SCIENCE: Portable DNA sequencing.
A new handheld DNA sequencer is releasing scientists from the confines of their labs, writes Katie Silver, aiding in projects from treating contaminated water to potentially testing for life on Mars.
Picture 15 to 20 scientists road-tripping almost 2000 kilometres across the north-east of Brazil in a minibus. Entomologists hop off and on, hurriedly collecting 1300 mosquito samples. They’re on a race against time to sequence the DNA of these itchy insects. The goal: to track the spread of Zika virus as it travels the country.
“The virus took the global health community by surprise,” says Dr Nick Loman of the University of Birmingham. “The world came to Zika very late.”
The team – whose results were published in last week’s Nature magazine – found Zika probably entered Brazil in February 2014, most likely brought over on planes from French Polynesia.
“It was a full year before the first case of microcephaly,” Loman says. “This suggests our surveillance isn’t working very well.”
Loman is a bioinformatician, meaning that he applies technology to biological and medical research. In this case, the technology is a mobile genomics laboratory. Specifically, a device known as the MinION, which experts say could revolutionise how we do science and medicine.
“Accessing DNA information allows us to understand all living things,” says Gordon Sanghera, cofounder of Oxford Nanopore Technologies, the company behind the MinION. The device is a pocket DNA sequencer that fits in the palm of your hand.
“Traditional sequencers provide a black-and-white picture. Here, you get colour,” he says.
To sequence a sample, users insert a small vial of a solution containing DNA into the machine using a long and thick syringe-like tube. The MinION then passes a current through this solution. The DNA’s molecule determines how the current changes. It uses this to spit out up to 10 gigabytes of data, providing the scientist with the source code to any living thing.
MinION is changing the game for genomics. Traditional DNA sequencers are large pieces of equipment that cost $100,000 to $10 million. They can only be used in a lab and take days to produce data. This portable device, on the other hand, costs $1000 and can produce data in real time anywhere, from jungles to the sea to space. They are already being used in everything from cancer research to environmental protection to sequencing the tomato genome.
Dr Zamin Iqbal, from Oxford University’s Wellcome Trust Centre for Human Genetics, is using MinION to diagnose tuberculosis, a disease that infects some 10 million people globally each year. Normally diagnosis is slow and expensive, requiring a spit sample to be sent away for up to two months. Given the demographics of the people TB typically infects, this is particularly problematic.
“In low-income countries, someone’s walked 30 miles to get to the doctor,” Iqbal says. “In the UK, it’s the poor, homeless and drug takers who are most likely to have it.” It’s hard to get these populations to return to doctors. “So, there’s a real push to get faster tests. You want a portable test to use in slums.”
Earlier this year, Iqbal’s Oxford team found that this two-month time span could be reduced to 12 hours using on-the-go sequencing. “In 18 months, we’ll be down to three hours,” he says.
He’s collaborating with labs in 19 countries, including Germany, China, India, Peru and Vietnam, to use the MinION to fight drug-resistant tuberculosis. “It’s becoming easier and easier to use. It’s still expensive, but it’s becoming much cheaper.”
The process is still not perfect. Iqbal cites the need for a sample to be tested in a solution as a drawback.
“We want to turn it into a device that someone actually spits in. At the minute, they haven’t even done the prototypes for this.”
But the technology has other capabilities beyond many traditional DNA sequencers, including being able to isolate the particular fragments of DNA you wish to analyse. “This is the reason people are so excited about it,” says Iqbal. “It makes it much more of an easy puzzle to solve.”
There is such hype in the scientific community that 400 researchers met at a conference in London last month to share how they’re using MinION.
One attendee was Sarah Stewart Johnson, a planetary scientist from Georgetown University in Washington, D. C. Earlier this year, she led an expedition to the McMurdo Dry Valleys in Antarctica – a place that hasn’t seen rainfall for two million years.
“Antarctica is one of the harshest places on the planet,” Stewart Johnson says. “The largest living thing you can see is a midge. The landscape is entirely dominated by microbes. We were trying to see how cells persist when pushed to the very limit.”
She and her team used the MinION to sequence these microbes’ DNA on the ground. It was the first time sequencing had occurred on the southern continent. By getting information back in real time, they could change the path of their research.
“It has the potential to completely revolutionise how we do remote field science. There’s still vast parts of our biosphere we don’t know about – beneath glaciers, under the ocean down in deep sea vents, or even in the dry valleys.”
With technological improvements, DNA sequencers could be left in these places, over the Antarctic winter for example, and provide a constant data stream back to their laboratories. If it was possible to automate how samples are prepared, Stewart Johnson says scientists could examine inaccessible places year-round.
Perhaps an even more exciting aspect of pocket DNA sequencing is what it might make possible to learn about other planets. Stewart Johnson is currently visiting scientists at NASA, working out how it might be possible to send the technology to Mars or Saturn. Experiments are already up and running in space and in Chile’s Atacama Desert.
“We’re testing how the machines hold up in different radioactive environments, such as on Mars,” she says. “At the most elemental level, I’m captivated by this idea of whether there might be life on Mars. We’re beginning to scratch the surface.”
Back on Earth, Dutch microbiologist Aleida Hommes-de Vos van Steenwijk is using the technology to help clear up contaminated groundwater. Much of her work is on a slurry outside Rotterdam, where her team from environmental consultancy Orvion BV analyses water specimens to see if particular bacteria need to be added.
“We know that certain bacteria eat certain contaminates,” Hommes-de Vos van Steenwijk says. “Basically, what we do is we take out all the DNA, throw it on the MinION and through sequencing, we can work out the whole population.”
In the past the team did this using external sequencing labs, but it was an expensive, logistical nightmare.
“There was an extraordinary time waiting for results, up to eight weeks. Things change a lot with microbial systems in that time.”
Next up Hommes-de Vos van Steenwijk wants to use DNA sequencing on sewage. “Sewage all ends up in our treatment plants but we don’t know – is that going to have an effect on humans?” she says.
Further afield, she hopes pocket sequencing can be used to improve drinking water in developing countries. “With sequencing, we can test if water is safe and check up on the people who are meant to be providing it,” she says. “It also helps with decision-making – is this the best place for a well, or elsewhere?
“There’s so much data in the environment and I think DNA sequencing is a way to learn about that data. And to keep the world more sustainable.”
When it comes to biosecurity, Zamin Iqbal says DNA sequencing could vastly affect the spread of infectious diseases around the world.
“You’re getting off a plane in Australia – you could brush the bottom of your feet, sequence that and see what bugs come up,” Iqbal says.
Nick Loman agrees. While his research may be too late for the thousands of Brazilian children born with microcephaly, he hopes that charting how Zika spread across the continent might help stop future epidemics.
“We tend to look for pathogens that we know about,” he says. “The next step is to start doing this kind of genome sequencing in a much more untargeted way worldwide. Be constantly on the lookout for viral pathogens.
“Zika was a warning to the world about how vulnerable we are. But we have methods now that help us do surveillance much better than before. If you’re faced with another Ebola or Zika and you can see how the transmissions are happening, it allows you to stop
• it earlier.”