'At Least Our Pituitaries Will See the World': Pituitary Gland Export from Communist Bulgaria

ARTICLE ‘At least our pituitaries will see the world’: Pituitary gland export from communist Bulgaria Daniela Koleva Institute of Ethnology and Folklore Studies with Ethnographic Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria Email: [email protected] Abstract The article focuses on the export of cadaveric pituitary glands from communist Bulgaria in the 1980s, used for the production of human growth hormone. The case is explored in the broader context of practices and transnational networks for the supply of pituitaries. Special attention is paid to the changes resulting from the turn to the production of recombinant growth hormone in the mid-1980s, which put an end to the international ‘market’of pituitary glands. In the last sections, different perspectives are explored to make sense of the case under scrutiny: those of bioethics and biolaw, on the one hand, and of bioeconomy in a globalising world, on the other. Keywords: Pituitary; Growth hormone; Bulgaria; Biolaw; Bioethics; Bioeconomy This article focuses on a specific case of transnational linkage and exchange, of a type that has so far largely remained under the radar of medical history research, although it has occasionally attracted public attention. Assuming that the Iron Curtain was in many respects a ‘nylon curtain’, that is, permeable, I am trying to understand what used to ‘flow’through it and in which direction. The case under study refers to a crucial moment in the development of biotechnology geared to the treatment of pituitary dwarfism –the short stature and slow growth in children due to the deficiency of growth hormone. I am interested in the practices and networks for the supply of pituitary glands extracted from human cadavers for the production of the hormone, and the changes resulting from the turn to recombinant growth hormone in the mid-1980s. This turn brought an abrupt end to the international ‘market’in pituitary glands and hence to the questionable practice of their harvesting and export by some Soviet bloc countries, which started in the 1970s and flourished throughout the 1980s. I shall first describe this practice in two of these countries: Hungary and Bulgaria. While the Hungarian case is only briefly sketched, I have studied the Bulgarian one in some depth, based on the archives of the Medical Academy in Sofia and of the National Television, as well as on several interviews with contemporaries: medical personnel from the institution exporting the pituitaries, and the journalists who in 1991 reported the practice in national media. Then, I shall zoom out to the broader international context of the production and distribution of growth hormone and the sharing of related knowledge. Finally, different perspectives towards the case at hand will be discussed: of bioethics and biolaw on the one hand, and of bioeconomy on the other. I believe that their juxtaposition leads to a deeper understanding not only of this particular practice, but of some specificities of the scientific internationalism of the late years of the communist regimes in Europe. Travelling pituitary glands In 1987, a public scandal broke out in Hungary, following an appeal to the Supreme Court: a renowned professor at the University of Szeged, head of its Endocrinology Department, was accused of an unusual © The Author(s), 2025. Published by Cambridge University Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. Medical History (2025), 1–14 doi:10.1017/mdh.2025.10029 https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press barter. 1 He was found to have acquired consumables for his research from the Italian pharmaceutical company Serono 2 in exchange for pituitary glands (hypophyses) extracted from cadavers during autopsies in Hungarian hospitals. This weird cooperation had lasted for about ten years, resulting in the export of several thousand pituitary glands in the luggage of passengers crossing the Hungarian border. In 1986, the customs officers found the precious goods, and the ensuing investigation resulted in charges against the professor. What the Hungarian court had to decide, however, was not whether this was a misappropriation of human cadaver tissues without the knowledge of the relatives or the opportunity of opting out, but whether this activity had led to private financial gains, causing loss of profits for the state. As it turned out, awkwardly, the state-owned Human Vaccine Substance Production Company had engaged in the same type of transactions with a few Western European companies, including Serono. Both the professor and the state company argued that their only aim was to provide resources for medical research and to improve the quality of healthcare in Hungary. The public, however, was less interested in what the pituitaries had paid for; the scandal brought attention to the fact that Hungarian citizens had been organ donors for years without knowing it. With this ‘turbulent historical retrospect’, Judit Sandor opens her article on patients’rights in the context of organ and tissue donation. 3 I shall contextualise the case from a different perspective, as an example of a ‘bioeconomy’of sorts taking place across the Iron Curtain. A couple of years later, a similar scandal burst out in Bulgaria: on 25 July 1991, the national television aired a report on the patho-anatomy department of a Sofia hospital, followed by an interview revealing the practice of the extraction of organs from the bodies of patients who died in hospitals. 