The Competitiveness of Nations in a Global Knowledge-Based Economy
Alberto
Cambrosio † and Peter Keating ††
“Going Monoclonal”: Art, Science, and Magic in the Day-to-Day Use of Hybridoma Technology *
Social Problems, 35 (3)
June 1988, 244-260
Content
Local
Knowledge and Tacit Knowledge
The
Art of Producing Hybridomas
The
Objectification of Procedures
Hybridoma
Technique and Its Variants
The
Problem of Standardization
Recent
work in the sociology of science has highlighted the local and tacit dimensions
of scientific work
Against the widely held assumption that we are here dealing with
a form of knowledge largely beyond the control and manipulation of scientists,
we will argue that the unsaid is indeed a part of conscious scientific practice
- and hence subject to negotiation, discussion, and construction. Based on a study of the transmission of hybridoma technology, this paper will show that questions
of local knowledge, tacit knowledge, and “magic,” far from being ignored by
scientific researchers, are explicitly a part of their daily practice. It will be seen that these questions give
rise to a series of social and technical distinctions which are constitutive of
scientific work.
In recent years, the sociology of
science has moved from the study of scientific communities to the problem of
the construction of scientific knowledge (Knorr-Cetina
and Mulkay, 1983).
This change in interest has resulted in a shift in the scope and object
of sociological inquiry as evidenced by the many “laboratory studies” and
analyses of scientific controversies, both of which have tended to highlight
the contingent elements of scientific knowledge. Laboratory studies, for example, have
described the local dimensions of scientific knowledge and the processes
whereby the latter are integrated into the sanctioned corpus of science (Latour and Woolgar, 1979; Knorr-Cetina, 1981; Lynch, 1985; Star, 1983). Similarly, research bearing on the conduct of
scientific controversies has stressed the negotiable elements in these episodes
and the role played by tacit understanding in the replication of disputed
experience (Collins, 1985; Pinch, 1986).
In this context, the categories of “local knowledge” and “tacit
knowledge” have gained central importance.
However, the meaning given to these notions is hardly uniform, and there
is indeed some confusion surrounding their use.
To begin with, let us consider the relation between local knowledge and
tacit knowledge.
Local Knowledge and Tacit Knowledge
While these two terms have often been
used as either synonymous or overlapping categories of knowledge, some authors
have taken great pains to distinguish them.
Knorr-Cetina (1981:37-40, 127-130), for
example, has proposed an analysis of scientific knowledge that distinguishes
public knowledge, tacit knowledge, and local knowledge (know-how). The first two categories are separated from
the third on the basis of “availability.”
According to Knorr-Cetina, public knowledge
and tacit knowledge refer to scientific knowledge that is “generally
†Université du Québec a Montréal;
††
*
A preliminary version of this paper was presented to the meeting “Senses of
Science’ of the European Association for the Study of Science and Technology
(Strasbourg, 1986). We would like to
thank Michel Callon for his comments on the final
draft. Research for this paper has been
made possible by post-doctoral fellowships awarded to the authors by the Social
Sciences and Humanities Research Council of Canada as well as by S.S.H.R.C.
grant 410-86.0341. Correspondence to: Cambrosio, Centre de recherche en
evaluation sociale des technologies (CREST), Université du Québec a Montréal,
C.P. 8888, Succ.
A, Montréal,
available” to the scientific community, while local knowledge
is composed of the largely inaccessible idiosyncrasies of the individual
researcher or laboratory. Knorr-Cetina’s classification of knowledge corresponds, on
the one hand, to the categories of scientific institutions used by sociologists
and historians (i.e., field, discipline, institute) and, on the other, to the
classification of knowledge used by scientists in their daily practice (i.e.,
science, art, magic; see also, Fujimura, 1987).
Michael Lynch’s
(1982; 1985) notion of tacit knowledge is similar to Knorr-Cetina’s
notion of local knowledge. Lynch,
however, has gone further in removing all reference to individuals as possible
“repositories” of knowledge. For Lynch,
tacit knowledge, unlike Knorr-Cetina’s local
knowledge, is “not anybody’s knowledge.”
In fact, Lynch’s ethnomethodological
approach is an attempt to go beyond the description of the unwritten knowledge
which circulates within a given scientific discipline in order to describe a
more fundamental form of knowledge, incorporated in the practices
themselves. This knowledge is “taken for
granted” by the researchers and, although unnoticed, plays a central role in
the conscious evaluation of experiments and experimental results, giving rise
to what Lynch terms “endogenous critical inquiry” (as opposed to professional
sociological inquiry).
H.M. Collins’s work on scientific
controversies also relies to a great extent on the notion of tacit
knowledge. And, here again, the notion
is given a somewhat different meaning than that attributed to it by Knorr-Cetina and Lynch.
In Collins’s work, the notion of tacit knowledge is intended to provide
the key to understanding the author’s emerging “science of knowledge” (Collins,
1987). In particular, Collins has
recently proposed an analysis of the domain of cognition into four components:
facts and rules, heuristics, manual and perceptual skills, cultural skills. The last two elements of Collins’s analysis
are members of the category of tacit knowledge, which is the knowledge required
to use formal and informal rules but which cannot, without being fundamentally
transformed, be verbalized or formalized.
Applied to the analysis of scientific
controversies, Collins’s approach results in the characterization of these
practices as proceeding along the lines of the “experimenter’s regress,” which
is described as the following situation.
Because of the artisanal nature of scientific
experiments, a researcher’s competence and the reliability of his/her
experiment can only be assessed on the basis of the results obtained. Since, however, the results can be considered
valid only if they are obtained from reliable experiments, any assessment is
necessarily flawed by circular reasoning.
Collins argues that scientists are able to break this circle of reason
by negotiation, the consensual resolution of which depends upon the prior existence
of a network of social relations and therefore an institutionalized “form of
life” for the researchers (Collins, 1985).
This model of scientific practice,
referred to as “enculturational,” allots tacit
knowledge the key role in the production of new knowledge and is, thus, at
variance with what Collins terms the algorithmic model defended by researchers
when they are asked to account for their activity. According to this latter model, scientific
practice is described as the application of rules (scientific knowledge being
composed solely of formal and informal rules).
