From public health to medical research, from INH to Inserm, 1941-2001 (M. Adamson, J.-F. Picard, 2003) |
The origins of scientific medicine
At the beginning of the nineteenth century in France, the rise
of the descriptive sciences, nosology and anatomical pathology gave birth,
in the hospital, to scientific medicine. But if these disciplines lifted
the clinical art to its greatest height, they included hardly any therapeutic
applications. A few decades later, Claude Bernard with physiology and Louis Pasteur
with microbiology brought medicine into the field of experimental
science. The development of vaccines against rabies, diphtheria, and
tetanus, of BCG, opened the way to preventive medicine. Thus the first
labs dedicated to medical research arose more out of public health than out of the clinic. The turn of the twentieth century witnessed the
creation of the Instituts Pasteur in Paris, Lille and overseas, or even
the Office national d'hygiène sociale that was created in 1924 to
direct the fight against tuberculosis. Louis Bugnard, director of the
INH, later recalled, "Since for several centuries one had been concerned
to improve the human condition, the discovery of germ theory, and the notion
of contagion which resulted and which made immunization possible imposed
on governments an increased responsibility in the field of health care. Therefore,
national health services were created and developed in each country around
the globe".
1941 - The birth of the Institut national d'hygiène (INH)
The great conflicts of the twentieth century proved
propitious as far as concerns the development of medical research in public
health. In occupied France, André Chevallier,
a professor on the faculty of Marseilles, sent a note to his friend, Dr.
Serge Huard, State Secretary for Health in the Vichy government. In his letter
Chevallier explained: "The State Secretary
for Family and Health will not be able to accomplish the technical task incumbent
on him and thus assume the place deserving of a great technical minister
having at his side an organization presenting all scientific certitude".
Thus, thanks to the
strong support of the Rockefeller Foundation, a law passed 30 November 1941 by Marshall
Pétain created the INH, a public establishment. Put under the
direction of Pr. André Chevallier, it was endowed with a dual
mission : to carry out laboratory work related to public health, and to coordinate
public health studies to be directed in a country conquered and occupied
by the Germans.
The four divisions of the INH
- The `Section de la Nutrition' dealt with child nutrition.
Professor Chevallier, author of noted works concerning the amount of vitamins
in the human diet, was reminded that here lies a crucial problem in a country
subject to rationing, in addition to being one with the greatest observed
demographic shortfall in the world - The `Section des Maladies Sociales' was devoted to the study of tuberculosis, alcoholism and syphilis, as well as cancer. In 1942, Dr. Pierre Denoix assembled, from 35,000 case files provided in part by the Parisian welfare service, the first French survey of cancerous maladies. - The `Section d'Hygiène' was charged principally with the problem of water supply and workplace health care. - The `Section d'Epidémiologie,' directed by a woman, Dr. Alice Lotte, published mortality statistics in the Recueil des Travaux de l'Institut National d'Hygiène. |
1945 - modernizing medicine
As a leader of the Conseil médical de la Résistance, Pr. Robert Debré,
an important clinician who directed the pediatrics service at the Hôspital
des Enfants Malades of Paris, elaborated a plan - a plan destined to modernize French medicine - in which he expressed a two-fold concern : to carry out
this indispensable effort in such a way as not to leave behind the clinic,
while avoiding with the latter a socialization that might presage the creation
of the French social security health service (October 1945). While he outfitted
research laboratories in his 'Service des Enfants Malades' (directed by Georges
Schapira), Professor Debré was named President of the INH in 1946,
where he could supervise the launching of a Committe for Social Security
Health Studies, an organ intended to fund public health research. Debré's
other preoccupation was to find André Chevallier's successor at the
head of the INH. His choice was Louis Bugnard, a doctor,
polytechnicien, and professor of biophysics in Toulouse where ha had
been a resistant during the war.
Training medical scientists
Louis Bugnard's first task was to assemble a body
of medical researchers. While the INH was endowed
with a Scientific Council, a new decree fixed the legal status of its
researchers with that of their colleagues in the Centre National de la
Recherche Scientifique (CNRS).
