Micah Reed HysongThe year is 2060. As part of your family planning, you see a geneticist. They ask you what traits you would like your baby to have. What do you prioritize? Intelligence? Height? Eye color? Extroversion? Low risk of cardiovascular disease? A “healthy” body mass index (BMI)?
The first genetically screened embryo was born in 1990. Today, preimplantation genetic testing is a routine part of in vitro fertilization (IVF). It is typically used to identify serious, but rare, genetic disorders caused by mutations in a single gene, such as cystic fibrosis or muscular dystrophy.
But what about complex traits like intelligence, height, personality, or risk for common diseases like diabetes and heart disease? These aren’t controlled by a single gene. Instead, they are influenced by hundreds or even thousands of genes—along with environment, lifestyle, and chance. That complexity makes predicting such traits much more difficult. So, how could a geneticist possibly estimate an embryo’s risk for something like heart disease or intelligence? And, perhaps more importantly, should they?
Over the past two decades, the cost of sequencing a human genome has dropped from nearly $3 billion to around $1,000. This rapid decline in cost has fueled an explosion in genomic research. One of the most transformative tools to emerge is Genome-Wide Association Studies (GWAS). GWAS identify regions of the genome associated with a particular polygenic (multiple genes) trait. In GWAS, researchers compare two groups: individuals with a disease (cases) and those without (controls). They sequence the genomes of both groups and use statistical and computational methods to identify genetic regions that differ between them.
Once scientists identify regions of the genome that appear to influence a particular trait—and estimate how strongly each one contributes—they can combine that information into a single number called a polygenic risk score (PRS). This score can then be used to estimate an individual’s genetic risk for any number of diseases.
While PRS was designed for risk management in adult populations, certain companies have already begun offering polygenic risk prediction for embryo selection. What once sounded like distant science fiction, has already happened: in 2021, Aurea was selected against other embryos based on their lowest risk for common complex diseases, becoming the first baby born following PRS-based embryo screening.
At face value, screening to reduce disease risk probably sounds like an easy win for both the individual and society as a whole by reducing disease burden. But it’s a bit more complicated than that. For starters, some of the scientists who developed the underlying genetic data explicitly prohibited its use for embryo selection in their data-use agreements. And while some companies may be eager to capitalize on this emerging technology, serious concerns remain. Experts have raised issues around scientific validity, lack of regulatory oversight, difficulties communicating risk for informed decision making, the potential for unforeseen harm, inequity in access and outcomes, and broader societal consequences.
Scientific validity
While PRS development has been a very active area of research over the past twenty years, there are still considerable barriers to their usage. For starters, a recent evaluation of current PRS found that classification of individuals as high risk for a specific disease was highly inconsistent across PRS developed from different studies. Additionally, there is considerable selection bias in who gets included in the GWAS, which affects how well the scores work in different groups. For example, most GWAS were conducted using participants of European ancestry, and therefore the scores are, on average, only 20% as accurate in populations with genetic similarity to African reference genomes. PRS accuracy has also been shown to vary by age, sex, smoking history, and even income.
While clinical trials are beginning to test how useful PRS might be for managing disease risk in adults, there have been no such trials for embryo selection. There are several reasons why using PRS for embryo selection may be less effective. Within a family, siblings share much of the same genetic background and environment, limiting the potential differences a PRS can capture. Moreover, because future generations will grow up in different environments, the predictive accuracy of today’s PRS is likely to decline over time.
Lack of regulatory oversight
In 1974, after the scientific breakthrough that allowed eukaryotic genes to be inserted into bacteria, a moratorium was called to pause all research using DNA cloning and evaluate potential risks. Subsequently, researchers gathered at the Asilomar Conference to establish safety guidelines for genetic engineering. Just a few years later, in 1978, scientists successfully produced human insulin from genetically modified bacteria. Today, nearly all commercially produced insulin is made using this method.
In 2019, another scientific breakthrough prompted calls for a moratorium, this time on human germline editing. This call was made by bioethicists and many of the scientists who helped develop the technology. They warned about the unknown long-term consequences of altering the human germline (the cells that carry genetic information from one generation to the next), such as unpredictable health effects and the potential misuse of the technology for non-therapeutic purposes, like creating “designer babies.” The temporary halt on gene-edited embryos is designed to allow time for public discussion, further research, and the establishment of clear safety and ethical guidelines.
While embryo selection is less risky than direct gene editing, without proper guidelines, what’s to stop companies from offering selection for non-disease traits—such as intelligence, personality, or even sexual orientation? While some countries, like the United Kingdom and the Netherlands, have limited preimplantation genetic testing to serious medical conditions approved by national regulatory bodies, there are no such regulations in the US. The American College of Medical Genetics and Genomics (ACMG) has recently called for a broad societal discussion about how risk-based embryo selection technology should be used, including which conditions we should be able to test for.
Risk communication and informed decision making
One of the biggest challenges to using PRS in everyday medicine is that even doctors can find the results difficult to interpret, let alone to explain clearly to patients. For starters, a PRS doesn’t tell you whether you will get a disease, it just estimates your level of genetic risk. That risk isn’t fixed and can change depending on your environment, lifestyle, and daily habits.
