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Tapping the genome

Illustrations: Angus Greig

The main room in the men’s toilets at Waterloo station is lined with urinals. As the assembled gents relieved themselves there in the summer of 2017 they were confronted by a curious advert, strategically positioned at eye-level. A cartoon showed two men in a maternity ward waiting room: one of them was clearly anxious, the other was relaxed, grinning, and dressed in a postman’s uniform. A bubble above 
the head of the worried man revealed the source of his concern.

Was it me or was it him?
The truth I need to find.
A Dadcheck test is needed
To give me peace of mind.

The Dadcheck service enables people who are worried about the paternity of their child to post off a swab of cells from the inner cheek of the kid – or indeed adult – in question, along with one from the putative father.

The key section of DNA from both sets of cells is copied 14 million times through a process called polymerase chain reaction (PCR) to make it large enough to use, then sequenced. Key genetic markers are compared between the two samples: the biological father, whether apprehensive poet or chipper postman, will match all of them with their child. The results are checked then despatched, to be met with cheers of delight or groans of despair at the other end.

Dadcheck is the brainchild of molecular biologist Neil Sullivan, 58, and geneticist Louise Allcroft, 45, who run the service from a beautiful old sandstone building in the village of Lanchester, just outside Durham. They had already formed a company to work on genetics projects together in 2000 when, in 2002, a colleague came to them with a common problem.

“She said, ‘I think my boyfriend’s got a child with someone else, but he’s not sure it’s his. Can you help?’” says Sullivan. “So we did the experiments and we helped. And Louise and I realised that paternity testing was a great way to take the complex science of genetics to the general public.”

Since then Sullivan, Allcroft and their team have delivered thousands of paternity verdicts to a broad range of customers. “We get everyone,” says Allcroft. “We’ve had people in their eighties and nineties who had affairs 60 years ago and want to know who their daughter’s father is before they die. But it’s not just paternity, it’s people who were adopted at birth, and they’ve searched and think they might have found their long lost brother. Or they were brought up believing Geraldine was their cousin and they’ve found out there are rumours that she might be their sister. There are all sorts of weird and wonderful family questions, and we can use DNA to help get people an answer.”

People will go and get a paternity test like they’ll go and buy an ice cream and pay less for it than they will for their weekly food shop” 
— Neil Sullivan

It’s not always the answer they want. “Sometimes the results can cause havoc because people have been covering things up,” admits Sullivan. “They’ve been lying to their partners. There’s no way around the fact that when those results come through, somewhere along the line there can be a bit of a family scrum. When people have got over that and it’s settled down, they’ve often come back to us and said, ‘Thank you so much. You’ve allowed us to move forward without this cloak and dagger stuff in our lives.’”

Sullivan says that there’s a moral as well as an economic mission behind the company’s work. “I do feel very strongly that we’re offering something very positive to society,” he says. “The drive to know your biological children or to know your biological father is absolutely immense. It’s so deep within your soul that it’s almost as strong as the desire to reproduce itself.”

The market has expanded dramatically since the launch of Dadcheck. “Back in the 1990s, paternity testing was a bit of a dirty word [in the UK],” says Allcroft. “Then you had the Trisha Goddard TV show which used them, then obviously there was Jeremy Kyle, God bless him. All of a sudden a paternity test became like the new Asbo for some people, it was almost a badge of honour.” Sullivan nods in agreement. “It has become an absolute commodity,” he says. “People will go and get a paternity test like they’ll go and buy an ice cream and pay less for it than they will for their weekly food shop.”

Paternity testing is the advance guard of personal genomics: it’s based on extremely robust, tried and tested science, and gives a straightforward yes/no answer to an important question. But in its wake, things are about to get a lot weirder…


It’s all about you

“You are unique, the product of thousands of generations of striving and success, of hardship and adaptation, of migration and mysterious ancient trysts,” runs the sales pitch for the Neanderthal app. “Certain ancestral lineages, during their migration across the world, encountered Neanderthals and interbred with them. Neanderthal looks at your DNA for signatures of these encounters.”

This prehistoric nookie-tracking service is one of many apps on the new Helix platform, which launched on 24th July 2017 promising to help you “Discover your DNA story”. The idea is simple: you send a tube of spit to Helix, a company based in the San Francisco Bay Area. Helix uses your sample to sequence and record key segments of your genome. You can then buy any of the apps on its platform and they’ll use your stored genetic data to bring you real-time, on-demand insights about your past and 
your future.

As well as finding out whether your forebears got lucky with a Neanderthal, you can discover things like how best to train or lose weight for your genetic type. Then there’s Wine Explorer ($29.99), which “combines an analysis of your DNA and taste preferences to match you with boutique wines we’re sure you’ll enjoy”. There’s SlumberType ($24.99), 
which will report on your “genetic similarity to self-reported ‘morning’ or ‘evening’ persons”. And once you and your partner have both been sequenced by Helix, you can use BABYGlimpse ($99.98 for two) to “get a preview into how your offspring might look while gaining fun and unexpected insights [about your future children] such as mosquito-bite size, sunlight sensitivity, and cilantro [coriander] 
flavour perception”.