4 The viewers saw the trepanation tools with which the organs were extracted and the facilities for their preservation. The extractor explained the procedure and cited the prices of the organs: five levs for dura mater, ten levs for tibia, etc. A few days later, the weekly humour and satire magazine Starshel [Hornet] published on its front page a brief but caustic text stating: ‘We knew that our minds belonged to the state, but honestly, we didn’t fancy that our bodies belonged to it as well, and in such a literal sense’. Referring to the TV broadcast, the author pitched into the export of ‘Bulgarian meat’:‘We may not be able to travel abroad, but at least our pituitaries will see the world’, he concluded sarcastically. 5 The accompanying cartoon showed a cow, a pig, a man and a woman flying up to heaven with angels’wings attached to their shoulders. The pig explained to bewildered God: ‘Their offal was sold in Maleev’s slaughterhouse’. The ‘slaughterhouse’in the case of hypophyses was the Research Institute for Endocrinology, Gerontology and Geriatrics (RIEGG), part of the Medical Academy (MA), and Atanas Maleev was the MA president and brother-in-law of Todor Zhivkov, head of the communist party and the state till 10 November 1989. Based on RIEGG archives and other archival material, I have tracked down the beginning and the development of this practice in the 1980s. My interviews with the TV reporter and the Starshel author, as well as with two former RIEGG researchers, one of whom was involved in the collection and preservation of the hypophyses, added not only factual details but also a sense of the professional ethos and the personal perspectives of participants and witnesses. The idea to export pituitary glands was launched by Ema Bozadjieva (1920–96), professor of endocrinology, who got her PhD degree in the Soviet Union in 1968 and was promoted to the position of Director of RIEGG in 1976. As a participant in the communist resistance during the Second World War and a member of the Bulgarian communist party, awarded with the prestigious Georgi-Dimitrov order, Bozadjieva was very well-connected in both professional and party circles. Her former subordinates described her as an excellent physician, very knowledgeable, fully devoted to her work, and an outstanding manager: energetic, enterprising and influential, albeit quick-tempered and nagging. Her research focused on the pathologies of the hypothalamic-pituitary and adrenal systems, in particular 1 I am grateful to Prof. Judit Sandor for sharing the details of this case. 2 Founded in 1906 in Rome; later relocated to Switzerland. 3 Judit Sandor, ‘Right to health and the human organ: Right as a consequence?’,Pravni Zapisi, 5, 2 (2014), 384–412. 4 Otzvuk [Echo] commentary studio, BNT archive, 25 July 1991. 5 Rumen Belchev, ‘Spi spokoino, hipofizo moya!’,Starshel, 2373, 2 August 1991, 1. 2 Daniela Koleva https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press pituitary tumours and endocrine hypertension. 6 Research on these topics was developed at RIEGG already in the early 1970s, which was reflected in its structure: one of its departments was the Diencephalic-pituitary one. 7 Bozadjieva’s guiding motivation was reported to have been the need for resources to set up RIEGG laboratories: ‘An institute without labs is a village hospital,’she used to say, according to the interviewees. They singled out her greatest success as head of RIEGG, where she established ten new laboratories and staffed them with top specialists. One of them was the Laboratory for Peptide Hormones, which is of interest here. In a report to the Chairman of the Committee for Science and Technical Progress dated 27 June 1980, Bozadjieva presented a research theme for which she sought funding: ‘Isolation of somatotropic and gonadotropic hormones from human pituitary glands from cadavers and development of a production technology and dosage forms for their administering’. She explained that the somatotropic/growth hormone (GH) was a complex polypeptide compound, which was not yet synthesised chemically, even though its composition was known. 8 Therefore, the treatment of pituitary insufficiency in children (the so-called hypopituitary dwarfism) depended on the extraction of GH from the pituitary glands of human cadavers, the hormone being species-specific. Bozadjieva defended her proposal, pointing out that in the Soviet Union, GH was produced and children were treated as of 1959–60. The GDR also produced its own GH but ‘refused’its export to Bulgaria. This was why by the time the report was written, no treatment had been provided for Bulgarian children suffering from pituitary dwarfism. 9 There is no clue in the report as to the number of those children, and hence the social significance of the issue. A 1982 survey identified a total of 209 such children and adolescents registered in the paediatric wards of the regional hospitals and a frequency of one out of 19,000 children. 