Insofar as Collins’s model is opposed to the scientist’s model of
scientific practice, it is reducible to the distinction between what can be
said and what can not: “... the crucial division in knowledge is not the
separation between information and heuristics... but between the articulateable and the tacit” (Collins, Green and Draper,
1985:329). Vincenti’s
(1984) typology of knowledge is also based on a dichotomy, this time between
explicit and procedural knowledge; the former encompasses descriptive and
prescriptive knowledge, the latter prescriptive and tacit knowledge. Prescriptive knowledge plays the role of
watershed between procedural and explicit knowledge. Tacit knowledge is only a subcategory of the
main dichotomy. Collins’s argument is
directed against this kind of typology.
Like Knorr-Cetina’s
and Lynch’s conceptions of local or tacit knowledge,
Collins’s typology suggests that tacit knowledge is impossible to articulate,
and yet it is not clear why this
245
should be so. If
tacit knowledge is that which one knows without knowing how to say it, and this
would seem to be what Collins believes, then there are certainly things that
are known and cannot be said that can nonetheless be shown and formally
transmitted in this manner. In this
respect,
“Rules of thumb” are also problematic
for the concept of tacit knowledge.
Collins, for example, has classified this species of knowledge (also
referred to as artisanal knowledge, tricks of the
trade, etc.) as “heuristics” in recognition of the fact that it can be
transmitted in more or less formal fashion.
It, therefore, does not count as tacit in Collins’s scheme. However, conforming to a widespread tendency
in the sociology of work (Jones, 1983; Jones an Wood, 1984; Kusterer,
1979), Collins himself sometimes uses terms like “rules of thumb” a synonymous
with tacit knowledge. One of the reasons
for this contradictory use of terms is that it is often assumed that tacit
knowledge is impossible to verbalize and that, hence, all non-verbal knowledge
is tacit.
However, it is rarely specified why
certain kinds of knowledge cannot, by their nature, be enunciated. One could easily imagine, on the contrary,
that some things are left unsaid not because of the impossibility of their
being said, but for a variety of other reasons.
For example, an individual’s silence may be the result not of an
inability to verbalize, but of the perception of the trivial nature of what
might have been said. Surely, some
things are generally accepted as being known to all within a given discipline
and hence trivial. One could, moreover,
conceive of knowledge unspoken for fear of sanctions or knowledge unspeakable
within a certain conceptual framework (or paradigm or disciplinary
matrix). In other words, the restriction
of the tacit to the unsaid does not necessarily entail that the tacit is by nature
non-verbal; much that is unsaid clearly has the possibility of being verbalized
but remains, for many reasons, unsayable,
unthinkable, trivial, secret, or censored (Descombes,
1977).
One of the effects of prescribing a
non-verbal, inaccessible, non-transmissible nature to tacit knowledge has been
to reinforce the assumption that we are here dealing with a form of knowledge
largely beyond the control and manipulation of scientists, that we have entered
the unconscious or, at least, non-conscious realm of science. Against this assumption, we will argue in
what follows that the unsaid is indeed a part of conscious scientific practice
and hence subject to negotiation, discussion, and (re)construction. Moreover, we will see that the distinctions
(formal, tacit, local) used by sociologists of science, even by
constructivists, inadequately describe scientific work.
Based on a study of the transmission of hybridoma technology, this paper will show that questions
of local knowledge, tacit knowledge, and “magic,” far from being ignored by
scientific researchers, are explicitly a part of their daily practice (for an
historical example of this awareness, see also Lawrence, 1985). It will be seen that these questions give
rise to a series of social and technical distinctions which are
constitutive of scientific work. It
follows then that the establishment of a typology of knowledge is not only the
preoccupation of the sociologist, but is also a recognized issue for
scientists. Rather than give a
sociological description of scientific practice with the help of such notions
as local or tacit knowledge, this paper seeks to describe the status scientists
attribute to such knowledge.
The development of hybridoma
technology began in 1975 with originators G. Köhler
and C. Milstein, who received the Nobel Prize in 1984. It is considered a scientific discovery of
great importance as well as one of the foundations of the
biotechnology industry. In order to
appreciate its status both as a scientific and a technical advance, recall that
antibodies, the product of hybridoma technology, in
addition to being a key element of the body’s immune system, are an essential
diagnostic and research tool in biomedicine.
Prior to 1975, only polyclonal antibodies - that is to say, a mixture of
antibodies directed against a variety of antigens or different parts of a
single antigen - were available to researchers.
As the cells responsible for the secretion of antibodies were impossible
to cultivate, antibodies were harvested from immunized animal sera. The disadvantage of such a procedure lay in
the fact that not only did the sera of immunized animals always contain an
inseparable mix of antibodies, but the quality and the composition of the sera
varied from one immunization to the other.
Köhler and Milstein’s 1975 discovery consisted
of a procedure for the production of an unlimited amount of a single type of
antibody. The technique called for the
fusion of cells producing antibodies with a particular type of cancer cells (myelomas). The
resultant hybrid, termed hybridoma, retains both the
capacity to produce a specific type of antibody and the immortal character of
cancer cells that makes the cultivation of hybridomas
possible. The specific antibodies
secreted by the clones of a single hybridoma are called
monoclonal antibodies.
Since 1975, hybridoma
technology has diffused rapidly through clinical and research biomedical
specialties, as evidenced by the exponential growth in publications concerning
monoclonal antibodies. According to Medicus, by 1984 the number of articles on this
technology had increased to over 10,000.
In the space of a few years, hybridoma
technology had gone from a highly specialized technique to a standard technique
that few biomedical laboratories could afford to be without.
