We don’t get to choose our genes. But parents are now able to select their children’s genes in ways never possible before. The first baby born as a result of being singled out from a number of possible embryos with different probabilities of developing certain diseases is now a reality. The ethical concerns are many - eugenics have a nasty past and there are fears that already worsening inequality might become cemented in the ability of some parents to choose healthier, brighter children. But this technology will be what we make of it, and given its potential for good, we have a moral obligation to pursue it, argues Julian Savulescu.
Aurea Smigrodzki is still unaware of her significance in history. She is the first baby born on the basis of a polygenic score assigned to her future health, having been selected from 33 candidate embryos. In Aurea’s case, her parents were worried in particular about her risk of future breast cancer and heart disease: both had affected family members.
Testing for single genes, such as BRCA in the case of breast cancer, is already embedded in standard practice. In some countries up to one in ten babies is born via artificial reproduction technologies, including IVF. Up to 40 % of IVF babies undergo some pre-implantation testing for single-gene disorders. But many diseases are polygenic: they are influenced by multiple genes and the interaction between them. A polygenic score is a formula that assigns a risk level according to the probability of disease occurring with a set of genes.
So why has Aurea’s birth stirred up so much controversy? There are several reasons. Some are scientific: the scores show a correlation, causation is not known. But the main concerns are ethical. Reducing the risk of heart disease, or cancer a little could have no real impact on an individual: perhaps they could avoid that risk anyway through managing their environment, or perhaps it would never have eventuated. But it could impact public health: over thousands of individuals it will lead to reduced burden of disease. This brings us to concerns about eugenics: state-sponsored selection of embryos for traits considered to be better. Moreover, disease risk is only one possible use of polygenic scores. Traits such as height, intelligence, and even likelihood of engaging in a same-sex sexual experience have polygenic correlations that have been identified (as well as of course environmental factors). Indeed, it is the potential of this technology to raise ethical concerns that is most troubling. Despite those concerns, we have a moral duty to pursue polygenic test scoring if it means ensuring a healthier life for future humans.
How polygenic risk scores work
The BRCA mutations causes about 5% of breast cancer. But 95% of breast cancer is influenced by multiple genes. We don’t know the spread of risk scores that Aurea’s parents had to choose from. But studies testing the predictive power of the technology by assessing the polygenic scores of adult siblings found that, where there is a large enough gap between the scores of the pair, “the predictors identify the affected sibling about 70-90% of the time across a variety of disease conditions” (albeit the authors are shareholders of companies in this area). The more siblings to compare, the greater the potential for reduction of risk.
Of course, Aurea’s parents considered multiple risks of disease. To do this, a formula addresses the likelihood of a disease and the impact of the disease to provide an overall score. On the face of it, if we believe we should or could select an embryo for a single-gene disorder, because we hope to save the future child from facing a challenging health condition, a polygenic score (either now, or when the technology improves) provides a richer and more complete picture, to enable parents to make the same choice, but with more information. In this way, Aurea is not so different from her peers, who may have been tested in the uterus, or during IVF to exclude future children with a range of single gene disorders.
It’s important to say that this is not the same as genome editing. The magnitude of the effect of selection is limited by the genes of the couple producing the embryos and the number they produce. The embryo has to come into existence naturally. But genome editing offers the prospect of radically changing the genome at hundreds or thousands of points. Diseases like Alzheimer Disease or schizophrenia could be almost eliminated. The limit would be the extent of heritability of a given trait.
At present, genome editing is too risky; polygenic selection is safe. We should treat polygenic selection as something of a dry run and monitor the birth of every child so selected to better understand its effects, before we embark on the perhaps inevitable path of genomic enhancement.
“Eugenics” literally means “well-born” and refers to the use of genetics to have healthier, longer-lived or more talented children.
The scientific and ethical concerns
As already mentioned, the scored indicate correlation, not causation. They may pick up irrelevant correlations to do with common environments that won’t be relevant when picking amongst siblings. The reference data is Eurocentric, and inaccurate in other populations. Moreover, not many people have 33 embryos to choose from, and a more typical number will mean that there is less likely to be a significant difference between the two or three. Moreover, even where the relative risk reduction between sibling embryos appears large, the absolute reduction can be very small: for example if both were rather unlikely to develop the disease anyway. Finally, there may be trade-offs due to ‘pleiotropy’, multiple effects of the same genes. For example, a recent paper urging that we pay attention to the limits of polygenic scores explains, “if an embryo is selected on the basis of the polygenic score for educational attainment, the risk of bipolar disorder is increased by 16% from an absolute risk of 1.0% to 1.16%”[ii]
On the ethical front, the key objections are as follows.
1. It’s eugenics and that’s what the Nazis did
“Eugenics” literally means “well-born” and refers to the use of genetics to have healthier, longer-lived or more talented children. In the late 19th and 20th centuries, it was used to create voluntary and involuntary programs targeting reductions in intellectual disability, psychiatric disease and poverty (believed at the time to be genetic). It led to sterilisations and, in the hands of the Nazis, mass exterminations in the pursuit of a racist, social Darwinist state ideology.