10 RIEGG focused primarily on such widespread and hence socially significant diseases as diabetes, hypertension, goitre, and atherosclerosis. Having meagre chances to garner support based on the social importance of the problem, Bozadjieva adopted a different tactic. She referred to the situation in Western countries, where there was a chronic shortage of GH. 11 Hence, the financial argument followed: Bozadjieva estimated that on average, 15–20 thousand autopsies were carried out in Bulgaria per year, which would account for 15,000 pituitaries. The GH extracted from them would be more than enough for Bulgarian needs, and a substantial share of it could be exported. The average price of a pituitary at the international market being USD 8, Bozadjieva estimated that the annual revenue from the export would reach 200–300 thousand currency levs per year. 12 In addition to the extraction of pituitary glands and clinical research to be performed at RIEGG, the proposal envisaged laboratory research, including experiments on animals and, last but not least, market-oriented production. 6 Ema Bozadjieva, Endokrinni hipertonii (Sofia: Medicina i fizkultura, 1979); idem, Georgi Papazov, Hormoni i mineralen obmen (Sofia: Medicina i fizkultura, 1984); idem, Lyubomir Karagyozov, Tumori na hipofizata (Sofia: Medicina i fizkultura, 1987). 7 Report on the fulfilment of the plan for research of the Institute for Endocrinology, Gerontology and Geriatrics for 1972. Sofia State Archive, holding 2265 (RIEGG), inventory 3, archival unit 10, sheet 6. 8 The biochemical structure of the growth hormone was first identified in the early 1970s by C. H. Li and J. S. Dixon: C. H. Li and J. S. Dixon. ‘Human pituitary growth hormone. 32. The primary structure of the hormone’,Archives of Biochemistry and Biophysics, 146, 1 (1971), 233–6. 9 Report by Prof. E. Bozadjieva, director of RIEGG, to the Chairman of the Committee for Science and Technical Progress, comrade Nacho Papazov ex. No. 694 / 27 June 1980, Sofia State Archive, holding 2265 (RIEGG), inventory 3, archival unit 31, sheet 14. 10 Lilia Peneva, Hiposomatotropizam v detskata i yunosheskata vyzrast. Unpublished Dr. Sci. dissertation, Sofia: MA, Research Institute of Paediatry, 1984, 88–9. 11 RIEGG management often used comparisons with other countries to push for more funding, a practice that was obviously not exceptional (cf. Paula A. Michaels, ‘Soviet medical internationalism amid destalinization, 1953-1958’,The Soviet and PostSoviet Review, 50 (2023), 40–63, 58). 12 Sofia State Archive, h. 2265 (RIEGG), inv. 3, a.u. 31, sheet 15. The ‘currency lev’was an accounting currency unit used for the recalculation of revenues and expenditures from foreign currencies into Bulgarian levs and vice versa. Its relation to Western currencies was arbitrarily defined each year and kept unrealistically low, and was highly differentiated by type of industry and type of currency. In the 1980s, the US dollar equivalent was close to double, i.e. 1 USD = 1.5–2 currency levs. I am indebted to Prof. Krassen Stanchev for these clarifications. ‘At least our pituitaries will see the world’3 https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press Bozadjieva was either unaware or preferred not to mention that some children actually did receive treatment at the Endocrinology clinic of the Research Institute of Paediatrics as part of a research project led by Dr Lilia Peneva (1929–2020). It started in 1970 with eight children and developed to include a total of 43 children and adolescents by 1984. They were treated with cadaveric GH produced in Bucharest, Romania, and in Dresden, GDR (Sotropin H), later also with Serono’s Grorm, received in exchange for pituitaries extracted from cadavers in MA clinics. 13 While these details were missing from the report, the small-scale informal exchange of pituitaries must have provided a powerful incentive for its author: one of my interviewees remembered Peneva’s name and those of two other doctors who collected pituitaries in acetone and handed them to a lady who periodically came from Italy (presumably from Serono). He did not know of Peneva’s research; rather, he believed that the pituitaries were simply sold, and even mentioned the price of USD 2–2.5 per unit –a practice closely resembling the one in Hungary. At about the same time, a representative of the Swedish pharmaceutical company Kabi 14 contacted RIEGG management and proposed a higher price, especially if the pituitaries were frozen. So, the chance was there to expand the enterprise and channel the revenue. Bozadjieva and her team did not miss their chance: the reports in the subsequent years focus mostly on the export of pituitaries and less on the research carried out at RIEGG. Only in 1987 did the RIEGG management report that GH was obtained and purified, and tested on animals. A radioimmunoassay was developed and prepared in commercial form. Hard currency 15 was secured for depyrogenation filters, which would allow the serial production of GH. 16 There is no evidence in the archive that the Paediatric Endocrinology clinic benefited from these achievements, and if they had any consequences for treating the Bulgarian children suffering from hypopituitary dwarfism. The boundaries between laboratory science and international trade proved rather porous. As can be seen from Bozadjieva’s further reports, her superiors seemed to be more interested in the export than in the research. Her report to the Director of the Import-Export department of the Medical Academy (MAIMEX), dated 28 January 1981, reveals her commitment to developing a large-scale harvesting of pituitary glands: following the instructions given by Kabi, she inspected a few regional hospitals to organise the extraction and the preservation of pituitaries. Their extraction did not create any problems, as, like in Hungary, performing an autopsy was required in each case of a patient dying in a hospital. 