Dirk Knemeyer

The Digital Life #169: Genomics and Life Extension

Episode Summary

This week on The Digital Life is the third in our special series of episodes put together in conjunction with our friends at the GET Conference, on the cutting edge of research science and technology.

In this week’s episode we explore the topic of genomics and life extension, with interviews by Dirk Knemeyer with James Crowe of the Human Immunome Project and George Church of the Personal Genome Project.

Genomics and the science of life extension are inexorably tied together, whether we’re talking about slowing down or reversing the processes of aging to extend the human lifespan or future breakthroughs in gene therapy and organ replacement, which might eventually enable humans to have indefinite lifespans.

Jon F.: Welcome to Episode 169 of The Digital Life, a show about our insights into the future of design and technology. I’m your host Jon Follett.

This week on the podcast is the third in our special series of episodes put together in conjunction with our friends at the GET Conference, on the cutting edge of research science and technology.

In this week’s episode we’re exploring the topic of genomics and life extension, with some really fascinating interviews by Dirk Knemeyer with James Crowe of the Human Immunome Project and George Church of the Personal Genome Project.

Genomics and the science of life extension are inexorably tied together, whether we’re talking about slowing down or reversing the processes of aging to extend the human lifespan or future breakthroughs in gene therapy and organ replacement, which might eventually enable humans to have indefinite lifespans.

Let’s start with our interview with James Crowe of the Human Immunome Project.

James: I’m James Crowe. I’m the director of the Vanderbilt Vaccine Center in Nashville, Tennessee.

Dirk: Wonderful. Now, tell us a little bit about the work that you’re doing in Vanderbilt.

James: Well, we’re interested in the human immune system, in all of its complexity and contradictions. The immune system is built with the capacity to respond to any threat that comes in, and it’s fascinating to think how does a single system respond immediately to such a wide diversity of threats that we encounter.

Dirk: How is the immune system similar or different to the greater ecosystem? Is the immune system like a microcosm of how the greater ecosystem in our world works, or are they different? Some of the language you used when talking about the immune system took me to the ecosystem, is why I asked that.

James: Well, there are, I think you’re referring to the idea of self-organizing systems, so the threats that we face, often, the microbial threats, they themselves are communities of organisms. One of the fears, I think, that we all have is we face organisms that are constantly changing. They’re hyper-variable, so HIV changes in your body every day if you’re infected, or flu drifts in birds. So there’s these collections of organisms that are morphing continually. What we need is our own immune system to be able to do the same thing, to move and change and adapt very rapidly. The question is, what is the genetics and what is the structure underlying that rapid adaptability in our own system?

Dirk: So our own system is in fact rapidly adaptable and you’re trying to understand why and how?

James: Absolutely. The genome of people is relatively small in terms of numbers of genes. It’s about 10,000, well, it’s about 20,000 genes, but four orders of magnitude, and yet the microbial threats that we face are millions or billions. So we’ve got to figure out how to do that. The way the immune system has done it is to use modules that are combined in combinatorial fashion. So using sets of pieces and stringing them together has allowed us to make an incredible diversity of recognition elements.

Dirk: What is the nature of your research? Like, what are some of the research tools or techniques that you’re using to try and figure all this out?

James: Our concept is very simple and it spins out the human genome project. Technology was developed to synthesize DNA very rapidly and cheaply, and this continues to be evolving, because now we want the genome of everybody. This is going to evolve into clinical care. So these sequencers are getting faster and cheaper. In the immune system, the challenge is there’s not 20 or 25 thousand genes. Each person may have 10 to the ninth antibody genes in them or a similar number of T-cells. So the amount of sequencing that we’ll need to do to get the genes sequenced in a single person is enormous, and we want to get every sequence on the planet. We’re just upscaling the sequencing efforts, and essentially we take blood cells out of people and we get the antibody express chains as RNA and we sequence them.

Dirk: That’s very interesting. Now, there are some sort of big-picture world themes that we’re interested in, and I’m curious how you see your research fitting into that. Some of these will be obvious, but I’d like to hear them in your own words. In terms of the future of life extension, helping humans to live longer, how do you think your research can contribute to that?

James: Right, so, there’s definitely immune senescence, so you see at the end of life there is lower function of the immune system, and probably that in part is due as a degradation of your immune repertoire. You just lose clones and your repertoire gets much smaller. We’re taking sort of a broader view to survey the immune repertoire throughout life. We’re going to start at birth, in cord blood, and look all the way to 100 years of age, and look at the size and the complexity of the repertoire over that time. We hope, just by defining and describing the sequences that are present, that will give us clues immediately to these issues of immaturity during infancy, high competence during healthy adult life, and then immune senescence at the end of life.

