8 Europe and the Genome

1. Introduction

In March 2014, the Wellcome Library organized a Witness Seminar on the history of the Human Gene Mapping Workshops. This London-held event gathered fifteen participants, mainly senior scientists who had been active in the medical genetics community. The aim of the seminar was to gather the recollections of these scientists as witnesses to the development of the Mapping Workshops. These workshops had been organized periodically for almost thirty years, between 1973 and the determination of the reference human genome sequence. They had become a main international forum for researchers mapping human genes and wanting to pool the results of their experiments.

Most of the contributors to the Witness Seminar had developed their careers in the United Kingdom (UK) and, to a lesser extent, the Netherlands. This led them to highlight the role of the European Commission and the Wellcome Trust in providing the financial support to ensure that, throughout the 1990s, Europe maintained an important role in human genome mapping and the organization of the workshops. However, Michael Morgan, director of research partnerships at the Wellcome Trust during that decade, expressed a feeling of “missed opportunities” in Europe. With its history of support to human gene mapping and institutions such as the European Molecular Biology Laboratory (EMBL), Morgan did not understand why “the European Union never got involved” in large-scale DNA sequencing (Jones and Tansey 2015, 88).

The perception of the human genome sequence in public imagination seems to endorse Morgan’s remarks. The determination of this genome is associated with a ceremony held in June 2000 in the White House, when the then president of the United States, Bill Clinton, announced the completion of the DNA sequence characteristic of humans and formed of three billion nucleotide units. The sequence was simultaneously determined by two large, multi-institutional groups headed by Francis Collins, then director of the National Human Genome Research Institute of the United States (NHGRI), and Craig Venter, CEO of the US-based company Celera Genomics. During the ceremony, Collins and Venter accompanied Clinton, who introduced the former as “director of the International Human Genome Project.” The audience included journalists from all over the world, and the ambassadors of Japan, France, Germany, and the United Kingdom, all of them countries involved in the sequencing effort. The then UK prime minister, Tony Blair, made a remote satellite intervention and praised the sequencing endeavor as the result of an “unprecedented international partnership.”1

This international collaboration was spelled out in the Nature publication that followed the ceremony. The article, which appeared in February 2001, was signed by an International Consortium that had completed “a draft sequence of the human genome.” No further individual scientist or institution was listed in the authors’ line, under the article’s title. However, a caption box on page two referred to twenty “genome sequencing centres,” which had made the most substantial contribution to the results. The centers were based in six different countries: twelve of them in the United States, five in Europe (France, Germany, and the United Kingdom), and three in Asia (China and Japan). A full list of institutions was provided at the end of the article. These additional institutions—whose role had comprised administration and computing analysis rather than sequencing—were based in the same countries as the twenty highlighted centers, with the exception of additional teams from Ireland and Israel (IHGSC 2001, 860–2).2

Stephen Hilgartner has accounted for the emergence of this International Consortium, building on more than a decade of extensive anthropological work. Hilgartner shows that in the late 1980s and early 1990s, there were different competing strategies of how to tackle the human genome and attributes the one embodied in the 2001 Nature article to the vision of a “genomics vanguard.” This vanguard was formed by a group of loosely connected scientists who lobbied different authorities for resources to enable the complete sequencing of the human genome. In their defense of whole-genome sequencing, they clashed with other proposals that rather than sequencing the full genome, advocated for prioritizing smaller regions connected to hereditary diseases. The vanguard scientists exerted a crucial influence at the US National Academy of Sciences and managed to ensure that the national Human Genome Project in the United States contemplated full sequencing from its launch, in 1990 (Hilgartner 2017, chap. 2).

Toward the second half of that decade, the US project converged with others in countries that would be part of the International Consortium. At that time, and particularly between 1996 and 1998, the vanguard scientists pressed two major funders of human genomics—the National Institutes of Health (NIH) in the United States and the Wellcome Trust in the United Kingdom—to channel their investments into five large-scale sequencing centers (Hilgartner 2017, chap. 7). Four of these centers were located in the United States and only one in the United Kingdom; they were based in the Baylor College of Medicine (Houston, Texas), Washington University (St. Louis, Missouri), the Whitehead Institute (Cambridge, Massachusetts), the Joint Genome Institute of the US Department of Energy (DOE) (Walnut Creek, California), and the Sanger Centre (Cambridgeshire, UK). They were collectively named the Genomic 5 (G5) and were deemed to have contributed more than 80 percent to the sequence that was reported in 2001 (García-Sancho and Lowe 2023).3

According to Hilgartner, a main reason for the success of the genomics vanguard was that they distinguished their proposed endeavor—sequencing the whole human genome—from the practice of “ordinary biology.” At the same time, the vanguard scientists did not impose “new burdens” to existing “molecular biology laboratories” (Hilgartner 2017, 228); rather, they presented themselves as continuing the molecular biology mission. The 2001 Nature article positioned the determination of the draft sequence as part of the “quest to understand the nature and content of genetic information” over the preceding century. In this narrative, the elucidation of the double helical structure of DNA in 1953 represented a pivotal event, since it had defined “the molecular basis of heredity.” The double helix and the discovery of its structure has been retrospectively presented by scientists as a foundational moment of the discipline of molecular biology.4 After the elucidation of the mechanism by which cells “read the information” contained in the double helix—largely by the first generation of self-declared molecular biologists—the article evoked a “relentless drive to decipher first genes and then entire genomes, spawning the field of genomics.” The deciphering of the sequence that the authors were reporting was attributed to the Human Genome Project, an initiative that had been launched “by late 1990”—the same year that the United States had started its national program—and concluded as “an international collaboration” (IHGSC 2001, 860–2).

