The commercial application of a scientific discovery: The case of the hybridoma technique

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This article is an examination of the diffusion of a particular scientific technique, the hybridoma/monoclonal antibody technique, focusing on its adoption (with various degrees of success) by five institutions in three countries - Canada, the U.S., and the U.K. - for use in diagnostic kits for Hepatitis B. As such, it is pertinent to the more general issue of the appropriation of scientific discovery for use in commercial products. Consequently the article also includes the exposition of a model to allow for a systematic comparison of the different strategies used by the institutions for adopting the hybridoma/monoclonal technique. The institution sample includes academic (research, hospitals), commercial (companies), and hybrid institutions.

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... 6. Mackenzie, Cambrosio, and Keating (1988). 7. The "technological trajectory" notion has been developed to great effect by Dosi (1984). ...
... 13). For a discussion in relation to the model see Mackenzie et al. (1988). For a somewhat critical discussion see Mackenzie (1985). ...
There has been some concern m recent years that economic interests in the biotechnology area could, particularly through patenting, have a constricting influence on scientific research. Despite this concern, there have been no studies of this phenomenon beyond isolated cases. In this article we examine the evolution of the biomedical field of hybridoma/monoclonal antibody research with detailed examples of the three types of patent claims that have emerged there—basic claims, claims on application techniques, and claims on specific antibodies. We analyze the impact of these claims and their legal histories on (1) the free flow of scientific information and, (2) the activity of scientific researchers. We conclude that such patent claims present severe restrictions for both, not only in the monoclonal area but in general, amounting to a subtle but significant shift in the political economy of science and technology.
... At nearly the same time in 1975, Cesar Milstein (a biochemist) and Georges Kohler (a biologist) developed the hybridoma technique which combined antibody producing B cells to mouse tumor cells. The discovery of genetic diversity and the hybridoma technique permitted scientists to create monoclonal antibodies of extremely high specificity in large enough quantities and helped them diagnose various diseases and infections accurately (Mackenzie et al., 1988;Cambrosio and Keating, 1992). Understanding the abilities of monoclonal antibodies for oncology, Lee Nadler, a 33 year old hematologist and oncologist at the Dana Farber Cancer Institute of the Harvard Medical School in Boston, and his friend Phil Stashenko (an immunologist and trained dentist) developed a monoclonal antibody which could identify non-Hodgkin's lymphoma, a form of cancer. ...
... Afin de poursuivre ces interrogations, nous proposons d'étudier ici les deux points suivants : 1. Quels sont les arrangements contractuels ou les règles communes d'attribution des résultats mis au point par les laboratoires et les entreprises pour faciliter leur coopération? 2. Le modèle d'organisation de la science et de la technologie défendu par Dasgupta et David (1994), fondé sur la séparation entre "la République de la Science", gouvernée par les normes de la "science ouverte", et le "Royaume de la Technologie", régi par l'appropriation de la rente d'innovation, est-il satisfaisant au regard des nouvelles formes d'organisation qui se mettent en place, caractérisées par l'émergence d'institutions hybrides (Mackenzie et al., 1988) du CNRS prescrit que « les résultats de l'étude sont la propriété du CNRS » Seuls neuf contrats prévoient un partage des résultats entre le laboratoire e l'entreprise tandis que quatre accords attribuent la propriété des résultats au seu laboratoire. Les formules de copropriété portent principalement sur des travau de développement de prototypes commencés à l'université. ...
In a European context of knowledge-based and information driven society, Catalonia is evolving to a new economic model for sustainable growth. Among all the research priorities and market opportunities, findings suggest that the commercialization of the nanobiotechnologies developed in Catalonia is a big issue for researchers and innovation managers. A subsequent analysis suggests that Catalan universities and science and technology parks are key players in the area of nanobiotechnology transfer and innovation, and thus they have a fundamental role in fostering the innovation and creativity that are emerging from the social and industrial nano-revolution, with special attention being paid to the nanomedicine field in the Barcelona area.
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.
This essay analyzes how academic institutions, government agencies, and the nascent biotech industry contested the legal ownership of recombinant DNA technology in the name of the public interest. It reconstructs the way a small but influential group of government officials and university research administrators introduced a new framework for the commercialization of academic research in the context of a national debate over scientific research's contributions to American economic prosperity and public health. They claimed that private ownership of inventions arising from public support would provide a powerful means to liberate biomedical discoveries for public benefit. This articulation of the causal link between private ownership and the public interest, it is argued, justified a new set of expectations about the use of research results arising from government or public support, in which commercialization became a new public obligation for academic researchers. By highlighting the broader economic and legal shifts that prompted the reconfiguration of the ownership of public knowledge in late twentieth-century American capitalism, the essay examines the threads of policy-informed legal ideas that came together to affirm private ownership of biomedical knowledge as germane to the public interest in the coming of age of biotechnology and genetic medicine.