Nonetheless, the production of
monoclonal antibodies has remained a largely artisanal
technique. Unlike a number of
biochemical procedures, for example, it has yet to be automated. The animals (rats or mice) must first be
injected with the chosen antigen in order to be immunized. The spleen of the immunized animal is then
extracted, and the antibody producing cells are mixed with myelomas
in the presence of a chemical (polyethylene glycol or P.E.G.) which promotes
cell fusion. Following fusion, hybridomas are separated from the un-fused cells; this is
accomplished by placing the mixture in a solution in which only the hybrids
will survive. After a period of growth
in culture, hybridomas producing the required
antibodies are selected using a variety of techniques (for example, so-called
immunoassays). The selected hybridomas are then cloned, cultivated, and frozen for
conservation. Subsequently, the hybridomas may be either cultivated in vitro in
order to harvest antibodies secreted in the medium or injected into animals
where they generate tumors which in turn secrete antibodies into the animal’s
internal cavity. Depending upon the
reason for which the antibodies were produced, the latter may be submitted to a
series of additional manipulations, including immunochemical characterization
of the antibodies and conjugation with radioactive or enzymatic labels.
Hybridoma technology is thus composed of a series of steps
which call upon different domains of expertise sometimes loosely identified
with different disciplines. The initial
immunization, for example, is most closely related to immunology, while the
immunoassays used for the selection of the hybridomas
as well as the various procedures used to characterize the antibodies are more
closely identified with immunochemistry or biochemistry. The hybridoma
technique invariably draws upon expertise in cell culture, the sterile
manipulation of biological material as well as the disciplinary domains related
to the antigen of interest (virology in the case of viral antigens,
bacteriology in the case of bacterial antigens, etc.). This break-down of the procedure into a
series of domains of technical expertise is not an analytical artifact but
corresponds to the way researchers approach hybridoma
technology.
Since 1975, hybridoma
technology has remained for the most part unchanged (French et al., 1986; Westerwoudt, 1985).
Nevertheless several improvements have been accepted by the
247
majority of researchers, the most significant being:
(1) the substitution of a chemical fusion promoter (P.E.G.) for the Sendai
virus initially used to promote fusion, and (2) the use of myelomas
that do not secrete their own antibodies and that therefore do not interfere
with the production of the required antibody.
Other “improvements,” though widespread, are still subject to
discussion. Such is the case with the
addition of “feeder cells” to hybridoma culture wells
and the use of a serum-free culture medium.
Finally, some innovations have yet to be widely adopted. Electrofusion
(i.e., the use of short electric pulses to promote fusion), despite the many
articles crediting it with great advances in fusion efficiency, remains
restricted in its application due apparently to high cost and the effectiveness
and availability of “traditional” procedures.
The Art of Producing Hybridomas
Hybridoma technology is often characterized by practitioners as
an art. What makes it “artisanal” and what does it mean to be such? In order to answer these questions, we will
consider both written sources, such as technical manuals, and informal
statements gathered through interviews and laboratory discussions. We will thus be able to assess what counts as
being “artisanal” and to show that this category is
indeed a component of scientists’ discourse.
It is well known that knowledge and
know-how in hybridoma-related fields have long
circulated informally. According to Goding (1983:3), “Immunochemistry has an oral tradition,
and a surprising number of key elements are not easily accessible from the
literature.” The artisanal
nature of hybridoma technology is evident in the fact
that the training necessary for its manipulation takes the form of an
apprenticeship. As one researcher (winter
1986) remarked, “it’s difficult to learn a technique
which is art from a paper.” Even manuals
offering instruction in the technique maintain a similar opinion:
The newcomer to hybridization is well advised to learn the technique in a laboratory which is already practicing fusion. It has been a frequent observation that newcomers to the technique are relatively unsuccessful initially and obtain many hybrids after some practice, although an experienced observer cannot see any difference between the technique used on the first day and in subsequent, successful experiments. The best approach is therefore to learn from an experienced laboratory and practice until hybrids are obtained (Zola and Brocks, 1982:4-5).
The artisanal
features of the technique are further reinforced by the often unpredictable
nature of the results obtained:
The waywardness of the original method, repeatedly
commented upon by its originators, is best
demonstrated by comparing tests set up and run under identical conditions. The wide scatter of results is typical: the
odds of obtaining hybrid clones in all culture cups or in none is about the
same (Fazekas De St.Groth
and Scheidegger, 1980:5).
It is quite common for a laboratory to have success
for several months and then failure for as long a period. So the immediate record of a laboratory is
more important than the long-term one.
Even within a research group one individual may fail where others
succeed and this is a reason for encouraging separate reagents and cell lines
(Campbell, 1984:156).
The fusion does not invariably work. Often a repeat of the fusion process without
obvious changes results in successful hybridization (Hybridoma
Techniques, 1980:4).
While the rate of successful fusions
does indeed increase with time, expertise is not identified with the
possibility of succeeding every time.
Rather, expertise is equated with the ability to operate “confidently”
in an experimental situation characterized by a high degree of uncertainty (Star,
1983). This persisting state of uncertainty
is said to follow from the interaction of “nature” and a given researcher’s
professional trajectory: “the diversity of published
approaches [to hybridoma technology]
reflects both individual biological problems and previous experience” (Goding, 1983:56).
To be experienced in an art, to have
expertise, implies the mastery of specific ways of seeing and doing. The nature of these skills and the difficulty
of their transmission can best be seen in the following example. After a certain growth period, it is
necessary to transfer the hybridomas from a 96-well microplate to another in order to ensure their continued
survival. If they are transferred too
soon, there is a possibility they will not survive the transfer; if too much
time elapses, there is a possibility they will die in the original microplate wells. It
is furthermore necessary that the hybridomas be left
in the original wells long enough to have secreted sufficient antibody to make
possible their screening as producers of the desired antibody. The moment of transfer is thus a crucial step
in the procedure, and its determination requires scrutiny of the color of the
culture liquid (which contains a pH indicator), the form of the cells, and
their size. However, these parameters
cannot be analyzed in isolation. The
decision to transfer depends upon the perception of a synthetic variable
referred to as the viability of the culture.
The perception of culture viability allows the experienced researcher to
decide when the fused cells should be transferred and requires learning how to
look at cells:
As the cells become very dense, they start to look
unhealthy, and viability drops (Goding, 1983:67;
emphasis added).
Sometimes the hybridomas do
not look “happy” after the replacement of HT with normal growth medium (Eshhar, 1985:22; emphasis added).
