Cracking the Longevity Code

J. Craig Venter, PhD, sheds light on a future powered by genomics & preventative medicine.

When it comes to achieving theStartUp Health’s Longevity Moonshot, Human Longevity, Inc. (HLI), is as close as it gets to adding 50+ healthy years to every human life. Through their pioneering work, Dr. J. Craig Venter, former CEO of HLI, and his entire team are redefining the way we think about preventative medicine, early disease detection, and organizing the world’s genomic data in a more efficient manner.

In a recent interview, Jane Metcalfe, CEO of NEO.LIFE, dug into the world of genomics with Dr. Venter and explored how HLI’s Health Nucleus is detecting diseases and cancers early and ultimately saving people’s lives.

What we know right now about the human genome

Jane Metcalfe: You’ve inspired a whole generation of geneticists, and biologists, and physicists, and health entrepreneurs, and doctors, with your science and your ability to harness technology to understand the potential of our DNA. So, my first question is, where are we? In in terms of collecting and parsing the data that will be required to really understand the human genome?

Dr. J. Craig Venter: That’s a good question. Not as far along as most people think. It’s still extremely early. We’re still around 1% of the knowledge that will be ultimately obtained. That’s the basis of why we started Human Longevity (HLI), so we could collect tens of millions of genomes, but in conjunction, having phenotype and clinical records on every person to make correlations between them.

Metcalfe: I want to talk a lot more about everything you just said. We know, or we understand 1% of the human genome?

Dr. Venter: I’d say we understand 1%. It’s more based on discovering how much we don’t know everyday. It means we know very little. It’s not a precise number, we have a very long way to go.

Metcalfe: It does boil down to databases doesn’t it? There is a lot of companies and projects, both public and private, that are collecting genomes and publishing literature and then deciding which literature to use to interpret the genome.

Dr. Venter: It starts with a fundamental quality of the data. We hired Bill Biggs to build out our sequencing facility three and a half years ago and various groups have validated that our data is the most accurate data out there. So it’s not a matter of buying a machine. It’s the whole process, and we’ve been doing this for well over 25 years now. It makes a big difference whether it’s a rare variant used to diagnose a trait or a disease, or a sequencing error. Each of us have around four or five thousand rare variants. Some have more, some have less. Rare variants means ones that we don’t find in any database at this stage. So, allele frequencies of less than 1 in 20000. So, when you’re at that level or lower, and you’re attributing something to it, you want to know that it’s real and not just some sloppy lab work.

The $5,000 check-up: HLI’s Health Nucleus

Dr. Venter: We’re rolling out a new product, called HNX, [for $4,950]. It’s the whole body MRI, the quantitative brain analysis, quantitative vascular analysis, the new Siemens MRI actually does a pretty extensive cardiac analysis in 12 minutes and the report is done by the time you get out of the MRI. Perhaps the most important thing we are finding is greatly elevated organ fat. Normal is 4%, or less. We’ve had people as high as 38% without knowing it. And so we’re trying to estimate how many of those go on for fibrosis and would need liver transplants. We found a correlation between the microbiome and fatty liver. I think that’s important.

We’re also finding age groups where calcium in the heart keeps going down. Recently, we had a 45 year old woman that was clearly not obese. No history of heart disease. She was in the 99th percentile for four different coronary vessels, which means she’s extremely high chance of having a major cardiac event in the next decade. She did have elevated blood lipids. But these unusual cases give us fodder to go back and look at the genome of these individuals as well. But we’re finding a shift in all diseases to younger and younger cohorts. Cancer as well. But, cancer has been replaced by heart disease in women as the number one killer. And most women don’t consider heart disease a woman’s disease. Most physicians don’t. It’s getting neglected. The kinds of tests that we do make it very clear whether you have it or not.

Redefining preventative medicine

Dr. Venter: We still have the HNX Platinum that people still ask for. It’s a full 8-hour one and takes two and a half hours to go through everything. So, it’s a big difference in time and dollar commitment, and you can use health savings plans to pay for this. We’re trying to get enough data where it makes sense for third-party payors to pay for it. But preventive medicine is hard to sell.

We just did a study on 125 people for a pharma company. Out of 25 people, we found one with a very serious cancer that they didn’t know they had. A couple with serious heart disease. And a spectrum of other diseases. So, all of which would have you know, they’re self-insured, so they would have had to pay for these once they revealed themselves.

5% of people over 50, we are finding a major tumor that they didn’t know they had. The good news is we’re finding these at stage 0, stage 1, and some at stage 2. Thus far, they’ve all been successfully treated. All the diagnosis were confirmed by the pathology. We’re doing really well with diagnosing things in the MRI. And we now have a machine learning algorithm that’s as good as the best pathologist for scoring high-grade prostate cancer straight from the MRI. We think in a year we will have the same thing for breast cancer.

Metcalfe: That’s the question I’m getting at too. As a consumer, $5,000 is still a fair amount of money. I’m not sure I would come unless there was something wrong with me that I was trying to figure out. In which case I might come to you instead of going to the Mayo Clinic.

Dr. Venter: That’s the wrong way to think about preventative medicine. It’s like, you’re not going to ever change the oil on your car until all of the oil drains out and your engine freezes. Because then you know something’s wrong. With these cancers, with the early detection, as I said, we’ve been a hundred percent successful, thus far, in treating them. All the individuals are cancer free. We’re dealing with four women in their 30s with stage 4 colon cancer. When you detect cancer from symptoms, the outcome is totally different. So getting pre-symptomatic, early discoveries, your odds are pretty high. If you’re over 50, 5% of people having a cancer they didn’t know they had is pretty stunning. In fact we’re having to re-educate the medical system.

