Repronews #60: Study finds polygenic editing could help prevent major diseases
Swiss experts divided on gene editing; first child born with new IVM technique; Singaporeans more open to genetic enhancement; ethics of gene editing in humans vs. animals
Welcome to the latest issue of Repronews! I hope the new year as treated you well. According to Nature, “We need to talk about human genome editing.” The links in this issue are certainly proof that people are talking more and more about this controversial emerging capability.
Highlights from this week’s edition:
Repro/genetics
Peter Visscher and colleagues find heritable polygenic editing could significantly reduce risk of heart disease, Alzheimer’s, and diabetes
Swiss experts divided on heritable gene editing, some fearing restrictions would lead to medical tourism to other countries
Jaime Roura-Monllor and colleagues argue more data is needed before offering polygenic embryo testing
Start-up Gameto has enabled the birth of a first child using novel in vitro maturation (IVM) technique
Study finds Singaporeans are more open to genetic enhancement for educational achievement than Americans
Further Learning
Genetic enhancement of animals is routine for research, food, and health, but scientists and policymakers are wary in humans
Repro/genetics
“Heritable polygenic editing: the next frontier in genomic medicine?” (Nature)
Peter Visscher, Julian Savulescu, and colleagues write on the prospect of heritable polygenic editing—the modification of multiple genes in human embryos—to reduce risk of heart disease, Alzheimer’s depression, diabetes, and schizophrenia.
The study estimates that polygenic editing can achieve “orders of magnitude” of greater reduction of risk than is possible with polygenic embryo selection.
The authors estimate that polygenic editing should become technically feasible within a generation (30 years).
The paper also considers the ethical implications of polygenic editing for health equality and genetic diversity.
In an editorial commenting on the piece, Nature writes: “Although it will be some decades before human-gene-editing science and technologies can be applied with precision and at scale, they are on their way; this is not a hypothetical issue. The intervening time should be used wisely. Societies need to be ready, understand the upsides and the dangers, and know what to do when that time comes.”
Experts’ perspectives on human gene editing in Switzerland (Journal of Community Genetics)
This study conducted exploratory interviews with 14 experts (scientists, clinicians, social scientists, lawyers) in Switzerland to assess their views towards human gene editing and how they expect the Swiss public to view such editing.
The study found general acceptance of Somatic Gene Editing (SGE), but opinions towards Germline Gene Editing (GGE) were more divided.
Participants emphasized patient autonomy and informed decision-making in pursuing gene editing treatments, with regulation being needed as with any other new therapy.
Some experts expressed concern that restrictive regulations would lead to healthcare outsourcing and medical tourism to other nearby countries, as it has in the past with other restricted technologies.
The analysis explored the unique Swiss context that is shaped by cultural diversity, conservative attitudes towards new medical technologies, and a democratic system that engages the public in policy and law making.
The authors also highlight differences found in expert opinion in other countries.
“Promises and pitfalls of preimplantation genetic testing for polygenic disorder” (F&S Reviews)
Jaime Roura-Monllor and colleagues provide a narrative review of the opportunities and risks of preimplantation genetic testing for polygenic disorders (PGT-P), which has been commercially available since 2019.
If current predictions are accurate, PGT-P can enable absolute risk reductions from about 0.02% to 10.1% for different diseases.
Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention. However, clinicians and professional organizations have many reservations.
Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients’ unrealistic expectations regarding “healthiest disease-free” embryos.
The authors argue that additional clinical validation data are needed prior to offering PGT-P to patients.
They also argue that systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable prior to the ethical implementation of PGT-P.
“Egg maturation supported by stem cells results in first live birth” (PET)
The first live human birth using a novel technology using induced pluripotent stem cells (iPSCs) to support egg maturation outside the body has been reported.
During in vitro maturation (IVM), immature eggs are removed from a woman’s ovaries and cultured in the lab until mature enough to be fertilized and implanted.
IVM is less invasive than conventional IVF because it requires less hormonal stimulation and follow-up treatment.
This technique is not new but so far it has been less efficient, with lower pregnancy and implantation rates than IVF.
New York-based biotech start-up Gameto has developed a novel technique, Fertilo, to overcome the main limitations of IVM.
“We are delighted to celebrate the world’s first live birth conceived using Fertilo,” said Dr. Dina Radenkovic, CEO and co-founder of Gameto. “This milestone marks a turning point in reproductive health and highlights the first application of iPSC technology in IVF and the immense potential of our technology.”
Previous IVM methods mainly rely on supplementing cell culture media with growth factors, small molecules, and hormones known to influence egg maturation. However, this may result in poorer quality and reduced embryo formation rates.