17 There was no legal obligation to seek consent from the relatives of the deceased, or even to inform them. 18 Therefore, Bozadjieva focused on practicalities: she asked for a dedicated order of the MA President, Atanas Maleev, ‘to regulate the collection’nationwide, 19 and for thirty freezers to secure the harvesting of 10–15 thousand pituitary glands per year across the whole country. The start of the collection campaign was promising: the partnership with Kabi worked smoothly, with their representative coming monthly to pick up the pituitaries and pay. RIEGG staff toured the country to collect them from the hospitals. At the next stage, two researchers visited Kabi laboratories in Sweden to get acquainted with GH production. In a letter to Maleev from 23 June 1982, Bozadjieva announced that 3000 pituitaries had already been collected for the first half of the year and urged him to order their harvesting all over the country. The price was already USD 16.5 per unit, but she reasoned that it would be economically more profitable not to export the unprocessed glands but rather a semi-finished product 13 Peneva, op. cit. (note 10), 83, 193; idem, R. Slavova, Zh. Zhelev, ‘Lechenie s choveshki rastezhen hormon na detsa s hipopituitarizym’,Pediatria, 15, 2 (1976), 98–106, 99; idem, Zaboliavania na hipofizata III. Lechenie na hipofizarnia nanizym, Pediatria, 21, 6 (1982), 547–53. 14 Founded in 1931 in Malmö. Nowadays part of Pfizer. 15 ‘Hard currency’was the term used to refer to Western currencies, typically US dollars and FRG marks. It was essential for the import of preferred, sometimes unique, equipment and consumables. 16 Information on the fulfilment of the Biotechnology Programme of MA by RIEGG in 1987. Holding 2265 (RIEGG), inv. 3, a.u. 33, sheet 69. 17 Public Health Act, Darzhaven Vestnik [State Gazette] No 88, 1973, article 37. According to the extractor interviewed in Otzvuk studio, the ‘big shots’, i.e. high-ranking party and state officials, were exempt from autopsy. 18 Ibid., article 34(2). 19 Sofia State Archive, holding 2265 (RIEGG), inv. 3, a.u. 13, sheet 2. 4 Daniela Koleva https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press obtained from them. 20 It was therefore necessary to equip a laboratory. 21 This request must have been taken into account: the annual report for 1983 boasts that the plan for ‘hard currency’was met, which was a chance for RIEGG to invest the revenue in the purchase of unique equipment. The collection of pituitaries was ‘rhythmic’due to the young colleagues’‘responsible and conscientious’participation. 22 The laboratory was installed by Kabi. It was a simple and practical structure assembled of containers with four rooms equipped with air conditioning to maintain low temperatures. The quality of the product was thus guaranteed, and the revenue increased. The exchange of pituitary glands for hard currency in the situation of growing national debt and chronic shortages was of great importance for MA. For 1985, the revenue from pituitaries was 702,000 currency levs, c. 30% of the total hard-currency revenue from MA’s production and international activities; 23 for 1987, the share was 26%. 24 The greater part of the earnings, as in the Hungarian case, was invested in equipment and consumables for research. Under the conditions of an over-centralised and inert planning system, this was not at all simple. In a series of reports to the President of MA, the RIEGG Director asked for permission to spend part of the foreign currency revenue for additional equipment and consumables, which had not been included in the plan but were urgently needed. By the early autumn of 1982, Bozadjieva reports, the export of pituitaries had yielded 76,249 currency levs; 45,313 were already allocated for the purchase of equipment and consumables, ‘the rest were profit’that was placed at the disposal of MA management. Bozadjieva asked for permission to spend part of it on additional equipment. Since further hard currency income was expected till the end of the year, these expenses would not impair the profit, she promised. 25 I could not find out if this request was approved or how long it took for the equipment to be bought and installed. As seen from other cases, the procedure was slow and cumbersome. First, the equipment had to be included in the plan for the next year (ideally –in the five-year plan), based on a proven need, i.e. that it was indispensable for the implementation of planned and approved research tasks; sometimes this also necessitated proof that equivalent equipment was not produced in any of the Soviet-bloc countries. Next, even if present in the plan, the purchase depended on the availability of funds, which were always in short supply, thus generating tough competition among heads of departments/institutes within the MA. 26 The success often depended on the winners’connections and positions in complex, largely informal, professional-political networks. 27 In this situation, the capacity of RIEGG to garner foreign currency boosted its prestige among the other institutes and departments as a donor to the currency budget of the MA. However, the situation worsened dramatically in the second half of the 1980s. In 1988, the new RIEGG Director Dragomir Koev fought for a budget of only 3000 currency levs for the Laboratory for Peptide Hormones in addition to the 7000 allocated to RIEGG as a whole. 