When inspecting cells by phase microscopy, you get a
feeling for just what the cells are doing, and how healthy they are by looking
at them. A good hybrid should look like
a little beach ball (an industrial researcher, winter 1986).
You look in the microscope at cells growing: are they
healthy or are they not healthy? You
learn that by association. The professor
says: these are healthy, those are not.
You learn by association, without knowing what you are looking at; you
learn to know when “it looks good” (an academic researcher, fall 1985).
When “apprentices” are taught the hybridoma technique, the instructor (technician, graduate
student, or professor) usually stresses the importance of the variables that
have not been written down. The latter
refer more often than not to visual and motor aspects of the procedure which
contribute to the learning of a gestalt.
This way of seeing and acting is not restricted to experimental practice
per se but is also essential to the understanding of formal written
instructions. To illustrate this, we
draw upon the experience of the first author.
At the beginning of this study, Cambrosio undertook a comparison of several different
experimental protocols for the production of hybridomas. He had not yet been able to attend a fusion
experiment but relied, to a great extent, on his previous biological
training. While one might expect that it
would be relatively easy to determine variations between the protocols, this was
true only in a “mechanical” or literal sense; to the untrained eye, the
protocols appeared to be arbitrary lists of instructions lacking any overall
sense. The situation changed
fundamentally when he was able to attend a training session in the technique. Once these instructions were embodied in a
series of gestures, they became confounded with other factors such as the
manual skills of a given person or that person’s degree of familiarity with a
piece of equipment. The comparison
between protocols now became possible, each line of instruction evoking shapes,
colors, time spans, and gestures that could be compared.
Ethnomethodology has developed the theme of the passage from written
instructions to actual experimental practice.
On this view, much of what is important to the understanding of an
experimental protocol is not contained in the instructions but is incorporated
in the various visual and corporal movements that make up the actual
practice. It is further maintained that
the experimental gestures themselves constitute an important part of the
reasoning peculiar to specific disciplines (Lynch, 1985). This fact has not escaped scientists.
249
Scientific researchers perceive the
circulation of fellow scientists (most notably “post-docs”) between laboratories
as the circulation of “incorporated” knowledge.
In one of the academic laboratories we visited, for example, a
“post-doc” had introduced a particular way of shaking test tubes containing
recently fused cells which, following centrifugation,
had a tendency to stick to the walls of the tube. This gesture, at first sight somewhat
innocuous, was quickly adopted by the other researchers in the laboratory who
pointed out that it could make the difference between the success or failure of a fusion. Bio-industrial laboratories are also well
aware of the importance and source of this dimension of scientific practice
and, hence, frequently offer post-doctoral fellowships in addition to
maintaining consultantships with university
researchers.
The Objectification of Procedures
The fact that hybridoma
technique has features that are widely recognized as “artisanal”
has not stifled attempts to objectify the “know-how” contained therein, for not
only do written protocols exist, as previously noted, but it has indeed been
possible for researchers to learn the technique through such protocols.
This, of course, does not imply that hybridoma “know-how” was transmitted in this way
alone. Insofar as hybridoma
technology links together a set of previously existing techniques, it can be
said that “learning by doing” happened at an earlier point. As noted by Collins (1987), the problem here
is one of the distribution of know-how within a given
field. Widely distributed know-how is
taken for granted and not perceived as know-how. This point can be related to Vincenti’s (1984:571) distinction between two different
modes of circulation for innovations: “diffusion pattern” and “simultaneous
pattern”, the difference between the two modes laying,
among other things, in “the range of availability of the necessary aptitudes
and expertise.” In what follows, we will
examine the ways in which the “tacit” is articulated through the
objectification and formal transmission of the technique.
There are essentially four kinds of
written documents describing the hybridoma
technique. The first is found in the
material and methods sections of scientific papers. The brevity of these descriptions may be
taken as a sign that the information contained therein is destined for members
of the same discipline or same technical area.
They are of little use to researchers unfamiliar with the procedure.
A second form in which the technique is
described is the experimental protocols produced in manuscript form by
university laboratories for internal use.
The protocols are also sent to researchers who request them. Industrial laboratories tend to produce more
formal versions of this type of document (“standard operating
procedures”). However, the informal
nature of some university laboratory protocols does not prohibit their transfer
to industry. This is carried out either
through transfer of a researcher or as part of a commercial package. Taggart Hybridoma
Technology, developed by an academic scientist and sold under licence by the HyClone Company,
provides buyers with a specific myeloma cell line, an
experimental protocol, and direct technical assistance through an 800 telephone
number. Research protocols offer a
condensation of a particular laboratory’s experience with a technique. They contain a combination of scientific, artisanal, and idiosyncratic rationales and hence require
strict adherence. As Eshhar
(1985:10; emphasis added) has remarked: “Fusion protocols are simple and easy to
follow and usually successful, if one sticks to them.”
Books dedicated solely to the detailed description of hybridoma technology are a third kind of description and
are generally justified by the importance of this technology for disciplines
other than that in which it emerged. For although the production of monoclonal antibodies draws upon a
variety of skills from different disciplines, it is not uniformly accessible to
members of all disciplines. Thus
an individual with experience in cell culture (e.g., a virol-
ogist) would have a certain advantage in learning the
technique over, for example, a biochemist. However, as a technical manual
notes:
It is not necessary to have extensive cell culture
experience or to be an immunologist to undertake hybridoma
work, although it helps... Hybridomas are rather
fastidious cells and the chances of producing them and maintaining them are
certainly higher if the worker has previous cell culture experience... The most
important prerequisite in terms of expertise relates to the antigen type to be
used and the assay for antibody against the antigen. Hybridoma
technology is secondary and can be learned, but it is essential to have
experience working with the material which is the subject of the project, be it
a virus or a peptide, a lymphocyte differentiation antigen or a pathogenic
parasite (Zola and Brocks, 1982:7).
As the above quotation clearly
indicates, the purpose of such manuals is to allow researchers from other
disciplines to acquire the technique without necessarily coming to grips with
the theoretical principles (and the practical consequences of those principles)
that underlie it. The technique is thus
attributed a secondary or peripheral status.
It is mere technique, a tool for the furtherance of other disciplinary
projects.
