Craig Venter Has Mixed Feelings On DNA Day Celebrations

It’s been 20 years since the human genome was sequenced, but Craig Venter is still not on board with the participation trophy. In addition to the 70th anniversary of Watson & Crick’s seminal publication on the structure of DNA, it has also been 20 years since the completion of the human genome project (HGP)—something Venter knows quite a bit about. I connected with Craig recently—ahead of the 2023 SynBioBeta Conference, where he will be present for a fireside chat alongside Martine Rothblatt [founder of United Therapeutics
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, who has been working with Venter on genetically altered pig organs for human transplantation]—and discussed what these two significant milestones meant to him.

Or at least I thought they were significant milestones until he told me otherwise. “You know that that was a fake announcement about the completion,” Venter quipped with a wry smile on his face, referring to the 20th anniversary of the HGP. As many of you may know, Venter comprised the commercial side of the race to complete the massive sequencing project. In the late 1990s, Venter became frustrated at what he perceived as the slow progress of the NIH’s sequencing team. So, with the backing of his company Celera Genomics and the use of automated sequencers, expressed sequencing tags, and his shotgun sequencing approach, Venter lit the fuse on the HGP powder keg.

As you can see from his previous response, Venter is not one to mince words. So I laughed nervously after his “fake announcement” remark, hoping he would explain what he meant. Instead, Venter implied that the government-funded portion of the HGP was “just trying to outdo Celera because, as you’ve seen almost every year, there’s been a new announcement that the genome has been completed. So that was a faux government celebration.” Venter remarked. “I don’t celebrate that anniversary, but the 70th one, I do. And you know, in general, every milestone in the human genome is worth celebrating.”

Venter explained that the only anniversary he believes should be celebrated is “2000 and the publications in 2001,” when the human genome was first announced and published in Science and Nature. He believes that everything “since then has been a refinement.”

He provided me with a history lesson from that era, explaining that the White House announcement on June 26, 2000, was based on when Celera finished the mathematical assembly of its genome. To provide affirmation of his account Venter noted, as he has in previous interviews, that the late John Sulston (Nobel Laureate and first director of the Wellcome Sanger Institute) stated in his book “The Common Thread: A Story of Science, Politics, Ethics and the Human Genome,” that the government-funded project was “a bunch of phonies” when they went to the white house as they didn’t have any real data yet.

A Truce for the Greater Good

However, in 2000, Celera had assembled the genome to the level of what they published in Science in June 2001—and because many were afraid they would announce ahead of the public consortium—President Clinton called for a truce between the two factions, and Venter agreed to the joint announcement. “But, in reality, at that time, Celera was the only one that had a human genome sequence,” Venter stated. “And that’s why they [the NIH] celebrate 2003 because that’s when they caught up with Celera.”

I wanted to know what the coordination of a truce like that entailed and if there was any fallout. So, I asked Craig if Bill Clinton brokered that deal and organized the troops, so to speak. “It was actually Ari Patrinos who coordinated it,” Venter explained. Patrinos was, at the time, the Director of the Office of Biological and Environmental Research in the U.S. Department of Energy. “He [Ari] did shuttle diplomacy and finally agreed to get Francis and me to meet for drinks at his townhouse. Of course, I was extremely reluctant then, as I couldn’t trust them as far as I could spit. But I did trust Ari,” Venter remarked.

The repercussions of the truce came swiftly on Venter and with a lot of internal grief. “My team, including Heather [Kowalski, currently COO at JCVI], who has been my wife since 2008, were so angry with me.” Venter exclaimed, “Heather wouldn’t speak to me for two weeks after I agreed to the truce!”

And in a moment of reflection, I saw some statesmanship come out in Venter. “Look, our goal was not to damage NIH or anything. President Clinton was a friend, and a good mutual friend is the one who convinced him that he had to step in and do something.” Venter said. He ended with a final thought on the retrospective he told me, saying, “So that’s why we celebrate the actual White House announcement and the first publications, which are the true first versions of the human genome.”

A Round of Applause, Twice

Because he had just provided me with fantastic insights into that exciting but turbulent period in science history, I had to ask Craig what he thought were some of the biggest challenges he and his team faced back then. The story he told was fascinating and one I wasn’t aware of previously.

“Well, we were trying a method that, in 1995, I used to sequence the first genome in history with, but that was a 1.8 megabase bacterial genome.”

