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INTRODUCTION
As we have argued on other occasions (2) , French genetics after
the Second World War drew on traditions and resources not readily
available to mainstream genetics in the United States, England, or
Germany. The differences between the French contributions to genetics
and those of other nations in the period from 1945 to 1960 rest in part
on differences in style, tradition, and institutions, but especially on
the very different strengths of the relevant subdisciplines of biology
in the different countries. In this paper, we examine the development
and the specific contributions of the three laboratories of genetics
founded by the CNRS at Gif-sur-Yvette, briefly comparing their work
with the work in genetics carried out at the Institut Pasteur and
elsewhere.
We seek a better understanding of the role of the
laboratories of the CNRS in fostering and shaping the distinctive
contributions of French workers to genetics during this period. To this
end, we will examine the roles of some of the individuals and some of
the institutional arrangements involved in establishing the
laboratories at Gif by the CNRS. We will also characterize some
distinctive features of the work in the CNRS labs vis-à-vis the
development of genetics internationally. We approach our topic from
three principal perspectives: the placement of genetics within French
biological research (especially that sponsored by the CNRS) during the
fifteen years after the war; some of the institutional peculiarities of
the CNRS laboratories of genetics (including certain difficulties
connected with the establishment of the physical facilities at Gif);
and the contributions of the work in genetics to the international
development of that discipline.
STAGE SETTING
1. The Place of the Labs in the CNRS
It is not widely known that the CNRS was committed, shortly after
the war, to the formation of a unified Institute of Genetics at Gif
.(3) In practice, this plan was not brought to fruition. Eventually,
three more-or-less independent laboratories of genetics were
established which, after many delays, were ultimately settled at Gif.
These were directed by three major founding figures of modern genetics
in France: Boris Ephrussi, Philippe l'Héritier, and Georges
Teissier.(4) The history behind the organization of these laboratories
is complex; serious administrative issues were at stake, including
problems regarding the chain of authority, difficulties with the
development of buildings and facilities, and barriers to the physical
relocation to Gif. We will examine some aspects of these matters below,
for they illuminate the directions taken by French genetics in the
1950s, reinforcing the separation into independent research traditions.
For the moment, however, it suffices to note that the establishment of
the laboratories at Gif was a long and involved process.
Ephrussi was the maître à penser for the most important work in
genetics during the formative years of the laboratories, and the
intended director of the Institute. Yet there were serious personal,
administrative, and financial difficulties between Ephrussi and the
directorate of the CNRS. Because of these, the three laboratories were
made autonomous and, for five years, Ephrussi refused to move his
laboratory from Paris to its intended quarters at Gif. In 1954, he also
turned back the monies he had been awarded by the Rockefeller
Foundation (RF) in 1950 to help equip his laboratory -- $54,000 to be
spent over three years, a very major grant in those days. We will
devote considerable attention to this story.
The difficulties surrounding the formation of the proposed Institute
and the administrative arrangements for the three laboratories that
took its place fostered and reinforced a separation among three
distinct programs of research which had originally been closely
intertwined. This separation, coming early in the institutionalization
of genetic research in France, shaped some of the major traditions
still found today. We will explore a few institutional and
administrative aspects of this history, noting the place of genetics in
the larger program of the CNRS. We will also examine the research
programs of the three laboratories, including a brief comparison with
work conducted at the Pasteur. We will conclude with a brief evaluation
of the research performed in the laboratories of the CNRS, 1945-1960.
2. The Place of Genetics in French Biology
Institutionally, genetics was a marginal discipline in France until
at least 1945. (5) There were no laboratories formally devoted to work
in that subject (although, of course, there was important work in
hybridization and breeding), there were no professorships of genetics,
the discipline occupied a minor place in the curriculum of the
institutions of higher learning, and few biologists were publishing
significant genetic research. The major exceptions were Ephrussi,
l'Héritier, and Teissier, all of whom had begun their work in genetics,
without direct French antecedents, in the early or mid thirties.
This situation changed rather dramatically after the war. A number of
scientists who had been active in the resistance or in exile -- e.g.,
the physicists Auger and Joliot-Curie, and the biologists Ephrussi,
Monod, Rapkine, and Teissier -- considered genetics to be a fundamental
biological discipline. Against the opposition of the biologists(6) ,
they supported the formation of the first chair of genetics in France
(at the Sorbonne) and included an Institute for Genetics in the plans
of the CNRS. The 1948 Colloque of the CNRS, "Unités biologiques douées
de continuité génétique," marks an important watershed; it raised to
prominence a distinctive line of work that came to characterize much of
the genetic work in France for the next two decades. (7) Our central
concern is the role of the CNRS labs in the formation of this tradition
of research during the critical postwar period.
INSTITUTIONALIZATION: THE DIFFICULT BIRTH OF THE LABORATORIES AT GIF
By the mid 1930s, it was widely recognized that the French system of
support for scientific research was badly in need of reform.(8) At the
end of the Second World War, the task of rebuilding the infrastructure
of fellowship support, research equipment, and laboratory facilities,
was far more urgent. In short, French science needed meat and potatoes
and (in some disciplines, at least) new leaders in order to foster
significant new research. Among its many charges, the CNRS was supposed
to provide the means needed for support of basic research.(9)
Doris Zallen ( 10) describes the RF's extraordinary support for the
CNRS's efforts to achieve this complex objective during the first
decade after the war. This support, in the form of conference and
equipment grants, was unusually free of conditions. Considerable
preliminary effort went into ensuring the consilience of the CNRS's
objectives with those of the RF and the competence of the CNRS to carry
out the aims in question, but once the RF was satisfied, the grants
were virtually unconditional. The RF's support was intended to enable
the establishment (or reestablishment) of strong and well oriented
working groups in areas particularly ripe for exploitation in France.
From the side of the RF, the effort was to concentrate on "a few good
men," equipped with the personal and scientific skills to lead strong
research teams to international prominence.
Among the sciences, biology, the favorite child of the Division of
Natural Sciences at the RF, was, in certain respects, in particular
disarray in France. This was partly due to a long-overdue generational
change, exacerbated by the loss of two generations of young scientists
in the two world wars, and partly due to the isolation of French
biology from developments abroad. These comments apply especially to
experimental disciplines, with the principal exceptions of physiology
and microbiology. There were many reasons for this relative disarray.
Some were institutional (e.g., the separation of experimental research
from university teaching, combined with the lack of adequate research
facilities outside of the universities),(11) some concerned the
complex, largely private, system of support for research. (12)
Scientific developments during the interwar years also contributed to
the difficulty. While French experimental biology was at a relative
standstill, such fields as biochemistry and genetics were developing
rapidly abroad. By the end of the war French biology was disadvantaged
in many such areas.
Even though French university biologists, especially the naturalists,
were, by and large, not interested in these disciplines,(13) a good
number of prominent physicists and biologists who, because of their
role in the resistance, came to shape the immediate postwar policies of
the CNRS, were greatly excited by the new research and were prepared to
insist that France play a role in their development. Such figures as
Auger, Joliot-Curie, and Teissier sought to make the CNRS into one of
the central vehicles for such a reorientation.
This reorientation particularly suited the purposes of the Natural
Sciences Division of the RF which, under the guidance of Warren Weaver,
sought to foster the application of the tools, techniques, and ways of
thinking of the "hard" (physical) sciences to biology.(14) The program
of the CNRS, especially as it was portrayed to Weaver by Louis Rapkine,
was congenial to the RF.(15) Given this confluence of interests, after
a complex pas de deux, the RF provided the CNRS supplemental funding
for equipment and for conferences aimed at reorienting research, with
special emphasis on experimental research in biology. Although the
funds in question were insufficient to ensure complete rebuilding after
the war, they allowed significant opportunities to establish and shape
serious programs of research.
The Heads of the CNRS Genetics Laboratories
At this point, it will be helpful to provide some information
regarding the three individuals who headed the CNRS laboratories. This
background will prove useful in the narrative that follows.
Philippe l'Héritier and Georges Teissier were both normaliens.
Teissier was seven years l'Héritier's senior; both were trained
primarily in mathematics, turning to zoology during their studies.
Teissier was particularly interested in biometry and in the laws of
growth; with Julian Huxley, he was one of the co-founders of the
mathematical study of allometry. He helped persuade l'Héritier, who
began his career at the Ecole Normale in mathematics, of the importance
of the mathematical study of biology and encouraged him to accept a
Rockefeller fellowship to study genetics in the United States, arranged
by the physiologist André Mayer.(16)
Before returning from the United States, l'Héritier conceived the idea of the population cage,
a device allowing one to follow the evolution of large, genetically
mixed, populations of Drosophila. He persuaded Teissier to join him in
a series of experimental studies using population cages during the
mid-1930s, among other things to determine the how selection would
treat "unfavorable" alleles. They demonstrated that such alleles could
be maintained in the population. Together they explored the mechanisms
(such as heterozygote advantage) involved. (17)
In the course
of this work, they made an accidental discovery: lethal sensitivity to
CO2 in some strains of flies. They found, to their astonishment, that
the CO2 sensitivity was not transmitted by the nucleus, as Mendelians
would expect, but cytoplasmically. They devoted considerable effort to
the analysis of this aberrant phenomenon; it became the main research
interest of the CNRS laboratory directed by l'Héritier after the war.
