BORN into a working-class family, “Olivia” was abused as a child. Her parents were emotionally distant and offered her little comfort. Now aged 56, Olivia lives near a busy road. She is poor, smokes, drinks much more than is good for her, and has panic attacks.
If Olivia really existed, she probably wouldn’t want many people to know all these details about her life – but a tiny drop of her blood could give it all away. The technology now exists to read in our blood all the kinds of information described above, and more. Such tests could tell others much about our health and habits, state of mind and socio-economic status. It could also reveal details from bygone decades, such as experiences from the furthest recesses of our childhood.
This is possible because the world we live in and the experiences we have leave subtle traces on our DNA, and we are now learning how to decipher these marks. On the positive side, this powerful tool could help doctors spot all kinds of diseases and disorders. It could also help police create a comprehensive profile of a suspect from a single drop of blood at a crime scene.
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But as the law stands, there is nothing to prevent such tests being used by unscrupulous insurers, employers and even journalists. Would you want anyone to be able to read your life story, one you are potentially giving away whenever you have a blood test or throw a bloody tissue in the bin?
It is already possible to learn a fair amount about a person from a drop of their blood, by looking at the sequence of their DNA. This can reveal your sex and ethnic background, and give a pretty good idea of your hair colour, eye colour and even skin colour. It can also hint at more personal things, such as whether you are a risk-taker, an early bird or have a behavioural disorder such as ADHD.
But who we are isn’t written in our genes. The stuff that really matters is the result of our lifestyles, experiences and environment. You might think this doesn’t have anything to do with our DNA. In fact, all kinds of labels get attached to the DNA in our cells as we go through life.
The most common form of labelling involves attaching a methyl group to one of the DNA letters. Methylation doesn’t alter the underlying sequence but it can shut down nearby genes. If you think of our DNA as a recipe book for making a human, then the methyl groups are like yellow stickies saying “don’t make this”. Some recipes have no stickies on them, while others end up plastered with them.
The vast majority of these labels get added as we laze in our mother’s womb, and shortly after. This is when cells are taking on specialised roles, and methylation helps switch off genes that aren’t needed, ensuring that a liver cell doesn’t express nerve cell genes, for example.
The upshot is that if you take cells of the same type from different individuals and compare the pattern of labels on the DNA – the epigenome – there will be many similarities. Many epigenetic changes are genetically programmed. But there are tens of millions of sites in the genome where methylation can occur, and no two individuals will have exactly the same pattern. This variation between individuals is at least partly to do with our lifestyles, and can therefore reveal much about our life history. “The epigenome is a snapshot of the major events in your life,” says Tim Spector of King’s College London.
“The epigenome is a snapshot of life events. You can even get an idea of what someone eats”
By looking at epigenetic marks, Spector can tell if someone is a smoker, an ex-smoker or has hardly ever taken a drag. He can tell if someone has, or has ever had, cancer. “You can even get an idea of what they eat,” he says. And because we accrue epigenetic changes throughout life, the marks can also reveal our age ().
Exposure to substances such as diesel fumes, pesticides and arsenic also produces . Analyse the epigenome, then, and you might be able to work out what chemicals a person has been exposed to, perhaps even where they have been.
This would have been unthinkable just a few years ago, when detecting methylation patterns was difficult and expensive. But the technology has advanced at an incredible pace. It is now possible, for instance, to buy a $200 off-the-shelf “chip” that shows which of 450,000 sites in the genome are methylated.
Window to your past
With the help of such tools, researchers have begun looking for correlations between methylation patterns and particular environments or experiences. All kinds of cells are being looked at, but blood cells are the most common, as they are easy to obtain. The last few years have seen a flood of studies highlighting patterns related to everything from to success in dieting.
One recent study in the US asked its 1000 or so participants to rate their wealth by ticking which of four assets – car, house, land and financial investments – they owned. The richest people had different methylation patterns to the poorest (). in the UK city of Glasgow. “There are clear signals that the epigenome is being affected by socially patterned factors,” says Ana Diez-Roux of the University of Michigan, Ann Arbor, who co-authored the US study.
The epigenome may even be a window to episodes from our distant past. Holocaust survivors have very different methylation patterns to people who haven’t had a severe traumatic experience, for instance. Adults with post-traumatic stress disorder (PTSD) also carry unusual profiles. It appears traumatic life experiences leave epigenetic marks long after physical scars have faded.
Among people with PTSD, the altered marks are more pronounced in those who were abused as children than those who were traumatised as adults, . “So there may be a trauma-prone period during childhood,” says study author Elisabeth Binder from the Max-Planck Institute of Psychiatry in Munich, Germany.
Quite how people end up with these different patterns is unclear. Nor is it known what, if any, effect they have. Some of the variations in methylation could be in regions of DNA that don’t do anything important. Other variations may impinge on key genes.
For instance, Binder suspects some of the epigenetic changes associated with trauma during childhood increase levels of hormones called glucocorticoids, involved in the stress response. This probably makes it harder for abused children to cope with stress later in life, and more vulnerable to conditions such as PTSD and schizophrenia as adults.
