Venter and Topol on the True Revolution in Medicine

A Better Way of Making Influenza Vaccine

Dr. Topol: [Let's continue with] synthetic biology, which is another area that you've been leading. When we were together at the WIRED for Health program in October, you were talking about making vaccines and about the way we now make flu vs the way we'll make them in the future. Can you give us a little snippet about that?

Dr. Venter: Take H1N1; by the time there was a vaccine available even for healthcare workers, the pandemic peak had passed. We have a very slow response for making flu vaccine. If the H1N1 pandemic had been as bad as people had predicted, we would have been in very deep trouble in the world. It would have been much more like the movie Contagion than it ended up being. We're looking for new ways to make the vaccine quickly. We now have it down to less than 12 hours by simply making the virus synthetically using synthetic DNA. Biomedical Advanced Research and Development Authority (BARDA) at NIH sends us a flu virus test sequence in an email. After that, we have 12 hours to make it, and then we get that to Novartis to take to its cell culture facility for producing flu vaccine in North Carolina, which makes the current practice of using 9 billion chicken eggs each year to make flu vaccine seem really archaic.

Dr. Topol: It's amazing, isn't it? It sounds like a much better solution. When could that get rolling?

Dr. Venter: It's basically waiting for FDA approval. We're ready for a pandemic, and that's the good news. We're trying to get approval to use this method with the annual influenza vaccine. The way the flu vaccine is chosen each year is, again, a pretty archaic process. It doesn't use molecular information, doesn't use sequence information. We're part of a group that just published the 10,000th flu genome. We're part of a group that's tracking the emergence of the flu virus around the world. We're developing algorithms to actually predict the changes going forward based on what we've seen, but synthetically we can have on the shelf a vaccine against every imaginable flu strain that you just pull down and expand if needed.

In fact, it's going to get even more exciting because we're building what we're calling a digital biological converter, being that digital information and DNA information are now interchangeable. So, as BARDA sends us an email of the pandemic sequence, we're trying to build devices that allow us to use electromagnetic waves to send a new vaccine around the world in less than a second. You just need one of these converters to download it. In the future, people will be able to download protein drugs. For example, if you have diabetes, you could download insulin from the Internet to your home. You'll also be able to download vaccines.

Twitter and Other "Fun" Stuff

Dr. Topol: Now we're really getting into the digital medical revolution. Let's get into some fun stuff, like Twitter. You're on that occasionally. What do you think of Twitter?

Dr. Venter: I think it's a good way to get information out quickly. Like anything on the Internet, the joke is that if you had an infinite number of monkeys and an infinite number of typewriters, you'd get all the great works of literature reproduced. I would say that the Internet proves that that's totally false. We don't get better and better literature out of it; we get worse and worse. But Twitter is a very effective way of getting information out quickly and getting responses. Quite often I can find things on Twitter before any of the news outlets have it. It's a great way for communicating to the scientific community. People think of it as the short stretch, but you can attach an awful lot of information to it.

Dr. Topol: No question.

Dr. Venter: I'm finding it very useful.

Dr. Topol: You're a biker; have you been on any trips lately?

Dr. Venter: I haven't had time for any long ones, but I had a very nice trip yesterday afternoon in an antique BMW with a sidecar.

Dr. Topol: Sounds pretty good. What about an electric car?

Dr. Venter: I came here today in a Tesla.

Dr. Topol: The roadster or the S?

Dr. Venter: The new S car.

Dr. Topol: What do you think of that?

Dr. Venter: It's actually going to change transportation. I had a Roadster before. That was more like a fancy go-kart. Tall people like you have trouble getting in and out of those. With the S car, there are no knobs or buttons. It's all touchscreen. It's just fantastic. Once people try it, they won't want to go back to other kinds of transportation.

In fact, we get software upgrades while the car is sitting in the garage because it's attached to the Internet all the time, even while you're driving. There was actually a problem with the car, so a technician in the Bay Area logged on to my car and repaired it while it was sitting in the garage overnight. As soon as we can do that with people we'll be all set.

Funding Science: Spending It Badly?

Dr. Topol: As you know, we're kind of in peril with research in this country, with things like sequestration and whatnot. Where do you see the funding going? The opportunities, perhaps you'd agree, are more exciting than ever. Then we have funding issues. Where are we going to go with that?