The two men were unusual in having both serious mathematical training
and training in classical zoology. Both were unusual in conducting
internationally recognized genetic research in France when there was no
institutional base for such research. (Ephrussi was the only other
person to do so in the thirties.) Both remained, to some extent, allied
to classical zoology. Teissier, for example, retained the love for
marine invertebrates that shaped the early phase of his career; (18) he
spent most of his summers at the (marine) Biological Laboratory at
Roscoff, of which he was director from 1945 on. And throughout his
career, he maintained a strong interest in biometry, a discipline to
which he made fundamental contributions. Thus "Génétique évolutive,"
including population genetics, was only one of his many research
interests; it enters into approximately one-fourth of his publications.
And the interest of this topic, for him, was less for the sake of
genetics as such than it was for the application of mathematical
methods and models to evolutionary problems. Partly for this reason,
l'Héritier found it difficult to persuade Teissier to sustain the work
on CO2 sensitivity.
Teissier was a central figure in the resistance. In this connection he
become a close co-worker of Joliot-Curie, who became Director of the
CNRS in 1945. Joliot-Curie appointed Teissier Assistant Director.
Teissier succeeded Joliot-Curie when the latter was appointed
Haut-Commissaire à l'Energie Atomique in 1946.
Throughout his career, Ephrussi was concerned with the regulation and
control of development; (19) his role in genetics was, in many respects
that of a physiological geneticist,
striving to reconcile the rich elaboration of Mendelian
(nuclear-chromosomal) genetics with the evidence indicating that
differentiation and a great variety of developmental phenomena were
controlled by events occurred in the cytoplasm. Trained under Emmanuel
Fauré-Fremiet, Ephrussi was keenly conscious of problems surrounding
the analysis of morphogenesis and development. His early work, though
diverse, exhibits a distinctively embryological focus. (20) In
particular, he sought to identify factors affecting development and to
analyze their contributions to the processes by which the organism
developed out of a fertilized egg. His widely-known work in the
mid-1930s with G. W. Beadle, characterizing the ways in which different
alleles of the genes vermilion and cinnabar affect the
formation of eye pigments in Drosophila, was based on embryological
rather than genetic techniques.(21) Indeed, the aims of this research
were more embryological than genetic: the point was to work backward
from the effects of various alleles on determinate characters to an
elaboration of the pathways by means of which the genes brought about
those effects. The aim was, thus, to discover and characterize the
points at which, and ways in which, developmental pathways were
affected by the activity of the genes.
Thus, although Ephrussi
was thoroughly trained as a geneticist, by the beginning of World War
II he had published only one paper in which he carried out a classic
Mendelian experiment.(22) Until that time, virtually all of his work in
genetics was concerned to elucidate the means by which genes affect
physiological and developmental phenomena, especially pigment
production. Together with Beadle and many other colleagues, he had
shown that certain diffusible substances (which were not yet fully
chemically analyzed) were present in the egg according as certain
alleles were present or absent in the egg. These substances could enter
the egg or the larva by other means -- e.g., they could be deposited in
the egg cytoplasm by the mother or they could be produced by certain
embryonic organs, including implants, of foreign genetic constitution.
They were soluble in hemolymph and could be injected into eggs or
larvae. As long as they were present, they allowed the host organism to
take certain developmental pathways which, in their absence, were
blocked. Ephrussi, noting that these substances acted at a distance,
acted on target organs, and were effective in minute quantities,
thought of them as hormones well into the 1940s. (23)
Unlike l'Héritier (who taught at Clermont during the war) and Teissier
(who, as already indicated, was active in the resistance), Ephrussi
left France during the war; he was one of the scientists brought out
under RF sponsorship. Although he was able to work in the United
States, his circumstances there were not entirely happy. His
collaboration with Beadle was over. The latter had already switched to
microbial and biochemical genetics, working with Tatum on Neurospora.
Beadle and Tatum's biochemical work led them to the one gene - one
enzyme hypothesis and was eventually rewarded with a Nobel Prize. (24)
Ephrussi had no comparable base and was unable to start a comparable
program during this period.
The Role of the RF in Shaping Genetics at the CNRS
The RF was not shy. It determined in its own way which individuals
it would fund, but it did far more. It evaluated the institutions in
which its fellows were placed, sought to help them find better
situations, and so on. (25) The RF required its fellows to return to
(or remain in) their homelands when it deemed the local situation
suitable, for it sought to foster international science even when that
meant some sacrifice of opportunities for an individual. In cases of
great concern, the RF was not above intervening (with some delicacy) in
institutional arrangements. One such case is of critical concern to the
history of genetics at the CNRS. The story is complicated, but also
quite important; in spite of the considerable space devoted to it
below, we can only provide an outline account here.
The key
instance to be explored concerns the award of $54,000 to the Institute
of Genetics of the CNRS. This money was intended to equip Ephrussi's
laboratory, but with the understanding that both Teissier and
l'Héritier would head laboratories with their own programs of research
within the Institute. The issues involved in this matter go in two
principal directions -- first, to the RF's vision of the political
circumstances in which sound science could be conducted and, second, to
the institutional difficulties within the CNRS in setting up the
laboratories at Gif.
# Background
The debate over Lysenkoism was at its height during the late forties
and the early fifties. In France, this debate was particularly acerbic.
(26) Furthermore, the long-standing sympathy for Lamarckism, together
with the recent interest in cytoplasmic inheritance among French
geneticists (including Ephrussi and l'Héritier), (27) suggested on both
historical and technical grounds that French genetics might well be
receptive to Lysenkoist doctrines. Teissier, the Director of the CNRS
from 1946-1950, was affiliated with the Communist Party. Although his
technical writings in genetics fit within the Morgan-Mendel tradition,
he had expressed some sympathy with Lysenkoist views, e.g., in
discussing the Lysenkoist interpretation of his experiments by Marcel
Prenant in La Pensée. For this and other reasons, he was
mistrusted by the officials of the RF as well as various figures in the
French scientific and political establishments. In January, 1950, he
was dismissed as Director of the CNRS by Yvon Delbos, Minister of
Education. The official reason, partly trumped up, concerned a
resolution passed by l'Union Française Universitaire on the last day of
1949, protesting the "conditions scandaleuses" under which some twenty
Polish teachers had been expelled from France as an "odieuse
provocation nuisible à l'amitié séculaire unissant nos deux
peuples."(28) Teissier was a "Président d'Honneur" of the UFU, which
had passed the resolution without his knowledge. Unlike the other
honorary presidents, however, Teissier was one of the founders of that
organization and sympathetic to the resolution. Thus, he refused to
resign as "Président d'Honneur" of the UFU or to disown its resolution.
In response, Delbos fired Teissier as Director of the CNRS. Teissier,
of course, retained his Professorship of Zoology at the Sorbonne; he
also remained in charge of one of the three laboratories of genetics in
the nascent Institute of Genetics at Gif.
# The Funding Decision
Against this background, Weaver wrote a remarkable letter to Ephrussi, dated Feb. 15, 1950, regarding the status of his application for a grant of $54,000 for equipment for the laboratories of the Institute of Genetics. It is worth quoting this letter at length:
"The record of the Rockefeller Foundation makes it hardly necessary to preface my remarks by pointing out that we exclude any questions of race, religion, or politics in judging whether we shall make a requested appropriation. This necessarily implies, however, that such considerations will also be excluded from any scientific research that we support. Otherwise, we should in fact - and against our policy - be indirectly involved in supporting racial, religious, or political interests.
Until recently this position has been one of principle and of
general interest, and assurances have not been required in specific
cases. Indeed, for over three centuries activities in science have been
specially free from the influence of such considerations. No one,
however, can sensibly disregard the fact that genetics and politics
have recently become interrelated, in some quarters, in a most
confusing, a most disappointing, and indeed a most fantastic way.
There
is no necessity to go into detail, for the whole matter has been widely
discussed by those who have special competence. The essence is well
stated by Huxley in the opening paragraph of his NATURE article, Soviet Genetics: The Real Issue (June 18, 1949, page 935),
"There is now a party line in genetics, which means that the basic
scientific principle of the appeal to fact has been overridden by
ideological considerations. A great scientific nation has repudiated
certain basic elements of scientific method, and in so doing, has
repudiated the universal and supranational character of science."
