DNA sequencing in the palm of your hand

22 January 2017
Posted by Kerstin Göpfrich.

It is smaller and lighter than your smartphone, it plugs into your laptop with a standard USB cable and it’s been to space. What is it? A new DNA sequencer. I tried it out with a bunch of schoolkids in a classroom – an experiment which would have been carried out in large sequencing centres at an unaffordably high cost until just a few years ago.

Think of a technology that has been improved tremendously over the course of your own lifetime. I wouldn’t be surprised if computers came to your mind. A room-filling apparatus used mainly by the army has been transformed into an omnipresent consumer product. Your smartphone can do what large computers were struggling with just a decade ago. After all, computing power is doubling every two years. And yet, computers are outpaced by DNA sequencers in many respects.

How DNA sequencing started

DNA stores the information of life in the form of the bases A, T, C and G – a bit like computers store information in a string of the numbers 0 and 1. Volumes of natural history are written in the ancient alphabet of life, which we are starting to decipher with DNA sequencers.

DNA sequencing means reading the order of the letters A, T, C and G of the genetic code. It started in the 1960s, soon after the discovery of the iconic double helix. The scientific efforts were fuelled by the hope that a better understanding of our genomes would open up an era of personalised medicine, allowing unprecedented opportunities to diagnose and treat disease. It wasn’t until 2003 that the first complete human genome, the three billion bases of our own genetic code, were read. This mammoth project required 13 years of work carried out by 150 scientists with a budget of three billion dollars. Today, just 13 years later, the same task can be carried out in about a day for just a thousand dollars. DNA sequencers now fit into my back pocket! The technology that enabled this sudden miniaturisation is shortlisted for the “Breakthrough of the Year 2016” award by the Science magazine.

DNA my smoothie!

I had the chance to try a DNA sequencer out with Kim Judge from the Wellcome Trust Sanger Institute. Together, we set out to challenge the kids at the Perse School in Cambridge to sequence some real DNA. But what were we going to sequence? DNA is in every living creature we know, so choices were vast. The kids? Ethically questionable. Some bacteria? Too boring. Then Kim suggested sequencing a fruit smoothie!

In the morning I prepared a smoothie with some mystery ingredients. Before Kim arrived, the kids helped me to get the DNA out of the smoothie. In a laboratory, we would carefully follow a refined procedure, but in the classroom, a “quick and dirty” method with household ingredients and equipment had to do the job.

What we ended up with looked, quite frankly, like a bit of whitish, stringy snot. That’s the DNA from the fruit in the smoothie. It should contain all the information we need to recover what went into the drink. Kim helped us dissolve the DNA in water and added some chemicals necessary for the sequencing process. With a pipette, we squirted some of the DNA into an opening on the DNA sequencer, which was plugged into a laptop.

What we couldn’t see is that, inside the sequencing device, there is an array of invisibly small channels called nanopores. When a strand of DNA is pulled through these nanopores, the DNA blocks part of the current which flows across it. Since the bases A, T, C and G are all slightly different, they cause slightly different blockades, which directly appear as different levels on the computer screen. A bit like different levels in sheet music correspond to different notes, these levels correspond to different combinations of DNA bases. This data is analysed on the Cloud and then sent back to the user as a spreadsheet full of the letters A, T, C and G. Depending on how much DNA there is to read, this can take anywhere from minutes to days. We left the sequencer to run overnight.

My PhD has taught me that experiments don’t often work the first time you try, but I was pleasantly surprised. Some of our DNA sequences we got back were of high enough quality that we could copy them into an online DNA database to compare it to the DNA of plants that have previously been sequenced. So what was in our smoothie? That’s for you to find out! Click here to have a go for yourself. Just to set your expectations – the school kids did get it right!

What can we do with a portable sequencer?
I certainly had fun with our DNA smoothie experiment, but to be fair, our taste buds may have given a quicker answer. So what difference is a portable, real-time DNA sequencer really going to make? Think of the horsemeat scandal. There is no better way to find out and to be absolutely certain what is in your food than to look at the DNA. Think of all the food you throw away because it might have gone bad. A DNA test would easily reveal if your soup is still safe to eat or, in remote places, if water is safe to drink. The same sequencer we had for our smoothie experiment is currently used to monitor the Zika epidemic in Brazil. The kids had their own ideas: “I would go to the jungle because there’s loads of different species and you could just find their origins.“ Ecologists are using nanopore sequencing for precisely this purpose. But in 2016 DNA sequencers have made it even further away from our laboratories. For the first time, DNA has been sequenced in space on the International Space Station. Again, an experiment that worked the first time it was attempted. Sequencing in space – what sounds like an expensive marketing gag - may actually be extremely useful, according to Dr. Aaron Burton who is involved in the NASA project.

“For the crew health standpoint, if you have a sequencer you can identify microbes in air, surfaces, and water and make sure that everything’s safe.” he states.

Sounds sensible. But what about more alien endeavours? In the future we may even be able to look for DNA on other planets. All life we know has DNA, so it will be interesting to discover if DNA is really the blueprint of life across the universe. And even if it isn’t, nanopore sequencers cannot only sequence DNA. They have been used to determine the sequence of DNA’s cousin RNA and even of proteins.

“You can imagine that if you had alien life that used a different alphabet you would still be able to pass those molecules through the nanopore and get that the change in current would be diagnostic of an informational molecule going through it,” says Aaron.

What will the future bring?
DNA sequencing has come on a long way: from a billion dollar multinational project into the palm of your hand within 20 years. But where will this technology take us?  It could open up the ability to sequence your own DNA, which opens up a can of ethical dilemmas and uncertainty. Would you like to know about a genetic problem with no cure? And could employers or insurance companies demand this information? Sequencing, however, could also change our ability to monitor food production, and track disease outbreaks, which could save lives. Like computers, DNA sequencers have the power to change our world– we just need to make sure it’s for the best.

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