This narrative has been subsequently reiterated by scientists and commentators, leading to a conflation of the US national genome program—which was also called the Human Genome Project—with the initiative undertaken by the International Consortium and reported in the 2001 Nature paper.5 Historians have forcefully argued that there was never an entity that managed or funded a coherent, unitary human genome project—one that can be represented as a single historical milestone (Fortun 1999; García-Sancho and Lowe 2023). Due to this, I will subsequently refer to the US national program as “US-HGP” and to the 2001 determination of the draft sequence as the International Human Genome Sequencing Consortium (IHGSC) endeavor.

Indeed, from the mid-1980s onward, there was a plethora of national human genome programs supported by governments and, to a lesser extent, health-related charities. With the exception of the US-HGP, these programs were rather cautious about the objective of sequencing the entire human genome. Human genomics “accelerated” in the mid-1990s, and some of these nationally funded initiatives converged with the US target of whole genome sequencing (Fortun 1999, 31; see also McLaren 1991; Jordan 1993; García-Sancho and Lowe 2023). Social science literature has addressed the British, French, and Japanese human genome programs, especially the elements that materialized in the 2001 Nature publication (Balmer 1996; Rabinow 2002; Kaufmann 2004; Rabeharisoa and Callon 2004; Fujimura 2000). However, little is known of transnational human genome efforts beyond the IHGSC endeavor.

This chapter will address one such effort and therefore provide a comparative angle to the volume, whose other contributions are mainly focused on NIH-funded projects. I will present the HGAP as part of a range of initiatives in genomic research sponsored by the European Commission. The HGAP was launched in 1990 and sought to foster collaboration between the Commission’s member-states in the fields of human DNA mapping and sequencing. Unlike the US-HGP and, later, the IHGSC endeavor, the HGAP did not pursue the determination of the whole human genome sequence. The collaboration it supported was more open-ended and aimed to foster both the cohesion of the European science system and the improvement of human health. The HGAP was totally eclipsed by the announcement of the 2001 draft sequence and remains largely overlooked in the historiography of genomics.6 Some of the laboratories supported by the European Commission—especially in France—were later involved in the IHGSC, but their contributions to the published sequence were much more modest than the G5.

In what follows, I will first frame the genesis of the HGAP in two overlapping genealogies that spawned the mid-to-late 1980s: the emergence of common biotechnology policies between the Commission’s member-states and the will of European scientists to remain visible within the medical genetics community. Section two of the chapter will address the establishment of shared centers for distributing genomic resources and the engagement in a strategy called complementary DNA (cDNA) for targeted sequencing as central features of the HGAP. I will argue that these two elements created a distributed approach to human genomics that distinguished the HGAP laboratories from the IHGSC and placed the European effort closer to that pursued by Celera Genomics. The rivalry between Celera and the IHGSC was one of the reasons that led some members of the G5 to challenge the European strategy, as I will show in section three. In the concluding remarks, I will argue that while the HGAP did not generate something as captivating as a full human sequence—and never explicitly sought to produce one—its underlying strategy may be useful to tackle a central problem of the current “postgenomic” era: how to better entwine the large amounts of sequence information available with the necessities of its users’ communities.

2. A Tale of Two Genealogies

One of the few mentions to Europe in the 2001 Nature article reporting the draft human genome sequence was to acknowledge the role of the “European Community” in the launch of “several international efforts, notably the programme to sequence the yeast genome” (IHGSC 2001, 862). Unlike in the IHGSC endeavor, Europe became the largest sequence contributor to the yeast genome through the collective action of a consortium of laboratories from member-states of the European Commission.7 The yeast sequencing consortium started in 1989, one year before the launch of the US-HGP. Both initiatives grew considerably as they developed and attracted other programs: in Asia and America in the case of the yeast consortium, and in Asia and Europe for the US-HGP. Yet both the overall membership and share of European institutions was larger in the yeast than in the human effort. Due to this, the historiography has tended to identify Europe with yeast and, indirectly, to de-emphasize the role of this continent in the sequencing of the human genome (Cook-Deegan 1994, especially chaps. 3–4; Joly and Mangematin 1998; Goujon 2001).

3. The Dimensions of Human Genomics in Europe

The HGAP was officially launched by the European Commission in 1990, one year after this institution had started the Yeast Genome Sequencing Project. Yet the preparation of both initiatives was simultaneous. At the same time Goffeau was recruiting laboratories for the yeast sequencing consortium, the European Commission created a working party with prominent genetic researchers and attendees of the chromosome workshops, among them Peter Pearson from Leiden University in the Netherlands and Malcolm Ferguson-Smith from the University of Cambridge in the United Kingdom. These scientists, who worked in-between medical schools and hospitals, chose “Predictive Medicine” as the initial name of the European program.12 The name had to be replaced by HGAP before final approval, due to the concerns that the German Greens and other parties in the European Parliament expressed about the eugenic connotations of prenatal diagnosis and other predictive techniques of genetic medicine (Cook-Deegan 1994, 202; Albayrak 2015, 23ff).