The
Rockefeller Foundation is not prepared to aid research in genetics
anywhere in the world unless it has assurance that this research can
and will be carried out in the true spirit of universal science. There
must be, of course, a complete dedication to the unbiased discovery of
facts - all the facts and not merely certain misleading or partial
facts which conform to a predetermined code. It goes without saying
that we could only be interested in aiding geneticists who are in a
position to affirm their devotion to the concept of properly controlled
experiments, fully described and fully open to the critical judgment of
the scientific world, carefully interpreted by modern quantitative
standards as to reliability and significance.
You
will not, I am sure, think that I am to the slightest degree suggesting
that any special set of scientific ideas are so sacred that they must
not be questioned. On the contrary, we all know that vigilant
skepticism and a steady willingness to shift ideas - or even wholly to
abandon old ideas - is one of the proud characteristics of science. But
true science shifts or abandons ideas on the basis of valid evidence
and logical reasoning, not on the basis of confused and obscure
polemics.
The new Institute of Genetics at Gif is
attached to the CNRS, under the control and management of its officers,
and is not a corporate part of the University of Paris with its
centuries of tradition and its large but well recognized systems of
authority. Furthermore, it is planned that the Institute will have
three main laboratories, each with its own director and with a
considerable staff. This is thus a project which may well reflect
rather more sensitively than is usual the scientific philosophy of its
leaders and the opinion of the men in its own higher levels of
administration.
Thus before we proceed further in our
consideration of your request, we would appreciate knowing whether and
in what form we could be furnished with assurance from the authorities
of the CNRS that the men in this Institute will be free to carry on
their work in the true spirit of modern universal science; and
assurance from the geneticists involved that their scientific work will
be uninfluenced by political considerations or party loyalties." (29)
Terroine's response to Weaver, quoted in n. 3, was hand carried by Ephrussi to New York. Addressing Weaver's concerns, Terroine wrote that a personal exchange of views was necessary. At his request, Ephrussi represented in person the views of the CNRS (which differed from Ephrussi's own)(30) at meetings which took place in the RF's offices in New York from 28 February through 3 March, 1950. From the available correspondence and the diaries of Weaver and G. R. Pomerat (an RF officer present at these meetings) (31) it is clear that Ephrussi was able to persuade the RF officers of a number of things which, taken together, relieved their concerns sufficiently for them to proceed with consideration of the grant. The following matters were established to the satisfaction of the RF officers: The political views of the three directors of the laboratories of the Institute of Genetics, far from being uniformly like those of Teissier, were quite divergent -- l'Héritier, for example, had strongly conservative, even royalist, sympathies. Ephrussi himself had no sympathy with Lysenkoism; indeed, he had spoken out against it privately and had helped persuade Huxley to take the stand supported in Weaver's letter, but had refrained from making public statements for fear that they would exacerbate the political situation, drive Teissier toward a break with Mendelian research (which he had both carried out in his laboratory and supported during his directorship of the CNRS), and make political interference in the affairs of the CNRS more likely. As the current changes in the directorate of the CNRS showed, the administration of the CNRS would not support a Lysenkoist bias as such; indeed, it had no desire to interfere in the scientific work of the Institute of Genetics; the CNRS's safeguards for academic freedom were essentially as strong as those of the University of Paris and the directors of those laboratories were, in the sense of Weaver's letter, honest scientists working "in the spirit of universal science." At the same time, the situation was highly charged and difficult; there could be no guarantee that the work would proceed smoothly and wholly without ideological interference or that Teissier might not be driven to a stronger stand for Lysenkoism for ideological reasons. (32) Indeed, in light of the rapidly changing situation in the CNRS, Ephrussi wrote the following, to Weaver on March 16:
"As I look back on our conversations, I still feel that I presented to you as honestly as possible my opinion concerning the risks of leftist Lyssenkoisim [sic], but I am not quite sure that I emphasized sufficiently the dangers to French genetics coming from the representatives of the still traditional French Lamarkism [sic], more frequently associated with political ultra-conservatism. A few days ago, we learned the results of the first round of the elections of the new C.N.R.S. Committees. Although it is impossible from these to predict the exact composition of the future "Directoire", it is not altogether unlikely that it will be weighted with some very conservative elements. This might recreate some of the difficulties which retarded the development of genetics in France in pre-war days."
Part of the risk, ironically, was that the conservative opposition
to genetics -- opposition that had prevented the founding of a chair of
genetics until after WW II, the very chair that Ephrussi occupied --
was sympathetic to some Lysenkoist doctrines in spite of their
Communist origin. The reason was simple: A Lysenkoist mechanism would
vindicate (Lamarckian) inheritance of acquired characters. This would
justify the long-standing preference in French conservative circles for
Lamarck over Darwin as well as conservative opposition to Morgan's
version of Mendelian genetics, according to which the genes were
splendidly isolated from the influence of the environment by the buffer
of the cytoplasm. (33) Indeed, l'Héritier and Teissier on the one hand,
and (as we will see below) Ephrussi on the other, had independently
discovered distinct and important instances of cytoplasmic inheritance;
these had been used to argue in support of Lysenkoist doctrines.
In spite (or, perhaps, because) of Ephrussi's frank portrayal of risks
in various directions, the balance of considerations seemed clearly
favorable to the RF officers; on March 3, the last day of Ephrussi's
trip, Weaver told him (as Pomerat put it in his diary for that day),
"we will lay E's request for an appropriation of $54,000 in the lap of
the gods - that is, we are prepared to present it at the April Board
Meeting [with no further reference to the issues raised in Weaver's
letter of February 15]." The award was officially approved on 5 April,
with the monies to be available to the CNRS as of 1 May, 1950, to be
expended over the next three years, primarily for equipment unavailable
in France.
# Institutional Difficulties; the Return of the Grant
After the great effort expended by Ephrussi and the CNRS and the
elaborate investigation by the RF to ensure that the grant would be
used appropriately, it is surprising to learn that the monies were
never expended -- indeed, that the grant was ultimately rescinded
because the Institute for Genetics never took the form intended under
the award. The story is a sad mixture of institutional constraints,
obstacles at the level of the Directoire, and personal pettiness. It is
all the sadder because the laboratory buildings, meant to house about
eighty research workers for the Institute, were largely completed by
1951.
In brief, shortly after the grant had been approved,
Terroine lost his positions on the Directorate and on the Committee for
Foreign Affairs. The Acting Director, J. Pérès, was replaced by a new
director, G. Dupouy. Dupouy and many members of the new Directoire had
not been parties to the planning of the Institute of Genetics which,
for various reasons, they considered an extraordinarily large
commitment in one direction, threatening distortion of the CNRS budget.
(34) Thus, a number of the promises that Ephrussi thought he had
obtained regarding the working conditions for the Institute at Gif, to
be described shortly, were not met.
The documents available to us do not allow a balanced evaluation of the
situation; nonetheless, it is quite clear that relations between
Ephrussi and Dupouy broke down badly. In consequence, both men
stubbornly refused to seek out compromises that might ameliorate the
situation. The result was an impasse lasting several years; by the
summer of 1951, by fiat of the Director, the planned Institute had been
separated into three independent laboratories, with separate budgets.
(35) From 1951 to 1956, l'Héritier and Teissier occupied facilities at
Gif, but with relatively minimal programs and in nearly complete
isolation, while Ephrussi remained at the Institut de Biologie
physico-chimique with a far more active program of research. (36) In
practice, his laboratory at that facility (which received considerable
support from the CNRS) was both a teaching laboratory of the Sorbonne
and the Laboratoire de Génétique physiologique of the CNRS, one arm of
the planned Institut de Génétique.
The principal conditions that Ephrussi claimed to be necessary for a
successful transfer of his laboratory to Gif were the following:
completion of some of the additional institutes (or suitable
alternatives) planned for that site so that the staff at Gif would not
work in physical and intellectual isolation; building of housing
facilities for a substantial portion of the staff so that they would
not have to commute from Paris; and full control of the grant monies
awarded by the Rockefeller for support of his own program of research.
Only the last condition seemed realizable by the fall of 1951, and
since the monies were intended to equip the new facility, to which
Ephrussi was unwilling to move in the circumstances, he decided to
postpone any expenditures from the grant until the situation had
improved.(37)
But it did not improve during the life of the grant. In spite of
efforts by Champetier, l'Héritier, Pomerat, and others to mediate the
differences between Dupouy and Ephrussi, as of February, 1953, as the
expiration date for the grant (30 April, 1953) approached, the
situation was basically unchanged. On 12 February, Ephrussi wrote
Dupouy to warn him of the impending end of the grant, with a full
account of the conditions of the award, asking, in effect, whether
there was any way to resolve the matter favorably.(38) Having received
no reply, Ephrussi wrote the RF on 24 February, enclosing a copy of his
letter to Dupouy, and indicating his desire not to seek an extension of
the grant. In spite of a complex series of maneuvers in which Dupouy
attempted to obtain an extension of the grant that would divide the
funds among Ephrussi, l'Héritier, and Teissier, and a year's
postponement by the RF to allow exploration of alternatives, the grant
expired, with revocation of the RF award at the end of April, 1954.