28 He explained that the sum was urgently needed for the import of materials and substances instrumental for the production of the radioimmunoassays planned for 1988. If the standard supply procedure were to be followed, these essential materials would arrive only in 1989, jeopardising the achievement of the plan. The reason was 20 Ibid., a.u. 7, sheet 40–41. 21 Ibid., a.u. 50, sheet 1. 22 Ibid., a.u. 26, sheet 8, 10. 23 ‘Report on the fulfillment of the currency plan of MA for 1985’, Sofia State Archive, holding 3863 (MAIMEX), inv. 4, a.u. 16, sheet 21. 24 ‘Report on the revenues in non-socialist currency on MA’s bank account in 1987’,ibid., sheet 46. 25 Sofia State Archive, h. 2265 (RIEGG), inv. 3, a.u. 7, sheet 48. 26 Repeated complaints can be found in the reports and the minutes of RIEGG assemblies that the system of planning and supply of laboratory consumables was ‘rather inert and does not meet our needs’(Sofia State Archive, h. 2265 (RIEGG), inv. 1, a.u. 9, sheet 28a) and that ‘we plan research tasks for the next year necessitating relevant equipment, which is also included in the plan, but we receive it in 3-4 years’(Sofia State Archive, h. 2265 (RIEGG), inv. 3, a.u. 4, sheet 7). 27 On the importance of personal connections, see Daniela Koleva, Ignat Petrov, ‘Socialist gerontology? Or gerontology during socialism? The Bulgarian case’,History of the Human Sciences, 36, 3–4 (2023), 178–201, https://doi.org/10.1177/09526951231178434. 28 Sofia State Archive, h. 2265 (RIEGG), inv. 3, a.u. 7, sheet 4-5. ‘At least our pituitaries will see the world’5 https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press not that Koev lacked his predecessor’s authority (which he did, in fact); nor was it only the deepening economic crisis in the last years of the communist regime. A look at the reports shows the actual situation: while RIEGG increased the plan for the export of pituitaries to 850,000 currency levs (to honour the 13 th Congress of the Bulgarian Communist Party in 1986), only 44.89% of this amount was achieved. 29 The negative tendency continued, down to a 10% execution of a plan already reduced to 400,000 currency levs in 1989. 30 To explain this collapse, a broader international perspective is needed. Helping children to grow The medicalisation of somatic realities, including short stature (especially for boys), started rather early in the twentieth century. As infant mortality declined, paediatricians’focus shifted towards issues of ‘normal’physical and psychological development. 31 GH therapy attracted the attention of researchers and the media by the 1930s. 32 Because of the hormone’s species-specificity, it had to be isolated from the pituitary glands of human cadavers and purified for therapeutic use. This only became possible in the 1950s. The preparations followed two methods, known as the Raben and Wilhelmi methods, whereby ‘[a]cetone-dried powdered pituitary tissue was subjected to repeated organic solvent extractions (Raben) or alkali and acid precipitations (Wilhelmi)’. 33 After 1975, the latter method was modified using frozen glands and a more gentle extraction procedure. 34 In the USA, where GH therapy was firmly established by the early 1960s, the supply of pituitaries depended on people’s decision to donate their organs post mortem, especially after the adoption of the Uniform Anatomical Gift Act (UAGA) in 1968. 35 The National Pituitary Agency (a federal body established in 1963 to standardise the collection, production and distribution of human GH) 36 and the Human Growth Foundation (an organisation of parents of small-stature children) energetically campaigned for the donation of pituitary glands. Still, the latter were in chronic short supply. Initially, the therapy required 1 mg of GH per day, which was extracted from one gland; so 365 pituitaries were needed per patient per year. About 10,000 of them were available in total. 37 That is, the annual yield of pituitaries in Bulgaria, with its population of slightly over eight million, was comparable to or exceeding that of the USA. In the 1970s, extraction and purification were ameliorated and ‘only’50 to 200 extracts were needed to provide one child with one year of treatment. 38 Still, the therapy was hardly available to all those who wanted it. Doctors had to single out those children who were in the greatest ‘need’for treatment, which led to a ‘rationing mentality’and affected the very definition of the condition as against the ‘normal’ 29 Sofia State Archive, h. 3863 (MAIMEX), inv. 4, a.u. 16, sheet 34. 30 Ibid., sheet 50. 31 On the medicalisation of social stigmas in relation to the development of the GH industry, see Aimee Lynn Medeiros, Heightened Expectations: The History of the Human Growth Hormone Industry in America. UCSF Electronic Theses and Dissertations (2012), https://escholarship.org/uc/item/5n8021rj. 32 Dr Harvey Cushing coined the term in 1909, and the growth-promoting effects of GH were proven in a groundbreaking study by H. M. Evans and his team in 1921 (Martin O.Savage, Abdullah Alherbish, ‘Growth hormone therapy for paediatric growth disorders: The past, present and future’,Dr. Sulaiman Al Habib Medical Journal, 2, 1 (2020), 4–9, https://doi. org/10.2991/dsahmj.k.200227.001. 