While the birth of Dolly the sheep triggered a flood of media attention in 1997,1 neither the technology of nuclear transplantation nor the ethical concern about it was new at the time. In Forgotten Clones: The Birth of Cloning and the Biological Revolution, historian Nathan Crowe uncovers the scientific ideas, experiments, ethical discussions, and sensational representations surrounding nuclear transplantation in the United States and Britain between the 1930s and 1970s. In doing so, Crowe weaves together intellectual and experimental trajectories within the laboratories and interpretations about them offered by other scientists, journalists, novelists, and politicians. The book reveals, in depth, the scientific work involved, the ethical concerns expressed, and often the complete disjunction between the two regarding nuclear transplantation before Dolly. One part of the narrative is about what has been virtually erased from our historical consciousness—the goals and processes involved in performing nuclear transplantation (Chapters 1–4). In the 1940s and 1950s, Robert Briggs, Thomas King, and Marie Di Berardino at the Lankenau Hospital Research Institute (LHRI) in Philadelphia aimed at examining the level of nuclear control in cell growth for understanding cancer etiology through their nuclear transplantation in the frog Rana pipiens. Little, if any, of the nuclear transplantation research by the end of the 1960s aimed at application in human reproduction. The other part of the narrative is about how common tropes of bioethical discussion became formulated by talking about nuclear transplantation via the lens of human cloning. For this, Crowe clearly articulates how discussions about nuclear transplantation in the 1960s and 1970s set up important precedents for discussions of other reproductive technologies (Chapters 5 and 6). In the 1960s, a few “visible scientists,” including Joshua Lederberg, vocalized their concerns about possible human cloning. This extreme case of technological intervention invited public conversations about the potential opportunities and hazards of what was perceived as an impending biological revolution. As journalists, novelists, science critics, and politicians echoed on concerns about the use of these techniques to alter humans, the original motivations for achieving nuclear transplantation in the laboratory became obscured. In the early 1940s, when Briggs started working at the LHRI, the institute had a vision that the study of differentiation and growth held the key to better biomedical understanding of cancer. Aligned with this vision, Briggs brought in his expertise in experimental embryology and biochemistry as well as his experience working on cancers of the frog. Briggs's move into cancer research not only reflected his own pragmatic bent but also a larger struggle of embryology as a discipline at the time. After the 1930s, a golden decade with Hans Spemann's transplantation methods and a proliferation of studies about the concept “the organizer,” experimental embryology faced increasing challenges. With Thomas Hunt Morgan's Drosophila genetics and successful applications of Mendelian genetics in agriculture, studies of heredity were dominated by attention to the nucleus and transmission of traits between generations. Even though many embryologists shared a conviction that the cytoplasm played an equally vital role in determining cellular growth and differentiation, they lacked a united front in ideas or methods compared to their geneticist colleagues. This contrast was reflected in a “methodological battle between the ‘orthodoxy’ of genetics and the ‘pluralism’ of embryology (p. 41).” The question about the relative importance between the nucleus and the cytoplasm in initiating normal or cancerous growth thus became a question about “disciplinary relevance.” Coincidentally, leaders of the LHRI research programs Stanley Reimann and Frederick Hammett saw tremendous value in understanding normal growth for cancer research. They advocated an integrative approach that employed diverse methods from different disciplines to tackle the problem. Nevertheless, studying cellular growth was conventionally in the turf of embryologists. In fact, Reimann and Hammett would coestablish the Growth Society to provide a forum for biologists to discuss the issue, which attracted predominantly embryologists and eventually became renamed the Society for Developmental Biology in 1965. Briggs designed the nuclear transplantation experiment in the hopes of elucidating the relative roles of the nucleus and the cytoplasm in directing cellular growth and differentiation and perhaps also shedding light on cancer etiology. It was not initially designed to address a 19th-century question of whether adult somatic cells and the fertilized egg were “cellular equivalents,” even if he attached such a purpose to the experiment in his coauthored 1952 paper.2 Making nuclear transplantation work in Rana, however, hinged upon a series of trials and errors, and involved intensive, delicate labor. Briggs and his coworkers tested various methods for extracting and injecting the nucleus without damaging it or the receiving egg cell. For the cellular material to be synchronized, two skilled experimenters, i.e., Briggs and King, would work at the same time—one focused on removing the nucleus from the egg, and the other on obtaining the nucleus from the adult donor cell and injecting it into the enucleated egg. Di Berardino, who was originally hired as a technician but eventually obtained her PhD and worked at LHRI as a research scientist, contributed to these technical operations while conducting her own study on Rana's karyotype. As Crowe shows, this pattern of local technical tinkering and reliance on women researchers' contributions has been replayed in the nuclear transplantation work conducted with other species and in other laboratories. In covering the many strands of research that followed Briggs' team, Crowe examines in detail the well-known work by John Gurdon done at Oxford University with the African clawed toad Xenopus laevis. Abundant and available for all seasons in Britain, Xenopus offered eggs whose nuclear material could be easily deactivated with an extra-low frequency of ultraviolet light. These receiving eggs thus did not need to be enucleated, saving much operational travail. Gurdon obtained a quite similar result to that of the Briggs's team, i.e., the more advanced the developmental stage a nucleus was