Our genes tell us a lot about our immunity — but how closely should we listen?

Thanks to advances in DNA sequencing and analysis, clinicians will soon be able to deduce how infectious diseases will affect you personally. But before we can use this information, we’ll have to work through several ethical dilemmas.

Lisa Shepherd
Predict

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Photo by Braňo on Unsplash

Picture this: the year is 2053, and Liam is working as a nurse at a busy hospital. A life-threatening pandemic is poised to sweep his country. Last week, he and his colleagues were sent for a genetic test that can identify high-risk individuals or superspreaders. Liam’s results have just come back — he’s at high risk. Should he be required to step away from work for a while?

Or how about this: Liam’s colleague Rachel refused to take the test last week. A manager explains that it’s not just her health at stake here — they need to know whether she’s a superspreader so they can minimise risk to patients. But Rachel insists she won’t share her genetic information with anyone. Should her choice be respected, or should she be dismissed?

Six months later, midwife Naomi hears that a vaccine has been developed for the disease, but in rare cases, the vaccine can have adverse effects. The government mandates that all healthcare workers must be vaccinated. However, a genetic test reveals that Naomi is at increased risk of having an adverse response to the vaccine. Naomi works with pregnant women, who are especially vulnerable to the disease and will be put at risk if she is not vaccinated. Should she be exempt from the vaccination requirement?

A treatment for the disease has just been developed, but it isn’t effective for everyone. Mark and Ben are both ill. Analysis of their genetic data suggests Ben is more likely to respond well to the new treatment than Mark. Resources are limited. Should Ben be given priority for treatment?

For now, these scenarios are science fiction — but they’re exactly the kind of moral mazes we’ll be forced to navigate in the near future.

The genomic revolution

Genome sequencing is far cheaper, faster and more accessible than it was twenty years ago. The Human Genome Project, which produced a composite of the human genome sequence, ran from 1990 to 2003 and cost US$2.7 billion. Four years later, the first individual human genome was sequenced for $100 million. Today, we can sequence a genome for just $600 — and experts suspect the $100 genome will be with us soon.

The genomic revolution has already proved invaluable to infectious disease management. We’re now able to carry out rapid, large-scale sequencing of pathogen genomes. This information can help us diagnose infections, keep track of drug resistance, describe patterns of disease spread and identify new targets for vaccines.

But in recent years, we’ve realised there’s plenty of useful information hidden in our own genomes too.

The warnings written in your DNA

Your response to an infectious disease is determined not only by the nature of the pathogen, but your own susceptibility. For example, we know that chickenpox poses a greater threat to adults than young children, and that people with preexisting health conditions are more likely to be severely affected by COVID-19.

Genetic variation is also key to understanding disease susceptibility. Adopted children have an increased risk of death from infection if one of their biological parents also died as a result of an infectious disease. Leprosy is more likely to affect both members of a pair of identical twins than a pair of fraternal twins.

A classic illustrative example is the relationship between sickle-cell trait and malaria. Sickle-cell trait is an inherited disorder in which a mutated form of haemoglobin distorts the red blood cells into a crescent shape. Having two copies of the mutated haemoglobin gene leads to anaemia, painful episodes and an increased risk of infection. But there’s a reason the gene has persisted throughout the years. Carrying just one copy provides partial protection against malaria.

Your blood type also affects which diseases you’re most susceptible to — and none of us get off lightly here. If you have blood type O, you’re more vulnerable to cholera, mumps and tuberculosis. Blood type B also increases your risk of tuberculosis, along with salmonella and E. coli infection. Blood type A confers a higher risk of smallpox. If you’re type AB, your risk profile (rather intuitively) contains a mix of diseases associated with types A and B: smallpox, E. coli and salmonella.

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Genome-wide association studies (GWAS) have begun to uncover subtler links between our genes and infectious diseases. In this type of study, genomes are rapidly scanned to identify variations associated with a particular disease.

Susceptibility to HIV, the world’s deadliest infectious disease, is influenced by our genes. Individuals with a mutation called CCR5Δ32, who comprise about 1% of Europeans, are highly resistant to HIV-1 infection, even following repeated exposure. Clinical outcome after infection also depends on our DNA. Mutations in the gene HLA-B can cause the disease to progress abnormally slowly — or quickly.

30% of people infected with hepatitis B die or experience significant illness, such as cirrhosis or liver cancer. A drug named interferon α (IFNα) can restrict the replication of the hepatitis B virus, but efficacy is limited and side-effects are common. Researchers have identified genetic variations that seem to affect how well an individual responds to IFNα. Specific gene variants also have been connected to the effectiveness of the vaccine for hepatitis B.