Establishment at Gif
In 1951, Teissier and l'Héritier established their laboratories at
Gif. Teissier, however, occupied the chair of Zoology at the Sorbonne,
directed the marine biological station at Roscoff and the "Laboratoire
de Biométrie Animale" at the Ecole Pratique des Hautes Etudes. Genetics
was only one (and not foremost) among his many interests.(39) The
development of a research program at Gif was low on his priority list;
it appears that he was seldom there more than once every two weeks and
that his laboratory there was relatively inactive. (40) L'Héritier's
group was more active, pursuing the characterization of the cytoplasmic
factor (later identified as the sigma virus) that caused CO2
sensitivity in Drosophila. Still, he and his group worked in relative
isolation, did not maintain strong contact with the Ephrussi's group or
the work in the Pasteur, and did not enjoy the sort of lively
interchange with American and British workers that characterized the
laboratories of Ephrussi, Lwoff, and Monod.
In 1956, after the
formal expiration of the RF grant to the Institute of Genetics in 1954,
Ephrussi was awarded another grant of $61,000 by the RF to support his
research program in physiological genetics. In the interim, Teissier
had undergone major surgery and, in consequence, reduced his personal
activity at Gif and l'Héritier (who would switch from teaching genetics
to teaching general biology at Orsay in 1959) was feeling increasingly
isolated at Gif. Partly in response to RF pressure(41) and partly in
response to new CNRS funding that enabled the founding of new
institutes of hydrobiology, plant physiology, and photosynthesis, a
rapprochement was effected between Ephrussi and Dupouy. The result was
that Ephrussi moved his laboratory to Gif in phases (1956 - 1958) and
that, after complex negotiations, the RF grant was formally funded and
administered under the auspices of the CNRS.
The institutional background to this transformation cannot be pursued
on this occasion. Indeed, to a first approximation, the move of
Ephrussi's laboratory to Gif, the separation in the Pasteur of Monod's
lab from that of Lwoff (1953-5), Monod's acceptance of a chair of
biochemistry at the University of Paris in 1959, and the formation of
the teaching and research laboratories at Orsay for the troisième cycle
in 1960 mark the transition to a more stable long-term configuration
for fundamental genetic research in France. Instead of pursuing these
institutional matters further, we turn to a partial account and
assessment of the scientific work carried out in this period.
CONTRIBUTIONS TO GENETICS
Our argument has shown that Ephrussi was the leading figure in the
founding of the laboratories at Gif. In this section, we will confirm,
briefly, our claim that his program of research came to occupy a
central place in the development of genetics in France. To do so, we
will characterize that program, compare it with the research of
Teissier and l'Héritier and make some remarks about its relationship to
the research carried out at the Institut Pasteur. We will conclude by
locating the work of the laboratories of the CNRS in the context of
international developments in genetics.
The Research
In the mid 1930s, l'Héritier and Teissier had developed a serious
experimental program in population genetics. They demonstrated a number
of important phenomena, including the maintenance of equilibria between
species, the evolution of sex ratios, and the maintenance of
disadvantageous alleles in a population. They also discovered a wholly
unexpected phenomenon, the cytoplasmic inheritance of CO2 sensitivity
which, because it would spread to all the offspring of all affected
mothers, was inherited in a distinctive and easily recognized manner.
Their collaboration ceased in 1938 when l'Héritier departed for
Strasbourg. They divided their materials, l'Héritier taking the CO2
sensitive flies, Teissier the population cages.
By 1951, when
each of these men had his own laboratory at Gif, they were no longer
close and performed no collaborative work. L'Héritier's laboratory was
called the lab of formal genetics. In practice it concentrated on the
analysis of the sigma viroid or virus, which proved to be the cause of
CO2 sensitivity. (42) To match its mission, the lab was renamed in the
mid-1950s; it became the Laboratory of Viral Genetics. (Later, with the
discovery that the virus was present in about 20% of natural
populations globally, l'Héritier's group also pursued the population
genetics of the sigma virus.)
Teissier's lab was devoted to population genetics, but was relatively
inactive, as indicated above. In 1957-8, Teissier was succeeded by
Boucquet, who directed the laboratory until 1977. Thus, although
Teissier founded an important tradition in population genetics,(43) he
no longer played a central role in the shaping of French genetics by
the mid fifties.
In the 1930s, Ephrussi and Beadle had demonstrated convincingly that
nuclear genes at least sometimes consisted of, produced, or controlled
the production of diffusible substances that altered the developmental
pathway followed by an organism. Their work also demonstrated the need
to carry out a biochemical analysis of the substances in question and
to find a system simpler than Drosophila with which to pursue the mixed
genetic and biochemical analyses required.
Like Beadle, Ephrussi self-consciously sought a microorganism suitable
for this purpose. Unlike Beadle,(44) Ephrussi's work was largely halted
by WW II. Even though he had tentatively chosen yeast as an appropriate
organism in the early forties, he was unable to start to work with it
until after his return to France after the war. Initially allied to
Beadle's Neurospora program, Ephrussi's program is of interest largely
for the surprises that it yielded, for the ways in which, following
behind Beadle's work, it came to point in an entirely different
direction. (45)
Those surprises, and the way in which Ephrussi and his colleagues
elaborated and exploited them, are, we shall argue, characteristic of
the programs of research that were central in French genetics in the
fifties, programs that would have been much more difficult to execute
starting from a mainstream Mendelian orientation. An exploration of
this research, its relationship to the work in l'Héritier's laboratory
and to some of the work in the Pasteur, and its contrast with related
programs of research in the United States and England thus provides a
useful characterization of the special contributions of the genetics
laboratories of the CNRS during the first fifteen years after the war.
In this context, it is particularly interesting to examine the role of
issues concerning the relationship between nucleus and cytoplasm. In
the late thirties, there was nearly total estrangement between
traditional Mendelians and students of development (embryologists,
physiological geneticists, and some workers in such fields as
ciliatology and protozoology concerned with developmental processes).
Using exaggerated stereotypes, traditional Mendelians believed that the
nucleus contained (virtually) all of the factors that determined the
ontogeny of the organism, while embryologists saw ontogeny as either
controlled by the cytoplasm or as involving some sort of complex
interaction between nuclear and cytoplasmic systems of control.(46) To
think like an embryologist on this issue was to think of intermediary
pathways, of the determination of cellular fates by such factors as
polarities within the (egg) cell, chemical gradients, relationships to
neighboring cells, and so on. To think like a (traditional Mendelian)
geneticist was to think that no matter how complex these intermediate
steps might be, the ultimate determination of cell fates, indeed the
very Bauplan of the organism was, somehow, determined by the (nuclear)
genes. And, for important practical reasons, researchers with these
diverse interests and points of view usually worked with different
organisms, so that there was no readily accessible experimental route
for resolving the differences between them. (47)
Immediately after the war, Ephrussi, l'Héritier, and Teissier were the
only figures active in France whose work in genetics was
internationally recognized. These men (Teissier included!) were all
good Mendelians, but Mendelian preoccupations had not been at the
center of their early biological training. There was no long-standing
Mendelian research tradition, (48) indeed no tradition of foundational
genetic experimentation, in France. Thus, in contrast to such countries
as England and the United States, there was no counterpoise to
programmatic shifts that, starting from a Mendelian base, placed
central emphasis on nucleo-cytoplasmic relations or on cytoplasmic
determinants of heredity. (49) Indeed, against the international
background, the need to find a distinctive niche not already occupied
by advantaged elites may well have fostered the attractiveness of such
programs. And the prior French interests in general biology, microbial
physiology, and development generally would have supported precisely
such an orientation.
It is not surprising that l'Héritier's and Teissier's discovery of the
cytoplasmic transmission of CO2 sensitivity in Drosophila astonished
their (largely foreign) Mendelian friends but more-or-less fit the
expectations of the serious biological critics of Mendelism in
France.(50) L'Héritier's pursuit of that problem after the war,
inevitably, landed him in issues regarding the cytoplasmic transmission
of hereditary factors and in the interplay of genetic and cytoplasmic
factors in the control of viral and host genes.