33 C.J.Ellis, H. Katifi, R.O. Weller, ‘A further British case of growth hormone induced Creutzfeldt-Jakob disease’,Journal of Neurology, Neurosurgery, and Psychiatry, 55 (1992), 1200–2, 1201. 34 Ibid., 1201. For details see R. Lumley Jones, G. Benker, P.P. Salacinski, T.J. Lloyd and P.J. Lowry, ‘Large-scale preparation of highly purified pyrogen-free human growth hormone for clinical use’,Journal of Endocrinology, 82 (1979), 77–86. 35 http://www.uniformlaws.org/shared/docs/anatomical_gift/uaga%201968_scan.pdf, accessed 28 April 2025. 36 Renamed as National Hormone and Pituitary Program, NHPP. It repeatedly issued appeals to pathologists to engage in the collection of pituitaries, and to citizens to donate posthumously their pituitaries in order to help dwarfed children. Similar government-sponsored agencies were established in other countries, such as the UK, Canada, France, Australia, and Israel. 37 Robert M. Blizzard, ‘History of growth hormone therapy’,Indian Journal of Pediatrics, 79, 1 (2012), 87–91, 88, https://doi. org/10.1007/s12098-011-0609-4. 38 Medeiros, op. cit. (note 31), 151. 6 Daniela Koleva https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press state. 39 Patients were recruited as participants in research projects, as was the case at the Research Institute of Paediatrics in Sofia. Nevertheless, their treatment was often interrupted because of a GH shortage. 40 Only in the mid-1970s, with the introduction of commercial pituitary GH, did the supply increase. Its main producers were Serono and Kabi. The treatment with these medications cost between USD 9,000 and USD 20,000 per year. 41 The high cost, determined by the low supply, was yet another problem both public health agencies and patients’families faced. Since the supply of pituitary GH products was restricted due to the limited number of human hypophyses, both scientists and pharmaceutical companies turned to genetic engineering techniques in order to produce synthetic GH. In particular, Kabi, which dominated the global GH market, joined forces in 1978 with California-based laboratory Genentech (GENetic ENgineering TECHnology) 42 to obtain genetically modified bacteria capable of producing human growth hormone. Kabi funded the venture and supplied human pituitary material. It might be that some of the hypophyses extracted in Bulgarian hospitals and sold to Kabi were allocated to this research. The hormone was synthesised in 1979 and submitted to the US Food and Drug Administration (FDA) for approval. 43 The synthetic GH was expected to compete with the pituitary GH, which was considered more ‘natural’, and whose additional advantage was that it was often distributed by government agencies free of charge. The technology was new, and the approval necessitated extensive trials over a relatively long period of time. However, the FDA trials ended abruptly, and the approval was urgently granted in October 1985, in the midst of a crisis triggered by an alarming discovery: a link was proven to exist between cadaver GH treatment and cases of a rare and fatal brain disease, Creutzfeldt-Jakob disease (CJD). The victims were young adults from several countries, including the USA, the UK, and France. The problem was very serious, bearing in mind that for nearly thirty years, more than 27,000 children worldwide had already been treated with cadaveric GH. 44 The public outcry was significant, due to both the young age of the victims and the long incubation period, which led to the perception of the disease as a constant hidden threat for the patients and a potential risk for their families and the wider public. 45 Furthermore, the 39 Maureen D. McKelvey, Evolutionary Innovations: The Businessof Biotechnology. (Oxford: OxfordUniversity Press, 2000), 231. 40 Evan Graber, Edward O. Reiter and Alan D. Rogol, ‘Human growth and growth hormone: From Antiquity to the recombinant age to the future’,Frontiers in Endocrinology, 12 (2021), 1–19, 6, https://doi.org/10.3389/fendo.2021.709936. This was also the case in Sofia, as Peneva repeatedly explained. The irregular supply and the high price of the GH led her to experiment with intermittent treatment after the first year. Peneva, op. cit. (note 10), 337; op. cit. (note 13), 551; Peneva et al., op. cit. (note 13), 99. 41 Medeiros, op. cit. (note 31), 184. 42 Genentech, in collaboration with Eli Lilly, developed recombinant human insulin, the first biotech therapy approved by the FDA in 1982 (Priya Venkasten, Michael A. Peters, ‘Biocapitalism and the politics of life’,Geopolitics, History, and International Relations, 2 (2010), 100–22, 107). 43 Medeiros, op. cit. (note 31), 186–8. 44 Until 2021, more than 250 individuals who had received cadaveric GH treatment were diagnosed with CJD worldwide (Graber et al., op. cit. (note 40), 6). Some studies established a possible genetic predisposition to iatrogenic CJD (John Collinge, Mark S. Palmer, Aidan J. Dryden, ‘Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease’,The Lancet, 337, (1991), 1441–2), others pointed out that most CJD patients received treatment before 1977, the year when the method of extraction was significantly improved (Joseph Y. Abrams, Lawrence L. Schonberger, Ermias D. Belay, Ryan A. Maddox, Ellen W. Leschek, James L. Mills, Diane K. Wysowski, Judith E. Fradkin, ‘Lower risk of Creutzfeldt-Jakob disease in pituitary growth hormone recipients initiating treatment after 1977’,Journal of Clinical Endocrinology & Metabolism, 96, 10 (2011), 1666–9). Still, a muchdiscussed French study revealed that the new method did not fully exclude contamination (T. Billette de Villemeur, J.P. Deslys, A. Pradel, C. Soubrié, A. Alpérovitch, M. Tardieu, J.L. Chaussain, J.J. Hauw, D. Dormont, M. Ruberg, Y. Agid, ‘CreutzfeldtJakob disease from contaminated growth hormone extracts in France’,Neurology, 47, 3 (1996), 690–5, https://doi.org/10.1212/ wnl.47.3.690). Recent studies have suggested a connection between cadaver GH treatment and Alzheimer’s disease (G.Banerjee, S.F.Farmer, H.Hyare, Z. Jaunmuktane, S. Mead, N.S. Ryan, J.M. Scott, D.J. Werring, P. Rudge & J. Collinge. ‘Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone’,Nature Medicine, 30 (2024), 394–402, https:// doi.org/10.1038/s41591-023-02729-2). 