The HGAP was funded by the Second Framework Programme of the European Communities (FP2) and managed by the Directorate-General XII (Science, Research, and Development) of the European Commission, as the yeast project was. Like many of the initiatives supported by the framework programs, both the HGAP and the yeast project had an initial life span of three years, the latter to complete the pilot sequencing of S. cerevisiae’s chromosome III. However, as we will see below, while the Yeast Genome Sequencing Project managed to retain its independent status beyond this three-year window—and across different framework programs—the HGAP was subsumed into a broader funding scheme after 1992. The day-to-day running of the HGAP and the yeast project was overseen by different civil servants, since the former belonged to the FP2 area of biomedicine rather than biotechnology (Hallen and Klepsch 1995, v–vi).

This different area framing was due to the HGAP having as its main and foremost objective “the prevention and treatment of human diseases.” The way in which this objective would be accomplished was through the improvement of the linkage and physical maps (see Figure 8.1) to which Pearson, Ferguson-Smith, and other medical geneticists within and outside the working group were contributing through the chromosome workshops. One of the main fields of activity of the HGAP was thus in supporting the organization of chromosome workshops in Europe and the participation of European geneticists. The maps that the chromosome workshops and the HGAP would develop were intended to encompass either the “complete [human] genome” or “genes of medical importance.”13

The ambivalence of the HGAP contrasted with the explicit goals of sequencing the whole yeast genome in Europe and human genome in the United States. This ambivalence was shaped by the limited time frame of the HGAP: following the end of its initial three-year funding (1992) the status of human genome analysis in the European Commission shifted from a program in itself to being an area of a wider funding scheme for Biomedical and Health Research (BIOMED-1, part of the Third Framework Programme). The administrative trajectory of the HGAP shows that completing the human genome was never the main objective of the European Commission. Building on the organization of the yeast consortium, this institution rather pursued the formation of “networks of laboratories” among its member-states.14 By pooling their mapping results, these laboratories would both deepen the analysis of the human genome and foster its application to broader biomedical problems.

4. Factory Operation vs. Cottage Industry

Patenting was not the sole reason that the HGAP became unpopular in some quarters. The network approach and the continuous user feedback that the European Commission promoted made the generation of map and sequence data slower than some scientists and funders expected. This feeling of slowness was especially acute among those who defended the mapping and sequencing of the entire human genome. Two of the main advocates of this whole-genome approach, John Sulston and Robert Waterston, became increasingly critical of the collective and gradual production of results that the HGAP embodied.

Sulston and Waterston shared a career that had been strongly influenced by the Laboratory of Molecular Biology of Cambridge (LMB, in the UK). The LMB was widely regarded as the Mecca of molecular biology, since it had been the home institution of self-declared founders of this discipline: Francis Crick—the co-elucidator of the double helix of DNA with Watson—and Sydney Brenner—the proponent of the worm C. elegans as an almost universal model to study the genetics of development and behavior. Sulston had become one of Brenner’s first C. elegans collaborators in 1966, following a PhD in chemistry and a postdoctoral spell at the Salk Institute in California. Waterston had started his postdoctoral career at the LMB five years later after an MD at the University of Chicago, and was also mentored by Brenner (Sulston and Ferry 2002, chaps. 1–2).

In the mid-to-late 1980s, Sulston and Waterston started a collaboration to construct a physical map of C. elegans. This project ran in parallel to Olson’s mapping of yeast and was also partially conducted at Washington University, where Waterston had moved after his Cambridge postdoc leaving Sulston, who had remained at the LMB. As in the case of S. cerevisiae, the worm C. elegans was chosen by Watson to become a platform for the US-HGP. The mapping stage of the worm showed a similar pattern to yeast and, more generally, the genome projects supported by the European Commission. Sulston and Waterston’s work anticipated that of the HGAP resource centers, in the sense that they curated clone libraries and acted at the request of external, user laboratories investigating C. elegans genetics. These laboratories sent DNA samples related to genes of interest for the worm’s development and behavior, and Sulston and Waterston screened them against their libraries and placed the corresponding fragments within their expanding physical map (de Chadarevian 2004; García-Sancho 2012b).