There are many other infectious diseases for which susceptibility and/or progression has been linked to genetic variation in human hosts. These include influenza, dengue, meningococcal disease, herpes, Creutzfeldt-Jakob disease and tuberculosis.

These findings are interesting enough on their own — but what we’re really concerned with here is how they could alter our management of infectious diseases.

Implications for disease management

At present, most efforts to combat disease spread, such as vaccinations, have been aimed at universal coverage. But more vaccines are being licensed, causing costs to escalate. And as we know, the costs of genome sequencing are shrinking.

What happens when a genetic profile costs less than a vaccine? Will it become more cost-effective to target vaccines towards people who are most likely to benefit from them? And is it morally acceptable to do so if vaccinating everyone is also a feasible option?

A similar dilemma could be posed about disease treatment. Should we stratify patients for treatment based on genotype?

Saving resources may not be our only motivation for refusing to treat someone. Nowadays, antiretroviral therapies for HIV are highly safe and effective, and it would be ethically unsound to withhold them. But until recently, the available forms of HIV treatment were not 100% effective and were associated with far more severe side effects than modern drugs. In those years, genomic information may have been useful for clinical decision-making.

We should also consider that for most diseases, “treatment” and “no treatment” are not the only options. If we’ve developed several treatments for a particular disease, genetic testing may enable us to find the best option for each individual.

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Privacy

Public health sometimes comes into conflict with our rights, like privacy, freedom of choice and the right to know — or not know — certain things about ourselves. Generating genomic data on a mass scale raises a range of new ethical issues. These issues relate to both the initial gathering of the data and how it is used.

What information should people have in the context of infectious disease prevention and management? Many of us balk at the idea of taking commercial genetic tests that will tell us if we’re especially likely to develop conditions such as diabetes, Alzheimer’s and certain cancers. For every person who’d like to be warned so they can manage the risk, there’s someone who doesn’t want those worries hanging over their head.

Inevitably, some people won’t want to know whether they’re likely to catch or develop severe responses to certain infectious diseases either. But it’s hard to use genetic information to personalise treatment or preventative measures without letting people know what you’ve found out. Additionally, infectious diseases differ from conditions like cancer or diabetes in that they’re transmissible. Opting out of genetic testing has implications for the health of those around you as well.

Yet the desire for privacy is perfectly understandable, especially when we consider the social implications of gaining access to this new genetic information. Knowing that a certain variant increases the chance of transmitting a disease may lead to stigmatisation or marginalisation of those who carry the variant. Most of us are reasonable enough not to scorn someone for their genes . But if a dangerous virus was going around, you might think twice about meeting up with a friend who had been diagnosed as a superspreader.

Let’s also consider the lucky people who might learn they’re at low risk of catching a certain disease. This information could give them a false sense of security and make them more likely to participate in high-risk behaviours. A person at low risk of catching an STD may be more likely to have unprotected sex. A drug user with a low risk of contracting HIV may worry less about needle sharing. In a lockdown, certain people may feel justified in disregarding the rules.

The law

Right now, many countries have laws in place to protect people from genetic discrimination. For example, in the US, the Genetic Information Nondiscrimanation Act (GINA) prohibits discrimination on the basis of genetic information in any aspect of employment, including job placement.

In the near future, genetic data may allow us to determine who will be able to work more safely in a high-risk job placement during an infectious disease outbreak. You might argue that current laws should be adjusted to permit precautions like this — or perhaps you believe such ideas are exactly what these laws were meant to prevent.

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Advancements in genetic testing will also open the door to other policies that may be well-intentioned, but could certainly be classified as genetic discrimination. Imagine an alternate version of the 2020 COVID-19 outbreak, in which harsher restrictions were placed on people with some genotypes than others. (You know, in case the actual quarantine policies didn’t drum up enough controversy for you.)

What do you think?

There are no easy answers to the ethical dilemmas I’ve raised here. We all want medicine to be as effective as possible, but we also understand the importance of nondiscrimination, privacy and personal freedoms. These are new issues — perhaps this is your first time thinking about some of them — and many of us will need time to work out the nuances of where we stand.

But the important thing is that we do work out where we stand. Sequencing is getting cheaper. Our understanding of the links between infectious diseases and genetics is growing stronger. It won’t be long until we’re able to implement the technologies and policies I’ve described here. And before that, we need to decide whether we want them.

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Lisa Shepherd
Predict

Science writer with a passion for all things biology.