45 For the UK see Tim Kelsey, ‘Doctor blocked growth hormone in 1970s: Pressure grows to compensate patients at risk of incurable brain disease’,Independent, 19 August 1993, https://www.independent.co.uk/news/uk/doctor-blocked-growth-hor mone-in-1970s-pressure-grows-to-compensate-patients-at-risk-of-incurable-brain-disease-tim-kelsey-reports-1462154.html. On the social construction of GH as dangerous in another context see Bernat Lopez, ‘Creating fear: The social construction of ‘At least our pituitaries will see the world’7 https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press iatrogenic nature of the CJD made it look like ‘friendly fire’, which undermined public trust in biomedicine. 46 Under the pressure of the controlling agencies, the pharmaceutical companies had to withdraw their cadaver-based products from the market. However, with thousands of children’s treatment interrupted, the FDA and the controlling bodies in other countries were themselves under pressure to provide an alternative. As a result, the synthetic (recombinant) GH (rGH) was speedily approved, and the expected bias against its ‘artificiality’did not materialise. By the late 1980s, the treatment with cadaveric GH was discontinued, first in the USA and the UK in 1985, then in the rest of the world as well. Its replacement, the rGH, is considered to have ‘an enviable track record of safety’. 47 Still, lessons learned from the CJD crisis led to acute awareness of potential adverse effects. Therefore, many countries established registries of patients treated with rGH to monitor potential side effects. 48 These developments explain the problems RIEGG was facing in meeting its export plans in the second half of the 1980s. Even after the planned revenue from the export of pituitaries was decreased, the failure to meet it was spectacular, due to the rapidly shrinking demand. This meant less foreign currency, less laboratory consumables and reagents and consequently, failure to perform planned research tasks. The plan was geared to the major political event in communist Bulgaria, the 13 th congress of the Bulgarian communist party, and did not even take notice of, let alone analyse, the actual situation of the therapy based on pituitary GH. In 1991, in the wake of the public scandal, the RIEGG Director informed his superiors that legal advice had been sought and a change of the law was needed in order to continue the export of pituitaries. However, there was no more demand for them. Legal and ethical dilemmas of cadaveric donation The hypophyses case can be viewed from different perspectives. The broader story is one of a biotechnological breakthrough: a better and safer product was invented, allowing many more patients to receive effective treatment. 49 As of 1993, Bulgaria started to import rGH, and Bulgarian children suffering from hypopituitary dwarfism received treatment with good results. In the subsequent years, patients with other conditions related to GH deficiency became eligible for such treatment. 50 The availability of appropriate drugs played back onto the definition of the norm and pathology in relation to the levels of hormone secretion and hence the criteria for eligibility for treatment. 51 The cut-off GH level separating normality from GH deficiency fell from 10 to 7μg/L. 52 The question was now where to draw the line between the norm and pathology, therapy and cosmetic enhancement. The kind of knowledge needed to implement such differentiations went beyond laboratories into the legal and moral sphere. human Growth Hormone as a dangerous doping drug’,International Review for the Sociology of Sport, 48, 2 (2012), 220–37, https://doi.org/10.1177/1012690211432209. 46 Paul Brown, Michael A. Preece, Robert G. Will, ‘”Friendly fire”in medicine: hormones, homografts, and Creutzfeldt-Jakob disease’,The Lancet, 340 (1992), 24–7. 47 Ron G. Rosenfeld, Pinchas Cohen, Leslie L. Robison, Barry B. Bercu, Peter Clayton, Andrew R. Hoffman, Sally Radovick, Paul Saegner, Martin O. Savage and Jan M. Wit, ‘Long-term surveillance of growth hormone therapy’,Journal of Clinical Endocrinology & Metabolism, 97, 1 (2012), 68–72, 68. 48 For details, see ibid. and Anders Tidblad, ‘The history, physiology and treatment safety of growth hormone’,Acta Paediatrica, (2021), 215–24, https://doi.org/10.1111/apa.15948. 49 For an overview of the development of the GH therapy over the past 100 years, see Michael B. Ranke and Jan M. Wit, ‘Growth hormone –past, present and future’,Nature Reviews/ Endocrinology, 14 (2018), 285–300, https://doi.org/10.1038/ nrendo.2018.22. 