Nevertheless, C. elegans differed in some respects from yeast. As with S. cerevisiae, the worm was furnished with a longstanding trajectory of use as a biomedical model organism, but had never been deployed as an industrial tool for brewing or genetic engineering purposes. C. elegans was thus investigated solely for its similarities with biological processes in higher organisms, including humans, and its users were mainly interested in the genetic basis of development and behavior rather than fermentation or other aspects of cell metabolism, as had been the case for yeast. This meant that Sulston, Waterston, and other C. elegans researchers were as keen on learning the regulation mechanisms of DNA over embryo formation or brain synaptic transmission as they were on finding new genes, and sought from the onset the full mapping and sequencing of the worm’s genome. In 1989, when Watson agreed to support C. elegans as a precursor of the US-HGP, Sulston proposed a “factory style operation” in which the worm would be a pilot to test the necessary technologies and intensive, large-scale procedures to tackle the human genome.25

Sulston’s proposal became a three-year project aimed at 3 percent of the worm’s genome and funded by the UK Human Genome Mapping Project, with additional support from the US-HGP’s budget devoted to the sequencing of pilot organisms. The project was jointly conducted with Waterston, who had acquired his own funding via the pilot sequencing program of the US-HGP.26 Both scientists continued the physical mapping of C. elegans and started a sequencing operation that differed from the HGAP in two crucial aspects: (1) Sulston and Waterston mapped and sequenced the worm at their own initiative rather than creating inclusive networks or acting on demand, and (2) the goal was determining the full C. elegans sequence through comprehensive, intensive work. This high-throughput production of map and sequence data was simultaneously conducted at the LMB (where Sulston had become a team leader) and Washington University (where the parallel yeast mapping project had also transitioned to a large-scale sequencing operation).

Upon conclusion of this project, in 1992, Sulston and Waterston applied for additional funding to complete C. elegans and yeast, as well as expanding their work to include the human genome. Given the scale of their proposal, they requested the mapping and sequencing projects to be developed in purpose-built facilities. The one at Washington University was already being implemented by the NIH and also hosted Johnston’s S. cerevisiae team. In the United Kingdom, a new institution called the Sanger Centre was established in a rural area near Cambridge under the leadership of Sulston, who coordinated teams devoted to the human, C. elegans and yeast genomes—the latter outside the European consortium. The magnitude of the Sanger Centre operation exceeded the financial and logistic capacities of State-supported biomedical programs in the United Kingdom. This led the Medical Research Council—the body of the British government that sponsors biomedical research—to ally with the Wellcome Trust, a UK charity that by the early 1990s was increasingly focused on supporting genetic research and had exponentially multiplied its funding base (García-Sancho and Lowe 2023, chap. 4). The grants for the Sanger Centre and Washington University Genome Sequencing Center were both awarded in 1993 for an initial period of operation, with their budgets being periodically reviewed and adjusted accordingly.27

Soon after the creation of their sequencing centers, Sulston and Waterston realized that the successful accomplishment of their goals required new arrangements in the existing human genome programs. This necessity was even more pressing in the face of Venter’s EST approach and other efforts at patenting DNA sequences. For Sulston, Waterston, and their funders, the free dissemination of sequence data was of paramount importance. This public dissemination of results had been an integral part of the ethos of molecular biology—their home discipline—and was proving decisive in the timely completion of the worm project (García-Sancho 2012b; Strasser 2019, chaps. 5 and 6). As well as improving speed and efficiency of sequencing work, the rapid and unrestricted release of data was the best way of countering Venter and other proprietary efforts, so by the time they filed their patent applications, all the human DNA sequence would be available in the public domain (Sulston and Ferry 2002, 135ff).

The first articulation of these ambitions was in an email that Waterston sent to Sulston in September 1994, entitled “an indecent proposal.” The email outlined a strategy to accelerate human genome mapping and sequencing via a concerted effort, and an enhanced, long-term commitment of the funding institutions. Waterston’s message, and Sulston’s reaction to it, triggered an intense recalibration of their collaborative sequencing endeavors. This intensity can be observed in Sulston’s Papers and Correspondence at the Wellcome Library in London (UK): Following receipt of the email, the paper trail becomes crammed with tables, calculations, and manuscript notes in which Sulston, Waterston, the Wellcome Trust, and the NIH estimated the maximum number of nucleotides that each center could sequence over a time period and the financial cost of that increased sequencing capacity (see Figure 8.3).28 The figures formed the basis of Sulston and Waterston’s proposal to the Wellcome Trust and NIH for their next cycle of activity, due to start in 1998. Both scientists requested a rise in the level of funding and more systematic cooperation with the other sequencing centers, so the data could be assembled into a whole genome and released ahead of the projected timescales.

The strategy of the HGAP and, more generally, the distributed networks it promoted were at odds with Sulston and Waterston’s vision. In July 1994—a few months before Waterston’s email—a workshop focused on human chromosome 22 in Cambridge (UK) had revealed that tensions were brewing between different types of genome mappers: Some of the human and medical genetics attendees complained that the rapid, whole-genome technologies of the Sanger Centre were stepping on the chromosomal regions they were working on (Sulston and Ferry 2002, 131). Apart from the European Commission, the Wellcome Trust had co-sponsored these workshops in the past. Sulston believed that they meant “pouring the budget into half efforts” and called funders to concentrate their support on a comprehensive and centralized human genome initiative.29

