From Haldane to Jiankui: An Introduction to Cloning
The history of human cloning commenced around the climax of the second industrial revolution, where the landscape of information technology and medical capabilities converged at astronomical rates. The conception of reproductive technology was first penned in Aldous Huxley's dystopian social science fiction novel, "Brave New World" in 1932. Thirty-one years later, British scientist, J.B.S. Haldane, who is well-known for being the first to introduce a solidified thesis of human cloning, referenced Huxley's novel when orating his vision to an audience of scientists in 1963 (Haldane 359). Over the course of fifty-nine years, medical institutions, embryologists, and lawmakers have intimately dissected the bioethics of genetic cloning of humans. Countless experimentations have been performed on mammals since Haldane's discourse, however, the terrain is significantly more intricate when conducting clinical trials on human health. In this report, I will provide a synopsis of Haldane's work, mammals cloned, present in-depth information on CRISPR technology, while encompassing this research paper on the 2018 bioethical controversy of He Jiankui. Lastly, I will examine whether or not the existing moratorium on gene-editing regulations must be extended based on contemporary research and findings from the He Jiankui study.
Genesis: Dolly the Sheep
The First, But Not Last Conversation: An Intro to J.B.S. Haldane
In 1963, J.B.S. Haldane — a British scientist who specialized in physiology and genetics — was the first to present the conception of human cloning (Haldane 337). Haldane articulated his vision at The Ciba Foundation Symposium on “Man and his Future” where his speech, “Biological Possibilities for the Human Species of the Next Ten Thousand Years,” piloted into the uncharted scientific territory of biological capabilities. Haldane was optimistic that “some human cell lines can be grown” for populations of fifty and older while reserving “precisely known chemical compositions” for citizens who harbored notable status in society such as “athletes and dancers,” whose genetic makeup would be stronger (Haldane 338). Over the next three years, renowned geneticists and bioethicists were debating the prospects and perils of genetic engineering. From Joshua Lederberg, who championed human cloning, to Leon Kass, who opposed Lederberg, by penning in The Atlantic that “the programmed reproduction of man will, in fact, dehumanize him” (Watson). In the same year, biologists and embryologists saw the subsequent stage in cloning was to experiment with a Finnish Dorset sheep.
1996: The Birth of Dolly the Sheep
Dolly the sheep — July 5, 1996, to February 14, 2003 — was the first mammal cloned from an adult somatic cell, by embryologists, Keith Campbell and Ian Wilmut of The Roslin Institute in Scotland (Niemann). Dolly's cloning confirmed that a cloned organism was able to be constructed from an adult cell from a mammary gland. For mammals, the technique of somatic cell nuclear transfer can have benefits in conserving imperiled species, moreover, may evolve to a feasible mechanism for biomedical research. However, for human cloning, the scientific methodology is more intricate and comprehensive, as the long-term ramifications of a gene-edited embryo are novel in decades following the procedure. In 2007, Wilmut stated that “the nuclear transfer technique may never be sufficiently efficient for use in humans” (Roger). The research accomplished twenty-six years ago by Campbell and Wilmut invites contemporary embryologists and lawmakers to examine whether or not existing technology is safe to use today. If not, what experiments and techniques have been conducted in current research to lead to that case?
Genome Editing: Understanding CRISPR Technology
CRISPR (clustered regularly interspaced short palindromic repeats) gene editing is a congenital biological engineering practice in molecular biology in which the genomes of living organisms can be altered (Rodolphe 37). The technique is founded on an austere rendition of the bacterial CRISPR-Cas9 antiviral defense system. By furnishing the Cas9 nuclease coupled with an artificial guide RNA (gRNA) into a cell, the cell's genome can be trimmed at a distinct locality, ultimately authorizing living genes to be terminated and new ones counted in vivo — in living organisms (Rodolphe 39). The technique is regarded as highly consequential in bio-engineering as it permits the genomes to be reworked in vivo with extraordinarily increased accuracy, inexpensive, and with alleviation. Nonetheless, its use in human germline and genetic adaptation is deemed controversial. Numerous bioethical concerns have been raised about the prospect of employing CRISPR for germline editing, primarily in human embryos (Rodolphe 42).