A close formed between the two organizations. It was strengthened in
1950 when Bugnard was named president of the CNRS 'commission of
experimental medicine'. The INH thus paid for a hundred personnel,
including doctors who would leave a historical legacy : obstetrician
Alexandre Minkowski, cancerologist Maurice Tubiana, Constant Burg or
Philippe Laudat, these two to become later Inserm CEOs. Thanks to contacts with Anglo-Saxon
research - notably through the Rockefeller and Ciba foundations - Bugnard
established a system of grants that allowed him to send several young interns
to the United States to complete their training, as well as enabling him
to collect the precious technical means needed to modernize French medical
research.
| The first budgets ot the INH, a modest draw on the public coffers In 1942, the initial budget of the INH was 15 million Francs. This annuity was raised to 21 MF in 1944 and 50 MF in 1947. At the time, this represented only a miniscule part of the overall budget for public research (13 billion F in 1948) compared to the one billion allocated to institutions like the CNRS, CEA or Institut Pasteur. In 1964, the INH budget reached 54 million new francs (one new franc = 100 old francs), following a spectacular augmentation in 1958. As far as concerns the number of personnel supported by the INH, from 100 agents in 1944, numbers rose to 200 by 1958 and in 1963, on the eve of the creation of Inserm, 700. |
Medical physics
In the matter of research, Louis Bugnard vectored the INH towards
medical physics. In close cooperation with the French Atomic Energy Commission
(CEA), the INH developed and expanded the use of radioelements, the isotopic
markers indispensable to cellular biology. On the therapeutic front, the
INH participated in the installation of the first large-scale instruments
for cancer treatment. One, a betatron, was installed in 1948 at Villejuif,
while at the same time Bugnard organized training for those doctors using
radioactive isotopes. The INH contributed as well to the development of a
dosage system intended for workers in the nuclear industry and it took part
in a study of atmospheric fall-out from American and Russian atomic explosions.
The Institute became one of France's principal national correspondents with
the World Health Organization (OMS), while it also encouraged the creation
in 1956 of the SCPRI (Service for the Testing of Ionizing Radiation).
The meeting of medicine and biology
Restricted by its modest budget and also by the priority given
to problems in medical physics, the INH found no way to respond to the new
expectations of the clinic. At the conclusion of the war, a new generation
of clinicians were concerned that medical research be included in the veritable
revolution sweeping the life sciences. If until then issues of public health
had acted as engines of medical progress, cellular physiology and then molecular
biology, biochemistry, and indeed genetics seemed to open new, extraordinary
perspectives in pathology and therapy. Thus, the neo-clinicians were more
interested in cancer, nephritis, cardiovascular disease - then in infectious
maladies which seemed close to being eradicated by the new antibiotics (sulfamides,
penicillin, etc). In 1952, at the instigation of the neo-clinicians, the Parisian hospital admininistration
(Assistance publique de Paris) created the `Association Claude Bernard',
an organization that would install their laboratories in hospitals
- an enterprise soon taken over by the INH, then by Inserm.
Research Centers
established by the Association Claude Bernard, the INH (to become Inserm units in 1964)
1950, by INH 1956-1959, by
Association Claude Bernard and INH 1960-1962 |
1958 - a period of reform
With the return to power of General de Gaulle in 1958, the
Fifth Republic gave new impulse to the modernization of the country. Initiated by Robert Debré
and Jean Dausset, the ordinance of 30 December 1958 called for the fusion
of clinical and medical faculties into Centre Hôspitalo-Universitaires
(CHU).
Greatly
increased (in 1959 to 400 MF, almost 170% greater than the year before) this
research budget permitted the launching of plans of action (Actions concertées)
that would boost new scientific fields.
Among the first twelve 'Actions concertées', five dealt with medicine
and biology: `Neurophysiology and psycho-drug dynamics,' `Nutrition,'
`Applications of genetics,' `Cancers and leukemias,' and `Molecular
biology.' This last was conferred to Jacques Monod, who would receive
the 1965 Nobel prize along with his Institut Pasteur colleagues André
Lwoff and François Jacob for their work on genetic regulation. Inspired
by the American medical reformer Abraham Flexner, the `Debré reform'
established a body of full-time hospital university professors
(designated PU-PH) whose task, in theory, would be to ensure the triple
function of care, instruction, and medical research. Between 1964 and
1967 the ordinance was finalized by a series of implementing decrees,
one obliging each CHU to set aside square meters for research labs,
another giving intern examinations the status of post-graduate study.
Simultaneously, the Fifth Republic created the Délégation Générale à la
Recherche Scientifique et Technique (DGRST), in practice if not in name
a veritable ministry of research. This institution managed a budget
equivalent to all other public research combined (enveloppe recherche).
