Taking Human Genetics Digital: ‘Mendelian Inheritance in Man’ and the Genealogy of Electronic Publishing in Biomedicine

As of my writing on April 12, 2018, there are 24,506 known or suspected human genes out of roughly 3 billion base pairs in the reference sequence of the human genome.[1] While the bulk of these were identified during the course of the Human Genome Project (HGP), which ran from 1990–2003, a majority of the 5,000 or so with a well-characterized clinical phenotype—a genetic trait visible in human anatomy and physiology with consequences for human disease manifest above the cellular level—were cataloged beginning in the 1960s, long before genetic sequencing was possible. Medical geneticists worked to identify heritable traits in study populations that manifested unambiguously in family lineages. They set up clinics around the world and established sections in academic hospitals.[2] In a discipline that was still marginal to mainstream medicine and tainted by its incomplete severance from eugenics, breaking apart old categories and multiplying new ones became a legitimation strategy, one that required physicians and counselors across the country to be on the same page.

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Enter Mendelian Inheritance in Man (MIM), the most influential and comprehensive encyclopedia of human genes and the standard reference for medical geneticists. It is a largely bibliographical resource that organizes literature in the field into specific gene entities divided up alphabetically and by their mode of inheritance. This is not a handbook in the traditional sense. However, I want to suggest that we can see catalogs less as neutral repositories and more as active guides or protocols that coordinate and shape communities. They serve as “technologies of valuation” rather than mere extensions of access, and both their organizational structure and unintended uses have consequences.[3] Historians of science have long been attentive to how classification schemes do cultural and political work. They lump and split. They include and exclude.[4] The media that maintain them warrant further study in their own right.

While historians of the book might argue that all such reference material can be understood as a kind of information technology, MIM has been a computerized database since its inception in the early 1960s. It was published directly from computer printouts using photolithographic techniques in twelve editions from 1966 to 1998 (Figure 1), and brought online in 1985 (though not widely available over the Internet until 1987) with a new search engine technology developed by the National Library of Medicine. Victor A. McKusick, often described as the “founder” of medical genetics, oversaw the entire collection, authoring, and publication process behind MIM. He stressed internal control, cost-effectiveness, and updated editions tied to the growth of knowledge as an alternative to the sales-based norms of academic publishing. Accounts of genetics and computing have tended to focus primarily on the production and circulation of genetic sequence data: strings of A, C, T, and G. A media history of MIM can help us think about how clinicians managed their own perceived information overload of classifications and data coming from firsthand observation, family history gathering, and attempts to measure the linkage between different traits.[5]

Figure 1  Successive editions of Mendelian Inheritance in Man (missing 4th ed.) and associated material atop author’s desk, February 2018. Photo by author.

The project that led to MIM seemed to arise naturally enough. Beginning in 1957, McKusick was tasked with reviewing the literature in medical genetics for the Journal of Chronic Diseases, and he began holding a journal club at his Maryland home for fellows of the Moore Clinic he ran at Johns Hopkins (Figure 2).[6] Divided up by medical specialty, each fellow would produce a notecard for each relevant article, listing the full reference on one side and indicating relevant disorders and points of interest on the other. One day, as perpetuated legend has it, McKusick’s computer specialist observed him shuffling through cards, and recommended that he explore the use of electronic computers to keep track of the information. McKusick’s own research interests in genetic disorders among the Amish, which required a large repository for organizing records of family history according to phenotype, aided this shift toward digitization.

Figure 2  Victor McKusick with members of the Medical Genetics Journal Club, 1965, by Bernard Cole. Courtesy of National Library of Medicine.

The apparent affinity between managing notecards and punch cards conceals the effort that went into this transition. Entries had to be reorganized around individual phenotypes rather than observations tied to different medical specialties, which meant that the information to manage lost its specialist framing. Further, McKusick relied on computing resources developed at Hopkins’s Applied Physics Laboratory, where computer operators preferred the approach of a single master file with predetermined search keywords, rather than a more permanent and scalable database model.[7] The first three editions of MIM had completely different ID number schemes, much to the frustration of readers. Eventually, however, the publication system stabilized and McKusick began to include relevant tables of related disorders and maps of the human chromosomes to mitigate the relatively undisciplined organization of alphabetical entries.

As genetic knowledge changed, so did the organization of entries. Disorders that attracted attention from the research community, like myotonic dystrophy, grew unruly while others remained relatively stable. Some references had to be linked together without being fully collapsed into one another. Finally, the organizing distinction between dominant and recessive modes of inheritance was abandoned in 1994, as knowledge in molecular genetics had eroded the basis for these distinctions.[8] Mendelian Inheritance in Man was no longer Mendelian.