There are also two main ways in which risk can be communicated: relative risk and absolute risk. While relative risk tells you how likely you are to develop a disease compared to the general population, such as “twice as likely”, absolute risk tells you how likely you are to actually develop the condition. For rarer conditions, you can be twice as likely to develop the condition and still only have an overall risk of 1%. This effectively means that companies can make their risk reductions sound better than they are. This is an area where regulatory oversight could strengthen public trust by ensuring companies responsibly communicate results to patients and provide access to genetic counselors to guide informed decision making.
Potential harms
One of the major potential harms is unnecessary exposure to IVF. While these screens are currently offered to patients already undergoing IVF, there’s a risk that parents could be persuaded to pursue IVF just to access embryo screening even though IVF itself carries risks.
Another consideration is information overload and decision fatigue. For example, if these screens include results for 10-20 conditions, how will the parents choose between embryos with lower risk for some diseases but higher risk for others?
Importantly, we still don’t understand the psychological impact of knowing a baby’s genetic risk for multiple adult-onset conditions. A common approach embraced by the medical genetics community has been “just-in-time” screening, in which conditions are only screened for at the time at which they are relevant to a person’s health or life stage. Even if parents select the “healthiest embryo”, learning that it still carries, for example, a two-fold risk for a rare condition could cause anxiety and prompt overly burdensome lifestyle changes. Moreover, the psychological effects of knowing that one’s own or one’s child’s genome has been “optimized” are unpredictable and could influence self-image, expectations, and mental health in unforeseen ways.
Inequity: access and outcomes
Equity is a major concern when it comes to PRS-based embryo screening. For starters, as mentioned above, PRS are less accurate in individuals with genetic similarity to non-European populations, as well as in populations whose environments differ from those represented in the original research. Because the scores work best for people of European ancestry, and as the scores for some traits—like BMI— are partly linked to ancestry itself, ranking embryos by PRS could unintentionally select for babies with lower proportions of certain ancestry groups. Access is another key issue. Wealthier individuals are more likely to afford this screening, and existing racial socioeconomic disparities could give white and higher-income families greater opportunities to reduce disease risk. Taken together, these factors could exacerbate existing health inequities.
Societal consequences
There are also broader societal considerations at play, including genetic essentialism and eugenics. Genetic essentialism is the belief that all traits are determined solely by genes. In the context of PRS-based embryo screening, this could lead individuals to think that the future of their health is written in stone. Such a mindset can undermine people’s sense of agency and self-efficacy, making them feel powerless to influence their own abilities, health, or future.
With genetics’ fraught history, genetics research should include thoughtful consideration of eugenics. The National Human Genome Research Institute defines eugenics as “an immoral and pseudoscientific theory that claims it is possible to perfect people and groups through genetics and the scientific laws of inheritance.” Eugenicists inappropriately used early genetic concepts to justify ideas of “racial improvement.” Decisions about which groups were deemed “unfit” were entirely biased, reflecting the prejudices of those in power, and eugenics was used to target ethnic and religious minorities, people with disabilities, the poor, and LGBTQ individuals.
This historical context underscores why it is critical for both science and society to engage in broad discussions about which traits should be included in screening. Currently, there is nothing stopping companies from offering parents the ability to select against babies that are more likely to be gay or trans or have lighter skin color. Let’s consider a “less controversial” example: attention-deficit/hyperactivity disorder (ADHD). The term “deficit” carries negative connotations, already indicating how society tends to view this trait. And while ADHD undoubtedly presents real and significant challenges in modern society that often require accommodation, the same traits that can be challenging in one context may be highly advantageous in another. For example, recent research indicates that ADHD may have played an important role in our evolution by helping humans explore new environments, respond quickly to threats, and adapt to changing environments. In modern contexts, these same traits can foster creativity, problem-solving, entrepreneurial thinking, energy, and hyperfocus. Moreover, ADHD is advantageous for certain professions including emergency room doctors, firefighters, entrepreneurs, teachers, graphic designers, and software developers.
Another example is BMI. In today’s environment, where calorie-dense and nutrient-poor foods are widely available, a slower metabolism can contribute to health problems. However, in times of food scarcity, lower metabolism can be advantageous. For instance, descendants of famines have been found to have higher BMIs. What if we were to select for lower BMIs now, only to face a global food crisis in the future? Removing such traits could unintentionally reduce the resilience and adaptability of future generations.
Where do we go from here?
Given the lack of decisive clinical validity and the numerous potential harms, including equity concerns, the benefits of PRS-based embryo screening do not clearly outweigh the risks. Premature adoption could undermine public trust in genetics and reproductive medicine, especially, if marketed without solid evidence or proper counseling. These considerations underscore the need for careful ethical oversight, broad public discussion, and thoughtful deliberation about which traits, if any, should be screened.
Peer edited by: Rachel Sharp & Snehasudha Sahoo