We diagnosed one man in his 70s as having high grade renal tumor, because we use our algorithm that’s post-processing, with no contrast media. He went to a clinic up here in the Bay Area and was told, they put him through a standard MRI and was told he just had cysts and to ignore it. So, we found somebody in San Francisco that knew how to read this new technique. And confirmed that he actually had renal cancer and was operated on a week later and it was confirmed that it was a high-grade tumor not yet metastasized. Most of the medical community is not even aware of these new techniques, that you can do non contrast MRI with all this post processing algorithms. But you’d be smart to go through, because then you become a baseline. You are your own control level for things.

HLI’s moonshot goal

Metcalfe: How many genomes would you like to sequence by the end of, let’s say, 2018?

Dr. Venter: As soon as possible, to get 10000 individuals through the Health Nucleus. Because that gives us a really good starting data set for the machine learning to compare all the traits back to the genome.

Metcalfe: What can you discover with 10000 verses 100000, versus a million?

Dr. Venter: The higher the numbers go, the better chance of finding things with the really rare alleles. So, one of the interesting things, is we saturated the common alleles in the human population at about 8,000 genomes. The common alleles is what most people use on gene chips to measure things. So, by the definition being common alleles, they’re not the cause of disease. The ones you want to measure in yourself are the extremely rare alleles. And so, with each person, we actually give a ranking, we have a really nice tool that looks at your entire genome in 200 milliseconds. It gives the allele frequency for that variant and our population dataset. So, when you’re looking for things of significance, if 75% of the population has it, we just ignore it. If 1 out of 20000 have it, we pay a lot of attention to it.

We’ve also mapped the genome so we know sites that are very susceptible to mutation, and ones that aren’t. There’s places that, if you have a variant at that site, it’s incompatible with life. Those are probably associated with early spontaneous abortions, for example. Just mapping transmembrane receptors, if a change occurs in the transmembrane section, that usually leads to a loss of function mutation. From just mapping the genome to combining it with this data, it’s pretty exciting every day of what we’re finding.

Power of early diagnostics to achieve the Longevity Moonshot

Metcalfe: What do you think are the most promising avenues of research to pursue in the cause for longevity?

Dr. Venter: About 30% of people that reach the age of 50 will die before the age of 74 right now. So, when you’re talking about increasing lifespan, finding a tumor in a 50 year old that can be completely cured probably changed their lifespan by 30 or 40 years, if they were going to die from metastatic cancer.

Metcalfe: So you’re saying early diagnosis is going to give us 25 years?

Dr. Venter: We had a twenty something that we found, she had changes with insulin sensitivity, increased organ fat, a pear-shaped, peripheral fat distribution, and elevated lipids. She can go one course where it develops into diabetes, you get cardiac complications with that. With cardiac complications you get early brain damage and dementia. Or, you can totally prevent that pathway into developing diabetes in the first place. The same thing with heart disease. The same thing with the early detection of cancer.

Metcalfe: Early detection buys us 25 of the 50 years that we’re going for?

Dr. Venter: For some people it could buy them 90 years. When we look at the total distribution. So we’re, we started one program at the Venter Institute with a 16 year old girl whose younger brother died at age 12 from a neuroblastoma. On sequencing her genome, she had multiple oncogenes that were mutated, the same as her younger brother. Her parents were sure that she was going to develop cancer. So we set up a program, she’s now 18, a student at UCSD. she comes to HLI every 6 months for a whole-body MRI with a goal, knowing she’s at risk for cancer, of detecting it at stage 0, stage 1. It’s like doing the preventive maintenance, the more you know early on, the better the chance of detecting things early enough.

Dr. Venter’s hopes for the future

Metcalfe: What would you hope to see happen in your field, whether it’s genetics, longevity, synthetic biology, in the next 30 years? What do you want to see happen before you die?

Dr. Venter: The biggest challenge. I didn’t realize it would be such a huge challenge. And you’re an example of it, because you were hesitant to do these tests, is getting people to do preventive medicine.

It’s a Jupiter shot, or something. So, the moon would be easy, by comparison. If you look okay and feel okay you deem yourself healthy and the medical establishment deems you healthy. You can’t tell me you’re healthy. I can tell you whether you’re healthy or not after going through the clinic. I can tell you whether you have cancer, whether you’re developing early dementia, whether you have metabolic disease, all of which you could be completely unaware, because it’s at stages that haven’t started yet.

Metcalfe: You announced a DNA printer last year, right? We could email a file to some off-planet colony and print humans. Or at least vaccines, or something. So, how far can you imagine something outrageous happening between now and the end of your lifespan?

Dr. Venter: If the 40% of men that die before they reach 74 get preventive medicine and don’t die, that’s changes the economy, that changes productivity.

Look at the list of top people still in the prime of their lives that die each year. We are losing that knowledge and we sort of have to start with each generation and reteach all the things, like, vaccinations are actually important. They keep disease away.

I think if we made preventive medicine and using these new tools of science to find out whether you were healthy or not, it’s actually probably one of the most important things I could have accomplished in my life and particularly if the genome makes that predictable as a triage, that would be pretty satisfying.