Welcome to the future: Discovery helping DNA mapping move from sci-fi to reality

There could hardly be a more appropriate day for this interview. Today is the 69th birthday of J. Craig Venter, the American scientist who, in the year 2000, stunned the world by unveiling the first ever sequencing of the human genome – a project that took 15 years and $100m. The implications of the discovery many believed impossible can hardly be overstated – presidents clamoured to have their pictures taken with Venter and magazines honoured him with more “man of the year” awards that he could probably remember. Fifteen years later, Venter’s discovery is finally going mainstream. South Africa’s Discovery Health has become the first company to sign a bulk DNA analysis deal with Venter’s well-funded young company Human Longevity Inc (HLI). The business needs thousands of DNA samples to create a database large enough to on-sell to researchers like those in pharmaceutical companies, for whom the data is more precious than gold. For its part, health insurer Discovery would love to know the kind of information about its 4m clients that only DNA mapping can provide. And, not surprisingly, many of Discoveries clients are keen to acquire information about their own DNA at a heavily subsidized price. From January, South Africans will be able to sign up for a personalised DNA map, at $250 a pop and a simple saliva swab. The man who engineered the groundbreaking deal, Discovery’s Jonny Broomberg, took us through the way it works, what it means and why this revolutionary innovation by the Johannesburg-based business has massive implications. Fascinating, even for non-scientists. – Alec Hogg

Johnny Broomberg from Discovery is with us for this special podcast today. Discovery has struck a deal with J. Craig Venter. No South African connection.

None as far as he knows, although he thinks maybe somewhere back in the day.

Tell us about him.

Alec, he’s a world famous genetic scientist. He’s the man who’s known as having led the team that decoded the first human genome. It was his own genome, actually. It took them 15 years, cost $100m, and he raced the U.S. Government, which had a consortium trying to do the same thing. He’s known as having gotten their first with his team but I think they had an officially brokered deal that resulted in them officially being regarded as doing it at the same time.

Why is this so important – the human genome?

Well, it really is the clue to a huge amount of information about what makes us who we are. From ancestry (where we come from), our traits such as hair colour and eye colour and must more importantly, issues like what kind of diseases we’re at risk for and for example, what kind of exercise or nutrition might work for you or for me. All of this coded in our genetic map and we’re now at a point where the technology’s cheap enough to allow it to be done on everybody. When Craig Venter’s team finished the first one, (which as I said, took 15 years and cost $100m to do), today in South Africa we’re offering it to our clients for $250.00 per person. Think of $100m and $250.00. It’s about the advanced of technology.

It’s extraordinary. Maybe go back a little bit. I saw a play in London, called Photograph 51. I don’t know if you’ve come across it.

I have not.

It’s about the early days of the discovery of DNA in the 50’s. Why were the scientists so obsessed about finding out about DNA? Explain as though to someone who’s never heard of the three letters before.

DNA codes all the proteins that make up our body and so it is really, ultimately, the map of everything that makes each person who they are and makes humans human. It is the ultimate ‘bible’ of who we are, where we came from, and what each of us will become.

We’re all unique, too.

We’re all unique. We have a lot in common. People don’t know that all humans in fact, are 99.9 percent alike in their DNA in the human genome, but the 0.01 percent difference obviously creates a huge amount of what looks to be very different. It’s very interesting that we actually have a huge amount in common as well as these unique differences.

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Where are we not in common? That’s clearly, where you’re focusing, to try to help improve health.

Exactly. Firstly, the short answer is that we don’t even know today, exactly where we’re not in common but we do know certain things. In the genome test that Discovery will be offering our clients today, the state of the art would allow the scientists to report on about 1700 genetic mutations that are known from the evidence to alter your risk of, for example, certain diseases. Cancer would be a common one – many different cancers. Dementia, pre-senile dementia, Alzheimer’s and various other disorders. Bear in mind that we’re right at the beginning of this so as the months go by and more and more genetic data is collated, the scientists will be able to understand that this kind of mutation creates this proportionate increased risk in that condition. We’re right at the beginning of that journey.