In other instances, hybridoma
technique may be accorded a more central status. In such cases the technique is no longer the
tool of a particular discipline but a vehicle for advanced knowledge as well as
a manifestation of the practical mastery of that knowledge. [1] As one immunologist
noted:
There are different strategies to make hybrids very
specific against what you want: more and more fine questions are asked and you
then need more specific monoclonals. You may produce hybrids “one by one”, and
keep looking, but the more specific you want your monoclonals
to be, the longer it gets. Now, very few
people understand how the immune system works and the best way to do
hybrids. People who are not
immunologists produce monoclonals by following
instructions in the books, in other words, very inefficiently (an academic
researcher, fall 1985).
Not only are there different ways of
objectifying the hybridoma technique, but the
technique may be objectified or formalized to different degrees; the more the
technique is formalized (or “packaged”), the more it tends to be seen as “pure
technique” and thus less central to the scientific preoccupations of the
discipline. Hence, it cannot be decided a
priori whether the hybridoma technique is of a
formal or artisanal nature or whether, in fact, it is
“only” a technique. These attributes are
determined through practice and thus can serve only as descriptions of the
technique within a particular institutional or disciplinary context. The changing status of the technique, which
may be described as socio-technical (Callon
and Latour, 1986), appears furthermore to depend upon
the shifting relationship between disciplines as well as industrial and
academic institutions.
In contrast to the “material and
methods” sections of scientific papers, scientific manuals offer what attempts
to be an exhaustive description of a “standard” procedure. Some authors go so far as to seek a reconciliation
of the two extremes we have just described by offering both principles and
technique for the uninitiated:
I have written this book because 1 believe
that previous accounts of the production, and particularly the usage, of
monoclonal antibodies have been too dogmatic and inflexible. “Recipes” have been given which work if
followed to the letter, but little attention has been given to the underlying
principles... I have therefore tried to emphasize the important variables which
make for success or failure in the use of antibodies... I have also tried to
point out areas in which the literature gives misleading impressions (Goding, 1983:3).
1.
This wavering between a “disciplinary” and a “purely technical” status is
reminiscent of the controversy surrounding the introduction of molecular biology
into an Australian research institute (Stokes, 1983). It may also be noted that this ambiguous
status is reflected in the fuzzy institutional arrangements surrounding the
introduction of hybridoma technology within academic
and industrial research centers (Mackenzie, Cambrosio,
and Keating, forthcoming).
251
Like the protocols produced for
restricted diffusion, manuals represent a form of packaging and, consequently,
a form of standardization such as that described by Fujimura (1987). Presumably, the proliferation of such manuals
will result in the reduction of the importance of “golden hands” in the production process. However, as we have seen, not only are there
different degrees of packaging but the relevance of a “standard technique”
varies according to a number of factors such as the discipline within which it
is to be used.
It should finally be noted that articles
bearing on specific features of the technique appear regularly in journals such
as the Journal of Immunological Method.
Often, these articles offer improvements in the technique. However, the status of these improvements is
somewhat ambiguous for, as several researchers pointed out, such advances in
“protocol” are best confined to manuscript documents for internal use and do
not, in themselves, represent much of interest in
terms of scientific recognition.
Hybridoma Technique and Its Variants
Numerous differences exist between the
written procedures used in different laboratories; further, the practical use
of these instructions within the same laboratory varies. This is a fact openly recognized in technical
manuals:
There
are a large number of fusion protocols in general circulation and most of them
work... It has been emphasized throughout this book that the number of
variations in procedure is immense (Campbell, 1984:127-31).
An adequate description of this
variation, as we already noted, would necessarily call forth both “technical”
factors (i.e., the biological problem at issue) and “social” factors (i.e., the
previous experience of the researcher).
An individual’s choice of procedure depends, more often than not, on
“social” factors relating to the origin of the protocol in question:
There are people who, if they see a protocol
originating from an institution or an individual they don’t consider to be
“prestigious,” will not try that protocol; it could be the world’s greatest
protocol, but they won’t try it (an industrial researcher, winter 1986).
Variants of the hybridoma
technique may be loosely classified in the following categories. There are, first of all, “formal” variations
that are duly noted in written protocols.
If limited to the central phase of the fusion
procedure, these variations would include such factors as the concentration of
the fusion agent, the temperature, the means of sterilization of P.E.G.
(autoclave or filtration), and the precise duration of the fusion. Some of the variants are subject to
controversy within the manuals. “Feeder
cells” are a case in point. Consisting
of a cell preparation, they are often added to cultured hybridomas
in order to promote their development.
Despite the term “feeder,” little is known about the mechanism of their
action (Goding, 1983:71). Some say they are useless while others
declare them to be a major improvement of the technique (Fazekas
Dc St.Groth, 1985:5).
Still others maintain that while their benefits may be unknown, they
certainly don’t do any harm (Goding, 1983:71; Zola
and Brocks, 1982:25).
There are, secondly, informal variants
sometimes known as “shortcuts.” For
example, rather than count B cells and myelomas under
the microscope in order to obtain a given proportion, say 10:1, it is possible
to simply compare the volumes of two pellets of cells. Given that myelomas
are about 10 times larger than B cells, equal volumes of each gives the desired
proportion. The result of experience
acquired in the course of many fusions, these “shortcuts” do not appear in
written protocols, not even those for internal use, and are transmitted orally.
“Shortcuts” of the latter type may be
distinguished from the use of “sophisticated” techniques (sometimes also
referred to as “shortcuts”) which may replace certain parts of the
procedure. For example, rather than
screening the hybridomas by searching for the
required
antibody in the cell culture supernatant, it is possible, with
the help of DNA probes, to determine the presence of the gene coding for the
sought-after antibody. Using such a
technique allows one to screen a much larger number of hybridomas
than would otherwise be possible (cf. Vincenti,
1984:562).
Within the private sector,
“sophisticated” procedures of the type just mentioned are not often patented
but are protected as “trade secrets” because to patent this form of
intellectual property would result in diffusion of the knowledge without the
ability to control its use. However, if
a “trade secret” remains entirely secret, it loses part of its commercial
value. Fully aware of this problem, a
company like Hybritech advertises a “secret” system
allowing its employees to rapidly screen large number of hybridomas.
