Repronews #24: Significant patient interest in polygenic embryo selection
Genome editing in South Africa; OCD 50% heritable; Beth Shapiro on biodiversity & health benefits of “de-extinction”; child brain differences by socioeconomic background; genetics of piglet survival
Welcome to the latest issue of Repronews! Highlights from this week’s edition:
Repro/genetics
Significant patient interest in polygenic embryo screening, while clinicians more skeptical
Researchers suggest principles for heritable genome editing in South Africa
Genetic Studies
First twin study of obsessive-compulsive disorder (OCD) confirms a heritability of 50%, with the rest due to non-shared environment
Further Learning
“De-extinction”: Interview with Beth Shapiro on the effort to resurrect the wooly mammoth and other species, and how this could also benefit humans
Norwegian researchers find brain differences in children of different socioeconomic backgrounds
The genetics of piglet survival
Repro/genetics
“Patient interest in and clinician reservations on polygenic embryo screening: a qualitative study of stakeholder perspectives” (JARG)
The study explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and IVF patients regarding polygenic embryo screening, a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future.
As revealed through semi-structured interviews, clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Both groups envisioned multiple potential benefits or uses of polygenic embryo screening and raised multiple potential, interrelated concerns.
Clinicians expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer polygenic embryo screening to patients or were willing to do so only under certain circumstances, while many patients expressed interest.
The authors conclude a gap exists between clinician and patient attitudes toward polygenic embryo screening. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits.
Review of the Third International Summit on Human Genome Editing and developments in South Africa (Journal of Bioethical Inquiry)
This article reviews the Third International Summit on Human Genome Editing which was held in London in March 2023 and comments on the latest developments in the regulation of heritable human genome editing.
The previous Summit, held in 2018 in Hong Kong, featured the presentation by Chinese scientist He Jenkui of his work leading to the birth of two gene-edited babies. He was subsequently imprisoned but has since been released and has resumed work (reportedly on somatic, no longer germline, gene editing).
Human genome editing presents the possibility of curing serious illness, as well as removing serious illness from an individual’s family tree. However, ethical controversies make it difficult for the scientific community to develop its research into marketable therapeutics addressing the population’s health needs.
Germline gene editing leads to heritable changes in an individual’s genome. Beyond safety and efficacy, this type of gene editing is fraught with legal and ethical issues. There has been significant discussion of heritable human gene editing, e.g. by the U.S. National Academy of Medicine and in academia.
The Third International Summit on Human Genome Editing, which was convened by the U.K. Royal Society, U.K. Academy of Medical Sciences, U.S. National Academies of Sciences and Medicine, and the World Academy of Sciences, aimed to discuss progress, promise, and challenges in research, regulation, and equitable development of such technologies and therapies.
The Summit emphasized that remarkable developments had been made in the field of somatic (non-heritable) human genome editing. However the high cost of somatic therapies was highlighted as unsustainable and participants called for a global commitment to ensuring equitable access to treatment.
Many countries lack explicit laws on the legality of human genome editing. There were no laws in China when He did his research and as a result he was charged with practicing medicine without the required licence, which was the only charge which the Chinese authorities could lawfully bring against him. The children themselves were gene edited at the embryonic stage, at which point they did not possess any legal recognition as persons capable of possessing legal rights.
The most significant general rule on embryos is the “14-day rule” which prohibits research on a human embryo once it reaches the 14th day of development. This rule has been enshrined in the law in the legal systems of many countries, including South Africa.
While South-African law does explicitly discuss heritable human genome editing, the bioethicists have derived certain principles from existing statutes:
Principle I: Given its potential to improve the lives of the people of South Africa, heritable human genome editing should be regulated, not banned.
Principle II: Heritable human genome editing’s clinical applications should be made accessible to the public only if they are proven to be safe and effective.
Principle III: Non-therapeutic heritable human genome editing should be regulated in the same way as heritable human genome editing, with the rider that it should not in any legally relevant sense cause harm.
Principle IV: The decision whether to use heritable human genome editing in a prospective child should, subject to principles I, II, and III, be left to the prospective parents.