Bento Lab is a laptop-sized mini laboratory that will allow anyone with a 
few hundred pounds to spare to carry out genetic tests at will”

Among these lighter-hearted
uses of the double helix are some strikingly serious options too. CarrierCheck™ ($199) will analyse the data held by Helix to see if you are a carrier of gene variants associated with any of 67 genetic conditions, including sickle cell disease, cystic fibrosis and Tay-Sachs. Its aim is to tell you “how your DNA may affect your family and future children”, and it comes with a free online genetic counselling session.

Elissa Levin, Helix’s director of policy and genomic services, is quick to point out that Helix is just a platform, and that the responsibility for giving people highly sensitive and potentially upsetting details about their DNA – like their propensity for passing on hereditary diseases to future children if they stay with their current partner – lies with the creators of the apps themselves. “We’re not actually building these products and these insights,” she says. Instead, Helix places a set of demands on the service providers: they need to have support services, educational materials and to write things “in a really intuitive, consumer-friendly way”.

App providers also have to offer information 
on the robustness of the scientific research behind 
their claims, the use of the results they generate (“Reported [Neanderthal] traits are for 
entertainment purposes only,” reads one warning) and the extent to which genetics actually plays a role in comparison to environment (SlumberType admits on its page that “external factors like 
stress and caffeine influence your Zzzs more than what we currently know from your As, Cs, Ts 
and Gs”.)

Helix is only a few months into operation, but in ten years, reckons Levin, “it will be enabling people to have this [genetic] information at their fingertips, and incorporating it into their daily life in ways that we can’t even imagine today”. She believes that consumers using services like Helix will push their doctors to integrate personal genetic information into their healthcare. “Patient-initiated healthcare is such a growing trend,” she says. “Consumers want access to their information.”


Gene hack man

In a quiet corner of a startup community in Bermondsey, south London, synthetic biologist Philipp Boeing, 27, is putting the final touches on a product that will allow anyone with a few hundred pounds 
to spare to carry out genetic tests 
at will. Bento Lab is a laptop-sized mini laboratory containing a centrifuge to extract DNA from a biological sample; a thermocycler to target a specific piece of DNA and copy it; and an illuminated gel unit to visualise 
the results.

Before Bento Lab, would-be geneticists had two options. They could embark on a degree in biochemistry and gain limited access to the highly expensive sequencing equipment locked away in the university lab. Or they could take matters into their own hands. “You had to become a hardware expert,” says Boeing. “You had to teach yourself programming and electronics and how to refurbish old equipment. You’d take a year or two until you had your lab set up. By then you’d be an expert in building a lab, but you wouldn’t have done any biology yet. 
We thought, why isn’t there a kit and a community where you can just start with biology?”

So together with his co-founder Bethan Wolfenden, Boeing built the kit, Kickstarted it to the 
tune of £150,000 and is about to start shipping the first units. Recipients will be able to use their miniature laboratory in conjunction with a tutorial starter package which, over the course of a month, will teach them how to be an amateur geneticist. 
A series of 15 suggested experiments are included: one enables you take a sample of a hamburger and work out whether it contains horse meat; another lets you take a swab of human DNA and work out whether its owner is lactose intolerant.

“We always get emails asking, ‘Can I do a paternity test with Bento Lab?’” says Boeing. “Technically you can but they have a much higher throughput setup. I wouldn’t want to do it myself because it would take forever. But, yes, it’s the same scientific principle.” And could the device be used for even more serious tests? Could it, for example, be used to tell whether a person has mutations in their BRCA genes, of the sort which are linked with breast cancer?

“We don’t include the bio-markers for identifying things for things like mutations in BRCA but, 
scientifically, it’s the same process,” says Boeing. And is there anything to stop someone out there selling such bio markers? 
“We think about that,” says Boeing, “and obviously, we can’t really stop that. It could definitely happen. 
What we’re trying to do is to bake as much of a point of view as we feel is right into the design language, especially in the starter kit, without saying, ‘Don’t do this. Don’t do that.’”

Complement Genomics will sequence your dog’s DNA and tell you exactly which breeds it’s made up of – and in what percentage”

Boeing’s excited about the work that will be done with Bento Labs. The prototypes that are already in the market have been used by field researchers studying diseases in Brazil and Cambodia. “They can do the analysis on the day they collect the sample, rather than waiting for weeks until they’re back in the laboratory,” he says. “They take Bento Lab into a field camp, or into their hotel room, or their Jeep, and run an analysis there: it gives them a preliminary result that’s pretty accurate.”

The obvious next step beyond Bento Lab’s democratisation of genetic analysis would be to move from passive to active: not just mapping genes in the comfort of your own home but also manipulating them by modifying cells with inserts of new DNA. “I come from this field called synthetic biology, which is really the idea that biology can be made into a design discipline,” says Boeing. “We’re interested in anything that would make this more accessible.”


