The complicated legacy of J Craig Venter

Many obituaries for Craig Venter, the biotech entrepreneur who died on 29 April aged 79, presented him as ‘controversial’ or as a ‘complicated man’. Such phrases are often euphemisms for a difficult personality – witness the obits for James Watson last year, with whom Venter has been compared for the contributions both men made to our understanding of the human genome.

But while the controversies around Watson centred on his racist and sexist remarks, Venter divided opinion largely because of his business activities. As founder and president of Celera Genomics, he led the privatised efforts to sequence the entire human genome in a race with the publicly funded Human Genome Project (HGP). Venter’s enterprise initially planned to retain some data for commercialisation, while the HGP was determined to keep it in the public domain. In the end Celera and the HGP ended up announcing their results jointly in 2000, the race morphing into an uneasy collaboration.

This, however, was not the full extent of controversy in Venter’s career. He would probably not have denied himself that he was driven by ambition and ego, and he could be rude, aggressive and opinionated. All the same, he seems now like an entrepreneur from a happier time, when billionaire tech leaders were keen to work alongside scientists to create productive knowledge rather than to impose their own ideological vision on the world.

Pushing limits on patents

Venter had serious bona fides as a scientist. Trained in biochemistry and pharmacology, he began to work on gene sequencing in the 1980s at the US National Institutes of Health (NIH)’s National Institute of Neurological Disorders and Stroke, where he studied genes active in the human brain. He provoked furore by announcing the NIH’s plans to patent gene sequences – a scheme that Watson denounced as ‘sheer lunacy’, and which led to a court ruling that genes could not be patented if their function was unknown.

In the 1990s Venter co-founded (with his then wife, genomicist Claire Fraser) the private nonprofit Institute for Genomic Research (later merged with his J Craig Venter Institute, JCVI), where he began to develop the technique called whole-genome shotgun sequencing. The idea was to randomly cut up the genome into fragments, sequence them, and then use computer software to work out how the pieces related to one another. The method was faster and cheaper than the HGP’s approach of slogging systematically through the genome, although it was also considered less accurate. So even though the HGP had already sequenced a fair portion of the human genome when Celera came on the scene, Venter’s effort threatened to overtake it – and to withhold some of the sequence for commercial exploitation.

In the end Celera agreed to make its data freely available (albeit placing limits on access). But its efforts spurred the HGP to speed up, and thus Venter is widely regarded as having driven much of the technological advance that has now made gene sequencing so cheap and easy. He founded the JCVI after being fired from Celera in 2002 because of internal conflicts, and he continued to drive whole-genome sequencing forward, announcing those of the fruit fly, mouse, rat – and in 2007, the first human genome from a single individual.¹ That individual was, of course, Craig Venter.

Grand ambitions

At JCVI Venter assembled a remarkable team, including Nobel laureate microbiologist Hamilton Smith and biochemist Clyde Hutchinson, who had worked under sequencing pioneer Fred Sanger. With such formidable expertise, the JCVI continued to do wonders. In 2010 they announced a bacterium with the first genome created entirely by chemical synthesis² – an achievement controversially touted as the creation of synthetic life. The JCVI team later made a ‘synthetic minimal cell’, a bacterium with a stripped-down genome of just 473 genes,³ which they saw as a potential ‘chassis’ for designer microbes.

Say what you will about the grandiose framing of such work; it was surely remarkable in ambition and delivery. It also bolstered Venter’s apparent conviction – here at least he’d have agreed with Watson – that the genome programs the organism. He was no crude genetic determinist, saying that ‘any geneticist worth their salt will tell you that genes do not account for everything. Environment and chance events also shape life outcomes.’ And perhaps we can forgive a little hyperbole when he said at the announcement of the human genome sequence in 2000 that ‘the inanimate chemicals that are our genetic code [sic] give rise to the imponderables of the human spirit’. But his conviction that, for example, genes could be used for face recognition suggests an excessive faith in what that ‘code’ embodies – and reminds us that, as with AI, the folks who build the tech aren’t always the best judges of what it means.