Principle V: Concerns about exacerbating social inequalities should be addressed by measures to increase access.
Regulatory guidelines embodying these principles have been submitted for possible inclusion in the revised National Health Research Ethics Guidelines which set out the norms and standards for research in South Africa.
The authors argue that proper regulation of genome editing can reduce the risk of unethical research and a rights-based approach to science can ensure that scientific progress may continue within legal parameters. They hope that the guidelines suggests will enable South Africa to move closer to a clinical pathway to heritable human genome editing.
More on repro/genetics:
“‘Racist undertones’: Pro-eugenics arguments submitted in Supreme Court abortion pill case” (LiveAction)
Genetic Studies
“Heritability of clinically diagnosed obsessive-compulsive disorder among twins” (JAMA Psychiatry)
Obsessive-compulsive disorder (OCD) is thought to be moderately heritable (around 40%-50%). Evidence comes from extended family pedigrees of individuals with clinically diagnosed OCD and, indirectly, from nonclinical twin studies of research volunteers self-reporting current obsessive-compulsive symptoms.
This is the first study, to our knowledge, to estimate the heritability of clinically diagnosed OCD from a sample of twins.
The study linked the Swedish Twin Registry, which includes 143,853 twins born between 1886 and 2008, with information on diagnoses from the National Patient Register (NPR), registered between 1973 and 2020.
Results: Genetic factors accounted for 50% of OCD variance, with nonshared environmental factors (including measurement error) accounting for the rest.
More on genetic studies:
“Does conservative religiousness promote selection for intelligence? An analysis of the Vietnam experience study” (Clear Language, Clear Mind)
Further Learning
“What ‘de-extinction’ of woolly mammoths can teach us: a Q&A with evolutionary biologist Beth Shapiro” (STAT)
Humans have long tinkered with the evolutionary trajectories of other species. Thousands of years ago we tamed wolves into dogs and transformed a wild grass into the agricultural wonder wheat. Within the past few centuries, we exterminated the Tasmanian tiger and doomed the dodo bird to oblivion.
Now, biotechnology may enable humans to resurrect species through “de-extinction.”
Beth Shapiro, an evolutionary biologist, is interviewed on the prospects of de-extinction. She has collected fossilized bison bones from Arctic permafrost, co-led the Paleogenomics Lab at the University of California, Santa Cruz, was a Howard Hughes Medical Institute investigator and a MacArthur Fellow, and is the author of the books How to Clone a Mammoth: The Science of De-Extinction and Life as We Made It: How 50,000 Years of Human Innovation Refined—and Redefined—Nature. In 2022 she announced that her team sequenced the genome of the dodo.
Recently, Shapiro was named chief scientific officer of Colossal Biosciences, a biotech company aims to bring back such fallen fauna as the woolly mammoth, dodo bird and Tasmanian tiger (also known as the thylacine).
CRISPR gene editing may be used to make an elephant cell’s DNA more mammoth-like, by comparison with sequenced mammoth genomes.
All the core technologies to create a mammoth are available, but these need to be successfully tweaked for application.
Extinction and speciation are important processes in evolution. The rate of extinction today is somewhere on the order of 1,000 to 10,000 times faster than the average across the fossil record, in large part because of human activity. In many cases, the pace of change is too fast for evolution by natural selection to keep up. De-extinction can help sustain threatened species.
The technologies to resurrect the mammoth, dodo, or thylacine will also have immediate application outside of those specific applications. Tools are needed for multiplex genome editing, for introducing large fragments of DNA, all of which will have application to using CRISPR gene editing technologies in humans and other species.
Shapiro argues that by better understanding genomes from across the tree of life, and more complete understanding of how DNA translates into the way something looks or acts, we will also be able to better understand the links between genotypes and diseases.
Such technologies may be used to resurrect other recently-extinct species, such as the Xerces blue butterfly (which human activity drove to extinction in the 1940s in the San Francisco Bay).
