Louise Brown was the first IVF-born baby in 1978. This sparked a media frenzy. A little girl called Aurea, who was born via IVF in May 2020, went almost unnoticed. She is a landmark first in assisted reproduction. Her embryo was chosen from other embryos based on polygenic screening prior to implantation. This allowed her to maximise her health prospects.
This new method of genetic screening is controversial for both ethical and scientific reasons. The nonprofit California-based organisation the Center for Genetics and Society (CGS) has called its use here a considerable reach by the assisted-reproduction industry in the direction of techno-eugenics.
Genomic Prediction, a New Jersey-based company, provided the polygenic screening for Aurea. Orchid Biosciences, a California-based gene-sequencing firm, now offers an embryo-screening package which assesses the risk of common diseases like diabetes and heart disease.
Preimplantation genetic diagnosis (or PGD) is a method of screening IVF embryos for potential health issues. It is not a new concept. The Human Fertilization & Embryology Authority (HFEA) in the UK allows it to be done. It looks for gene variants that are associated with approximately 500 diseases such as cystic fibrosis or Tay-Sachs.
Louise Brown was the first to be conceived through in vitro fertilization in 1980. Although once controversial, IVF and PRSs may soon be considered just another aspect to parenthood. Photograph by Jane Bown/The Observer
Most of the diseases that are conventionally screen with PGD are caused by mutations in one gene. These diseases can be very serious, but they are rare. Polygenic health issues, such as type 2 diabetes and heart disease, are more common than they seem. They are caused by complex interactions between many genes, sometimes many. Even though certain gene variants have been shown to increase the risk of developing breast cancer, like the BRCA1/2 variants, there is no guarantee that they will be affected.
This is how genes work. They are interconnected, complex and poorly understood. The gene variants that an individual carries doesn't guarantee the traits they will develop. Environment factors like upbringing, diet, and unpredictable aspects of embryo development all play a part. These were products of (genetic), nature, nurture, chance, and an interplay among all three.
Despite the fact that genome sequencing costs have dropped and genomic profiling companies like Orchid and 23AndMe are more popular than ever, we now have genetic data for thousands of people. This has made it possible to understand how genes and traits relate. A genome-wide association study (GWAS), which can be used to search through large databanks for statistical associations between gene variants and any trait, is a technique that allows us to analyze these databanks. These studies often reveal that significant differences in individuals can be linked with different variants (or alleles) of multiple genes. Although each gene may have a small effect that is not obvious without lots of data, it can have a significant impact on the outcome.
The genetic profile of a person can be used to predict, for example, their likelihood of developing heart disease later in life. A polygenic risk score (PRS), can be assigned to them for this condition. Aureas embryo was selected because it had low PRSs for diabetes, heart disease and cancer. PRSs can also be used to predict other factors, such as the child's intelligence and educational attainment.
Orchid Biosciences preconception screen kit can help couples who are considering having a baby to get an idea of their offspring's potential predispositions to certain diseases and conditions. Photograph: guides.orchidhealth.com
However, such predictions can only be made because it is impossible to predict how genes will influence a trait. A PRS is not deterministic or unpredictable. A person with a high PRS may not develop skin cancer, but someone with a low score might. A person with a low IQ may be brilliant because of their genetic profile.
It is also one reason that the legality of using PRSs for embryo screening in the US is controversial. It is not possible to place much faith in the prediction of polygenic traits, unlike single-gene disease, which can almost guarantee a positive outcome for health. We make decisions based on probabilities every day. Although we cannot be certain that a school is the best, it may be that it will increase the chance of a positive outcome. It makes sense to choose the first embryo if one embryo has low PRSs and another has high. Rafal Smigrodzki from North Carolina, Aureas father, argued that a parent's duty is to ensure their child does not get sick. He says polygenic testing is another way to do that.
BRCA1 and 2 are already being used in embryo screening. However, it is not certain that breast cancer will be a result of these tests. PRS screening advocates claim that it improves risk assessment by allowing more genetic factors to be considered. According to Genomic Predictions founder Stephen Hsu (a professor of Physics at Michigan State University), most families without a history or breast cancer would not benefit from polygenic screening. There are enormous public health benefits. Sarah Munday and Julian Savulescu, both ethics philosophers, have advocated for polygenic screening.
What could stop a company from offering to screen for intelligence or height, which is not a disease trait?
