Want a bespoke baby? Check the beauty, brains, or brawn boxes on the embryo order form. Genetic tinkering is no longer science fiction\u2014it\u2019s a market without legal guidelines or societal buy-in. But what happens when we rewrite the human before reading the fine print? <\/p>\n
The secrets of our genes can be mined or misused. Our challenge is to sift through the data, utilize the tools, knowledge, and wisdom of what we can handle, and resist the temptation of tangling with the remainder. Otherwise, we risk creating the Sorcerer\u2019s Apprentice, incorporating unintentional tweaks, errors, or mutations capable of reproducing for all eternity, without \u201cthe undo\u201d or \u201cnever mind\u201d code. This takes courage, willpower, and enforceable international regulations, which as of now go wanting.\u00a0<\/p>\n
To Recap<\/p>\n
Somatic cells regulate cellular function; their information is not inherited, and genetic editing of mutated or defective somatic cells can be made without fear that mistakes will be transmitted across generations. By contrast, editing of germ cells has the potential to change cells on a hereditary basis, and therein lies the rub.\u00a0<\/p>\n
Biological concerns of germline editing include the fear of unintended consequences, creating irreversible errors, and knowledge gaps, such as the role of\u00a0epigenetics<\/a>. Legal,\u00a0ethical<\/a>, and moral questions trigger fears of privacy incursion, unintended use by insurance companies, schools, and employers, as well as a lack of societal buy-in and discourse.<\/p>\n Notwithstanding the dangers,\u00a0germline engineering<\/a> has been carried out at least once, to uniform and international (albeit ad hoc) condemnation. The objections were so loud that the perpetrator, Chinese doctor He Jiankui, was jailed. Bans were enacted in the Oviedo Convention in Spain, which legally bound members of the Council of Europe, \u00a0and regulations were promulgated in Britain and Canada. By comparison, in the US, the sole effective constraint is the unavailability of federal funding. However, little stops the intrepid, wealthy tech-bro from renting an offshore island and setting up shop.<\/p>\n While scientists rant about the lack of regulation, and entrepreneurs are busy renting office space, lawyers, ethicists, influencers, and the public remain generally ignorant of the uses and dangers.\u00a0<\/p>\n Dangers- What dangers?<\/p>\n To begin, genes often have multiple roles, a property called\u00a0pleiotropy<\/a>. In most cases, we don\u2019t know the full extent of a gene\u2019s capacities. Editing one gene may cause off-site effects, and deleting a \u201cbad\u201d gene may inadvertently remove a protective effect for the gene pool. Thus, people with two copies of the HBB gene can develop sickle cell anemia, but that gene also conveys resistance to malaria. Deleting the HBB would prevent sickle cell anemia, but also increase the risk of malaria. On an individual basis, this may be OK. On a population basis, not so much. The CCR gene, hubristically edited by He Jiuankui to prevent HIV\/AIDS, is now thought to be related to cognition and dementia. The far-reaching and yet unknown ramifications on future generations are unclear.<\/p>\n A bioethical offshoot of this issue revolves around the impact of permanent changes to the human gene pool \u2013 even those currently regarded as beneficial. Genetic editing that favors socially preferred genomic avatars or genetic signatures (e.g., blonde, blue-eyed, buxom, Barbie-like beauties) would limit genetic diversity, a guarantor of a species\u2019 survival. \u00a0And since financial resources will determine who avails themselves of the technology, we can expect exacerbation of a two-tier society. These issues, in turn, birth the question of who will be empowered to decide which species-permanent changes we make?<\/p>\n Beyond Nature<\/p>\n While some diseases are governed by individual genes, such as Tay-Sachs or Huntington\u2019s disease, and are amenable to genetic repair, most conditions, like diabetes or heart disease, are governed by\u00a0multiple genes<\/a> acting in concert. These diseases are not simply a product of genetic programming, which creates our genotype, but require mediation by a constellation of environmental and lifestyle factors to produce a particular effect, our phenotype.\u00a0<\/p>\n To target the gene groups involved in multifactorial diseases or traits, some companies are producing algorithms to compile a\u00a0polygenic risk score<\/a> (PRS).\u00a0<\/p>\n \u201cPolygenic risk scores (PRSs)<\/a> summarize genome-wide genotype data into a single variable that measures genetic liability to a disorder or a trait. \u2026\u00a0 summing the number of risk alleles carried by an individual, weighted by the effect size \u2026. The PRS is seductive in its [apparent] simplicity\u2026.\u201d<\/p>\n These scores are commercially marketed for individual, clinical use, although verification of their validity for these purposes is non-existent. And while PRS may be useful for public health purposes, the predictive value is limited by the test population\u2019s genetic variations, making generalization to individuals more akin to snake oil than prescriptive care. \u00a0They ignore considerations of environmental and lifestyle factors influencing the expression or realization of the targeted genotype or traits, meaning you might not even get what you signed up for.