Sulston and Waterston’s arguments persuaded the Wellcome Trust and NIH to increase their support and channel it to a smaller pool of large-scale sequencing centers. In 1994, Francis Collins, a medical geneticist formerly at the University of Michigan, succeeded Watson as responsible for managing and funding human genome research within the NIH. Unlike other geneticists, Collins had focused his career on the mapping of genes underlying different diseases rather than deepening knowledge on the sequence variations connected to a specific condition. Under his directorship, the NIH made the free release of the sequence information a driving principle of the US-HGP. This was shared by Michael Morgan, the liaison between the Wellcome Trust and the Sanger Centre (as well as an attendee to the witness seminar with which I started the chapter). In 1996, at Sulston and Waterston’s request, both funding agencies organized a landmark conference in the Isle of Bermuda in which the Sanger Centre, Washington University, and other large-scale mapping and sequencing institutions—some of them from Europe, such as Généthon—agreed to unify their sequencing practices and submit the resulting information to open access databases (Hilgartner 2017, 172ff; Maxson Jones et al. 2018; García-Sancho and Lowe 2023, 141ff).30

After Bermuda, the Sanger Centre and Washington University emerged as major sequencing players, along with the other institutions of what became known as the G5: the Baylor College of Medicine, the Whitehead Institute, and the Joint Genome Institute of the US DOE. This G5, together with administrative agencies, bioinformatics institutes and fifteen other large-scale sequencing centers, constituted the international consortium (IHGSC) that, in 2001, signed the first draft human genome sequence paper in Nature. It was the selective club of institutions that Clinton had praised the year before and identified with a coherent, successful, and unified Human Genome Project. Clinton’s speech, and the subsequent publication of the draft sequence, has led many scientists, scholars, and commentators to believe that the mapping and sequencing of the human genome was always organized in this fashion. However, a look back at the multiple initiatives at play during the 1990s shows that human genomics faced constant bifurcations throughout its history. While the route taken by the IHGSC was clearly the most effective to complete the human genome—and the most visible—other pathways such as the HGAP may prove useful to think about what to do now with the resulting sequence data.

5. Conclusion

Walter Bodmer, a prominent human geneticist and director of the ICRF during the creation of its resource center, was another attendee to the witness seminar discussed at the beginning of this chapter. Bodmer had been an active participant and driver of the chromosome mapping workshops as president of the HUGO, the body that coordinated them by managing the funding provided by the HGAP, Wellcome Trust, and other institutions. At the witness seminar, Bodmer lamented that due to the rise of large-scale genome centers throughout the 1990s, the mapping and sequencing of human DNA had been “lost from the hands of the involved community.” For Bodmer, those genome centers had established a “top down” approach—one in which the map and the sequence were compiled by a small group of institutions deploying high-throughput technologies rather than a larger community of geneticists sharing their results at the human chromosome workshops. Despite feeling uneasy about this outcome, Bodmer considered it “inevitable” (Jones and Tansey 2015, 76–77).

Bodmer’s claim resonated with the impression, also expressed at the witness seminar, that Europe had missed the opportunity to become a main player in human genomics. According to this view, the HGAP and other genome projects sponsored by the European Commission failed to follow the inevitable pathway of genomics since they pursued a distributed approach in which the mapping and sequencing were conducted by various participants rather than a selective club of large-scale centers. This led to the distributed approach being sidelined from the standard narratives of a single, coherent, and successful Human Genome Project that had culminated in the determination of a complete reference sequence by an international consortium of large-scale genome centers (the IHGSC). In being more proactive in the establishment of these centers, the United States—rather than Europe—had thus headed the natural course of the history of genomics.

A necessary precondition for this narrative of European failure to stand is taking the mapping and sequencing of whole genomes as the sole objective of genomic science. Although this objective may seem self-evident today, it was initially strongly localized in the United States and, more specifically, in James Watson’s vision as the first director of the Office for Human Genome Research of the NIH. Between the late 1980s and early 1990s, Watson sought to overcome Europe’s cottage industry approach by using model organisms of genetics research—among them the yeast S. cerevisiae and the worm C. elegans—as platforms to develop the technologies for comprehensive human DNA mapping and sequencing. To do this, he sponsored the full sequencing of these organisms at genome centers and appointed as directors of these institutions a younger breed of molecular biologists—the discipline that Watson had decisively contributed to establish by co-determining the double helical structure of DNA. Both C. elegans and S. cerevisiae were acquainted with a long trajectory of investigation into the molecular bases of developmental and cell biology.

By shifting the gravitational center of this chapter from the United States to Europe, I have argued that full genome mapping and sequencing was not the only—nor the most widespread—objective during the formative years of genomic science. An examination of the many human genome programs emerging nationally and internationally from the mid-1980s onward reveals that the United States was the exception rather than the rule. The United Kingdom, France, and supranational organizations like the European Commission prioritized the pooling of mapping and sequencing results by existing laboratories over the creation of new genome centers. These existing laboratories were led by geneticists interested in specific chromosomal areas connected to diseases rather than the sequencing of the whole genome. What motivated the European scientists sponsored by the HGAP was thus the potential medical uses of map and sequence information connected to genes rather than finding new answers to development, cell metabolism, or other questions for which the non-genic parts of the sequence were already considered to be important.31

The contrasting geographies and strategies that the HGAP reveals show that Europe may have been successful in fulfilling its own goals. Instead of seeking to determine the full human genome sequence, the HGAP created networks that enabled biomedical research centers, medical schools, and hospitals to use map and sequence data in their investigation of genetic disease. These institutions constituted the community that by liaising with Généthon and Bodmer’s ICRF—the HGAP’s resource centers—could access information, biological samples, and other materials that helped them position in the human genome the DNA they were working on. With this positioning, they narrowed down on the chromosomal location of the genes underlying their target conditions. The HGAP’s concept of resource center is at the heart of the central facilities that proliferate today across large research institutions and conduct a la carte sequencing adapted to the requirements of different laboratories.

