The SG100K genetic study is a step in a potentially revolutionary field. But as with all tech breakthroughs, there are ethical and other dilemmas that need attention as well, said Singapore’s Health Minister at last week’s official launch of the research project. Here are edited excerpts of his speech.

In 1990, the Human Genome Project generated the first sequence of the human genome, which cost many billions of dollars and took many years. Now, with a small blood sample, it can be done in a few hours on a laptop, costing a few hundred dollars. That is how far and how fast genomics science has progressed.

Under SG100K, with the blueprints of 100,000 participants, the researchers will monitor and follow their health and well-being through the years. Researchers will cross-reference disease registries, and to health, social and environmental records.

Governments around the world – including the United States, United Kingdom, Denmark, Finland and Japan – have initiated similar studies. While their studies have a larger base of participants, SG100K took a multi-ethnic approach, involving population segments that may have been under-represented in previous studies in other countries.

This will give scientists a deep understanding, in an Asian context, of the interactions between nature – the genome – and nurture – social and environmental conditions and factors.

Implications for healthcare

What are the implications of that knowledge, especially for healthcare? In short, it will enable and turbocharge the development of precision medicine.

Let me give a layman’s explanation.

When we want to repair a machine or maintain a building, having a full blueprint of the subject makes a huge difference to the engineer or technician. They will know exactly where to find the problem and fix it. Similarly, if an IT specialist knows the source code of a computer virus that is causing a lot of problems, they can zoom in to the specific lines of source code to neutralise it. That is the value of a blueprint.

In precision medicine, with this human blueprint in hand, we can fix diseases in very precise ways, at their roots, and even customise treatment and care for patients. Let me give a couple of examples of what is possible, starting with targeted and optimised disease treatment.

On average, only about one in four patients diagnosed with cancer or Alzheimer’s disease responds to medication that is currently available. For many other common diseases including diabetes, irregular heartbeat and asthma, the corresponding figure is in the range of 50 per cent to 75 per cent.

This means that while patients may be given the same treatment, not all will experience the same expected benefits, and it must be so because every human being is different.

We all have different blueprints. Precision medicine enables clinicians to move beyond this “one size fits all” approach to medication and treatment. If the clinician knows the genetic make-up of the patient, he or she can potentially understand which drugs work better for that particular patient.

Precision medicine can be used to identify individuals who are at higher risk of developing certain diseases. This provides the basis for early preventive interventions.

For example, studies showed that familial hypercholesterolemia (FH), an inherited condition that results in very high cholesterol levels, can lead to higher risk of heart attacks, even at a young age. Hence in the UK, first-degree relatives of those with suspected FH are genetically screened to determine if they are at risk, and where necessary, to start them on preventive oral medication early.

With the findings of SG100K, we can identify many more correlations between patients’ genetic make-up, their social and environmental factors, and onset of severe diseases. These provide powerful bases for preventive care.

Recently we read in the news that Chris Hemsworth, the Australian Hollywood star who acted in Marvel superhero movies, did a genetic test, and found that he is at heightened risk of developing Alzheimer’s disease. This has prompted him to declare that he is changing his life goals, including to spend more time with his family.

But more importantly, people like him can start taking steps to reduce the risk of developing Alzheimer’s disease.

The journey ahead

What are the steps that we need to take now, given the profound and potentially revolutionary implications of precision medicine.

We must first recognise that all major technological breakthroughs, from gunpowder and nuclear energy to the Internet and artificial intelligence, are double-edged swords. They promise to deliver a lot of good to humankind, but they also inadvertently present risks and downsides. We need to ponder quite deeply and take steps to harness the good of technology, while minimising the risks and downsides.

Precision medicine is no different. In this regard, I think there are at least two major areas of work that we must embark on.

The first, and which I think is a no-regrets move, is to start delivering preventive care universally to the public. This is in essence what we are doing under Healthier SG.

We are putting the key pieces of the preventive care system in place. We are mobilising family doctors and anchoring residents to dedicated doctors. We are developing more health protocols to manage chronic diseases through family doctors. In time, when precision medicine and genetic screening are ready to play a larger role in preventive care, the policies, systems and processes will be ready too, to embrace this scientific breakthrough and put it to good use.

For example, you can imagine, family doctors can administer or facilitate genetic screening for their patients. Preventive interventions will be readily available in the community, especially when it concerns many diseases where preventive steps tend to converge on good diet, proper sleep and appropriate physical activities.

