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Medical translation in the history of modern genomics

Periodic Reporting for period 3 - TRANSGENE (Medical translation in the history of modern genomics)

Reporting period: 2019-10-01 to 2021-03-31

This project investigates how different institutions collaborated in the mapping and sequencing of the yeast, human and pig genomes between 1980 and 2015. We are particularly interested in looking at the ways individuals and institutions envisaged the future use of the map and sequence data for medical, industrial or agricultural purposes. Our initial findings suggest that after 1996 the planning for the future use of the data was de-emphasised in favour of the rapid completion of the genome of the three organisms via high-throughput sequencing technologies. This prioritisation of systematic completion included the immediate open release of the sequence data and became the preferred strategy of the National Institutes of Health of the United States, the Wellcome Trust and other key policymakers. We are now analysing factors that led to this transition to full genome sequencing and reflecting on what lessons policymakers in charge of biomedical research can learn from this story.

After three years working on the project, we have redefined our objectives as follow:
a) The combination of qualitative and quantitative social science methods in the study of how human, yeast and pig genomics were organised and how this organisation changed.
b) The development of a connected and transnational history of human, yeast and pig genomics by looking at who was sequencing DNA at different time periods rather than just focusing on a particular country, geographical area or high profile genomic initiative.
c) The design of an interdisciplinary methodology that addresses medical and agricultural translation as processes that unfold over time. This is enabling us to realise that DNA mapping and sequencing projects may be part of translational strategies rather than just exercises of data accumulation.
After collecting a comprehensive corpus of evidence on the history of genomics, the project has now concluded the analysis of these materials. They include over 20 interviews with scientists and technicians involved in the sequencing of yeast, human and pig DNA, and policy records from the archives of the institutions in which these sequencing practices were conducted, among them the Stanford Genome Technology Center, the Massachusetts General Hospital and the Institute National de la Recherche Agronomique (INRA). We have also compiled a quantitative dataset of over 28,000 publications that described for the first time yeast, human and pig DNA sequences in the scientific literature and information on over 13 million submissions of these new sequences to the European Nucleotide Archive – an open access database – between 1980 and 2015. This quantitative evidence is now freely available at the Data Repository of the University of Edinburgh and a brief note describing it has been published by the journal F1000 Research.

Combined, this qualitative and quantitative evidence represent an invaluable source for addressing the history of genomics globally. The quantitative and qualitative data have enabled us to look at individuals, institutions and endeavours that were obscured by the furore around cutting-edge sequencing centres and initiatives such as the Human Genome Project. The analysis of the materials involved the collective work of a team that included experts in quantitative bibliometrics, qualitative social science, history of science and innovation studies. This collective dimension of the work is unusual in history of science research, which has traditionally been the province of the lone scholar or small, strongly disciplinary-focused group.

The results of our work have been submitted as a special issue to the journal Historical Studies in the Natural Sciences. The volume is formed by five articles: one describing our interdisciplinary teamwork, three applying our qualitative and quantitative methodology to the study of the history of yeast, human and pig genomics and a final reflective essay comparing our results across the three species. Subject to satisfactory peer-review, the special issue will be published in 2021.

In parallel to this, the project’s team has published four peer reviewed articles, the first one reflecting on the connections between the practice of sequencing and the discipline of genomics, the second one on the creation of transgenic animals, the third one on the history of quantitative animal genetics and the fourth one on how the notion of the yeast genome was mobilised as a discursive strategy.
The project has developed a methodology that combines quantitative and qualitative approaches. We have attempted to do this in a different way from other examples of mixed methods in the fields of history and sociology of science. In our project, neither the quantitative, nor the qualitative evidence take precedence over the other. We address both the quantitative and qualitative data as corpuses of evidence that co-constitute each other: without the qualitative information provided by interviews and archival research we would not have been able to interpret our quantitative data and, conversely, without a large quantitative dataset our investigation would have been restricted to a subset of already available qualitative evidence. Our interdisciplinary team formed by historians and social scientists whose expertise range from bibliometrics to Science and Technology Studies has been crucial for the design of this approach. With it, we seek to avoid two unwanted extreme positions: approaching the quantitative data as a superior form of evidence or using it only to justify a number of pre-conceived qualitative ideas.

This interdisciplinary, mixed methods approach has enabled us to find hidden actors and connections in the history of genomics, thus overcoming a too narrow focus on the Human Genome Project or other high profile case studies. The DNA sequencing practices that our hidden actors mobilised may help current policies aimed at improving the medical and agricultural translation of genomic data. Our project is showing that translation is an essentially local activity in which the specific context and the end user should be carefully taken into account. This seems somehow at odds with high-throughput sequencing technologies, and more aligned with the smaller-scale, goal-oriented strategies that proliferated in the early-to-mid 1990s and our project is making visible again.

Our objectives until the end of the project are:

a) To write a monograph provisionally entitled A History of Genomics across Species and Projects, to be submitted to Palgrave Macmillan in June 2021. The proposal has already been accepted by the publisher and the resulting monograph will gather the main conclusions of our investigation on the history of yeast, human and pig genomics.
b) To publish a special journal issue in Historical Studies in the Natural Sciences. The constitutive five articles describing our methodology and its application to the study of the history of yeast, human and pig genomics were submitted for peer review in December 2019.
c) To finalise a number of stand-alone articles on different aspects of yeast, human and pig genomics that have been submitted to different journals in the fields of history of science, and Science and Technology Studies.
d) To write and submit a follow-up funding application, and transform the project’s Research Fellow into an independent scholar.