This institutional proximity and adaptation to specific demands may be useful to solve broader problems in the so-called post-genomic era (Richardson and Stevens 2015). Current attempts at realizing the clinical potential of the reference human sequence have revealed the key importance of aligning this information with local knowledge and highly contingent data such as health records, the sequence variants of specific patients, or the know-how of physicians (see chaps. 12 and 18, this volume). Against the backdrop of these postgenomic concerns, the HGAP starts looking less of a missed opportunity and more of a potential solution. By delving into its history and uncovering the objectives that this European initiative pursued—rather than conflating them with the US-HGP and subsequent IHGSC endeavor—one can draw lessons on the networking skills, brokering practices, and mediation processes that are needed in current translational research (Fischer 2012; Solomon 2015).

6. Acknowledgments

I would like to thank colleagues within and outside the University of Edinburgh for their invaluable feedback, particularly James Lowe, and attendees, co-presenters and organizers of the workshop from which this volume originated, held in November 2018 at the NHGRI. Alan Love and Christopher Donohue undertook the volume’s editorial process and led the organization workshop. Another key event at which an earlier version of this chapter was presented was a session that my research team organized at the 2018 European Society for the History of Science conference.

I am also grateful to Carry Koolbergen at IOS Press, Victoria Sloyan at the Wellcome Archives, and the UK Medical Research Council for kindly granting permission to quote and reproduce third-party material. Jane Peterson and Martin Bobrow agreed to be interviewed and provided further recollections and qualifications by email ahead of publication.

The research and writing of this chapter were conducted through the “TRANSGENE: Medical translation in the history of modern genomics” Starting Grant, funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, grant agreement No. 678757. Without this support it would not have been possible to produce this work.

Notes

1. 1. Quotes from transcript of the ceremony, available at https://www.genome.gov/10001356/june-2000-white-house-event. A video of the different interventions can be watched at https://www.youtube.com/watch?v=slRyGLmt3qc (both links last accessed March 2026).

2. 2. Venter’s Celera Genomics published an alternative draft sequence in the journal Science the same week as the International Consortium. The dominance of US institutions was even higher in this article: out of fourteen teams involved, only two were based outside this country—one in Israel and one in Spain (Venter et al. 2001).

3. 3. This figure was provided in the embargoed press releases that the NIH and the Sanger Centre issued to announce the White House ceremony: http://www.sanger.ac.uk/news/view/first-draft-book-humankind-has-been-read and https://www.genome.gov/10001457/2000-release-working-draft-of-human-genome-sequence (last accessed March 2026). In the caption box of the 2001 Nature paper, the sequencing centers were listed per order of size of contribution; the G5 institutions appeared in the top positions (IHGSC 2001, 861).

4. 4. For a critical appraisal of this presentation and the consequences of the mystification of the double helix in the historiography of twentieth-century biology, see de Chadarevian (2002), Part II.

5. 5. For accounts that develop the narrative of the Nature article see Judson (1992) and Sulston and Ferry (2002). James Watson, co-discoverer of the double helical structure of DNA and the first director of the Human Genome Project in the United States, claimed that he wanted the full sequence to be determined within his lifetime because this would represent a “wonderful end” to his career as a molecular biologist (Watson 1992, 164). In 2003, a more definite version of the human genome sequence was announced by the same International Consortium that had determined the first draft plus some extra membership. This date was intentionally chosen to mark the fiftieth anniversary of the elucidation of the structure of the double helix. On genetic reductionism as a common foundation of molecular biology, genomics, and more recent gene-editing technologies, see Sarkar (1998, and this volume).

6. 6. An exception to this is Gulsah Albayrak’s unpublished pre-doctoral thesis (2015), on which my contribution largely builds. There are also small sections on the HGAP in books or special journal issues devoted to human genome mapping and sequencing (Ferguson-Smith 1991; Jordan 1993, 141–42; Cook-Deegan 1994, 201–3).

7. 7. The laboratories of the European consortium sequenced 6.8 million nucleotides, approximately 57 percent of the overall twelve million nucleotide units that constitute the yeast genome. The remaining 5.2 million nucleotides were sequenced by Washington University in St. Louis, the Stanford DNA Sequencing and Technology Center, McGill University in Canada, the Riken Institute in Japan, and the Sanger Centre in the UK (Parolini 2018, 7).

8. 8. Another instrument for the achievement of these goals was the Eureka consortium, founded in 1985 as an international organization integrated by all the EEC member-states. Through the launch of funding calls in different areas—including biology—the Eureka consortium sought to promote scientific and industrial partnerships around products that would be manufactured and commercialized from Europe. The European Commission was a member of the Eureka consortium, but not its coordinator. One of the areas that Eureka’s funding sought to foster was the development of automated laboratory equipment. On the Eureka programs, see Commission of the European Communities (1986) “Communication from the Commission to the Council: Eureka and the European technology community,” National Archives of the United Kingdom, Kew (London), file number FD 7/1985.

