SAN DIEGO—More than two decades after making history by being an integral part of the Human Genome Project celebration, J. Craig Venter, PhD still holds a few surprises up his sleeve. In a public appearance at the annual Molecular and Precision Med TRI-CON event, he revealed how he nearly pulled out of the White House celebration in June 2000 after objecting to a first draft of British Prime Minister Tony Blair’s prepared remarks.
The TRI-CON event, hosted by Cambridge Healthtech Institute, celebrates its 30th year this year.
In a fireside chat, moderated by Kevin Davies, PhD, (Executive Editor of GEN’s sister journals The CRISPR Journal and GEN Biotechnology), Venter reflected on his career pioneering advances in genome sequencing and the evolution of genomic medicine over the past 30 years.
“[The genome revolution] has fallen way short. The sequencing technology has improved by so many exponents but people think that the sequencing is sufficient,” said Venter. “I learned through my assumptions made on my own genome that without measuring the comprehensive phenotype, the genome was virtually worthless.”
Venter emphasized that studying human biology in conjunction with the genome is required to make strides in genomic medicine. “If I had to choose between having my genome sequence and a whole body MRI for health,” Venter said, “I would take the whole body MRI. But the future is combining the two.” Venter co-founded Human Longevity, a company offering state-of-the-art personal genome and imaging screens for clients, in 2013.
Venter’s legacy as a genomics legend established its roots over 30 years ago, starting with a paper published in Science in 1991, in which Venter’s team at the National Institutes of Health applied random cDNA sequencing to identify more than 300 human genes of plausible biological function, coining the term “expressed sequence tags.”
“My institute director of neurology complained that I was wiping out all these PhD theses randomly by publishing all these sequences. Of course, that wasn’t the goal. The point was that I’d spent 10 years trying to get one gene and I didn’t want to have to do that again.”
Throughout the 1990s, Venter’s notoriety steadily grew with controversy over the commercialization of DNA discoveries. In 1995, Venter’s team at his non-profit, The Institute for Genome Research (TIGR), published the first microbial genome sequences. In May 1998, he stunned the public HGP consortium by announcing a for-profit effort to sequence the human genome, which later became Celera Genomics.
Venter remembered the day at the White House, June 26, 2000, when President Bill Clinton celebrated the completion of the first draft of the human genome alongside National Human Genome Research Institute director, Francis Collins MD, PhD. The event was the culmination of a diplomatically negotiated truce of sorts.
The White House ceremony “was dictated by when Celera finished the first assembly in its computer. That’s when we actually had the first genome. There was a lot of back and forth politics because the public effort hadn’t finished their assembly yet,” Venter said.
Venter recalled reviewing British Prime Minister Tony Blair’s speech the night before the ceremony and nearly withdrew from the White House event. “[Blair’s speech] was totally lopsided, attacking Celera and companies sequencing genomes. I said, ‘If you want me to show up, you’ll change the speech.’ [After a back and forth] the White House science advisor called me at 1 am and assured me that the speech had changed.”
Venter’s decision to agree to a joint declaration was “a moment of pragmatism” that actually angered his team and wife, whom Venter says did not speak to him for a week.
“The reality was that Celera was so far ahead and people just wanted to announce and publish it. I thought it wouldn’t help science at all if we undercut the NIH and decided that the best thing for science and the public was to have a truce,” stated Venter.
The personal genome
Since the White House announcement in 2000, the field of genomics has continued to boom, most recently culminating with the Telomere-to-Telomere (T2T) Consortium’s sequencing of the entire human genome in 2022. Asked for his thoughts on these advances, Venter was unfazed.
“We ‘finally finished’ [the human genome] so many times that I lost track! It’s never finally finished, as each of us has a completely unique genome sequence.”
Venter emphasized how each individual’s diploid genome presents orders-of-magnitude more variation than the haploid representation, noting how Sam Levy PhD and colleagues from the J. Craig Venter Institute published the first relatively complete diploid genome— Venter’s personal genome—in 2007.
When asked about the value of genome data to the personal owner of the genome, Venter reflected on his own experiences sharing his genomic information with the public.“My sequence has been out there for so long. There were many people publishing papers of new childhood diseases that I should have died from!” said Venter.
Venter stated that genomic information should be personally controlled, where individuals make the decision on whether to make it publicly available the same way that he did. In addition, Venter said his decision to share his genome was in response to the fear of genome sequencing at the time.
“You might recall editorials [stating] how dangerous it was to have your genome sequenced. Donating my genome and making it available was meant to prove that it wasn’t something to fear,” said Venter.
Under the sea
Venter closed the interview by describing the expansion of his work into metagenomics and his new endeavors sailing the world, a vision that Venter said “kept him sane” during his time as a medical corpsman in Vietnam.
“Once we [sequenced the first genome], we got tons of funding to sequence every genome on the planet,” said Venter. “We did what the Challenger expedition did in the 1870s, where we sailed around the world to examine the bottom of the ocean,” Venter continued.
Venter described shotgun sequencing of filtered sea water samples and being “blown away” by [the diversity of organisms]. He published this sequencing work from the Sargasso Sea in Science in 2004. Venter painted the voyage as a mix of scientific discoveries, logistical challenges and near catastrophe.
“Darwin had it easy!” Venter said. “He could collect samples from anywhere. Nowadays, we need a permit from everywhere to take a water sample 200 miles off their coast. We got arrested by the French and British government. The French even threatened to sink our boat! There was a lot of excitement just to sequence these new genomes.”
Venter has documented these nautical adventures in his upcoming book, co-authored with David Ewing Duncan, called The Voyage of Sorcerer II: The Expedition that Unlocked the Secret’s of the Ocean’s Microbiome. It will be released in September 2023.