At several places in this paper we have made use of a well-known rhetorical device: an argument was made; a character —dubbed fictional reader — was then evoked who voiced some objections against that particular argument; and finally, we answered those objections, thus bringing to a close, at least temporarily, our argument. The use of this device raises a question: How is the presence of the fictional reader to be understood? Is it a mere rhetorical tool, or does this character designate some particular target? For instance, depending on the context, it could be seen as aimed at different straw men: traditionally minded sociologists, Whiggish historians, well-intentioned philosophers of science. Actually, none of these characters is behind the fictional reader. Rather, it refers, potentially, to any of the scientific actors (Milstein, Schwaber, Koprowski, Cohn, and so on) who inhabit our set of narratives. In other words, the fictional reader is an icon for the native reader/writer who simultaneously produces and questions the products of that particular literary activity known as scientific texts, by explicitly and implicitly raising the issue of the distinction between fact and technique.By following actors in their disputes about the novelty of K & M's contribution, it became apparent that it is not exactly clear which of the different elements of hybridoma technology should be regarded as novel. Was it the use of the P3 myeloma line? Was it the theoretical framework related to the notion of allelic exclusion? Was it ...? In each and every case, arguments can be made for or against the existence of a certain continuity or discontinuity with previous work. And in each case, the determination of novelty, as translated through the continuity/discontinuity issue, appeared to be hanging on the previous attribution of an epistemological status to the object that had allegedly been discovered: was it a fact or a technique?If one focuses on the relatively narrow network of immunogenetics, it could be argued that within that particular evidential context a series of facts had been established which, when transferred to other fields, such as the virological research being pursued in Koprowski's institute, were translated into a technique. However, as we have seen, even from an immunogenetic point of view the production of monoclonal antibodies can be viewed as being simultaneously a fact and a technique to establish that fact. Not only, as he himself noted,139 was Milstein not seeking to develop a technique for the production of monoclonal antibodies when the original experiments were carried out, but the significance later imputed to those experiments was not immediately attributed to them. The paper was seen as one among other papers that used cell fusion techniques to dissect the genetic control of antibody diversity. Distinctions that now appear crucial (e.g.: were the fusion partners two myelomas or a myeloma and a spleen cell?) were easily overlooked. At some point, around 1977, the production of monoclonal antibodies became a goal in itself, no longer linked to the initial immunogenetic network. The transformation of [MILSTEIN 75] into the foundational event of hybridoma technology was thus achieved. This transformation did not flow naturally from the original experiments. Rather, it involved specific investments which mobilized the activity of a large number of other scientific and industrial actors.140 A tentative generalization can be deduced from our case study. The dichotomy between fact and technique that underlines much of contemporary science studies seem to be fundamentally misconceived, insofar as the determination of what counts as a fact and what counts as a technique is not possible on a priori grounds. Historians and sociologists of science are confronted with a field of heterogeneous interventions where particular pieces of work are constituted as discrete entities and simultaneously attributed a technical or a factual identity. Novelty and innovation are precisely the result of such polymorphic attributional processes.
The Argument while reconizing that public sector research has long been managed by a wide variety of practices and techniques, this paper concentrates on the increasingly important role that patents are playing in the management and regulation of public sector research. It argues that as a specific form of technology, patents play a significant and growing role in facilitating the management of the scientific object and can also be seen as a particular instance of governmentality. More specifically, it argues that patents have had an important impact on the culture and political ecomomy of science. In this sence patents can be seen not only as a legal regime that provides limited property rights over technical information but also as a sophisticated tool of discipline and control that is used to regulate and manage public sector research. The paper suggests that with the increasing use of patents as a means of governing science, we are witnessing the growing juridification of science, the intervention of the law into an arena it hitherto largely ignored.
This paper suggests that the established and distinctive dualisms invoked to describe aspects of research and forms of organisation are unravelling and becoming less meaningful in 21st century innovation, particularly as exemplified by university-industry collaboration in biotechnology. The basic-applied dualism to represent types of research activity and the public-private dualism to depict the nature of organisations are becoming redundant. Modern biotechnology draws on such an array of knowledge, from various disciplines and organisations, and with intricate, non-linear transfer mechanisms between actors, in order to deliver a broad range of applications, that conventional labels are becoming irrelevant. This has implications for the role and nature of the university in society.Journal of Commercial Biotechnology (2006) 12, 127-147; doi:10.1057/
Issues surrounding data access, ownership, and control raise important issues for science policy. The new sociology of science has examined many features of scientific knowledge and practice, but has made only preliminary efforts to study data access. Building on ethnographic studies of scientific laboratories (and other constructivist work), this article suggests how the new sociology of science can study data access empirically. The article develops a perspective based on an analysis of the process of scientific production and the creation, packaging, and exchange of data streams. It also provides an example of how constructivist studies can contribute to policy analysis.