If you just want to use epigenetic patterns to reveal someone’s life history, though, it isn’t necessary to understand how the variations come about or how they affect a person. All that matters is that the patterns exist. “Epigenetic marks show a lot of promise as biomarkers,” says Adrian Bird of the Wellcome Trust Centre for Cell Biology in Edinburgh, UK. The issue is how reliable they are, he says. The studies done so far have only involved small numbers of people and have used disparate methods. “It’s difficult to base predictive science on them at the moment,” Bird says.
The situation echoes the early days of cheap DNA testing, when tens of thousands of potential biomarkers based on single DNA letter changes were highlighted by small-scale studies. Most results couldn’t be replicated. But larger, better-implemented studies have turned up reliable biomarkers.
“We have to learn from that,” says epigenetics researcher Stephan Beck of the University College London Cancer Institute. “The studies need to be massively scaled up. Only then will we see how reliable the markers are.” However, epigeneticists are hopeful that even if many of the patterns discovered so far do fall by the wayside, some will prove resilient and many more will be discovered.
The autobiography within
The level of detail encoded in these patterns also remains uncertain. Will an epigenetic test give us only a summary of our life story – like chapter headings in an autobiography – or can it tell us more? For instance, although a person’s methylation profile can show whether they experienced something very stressful as a child, it cannot tell us what that was – at least, not yet. As we learn more, we may be able to read finer details. “We need to better understand which environments leave which marks,” says Binder.
We also need to start thinking about the implications. As yet, no one has looked for multiple epigenetic patterns within the same person, but there’s no reason why it can’t be done. One blood sample and one chip could yield enough information to scan for thousands of methylation signatures, revealing a wealth of information about someone’s current lifestyle and their past.
To investigators trying to identify someone based only on blood from a crime scene, this will be of great interest. In some countries, police are already using genetic tests that predict hair and eye colour, for instance. Add in epigenetic clues to someone’s age, social status and even where they live, and investigators could get a much better idea of who they are looking for.
Epigenetic tests may also be able to tell whether someone has taken illegal drugs or violated a drinking ban. In some countries, various kinds of tests are already being used to monitor illegal drug use or enforce compliance, such as anklets that measure blood alcohol. If they prove reliable, epigenetic tests could become part of this toolkit, although such evidence is unlikely to be admissible in court any time soon.
Methylation patterns have also been linked to numerous diseases, including diabetes, and to psychiatric disorders such as depression. In theory, a single, cheap blood test could reveal not only the state of your health but also your medical history and maybe your medical future. Spector, for example, has identified a methylation profile involving around 400 sites that can, he claims, give five years’ warning of the onset of breast cancer ().
While epigenetic profiling could be a powerful tool for catching criminals and saving lives, there are as ever potential dangers. What if you had episodes in your past you wanted to hide? You might not worry about your doctor having access to your epigenome, but what about your life insurance company? Could they increase your premiums or refuse to insure you on the basis of what your epigenetic profile reveals? How would you like your employer or school to get their hands on this information?
“There’s a whole host of legal and ethical issues surrounding epigenetics,” says bioethicist Mark Rothstein of the University of Louisville School of Medicine in Kentucky, “but people are ignoring them for reasons I just don’t understand.”
In the UK and some US states, it is illegal to analyse someone’s DNA without their consent, but there’s nothing to stop you analysing their epigenome. It’s a similar story with discrimination by employers and insurers. The UK and the US (unlike Australia) have laws addressing genetic discrimination. “But there are no specific laws for epigenetics,” says Rothstein. “It’s very alarming.”
Rothstein thinks we need to ban non-consensual epigenetic testing. Then we can start to think about the beneficial uses of these tests, and build up the legislation around them. There’s a whole debate to be had. “We need to get it started.”
Wiping the slate clean
Subtle traces on your DNA can reveal what’s happened to you during your lifetime (see main story). Although the vast majority of studies have focused on negative life experiences such as childhood abuse, this kind of testing doesn’t have to be all doom and gloom. Positive experiences alter our epigenome as well. “Positive events can change you every bit as much as negative ones,” says Rachel Yehuda, a clinical neuroscientist at Mount Sinai Hospital, New York. “Biology doesn’t discriminate between the two.”
At least some changes to the epigenome are reversible. So when epigenetic marks, as they are known, turn out to have undesirable consequences, we can try to change them. A handful of drugs that affect DNA methylation already exist, and are being used to treat cancers in which faulty gene labelling plays a role. But even things as simple as diet, meditation or counselling should alter the epigenome too.
Yehuda has been looking at combat veterans with PTSD. In a small preliminary study, she has shown that psychotherapy, the first line of treatment for PTSD, can alter the activity of a stress hormone by altering the methylation of a specific region of DNA. What’s more, the methylation status of another region seems to predict whether people will respond to psychotherapy or not (). So epigenetics can not only help us tell what’s wrong with someone, it may also reveal the best way to treat them and help check how effective that treatment has been.
As yet, it remains unclear to what extent the epigenome can be rewritten. Do telltale traces of major life events persist until death? Or can all changes be reversed, meaning there’s a limit to what epigenetics tests can tell us about people’s pasts?
We don’t yet know the answer, but it is already clear that to a large extent our epigenetic narratives are not cast in stone. We don’t just write our epigenetic story – we have the power to edit it too.
This article appeared in print under the headline “Written in your blood”