If you have parents who have died of a heart attack, cancer, or some other dread disease; by knowing for sure that you have the same traits/genetic makeup, you can prevent the same thing happening to you.

Yes. One has to be careful, given the state of science today, not to overpromise but certainly, there are some genes today. The one that Angelina Jolie made famous is the BRCA gene. If you have a mutation in that gene and a positive family history, scientist would tell you that as a woman, you have a 90 percent lifetime risk of developing breast cancer.

That’s why she had a double mastectomy – on science.

Yes, on hard science. There aren’t that many genes where the science is that definitive but I would predict that within a few years, more and more would become that definitive. The good news about having the test done now is that you only ever have to have it done once. Then your map is available in the database and as knew information emerges, we can provide our clients with an updated reported that says ‘there’s new evidence that your mutations mean you should eat this kind of food as opposed to that kind of food’.

You can therefore, either prove or disprove Tim Noakes once and for all.

Well, what I’ve been saying about this debate is I think what it will turn out to be, is an absurd debate where we’re thinking ‘one size fits all’ of any kind of diet. I think we’re moving into an era, both in wellness and in medicine, of highly personalised approaches. Alec, the Banting diet may work well for you, but not for me so we won’t be ‘this diet versus that’ for everybody. Another very interesting field that’s emerging as we can access people’s genomes more cheaply, is a field called pharmacogenomics. This is the science, which tells us that your genetic makeup will make you, for example, highly allergic to a particular medication. There are already a few medications where that can be predicted, or you would be more sensitive. One of the common ones is Warfarin. Thousands of people take the blood thinner.

In the genome, you can detect whether some people would be more or less sensitive to that drug and therefore, need a lower dose.

We know that in Johannesburg at the moment, we haven’t had rain this spring and the pollen count has gone through the roof. I have red, bloodshot eyes and I can’t sleep at night. I’m completely clogged up as a consequence. I’m sure thousands of other people are having the same experiences. Is there anything in the genome that would be able to show you whether you have a predisposition towards pollen allergies, etcetera?

I don’t know the answer to that, but it’s quite possible that there will and if not today, then in future. Just to make the story a little bit more complicated, what the new genetic technology can also do very cheaply these days is analyse the genetic makeup of the bacteria that live in our intestines and on our skin. Scientists are starting to show that the DNA of the bacteria interact with our own DNA. Ultimately, I think the personalised approach would say ‘you have this kind of gut bacteria, this kind of DNA that you inherited from your parents and that means we need to treat you in this way, or prevent cancer by doing that’ etcetera.

Is there a possibility that you could go into the DNA and change it if, for instance, there’s a kink somewhere in the system, which says ‘you are predisposed to getting colon cancer’ – that you could adjust that?

It’s funny that you should ask because just in the last two years, some scientist in the U.S. and Europe have perfected that technology. They call it CRISPR. It’s a gene editing technique, which has been perfected in the laboratory. It’s very precise. Go in, slice out the wrong part of the gene, and substitute with a correction. It’s leading to enormous debate at the moment at an ethical and government policy level. UNESCO recently published a report, calling for a moratorium on gene editing until there can be proper rules and regulations around it. You can imagine on the one side how wonderful that technology would be for treating genetic syndromes. On the other hand, you can imagine the kind of Frankenstein fear of creating new species, etcetera via the gene splicing technology but the technology is available.

We don’t know what we don’t know at this point.

Exactly.

However, on the other side, lots of research is telling us that children born today will live until at least 120 and those who are alive today can have their lives extended by these types of scientific discoveries. Given that as background, it’s strange to me that Discovery is the only company so far that has done something like this with Venter.

Yes. We like to be ‘first movers’ and be innovative. No doubt, other insurers will go down this road in due course. For us, the excitement here is (1) it’s a completely voluntary offer. No client needs to do this. We identified Craig Venter’s business at an early stage in their development where they are very keen on large sample groups. We’re unique in that we not only have access to a large group of clients, but we also have a very rich set of data on those clients from their medical claims. Since most of them are in Vitality, we have a huge amount of biometric data: body weight, BMI, and exercise patterns. When you add all of that up together and you put it into an anonymised database, it’s hugely powerful for research. One of our areas of great interest is to make that database available to local researchers (and global), but local certainly, who could look at things like exercise, nutrition, and what genetic data can tell us about how people will respond to different forms of exercise or diet.