In my current research, I am grappling with how these changes in knowledge relate to systems of credit. One angle I am interested in exploring further is the labor of translation and the maintenance of knowledge. McKusick is listed as the sole author of MIM until the 1990s, and while this appears in some sense to be true, he relied upon the work of fellows and networks of specialists throughout the world to help update and edit this encyclopedia. Beginning in 1993, as HGP work scaled up the number of identified genes, the National Center for Biotechnology Information maintained a staff of editors and medical writers for the project. Though McKusick remained executive editor, this new staff (reorganized around clinical specialty) helped to even out the entries and provide clear and useful information for both the broader public and consumer genetics companies looking to capitalize on interpretation of genetic information.

Visit omim.org at present and you will be greeted by a pop-up (Figure 3), requesting donations to support a staff no longer fully covered by the NIH. Through my research, I aim to show how MIM helped make medical genetics a viable specialty of its own and a general kind of knowledge at the basis of all clinical disciplines that prefigured the rise of molecular genetics. Moreover, it can tell us something about the changing political economy of biomedical knowledge. At the basis of the consumer genetics and biotech industries is the promise of translation: making findings from the biomedical literature useful for diagnosis, counseling, and treatment. This, in effect, leaves the accessibility of meaningful information from government-funded research up to the market. If we thought differently about the value of knowledge translation and maintenance, perhaps a public good like OMIM could be seen as the foundational knowledge infrastructure it is, rather than a one-man job or charity case.

Figure 3  OMIM donation request pop-up, author’s screenshot of omim.org, April 12, 2018.

Michael McGovern is a PhD student in the history of science at Princeton University.

  1. “OMIM Entry Statistics,” Online Mendelian Inheritance in Man, http://omim.org/statistics/entry (accessed April 12, 2018).  ↩
  2. On the history of medical genetics in America, see M. Susan Lindee, Moments of Truth in Genetic Medicine (Baltimore, MD: Johns Hopkins University Press, 2005); Nathaniel Comfort, The Science of Human Perfection: How Genes Became the Heart of American Medicine (New Haven, CT: Yale University Press, 2012); Andrew J. Hogan, Life Histories of Genetic Disease: Patterns and Prevention in Postwar Medical Genetics (Baltimore, MD: Johns Hopkins University Press, 2016).  ↩
  3. Alex Csiszar, “How Lives Became Lists and Scientific Papers Became Data: Cataloguing Authorship during the Nineteenth Century,” The British Journal for the History of Science 50, no. 1 (March 2017): 25, https://doi.org/10.1017/S0007087417000012.  ↩
  4. For a classic account, see Geoffrey C. Bowker and Susan Leigh Star, Sorting Things Out: Classification and Its Consequences (Cambridge, Mass.: MIT Press, 2002). For a more historical take on the botanical classification practices of the British Empire, see Jim Endersby, Imperial Nature: Joseph Hooker and the Practices of Victorian Science (Chicago: University of Chicago Press, 2008).  ↩
  5. Reviews of MIM in the 60s and 70s stressed the “information overload” angle, and the promise and peril of computing, e.g., Bentley Glass, “Review of Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotypes, by Victor A. McKusick,” The Quarterly Review of Biology 50, no. 4 (December 1, 1975): 456–57.  ↩
  6. Krishna R. Dronamraju and Clair A. Francomano, eds., Victor McKusick and the Development of Medical Genetics (New York: Springer, 2012), 54–55, http://dx.doi.org/10.1007/978–1–4614–1677–7.  ↩
  7. F. L. Kennedy and M. E. Brown, The Applications of Computers to the APL Storage and Retrieval System, Technical Memorandum (Johns Hopkins University, Applied Physics Laboratory), TG–669 (Silver Spring, MD.: Johns Hopkins University, Applied Physics Laboratory, 1965).  ↩
  8. Victor A. McKusick, “Mendelian Inheritance in Man and Its Online Version, OMIM,” American Journal of Human Genetics 80, no. 4 (April 2007): 588.  ↩
Suggested citation: Michael McGovern, “Taking Human Genetics Digital: ‘Mendelian Inheritance in Man’ and the Genealogy of Electronic Publishing in Biomedicine,” History of Knowledge, May 7, 2018, https://historyofknowledge.net/2018/05/07/taking-human-genetics-digital-mendelian-inheritance-in-man-and-the-genealogy-of-electronic-publishing-in-biomedicine/.