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Joe Mugford
November 2016.
56
Which new genetic breakthroughs will change our lives?
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The thing you're most likely to have heard of recently is gene editing, or genome editing, which has certainly entered popular consciousness in the last couple of years. There are indeed a lot of new tools that we can use on this front, of which CRISPR is the best known and also the most useful. In some ways, though, this is just another way of doing genetic engineering as we have for some decades now: what it gives us is an enormous degree of precision in how we do things, where before we were using some quite clumsy tools and just hoping for the best.

But in addition to that, we now have the ability to synthesise large amounts of DNA, in different fragments, and then stick them together. This is essentially chemistry - building genes from chemicals - rather than altering something in existing living cells. Our genes are essentially great long strings of the DNA molecule, with four constituent parts - the “letters” as we call them - in different orders encoding information. 20 years or so ago, we started being able to read this information with great precision, to be able to read out whole genomes - and now, we're just about in the position where we can write our genomes. You can think of this as having a computer printer for DNA.

Four or five years ago, the first fully synthetic living bacteria was made by Craig Venter, one of the pioneers of genome sequencing. He works in the private sector, and he and his company made a bacterium called Synthia, which is basically an artificial copy of an existing organism. They read the genome of a bacterium called Mycoplasma, then they made this genome from scratch in a test tube according to the information they'd read - printed it out, as it were - put it into an empty bacterial cell, and essentially created life. As far as we know, this is the second time that life has been created on Earth - which is quite a big deal.

But bacteria are incredibly simple things. If you think of the number of genes as the number of moving parts in a machine, a bacterium has a few hundred to a few thousands, while we humans have got somewhere in the tens of thousands, and then the way they're stuck together is way more complicated, so that makes our genes orders of magnitude more complex. Now a project was announced earlier this year, called The Human Genome Project: Write, so they're going to synthesise a whole human genome, as Venter did with a bacterial one.

Whether they can then get it into a human cell and reproducing is another matter. It's one of those “moon shot” projects, where you don't know if you can do it until you do it, but if you do then the implications are immense. Essentially, if you can write a human genome, then you can edit it. There are many achilles heels in our genomes – there are a few genes, for example, that are associated with most cancers – so if we can see where we can change them and edit them, then we can certainly leave people much less susceptible to cancer in future generations.

“If you can write a human genome, then you can edit it, which means you might be able to edit out the genes associated with most cancers.”

Our ability to read genes continues to advance too. In 2000, we read the human genome for the first time, and actually that's feeling old hat now. The pace and the technology with which we can do that has accelerated enormously. It took about ten years and ten billion pounds for a multinational collaboration between thousands of researchers to sequence a single human being's genome: that was the original Human Genome Project; or Human Genome Project: Read as some now call it. Now, you can do it in an afternoon, in a lab, on your own, for about a thousand pounds.

So we're now sequencing everything under the sun. If you're working on an interesting organism, you don't really think twice, you just sequence its genome simply because you can. When I started doing research science, we just about had the gene sequence of one favourite cress plant that's commonly used in research - and that was incredibly useful, it felt like a very exciting time. But now we've got the genomes of most organisms you could think of, including some very rare and interesting ones, and within another ten years, we should have sequenced pretty much every organism that we know about on earth.

But then, once you've got a representative genome for each organism, you then want multiple ones for each because, of course, every individual is different. 16 years ago, we had one representative human genome sequenced, now organisations are sequencing the genes of hundreds of thousands of individual people to generate information for study. The amount of information out there now is phenomenal. Increasingly you can't be just a “bench scientist” or an information analyst, you have to be both in order to understand all this. We may not be able to say what discoveries this will lead to next, but we certainly can say that the opportunities for discovery have exponentially expanded.

We’re now at the stage where geneticists understand both the power of big data, but also the limitations. There was a point where a lot of people thought they would make much faster progress in their research by generating all the data that was possible. However, while the technology can produce the data, and the computational tools can extract a signal from the noise, they can’t understand it for you. With so much information, you need to know where to look, so there’s still a very important place for hypothesis–driven science. The nature of the science is changing constantly due to the amount of data we have, but the role of the scientist in knowing where to look, and what questions to ask, is more important than ever.