As of March 2015, numerous global research groups had announced ongoing experiments with "the intention of laying the foundations for applying CRISPR to human embryos," for human germline engineering, including labs in the People's Republic of China, the United Kingdom, and the United States (Regalado). Scientists, including a CRISPR co-inventor, instructed a global moratorium on using CRISPR in the human germline, specifically for clinical use (Baltimore 36). The group of geneticists urged "scientists [to] avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans" until the full implications "are discussed among scientific and governmental organizations" (Baltimore 37). The scientists support further low-level research on CRISPR and do not regard CRISPR as developed adequately for any clinical use in assembling heritable changes in humans.
A Modern Frankenstein: The 2018 He Jiankui Gene-Editing Controversy
Human Gene-Editing Experiment
In April 2015, Chinese scientist, Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, reported results of an attempt to alter the DNA of non-viable human embryos using CRISPR to correct a mutation that causes beta-thalassemia — a blood disorder that diminishes the rate of hemoglobin (Cyranoski). The examination had formerly been rejected by medical journals "Nature and Science in part because of ethical concerns," however the clinical trials resulted in successfully altering "only some of the intended genes," while having off-target effects on other genes (Cyranoski). Huang and his colleagues stated that "CRISPR is not ready for clinical application in reproductive medicine" as additional research and analysis must be conducted (Cyranoski).
In December 2015, an International Summit on Human Gene Editing took place in Washington, DC, where members of the national scientific academies of China, the U.K., and the U.S. examined the ethics of germline modification (IHS). The council members agreed to support basic and clinical research under certain legal and ethical guidelines. A meticulous disparity was established between somatic cells, where the consequences of edits are restrained to a single individual, and germline cells, where genome changes can be inherited by an offspring. Heritable modifications could have unintended and far-reaching consequences for human development (IHS). Two years following Huang's unsuccessful attempt at non-viable human embryos, a "rogue scientist in China," executed a gene-editing experiment without public approval in his scientific district, which ultimately led to his downfall and a mountain of debate encompassing human gene-editing (Low).
Profile on He Jiankui
He Jiankui, who is commonly referred to as "China's Dr. Frankenstein," and a "mad genius" was a Chinese scientist who initiated an undertaking to aid parents with HIV-related fertility difficulties — chiefly concerning HIV-positive fathers and HIV-negative mothers in October 2018 (Low). Jiankui learned CRISPR/Cas9 — gene-editing techniques — as a postdoctoral researcher at Stanford University. Jiankui and his three colleagues' unethical experiment, "offered standard in vitro fertilization services...and CRISPR gene editing" (Low). The embryos' genomes were reworked to remove the CCR5 gene with the intent to vest genetic resistance to HIV. The researchers operated in sub rosa, until "MIT Technology Review broke the story of the human experiment" from data gathered from the open-source Chinese clinical trials registry (Low). Following the MIT report, Jiankui publicly announced that he had edited two human embryos to attempt to disable the gene for CCR5, which codes for a receptor that HIV uses to enter cells. Jiankui said that the twin girls, Lulu and Nana, had been born weeks earlier, in October 2018, while still carrying operative copies of CCR5 along with disabled CCR5, which meant they were still vulnerable to HIV. At the onset of Jiankui's significant scientific development, he was met with positive recognition, which momentarily pivoted to condemnation, for unethically concocting the first human genetically edited babies (Low). The work was widely denounced as “unethical, dangerous, and premature,” and an international group of scientists called for a global moratorium on genetically editing human embryos (Regalado).
On December 30, 2019, the Shenzhen Nanshan District People's Court sentenced Jiankui to three years in prison, in addition to a $430k fine (Normile). Jiankui and his collaborators were found guilty of having "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos into two women." (Normile). Based on Jiankui's unethical actions, does the existing moratorium on gene-editing regulations need to be extended based on current research and findings from the He Jiankui study?
