4 min readMay 18, 2026 06:50 AM IST
First published on: May 18, 2026 at 06:25 AM IST
“I have the modest goals of replacing the whole petrochemical industry,” Craig Venter said in one interview. “We have learned nothing from the genome,” he said in another, a decade after winning the race to read it. The two statements sound contradictory. They aren’t. The geneticist who built the smallest self-replicating cell, wanted to do everything biology had not yet done, and he was scornful of how little had actually been understood in the process. He held both views at once, without trouble.
Towering, sharp, impatient with anyone who wasn’t already moving, the first time I met him, that was the register I remember. He was easier to admire from a distance, but his critics underestimated how often he turned out to be right. He died on April 29 in San Diego, aged 79, of complications from a recently diagnosed cancer. The obituaries since have reached for the predictable (maverick, swashbuckler, pioneer), including the well-known genome race against Francis Collins. But for those of us in synthetic and systems biology, the obituary that matters is the one written, unintentionally, in the genome of his own creation. It isn’t a tribute so much as an unfinished problem.
In 2016, Venter and his team at JCVI published in Science the smallest self-replicating cell ever produced. They called it JCVI-syn3.0: 473 genes, 531,560 base pairs, no relatives in nature. Every base was either designed or deliberately retained. It is as close as biology has come to a parts’ list of life. Of the 473 essential genes in JCVI-syn3.0, 149 had no known function. Knock any one out and the cell dies; put it back and life resumes. But what those genes actually do, what proteins they make, what jobs those proteins perform, why a cell stripped to its absolute minimum still needs them Venter and his colleagues could not say. For 79 of the 149 they couldn’t even assign a broad functional category. JCVI-syn3.0 is the cleanest experimental statement of the reductionist programme biology has been chasing for half a century. The promise was simple: List the parts and the whole will follow. Venter delivered the list. But the whole hasn’t followed. By 2022, the count of unknown-function genes in JCVI-syn3A, a more tractable derivative, had dropped from 149 to about 92. Hard-won progress, and yet a fifth of the genome still resists explanation. These are the load-bearing minimum, and we do not know what they do.
This is a problem the synthetic biology community has not been honest enough about. We talk about designing cells, engineering life, borrowing freely from disciplines where the parts are understood before they are assembled. Venter’s minimal cell is the most rigorous demonstration we have that, at the bottom of biology, we are not yet engineers. We are bricklayers who don’t know what half the bricks are for.
There is a way to honour him that isn’t eulogy: Take the 30 per cent problem seriously as a programme, a central scientific question his career posed and didn’t answer. What does a cell need that we cannot yet name? Until that has an answer, the field he largely built is not the engineering discipline it sometimes pretends to be. It is still discovering its own first principles, which, as Venter himself would probably have said, is no small thing.
The writer is chief scientist, CSIR- National Chemical Laboratory, Pune. Views are personal