After the war, the climate in France (and in some interstices
internationally) encouraged such departures from a narrow Mendelian
orientation. This is the special interest of Ephrussi: during this
period, his most pressing concerns centered on nucleo-cytoplasmic
relations.(51) These issues also came to be the focus of the best-known
genetic research at the Pasteur. It is the place of these problems to
which we turn in closing this paper.
Ephrussi's embryological concerns and his interest in relating genetics
to development surely predisposed him to pay close attention to
phenomena bearing on nucleo-cytoplasmic relations. Shortly after
starting to work with yeast, he made the fortuitous discovery that
acriflavin (a chemical mutagen) systematically caused yeast (which can
live either anaerobically or in the presence of oxygen) to lose the
ability to respire -- and that the loss was usually inherited by 100%
of the progeny of the altered yeast. In a series of fundamental
studies, Ephrussi and his co-workers (including, especially, Slonimski)
(52) demonstrated that the phenomenon was caused either by the loss of
a great number of cytoplasmic particles or by their loss of the ability
to manufacture the soluble enzymes required for respiration. In a long
and exhaustive series of genetic studies, Ephrussi proved that the
phenomenon was not caused by nuclear genes (though certain nuclear
genes were required to maintain respiration), while Slonimski
characterized the complex biochemistry of the enzymes lost under a
variety of genetic conditions.
These studies, though they yielded extremely complex results, produced
some clear conclusions by the mid-fifties. Respiration required the
manufacture of enzymes by both the nucleus and the extra-nuclear
particles, tentatively (but correctly) identified as mitochondria. The
inheritance of a sufficient number of extra-nuclear particles competent
to manufacture the necessary enzymes was absolutely required for
respiration. Loss of the ability to manufacture those enzymes was
irreversible and almost certainly involved the simultaneous loss of
several genes or a complex of genes carried by the cytoplasmic
particles. These particles were classed as "unités douées de continuité
génétique." (53)
Several distinct genes were involved since several enzymes could be
distinguished and, occasionally, separately lost. Under specific
conditions, cells could be produced with just enough functioning
cytoplasmic particles to yield one respiratory competent and one
respiratory incompetent cell on division. In such cases the respiratory
incompetent cells never yielded respiratory competent progeny, whereas,
depending on culture conditions, the respiratory competent ones would
do so or not in a manner suggesting that the key issue was the number
of "healthy" cytoplasmic particles transmitted to the daughter cells.
Biochemical (and, ultimately, genetic) analyses of the differences
between the particles yielding respiratory competent cells and those
yielding respiratory incompetent cells were executed, eventually
serving as a foundation for the now-flourishing field of mitochondrial
genetics.(54)
This line of research, in which Ephrussi was directly involved, was
only one of several pursued in his laboratory. His successful 1956 RF
grant application seeks support for the following research programs:
his own analysis of the genetics of the cytoplasmic particles and their
relation to mitochondria; three distinct programs (Slonimski's and two
others) investigating various biochemical mechanisms and gene-enzyme
relationships controlling the synthesis of a great variety of yeast
enzymes; that of his wife, H. Ephrussi-Taylor, analyzing the mechanisms
by which DNA transformed bacteria and the physical and chemical
structure of bacterial DNA; that of G. Rizet on two
cytoplasmically-inherited phenomena in Podospora ("barrage" and
"senescence"); that of M. Gans and others on the genetics of
basidiomycetes; and that of J.-M. Goux on the genetics of chlorophyll
mutants in Chlamydomonas.(55) These programs were carried out in
collaboration with a series of distinguished guest scientists; those
for 1956-7 included four Americans, two Poles, and one French
scientist.(56) By 1960, some of these research programs had been placed
elsewhere; the three principal programs in the lab were Ephrussi's on
nuclear genes affecting mitochondrial synthesis of respiratory enzymes,
H. Ephrussi-Taylor's on DNA recombination as a mechanism of bacterial
transformation, and Slonimski's on a wide variety of biochemical and
genetic aspects of enzyme synthesis and regulation in yeast.
Some Comparisons
We have suggested that the study of nucleo-cytoplasmic relations was
a distinctive strength of French genetics at the time of its rapid
assumption of international prominence during the late forties and
fifties.(57) This was a formative period for modern biochemistry
(especially, biochemical kinetics), biochemical cytology (cf. J.
Brachet and T. Caspersson), the study of gene expression and regulation
(to use anachronistic terms), and what would eventually come to be
known as molecular biology (really molecular genetics).
We
believe that close attention to the French contributions, employing
background of the sorts examined here and in our other relevant
writings, would improve the historiography of the transformations
involved. For it is clear that the stream of visitors to the labs of
Ephrussi, Lwoff, and Monod, and others took back with them something
more than a panoply of techniques, something more than the fruits of a
year of intensive work away from home. They took away a characteristic
set of questions and a fusion of physiological, biochemical, and
genetic approaches to those questions, well represented in the work of
Ephrussi, Jacob, Lwoff, Monod, Wollman and many others on the French
scene. In this concluding section, we will provide a thumbnail sketch
of the distinctive features in question.
The French work of the early fifties is striking for its concentration
on nucleo-cytoplasmic relations and (in Monod's, Slonimski's, and
Wollman's work, but not in Ephrussi's) its use of biochemical kinetics
as a means of getting at the control of cellular functions. Also
striking is the use of a mix of skeptically controlled speculation and
severe experimental test. The point is illustrated by the fact that, in
the face of various alternative hypotheses that Ephrussi and his
colleagues cooked up, it took him some seven years to accept the claim
that mitochondria are the cytoplasmic particles controlling the
manufacture of respiratory enzymes. This example also illustrates the
typical distrust of morphological findings in the absence of
confirmatory genetic, physiological and biochemical results.
A nice marker for the distinctive approach we are seeking to
characterize is the name for the informal city-wide seminars, held at
the Institut Rothschild on the rue Curie until Ephrussi moved out to
Gif. These were sessions at which international visitors joined many
Pasteurians, workers from the CNRS labs, and some others to report on
their findings. The name employed was the "Club de physiologie
cellulaire."(58) This, we believe, nicely defines the distinctive
approach conveyed to foreign visitors, an approach rare elsewhere in
the world. (59)
The long-standing French traditions exploring the control of cellular
function and the correlated skepticism regarding simple (e.g.,
Mendelian) structural answers to major questions regarding the control
of cellular function, differentiation, and (thus!) heredity, were now
able to find the right tools with which to tackle the connections
between cellular structures (including, ultimately, molecules) and the
entities and processes responsible for the regulation and control of
cellular properties, the manufacture of enzymes, and so on. The
uniqueness of the French school is marked by its ability to draw on
this background, while working with full command of genetic techniques
as practiced elsewhere.
It remains only to say a few more words about the contributions of the
CNRS labs in particular to the flowering of French genetics. We are
keenly aware that we have not addressed important institutional
questions regarding the relationship of the CNRS labs to the
universities and to the Institut Pasteur. The sources presently
available to us do not allow us to do these topics justice. In the
period up to 1960, as far as genetics was concerned the relationship
between the University of Paris and the CNRS labs was symbiotic; the
head of each laboratory had a professorship and was able to use it to
recruit research students to work in his or the others' laboratories.
The content of the Certificat
in genetics was, more-or-less, in their control. Much of the same
equipment was used in the programs of teaching and research. With the
revision of the troisième cycle in 1960, laboratory equipment that had
been used both for teaching and research at Gif had to be sent to Orsay
and replaced at Gif; this was one of the bases of Ephrussi's
application for Rockefeller funding in 1960.(60) But beyond these small
points, we can presently contribute little to this important area of
investigation. We hope to pursue the topic further in the near future.
As our argument has shown, Teissier did not play a central role in the
shaping of the new discipline of the fifties (except, it should be
added, for his considerable influence on the population genetics
tradition that we will not explore further here).
L'Héritier's research focussed on a particular and important problem
concerning the non-Mendelian inheritance of CO2 sensitivity but,
although it landed him in the thick of issues concerning
nucleo-cytoplasmic relations, he did not play a central role in the
development of the research tradition in that area. He did not attend
the sessions of the Club de physiologie cellulaire regularly, (61) he
was somewhat physically isolated at Gif, and, because his system
required the intermediation of the Drosophila life cycle, he did not
develop crucial techniques for working with microorganisms in vitro (a
virtual necessity if one were to make rapid progress on this topic). He
did, however, recruit students who pursued genetic careers under the
auspices of the CNRS and the universities, many of whom would appear in
important roles in a full history of the material covered all too
briefly here.