A second area of work requires much deeper thought, analysis, weighing of pros and cons, and even societal soul-searching. Because the policy implications of precision medicine are profound.

We have gone through similar technological spurts before. When the Internet first appeared, it opened up all kinds of possibilities and filled the world with wonderment, with so much stuff that we can do with our computer. But then came the dot.com burst, cyber bullying, propagation of extreme ideas, child pornography, mobilisation of riots, et cetera. So while the Internet has become an integral part of our lives now, societies all over the world are still playing catch-up, putting in place policies and legislation to protect themselves against the darker side of the Internet.

We are likely to face similar dilemmas with precision medicine. A technological breakthrough like this opens up a broad spectrum of possibilities. At one end are those that are convincingly good – more cost-effective treatments with better outcomes, targeted clinical interventions to prevent diseases or their progression, optimised medication to minimise severe drug allergies.

At the other end are possibilities that are undeniably bad – for example, organisations that hire based on genetic profiles, which could be possible; couples testing for genetic traits of a foetus before deciding whether to keep it. Today, the Ministry of Health already imposes a moratorium on the insurance industry against genetic discrimination in health insurance coverage. At some point, it would probably need to become law.

In between the convincingly good and undeniably bad are many shades of grey, possibilities with pros and cons, or benefits that we can realise provided we address the key concerns.

You might have read recently, a news report concerning Alyssa, a 13-year-old girl in the UK who has leukaemia. She participated in a clinical trial using genetic “base editing” technology, where she received T-cells from a healthy donor that were genetically modified to attack the cancerous cells in her body. Today, she is in remission.

This is great news. But we also need to understand the context, the implications and issues it has raised.

Alyssa is likely a unique case – someone who did not respond to traditional treatments and was found to be suitable for gene therapy. So “gene editing” technology is yet to be a mainstream treatment that is suitable for most people.

Even amongst those found suitable for the treatment, it may not work well for everyone, as it did for Alyssa.

And even if it is effective and the patient is suitable, there is the issue of cost. Novel treatments like this are in the range of multiple millions of dollars per patient. Unlike traditional treatment, the cost is not in research and development, but in the customisation and delivery of the therapy.

Hence, if and when this technology is proven to be efficacious enough to become mainstream, we must ensure that it can be accessible to the patients who need it clinically, and not just those who can afford it. This will require a major rethinking of healthcare financing policies and healthcare safety nets. No healthcare financing policy in the world is now designed for this.

Similarly, in the area of preventive care, while genetic sequencing of an individual can provide useful signposts for future possible diseases, we also don’t want a population of hypochondriacs and unnecessary medical interventions all over the place. The benefits therefore, are not straightforward, in the absence of proper rules and clinical protocols.

We need to decide: to what extent will we allow the extrapolation and interpretation of genetic test results? To what extent will we allow the results to be translated to clinical actions?

Hence, for us to fully benefit from precision medicine, much work needs to be done, in clinical development, ascertainment of cost and medical effectiveness, healthcare financing policies, legislation, and determining what is encouraged, allowed and proscribed.

We need to conduct a great deal of studies, consultations and engagements with policymakers, physicians, economists, regulatory bodies, bioethicists, the public and patients.

The moon shot

From time to time, we hear about the medical moon shot – a major breakthrough like curing of cancer, that is as significant as sending a person to the moon. Indeed, we are on the cusp of witnessing the medical moon shot, because of precision medicine.

The moon shot and precision medicine differ in in one key aspect – which is that very few people are astronauts, while healthcare touches the lives of almost everyone, directly or indirectly.

The promise of better treatments is always good news, but it always comes with many uncertainties, and moral, ethical and policy dilemmas.

There are however powerful similarities between the two as well. First, they are both not about advancement in just one technology. Many strands of breakthroughs come together to make the moon shot possible. All need to be ready and come together to make the endeavour successful. Similarly, for precision medicine to serve humankind well, technology, delivery systems, legislation, clinical protocols, ethical standards, patient education, et cetera, have to be concurrently in place.

The most important similarity is the human spirit driving such advancements. Human beings are always determined to march forward, venture into the unknown, to embrace scientific advancement for the benefit of our present and future generations. Each society and country will do its part. SG100K represents such a step forward, to help us learn more, improve and seek answers, in Singapore.