Geneticist J. Craig Venter: ‘I consider retirement tantamount to death’

The Voyage of Sorcerer II: The Expedition That Unlocked the Secrets of the Ocean’s Microbiome J. Craig Venter & David Ewing Duncan Belknap Press (2023)

Geneticist J. Craig Venter is best known for his role in sequencing the human genome and creating a ‘synthetic’ cell containing only genes that are necessary for life. The Voyage of Sorcerer II details his time sailing around the world as part of the J. Craig Venter Institute’s Sorcerer II Global Ocean Sampling Expedition, collecting samples of marine microorganisms for DNA sequencing while braving ferocious tempests, dodging howler monkeys and diving in shark-infested waters.

Since 2004, Sorcerer II has travelled more than 100,00 kilometres, spent more than two years at sea in total and has visited 23 countries and islands across four continents. His team has collected millions of genes and sequenced nearly 1,000 marine microbial genomes, many for the first time. During cruises in 2017 and 2018, they examined microbes that colonize plastics in marine environments.

Venter talked to Nature about the expedition, his reputation as an iconoclast and his venture into early disease detection through his company Human Longevity, based in San Diego, California.

Are you still spending much time afloat catching microbes?

I’m still sailing, but after 65,000 miles, I’m not anxious to go overseas anymore. The scientists at the institute are still taking samples. People got overwhelmed with the data. When we first published just from the Sargasso Sea, we put all the data in GenBank. And then people started complaining that, when they did searches, all they did was hit my data. So many genes were unknown, it confused everybody.

Some of the criticism I got for starting the expeditions was that they were fishing expeditions. We did do a lot of fishing. But that’s how Darwin discovered so many species. He went out and just asked questions about nature. If anything, our approach has shown that discovery science is not a thing of the past.

Do you have a favourite microbe?

To me, the most interesting ones are the incredibly diverse group [of cyanobacteria] that produce the oxygen that keeps us alive — if we don’t destroy them. These guys are constantly mutating but maintaining the ability to convert sunlight into oxygen.

The other thing that [we] discovered is that the phage [bacteriophage viruses] that grow off photosynthetic organisms actually regulate them and bring in new genes to constantly upgrade the software of their host cells. So instead of viruses wanting to kill off their cells, they’re making sure their hosts stay alive.

Your book refers to you as a maverick. Is that how you think of yourself?

Well, it was considered brash and irrational to go out and start studying the biome of the ocean because I was not a trained oceanographer. In my view, I’m following my intuition and doing an experiment. It’s not trying to push people aside, but so much of science is based on undoing approaches that previous scientists have laid down.

I learnt from the late Nate Kaplan, my PhD mentor, who said the trick to being a successful scientist is to not be afraid to do the experiment. I’m not afraid to ask the questions. The fortunate thing is, most of my ideas and intuition have been right.

Has sequencing microbes informed your work on diseases?

It certainly informed it — we are a microbial planet. We depend on them for our lives. We consider microbes and viruses bad because they cause disease, but only a tiny fraction of them do that. They’re more important for keeping us alive.

We’d be in the water in the South Pacific and it was crystal clear — you could see 200 feet. It was hard to imagine that every millilitre of that had one million bacteria and ten million viruses in it because it looked like pure water. It’s only because of genome sequencing and shotgun sequencing that we can see them. When you look at seawater under a microscope it pretty much all looks the same.

One recurring theme in the book is the difficulty of getting permits to take samples. Why?

I think it’s absurd. When you are sailing from the Galapagos to the Marquesas, which is an open stretch of ocean, there’s a one-knot current. All the species belong to nobody. There are no regulations covering them. But as soon as the currents move those microbes across the 100-mile line off French Polynesia, all of a sudden those microbes become French. Protecting fishing rights makes sense but protecting microbes that drift in and out doesn’t.

We made it clear that all the data were going into the public domain and nothing was being patented. Then we started to get the opposite complaint: that because we’re putting it in the public domain, we were ruining [nations’] patent rights. And we barely scratched the surface of things. I don’t think there have been any billion-dollar bugs (microbes) that came out of the species that we’ve discovered.

Could one become valuable, for example, a plastic-eating bacterium?

You know, there are a lot of plastic-eating things. I think what’s going to happen with synthetic biology is that the synthetic pathways from these organisms will be taken and put into new bugs for manufacturing. But we just did an initial survey. There are tens of millions of microenvironments in the ocean. There’s wind stirring up the water. The diversity is constantly changing. We could keep doing this for the next 100 years and still not have a complete picture.

What made you switch to early disease prevention?

Human Longevity was based on early analysis of my genome. According to the data, I was at risk for early-onset Alzheimer’s disease. [But] you can’t just look at the genome and understand it. So I asked my neurologist friends if they would do a brain MRI on me. The neurologist said that the MRI showed that I had the brain of a 30- or 40-year-old. Good news.

So, the mutation was not, in my case, predictive. That’s where I got the idea to set up a clinic where we do extensive phenotyping along with sequencing the genome to try and get real data on these things. I stipulated that we were only going to do tests on asymptomatic people. And just by doing these tests — like sampling in the ocean — we discovered that roughly 50% of the self-described healthy people that came through have a significant disease or risk of disease that they were completely unaware of.

I wanted to be the first one through and the radiologists told me that I had high-grade prostate cancer that needed to be operated on immediately. I would have had fewer than five years from that point to live from having such aggressive prostate cancer. So I had surgery, it’s been six and a half years, and I’m cancer free. We discover a major tumour unknown to the individual in 5% of people over 50.

Are you concerned about overdiagnosis?

We’ve found so many different diseases early because it was a pretty comprehensive physical. Now we have major grant applications pending to start two mobile clinics, one largely for Indigenous and underserved populations, where the cost would be free. But we’ve had to battle with the medical community. I’ve angered a lot of physicians who think that it’s wrong to do tests on apparently healthy people.

How do you think artificial intelligence (AI) will change the medical landscape in ten years?

It’s going to help immensely, but there is a downside. Until you can sue a computer for malpractice, a high percentage of times the AI systems will just make things up. Until we can trust AI systems to give a truthful answer, we can’t just turn over medical diagnosis to them. The thing to do is limit the AI’s training set. I’m on the scientific advisory board of a company that is using AI to diagnose cancer. I’m optimistic about it as long as we don’t just turn over the systems blindly to the AIs that don’t have good training sets. All these people are saying that AI is going to be the end of humanity. If humans are smart, that won’t happen.

I’m assuming retirement is not on the cards?

I consider retirement tantamount to death. I have my own research institute and an incredible team. Until we run out of interesting ideas, I want to keep going.