The future of fingerprinting

Kat -   Now, the big story this month has been Angelina Jolie - genetics finally hitting the headlines.  She announced in a very moving article in the New York Times that she'd had a double mastectomy after learning that she had an apparently 87 per cent chance of developing breast cancer and this is because she carries a faulty BRCA1 gene and she does seem to have some family history of this.  I mean, it's quite a big decision to make, isn't it?  

Matt -   Yeah, absolutely.  I mean, as we know, her mother died of ovarian cancer and since then we've learned that her mother's sister, so her aunt, also unfortunately died of cancer.  So, it was obviously a very, very difficult decision for her in having that test and being put to high risk of developing breast cancer and ovarian cancer.  

Kat -   And the figure of 87 per cent, it seems remarkably precise, but I'm guessing there's some kind of computer programme that they've put all sorts of things into.  

Matt -   Yes, absolutely.  I mean, the BRCA11 mutation can increase the lifetime risk for women between 60 and 90 per cent which is quite a broad range.  

Kat -   That's for breast cancer, isn't it?  

Matt -   For breast cancer, yes and 40 to 60 per cent for ovarian cancer.  The 87 per cent figure comes from sciences working out lots of other different risk factors, so other genetic factors, the particular type of mutation that a person might have - age, environment, and lifestyle factors.  So, all these stuff gets thrown into a computer programme and out comes the number of 8 per cent and it sounds so precise, but it's probably not quite as accurate as it first seems.  

Kat -   I mean, but it is basically very high.  I think the average risk for women in the general population is about a 12 per cent chance in your lifetime.  So that's, if there are 100 women, 12 of them would get breast cancer at some point whereas this is, we're talking about even up to 80 to 90 per cent risk.  So, it is very significant, but there's a wider context here as well because currently, the BRCA1 and BRCA2 - these are breast and ovarian cancer genes - there's a big patent case going on in the US right now and we should be hopefully quite soon expecting an answer on this.  What is this case about that?  

Matt -   Yes, it's a really interesting one.  So, there's a company called Myriad Genetics who developed a diagnostic test and this tests for the mutations in BRCA1 and the BRCA2 genes which we know increase the risk of breast and ovarian cancer.  Now, they own a patent that was granted in the US for that test and what's interesting is that patent also covers the whole gene as well.  So, rather than just the test they can sell, they actually own a patent on the gene which can actually prevent people from working on the gene and developing their own tests.  So, they have a bit of a monopoly on this testing for these mutations.  Now, to gain a patent, you have to show that there has been some invention and you could argue and perhaps quite sensibly that a gene is not an invention.  It's come about by an evolutionary process.  It happens in nature.  

Kat -   And also, everyone's genes are slightly different too.  

Matt -   Exactly, yes.  So, how can you pattern a gene?  They claim this when they take out of someone's cells and they break it up and put into their genetic test, that creates a new entity, and that's their invention, and that's where they're patent lies.  But it's a bit of a grey area.  

Kat -   It's a very interesting issue because it is basically who owns your genes on the right to test for them because the BRCA1 and 2 tests are very, very expensive.  They're several thousand dollars, I understand, whereas now, the cost of genetic sequencing and genetic testing should be coming right down.  I think it could be a landmark case.

Matt - Absolutely.  I mean, because they own this monopoly, they can charge vast sums of money and that could prevent some women having access to the test for something that could be done for maybe a couple of hundred dollars.  And we'd also wouldn't want researchers who are looking at alternative ways, cheaper ways, perhaps there's new discoveries to be made on the BRCA1 mutation.  So, it's really important that doesn't happen.

An international team led by researchers at the Universities of Manchester and Newcastle have tracked down a gene fault linked to a type of heart defect in newborn babies known as "a hole in the heart". Writing in the journal Nature Genetics, the researchers scanned through 500,000 genetic variations in more than 2,000 patients born with congenital heart defects, and compared them with the same variations in more than 5,000 healthy people. They discovered that a particular variation near a gene called Msx1 was found in  around ten per cent of people born with a hole in the heart - a condition known as an atrial septal defect, which is one of the most common forms of congenital heart disease. It's not exactly clear whether Msx1 itself is responsible, but the team are now trying to figure that out.

Kat - But now it's time to hear more from the Genetics Society Spring Meeting. Perhaps the most futuristic talk came from Professor Sir John Burn, from the University of Newcastle, who talked about the latest developments in bringing gene technology directly to patients' bedsides - something that could revolutionise medical care in the not-too-distant future. It turns out that a handheld gene scanning device - not too dissimilar from Mr Spock's fictional tricorder - may not be too far away.  I asked him explain more about the exciting developments in technology, and what the future of genetic analysis might look like.