Finally, procedural elements that are
perceived of as the most immediate expression of local idiosyncrasies are
dismissed as “magic” in opposition to practical scientific know-how. The use of similar terms has been noted by
sociologists of science. Lynch
(1985:108-11) has documented instances of “superstition,” and Fujimura (1987)
of “black magic.” According to one of
our informants:
I consider that the actual fusion has a lot of
voodoo. There is
a lot of things people do, they don’t know why.
I don’t know why but I just copy what they do and they say: “if you do
it differently, it will not work.” They
told me I had to spin the fusing cells with the top open. Why the top open? It doesn’t make any difference, this is a
small, desk top centrifuge, it doesn’t matter whether
the top is open or closed. I think the
history of it is [laughter] that you can’t regulate the speed that well, so
initially when people used to do it, they would open the top and see how fast
it would spin. Now people know how to
regulate the speed and they don’t really have to look at it anymore, but they
leave the top open! They told me I had
to leave the top open, I am supposed to be a scientist, I don’t believe the top
has to be open, but I am not going to put it down, because if the fusion did
not work, they would tell me it’s because I left the top down (an academic
researcher, fall 1985).
Some “magic” is written down while other
“magic” is transmitted through personal contact and thus circulates in the same
manner as “tricks of the trade.” Still
other “magic” circulates under the guise of reason: if a researcher is forced
to spend 10 minutes on the telephone in the course of an experiment and if that
experiment is successful, then it is possible that the subsequent protocol will
contain the instruction “leave for 10 minutes.”
“Magic,” in turn, may hide experience.
Such is sometimes the case with the optimization of experimental
conditions:
We had to do experiments - with different kinds of
feeder cells, with different kind of serum - that you never write out but allow
you to go some place later and to become “a wizard.” At the end, you end up with a kind of “voodoo
ceremony” with all these experiments you know make a difference, but you don’t
know why (an academic researcher, winter 1986).
The Problem of Standardization
Despite the fact that it is hardly
possible to test all variables and their interactions, technical manuals and
laboratory discourse often propose the future reduction of experimental
incertitude as much as possible.
However, it is more often the case that methods “become established as
soon as they happen to work at all” (Fazekas Dc St.Groth and Scheidegger,
1980:1). The decision not to standardize
is based on a variety of considerations.
First of all, scientists argue that, to
the extent that the technique “works,” it is not worth the effort to clarify
details that have no direct relation to research objectives. This distinction between technique as an end
in itself and technique as tool often refers, in turn, to prior social
distinctions between university and industry and between researchers and
technicians. For example, university
scientists may claim that in industry, where routine work is carried out
253
by technicians, the researcher in charge will surely
have written up protocols allowing a mechanical reproduction of the
technique. As noted in a technical
manual:
Experiments to study all these variables are tedious and relatively uninteresting at a time when investigators are anxious to produce some useful antibodies, irrespective of the efficiency of the process. Thus, it is not surprising that successful procedures become entrenched, and that dogmatic statements about technical variables are accepted unchallenged. As the initial excitement wears off, it is to be expected that much work will be done on technical aspects and that the procedures will lose much of their empiricism and mysticism (Zola and Brocks, 1982:4-5).
The prediction advanced in the last part
of the paragraph is far from being true for all researchers. While the move from art to science is indeed
possible, so is the reverse:
You can make different parts scientific. When we do experiments and record what the results were, in a sense we are making things scientific. But sooner or later, it goes back to art: we know the technique that works, therefore we do it, even though the next generation has never tested it: so it becomes an art. The value of making it science is not necessarily high, the value of making it work is high (an academic researcher, winter 1986).
Concern over recognition within the
network of scientific relations may also militate against the pursuit and
publication of technical improvements seen as “minor” or “trivial”:
If you want to publish a technique, you do it in Journal
of Immunological Methods or Hybridoma, but
they are not prestigious journals, many scientists don’t even get them; it’s
not worth your time to write papers for them, so you don’t. If people want to know your technique, they
just call you up, and if they have problems, they send somebody to see how you
do it (an academic researcher, winter 1986).
Moreover, optimizing experimental
conditions (“experimenting around”) is seen as work suited mainly for doctoral
students: “Post docs have to start immediately to write papers, they don’t have
the time” (Interview
with an academic researcher, winter 1986).
Nonetheless, these perceptions are not universal and vary according to
the prestige and centrality of the laboratory.
Disciplinary formation often determines
attitudes toward technique. Some
researchers once claimed that if P.E.G. is purified by recristallization,
it would lose its fusogenic qualities, which apparently
reside in the impurities contained in the commercial lots and not in the P.E.G.
itself. Other researchers argued
otherwise (Art to Science in Tissue Culture, 1983). The researcher who mentioned this controversy
to us pointed out that while he was attempting to perfect his own technique, he
had chosen to ignore this particular problem and the line of research it
suggested. He explained: “I’m a cell
culturist and not a chemist; that’s how you chose.”
Artisanal elements of laboratory work are often held to
constitute the “style” of a laboratory, which can be seen as either an obstacle
to standardization or as yet another form of it. Researchers in two different laboratories
within the same university distinguished between the two labs on the basis of
their styles of equipment procurement and maintenance. One lab was characterized as possessing
“Gucci” equipment (“You know - like Gucci leather”), while the other maintained
less fancy apparatus:
Spencer’s lab is known for what they call their
“Spencer grade”: it’s low-tech, but it always works. If they have a broken piece of equipment,
they say “it’s Spencer grade”; the way I interpret it is that their equipment
is all very well used, they have nothing fancy, but everything is functioning,
and it is an excellent place to learn hybridoma
technology (an academic researcher, fall 1985; Spencer is a pseudonym).
The decision to use more rudimentary
equipment allows researchers in Spencer’s lab to display artisanal
dexterity foreign to the “Gucci” lab: “When ‘plating out’ the fused cells I am
of the old school, I use a pipette with the finger on it; some people use
multiple pipettors, I
don’t trust them” (an academic researcher, winter
1986). It has also allowed members of
the laboratory to “trade-mark” their style (see also Traweek,
1984):
We have T-shirts: “100% Spencer grade.” The philosophy behind this is “do as much as
you can with as little as you can,” use old instruments etcetera, that is
“Spencer grade” equipment (an academic researcher, winter 1986).