Because his central study involved a virus attacking a eucaryote, it
was extremely difficult to separate issues concerning infection from
those concerning heredity and to carry out a detailed mechanistic
analysis. In short, l'Héritier was more a consumer than a producer of
the foundational theorizing for which the French genetics of the period
is known and his experimental work, though carefully followed and of
great interest, was not central to the theoretical innovations in
question.(62)
This leaves, as our closing question, the relationship between
Ephrussi's work and that at the Pasteur. There are many questions here
with which we would like to cope, but which we cannot answer for lack
of information. We speculate that there had been some sort of
flirtation between Ephrussi and the Pasteur before the war (an idea
advanced by some of our informants in interviews), but that nothing had
come of it, leaving Ephrussi somewhat embittered. It is quite clear
that Ephrussi was an unusually hard man to work for; Slonimski was
known as "le mutant résistant" because he managed to work at close
quarters with Ephrussi for years, and Monod, notoriously, would not
work under him.(63)
In terms of the content of Ephrussi's research, his central focus on
the role of nucleo-cytoplasmic relations in genetics seems to precede
the parallel focus in the work of Jacob, Lwoff, Monod, and Wollman.(64)
Perhaps precisely because Ephrussi was far weaker in biochemistry than
these other figures (indeed, he was thoroughly dependent on Slonimski
to carry out the required biochemical analyses), he concentrated on
genetic aspects of the problems of this domain. What is clear is that
in the late forties he, above all others, saw the need to place
genetics at the center of the agenda, that he directed the first
full-fledged program in France employing genetic techniques in the
investigation of nucleo-cytoplasmic relations in microorganisms,(65)
and that, in those early days, his lab was as major a bridge between
American and French research programs on the genetics of microorganisms
as was Lwoff's in the Pasteur. For these reasons, given also the first
class work in his laboratory and the skeptical power with which he
tested his hypotheses (exceeded, later, in that respect only by Monod),
it is, perhaps no exaggeration to say that he was the maître à penser who introduced modern genetics into France.
Thus, in spite of all of the institutional difficulties that the CNRS
encountered in establishing its three genetic laboratories at Gif, the
programs of those labs are of comparable historical importance with
those of the Pasteur. They exercised a strong influence on the
directions taken by genetics after WW II in France. They deserve a
comparable share of the glory and the misery that entails.
Notes
(1) We wish to acknowledge, with deep gratitude, the help of Doris Zallen, our collaborator in this work. Her assistance in obtaining materials from the Rockefeller Archive Center and her advice were of critical value to us. We are also grateful to the Rockefeller Archive Center, the Archive of the Institut Pasteur, and the Laboratoire de Génétique moléculaire at Gif-sur-Yvette, and their extremely helpful staffs for supplying various documents, to Michel Veuille for documents and advice, and to Georges Cohen, Philippe l'Héritier, André Lwoff, David Perrin, Piotr Slonimski, Mary Weiss, Elie Wollman and various others for submitting to interviews and encouraging the work of which this paper forms a part. Portions of this research were funded by grants from the (U.S.) National Endowment for the Humanities and National Science Foundation and by Virginia Polytechnic Institute and State University. The help of these people and institutions, and others too numerous to list, have made this project possible.
(2) Voir aussi l'article princeps : Burian (R.), Gayon (J.), and Zallen (D.), "The Singular Fate of Genetics in the History of French Biology, 1900-1940," J. Hist Biol. 21 (1988): 357-402; Burian, "French Contributions to the Research Tools of Molecular Genetics, 1945-1960," in Bénichou (C.) and Fischer (J.-L.) (eds.), Histoire de la Génétique, Paris, Vrin, 1989?; Burian and Gayon, "A Bernardian Evolutionist at the Pasteur? Ciliate Morphology and Physiological Evolution in the work of André Lwoff, 1921-1950," scheduled for Morange (M.), ed., proceedings of a symposium for the 100th Anniversary of the Institut Pasteur; and Zallen, "The Rockefeller Foundation and French Research," forthcoming in the Cahiers pour l'histoire du CNRS.
(3) Of the $250,000 granted by the Rockefeller Foundation (RF) to the CNRS for equipment in 1946, described by Zallen, "Rockefeller Foundation" (n. 2), $18,000 was allocated to the Institute for Genetics, directed by Boris Ephrussi. In late February, 1950, in light of difficulties (discussed below) with Ephrussi's application for an RF grant to that Institute, E. Terroine (Chair of the CNRS Committee on Foreign Affairs) described the CNRS plans for the Institute of Genetics in a letter to Warren Weaver of the RF. The Institute was part of a larger structure; the CNRS planed to build "a veritable city of institutes devoted to research in the field of biological sciences and closely related disciplines." The CNRS would particularly "favor those disciplines which, for some reason or another, have lagged in their development in [France]." Terroine listed two further institutes specifically: "an institute of embryology, directed by Prof. Etienne Wolff and an Institute for research on large molecules, directed by Professor Sadron." (Terroine to Weaver, internal translation by the RF, undated [Fev., 1950]. Rockefeller Foundation Archives [hereafter: RFA]. Arch 2. Series 500D. Box R1050. Rockefeller Archive Center. (Unprocessed material.)
(4) They were called, respectively, the Laboratoire de Génétique physiologique, the Laboratoire de Génétique formelle [later: des Virus]), and the Laboratoire de Génétique évolutive et de Biométrie. All three originally belonged to the institute under Ephrussi's direction, but they became budgetarily independent entities in 1951, when l'Héritier and Teissier occupied buildings in Gif. Until that date, Ephrussi's publications listed his address as "Institut de Génétique du CNRS et Institut de Biologie physico-chimique." In 1951, he dropped the former title, sometimes replacing it with "Laboratoire de Génétique physiologique;" he kept his laboratory in the facilities of the Institut Rothschild (Institut de Biologie physico-chimique), rue Pierre Curie, Paris, until he moved to Gif in stages during 1956-1959.
(5) Cf., Burian, Gayon, Zallen, "Singular Fate," (n. 2) and Buican, (D.), Histoire de la Génétique et de l'évolutionnisme en France, Paris, PUF, 1984. Buican's book must be used with great caution; in spite of its documentary richness, it is filled with partisan distortions.
(6) Especially naturalists. We cannot pursue this important story here. Our claim is based on interviews with P. l'Héritier, P. Slonimski, and others. We will make our interviews available to interested parties on request.
(7) Cf. Burian, "French Contributions," (n. 2). A characteristic text is the following, from Monod's first major review article in English: "The essential reasons for [interest in enzymatic adaptation], which is especially manifest among geneticists and embryologists, are obvious. The widest gap, still to be filled, between two fields of research in biology, is probably the one between genetics and embryology. It is the repeatedly stated -- and thus far unresolved problem -- of understanding how cells with identical genomes may become differentiated, that of acquiring the property of manufacturing molecules with new, or at least, different specific patterns or configurations." Monod (J.), "The Phenomenon of Enzymatic Adaptation" in Growth Symp. 11 (1947): 223-289, p. 224.
(8) Cf., e.g, Picard (J.-F.)and Pradoura (E.) "La longue marche vers le CNRS (1901-1945)" in Cahiers pour l'histoire du CNRS (1988-1),
pp. 7-40.
(9) Cf. Prost (A.), "Les origines de la politique de la recherche en France", ibid , pp. 41-62, for discussion of limitations on the missions of the CNRS. Although the law of 2 Nov., 1945, Art. 2, charged the CNRS "d'assurer la coordination des recherches poursuivies par les services publics, l'industrie et les particuliers en établissant une liaison entre les organismes et les personnes qui se consacrent à des recherches" (quoted by Prost, p. 43), organizations conducting research were distributed among many ministries and industries in the private sector; they thus remained beyond the effective reach of the CNRS.
(10) "Rockefeller Foundation", (n. 2).
(11) See Burian, Gayon, and Zallen, "Singular Fate" (n. 2). But cf. Paul (H.), From Knowledge to Power, the Rise of the Scientific Empire in France, 1860-1939, Cambridge, Cambridge University Press, 1985, for an argument that the lack of support has often been exaggerated. Further study of the strong extra-university traditions of research is desirable in this connection.
(12) See Picard and Pradoura (n. 8).
(13) This was true for the appointments of Ephrussi and l'Héritier. Slonimski and l'Héritier, in interviews, allege that the pattern was quite general. L'Héritier claims that many physiologists favored the incorporation of genetics into programs of research and teaching against the wishes of naturalists and other biologists.
(14) Cf. Weaver (W.), Scene of Change: A Lifetime in American Science , New York, Charles Scribner's Sons, 1970, and the literature cited in Zallen "Rockefeller Foundation (n. 2.) For additional literature and references, see Kohler, (R.), "Warren Weaver and the Rockefeller Foundation Program in Molecular Biology: A Case Study in the Management of Science," in Reingold (N.), ed., The Sciences in American Context: New Perspectives, Washington, 1980, pp. 249-293, Abir-Am, (P.), "The Discourse of Physical Power and Biological Knowledge in the 1930s: A Reappraisal of the Rockefeller Foundation's 'Policy' in Molecular Biology," Social Studies of Science 12 (1982): 341-382, and the replies to the latter article (with the author's response) in ibid, 14 (1984): 225-263.