The hunt for the £3 million falcon

It’s unlikely that citizen scientists armed with Bento Labs are going to take the place of Dadcheck’s paternity tests any time soon. What is more likely to upset Dadcheck’s business model is automation. At some point, if there’s sufficient demand, the speed of the sequencers will increase to the level where you can take a couple of swabs to a machine at the Post Office and run a paternity check in the same time it takes to get passport photos.

But Sullivan and Allcroft haven’t limited themselves to paternity: they’ve diversified. Under the umbrella of their wider business, Complement Genomics, they’ll sequence your dog’s DNA and tell you exactly which breeds it’s made up of and in what percentage. “People love to look at their dogs and say, ‘Oh yes, it’s got a bit of poodle in it, got a bit of Labrador in it’ – they debate this sort of stuff for hours,” says Sullivan.

They’ve also got a nice sideline in sexing peregrine falcons. When these birds hatch, it’s not possible to tell their gender, and breeders have to wait for several years to work out their sex from their size. So Sullivan and Allcroft’s team test the egg membranes and accelerate the identification process, meaning trainers only bother with training the females, which fetch a far greater price among the Gulf Arabs who race them. The stakes are high. One competition, the President’s Falconry Cup in Abu Dhabi, has a prize fund of £3 million: it’s like Formula 1 for birds of prey.

The real endgame for Sullivan and Allcroft, however, is not accurately sexed falcons or telling you who’s the daddy, but personalised medicine. They’re not interested in finding out their propensity to get a certain disease. “Say we send you a report that says you’ve got the polymorphism [genetic variation] for Alzheimer’s disease. If you got that report, what would you do?” asks Sullivan. “It’s information you aren’t able to use. Are you actually going to get Alzheimer’s? I don’t know. Because you may well have the polymorphism but as a geneticist I know that you could have several compensating mutations that would override the effect of that one. There’s information going out that is not really interpretable by the individuals that get it.”

What does interest the pair is metabolism. Until recently, drug trials were one-size-fits-all 
affairs, as were the drugs that came out of them. 
But the way that individuals metabolise drugs, which is related to polymorphisms in their DNA, can make a radical difference to their efficacy. One-size-fits-all means that most of the time most people are either over- or under-dosing themselves – and in some cases may even have an adverse reaction related to the way their body breaks the drug down. This is all set 
to change.

“We use sequencing to predict whether someone is going to metabolise a drug quickly or slowly, and then on the basis of that, they get selected for the clinical trial,” says Sullivan. “The pharma companies are now saying that they want people who are poor metabolizers of a particular drug, because they’re going to do a formulation specifically for them, and then another, for a fast metabolizer, so everyone can get an effective dose.”

We’ve just got some poo in from one of my collaborators; we’re sequencing all of the bacteria that are in it” 
— Neil Sullivan

Complement Genomics has just bought a new sequencing machine which allows them to tackle another side of personalised medicine: the microbiome. “In the last few years we’ve discovered that the bacteria living within you and on you are an absolutely vital part of your metabolism and your predisposition to disease,” says Sullivan. “We’ve just got some poo in from one of my collaborators; we’re sequencing all of the bacteria that are in it,” he continues with what feels like an unwarranted level of enthusiasm. “And this is the next big thing, because the bacteria within you can predict your disposition to disease, and how diet and medicine will impact on your health.” In the future, Sullivan believes, we won’t just be interested in sequencing our genomes but also our gut bacteria. Programs will crunch our data and deliver a whole new world of individualised healthcare, as medicine moves from a blunderbuss to a sniper’s-rifle approach. “Personalisation is the missing piece of the jigsaw,” he says. “It makes sense of everything.”


The economics of genomics

The personalised genomics industry is still in its infancy but, driven by humanity’s twin obsessions with technology and gaining personal insights, both serious and frivolous, it seems likely to explode in the coming years. And the plummeting cost of sequencing is opening the industry up to hosts of new businesses. When the first genome was sequenced in 2003, as part of the Human Genome Project, it cost the equivalent of $4.87 billion in today’s money. By 2014 that price had fallen to under $1,000. Helix will now sequence a useful amount of your genome for you for just $80.

Huge amounts of money are being poured in as investors scent the possibilities: Helix was funded by $100 million from a series of biotech companies including Illumina, who make the tech behind genetic ancestry site 23andMe. And the business opportunities lie not just in flogging tests and smartphone apps but in building up huge, saleable databases of genetic data from your bank of customers.

So picture the scene. It’s a few years hence. You and your partner have spent a relaxing morning checking out the coriander preferences of your future children and peering into your dinner party guests’ genomes to see whether to serve them riesling or pinot grigio with the seabass tonight. An update from an app on Helix pops up on your phone: some new research is showing that you might have a propensity to develop a particular disease. You fire up your next-generation Bento Lab to look deeper into the results and, armed with a sheaf of diagnostic data and the latest sequence readings from your biome, you head to your doctor, to demand some made-to-measure drugs.

And then, a few years later, if synthetic biology has taken a great leap forward, maybe you don’t even need a doctor: just program a new strain of bacteria, insert it into your bottom and trust your gut to sort you out. Welcome to the future: no one said it would be dainty.


We hope you enjoyed this sample feature from issue #28 of Delayed Gratification

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