Shapiro questions whether Neanderthal de-extinction is needed, assuming it were ethical. “we have somewhere between 1% and 4% Neanderthal in our DNA. Less well known is that it’s not the same 1% to 4%. If you go around the planet and you collect all the bits of Neanderthal DNA that survive in people who are alive today, we can put together around 93% of the Neanderthal genome. So I’ll just end this by asking you if 93% of their genome exists today, are they really extinct?”
“Researchers find differences in the brains of children from different backgrounds” (Science Norway)
Many statistics show a positive impact of high parental income and education levels on children’s development. On average, these children have better grades in school, develop better language skills, and enjoy better physical and mental health compared to children with fewer resources.
Norwegian researchers examined MRI images of the brains of around 10,000 American children aged 9 to 11 years. In general, the brains of children with high and low socioeconomic status are very similar, therefore a very large dataset was needed to identify any effect.
The researchers found clear differences in the cerebral cortices of children who come from different socioeconomic backgrounds. Children whose parents have spent many years in school and have a high annual income have a larger surface area of the cerebral cortex.
The researchers also found that the frontal parts of the cerebral cortex are larger in children from a high socioeconomic background. These areas are crucial for regulating thoughts and emotions, and are important for good mental health.
Children from families with lower socioeconomic status also showed more symptoms of mental health problems.
Children with parents of low income and lower education appear to have more myelin in the cerebral cortex, a fatty substance that helps the nerves to efficiently send signals to each other, which is very important for brain function. The researcher are uncertain why this is the case, but it may be because increased stress has increased brain maturation in this area.
Fartein Ask Torvik, a senior researcher at the Norwegian Institute of Public Health (NIPH), said: “The social difference in mental health problems is very strong, also in Norway. Those with lower education and income have a much higher risk of mental health problems.”
In a 2021 study, Torvik found that children of parents with the very lowest income have a three to four times as high a risk of being diagnosed with mental health problems as children of the wealthiest families.
“We know that mental health problems are related to brain structure. Everything we think and feel happens in the brain,” Torvik says.
The recent Norwegian study used data from the U.S. Adolescent Brain Cognitive Development study (ABCD study). No comparable database exists in Norway.
Research into brain structure as a cause of inequalities is “sensitive” in Norway and some believe this means the inequalities cannot be addressed.
A recent Luxembourgish study has similarly found that health behaviors different significantly among teenagers of different socioeconomic classes.
“The genetics of piglet survival” (National Hog Farmer)
Piglet survival can be defined as the number of piglets weaned divided by the total number of piglets born. Piglets that do not survive until weaning are generally stillborn or die during lactation.
In the U.S., piglet survival has been reported to range from 77 to 79% in the commercial industry. Industry improvements in piglet survival would enhance animal well-being and farm profitability.
Genetic selection for litter size at birth may impair both piglet survival and piglet quality. Genetic correlation estimates suggest selection for increased total number of piglets born would reduce piglet survival, decrease average piglet birth weight, diminish average piglet weaning weight, and lower the number of available functional teats per piglet.
There are multiple pathways to genetically enhance piglet survival. Genetic selection can be used to select directly on piglet survival or indirectly on a component trait of piglet survival such as piglet vitality, piglet birth weight, colostrum characteristics, milk yield, or functional teat number. The appropriate component trait for selection may depend on population weaknesses and present genetic variation.
More on human nature, evolution, and biotech:
“Intelligence and kindness are the most valued traits in romantic partners, study finds” (PsyPost)
Head of U.S. biotech association: “For national security, the U.S. must maintain its biotech dominancy” (STAT)
“Reactions to research on sex differences” (Nature-Nurture-Nietzsche Newsletter)
Alex Byrne and Carole K. Hoover, “The problem with saying ‘sex assigned at birth’” (New York Times)
AI predicts sex based on human brain imaging with 99.7% accuracy (NeuroImage)
“Innovation … the most effective foreign aid programme ever discovered” (Quillette)
Disclaimer: The Genetic Choice Project cannot fact-check the linked-to stories and studies, nor do the views expressed necessarily reflect our own.
The piglet stuff is so interesting. As so often with herd heritability I have idea how they control for non-genetic pre birth environment eg endemic disease prevalences wrt stillbirth and other characteristics at birth