”?
Precisely, translational research aims to ease the translation of scientific advances into concrete applications of benefit to all. From the earliest days of the HIV, epidemic clinical and epidemiological studies created fertile terrain in the laboratory from which rose the essentials to rapidly create tools that could be immediately deployed to defend public health. In addition to screening, other examples are easy to find. With better understanding of the virus lifecycle, and characterization of the viral proteins contained within, research led to the creation of antiviral inhibitors based on specific target proteins, most notably viral enzymes such as reverse transcriptase. An understanding of how the HIV genome is organized is the base from which we have developed molecular diagnostics to examine viral load and resistance to medication.

When researchers establish close relationships with patients, do they surrender some element of control? Does this restrict their freedom to conduct independent research?
No, the patients enter the discussion and become genuine partners in the outcome. We present and discuss research projects with them. Patient advocacy representatives are at our side whenever discussions are held over important decisions and also when occasions arise to appear at board meetings right up to the level of hearings before the scientific committee of France’s national agency for AIDS research, ANRS. Everyone benefits from the arrangement! On the patient side, they receive information on the latest advances or the importance of a particular clinical trial. For us, we receive critical feedback which is of enormous benefit when searching for ways to improve research programs and ensure they remain focused on the goal of improving public health. Patient networks are in any case often more open to new concepts than evaluation committees or the scientists themselves. In many cases patient input helps drive research teams to more innovation.

Are private foundations such as the Institut Pasteur better equipped to advance science?
In my domain, it is clear that as a private foundation labeled “in the public interest”, the Institut Pasteur, allowed us to rapidly obtain the resources we required to build a secure laboratory and mobilize research teams to effectively analyze the genetic makeup of the virus very swiftly after it was first identified. Private foundations have the ability to invest rapidly in a way that public institutions do not. Administrative procedures are more streamlined and better able to respond to a public health crisis such as the emergence of infectious diseases. This was the case with the emergence of HIV/AIDS and again, more recently, epidemics such as the mosquito-borne Chikungunya, Severe Acute Respiratory Syndrome (SARS), or the bird flu and swine flu outbreaks.

Would the battle against HIV have been possible without backing from the state?
No, because the nature of the epidemic also required political will. At the end of the eighties, French authorities played a crucial role by providing the political capital to create ANRS in 1988, mobilizing researchers and grouping all the institutions with a stake in the fight under one roof. With a national agency to coordinate, encourage, guide, and of course finance research, previously fragmented initiatives to understand HIV were given a more unified vision. Researchers were given the power to direct policy and set the agenda in terms of scientific priorities.

Doesn’t this arrangement make scientists both players and referees?
It’s a criticism I’m used to hearing. In reality however, all the governing bodies of ANRS contain external experts and policy decisions are subject to review before an international scientific committee to maintain coherence and grant legitimacy to whatever choices are made.

Is the ANRS model still relevant in 2011?
More than ever and a number of my overseas colleagues are full of praise for the ANRS “model”. Americans envy our ability to maximize the relationship between cost and efficiency and I have to agree that sometimes, I find what I see in the United States wasteful. As a result of equal opportunity policies, many projects get financed without demonstrating much potential for success whereas in France, with more limited budgets, we do not have this luxury. We demand excellence in our research and insist that it be truly innovative.

In the future, how will you optimize the intellectual capacities of the organization?
Here again the structure of ANRS can serve as a basis for further reflection as it encourages the flow of information through various interfaces linking together a wide range of disciplines: clinicians; health care professionals; biomedical researchers (virology, immunology, epidemiology, molecular biology, genetics, bioinformatics, biostatistics, etc.); and researchers in physics, chemistry, and the social sciences. With everyone working together, positive outcomes are created for very specific problems, such as one cohort of patients, by harnessing the power of the interdisciplinary approach to information. The number of issues to which our framework can be applied is limited only by the imagination…

So has the ANRS “model” already been imitated?
We ourselves have seen our model expand beyond its original remit as we are now responsible for hepatitis research. French medical research is more and more being oriented around broad themes and spread across multiple organizations. Some examples of this trend in France are the institute of infectious diseases; the national cancer institute (INCa); and the institute of neuroscience, cognitive science, neurology, and psychiatry. All demonstrate the potential to expand along the same lines as ANRS with the important condition that funding be drawn from a public and private mix, so essential to ensuring resources are there for future investment.

What is your long-term outlook on AIDS: elimination, mutation, expansion?
I believe we can eliminate AIDS but only under certain conditions. Investment in research needs to intensify and be more global in reach to bring in less developed countries. Screening needs to be expanded, prevention efforts increased, and care and treatment made more accessible. The stakes are high and I fear if we slide backwards and these conditions are not fulfilled we could see the AIDS epidemic reach crisis proportions again.

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