It may be argued that characterizing
differences between laboratories, such as the choice of myeloma,
in terms of style, itself conceived as a sort of epiphenomenon with regard to
research, tends to eliminate the problem of the existence of different and
sometimes contradictory prescriptions of the hybridoma
technique. However, questions of style
involve both problems of content and form (Goodman, 1978:23). It is, therefore, worth asking how the
researchers themselves account for variations in hybridoma
technique.
Some researchers divide protocols into
the “reproducible” and “effective” and those which must be assumed to be
idiosyncratic and futile. According to
French et al. (1986:345), for example, “A number of fusion protocols use polyethyleneglycol to promote fusion. We have found the protocol described by Fazekas de St.Groth to be
reproducible and effective.” However,
even from a researcher’s point of view, such a solution is not entirely
satisfactory since it tends to remove the recognized role played by artisanal elements.
Other researchers prefer thus to
distinguish between “rigid protocols” and “minimal type protocols”:
I have “minimal type” protocols. Hybridoma
technology is mostly a question of instinct and experience. I look at cultures by their color, I don’t do
cell counts. I’m not a very rigid type,
but I do know people who have very rigid protocols as far as feeding,
splitting, and manipulation of cells goes.
I believe rigid protocols are overdone (an industrial researcher, winter
1986).
In general, however, both scientists
interviewed and texts surveyed tend to distinguish between important and
accessory parts of research protocols.
Important steps refer to those which are supposed to have a direct and
determinant effect on the experimental results.
As such, they are subject to careful experimentation with regard to the
parameters they entail. Accessory steps
exercise only a secondary influence on the hoped-for outcome and are therefore
considered to be subject to the idiosyncrasies of the laboratory
concerned. A similar distinction is also
introduced with regard to the elements whose presence or absence defines the
“rigidity” of a given protocol. The
following quote deals with the possibility of including within written
protocols instructions concerning the transfer of cells:
We do that in some cases. The indicator cell line for the assay of
T-cells has to be passed every two days, given a supplement every two days:
people who tried to stretch that ran into problems. For other cell lines, I haven’t written it
down; some you write down, some you don’t: every cell line is different, so
writing it down doesn’t mean a lot. But
for indicator cells it is important. If
necessary, we do it; most of the time it’s not necessary. Some people are better at that sort of thing
than other people. Depends on how good a
farmer you are” (an academic researcher, winter 1986).
When questioned about the lack of consensus as to the criteria for “important” and “accessory” and the fact that laboratories using protocols differing in important steps still manage to produce hybridomas, researchers have recourse to finer distinctions. Hybridomas themselves are divided into “ready-to-wear” (i.e, directed towards extremely immunogenic antigens and thus, by definition, easy to produce) and “sophisticated.” Laboratories are divided into “advanced” (“We are a year and a half ahead of everybody else.”) and “ordinary,” or industrial and academic, or distinguished according to disciplinary affiliation wherein the technique has central or secondary meaning for the problematic. As can be seen, the understanding of research protocols by scientists implies a distinction between the “technical” and the “social” which forms a part - call it a sociology - of the researchers’ practical reasoning.
255
The terms “science,” “art,” and “magic”
have so far been used to describe different parts of the hybridoma
technique. In this final section, we
examine how these categories have been applied to hybridoma
technology as a whole.
“From art to science” is a common
expression in areas such as immunology and cell culture (for an example from
engineering, see also Schön, 1983). It also appears regularly in the various
essay reviews and technical manuals devoted to monoclonal antibodies. In spite of what has been said so far
concerning the artisanal and sometimes “magical”
character of hybridoma technology, this technology is
often presented as a decisive step forward in the move from art and/or “magic”
to science in the antibody domain:
Prior to 1975, the production of antibodies was
considered by some to be a black art practised by
immunologists... The uncertainties about the specificity of individual antisera led to many prolonged and acrimonious
debates. All that has
now changed (Goding, 1983:1-3). Serology involving conventional polyclonal
antibodies used to be an art bordering on science, and immunologists could be
divided into those who believed in immunochemistry and those who believed in “immunomagic.” While
the latter school will always be with us, the discovery of hybridoma
antibodies has done much to put serology on a firm scientific basis (Goding, 1983:40).
The theme of a move from art to science
is not restricted to university researchers.
It surfaces regularly in the advertising brochures of companies
specialized in the sale of scientific equipment and reagents. A technical bulletin distributed by the HyClone company, purveyors of the “Taggart Hybridoma Technology” mentioned above, bears the title Art
To Science in Tissue Culture . The Invitron company publicizes its
cell culture products proclaiming that “The Art of cell culture has passed
away... The Science of cell manufacturing has arrived.” According to Invitron,
the art of cell culture was characterized by the use of “Ascites
Fluid” and “Esoteric Protocols,” whereas the new “Science” requires the use of
“Computerized Automation” and “Bioengineenng.”
There are, however, different roads from
art to science. In Invitron’s case, it would appear
that the route is entirely technical.
Not only is the transformation accomplished through sophisticated
technical equipment, but the vision of science advanced is one of a series of
technical operations largely devoid of conceptual content. University researchers, on the other hand,
tend to see the transformation conducted at the level of the concepts
themselves. Arguing that the production
of monoclonal antibodies has made many artisanal
aspects of immunology scientific, Goding claims that:
The old uncertainties of specificity and
reproducibility have been replaced by the promise of unlimited supplies of
standardized, monospecific antibodies. Terms like “titre”
and “avidity” have become virtually obsolete.
We can now talk about mass and affinity of antibody in a very precise
way (Goding, 1983:40).