(15) Zallen, "Rockfeller Foundation" (n.2)
(16) Cf. Picard (J.-F.) and Raguenel (C.) "Entretien avec Philippe l'Héritier, Ambert le 3.07.86", kindly supplied by M. Picard, or R. Burian, "Interview with Philippe l'Héritier, Ambert 22 Nov., 1984." Cf. also l'Héritier (P.) "Souvenirs d'un généticien", Revue de Synthèse , 102, (1981) : 331-350 and the account in Gayon (J.), La théorie de la sélection : Darwin et l'après-Darwin, Thèse de Doctorat, Université de Paris I, July, 1989, pp. 703-710.
(17) E.g., l'Héritier and Teissier, "Une expérience de sélection naturelle. Courbe d'élimination du gène 'bar' dans une population de Drosophiles en équilibre", C.R. Soc. Biol. 117 (1934): 1049-1051, "Elimination des formes mutantes dans les populations de Drosophiles. I. Cas des Drosophiles 'bar'", C.R. So. Biol. 124 (1937): 882-884, and "L'élimination des formes mutantes dans les populations de Drosophiles", C.R. Acad. Sci. 205 (1937): 1099-1101.
(18) See the Titres et travaux scientifiques de Georges Teissier, Paris, Prieur et Robin, 1958, and the Supplément aux titres et travaux scientifiques de Georges Teissier, Paris, Robin et Mareuge, 1962.
(19) Cf. Burian (R.), "Boris Ephrussi and the Foundations of Developmental Genetics," scheduled for Gilbert (S.), ed., Developmental Biology, New York, Plenum, 1990. The best account of Ephrussi's work to date is in Sapp (J.), Beyond the Gene: Cytoplasmic Inheritance and the Struggle for Authority in Genetics, New York, Oxford University Press, 1987. This book offers a useful comparative analysis of the competition between programs of research treating the nucleus as the dominant locus of genetic control and those locating control of development and differentiation in the cytoplasm.
(20) A small sample of Ephrussi's early publications includes: "Sur le chondriome ovarien des Drosophila melanogaster et simulans," C. R. Soc. Biol. 94 (1925): 778-780; "Sur la transformation de fibroblastes en microphages," C. R. Soc. Biol. 105 (1930): 697-699; "Sur les facteurs limitant l'accroissement des cultures des tissus in vitro. Signification de l'energie residuelle, C. R. Acad. Sci.192 (1931): 1763-1765; Croissance et regeneration dans le culture des tissus, Paris, Masson, 1932; Contribution a l'analyse des premier stades du developpement de l'oeuf: Action de la temperature , Paris, Imprimerie de l'Academie, 1932; "Sur le facteur lethal des Souris brachyures," C. R. Acad. Sci. 197 (1933): 96-98; Génétique physiologique, Paris, Hermann, 1939.
(21) Burian, Gayon, Zallen, "Singular Fate" (n. 2), pp. 389-400.
(22) Ephrussi, (B.), "The Absence of Autonomy in the Development of the Effects of Certain Deficiencies in Drosophila melanogaster," Proc. Natl. Acad. Sci., 20 (1934): 420-422.
(23) Cf. Burian, Gayon, Zallen, "Singular Fate", pp. 396 ff. for an account and references.
(24) Cf. Kay (L.), "Selling Pure Science in Wartime: The Biochemical Genetics of G. W. Beadle," J. Hist. Biol. 22 (1989): 73-101.
(25) Examples are readily found by examining the diaries of the RF's officers, who made extended tours to examine the situations of the RF fellows, maintain a large network of scientific contacts, locate new and promising individuals and lines of work, etc. The relevant diaries are available at the RFA, RG 12.1; they have provided invaluable assistance to many scholarly projects.
(26) Cf. esp. chapter 1 of Lecourt (D.), Lyssenko : Histoire réelle d'une 'science prolétarienne', Paris, Maspero, 1976, pp. 23-44.
(27) Cf. Burian, "French Contributions," (n. 2).
(28) The expulsions served to retaliate for various Polish expulsions, including that of a member of the French ambassadrial staff, on grounds of espionage. See "L'affaire Georges Teissier", a 23 page pamphlet published by the Union Française Universitaire in 1950. Included is an appendix (pp.16-22) containing relevant documents. Because the source is partisan, we have also reviewed the newspaper report in Le Monde and Combat from 13-19 January, 1950. The descriptions provided above are supported by all of these documents. The two other honorary presidents of the UFU, Sarailh, Rector of the University of Paris, and Donzelot, Director of Higher Education, both retained their positions; they stated publicly that they did not approve of the position of the UFU. We are grateful to Michel Veuille for having supplied us with the UFU pamphlet and photocopies of the newspaper reports.
(29) Weaver to Ephrussi, February 15, 1950, RFA. Arch 2. Series 500D. Box R1050. (Unprocessed material.)
(30) Terroine, letter to Weaver (n. 3).
(31) See Weaver to Terroine, March 6, 1950, Terroine to Weaver, March 10 and April 18, 1950, Weaver to Ephrussi, March 15, 1950, and Ephrussi to Weaver, March 16, 1950, all in RFA. Arch 2. Series 500D. Box R1050. (Unprocessed material.) See also, crucially, the officer's diaries of W. Weaver for Feb. 28, 1950 and G. R. Pomerat for Feb. 28, Mar. 1 and 2, 1950. RFA. RG 12.1.
(32) Point 9 of Pomerat's long summary of the conversations of Feb. 28-Mar. 2 in his diary includes the following : "E. explains that until now Teissier has continued to publish scientific papers that report research in modern Western aspects of genetics along Mendelian-Morgan lines... E. emphasizes, however, that he cannot guarantee in any way that T. will not produce scientific studies having a Lysenko bias or that he has not made and will not make popular talks or write popular articles which have a Lysenko bias." Ibid. L'Héritier (in the interview with Picard and Raguenel (n.16, p.11), claims that "l'affaire Lyssenko a mis Teissier dans l'embarras à cause de ses opinions politiques. Mais il n'a jamais cru aux thèses Lyssenkistes."
(33) L'Héritier interviews with Burian and Picard and Raguenel (n. 16). In these interviews, l'Héritier suggests that Catholic moral training may be partly responsible for this conservative tendency -- for only thus could the sins of the fathers be visited on their sons. He believes this to be a major reason for the relatively slow acceptance of Mendelism in Catholic countries.
(34) Cf. Pomerat, Officer's Diary, 5 June, 1953. RFA. RG 12.1.
(35) Weaver's diary for June 18, 1951, (RFA. RG 12.1) describes how Dupouy obtained, without Ephrussi's knowledge, first Teissier's and then l'Héritier's consent to administrative and budgetary autonomy from Ephrussi while occupying the new facilities of Gif. Ephrussi's letter to Weaver, August 13, 1951 (RFA. Arch 2. Series 500D. Box R1050. Unprocessed material), also describes the way in which he learned, without advance knowledge, that he was "Monsieur le Directeur du Département de Génétique physiologique" instead of "de l'Institut de Génétique" and his unsuccessful attempts to clarify the situation with Dupouy.
(36) In his interview with Picard and Raguenel (n. 16), l'Héritier indicates that he commuted between Gif and the rue Curie as early as 1948, when a gardener's shed at Gif was made available to the Institute of Genetics. He also points out (p. 7) that Teissier's Calvinist view that each doctoral student should work wholly unassisted so that (s)he could say "I have done this work on my own, it is truly mine" meant that Teissier had few students and that those students received little guidance. M. Lamotte, one of Teissier's students, in an interview with R. Burian (Paris, 18 May, 1986, notes available on request), expressed precisely the same opinion.
(37) Cf. the interviews with Ephrussi recorded in Pomerat, Officer's Diary, 9 Sept., 1950, 3 June, 1952, and 5 June, 1953 (RFA. RG 12.1) as well as the letter to Weaver cited in n.34. The general picture provided here has been confirmed in a series of interviews with P. Slonimski, Ephrussi's successor at Gif.
(38) "En conséquence, je me trouverai, dans un proche avenir, dans
l'obligation d'informer la Fondation Rockfeller de l'état de la
question que je viens de vous rappeler, ce qui revient en fait, pour ma
part au moins, à renoncer à la subvention.
Etant donné les
relations entre le CNRS et la Fondation Rockefeller, j'ai cru qu'il
était de mon devoir, avant d'entreprendre cette démarche, de vous
rappeler l'état de la question. En effet, outrequ'elle est embarassante
pour moi en tant qu'auteur de la demande de subvention, elle place
également dans une situation délicate, vis-à-vis de de la Fondation
Rockefeller, le Centre National de la Recherche Scientifique, dont l'un
des organismes devait bénéficier de la subvention" (RFA, Arch 2. Series
500D. NCSR-G, 1951-56. Box R1050. Unprocessed material).