Dirk: Excuse me, sorry. What about in terms of life enhancement, so not necessarily helping people to live longer, but to make the life they live a better life?

James: Well, there’s several ideas there. One, the most important biomedical advances of the twentieth century were really vaccines. Hundreds of millions of people died of infectious diseases prior to vaccines. Now, many of us get 30, 40 vaccines and we never know that we’re encountering these organisms silently and safely. So I think the principle enhancement that we’re going to get out of understanding immunity is even better vaccines, but we might extend the idea of vaccines beyond infectious diseases to things like cancer or neuro-degenerative disease and that sort of thing. And the opposite is true. Many diseases are due to the immune system gone awry, such as auto-immunity, rheumatoid arthritis or these types of diseases. If we can learn how to turn the knobs on the immune system and modulate these repertoires, so we get more of the good things we want and then we turn down the auto-reactive things that we don’t want, having that knowledge will help us to avoid infections, cancers and also auto-immunity.

Jon F.: Next, we’ll hear from George Church of the Personal Genome Project.
George: I’m George Church, professor of genetics at Harvard Medical School and founder of the Personal Genome Project.

Dirk: Excellent. Tell me about the work you’re doing at the Personal Genome Project.

George:It started about 11 years ago with a couple of articles, one in Scientific American and one in MSB, on the idea of changing a few things about human subjects research. In particular, that people should get access to their own data, that they should not think of themselves as so de-identified that they have no rights, so de-identified that no one can re-identify them because that was already a problem 11 years ago, data escape, and most importantly, encouraging sharing where all the subjects know what they’re getting into. They’re not signing some long document written in legalize. And then finally as a test bed for testing new technology and integrating all different kinds of data sets and getting lots of different studies that all could use the same cohort … All of these things that I just mentioned were unprecedented in 2005, and now they’re actually getting pretty close to standard practice, at least within our project.

Dirk: Given that it was unprecedented back then, what was the inspiration for you and the other leaders to make it happen in this way?

George: What happened was I had written a grant, and we got the grant. Center of Excellence in Genome Science is a big grant, and it had a component in it for ethical, legal, and social implications of the research. The NIH, even though they fully funded the grant, they were a little concerned about that. Actually, I didn’t know they were concerned until I went and got IRB approval for that part. The grant was to develop technology for next-gen sequencing, which we did, and we jumped from a goal of doing a million base pairs, basically, to an actuality of doing 5 whole human genomes at 6 billion base pairs each, so 30 billion. So we promised 1 million and we delivered 30 billion. As we got to the point where I thought we were serious about doing human genomes, I said, “Gee, we should get … I should learn more about human subjects research,” and that’s how it all started, basically. Also, to try to get the NIH convinced that we should be able to do the ethical, legal, and social implications section that we wrote, I got a law student and a bioethicist, Jeantine Lunshof, to help me write a white paper, which them became a bioethics paper in Nature and Genetics.

Dirk: Excellent. So there’s a few themes that we’re interested in in terms of-

George: Dan Vorhaus, sorry, was the law student.
Dirk: Oh great, thanks for mentioning Dan. There’s a few themes that we’re interested in for the future of humanity. I’m interested in how the work you’re doing you see fit into that. So human life extension and humans living significantly longer lives is something we’re interested in. How is the work you’re doing going to contribute to that?

George: So we have a number of projects in the lab focused on human gene therapy, and the Personal Genome Project has been providing us with cellular as well as information resources, so we have one of the few cell resources that induced pluripotent stem cells is freely available and comes along with all the documentation of a real person rather than something where you don’t really know what the induced pluripotent stem cells correspond to. Anyway, we’re using those and animal models to test a lot of stuff that’s in the literature pretty well established on longevity or aging reversal in small animals, and we’re testing them in larger animals and then in humans. The gene therapy is a really nice approach because you can go straight from hypothesis to therapy without going out some interminable and expensive search for a small molecule. We’ve got 45 gene therapies in the pipeline right now.

Dirk: Wow. Another thing that we think a lot about is life enhancement, and specifically where science and technology meet. We’re starting to see more concrete manifestations of cyborgs with things as simple as the legs of an Oscar Pistorius becoming much more sophisticated things going into the future. How might your work help fuel life enhancement through the synthesis of biology and technology?