This paper investigates the industrialization of biomedical materials at the New England Enzyme Center (NEEC) from its establishment as a federally supported biochemical resource center in 1964 through its demise and refashioning into several commercial biotech companies in the late 1970s. It sets this history within the long-standing debate on the proper relation between science and American economic and political traditions. The NEEC sought to embody two aims that stood in tension: academic independence in knowledge production and the market-driven interests of the biomedical industry. A clash of values ensued, but built on a particular notion of independence: scientists pragmatically accepted the primacy of the market in the age of the 'federal research economy.' The question became how to carve out a space for science and scientific values in the market - an intellectual position that some legal and economic scholars have referred to as a scientific commons. Even so, industry executives came to see the idea of a scientific commons and public knowledge as obstructive to industrial innovation. This paper argues that, as seen through the case of the NEEC, the ascendancy of market values and attitudes in the 1970s played a critical role in reconfiguring the science-industry relationship and in 'industrializing' the life sciences. As illustration of this change, I look at a commercial firm - Genzyme - born out of NEEC's dissolution.
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This paper analyzes expert testimony from a patent dispute involving two California biotechnology companies. This case provides us with an opportunity to study “science” and “law” as they interact, instead of contrasting them as separate, although parallel, practices. In the court, “science,” which usually bears the marks of objectivity and certainty, appears uncertain and subject to interpretation. Through an examination of the representations made by scientific witnesses during the trial as to the origin, novelty, and non-obviousness of the disputed object of discovery, we show that, while one might expect “technical” arguments to play a central role in the proceedings, “social,” “historical,” “economic,”or “philosophical” arguments are coextensive with and constitutive of the “technical.”
This article reports on the research and development of a cutting-edge biomedical device for continuous in-vivo glucose monitoring. This entirely public-funded process of technological innovation has been conducted at the University of Barcelona within a context of converging technologies involving the fields of medicine, physics, chemistry, biology, telecommunications, electronics and energy. The authors examine the value chain and the market challenges faced by in-vivo implantable biomedical devices based on nanotechnologies. In so doing, they trace the process from the point of applied research to the final integration and commercialization of the product, when the social rate of return from academic research can be estimated. Using a case-study approach, the paper also examines the high-tech activities involved in the development of this nano-enabled device and describes the technology and innovation management process within the value chain conducted in a University–Hospital–Industry–Administration–Citizens framework. Here, nanotechnology is seen to represent a new industrial revolution, boosting the biomedical devices market. Nanosensors may well provide the tools required for investigating biological processes at the cellular level in vivo when embedded into medical devices of small dimensions, using biocompatible materials, and requiring reliable and targeted biosensors, high speed data transfer, safely stored data, and even energy autonomy.
Beyond the much too simple view that sees basic and industrial research - universities and the economy - as being opposed, a series of more or less explicit contracts link actors' rationales. This analysis of 158 contracts signed between laboratories and industrialists over a 20-year period shows that multiple situations are created, as well as various forms of compromise that defer to actors' rationales while taking into account legal requirements, the need to publish and hierarchies of knowledge.
This paper suggests that the established and distinctive dualisms invoked to describe aspects of research and forms of organisation are unravelling and becoming less meaningful in 21st century innovation, particularly as exemplified by university–industry collaboration in biotechnology. The basic–applied dualism to represent types of research activity and the public–private dualism to depict the nature of organisations are becoming redundant. Modern biotechnology draws on such an array of knowledge, from various disciplines and organisations, and with intricate, non-linear transfer mechanisms between actors, in order to deliver a broad range of applications, that conventional labels are becoming irrelevant. This has implications for the role and nature of the university in society.
This paper examines the evolving relationship in science between the reward structure and entrepreneurial activity. We draw a distinction between two types of property rights. Basic science is fostered by a mechanism of reputational rights; technological advances-and the products and processes they produce - are fostered by a mechanism of proprietary rights. The two forms of property rights differ markedly in terms of the incentives they provide to share information in a timely fashion. We argue that because of a host of factors university-based scientists in certain fields are more likely to “privatize” knowledge today than in the past, trading reputational rights for proprietary rights. Events in the life sciences serve as a case study. A discussion of how privatization affects basic science follows. Although the evidence is far from complete, we conclude that the movement towards privatization may be more beneficial to product development and the scientists engaged in the activity than to basic science.
Observing that the notion of economic crisis per se has, from its origins, been closely tied to the idea of technological progress, this article examines the roots and development of this liaison in Marx, Schumpeter and the recent contribution of Freeman, et al. (1982). A concept (the Third Sector) is proposed for the relation between the structural evolution of economic organization and technological progress; this concept is developed through a critique of Marx and Schumpeter in the light of contemporary economic circumstances, and as complementary to the more technology‐generic “new technology systems” approach of Freeman, et al. In conclusion it is found, on a cursory examination, that the organizational changes implied by the Third Sector are corroborated by the evolution of technology‐based multinational corporations, while echoing Marx and Schumpeter in their possible consequences for economic crisis in the 1980's.