John - We're seeing, I think, a diversity of delivery.  There's been a lot of emphasis on whole genome sequencing and looking at all your genes in one go and that's clearly part of the story and the machinery for that is getting even more powerful but also, point of care testing.  There are a lot of situations - infection diagnosis, pharmacogenetics in people being prescribed drugs where you might just want to do a test here and now, and a very specific test targeted to a particular purpose.

Kat -   So, just a couple of genes, not the whole lot.

John -   Yeah, exactly and it takes a lot of issues about protecting your data and so on.  I mean, you could reliably give that to a much more diverse populations of clinicians like pharmacists and GPs because they're not asking for genome questions.  They're just asking the question they need an answer to for this particular circumstances.  I'm currently in a debate and I'm obviously bias because the company I'm part of has now got a very powerful point of care technology which is using nanowires.  On that basis, you end up testing a yes, no sort of question - is this or is this not present?  And then from there, we're moving on to sequence short runs of DNA and we think we can actually take that to the next level, and actually sequence whole stretches of DNA by using nano channels lined with nano wires.  So, it's actually very exciting because it means we actually can really now see the prospect in our gadget - the first of which arrive next month - of doing sort of 20 tests for 20 pounds in 20 minutes, which changes the whole game in terms of point of care testing.

Kat -   So, just to get an idea of this kind of technology, what sort of scale are we talking about - the size of a microwave, the size of a phone?  What's the future going to look like for these kind of point of care genetic tests?

John -   There are lots of machines around and they vary in size and complexity.  The one that we're working with, QuantumDX, we have our first machine that looks like a big old fashioned computer or a microwave is a good comparison.  But that's actually because we're still playing with the constituents.  By the end of this year, we'll have something that will be with a screen about the size of an iPad that's easily portable.

Kat -   So, a laptop kind of size.

John -   Yeah, sort of a laptop size but a bit deeper.  But in fact, our intention is to end up with what you might call the sort of overinflated iPhone which would actually be able to take a cassette plugged in the top and the cassette carries all of the necessary DNA extraction amplification and testing chemicals.  So, the same little machine will give you a test for TB or a test for drug sensitivity, or test a tumour sample, depending on what the question is you need answered.  And that's actually within sight in the next couple of years.

Kat -   Because that sounds like something science fiction.  You put a bit of someone's blood in this little device and it tells you, they need this drug and not that drug, they've got this infection, not that infection.  Does it kind of stagger you when you look back over your career that we've got to this point so fast?

John -   Absolutely.  I mean yes, in fact, we've talked to the people in America who are trying to make the tricorder which was of course what Captain Kirk used or Mr Spock used.  In fact, Captain Kirk used captain's log on a pad, so the name iPad actually was derived from that era.  And yes, I think the tricorder is getting closer.  I mean, the idea that you can spit in the end of the machine and for next or nothing in no time, know the DNA result was unimaginable.  I mean, when I started genetics, we can do any DNA tests.  I actually pre-date the DNA era which is quite scary.

So, I think we've got to keep changing our perception.  DNA was sort of a hypothetical concept when I started then it became something very few people could do, then it became dramatically more accessible but still, big technology driven by people who are very clever and not part of the common sort of routine clinical practice.  What we're now moving into is that period where it sort of disappears in a way.  Our iPhones and our smartphones have got enormously powerful computers, but we don't think of them as enormously powerful computers - it's just a phone. And I think sequencing in DNA will just be a test.  It will just be a part of our routine practice and I think that's where we're at now.  I think that's where we're at now.  I think it's going to become completely ubiquitous at certainly in terms of these simple tests.  And potentially of course, if we get 100,000 genome project to work in our medical records, we'll carry a whole host of the useful information in a few years' time that will help us get more personalised care.

Kat -   And where do you see are the really potential big wins that could come quite quickly from getting more genome sequencing technology available in the clinic in the UK?

John -   I think that we shouldn't be underestimating the logistical challenge of understanding complex traits because there's so much we don't know about the genome in terms of noncoding RNAs, epigenetics and so on.  There are genes being switched on and off by environmental factors.  So, I want to concentrate on areas for example with hereditary breast cancer, hereditary bowel cancer, familial hypercholesterolemia, where we've got those three conditions in England or in the UK.  There are about a third of a million people carrying genes, high penetrance genes, and in each case, we have a very effective intervention that could reduce or avoid them developing cancer.  The one I'm obviously most interested in is colon cancer because we've shown that 2 aspirins a day will half - you're a cancer risk if you've got hereditary cancer [genes] and that's a very cheap treatment.  But there are 60,000 people out there in Britain based on the best evidence and we only know 6,000 of them.  So, we've got to find those people and that's where I think there's going to be a major development in the near future.  But once we proved it worked for them where the ethics is clear, the research is encouraged by the patient group, we can roll it out into a bigger population. And 5 years from now, I think all genome sequencing is a sort of fairly routine thing that if you turn up with a medical problem.  It's entirely within vision.

Kat - That was John Burn, from the University of Newcastle and the company QuantuMDX