Today, clinical genetics, including the use of polygenic scores, aims at the well-being of the children born and gives couples information and choice. As long as such programs are properly focussed on the well-being of the child, and parents have voluntary control, they do not represent objectionable eugenics. The paradigm example of modern clinical genetics is Down syndrome screening and this would be an extension of that. A recent court case highlighted persisting concerns about the discriminatory nature of this kind of selection. Once again, the ethics of polygenic scores reflects on current accepted practices.
2. Gattaca: it will lead to inequality and a two-tiered society
One dominant concern is that this technology will only be available to some - the rich, those of European descent, or some other already privileged group. It will increase existing social inequality, writing it into the genes of the next generation. One example appears in the ‘90s film Gattaca.
It is certainly true that the use of polygenic selection could increase inequality if they are only selectively available. However, there is already great natural genetic inequality – not all genes are equal. Some people are born with great natural talents, health, longevity – others born with significant restrictions, disease and short lives. Some of that is due to single gene or chromosomal abnormalities. Some is due to environmental factors, social construction, or personal choice. But some is also due to polygenic variation. Polygenic risk scores could be used to reduce polygenic disadvantage.
For example, the proportion of the variance in intelligence (and educational attainment) believed to be due to common genetic differences is 25%. This means these tests could be used to predict which future children would do better at school, though a recent influential article in the New England Journal of Medicine questioned the magnitude of the predictive ability in this context.
It is certainly true that the use of polygenic selection could increase inequality if they are only selectively available. However, there is already great natural genetic inequality – not all genes are equal.
To promote equality and justice, these tests need to be available to everyone, to include racial and ethnic minorities in data sets and, better, give priority to those couples whose offspring is predicted to be the most disadvantaged. This is our choice: because of the significance of polygenic selection, it should be treated as other universal health measures.
3. Genetic determinism and devaluing difference
Another objection is that by focusing on the polygenic contribution to disease and disadvantage, we will falsely believe that inequality is written entirely into our genes. We will ignore more important social constructions of disadvantage and we will express a negative view of the lives of those living with disease or disadvantage. “Better to be dead than disabled” is a slogan which often captures this negative expressivist view.
This objection is not unique to polygenic testing but also applies to single gene and chromosome testing. For example, the same objection applies to Down Syndrome screening. But a better response to such risks of genetic determinism and negative expressivism is to educate people about the equality of all human lives and promote social justice for people with Down syndrome, rather than banning or discouraging testing. Similarly, polygenic testing of embryos should be paired with social justice and educational campaigns.
4. Instrumentalising Children
Once we get away from selecting against diseases, and start selecting for musical, sporting or academic ability, aren’t we instrumentalising children? Aren’t we forcing children to “live in shadow of our expectations”? Aren’t failing to accept them as gifts? Michael Sandel has pointed to the tendency already to “hyperparent” as a major objection to selection.
Yet this is really on objection to how we parent, or the opportunities that are afforded to children, not genetic selection. Already, many parents fall short and that should be an object of social improvement. It is important to give Aurea her own life, allow her to explore her own possibilities, whatever her talents and limitations. But genetic selection doesn’t preclude that.
5. There is no “best” or “better” life
A pervasive objection is that, once we get outside serious diseases, there is no agreement on what a good life consists in, or what well-being is. It is subjective or relative to the individual.
This is particularly the case when it comes to pleiotropic polygenic traits. Increasing intelligence brings an increased risk of bipolar and autism spectrum disorder; schizophrenia is associated with creativity.
Value pluralism and imprecision makes it difficult to evaluate such complex “packages”. But this objection is not overwhelming: there will still be some dispositions that are uncontroversially bad, such as a genetic disposition to psychopathy (callous unemotional personality in children, which may go on to psychopathy, is about 80% genetic). And we do need more scientific work to unravel these associations and ethical work to unpack human well-being.
6. Selection is identity-determining
But there is one important feature of embryo selection that makes it unique: it determines which individual comes into existence. Selection on the basis of polygenic scores just selects an embryo that nature could have selected. In Aurea’s case, nature or doctors could have selected her from the 33 embryos.
Selection on the basis of polygenic scores just selects an embryo that nature could have selected.
In this way, concerns about harm to the child must fall flat: Aurea owes her very existence to her parents’ choice. She cannot in the future claim to have been harmed because without their choice to have IVF and genetic selection, she would not have existed. In so far as we should be grateful for a life worth living, she should thank her parents.
Genetic selection, then, is in a very important way, less troubling than we might think. If, for example, Aurea went on to develop schizophrenia, it is not as if she could have been born with a lower chance of schizophrenia – it would have been a different child.
And here we arrive at the main point. There is massive genetic inequality, and this is the first step to attacking this biological inequality in a general way. It is a massive step forwards in rationally taming the blind process of evolution that leads many human beings to experience a life which is “nasty, brutish and short” even in spite of the best efforts to socially construct a just society. For this reason, we have a moral obligation to pursue it.
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