Children walk home with their guardians after school in Singapore on May 17, 2021, as the country prepares to shut all schools and switch to home-based learning until the end of the term due to a rise in the number of Covid-19 coronavirus cases. (AFP / Roslan RAHMAN)
Genetic testing has recently attracted much interest in Singapore, with the Ministry of Health (MOH) issuing a public warning on the risks of consumer genetic testing, as well as announcing subsidies on IVF (in vitro fertilization) embryo genetic testing for some patients at risk of transmitting heritable genetic defects to their offspring.
In May 2021, the ministry placed a moratorium on genetic testing and insurance, which bans insurers from requiring their clients to provide predictive genetic test results for disease susceptibility.
A more controversial development is the use of predictive genetic tests to select IVF embryos for good health and intelligence, in what is known as pre-implantation genetic testing for polygenic risks (PGT-P).
As good health and intelligence are complex traits determined by the combination of multiple genes, polygenic risk scores (PRS) are used to estimate an individual embryo’s likelihood of developing an adult-onset, multi-factorial trait by analyzing the combination of specific genetic variants within its genome. The risk here is because there is no genetic modification, there are minimal risks involved, as it is basically a technique for picking the “winning ticket” in the “genetic lottery” for good health and intelligence.
It must however be noted that there is an important distinction between embryo testing and selection to avoid serious harm from known genetic defects and for so-called ‘enhancement’, like better health and greater intelligence. The latter raises a range of ethical concerns and is a highly controversial topic that has evoked much-heated debate among healthcare professionals, biomedical scientists, lawmakers and religious leaders.
Nevertheless, in countries with more liberal regulation of fertility treatment such as the USA, PGT-P is being aggressively marketed by some private testing companies to IVF patients as being useful in selecting embryos with the least risk of disease susceptibility, as well as the best chance of intellectual development in later life.
This is a lucrative business model, because parents naturally and instinctively want the best for their children, particularly in our hyper-competitive society, where the educational rat-race often starts early in life.
"it is imperative to critically examine the various ethical and moral pitfalls of embryo genetic testing for optimizing health and intelligence"
Social pressure may make it difficult to resist such genetic testing, especially among the affluent, if this becomes a trend and fashion. They might also feel a sense of “guilt” about not doing such genetic testing that would give their offspring the best start in life, which in turn makes “autonomous choice in medical treatment” an illusion. Hence, it is imperative to critically examine the various ethical and moral pitfalls of embryo genetic testing for optimizing health and intelligence.
Most disturbingly, this could lead to the non-judicious use of IVF and other clinical assisted reproduction procedures, which were originally developed and intended for the treatment of infertility. Healthy and fertile couples might deliberately choose to have a child via IVF, just to avail themselves of embryo selection to optimize the health and intelligence of their offspring.
Not only are such treatments expensive, but they are also highly invasive and risky. Hence, unnecessarily subjecting healthy and fertile patients to such grueling medical procedures just for the sake of genetic testing and embryo selection must be considered clinical malpractice.
Even in the case of patients with genuine fertility problems, PGT-P would place undue pressure on women to unnecessarily undergo multiple IVF cycles to produce excess embryos for genetic testing and selection. This could therefore add unnecessary stress and confusion to the already difficult IVF process, as well as encourage patients to discard embryos unnecessarily; which would thus detract from the primary objective of conceiving a child in fertility treatment.
Then, there are also psychological and social issues. After spending so much money, parents may start to have unrealistic expectations of their “specially-selected” offspring. Children born through such procedures may have disturbing feelings of being treated like “lab rats,” and that their parents do not love them unconditionally as who they are.
Being such a lucrative business model, clinics and doctors may be tempted to hard-sell PGT-P to IVF patients. In countries with lax regulation of IVF treatment, clinics and genetic testing companies can make unrealistic and exploitative promises. Hence it is imperative that patients should be made aware of the various technical limitations of PGT-P.
"Is it a mere coincidence that so many creative geniuses in history suffer from various neurological deficits such as bipolar disorder and schizophrenia?"
First and foremost, it must be noted that in reality, many so-called “bad” genes exist, simply because these confer survival advantages to our species under specific environmental conditions.
Take for example the case of the sickle cell anemia gene prevalent among African populations. When present in one copy (inherited from one parent), it confers resistance against malaria, while when present in two copies (inherited from both parents), it causes the deadly sickle cell anemia disease.Likewise, there is scientific evidence that genetic predisposition to obesity and type II diabetes actually conferred survival advantages to our distant ancestors in a nutrition-poor environment. What if future climate change results in famines and food shortages? Would such “bad genes” that enable more efficient energy metabolism with low food intake now be considered “good genes”?
Similarly, genetic predisposition to autism spectrum disorders has been linked to high IQ. Children of high IQ parents are more likely to be autistic. Is it a mere coincidence that so many creative geniuses in history suffer from various neurological deficits such as bipolar disorder and schizophrenia?Hence, many of these so-called “bad genes” are the unique heritage of the human race, which have previously enabled our survival over countless famines, infectious disease epidemics and climate change events. Such genes could therefore be an insurance policy for our future survival as a species in a chaotic, uncertain and ever-changing world. It would be a fallacy to want to completely weed these out through embryo genetic testing.
An obvious technical limitation of polygenic screening through PGT-P is that most selections occur between embryos with the same parents, which substantially limits genetic variability, and therefore reduces its usefulness in targeting complex traits such as intelligence and disease susceptibility. There is a much-reduced number of possible outcomes when selecting for specific characteristics within such a small sample size with little variability, which obviates the usefulness of any selection methodology.
"There is good reason for genetic testing companies to downplay such complex information and just present simplistic notions of 'good' and 'bad' genetics"
Another limitation is that many genes often have multiple complex functions, which is further complicated by the multitude of interactions with other genes. An increase in the probability of one good trait could lead to a corresponding increase in the risk of a bad trait. For example, there is some genetic correlation between higher intelligence and the risk of bipolar disorder. Trading off risks between high IQ and bipolar disorder would certainly be difficult for any prospective parent, but when other traits such as genetic predisposition for obesity, height, and eye color are thrown into the mix, decision-making becomes overwhelmingly confounding and almost impossible.
Hence there is good reason for genetic testing companies to downplay such complex information and just present simplistic notions of “good” and “bad” genetics to prospective parents, or else they would not have any customers left if patients become aware that they have to face such confounding paradox of choices.
Yet another caveat is that current algorithms for polygenic risk scoring of embryos are based mainly on populations of European ancestry, which would therefore limit their usefulness in selecting specific traits in embryos of Asian or African ancestry. This deficiency could however be remedied in the near future.
At the end of the day, prospective parents must note that besides genetics and a controlled nurturing environment, it is in fact the rough and tumble of the real world, the experience of adversity and failure, which actually builds character, resilience, grit and motivation, all of which are key determinants of success in life. Taking a page from Singapore’s history, was not the stunning success of our founding fathers and pioneer generation forged in the fire?
Even if embryo genetic testing has little real value in forecasting the prospects of a child, a market will evidently still exist for such services, given the natural inclination for parents to always want the best for their child. It is therefore imperative that Singapore rigorously scrutinize and even ban such new technologies, given the profound moral and ethical issues involved.
Dr Alexis Heng Boon Chin is an Associate Professor of Biomedical Science at Peking University, China. He had previously worked in the field of human clinical assisted reproduction research in Singapore, and has authored 50 international journal publications on ethical and legal issues relating to new reproductive technologies, and published more than 270 scientific journal articles. The views expressed in this article are those of the author and do not necessarily reflect the official editorial position of UCA News.
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