50 E. Stefanova, ‘Lechenie s rastezhen hormon v detska vyzrast’,Prakticheska pediatria, 16, 11 (2014), 4–6. The list of approved indications for GH therapy grew substantially from the 1990s onwards. See Vageesh S. Ayyar, ‘History of growth hormone therapy”,Indian Journal of Endocrinology and Metabolism, 15, Supplement 3 (2011), 162–5, 163–4; Graber et al., op. cit. (note 40), 6–12. 51 McKelvey, op. cit. (note 39), 232. 52 Martin O. Savage, ‘The changing face of paediatric human growth hormone therapy’,Endocrines, 3 (2022), 419–27, 420, https://doi.org/10.3390/endocrines3030033. 8 Daniela Koleva https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press The hypophyses case, however, poses another type of ethical issue. It can be viewed in the context of decades-long legal and ethical discussions on the utilitarian treatment of the donors. In the situation of short and unpredictable supply of organs and tissues for transplantation, some legal scholars have argued for ‘organ conscription’, i.e. a universal and mandatory post-mortem draft of organs and tissues, seeing the law as a mediator between the medical needs of the living and deep-rooted sentiments towards the dead, and insisting on its role to ‘implement common will and wisdom where voluntary incentive is lacking’. 53 Such a position views the human body as a kind of natural resource ‘on extended loan from the biomass’to which it returns after death. 54 Its proponents argue for the ‘automatic’availability of cadaver organs, 55 prioritising (not without good reason) the needs of the living over the interests of the dead. Others, however, have emphasised the integrity of the human body. They have pointed to the specific ontological status of the corpse, asking if the human body turns into an object after death, and, if so, who has ownership rights on that object. 56 Still others have argued that a corpse ‘can be said to have limited human rights, “passive”rights, to be sure, but rights nonetheless’since, before the burial ritual, which delivers it to the world of the dead, ‘the corpse remains to some degree a member of the living human community’. 57 Its ‘rights to bodily integrity, dignity, and respect’are ‘a reinscription of obligations and expectations that constitute social life’. 58 Therefore, the dead body does have specific rights and ‘an ethical status above that of property’. 59 In any case, as many of these scholars agree, ‘economic considerations cannot overrule ethical ones’. 60 Coming back to the hypophyses case in Hungary and Bulgaria, a conclusion that the totalitarian communist states disposed of the bodies of their citizens as if they were yet another state property would be a hasty and perhaps a superficial one. Indeed, the practice of organ and tissue harvesting for purchase by pharmaceutical companies, based on the assumption of tacit consent, was not limited to communist and so-called ‘Third World’countries. After the scandals in Hungary and Bulgaria, another one burst out in Ireland in 1998, when it became known that in the 1970s, pharmaceutical companies had paid pathologists to extract pituitary glands and other organs from cadavers, especially those of children, without informing their parents. The price they were paid for a pituitary gland in 1978 was £1.50, and in 1985 it grew to £3.50. The families of the deceased children established the ‘Parents for Justice’group to investigate the issue, which they defined as ‘the worst kind of theft’. Although at the time there had been no explicit regulation requiring informed consent, the practice was criticised on ethical grounds as a violation of the public’s trust in biomedicine and condemned as ‘dark age medicine’. 61 The debate on public trust in medicine and its institutions and procedures was also simmering in the USA, although there, the supply of pituitaries was considered to have been better regulated. Not so long ago, the former director of the National Pituitary Agency (NPA) admitted that the extraction and collection of pituitaries had been ‘a tale of intrigue and secrecy’. 62 The extractors were paid $2 for the collection, storage and shipment of a pituitary gland to the NPA. However, the competition for pituitaries was so strong that a black market developed. As it turned out, NPA was not always successful in its regulating and standardising role, which led to ‘questionable occurrences in conjunction with the NPA’s collection’. 63 53 Theodore Silver, ‘The case for a post-mortem organ draft and a proposed model Organ Draft Act’,Boston University Law Review, 68, 4 (1988), 681–728, 697. 54 H.E. Emson, ‘It is immoral to require consent for cadaver organ donation’,Journal of Medical Ethics, 29 (2003), 125–7, 126. 55 John Harris, ‘Organ procurement: dead interests, living needs’,Journal of Medical Ethics, 29 (2003), 130–4, 130. 56 Stoyan Stavru, Veshtnopravno deistvie na smartta. [Implications of death for property law] (Sofia: Cibi, 2008). 57 John Sutton Baglow, ‘The rights of the corpse’,Mortality: Promoting the interdisciplinary study of death and dying, 12, 3 (2007), 223–39, 224. 58 Ibid., 235. 59 Thomas H. Champney, ‘The business of bodies: Ethical perspectives on for-profit body donation companies’,Clinical Anatomy, 29 (2015), 25–9, 28. 60 Sandor, op. cit. (note 3), 399. 61 Sabine Louët, ‘Dark Age medicine’,Nature (12 Oct. 2004), https://doi.org/10.1038/news041011-4. 62 Blizzard, op. cit. (note 37), 88. 63 Ibid., 89. ‘At least our pituitaries will see the world’9 https://doi.org/10.1017/mdh.2025.10029 Published online by Cambridge University Press