Ultimately, Vitality could become really, highly personalised as opposed to today’s ‘one size fits all’ type of recommendation.

Presumably, the African, European, Middle Eastern, and all the various types of genetics that we have in this country in the cosmopolitan nature of our society would also be pretty useful from a global perspective.

Extremely. Most of the genome databases around the world today are Northern European. They come either from Scandinavian countries, or from the U.S., so there’s very little African genetic material in the databases. As you’re rightly hinting, there are very important variations that link to disease patterns. Let me give you one interesting example. When you look at the Middle East today, countries there have huge burdens of conditions like diabetes and this all lies in the genetic origins. These are the native populations of that region, which evolved to be highly adaptable to desert climates – very efficient bodies at storing fat and being able to survive long periods of drought and lack of food. That DNA is hundreds of thousands of years old. It takes very long to evolve but in a much faster period than that, the diet in those regions has moved to a western diet. Lo and behold, an explosion of obesity and diabetes because the body is adapted for very different kinds of food so these things are very important.

Just to get back to the relationship that you have with Craig Venter. You did bring him to South Africa recently for your Vitality summit.

Actually, he wasn’t in the country. We had him in via Live Link (video link).

Was that as part of the deal – that you’re doing this deal with him on the one side?

No. It was just a goodwill thing. We had been interacting with him and his team extensively over more or less nine months. We had reached the key terms of the deal at that point and we asked whether he’d be willing to do this, and he was willing to do so.

Why him?

It’s not really him as much as the business that he’s set up. Many of the competitors today fall into two camps. (1) Academic institutions using government-based research funding and therefore, are not really able to provide the genome sequencing at a price that would be affordable for South Africans. This a company – Human Longevity (Craig Venter’s company), which has raised capital that is very hungry for a database and is doing deals with the likes of us, pharmaceutical companies, and others to populate its database and is willing to heavily subsidise the cost of that.

You say ‘raise capital’. How much has he pulled in so far?

I don’t have the full details. It’s confidential. However, I do know they had a very successful initial capital raising and I believe they’re out now on a very successful second round.

It’s hundreds of millions, though. It’s not just a few Dollars.

HLI (as we call it) has the world’s largest genome sequencing laboratory as we speak so to have dozens of these very high-powered machines… Remember, it’s 15 years for the first one so one machine in the laboratory today can do eight at a time and it takes 60 hours, and they have dozens of these machines so they can process thousands every month and are building up this database very quickly.

They’re going to be subsidising the analysis of South Africans.

Yes.

Why would they do that?

Their business model is to build an anonymised database, so each one of our clients who is interested in this will sign a very clear consent. That consent will include, among other things that their data can be stored in the HLI database – anonymised, with no link back to their name or any other way of identifying them – and that HLI will have the right to commercialise that database.

How would they do that?

Pharmaceutical companies today who are doing Research & Development on new compounds: the hottest data they can get their hands on is genome data because that is where the new pharmaceutical research is going. HLI are betting that pharmaceutical companies will pay large amounts of money in annual license fees, to access the database so that is mainly how they would commercialise it.

John, it’s kind of a ‘win-win’ all the way. South Africans can get their genetic makeup analysed for them at a very cheap price because you are consolidating them. Once you see that, you can perhaps advise them individually on what to do and what not to do. This will save Discovery (or the whole pot, if you like) money and time and Craig Venter is quite happy to subsidise party of this analysis because he’ll be able to sell it onto pharmaceutical companies who’ll be able to make better drugs.

Correct. I think there’s a third, very important leg to it Alec, which is that what we’ll be doing here is creating a database of African DNA, which we also have the right to make available at no cost should we choose to, to local universities for example. There’s a very interesting public project called H3A. It’s an Africa-wide human genome project, trying to build a database of African genomes. We’re delighted that we could hopefully collaborate with them and with other parties to say, “Look, here’s a growing database of African material. It’s curated. It’s stored. You have free access to that, courtesy of our clients, ourselves, and HLI”. That’s creating a real asset for South Africa as well.