Current Programs and Regulations for Cloning and Genetic Engineering
The unethical practices of Jiankui led policymakers to review existing laws for human cloning. As of 2018, 70 countries have outlawed human cloning — and the U.S. is not in that group. Since 1998, U.S. Congress has fallen short on countless cases to enact a bill forbidding human cloning (Cyranoski). The map below depicts regions that have installed human cloning laws.
The regions shaded blue indicate countries where human cloning is illegal, yellow; where there are some forms legal, red is legal, and grey illustrates data that is insufficient/or no data.
Ethical Implications of Human Gene-Editing
In Support of Gene-Editing
The ethical implications of human cloning have been argued for and against the practice by prominent scientists to lawmakers. In a 2016 Worldwide Threat Assessment of the US Intelligence Community statement, U.S. Director of National Intelligence, James Clapper, designated genome editing as “a potential weapon of mass destruction,” furthermore, stating that genome editing conducted by countries with regulatory or ethical standards are "different from Western countries" who are likely to boost the risk of the creation of harmful biological agents (Baltimore 38). Clapper argues against genetic engineering for both mammals and humans, as the former Director of National Intelligence stated in the report that the operations “broad distribution, low cost, and accelerated pace of development” and advanced technology, whether “deliberate or unintentional misuse,” have grave economic and national security implications. (Baltimore 38).
In support of gene editing, many transhumanists — an intellectual movement that advocates for the augmentation of humans' longevity and cognition — regard genome editing as a potential tool for human enhancement (Regalado). Australian biologist and Professor of Genetics David Sinclair remarks that "the new technologies with genome editing will allow it to be used on individuals…to have…healthier children" or designer babies. The purpose of “designer babies,” is to use CRISPR-Cas9 gene drives to modify genes associated with genetic diseases (Regalado). Furthermore, transhumanists would use CRISPR technology to eradicate diseases and conditions that humans are predisposed for, thus selecting which genes their offspring will have. With this new scientific system, embryologists will be able to take the genes of a human sperm cell and egg and replace the genes that activate cancer or other abnormal or unwanted defects or diseases. This system will take the stress off from parents concerned about having a child not being able to live a normal life. After one generation undergoes this process, the entire lineage wouldn't have to be distressed about diseases or predisposing conditions.
Against Gene-Editing
In a report by Nuffield Council on Bioethics, employing CRISPR technology can have unintended consequences which could harm not only the child but also their future children, as the altered gene would be in their sperm or eggs. Council members of the NCB regard the existing gene-editing technology as unsafe for the gene-edited child, as the adolescent's development is too risky and modifying a child's genome can make detrimental “changes pass[ed] on to future generations” (Jiang). The safety and long-term consequences need more clarity, as existing research is too ambiguous. In a joint statement by The American National Academy of Sciences and National Academy of Medicine, both institutions gave support for clinical trials for human genome editing, in the future, “once answers have been found to safety and efficiency problems ‘but only for serious conditions under stringent oversight,’ as the safety is a paramount concern in the process (Jiang).
Closing: What Does The Future Hold For Human Cloning
Since Haldane orated his 1963 speech, the rift between transhumanists advocating for gene-edited babies and lawmakers institutionalizing laws to ban the act has widened. From a transhumanist point of view, the benefits of gene-editing, where a child wouldn't have deformities or diseases, outweigh the risk. However, with emerging technology, and advancements with CRISPR, generational human health is uncertain. As of January 7, 2022, there are "156 clinical trials registered in the WHO Human Genome Editing Registry" (Muigai). He Jiankui's unethical project was just the tipping point in a series of unethical and societal controversies. Jiankui's 2018 scandal shed light on the importance of the existing moratorium on gene-editing to be renewed, as the technology used in the procedure is relatively new and additional proctored examinations need to be administered for long-term ramifications for the child and future generations.
References
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