This paper summarizes various positions on appropriate technology and its relation to technological dependence, and certain contradictions within the concept are pointed out. An alternative approach to policy questions in appropriate technology assessment and independence is then proposed using a framework involving three economic sectors—the consumer goods sector, capital goods sector, and technological change sector.
As monoclonal antibodies enter their second decade, they continue to exhibit great potential for the diagnostic immunoassay industry. This is reflected in the current and future products which exploit their characteristics. However, much like a young child approaching adolescence, they are not without their share of peculiarities and growing pains. An awareness of the inherent advantages and disadvantages of the monoclonal antibodies themselves and the new technologies associated with them will continue to make their outlook bright for diagnostic and other applications.
Thèse (Ph. D.)--Université de Montréal, 1983. "Thèse présentée à la Faculté des études supérieures en vue de l'obtention du grade de philosophiae doctor (Ph. D.)."
THE manufacture of predefined specific antibodies by means of permanent tissue culture cell lines is of general interest. There are at present a considerable number of permanent cultures of myeloma cells1,2 and screening procedures have been used to reveal antibody activity in some of them. This, however, is not a satisfactory source of monoclonal antibodies of predefined specificity. We describe here the derivation of a number of tissue culture cell lines which secrete anti-sheep red blood cell (SRBC) antibodies. The cell lines are made by fusion of a mouse myeloma and mouse spleen cells from an immunised donor. To understand the expression and interactions of the Ig chains from the parental lines, fusion experiments between two known mouse myeloma lines were carried out.
The selection of monoclonal antibodies directed against hepatitis B surface antigen, and the effects of their subtype specificities is reported with a view to future development of an assay system for hepatitis B virus infections.
A new biotechnology with far-reaching practical applications is about to make a major commercial impact. Hybridoma technology was invented at about the same time as recombinant DNA but has grown up in its shadow. Yet the technique promises to revolutionize immunology and all the areas of research and medicine which immunology embraces. Hybridomas are artificially created cells that produce pure or 'monoclonal' antibodies. Having a constant and uniform source of pure antibody, instead of the usual mixture produced by the immune system, not only affords a powerful research tool but can be expected to provide quicker and more accurate diagnosis of viruses, bacteria, and cancer cells. The long-range promise of monoclonal antibodies is that they will be therapeutically useful as vaccine replacements and in the treatment of cancers. The hybridoma technique was invented in 1975 by Cesar Milstein and Georges Kohler working at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, England. A mouse is injected with antigen and the antibody-making cells of its spleen are then fused in a test tube with a cancerous type of mouse cell known as plasmacytoma. The hybrid cell so formed produces the single type of antibody molecule of its spleen cell parent and continually grows and divides, like its plasmacytoma cell parent. Once the clone of cells producing the desired antibody has been selected, it can be grown as a continuous cell line from which large amounts of the pure or monoclonal antibody can be harvested. The power of the method is that one or more specific antibodies can be developed against any organism or substance antigenic to the mouse. By contrast, the natural antibodies made against a given antigen are a mixed bag of molecules, with each type targeted against a different feature of the antigen. Monoclonally produced antibodies also have the virtue of consistency - each rabbit produces a different mix of antibodies against a given antigen - and their production costs are cheaper.
This chapter discusses the strategies and procedures for the preparation of monoclonal antibodies (McAb). The derivation of permanent lines of hybrid cells, producing McAb, exhibiting certain desired properties, presents widely different degrees of difficulty. Desired properties include not only specific recognition of an antigen and other no less critical properties are the fine specificity of the antibody, avidity and kinetic parameters important for radioimmunoassays, cytotoxic properties necessary for direct complement-dependent lysis. The insoluble antigen and the antibody in the culture fluid are allowed to react. The free antibody is washed away. The amount of monoclonal antibody bound is measured directly or by binding of a second, labeled antibody capable of recognizing the first. Monoclonal antibodies can be easily labeled internally at high specific activity, using radioactive amino acid precursors. The choice of these is based on the efficiency of incorporation of labeled amino acids into secreted immunoglobulin in culture conditions. The hemagglutination assays are based on the ability of an antibody to agglutinate red cells, carrying the specific antigen. These assays have all the advantages in terms of extreme simplicity, speed, and direct visual reading of the results.
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Hybritech sues Abbott on antitrust violations in diagnostic market, McGraw-Hill's Biotechnology News-watch 4
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Laboratory Robots in the Forefront of Automation Trend in Biotechnology
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Biotechnology Marketing Strategies: Case Studies from the Monoclonal Antibody Field
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