9. 9. The sequencing of the remaining chromosomes I, VI, IX, and XIII was led by McGill University in Canada, the University of Tokyo in Japan and the Sanger Centre in the United Kingdom, respectively. The Sanger Centre sequenced both IX and XIII outside the European Consortium (Szymanski et al. 2019).

10. 10. The main role of genes is synthesizing proteins in charge of muscular contraction, processing of nutrients, and many other functions essential for life. Deficiencies in those proteins and the genes that synthesize them are therefore a main cause of disease. Today, it is estimated that only 1 percent to 1.5 percent of the reference human sequence comprises protein-coding regions; the rest regulates those regions switching genes on and off, or has not known function. In the mid-to-late 1980s, the percentage of genetic regions was believed to be higher, but still a minority within the whole genome.

11. 11. HUGO’s lack of strength as an organization encompassing the whole field of human genomics has created what Fortun defines as a myth of origins: a less representative grouping—the IHGSC—constructed a retrospective account of a unified large-scale effort that they called the Human Genome Project and deemed as concluded in the 2001 and 2004 publications where they described the reference sequence (Fortun 1999).

12. 12. On the initial discussions of the working party, see L. C. Dane (1988) “UK/FRG/F/I/Commission meeting, 28 March, Frankfurt” in National Archives of the United Kingdom (Kew-London), Medical Research Council Collection, file FD23/3441. See also Papers and Correspondence of Sir Walter Bodmer, Bodleian Library (Oxford), shelfmarks MS.Bodmer.1296 and MS.Bodmer.1297.

13. 13. Quotes from “Council decision of 29 June 1990 adopting a specific research and technological development programme in the field of health: human genome analysis,” Official Journal of the European Communities: 8, 11, and 12. Due to the huge increase of attendees and reported results, the workshops shifted to being devoted to specific chromosomes rather than the whole human genome from 1992 onward. The HGAP funded the newly opened European HUGO Office as the body that would deal with the logistics of the workshops. Ferguson-Smith, director of that office, organized over fifty single-chromosome workshops in Europe between 1992 and 1997 (Ferguson-Smith 1995, 1998; see also Jones and Tansey 2015).

14. 14. “Council decision of 29 June 1990 adopting a specific research and technological development programme in the field of health: human genome analysis,” Official Journal of the European Communities: 12.

15. 15. The full funding of the BIOMED-1 and BIOMED-2 programs was 151 million ECU and 374 million euros for the periods 1990–1994 and 1994–1998, respectively: see https://cordis.europa.eu/programme/id/FP3-FRAMEWORK-3C and https://cordis.europa.eu/programme/id/FP4-BIOMED-2 (last accessed March 2026). The HGAP was awarded a budget of 15.6 million ECU between 1990 and 1992 (Hallen and Klepsch 1995:v). Unlike in the BIOMED programs, the HGAP support was ring-fenced to be exclusively spent in human genome analysis.

16. 16. J. Peterson, interview with author, National Human Genome Research Institute (Bethesda, US), November 15, 2018.

17. 17. Some US institutions, especially those outside the IHGSC, integrated users of map and sequence data into their genomic work. This was the case of Celera Genomics, whose sequencing operations were partially driven by the necessities of medical geneticists—a strategy that, as we will see below, had some similarities with the HGAP despite being more large-scale and clearly oriented toward the whole genome (García-Sancho et al. 2022a). On the intertwinement of producers and users of map and sequence data in the history of genomics more generally, see Leng et al. (2022).

18. 18. Based in Heidelberg and funded by different European governments, the European Molecular Biology Laboratory (EMBL) was furnished with a strong tradition in the development of sequencing technologies, as well as housing a centralized database of DNA sequences (Krige 2002; García-Sancho 2011). This led the European Science Foundation (ESF, an independent advisory body) to recommend to the European Commission that the EMBL or a similar institution act as a central node in the HGAP. However, the EMBL scientists—mainly molecular biologists at the start of their careers—were reluctant to be seen as providers of mapping and sequencing services. In the light of this, the European Commission decided to extend to the human genome the network approach that it had already deployed with yeast, something that had been defended by a group of scientists from the Academia Europaea in a rival report submitted at the same time as the ESF proposal (Cook-Deegan 1994, 202–3; Albayrak 2015, 21ff). The EMBL thus participated in the collaborative networks, but as one more institution rather than the central node.

19. 19. On Généthon mapping efforts and subsequent involvement of Genoscope in the IHSC, see Jean Weissenbach’s presentation at Cold Spring Harbor Laboratory symposium on the development of sequencing technologies: http://library.cshl.edu/Meetings/sequencing/video-pages/Weissenbach.php (last accessed March 2026).

20. 20. Their main application was made to Eureka, the intergovernmental, pan-European fund to promote collaborative projects between laboratories and industry. The proposal and application document can be found at Papers and Correspondence of Sir Walter Bodmer, Bodleian Library (Oxford, UK), file MS. Bodmer 1701 (2/8). On the Eureka consortium, its funding programs and its role in the development of the biotechnology market in Europe, see note 8.