George: Well, say that … Eliminating diseases like malaria, polio, and small pox. We’re almost done with the last two, but malaria’s a big deal. Gene drives is something our lab is working on. Lyme disease is another, along with Kevin Esvelt, who is now a professor at MIT Media Lab … That would be a huge enhancement. Getting off the planet, we’re all in danger of super-volcanoes and asteroids, so at least some of us need to get off, and that may require changes in radiation and osteoporosis, which may also be beneficial on Earth as well. Of course, aging reversal is extremely important since 90% of us are going to die of something that doesn’t affect 20-year-olds, and it’s a huge economic burden right now. We have this aging population, which are no longer working, although many of them would like to work, and their health care costs are skyrocketing. If you could just reverse their clock 20 years, they could go back to work and they could reduce their medical costs to society.

Dirk: Yeah, that makes a lot of sense. The final theme that we’re really interested in is the progress of artificial intelligence and how, over a longer time frame, that will manifest some form of artificial life. Are there ways in which you’re already imagining the work that you’re doing will inform and help lead what artificial life looks like in the future?

George: Absolutely. We’re developing bacteria that are fundamentally different, have a new genetic code unlike any natural or synthetic bacteria prior to this. But, more importantly on the intelligence front, I personally think that the most intelligent computer on the planet right now is the human being, and even though computers can do pretty well at non-human things like chess, and Go!, and Jeopardy!, they really can’t do very well at, say, recognizing the sight of somebody’s face moving in a crowd, which a 3-year-old can do. They can’t do what Einstein and Marie Curie did on a good day. So, I think if we continue to improve that, which I think we can and will, there’s going to be a lot of motivation to fight cognitive decline via cognitive enhancement. That will be considered highly medically-actionable. It’s very hard to develop preventative medicines or augmentation on a healthy individual because the FDA sees it as, “You’re only gonna hurt them.” It’s all about safety, and I fully agree. But, developing things that help with someone who’s got the early stages of Alzheimer’s, or maybe just pre-Alzheimer’s, has very high risk factors, that’s easy to get. Also, we’re doing transplantation from pigs into humans. You can make preventative medicine on the pig organs that are getting transferred that you would never get approval for changing the human organs in the human. One of the reasons I’m excited about the pigs transplantation is not just that we have a transplantation crisis, but it’s also this opportunity of doing augmentation to make them cancer-resistant, aging-resistant, and pathogen-resistant. You would be very hard to get those three things approved in a human, adult or otherwise.

Dirk: That’s very interesting, both from a research and a regulatory perspective. The last question is, of course, you’re the impresario here of the GET Conference. Tell us what are you hoping to have happen over these next couple days. Why do you host this, and what should our people look forward to?

George: This is an absolutely unique and extremely exciting conference. There really aren’t even any decent imitators yet, although I look forward to it. We are spreading internationally. We now have 5 sites over the world, including Vienna, London, Toronto, and so forth. What’s exciting here, and truly unique, is that we have patients, really “participants” is what we call them, who wear name tags. This whole idea that we can protect your identity is something that we questioned 11 years ago, and so we recruited people who knew what they were getting into, knew that their data could escape and get re-identified. In fact now, not just from research projects but from your regular medical care, there are hackers who have hacked into basically everybody’s medical records, so what we predicted in 2005 is definitely true today. The value of your medical records is now 10 to 20 times higher than the value of your credit card because your credit card is temporary and what’s in your medical records, including your mother’s maiden name and your social security number and all that stuff, are semi-permanent. Misguided identifiers, but they’re there. Anyway, this conference is something where people get together: the participants who are the human guinea pigs, the engineers that are making fundamental changes in technology, and then the medical researchers and so forth. They can all get together and exchange notes, and each year, we get more data on the cohorts. The cohort becomes more and more valuable the more data we have, so it’s not just genomes and micro-biomes and viral analysis and FMRI of the body and the mind and so forth. It just keeps getting bigger and bigger, and each new one that comes in doesn’t have to do all the stuff that was done before, or they benefit from the prospective time series data that we have.

Dirk: Well, thank you so much for the conference and thank you for your time.

George: My pleasure.

Jon F.: Listeners, remember that while you’re listening to the show you can follow along with the things we are mentioning here in real time. Just head over to thedigitalife.com – that’s just one “L” in thedigitalife – and go to the page for this episode. We’ve included links to pretty much everything mentioned by everybody, so it is a rich information resource to take advantage of while you are listening or afterward if you’re trying to remember something you liked.

You can find links to the complete interviews, and others from the conference in the resources section for this episode.

You can find the Digital Life on iTunes, Soundcloud, Stitcher, Player.fm and Google Play.

And if you want to follow us outside of the show, you can follow me on Twitter @jonfollett. And of course this whole show is brought to you by Involution Studios, which you can check out at goinvo.com, that’s g-o-i-n-v-o dot com.

That’s it for Episode 169 of The Digital Life. I’m Jon Follett and I’ll see you next time.

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