Venter’s anecdote began. “We did a test at Celera, before the human genome [using] the Drosophila genome to see if it would work on a large, complicated, multi-chromosomal genome. We were scheduled to speak at the annual Drosophila conference, and the computer, which at the time we built it, was the third largest civilian computer in the world that we built to assemble the human genome.” By comparison, the Drosophila genome is approximately 100 times larger than the bacterial genome Venter sequenced first.

“The calculation took weeks and weeks to run on this huge, like one-and-a-half teraflop computer, and we had no idea whether we had a Drosophila genome or not until the day before the meeting,” Venter continued. As it turns out, the calculations worked, and the Celera team quickly made about 500 CDs with the sequence on them. “We distributed the CDs to all the Drosophila scientists at the meeting. We put one on everybody’s seat,” Venter reminisced with a smile. “It was the second standing ovation I got in science,” he beamed.

The first ovation was a few years earlier, in 1995, at the American Society for Microbiology’s annual conference when Venter and his team made history by unveiling the first organisms to have their genome sequenced: Haemophilus influenza and Mycoplasma genitalium.

Interestingly, Venter shared with me that his repeated attempts to get his novel technique for DNA sequencing funded by the NIH were met with much resistance. “Ham Smith [microbiologist and Nobel laureate known for discovering type II restriction enzymes] and I wrote a grant in 1994 proposing to sequence the Haemophilus genome with this new method—we proposed our shotgun sequencing. And it got turned down with extreme prejudice,” he pointed out. “So we went ahead and self-funded it.”

Needless to say, a few months later, Venter, Smith, and their colleagues published the first-ever genome sequence for any organism in Science.

On The Right Track

Because of their success with the Drosophila genome, Celera scientists knew they were moving in the right direction, and there was an excellent chance their strategy would work well in humans. Arguably, going from bacteria to fruit flies was a much bigger leap than the flies were to humans. Humans have about ten times more DNA compared to flies versus the 100-fold jump the Celera team made previously. But that didn’t mean it would be easy or the scientists would make it in time.

“Until this giant calculation ran and ran and ran for weeks, we had no idea whether we had a human genome or not,” Venter stated. “And I would get calls from the White House every day, you know, is it soup yet? Is it done? They were getting very nervous because they had to pick a date and schedule everything with all the dignitaries and people coming. And so, they were getting very nervous at the last minute.”

This was all brand-new science, and at any given time, so many things could have gone wrong. Venter explained that the computer was new, the algorithms were new, the technology was new, and the whole approach was new. “Gene Myers [computer scientist best known for pioneering the BLAST sequence alignment tool] wrote this algorithm. It was 500 lines of computer code that he wrote in about six weeks,” Venter added. “Nobody had ever done anything like this before.”

Venter concluded with a final thought that seems apropos for the scientist who has often been considered to be a rogue and needed to be self-reliant so often in his career, “I wrote in my book, even though I do things with extreme confidence because I believed in the methods and the team, I said, looking back, there are at least a thousand reasons why it could have and perhaps should have failed,” he said. “But it came together and worked. You know, sort of like a moonshot. And if everything works right, that’s amazing!”

Now, they often say that history is written by the victors, but in science, as it would seem, history is written by the persistent. Well, by anyone’s definition, Craig Venter’s scientific career epitomizes persistence, and there is no sign that he is ready to hang up his lab coat just yet. Toward the end of our in-depth conversation about his career, Craig told me about his second book dealing with his life at sea focused on the metagenomic sampling of various ocean life from around the globe. He told me some tales that, frankly, made me wish I had a copy of the book right now.

Venter’s quests on the high seas sound almost like the latest geopolitical drama on Netflix
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. Let’s just say that at one point, the US State Department, the US Navy, the French Navy, and the Tahitian government were all involved in the story. “You can read about Darwin and the Beagle, and I can be very jealous that he could just sail wherever they wanted to and he could pick up iguanas or samples or anything he wanted,” Venter exclaimed when discussing some of the legal battles he and his team faced when trying to collect samples around the Galapagos.

“The Voyage of Sorcerer II” is set to be released this September, and you can be sure I will have a full review of the book in an upcoming article. From the stories that Craig told, it sounds like a fantastic read that showcases a persistent scientist continuing to try and show the world the true power of genomics and sound science.

Thank you to Jeff Buguliskis, PhD, for additional research and reporting on this article. I’m the founder of SynBioBeta, and I discuss the impact of synthetic biology on numerous fields in our weekly digest newsletter.