The degree to which an experimental
practice is perceived as artisanal or scientific also
depends upon the perceptions and self-perceptions of the discipline in
question. The classification of a
technique as either art or science, for example, not only determines how a
given technique will be circulated, but is also often an expression of a hierarchy
among the laboratories involved in the circulation of the technique. A researcher told us that previously it had
been necessary to visit another laboratory in order to learn the hybridoma technique as applied to T-cells. Now, however, his own
laboratory had become a second possible port of entry into the domain. The classification of the technique may, in
addition, serve as a means of promoting technical changes as “improvements” or devalorizing changes as idiosyncratic “variations” of
little scientific impact. In such cases
the application of the label may serve to establish or disrupt scales of
credibility, which separate researchers.
Disciplines, too, may be implicated in
the process of classification. As the
quotation at the
beginning of this section suggests, immunology has often been
taxed with having indulged in “immunomagic.” This often occurs when researchers trained in
supposedly “harder” disciplines such as biochemistry or molecular biology
reflect on what appears to them to be the more arcane or esoteric procedures in
immunology. Having decided to devote himself to the study of immunology, a successful biochemist
we interviewed found that his former colleagues viewed his newfound interest
with skepticism bordering on hostility.
This conflict is reflected within immunology,
as Goding (1983:40) would have it, by those “who
believe in immunochemistry and those who believe in immunomagic.” Here, however, the dispute is exacerbated by
the fact that the relations between science, art, and magic form the basis of
the opposition between two schools of thought in modern immunology, the
“system” immunologists and the “step-by-step” immunologists. The latter school would be represented by
researchers who restrict themselves to the sequential solution of problems
dealing with a restricted number of variables.
The “system” school, on the other hand, would be represented by those
concerned with providing somewhat indirect solutions to very general problems
such as the causes of cancer. Because of
the opposing views of the relations between theory and practice, evaluation of
research becomes especially problematic:
If there are two ways of looking at immunology, what
do you do if you have a system immunologist who is a lousy scientist and you
cannot verify easily his results and he did a bad experiment? To account for his results, he usually
invents a complicated theory... Some of these people who are bad scientists and
who build a house of cards can become very prominent. In immunology, bad scientists cannot be
easily detected (an academic researcher, fall 1985).
In such cases, judgements
concerning the reliability of a researcher’s results can only be based on an
assessment of the researcher’s long-term performance; this, in turn, raises the
question of the “experimenter’s regress” as described earlier.
In the field of industrial production,
the classification of experimental procedures as art, science, or magic is
determined in part by the demands of commercial success as well as the
guidelines of the various regulatory bodies governing activity in a given
industrial sector. Comparing the
relative merits of two recent techniques, DNA probes and monoclonal antibodies,
on the basis of their possible use in commercial diagnostic kits, one author
noted:
Anything which involves a great deal of “art” or
extreme complexity will be relatively disadvantaged. Art particularly is anathema to rational
production decisions and to the regulatory and supervisory mechanisms in the
health care industry of most countries (Nash, 1985).
The standardization of procedures using monoclonal
antibodies has been described in the following mixed metaphor: “a jungle full
of pitfalls” (Haaijman et al., 1984).
From the point of view of the university
researcher, the perception of his practice of the hybridoma
technique as art has certain advantages with regard to his relation with
industry. First of all, it allows the
researcher to distance himself from industry by projecting the routine aspects
of hybridoma technology as industrial practices. At the same time, it allows the researcher to
reaffirm a relationship of mutual dependence between university and industry in
the domain of biotechnology. Given the
fluid nature of the boundaries between industrial and academic institutions in
this area (several biotech start-ups stress the quasi-academic climate of the
firm), it is no surprise to find that the opposition between art and routine is
also used within the industrial sector to distinguish one firm from another or
different departments within the same firm.
Finally, the classification of knowledge has many consequences for patenting practices. It may be argued that the passage from “magic” to “science” in the area of antibody production has opened the possibility of patenting an antibody against a given antigen. Questions relating to the status and the mode of circulation of patentable knowledge have played a central role in the court battles that have engaged two pioneers in the commercial exploita-
257
tion of hybridoma technology, Hybritech and Monoclonal Antibodies Inc. (Mackenzie, Cambrosio and Keating, 1987).
In this paper we have examined how
researchers using hybridoma technology classify their
knowledge and their activities using the categories of “science,” “art,” and
“magic.” We have seen that in the
establishment and diffusion of a scientific technique, which may be conceived
of as an embedded system of practices, scientists have recourse to many forms
of knowledge. That part which may be
considered tacit or local depends upon the network of relations within which
the scientists work. This network is
comprised of a system of heterogeneous elements (theories, machines, patents,
products). The articulation of these
diverse elements occasions the emergence of the scientists’ categories of
knowledge.
As noted in the introduction, recent
work in the sociology of science has attempted to construct similar
classifications of scientific knowledge and practice using such categories as
objective, declarative, procedural, tacit, and local knowledge. Despite the fact that the sociological
classifications are presumably the result of a concerted effort of reflection
and analysis, they are not, as we have seen, fundamentally different from the
supposedly naive, ad hoc typologies of the scientists. For although the sociological categories
presume to describe dimensions of science overlooked by or invisible to
scientists, they invariably make use of the scientists’ categories to achieve
this end. It is true that the use of
these categories by scientists is not always consistent and that the boundaries
between categories vary among institutions, practices
and interests. But the same may be said
of the sociologists’ categories. We have
attempted an empirical demonstration of the inadequacy of these categories,
considered fundamental by sociologists, and of the need to relativise
them. In particular, we believe that the
existence of “immunomagic” (i.e., that knowledge and
know-how that scientists have agreed to drop from discussion for a given period
of time) shows that these categories are unable to account for the strategies
employed by scientists.
As we have seen, while scientists often
present ideal, algorithmic accounts of their work, they also recognize and work
with tacit or local dimensions of knowledge whether they be
classified as “art” or “magic.” In many
respects, the scientists’ own descriptions of the kinds of knowledge with which
they deal on a daily basis are both more precise and more comprehensive than
the descriptions offered by sociologists.
Not only are the scientists capable of describing the choices open to
individuals and institutions, but they also recognize the many ways “tacit” and
“local” knowledge, contrary to the sociological definitions of these terms,
circulate among different scientific and technical cultures. Indeed, contrary to what some sociologists of
science argue, a common culture is not a prerequisite for the emergence of a scientific
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