The concept of PRSs has scientific support and it is a method of genetic assessment with a future in medicine, according to Vardit Ravitsky, a bioethicist at the University of Montreal. Many experts and regulators feel there is no reason to use them in an attempt to improve the health of IVF babies. Ravitsky says it is not ready for primetime. It is still in the research phase. It is still in research.
Hank Greely, a bioethicist at Stanford University, asks whether PRS can reduce the lifetime risk of type 2 Diabetes in your children from 30% to 27%. He says that this is very different from single-gene diseases being screened and avoided.
Once such screening methods have been approved, what will stop them? American couples are already able to screen their embryos for gender, skin tone, and eye color. A company could offer to screen for intelligence or height, as well as other non-disease traits. Katie Hasson, an associate director at the CGS, said that there is no reason to believe polygenic embryo screening will be stopped for conditions such as heart disease or diabetes. Already, screening for schizophrenia and other mental disorders is available. These are eugenic attempts to eradicate feeble-mindedness. This is not about deciding who should have children based on their good and bad genes.
Genomic Prediction used to offer the ability to screen for genetic variants that could cause intellectual disability. However, Hsu emphasizes that the company now only provides the service for serious diseases. He says that we decided that genetic traits such as height and cognitive ability were too controversial and would hinder our ability to help families reduce their disease risk.
Professor Stephen Hsu (right), with Boris Johnsons former advisor Dominic Cummings, on the steps at No 10 Downing Street. Stephen Hsu/Twitter
It is not clear whether screening for non-disease characteristics would work. Greely says that the PRS results for parents who are most interested in intelligence, sports, and musical ability will be very weak to nonexistent. In 2019, a study found that polygenic screening embryos for height and intelligence would make little difference and you might not end up with the best one.
What should be allowed? Hsu said: We hope society, possibly on a nation by nation basis, will come to a consensus about which non-disease genes are acceptable for embryo screening. Hsu's comments about whether there are differences in IQ among racial groups have also been controversial. However, he insists that he is not agnostic. In 2020, he was forced to resign as the university's senior vice president of research and innovation after there was outrage over his comments.
Hsu was also suggested by Dominic Cummings as a scientist to lead the UK's Advanced Research and Invention Agency. Cummings wrote in 2014 about how the NHS should pay for the cost of selecting embryos to test for IQ. In 2019, he was pictured outside the 10 Downing Street office with Hsu.
Hsu expressed hope that progressive governments would make this procedure available to everyone in order to avoid any Gattaca-style genetic stratification. However, Hasson is concerned that this would not solve the inequality problems that these techniques can cause. Even though PRSs for intelligence, as an example, may not have any predictive value, Hasson believes that the belief in genomic prediction can lead to extreme inequalities by reinforcing the idea of genetic determinism. If families invest time, money and hope in screening and selection, they will produce children that are considered genetically superior. Parents, educators, and care-givers will treat those children as superior.
Polygenic screening could be difficult to resist in hyper-competitive societies due to social pressure
If polygenic screening is offered in highly competitive societies, social pressure can make it difficult to resist. Ravitsky says that once you have IVF you will feel pressured to take any additional test or service offered by the clinic. Consider what happens to a woman who declines amniocentesis or prenatal screening. She says that many women feel judged by their peers and by healthcare providers.
Although PRSs are not useful in predicting the chances of a child's future, there is a market for them. Companies can make exploitative and unrealistic promises in countries like the USA, where assisted conception is not well regulated. Couples may choose to have an IVF-conceived child to take advantage of these opportunities. Although it is a difficult process with risks, women may feel compelled or even obligated to use it. Ravitsky believes that this would be considered malpractice.
But the genie is out the bottle. Hsu states that polygenic screening is likely to become a common practice in the near future. It will be difficult to believe that this technology has been controversial, as it was in the case with IVF. However, Peter Thompson, the HFEA chief executive, says that the UK currently prohibits the practice. He said that even if there was more scientific consensus on the value of PRSss, it is important to distinguish between embryo selection for avoidance of serious harm and enhancement like greater intelligence. He says that the latter would be a major shift in public policy.
Hasson says that we urgently need to have public and policy discussions about polygenic embryo screening. Liberal democracies face a fundamental problem: finding the right balance between autonomy, social responsibility and both is difficult. Greely says that we allow people to spend their money and make decisions that have a profound impact on their children based on far more bogus information then PRS.
Ravitsky says that we as a society are far from knowing how to use these technologies. However, she also said that we are already in the grey zone.