(39) Teissier Titres et Travaux (n. 18).
(40) There are many sources for this claim, some cited above. Corroboration may be found in Pomerat's diary for 11 June, 1954. RFA. RG 12.1 "As far as the genetics situation at Gif is concerned, that is not at all rosy. Some months ago Teissier collapsed at a luncheon and when he woke up he was recovering from a complete gastrectomy... Since than Teissier has devoted less and less time to his laboratory at Gif and has just about lost all his students. L'Héritier is therefore out there in almost complete isolation : this is preying more and more heavily on his mind. He talked about this with Ephrussi the other day and said that he was going to make a very strong effort to have Dupouy reconsider the possibility of getting Ephrussi to consent to move out to Gif. At a wedding party shortly after this, L'H. did speak to Dupouy and was rebuffed..."
(41) Cf., e.g., Pomerat's Officer's Diary, 9 June, 1953, for an extended description of a difficult interview with Dupouy. RFA. RG 12.1.
(42) The work of the fifties is summarized in L'Héritier, (P)., "The Hereditary Virus of Drosophila," Advances in Virus Research5 (1958): 195-245 and "Les relations du virus héréditaire de la Drosophile avec son hôte," Ann. Inst. Past. 102: 511-526.
(43) His students include Boesiger, Bocquet, Lamotte and Petit. Yet in the interview with Picard and Raguenel, following up on his comments reported in n.35 above, l'Héritier says, "Comme je vous l'ai expliqué, [Teissier] n'avait pas d'élèves... Son seul élève finalement, c'est moi, parce que nous n'étions séparés que par sept ans de distance. Il considérait que nous étions des camarades plutôt qu'un directeur et un élève" (p.13).
(44) Cf. Kay (n.24).
(45) The best historical account of this work to date is in Sapp, Beyond the Gene (n.9).
(46) These stances are nicely illustrated in a radically different context by Gilbert (S.), "Cellular Politics: Ernest Everett Just, Richard B. Goldschmidt, and the attempt to reconcile Embryology and Genetics," in R. Rainger, K. Benson, and J. Maienschein (eds.), The American Development of Biology, Philadelphia, University of Pennsylvania Press, 1988, pp. 311-346. Cf. also draft papers by Burian (R.), "Lillie's Paradox -- or, Some Hazards of Cellular Geography" and "Disciplinary Specialization and the American 'Dis-solution' of the Impasse Between Development and Heredity" (read at Gif, May, 1987).
(47) P. Slonimski, commenting on Burian, "Disciplinary Specialization," stressed the use of different organisms in embryology and genetics. Embryology, requires organisms with large transparent eggs, visible protoplasm, and sufficiently slow and complex early development to allow visual tracking of developmental processes. Genetics, in contrast, requires organisms with short generation times, small and simple eggs with large nuclei and few, but large, chromosomes, and distinctive adult features under clear-cut genetic control. "Domesticating" a laboratory organism for either purpose takes a long time; since the requirements of the two sorts of investigation are quite different, shortly after the turn of the century embryologists and geneticists did not appreciate the features of the others' organisms and found it very difficult to integrate the others' findings into their own framework.
(48) In spite of the early formative work of Cuénot, as we argue in "Singular Fate," (n. 2).
(49) A point emphasized by Slonimski in his interviews with us.
(50) Interview with Burian (n. 16).
(51) The best source for his approach to this issue during this period is Ephrussi (B.), Nucleo-Cytoplasmic Relations in Micro-Organisms: Their Bearing on Cell Heredity and Differentiation, Oxford, Clarendon Press, 1953.
(52) The first serious report was Ephrussi (B.), "Action de l'acriflavine sur les levures," in Unités biologiques douées de continuité génétique, Paris, Editions du CNRS, 1949, pp. 165-180. A series of eight articles by various members of Ephrussi's lab group, "Action de l'acriflavine sur les levures" was published in the Ann. Inst. Past. , the first six in vols. 76 and 77 (1949), the last by H. Marcovich in 81 (1951): 452-468. For a useful review see the First Lecture of Nucleo-Cytoplasmic Relations (n. 50). Slonimski bore primary responsibility for the biochemical analysis. Cf., e.g., Slonimski's Doctorat d'État, La formation des enzymes respiratoires chez la levure, Paris, 1953.
(53) This was the title of the RF-supported CNRS colloquium, co-organized by Ephrussi, in 1948. Ephrussi, Nucleo-Cytoplasmic Relations (n. 50), p. 35, characterizes the results of the yeast work to date as follows: "The only conclusion we may draw today with a high probability of being right is that the normal yeast and the vegetative mutants differ by the presence in the former and the absence in the latter of cytoplasmic units endowed with genetic continuity and required for the synthesis of certain respiratory enzymes." (Original italicized.)
(54) To this day, the laboratory is headed by P. Slonimski, and is one of the foremost laboratories of mitochondrial genetics.
(55) RFA. Application for a RF grant, Aug. 11, 1956, awarded as NS Grant RF 56162.
(56) Ibid. These were B. Bonner, D. Bonner, R. Milkman, H. Roman, S. Opara, W. Tyssarawski, and P. Galzy.
(57) We do not mean to exaggerate. Much work elsewhere was devoted to related problems. One need only think of such figures as Darlington, Lederberg, Lindegren, Luria, Sonneborn, Spiegelman, Waddington, and many others to realize that great caution is needed in thinking through the general patterns underlying the conceptual and experimental changes of the period. We should also point out that from here forward we are ignoring, unfairly, the important French contributions to population genetics during this period.
(58) Most of our information about meetings of the Club come from interviews with E. L. Wollman and with Slonimski, Nov., 1984, with corroborating details from D. Perrin (May, 1987) and various American scientists who visited Paris in the 1950s.
(59) This approach is very different than that of Crick and Watson, Delbrück, or Beadle and Tatum. We would argue that even such figures as Lederberg, Luria, Sonneborn, and Spiegelman, certainly far more physiologically and less structurally oriented than the men just listed, learned a great deal about how to clarify nucleo-cytoplasmic relations from the French workers although, obviously, there was a thoroughgoing two-way exchange in all such cases. If there is a large point here, it turns on the fact that the French workers were able to draw on traditions during the early parts of this period which were inaccessible and quite foreign to their British and American colleagues.
(60) RFA. RF grant 60187.
(61) According to Wollman, in interview, Nov., 1984.
(62) This judgment should not be understood as an underestimate of the importance of the sigma virus work, which showed that the issues of central concern to the rest of this community concerned eucaryotic as well as procaryotic organisms and played a central role in forcing Drosophila geneticists to expand their horizons beyond the usual Mendelian cases.
(63) These claims have been supported in interviews with Slonimski and many others. G. Cohen, A. Lwoff, and M. Weiss have confirmed the use of the nickname.
(64) Jacob was younger and did not begin his work until the fall of 1950. He and Wollman first published on a colicine in 1952 and on lysogeny in 1953. Lwoff, who to this day does not consider himself a geneticist, had done occasional genetic work earlier (e.g., Lwoff (A.) and Audureau (A.), "Sur une mutation de Moraxella lwoffi apte à se développer dans les milieux à l'acide succinique," Ann. Inst. Past. 67 (1940): 84-111), but it was not until he began his work on lysogeny with Gutmann and others in 1949 that there was a serious genetic component to his program of research. Even then, it was only after the induction of lysogeny was under adequate experimental control (in 1950 or 1951) that the problem of the control of induction could be experimentally explored in a form that would now be called, anachronistically, an instance of the problem of the control of gene expression. In short, the link from the physiological control of cellular states to genetic regulation came slowly in Lwoff's work precisely because his problems started from the former rather than the latter issue. Similarly for Monod, who recognized early on that he had to arrive at genetics, but whose path toward that point required him to gain complete mastery of the biochemistry of enzyme induction before he could enter seriously into the genetic work involved. The proof of this point, however, goes far beyond the present study.
(65) Though, as the quotation from Monod (which may have been partly influenced by Ephrussi) at n. 7 above shows, it was on Monod's agenda to reach the genetic analysis of the biochemistry of enzymatic adaptation (i.e., in the long run, of enzyme induction and synthesis) very shortly after the war.
Voir aussi : Boris Ephrussi et le contrôle génétique de la pigmentation de l'œil de drosophile par Jean Gayon (U. de Bourgogne) et Nobel de physiologie et de médecine de G. W. Beadle & E. L. Tatum, Boris Ephrussi (IBPC) se voyant injustement privé de cette distinction