The Fertilo technique supports egg maturation in vitro by supplementing the traditional culture media with human stem cell-derived ovarian support cells (OSC), thus mimicking egg development in vivo.
“Fertilo is a major advancement for women who cannot tolerate or do not want to undergo the burden of the traditional IVF protocol, bringing hope and new possibilities to a broader patient population,” said Dr. Luis Guzmán, who oversaw the Fertilo-enabled IVF cycle that led to the first live birth.
Gameto has secured regulatory clearance for Fertilo in Australia, Japan, Argentina, Paraguay, Mexico, and Peru and is preparing for Phase 3
clinical trials in the USA.
Study finds Singaporeans more open to genetic enhancement for top educational performance (Precise)
At the 2024 PRECISE-IHCC Conference of of Precision Health Research Singapore (PRECISE) and the International Health Cohorts Consortium (IHCC), Professor Julian Savulescu presented results of a study finding that Singaporeans more willing than Americans to use embryo selection and gene editing services if it could improve their child’s chance of attending a top college.
Savulescu also outlined ethical issues such as discrimination, social injustice when costs are prohibitive, and the ethical obligation for parents to want the best life for their child. He invited the audience to deliberate on what would be a good model to regulate gene-based technologies without impeding scientific innovation, and whether these technologies should be made available only for disease traits or also for behavioral ones, pointing out the possible impact disruptive behavioral traits, such as antisocial personality, have on society.
By integrating genetics, lifestyle and environmental factors, prevision medicine can provide targeted treatment for patients and has the potential to improve population health through disease prevention and early intervention.
There are concerns however that precision medicine is biased by largely Western genetic samples not representative of the global population. “There is a global sense of urgency in ensuring that our genomic databases accurately represent different populations and their subgroups,” said Professor Angela Ballantyne. “Yet, the reality is that we are still seeing marginalized and discriminated low-trust groups participating at lower rates.”
Through trust-building efforts, the share of Singaporeans being willing to share their genetic data as part of the country’s National Precision Medicine (NPM) program increased from 64% in 2020 to 83% in 2023.
Nota bene: The Conference took place in August, whereas this event wrap-up was published last month.
More on repro/genetics:
Casey Haining, Julian Savulescu, et al, “Polygenic risk scores and embryonic screening: considerations for regulation” (Journal of Medical Ethics)
Lílian Santos, Governance of Human Gene Editing and Transhumanism (Springer)
“Advancements and challenges in preimplantation genetic testing for aneuploidies” (Genes)
“Embryo selection, AI and reproductive choice” (AI and Ethics)
“Preimplantation genetic testing for hereditary angioedema as a potential dominant cost-effective intervention” (JACIIP)
“Haplotyping-based preimplantation genetic testing for inherited cardiovascular disease: a multidisciplinary approach” (Molecular Genetics and Genomics)
Podcast: “Why is postmortem sperm retrieval soaring in Israel?” (Irish Times)
Policies & Trends
Lyman Stone, “Are we headed towards ‘idiocracy’? A look at ‘dysgenic fertility’ (IfS)
Genetic Studies
“Genetic resonance: dissecting the heritability and genetic correlations of human hearing acuity” (G3)
“Functional genomics of height heritability” (Nature Genetics)
Further Learning
“Perspectives of genome scientists and policymakers on animal and human enhancement” (AJOB Empirical Bioethics)
Animals are regularly enhanced genomically with CRISPR and other gene editing tools as scientists aim at better models for biomedical research, enhanced agricultural animals, or animals otherwise better suited for other goals, such as organ xenotransplantation to humans.
This study investigated how genome editors and policymakers perceived ethical or policy benefits and drawbacks for animal enhancement and how perceived benefits and drawbacks are alike, or differ from, those for human genome editing.
Of the 92 participants interviewed, 81 were genome editing scientists and 33 were policymakers (22 interviewees being both scientists and policymakers).
Differences in ethical perspectives between human and animal editing were identified in the areas of experiential welfare, germline edits, environmental sustainability, and justice.
Overall, respondents considered animal enhancement to be free of the ethical complexities of human enhancement. These views may be related to perceptions of animals’ lesser moral status and because germline editing in animals is already common practice.
More on human nature, evolution, and biotech:
Evolution
“Top 10 discoveries about ancient people from DNA in 2024” (John Hawks)
Human nature
“How your workplace’s sex ratio affects your chances of divorce” (Steve Stewart-Williams)
“Most stand-alone personality traits
Disclaimer: We cannot fact-check the linked-to stories and studies, nor do the views expressed necessarily reflect our own.