Dr. Venter: We're not short on science funding in this country. We have incredible amounts of science funding. We just don't spend it very well. Peer-review funding is risk-averse. We have a few agencies, like Defense Advanced Research Projects Agency(DARPA), that go out on a limb and take risks. NIH is just the opposite. Nobel laureate Hamilton O. Smith, in 1994, submitted a grant to NIH with our new method to sequence the first genome in history. It was turned down with extreme prejudice, but as soon as we sequenced the first genome and published it, we could get all the funding in the world. So once it's proven and already established, you can get funding for it. You can't get funding for new ideas very easily. People like you were very successful and used last year's grant to fund the next thing because you're ahead of the game, but investigators with single grants can't do that. We need to find a way to become risk-liking. I just don't know whether the government can do that. They may have to contract independent parties, much as DARPA does. They bring in academicians for short periods of time to do the funding. We're not short on money; we just spend it really badly, and this has been a long-time problem.

Dr. Topol: I know. Can we have a peer review of the peer-review system? How do we get this thing shaken up to be better?

Dr. Venter: The academics might not like it, but peer review is like the prisoners running the prison. They're not going to vote for change. Universities like this system because it helps support the universities. We have to change it so that 25%, 30%, 40% of the money is set aside for true risk research with independent parties to do that. That's going to disrupt a lot of things. I argue that the American public should be outraged that there's not 10 times to 100 times more breakthroughs in medicine every year over what we're getting, particularly for the money that's being spent.

San Diego: A Hub for Progress

Dr. Topol: I couldn't agree with you more about that. Now, speaking of progress, San Diego is a hub partly because you're here. I know that you even got Bill Clinton to say some nice things about San Diego, but what are your thoughts about the future of digital-world genomics in this San Diego hub? You're obviously having a big impact here.

Dr. Venter: One of the reasons we came back here after going to school here a very long time ago, in the early 1970s, is that the spirit of cooperation here is greater than anywhere else. In Washington, DC, there are a lot of great universities and institutions. But they don't talk to each other. I was at NIH for 9 years. People on one floor don't talk to people on the other floor. It's really isolated and it's a different kind of culture. Maybe it's the sunshine here and the ocean, and people get outside and interact; whatever it is, we can get a lot more done here because of cooperation and collaboration than you can in other environments in this country.

Dr. Topol: We've got the life science industry here and IT wireless and so many academic institutions and institutes. It's really extraordinary, and it's great having you here to give it an extra jolt -- that's for sure.

Dr. Venter: It's a great place. There's such a talent pool here. We don't have any trouble hiring top people all the time, and that makes a big difference. You can't do that in an isolated center.

Life at the Speed of Light

Dr. Topol: Well, you had a great book, A Life Decoded.^[2] I learned a lot about you from that book. Are you going to do another book?

Dr. Venter: I have one coming out in October.

Dr. Topol: Tell us about that.

Dr. Venter: It's called Life at the Speed of Light. It really talks about what we've done in synthetic biology, basically within my lifetime and starting 2 years before I was born in 1946. In 1944 was when Oswald Avery's experiment was done to prove that DNA was the genetic material.^[3] Even the community was slow to accept that. People wanted proteins to be the genetic material. So, basically in a single lifetime we've gone from very screwed-up notions of what genetics was thought to be, to understanding with Watson and Crick in 1953 the structure of DNA,^[4] to Marshall Nirenberg^[5] working out the genetic code, and how we went on from this 4-letter code to making all the proteins, to understanding all of these structures. And now we can send things through the digital world -- the interconversion of the two. That's what we did by making the complete genome chemically from bacteria and transplanting it and getting a new species. We proved that, in fact, DNA contains all the information necessary for life.

People think that epigenetics is some separate field from genetics, but epigenetics is still genetics. It still starts with that 4-letter code and creates everything in the cell. All of this happened within the past 70 years. That's pretty extraordinary. I think people lose sight of that. These aren't ancient findings. A hundred years ago people had no idea what genetic material was. We're just at the start of the true revolution in medicine now that we can read it. We can read it on individuals. We can understand it. We can relate it back to physiology if we can define a human phenotype on a broad scale. In the next few decades, all the questions that we've had about nature and nurture will be answerable for the first time in history. That has to change how we do diagnostics, how we do preventive medicine, and how we treat diseases -- knowing who can really benefit from what pharmaceutical. I think it's going to be the most exciting era if we do it intelligently.

Dr. Topol: Undoubtedly you will have a profound impact, and in just a matter of time, right?

Dr. Venter: That's just it. Things do take a lot of time to get accepted in the community.

Conclusion

Dr. Topol: It has been fantastic watching the impact that you and all of your colleagues have had. Thanks so much for sitting down with us on Medscape One-on-One. We'll be following your work with interest, and I'll be looking forward to seeing your book this fall.