1964
- the metamorphosis of the INH into Inserm
The transformation of the INH into the Institut National de
la Santé et de la Recherche Médicale issued from these new
policies. They were a product of the will of the Minister of Health to keep
control of the organization charged with medical research, as well as the
need to harmonize public health initiatives of the INH with those of the
clinicians of the Association Claude Bernard. At the initiative of the Minister of Health, Raymond Marcellin, a 18 July 1964
decree created Inserm. Direction of the new organization was conferred
to the former Director-General for Health in Ministère de la Santé, Dr. Eugène
Aujaleu. Georges
Mathé, councilor to the Minister of Health, played an essential
role in this metamorphosis. Mathé, the founder of the Institute of
Oncology and Immunology, symbolized the irresistible rise of the fundamental
sciences within medical research. From this trend he came to conceive of
the scientific organization of the new institute. Inserm was invited to reinsert
in its scientific programs certain DGRST plans of action (100 million Francs
were budget for this purpose under the auspices of the Fifth Plan, 1965-1970),
while its new director launched a laboratory construction program (of which
half were located in the provinces) thanks to a new system of registration
with the Health Ministry that involved both university and regional hospital
centers. At the same time, Inserm's Scientific Council
created thirteen scientific departments,
the arrangement of which demonstrated that, from then on, priority would
go to biological research.
Inserm's scientific
divisions (commissions scientifiques spécialisées) in 1964
CSS 1 Cellular and tissue pathology, cancer research, radio-pathology CSS 2 Genetics, immunology, and molecular pathology CSS 3 Microbiology, and infectious and parasitic pathology CSS 4 Organic metabolism and hepatic and digestive pathology CSS 5 Inorganic metabolism, physiology, and renal pathology CSS 6 Physiology and cardio-vascular and respiratory pathology CSS 7 Endocrinal physiology and pathology CSS 8 Neurology, neuro-physiology, psychology and psychiatry CSS 9 Pharmacology and therapy CSS 10 Experimental surgery CSS 11 Environmental hygene CSS 12 Diet and nutrition, laboratory project for food additives, at Vésinet CSS 13 Epidemiology and preventive medicine |
The 70s - Pushed by the molecular biology wave, the immunology takes off
During the 1970s, under the auspices of its new directors,
Prs. Constant
Burg and Philippe
Laudat as well as its president, Pr. Jean Bernard Inserm
became a central actor in French medical research. Stemming from developments
in molecular biology, the work of Pr. Etienne-Emile Baulieu on the chemistry
of steroids led to the invention of the anti-progesterone RU-486 (the morning-after
pill). Immunology also witnessed remarkable developments. The term `immune
system' entered the Institute's scientific nomenclature (CSS 3), while new
teams entered the field. At the Hôspital Necker, Jean-François Bach succeeded
Jean Hamburger as director of U 25 (Auto-immune diseases, genetics, mechanisms,
and treatments). The Hayem Center at the Hôpital Saint-Louis expanded
in order to create within it the laboratories of Maxime Seligman (U 108,
Immuno-chemistry and immuno-pathology) and of Jean Dausset (U 93, Transplant
immuno-genetics) where work that led to the development of the Human
Antigene was undertaken (the discovery of the HLA system merited the 1980
Nobel Prize for Medicine). Work in this latter lab also included applied research
on organ transplant (France transplant). In addition, Pr. Jean-Paul Lévy created
U 152 (Immunology and oncology for retroviral diseases) which became the
nucleus of the future Institut Cochin for Molecular Genetics (ICGM), Axel
Kahn. There remained the question of developing centers of excellence
in the provinces. In Strasbourg, Inserm helped the Research Center for the
Biochemistry of cancerous Cells become the Institute for Cellular and Molecular
Biology and Genetics (IBGCM). Finally, following a move symbolic of the politics
of decentralization extoled by the powers-that-be, Inserm conferred to François Kourilsky
the task of setting up the Insitute of Marseille-Luminy, a scientific
campus created in cooperation with CNRS as a center for `Integrated immunology.'
That is to say, it was intended as much for the study of immune system response
as for developing genetic markers. Opening the door to the era of biotechnology,
the discovery of the first monoclonal antibodies encouraged the teams in
Marseilles to develop Inserm's first industrial subsidiary, Immunotech.
today directed by Pr.
Programmatic
research
At the beginning of the 1970s, Inserm, inspired
by the CNRS, adopted new measures of scientific planning: `Thematic Plans
of Action' (ATP) later re-baptized `Coordinated Research Programs (PRC).
Inserm's first `thematic plans of action' concerned not only advanced areas
like immunology, but other domains where french medical research suffered
some backwardness, such as in drug dynamics. Following an agreement reached
in 1974 between the French and American governments and according to the same logic of scientific planning,
Inserm became a French partner of the US National Cancer Program launched by pdt. Nixon a few years earlier.