What would they use that for?

Again, local research. There may be local consortium, which wants to do research on the link between diet and disease, and the link between genetic makeup of certain people and certain conditions. To build a database like that costs tens to hundreds of millions of Dollars. Here, in a sense, we’re creating that and providing it at no cost to local researchers.

What is it about Discovery – about your own DNA in the company – that you would be the first company in the world to do a deal like this with the man who discovered the human genome (not to put it into a too exaggerated form)? Why is you guys? What makes you tick?

It’s a good question, and not an easy one to answer. There are a few factors. (1) We’re continually pushing ourselves every single day, to identify new opportunities to add value to our clients. That means we’re travelling. We’re at conferences. We’re using networks. This particular example: a very good old friend of mine from my days at Oxford who told me that he was heading over to meet Craig Venter because he was looking at an investment. I said, “Won’t you please mention us?” He knows Discovery well. He mentioned it. He called me afterwards to say, “Craig is extremely keen to meet”, so I jumped on a plane with a colleague and the rest is history. We’re hungry for these kinds of things and we’re investing time and effort to look out for them and bring them to our clients.

What makes you hungry, though? What’s your incentive?

At the end of the day, we’ve developed a business model that is now being globally recognised, which says that if you innovate and create the right kind of products you can add tremendous value to your clients. You can create change that adds value to society at large and you can build a great business for your shareholders – all at the same time. The Discovery Health products, the life insurance, and our recent entry into car and household insurance are all examples of changing behaviour, and improving the lives of customers. Therefore, impacting positively, more broadly but building a great business at the same time.

I remember reading the various quadrants that human beings go through when they change their minds. Firstly, utter rejection, then resistance, then perhaps some compliance and only thereafter, do they get excited about the concept and commit to it. A lot of what you’re doing has to be going through those four quadrants. For instance, with Discovery Insure on motor vehicles. Drive better and you’ll make money or you’ll save money on your insurance policy. It takes a little while though, for society to click to this. How long do you think it will take for this particular project – this ‘please can I have my DNA assessed’ – to catch on amongst your client base?

To be very honest, I don’t think I could answer that in any kind of scientific way. We’re ambitious for this. We think that we’d love to see 100,000 clients over the next couple of years. That’s’ not a huge proportion of our total client base, but we’re very ambitious for it. On the other hand, we know that people have different levels of comfort with this, Alec. I’ve spoken to many colleagues and friends out there. When they hear about this they say, “I’m keen. When can I do this?” On the other hand, I’ve spoken to some people who say, “I don’t want to know anything about my future about which, I can take no action, so please don’t tell me I have a higher than average risk of Alzheimer’s because today, there’s not much I can do about it”. People are going to have different attitudes. We don’t want to push this too hard, at anybody.

I do believe that very quickly, within the next few years as the science emerges and more is written in the popular media, this will become more in demand. I would expect that over time – five or ten years from today – this kind of test will be as common as having cholesterol or your blood sugar checked. That’s the direction in which, we’re heading.

Possibly costing even less than $250, as well.

I would say, “Almost certainly”. As processing power increases, these things will become cheaper. It’s Moore’s Law – just another example of that.

Within the South African context – for your clients – how do they go about getting their DNA tested? What part of their body do they have to give you?

That’s extremely simple. The plan is a simple saliva swab. It’s very easy. It can be self-administered although for quality purposes, our plan is to have it professionally administered by a nurse. This will go live in January 2016. We’re very busy on all the logistics right now. Our clients will be able to order the test on our website. We will encourage them to fill in a very simple family history tool at the beginning of that journey. Family history is as important as the genome data and the two together are really, the powerful recipe. Once they’ve done that, we will arrange with clients to either send a nurse to home or work, or clients will be able to pop in to one of the network pharmacy clinics and this thing will take half-a-minute. Just a saliva swab in your mouth, into a kit, and that will be sent to San Diego for processing.

