Matthew Holmes
Cambridge, UK

Anne McLaren, Oxford-trained zoologist and first female Officer of the Royal Society, once claimed that “History may be circular, but the history of science is helical: it repeats itself, but each time at a deeper level.”¹ To see the helical nature of the history of science in action, we need look no further than the history of blood transfusion. Towards the end of the nineteenth century, Victorian polymath Francis Galton had carried out a famous transfusion experiment. Galton was testing pangenesis, the latest theory of his cousin, Charles Darwin, who argued that each cell of the body throws off a minute copy of itself. These subcellular copies then congregate in the sexual organs and are the means by which the physical characteristics of parents are passed onto their offspring. Galton took two varieties of rabbit and transfused blood from one to the other, hoping to spot some characteristic of his involuntary blood donor in the next generation. Yet he was disappointed. Blood transfusion led to no “alteration of breed,” demonstrating that “the doctrine of Pangenesis, pure and simple, as I have interpreted it, is incorrect.”²

Some eighty years later, during the early 1950s, McLaren encountered a near identical experiment during an Agriculture Research Council Fellowship alongside Peter Medawar at University College London. Medawar had been working on immunology and transplantation. In 1949 he had tackled the “freemartin” problem in cattle, where non-identical twin cattle, one male and one female, are born with the female calf sterile. Hugh Donald, an Edinburgh veterinarian, suggested that skin grafts might be used to distinguish these freemartins from identical twins. Donald reasoned that non-identical twins would not accept grafts from their genetically distinct sibling. Yet, to Medawar’s surprise, this was not the case. Non-identical cattle accepted grafts into adulthood, implying that tolerance was less to do with genetics than with cross-circulation of blood in the womb. Medawar and his team replicated this work at University College London during the early 1950s. Embryonic chickens and mice who received donor cells gained the ability to accept transplants from that same donor in later life. This phenomenon was evidence that immunological “tolerance” could be acquired over time.³

Yet at the height of the Cold War, transfusion and grafting were dangerous topics. On July 31 1948, Soviet delegates had gathered for the meeting of the Lenin Academy of Agricultural Sciences. Trofim Denisovich Lysenko, a peasant farmer turned agronomist, delivered the opening address. In what Stephen Jay Gould termed the “most chilling passage in all the literature of twentieth-century science,” Lysenko announced that his report on biological science in the Soviet Union had been given a stamp of political approval from the Central Committee of the Bolshevik Party.⁴ To thunderous applause, Lysenko denied the tenets of classical genetics and claimed it was possible “to obtain plant hybrids by means of grafting.”⁵ Lysenko theatrically gestured towards a table holding several plant chimeras with the combined characteristics of potatoes and tomatoes. Western observers scoffed and denounced Lysenko’s biology as pseudo-science. McLaren, a Communist Party member whose research interests focused on mice chimeras, found herself on the wrong side of a scientific divide.⁶ Although she never endorsed Lysenko, she admired Marxist biology and thought heredity could not be explained through genetics alone.

At the 1953 International Congress of Microbiology in Rome, McLaren was therefore excited to hear news of a young Czech scientist called Milan Hašek. Hašek claimed to have demonstrated the validity of Lysenko’s biology in animals, creating hybrids by joining the blood vessels of embryonic poultry—a process known as parabiosis. Once separated, the adult chickens could freely accept grafts from their former partners without an immunological response. Hašek had even connected the circulatory systems of different species. He found that when the blood supply of a turkey and a chicken were mixed, following their separation, evidence of this connection in the form of foreign blood cells remained in the turkey for as long as eight weeks. Hašek concluded that their presence could only be explained by the bird creating foreign blood cells in its own circulatory systems. According to immunologist Leslie Brent, this finding “has never been adequately explained.”⁷ If Hašek was right, then heritable traits could be freely swapped between species using techniques like grafting or parabiosis to create new hybrids.