\u00a0<\/p>\n Additionally, new technologies like\u00a0AI<\/a> alert us to greater genetic\u00a0complexities<\/a> not only in causing diseases, but also for non-disease traits like height, intelligence, and hair color, making genetic editing or relying on PRS even more fraught.<\/p>\n Getting Our Hands Around the Jello<\/p>\n Complicating assessment is the already muddy characterizations of the contents of Pandora\u2019s genetic box, including the sloppy cataloging and conceptualizing of genetic procedures: Roughly six types of interventions are now available or theoretically possible, although in addressing each, legal, ethical, and moral concerns are often lumped together:\u00a0<\/p>\n Somatic cell editing to treat or cure individual diseases (in utero or after birth). These procedures\/technologies have different purposes, risks, and benefits, present other dangers to our species, and trigger different social sensitivities. Some techniques will directly or indirectly affect the gene pool forever, highlighting questions over society\u2019s right to informed consent or eugenic concerns.<\/p>\n Playing to Greed and Ego<\/p>\n Latest on the genetic drafting table are\u00a0socio-economic polygenic\u00a0<\/a>scores (PGS). These are touted as being predictive of education, income, occupation, and more. They are erroneously perceived as carrying scientific weight, inviting interest from the\u00a0legal<\/a> community, admonishing influencers to maximize benefits while minimizing harms, and giving legitimacy to the scores when unwarranted. Indeed, the scientific fallacies involved in using these scores on a clinical basis are sidestepped, while population use is given credence, even though the scores have yet to be validated. What may be worse is that the biological ramifications to future generations go unrecognized by non-scientifically oriented influencers.\u00a0<\/p>\n Even without a rigorous social discourse on the ethics of genetic-tampering ventures, which I have\u00a0previously<\/a> and repeatedly<\/a> raised, these products and marketers are increasing.<\/p>\n Last month,\u00a0Nucleus Genomics<\/a> boasted new technologies to determine genes for sex, height, hair color, eye color, along with IQ and complex traits like anxiety and ADHD. Another new carrot in the PGS marketing tool-kit includes scores reflecting\u00a0longevity<\/a>, ranking embryos by likelihood of diseases impacting lifespan. That expression of these genes (even if all relevant ones could be identified and targeted) involves environmental and lifestyle components outside parental control, is not dwelt on.<\/p>\n Paradigm Shift<\/p>\n Not to be outdone, Brian Armstrong, creator of the cryptocurrency exchange Coinbase, is planning on going beyond embryo-selection and entering the ethically fraught world of\u00a0embryo-editing<\/a>.\u00a0Armstrong intends to implement newer, \u201csafer,\u201d gene-editing techniques, called base-editing, to make \u201chumans resistant\u201d to common conditions like heart disease or Alzheimer\u2019s. Related plans by co-founded company NewLimit, a \u201clife-extension venture,\u201d are exploring ways to reprogram old cells into an embryonic-like state, and pursuing \u201cimmortality\u201d research, including uploading human minds to computers.<\/p>\n Like all technologies, genetic tinkering can be used for both good and bad purposes. In this case, however, that dichotomy is muddied by unknowns and unintended consequences, polluted by profit-making matrices, and concocted to tantalize parental desires for better, brighter, brawnier kids. The stakes go beyond prettier and pricier progeny with genius genes. Newly fangled lures include the possibility of genetic intervention to prevent disease and increase longevity, along with raising the specter of eugenic selection, benefiting the rich while penalizing the poor.\u00a0<\/p>\n The scientific community is not amused.\u00a0 Recently, three organizations representing leaders in reproductive technology [1]\u00a0demanded<\/a> a\u00a0ten-year global moratorium<\/a>\u00a0on heritable human genome editing, warning that it remains \u201cfar too risky and ethically fraught for clinical use.\u201d\u00a0<\/p>\n I fear it\u2019s too late:<\/p>\n \u201cWhat was once controversial is now an everyday practice. The same is true with genetic optimization. The technology is now here and it\u2019s here to stay.\u201d\u00a0<\/p>\n – Kian Sadeghi, CEO of Nucleus, a company providing \u201cgenetic health insights\u201d<\/p>\n \u00a0<\/p>\n [1] Alliance for Regenerative Medicine (ARM), the International Society for Cell and Gene Therapy (ISCT), and the American Society for Gene and Cell Therapy (ASGCT<\/p>\n \u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"Want a bespoke baby? Check the beauty, brains, or brawn boxes on the embryo order form. 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\nGermline editing to eradicate monogenetic hereditary diseases.
\nEmbryo screening for IVF parents using PRS to deselect embryos with a genetic signature that may increase disease risks (considered socially acceptable)
\nEmbryo screening for IVF parents using PRS to select genetic signatures likely to produce favored traits (considered socially unacceptable), raising the specter of what I call \u201csoft-eugenics.\u201d
\nSomatic screening based on PRS for susceptibilities to diseases and the effects of certain drugs.
\nGenetic germline editing of embryos<\/p>\n