from, the less likely it could initiate normal development. He nevertheless drew a completely opposite conclusion. He argued that all adult cells with the normal karyotype retained a full developmental capacity. The work published in 1962 that showcased the full potency of normal adult cells3 would become the major work cited for Gurdon's 2012 Nobel prize. Others who picked up the nuclear transplantation experiments in the 1950s and 1960s followed divergent intellectual trajectories, which rarely gestured toward human reproduction. These directions included studies of gene regulation, continued research in cancer causation, and extending the technique to other species such as those of fish or rabbits. Crowe's delineation of this rich intellectual and technological expansion is unfortunately rushed (Chapter 4). Toshijuro Kawamura's work in Japanese pond frogs is mentioned without citation or indication of his institution (p. 137), for example. Work led by Tong Dizhou (T. C. Tung) is obscurely mentioned as being done, simply, by “Chinese embryologists,” even when Di Berardino's book, cited in the same line, documents Tong's research well (pp. 141–142).4 The chapter then takes an abrupt turn to the rise of science reporting in the United States before veering into a portrayal of the eccentric French author Jean Rostand and his vision of human cloning through nuclear transplantation. Perhaps Chapter 4 is condensed for the sake of transitioning to the stories of Joshua Lederberg and other well-known individuals in science and ethics who associated nuclear transplantation firmly with an imagined future of human cloning. These sequelae are detailed in Chapters 5 and 6. In the 1960s, the anticipation of a biological revolution propelled a small circle of elite biologists to take actions in stirring discussions about the promises and perils in the potential use and misuse of biotechnology. They did so partly to prevent a doomsday scenario resulting from a biotech fallout similar to the detonation of an atomic bomb. Among them, Lederberg articulated his speculations about potential future uses of human cloning in a series of conferences designed to discuss the role of biotechnology in humanity's future. In addition to these by-invitation-only conferences, Lederberg reached out to the public. His article “Experimental Genetics and Human Evolution” that exposes brave-new-world-like futures made with “vegetative propagation (p. 189)” of humans made a dual publication in The American Naturalist and Bulletin of the Atomic Scientists in 1966.5 It was reprinted many times, reaching a large readership. Even though Lederberg regarded the article as a thought experiment only, others often took it literally. A theology professor at Princeton University, Paul Ramsey, for example, entered the foray with ethical critiques including the potential issue of “playing God” in making human offspring via technological means. Ramsey's 1970 book Fabricated Man6 became a foundational text in the burgeoning field of bioethics. While preparing the book, Ramsey was in conversation with Leon Kass, then working as a scientist at the National Institutes of Health. Kass would soon leave science and take up his new calling in bioethics. Lederberg's interlocutors and readers, Ramsey included, took his speculations literally and became fully convinced that there were justifiable reasons to believe that, without proper intervention, a world with cloned teams of Adolf Hitler could be emerging in the near future. Meanwhile, the original intellectual and institutional context of Briggs' experiments was made increasingly invisible as the public discourse marched on. This trend of forgetting held true even for Briggs himself. When Briggs testified before the congress in 1978, he explained his work through the 19th-century question about cellular equivalents, not questions about cellular control of growth and differentiation in cancer that had motivated the work. This round of ethical discussions about nuclear transplantation reached a peak and then subsided after David Rorvik made farcical claims about the creation of the first cloned human baby in his book In His Image.7 A muscle memory of precaution and fear was nevertheless retained in how the public and bioethicists approached biotech controversies despite the almost two decades between the 1978 congressional hearing and the birth of Dolly. Such an apprehensive approach also shaped how the human embryonic stem cell research became debated in the early 2000s. Overall, Crowe offers a highly valuable, quite fascinating, and still timely account of one origin of myth creation and context removal in the public conversation about biotechnology and its future. The historical account about Briggs, King, Di Berardino, Gurdon, and others in their fuller, complex contexts provides a valuable antidote to our historical amnesia. It is a must read for historians, scientists, and ethicists interested in reproductive biotechnology and associated controversies. Given the centrality of “forgetting” as a problematic, however, Crowe does not seem to try to offer big-picture explanations that the gravity of the issue should deserve. A few questions regarding why certain content or context became forgotten while others were remembered or fabricated in the history of nuclear transplantation remains inadequately addressed. For example, regarding why Briggs himself omitted the motivations of studying nuclear control and cancer etiology in his later accounts, one may wonder whether failed attempts in explaining cancer through developmental biology in later years played a role. A longer-term examination of the LHRI's institutional history and the evolution of the Growth Society might be able to shed light on this issue. Even with a predominant Anglo-American focus, Crowe gestures toward an international scope and has attempted to incorporate selective work outside the English-speaking world, including experiments done in the Soviet Union, France, and Belgium. Some of the selective portrayals are more satisfying than others. Explanations regarding why some cloning work done after Briggs are examined while others are not, however, would have been helpful. In other words, reflections about how writing and publishing Forgotten Clones participates in the long train of selective remembering that makes certain actors more visible than others could have further enhanced the book's general purpose.
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