Inserm's first
Thematic Plans of Action
- Clinical pharmacology - Cellular interactions - Behavioral biology - Immunopathology of the nervous system - Epidemiology and mechanisms of premature birth, of fetal suffrance and malformities - Physio-pathological action of long-chain fatty acids on the myocardium (particularly the human myocardium) - Aging mechanisms - Bronchial-pulmonary pathology and pollution (excluding tobacco and silicosis); Effects of hormones on the digestive tract - Immuno-pathology of glomerulonephritis - Circulatory physio-pathology - Neo-antigens of experimental and human cancers - Alcohol: pharmacological aspects and psycho-sociological impact - Direct and indirect impact of water, considered as a biological factor, on human life |
1984 - Inserm becomes a Public scientific and technological establishment (EPST)
Philippe Lazar,
named Inserm's director in 1982, organized the `Assises de la recherche',
a general meeting of French scientists intended for a collective reflection
initiated by the new Minister of Research, Jean-Pierre Chevènement.
Here one contemplated the means to insure the freedom of fundamental research
in the spirit of rendering significant public service. Leaving the supervision
of the Ministry of Health for that of Research, Inserm became a Public Scientific
and Technological Establishment (EPST) as other French public agencies (CNRS,
INRA, IRD, etc.) . Philippe Lazar, a polytechnicien trained by Daniel Schwartz
in the school of statistical epidemiology, re-organized the Institute and
created for it a Council for Scientific Direction (CODIS). Researchers were
now included in the statute serving fonctionnaires (by the decree of 28 December
1984), thus leading to a significant recruitment of non-medical researchers
- in fact, three-fourths of recruits during this period. Finally, Inserm's
administration was decentralized by a 1983 decree that instituted Regional
Delegating Administrations.
| Inserm in the
1980s, a spectacular expansion When it commemorated its first twenty years of activity, the Inserm could boast its spectacular expansion : by 1984, its workforce, like the number of research units, had multiplied four-fold (1000 employees and 50 units in 1964, 4000 employees and more than 200 URs in 1984), while its budget tripled, increasing from approximately 50 MF to nearly a billion and a half Francs. In 1994, ten years later, Inserm's workforce had again grown by another thousand employees and its budget had topped 2.5 billion Francs. |
Enlarging the scope of human
sciences
Opening Inserm to fundamental research permitted it to tackle
all of the human sciences considered in their widest sense, from the most
reductionist of approaches (man as an ensemble of nerves) to the most holistic
(man as a social being). The pasteurien Jean-Pierre Changeux, named president
of the scientific council in 1983, supported the development of the neurosciences
whereas Philippe Lazar, anxious to enlarge epidemiological pursuits to the
level of dilemmas involving broader society, decided to introduce to Inserm
the human and social sciences. Nevertheless, the choice to privilege research
freedom over planning drove Inserm to envision cooperation with other organizations
created to deal with the evolving scientific circumstances. Thus, in 1987,
the resurgence of infectious diseases pushed the French administration to
create the National Agency for AIDS
Research (ANRS) with pr. J P Levy at the head and the 'Institut national
de veille sanitaire' under the supervision of the Ministry
of Health, while medical genome studies evolved first into
the Center for the Study of Human Polymorphism (CEPH), a private foundation
settled by Professor Jean Dausset, and then `Généthon' a network of laboratories settled in 1991 by the French Association against Myopathy (AFM).
The 90s
- Return to the `Clinic'
The 1990s marked a return to the clinic, as Inserm addressed
the latest clinical concerns. Predictive medicine produced advances in fundamental
research that might involve questions of public health as well as medical
practice. This movement gained its impulse from the Ministry of Health, which
launched a `Hospital Program for Clinical Research (PHRC). Simultaneously,
Inserm elaborated a plan for `federated research institutes' (IFR) destined
to re-organize the laboratories installed in the CHU and the CHR around a
new joint scientific strategy at a new unceasingly more complex
technical level. This return of the clinicians was embodied by the nomination
of two professors from the Hôpital Necker to direct Inserm - Claude Griscelli in 1996 and Christian
Bréchot in 2001. In fact, the nature of medical research had profoundly
changed since the beginning of the Institute in the 1960s. Henceforth, it
covered therapeutic trials as well as investigation genetic therapies. Thus,
Inserm generalized the mechanism of `Center for clinical investigations'
(CIC) envisaged by Professor Pierre Corvol, in the same time the Institute
supported research on gene therapy, such of U 429, the `Normal and pathological development of the
immune system' of Pr. Alain Fischer. In truth, this research, sometimes
qualified as `clinical,' often no longer differed from high-level fundamental
research - if such a fact only further confirmed its effectiveness. In regard
to problems of public health, from then on identified with the smooth functioning
of developed societies, they saw the social sciences put to the difficult
task of optimizing medical practice in order to render the most effective
service at the least cost.