McLaren relayed this information to a “somewhat disconcerted” Medawar.⁸ As they stood, Hašek’s findings were completely unacceptable to Western biologists. Hašek believed that his poultry were “vegetative” or “graft” hybrids, analogous to the plants unveiled by Lysenko at the 1948 Lenin Academy meeting. He toed the official line by stating that Lysenko had disproved Western genetics and stated that his research provided further support for Lysenko. Yet in 1954, Medawar and fellow immunologist Leslie Brent met Hašek and persuaded him that many of his findings could instead be interpreted through their own theory of acquired immunological tolerance. Medawar eventually helped Hašek to publish his findings in the journal of the Royal Society in 1956, albeit with all mention of Lysenko and graft hybrids safely removed. “Embryonic parabiosis,” Hašek now argued, “brings about an immunological tolerance which persists for a long time, sometimes perhaps throughout the individual’s life.”⁹ McLaren, however, continued to interpret Hašek’s findings through a Marxist framework. Decades after the Medawar-Hašek collaboration, McLaren still argued that Hašek had shown that “combining the characteristics of two strains vegetatively (e.g., by grafting or parabiosis) is analogous to combining them sexually by crossing.” In her own research, McLaren hoped that her mice chimeras would show signs of heterosis, or hybrid vigor. Like Hašek, she would then be in possession of her own graft hybrid. She felt increasing “irritation at the neglect of the role of environmental influences” in biology and in 1959 moved to what she saw as the more open-minded Institute of Animal Genetics at Edinburgh, where she remained for fifteen years.¹⁰ McLaren continued to argue in favor of alternative mechanisms of inheritance for the rest of her life.

The Cold War clash over the nature of heredity and the role of blood in inheritance left other legacies. Medawar went on to share the 1960 Nobel Prize in Physiology or Medicine for the discovery of acquired immunological tolerance. Yet he may have felt some measure of disquiet about his censorship of Hašek’s original interpretation. In 1964, Medawar provocatively asked, “Is the scientific paper a fraud?” in a BBC Radio broadcast, criticizing the inductive and artificial structure of the typical scientific paper. Scientists, declared Medawar, like ordinary human beings, are guided by imagination, intuition, and personal philosophy. By ignoring these elements, he claimed, we neglect a fundamental part of the scientific enterprise.¹¹ Medawar’s aversion to the unnatural structure of scientific papers can be adequately explained through his admiration for the philosophy of Karl Popper.¹² Perhaps though, he felt some responsibility for his own role in the removal of Hašek’s personal philosophy. Although Medawar’s actions had allowed Hašek to be published in the West, by doing so he had inadvertently helped to maintain a system he fundamentally disagreed with.

Following the downfall of Lysenko, we would now label Hašek’s poultry as chimeras—an organism containing two distinct genomes—rather than a graft or vegetative hybrid. Anyone who has received a blood transfusion can temporarily label themselves as a chimera, as least until their body replaces the donated blood with their own cells. McLaren, of course, understood this distinction, but remained hopeful that a chimera might one day display the characteristics of a true hybrid. Recent studies have demonstrated that genes can be exchanged between grafted plants, raising hopes that grafting “could provide plant breeders with new tools to create novel traits and crops.”¹³ For now we speak of blood and its properties in the language of immunology, antigens, and antibodies—rather than that of hybridization and species identity. Yet controversy over the essence of blood has emerged time and again, whether through the rabbits of Francis Galton or the poultry of Milan Hašek. As Anne McLaren once noted, the history of science may indeed be helical.

References

1. McLaren A. Too Late for the Midwife Toad: Stress, Variability and Hsp90. Trends in Genetics 1999; 15: 169-171.
2. Galton, F. Experiments in Pangenesis, by Breeding from Rabbits of a Pure Variety, into Whose Circulation Blood Taken from other Varieties Had Previously Been Largely Transfused. Proceedings of the Royal Society of London 1871; 19: 393-410.
3. Hamilton D. A History of Organ Transplantation. University of Pittsburgh Press, Pittsburgh, 2012 p.223.
4. Gould SJ. Hen’s Teeth and Horse’s Toes. Norton, New York; London, 1983 p.135.
5. Lysenko TD, Agrobiology: Essays on the Problem of Genetics, Plant Breeding and Seed Growing. Foreign Languages Publishing House, Moscow, 1954 pp.545-546.
6. Hogan B. From Embryo to Ethics: A Career in Science and Social Responsibility. Int. J. Dev. Biol. 2001; 45: 477-482.
7. Brent L. A History of Transplantation Immunology. Academic Press, San Diego; London, 1997, p.201.
8. McLaren A. International Rapprochement, 50 Years Ago. Transplantation 2003; 76: 1425.
9. Hašek M. Tolerance Phenomena in Birds. Proceedings of the Royal Society of London. Series B, Biological Sciences 1956; 146: 67-77.
10. Franklin S. Obituary: Dame Anne McLaren. Regenerative Medicine 2007; 2: 853-859.
11. Medawar P. Is the scientific paper a fraud? Listener 1963; 70: 377-378.
12. Calver N. Sir Peter Medawar: Science, Creativity and the Popularization of Karl Popper. Notes and Records 2013; 67: 301-314.
13. Le Page M. Farmers May Have Been Accidentally Making GMOs for Millennia. New Scientist 07 March, 2016.

Image source

A Early Blood Transfusion from Lamb to Man. Credit: Wellcome Collection. CC BY 4.0.