How long does it take?

We’re not exactly sure yet. I think the entire turnaround time will probably be two to four weeks, with transport and the sequencing in the laboratory. Then the reporting is very important and we also have to make sure that when the report comes back, if there are any significant findings that these are shared with our clients via their GP or a genetic counsellor. If there’s something significant, you certainly don’t want to mail a report via email, to a consumer who doesn’t know how to read a genetic report.

A genetic counsellor.

It’s a well-recognised profession. We don’t have enough in our country. We have way too few and we are the beginning of some conversations with the universities about whether Discovery could support growing the number of genetic counsellors. This is a university degree with Honours in genetics and then training in counselling so that you could sit with me if you’re a counsellor and talk me through what I could learn from my report, what this means, and whom I should go and see from a medical point of view, etcetera. It’s a person who understands the science of genetics and can interpret them in ways that are understandable by laypeople.

Your GP will presumably know a lot more than you would about the implications of all of this, but what kind of training do they have?

They don’t have much at all and I think they’d be the first to admit it. As the science moves at the speed of light really, almost anybody is out of data all the time. I think this will stimulate a need for GP’s, physicians, and other specialists to become knowledgeable. For complex conditions, there will always be real specialists in genetics. We’re reading a lot of literature now from the U.S. and others where these gene tests are being brought into the clinic. What they’re finding is that the GP’s are quite capable of reading up, learning, going to seminars, and being very competent at helping their patients interpret these reports. Quite a lot of the scare tactics, which are ‘we shouldn’t be doing this because no-one will know how to interpret it’ is actually, a false alarm.

That’s pretty obvious. You could build an app, which would be able to give you at least some kind of insight into what it is.

Exactly.

Once I pay my $250 or about R3000 in South African terms and have the swab taken, then it goes over to the U.S. What happens with the results? Do I get them? Are they only accessible through a genetic counsellor or a GP?

Alec, we’re working out the finer details as we speak, but there’s no doubt in our minds that any results, which have significant findings will have to come back to our clients via a health professional. The vast majority of reports will come back with no significant findings from a medical point of view, but with a lot of interesting information for you as a consumer. For example, where your ancestry comes from in the world, things like hair colour and where that comes from, and your eye colour, etcetera. There’s a lot of interesting (but not narrowly medical) information so there will be an app. People will be able to get their information on that. Updates will come via the app, but we are developing an algorithm that ensures that any significant report is channelled to you via a health professional.

What you’re saying is that within the big data, if stuff is exceptional – in other words, if I have a 95 percent chance of getting cancer – I need to know about it urgently, and that would be flagged in the results.

Yes. That would be flagged. The example you give is almost unheard of. There’s the BRCA gene which, with family history, you could develop that kind of certainty. Most others will be far less. There’ll be relative risk. You’ll have a 20 percent higher risk than the average member of the population, of developing colon cancer, for example. That’s not urgent, but it does mean you should be more alert and consider having colonoscopies perhaps more frequently than the average person would.

What about the longer-term consequences of this? Individuals are different. They shouldn’t all be paying the same rate of insurance cover as a consequence. The DNA results that come back: will you be able to price the risk accordingly?

It’s a very important question and that depends on two factors. One is the regulatory environment and the choices made my insurers. Let me give a bit of detail. In the U.K. and Europe today, there’s a moratorium on insurers using genetic data for pricing at all. In the U.S., it’s been banned by law. In South Africa today, there is not yet any regulation on this and so today, in terms of health insurance by law, no risks can be taken into account in setting premium. You would therefore have the same premium as a 90-year old with cancer/an 18-year old in the peak of health. Health insurance: no impact. Life insurance companies in South Africa today (even before the era of low-cost genomics) do ask new applicants ‘have you ever had a genetic test’ and if you answer ‘yes’, they may well ask you to provide them with results. As of today, I think it is unclear what life insurers will do with it.

This requires an important discussion with the regulators about what to do but many countries as I said, are moving towards saying ‘this cannot be used to discriminate against clients’.

Johnny Broomberg is the Chief Executive of Discovery Health