21. 21. Another main contributor of cDNA sequences to the HGAP was the Genzentrum, a research institute at the Ludwig Maximilian University of Munich that focused on the development and use of DNA-related technologies (Arnold and Domdey 1995). The Genzentrum also participated in the European yeast sequencing consortium and, during the early-to-mid 1990s, was one of the world’s leaders in volume of determined DNA sequence (García-Sancho et al. 2022b; García-Sancho and Lowe 2023, chap. 2).

22. 22. T. Vickers (1991) “The UK Human Genome Mapping Project: project manager’s report,” courtesy of Tony Vickers, quotes from page 4. The report also stated that the Resource Centre was leading a European cDNA consortium with Généthon in Paris, Genzentrum in Munich and the Institute for Cell Biology of the Italian National Research Council (Vickers 1991, 6 and 24). Report used by kind permission of the Medical Research Council, as part of UK Research and Innovation.

23. 23. T. Vickers (1992) “MRC review of the UK Human Genome Mapping Project: project manager’s report,” courtesy of Vickers (quotes from pages 7, 56, and 84). Available at Papers and Correspondence of James D. Watson, Codebreakers Collection, Wellcome Library (London, UK) and Cold Spring Harbor Laboratory Library and Archives, reference JDW/2/9/2/16.

24. 24. Venter’s patenting practices, along with the strong identification of the G5 with the unrestricted release of data, have led to a narrative that equates the former with a private, proprietary genome effort and the latter with a publicly funded and open access Human Genome Project, especially after the foundation of Celera Genomics and the formation of the IHGSC in the late 1990s. Scholars have challenged this dichotomous view by stressing the importance of charitable funding within the IHGSC and, more generally, the entanglement between private and state support in the sequencing of the human genome (e.g. Fortun 1999). This chapter further shows the complexity of funding and ownership regimes in human genomics by showing the alignment of a publicly sponsored endeavor (the HGAP) with Venter’s strategies.

25. 25. J. Sulston and A. Coulson (1989), “Mapping and sequencing the genome of Caenorhabditis elegans,” application for a project grant, released by the Medical Research Council after a Freedom of Information (FOI) request. The document is now available at the Papers and Correspondence of Sir John Sulston, Wellcome Library (London, UK), reference PP/SUL/A/2/1/3. During a previous stage of his research on C. elegans, Sulston had successfully identified all the worm cells, their changes and divisions during the process of embryonic and post-embryonic development. This comprehensive cataloguing effort had some resemblances with his subsequent involvement in full genome mapping and sequencing (de Chadarevian 1998).

26. 26. Robert H. Waterston (1989) “Sequencing of the C. elegans genome.” Grant application to the NIH available at the Papers and Correspondence of Sir John Sulston, Wellcome Library (London, UK), reference PP/SUL/A/2/1/5.

27. 27. On the Genome Sequencing Center at Washington University, see interview with David Schlessinger, National Human Genome Research Institute Oral History Collection: https://www.genome.gov/player/N_0SUvzMTQ0/PL1ay9ko4A8sk0o9O-YhseFHzbU2I2HQQp (last accessed March 2026). Most of the budget of the Sanger Centre—and all of the funds devoted to human genomics—came from the Wellcome Trust. According to Martin Bobrow, a geneticist who closely observed the events and was later appointed Wellcome Governor, the philosophy and strategy of the IHGSC human genome effort—in which the Sanger Centre became involved as a leading institution—were modeled on the C. elegans sequencing project: Martin Bobrow, interview with author, Cambridge (UK), June 2015 and personal communication, October 2021. Sulston’s original proposal is available at the Archives and Manuscripts of the Wellcome Library, reference PP/SUL/B/1/1/1/2.

28. 28. R. Waterston (1994) “An indecent proposal,” Papers and Correspondence of Sir John Sulston, Wellcome Library (London, UK), reference PP/SUL/B/2/1/1. See also Sulston and Ferry (2002, chap. 4).

29. 29. J. Sulston (1994) manuscript notes, Papers and Correspondence of Sir John Sulston, Wellcome Library (London, UK), reference PP/SUL/B/2/1/1. In his memoirs, Sulston has attributed the divergent approaches of the Human Genome Organization (HUGO, the coordinator of the workshops) and the Sanger Centre to the disciplinary differences between human genetics and molecular biology (Sulston and Ferry 2002, 80).

30. 30. In 1995, the Wellcome Trust had substantially increased its financial capacity by selling the remaining of the shares of its mother pharmaceutical company—Wellcome Foundation—to Glaxo. This selling of shares had been done gradually since the late 1980s and enabled the Wellcome Trust to use the money in funding biomedical research, including supporting the chromosome workshops and the establishment of the Sanger Centre (García-Sancho and Lowe 2023, 128ff).

31. 31. Throughout the 1990s, a new generation of geneticists started addressing common-complex diseases, such as cancer or diabetes (Heeney 2021). Unlike the conditions on which medical genetics had traditionally focused its attention, these common-complex diseases were triggered by the interaction between various genes rather than just one. The polygenic nature of these diseases made the new geneticists more sympathetic to the idea of simultaneously probing multiple locations of the whole genome and addressing non-genic areas, which had previously been considered to be junk DNA. The mapping and sequencing of human chromosomes at the Sanger Centre was led by representatives of this second breed of geneticists.

References