Gone to the worms

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A tribute to a scientist who was both of his time, and ahead of his time.

John Sulston died on the 6th March 2018. Having originally studied chemistry and carried out doctoral work on nucleotides, he subsequently made the switch to biology and was recruited by Sydney Brenner to join the Laboratory of Molecular Biology in Cambridge, UK. He went on to produce a complete atlas of the nematode (Caenorhabditis elegans) cell lineage, led the project to sequence its genome, then became director of the Sanger Centre, and both a leader and the face of the public effort to sequence the human genome in what became a race with a private effort carried out by Craig Venter’s company Celera. Both these main achievements (the former of which brought the 2002 Nobel Prize, which he shared with Brenner and Robert Horvitz) are fascinating for the way in which they both encapsulate science as it was then and anticipate science as it is now.

C. elegans is eutelic, meaning that it always contains the same number of somatic cells, and its development from a single fertilised oocyte to a mature adult worm is largely invariant. It is also one of the simplest animals to possess a nervous system. In 1963, just ten years after the structure of DNA had been solved, Brenner was fired by the conviction that “It is now widely realised that nearly all the “classical” problems of molecular biology have either been solved or will be solved in the next decade” (a conclusion that seems ever more charmingly naive as time goes by). He correspondingly set his sights on development – the translation of the genome into flesh. C. elegans was the chosen object of study. Sulston and Horvitz mapped its complete cell lineage, culminating in 1977 in a complete atlas of the worm.

No matter how much you prize the importance of this work, or eulogise its significance, one thing is unavoidable: it was descriptive. It was good, rigorous science that consisted of painstaking if not stultifying observation, but the output was a description. As such, it’s a vital remember and example of the fact that whenever you go into the unknown, description must come first. Nowadays, “descriptive” has become a slur, a casual and convenient means of denigrating others’ work, but Sulston’s effort is a reminder that it is just such work that underpins everything that follows.

But what is does it mean to be descriptive? In essence, it refers to work that provides no indication of causality. And in this sense, Sulston’s painstaking undertaking foreshadowed – or pioneered, rather – systems biology. It described the whole worm. Systems biology is a descriptive science – proteomics, transcriptomics, whatever high-throughput “omics” you care to mention, are all descriptive approaches, for all their methodological wizardry. They describe the state, or the changes, ongoing in a system (whether it be cell, organ, or organism), but do not – or at least not yet – shed much light on the mechanism, the causality, by which such changes occur. Ultimately, they are always descriptive (though their proponents would probably disagree with this assessment). As so often, Sydney Brenner pithily captured this philosophy by comparing systems biology to being taken into the cockpit of an aircraft and shown the multitude of dials there. “Look!” exclaims the systems biologist, “Look at all those dials moving!”. “Very impressive,” counters the now-unfashionable reductionist, “But what do they mean?

Oh, I’ve no idea”, comes the bathetic rejoinder, “But look at them move!

Sulston too kept moving. On to the genome, the grandest description of them all. The genome of C. elegans was published in 1998, with the draft of the human genome appearing a scarcely believable two years later. “In nature’s infinite book of secrecy, a little can I read” mused Shakespeare’s soothsayer, yet scientists were now reading the whole book, of human code at least.

It is hard to remember that time now, with things having changed so much since then. Genome sequencing is now fast approaching the level of a diagnostic tool, but in the late 90s the notion had a strange feeling, a sense of an intangible invasion of privacy – one made much more threatening by Celera’s intention to patent genes and charge access.

Here too, in his conflict with Celera’s head Craig Venter, Sulston bridges two eras. The public effort was built on relatively old-fashioned techniques (contigs, cloning), while Celera showcased the futuristic one –  computational power, shotgun sequencing…albeit piggybacking in its alignments on the same public data with which it was openly competing in terms of output.

Despite the public effort being the less sophisticated one, it’s Sulston’s stance in those years that seems ahead of its time, and to better embody the sprit of the world we now inhabit. Railing against Venter’s and Celera’s intentions, he excoriated the assault on privacy that patenting something common to all represents, defended public access, and stressed the importance of information being freely available. It’s a philosophy embraced by Wikipedia, enshrined in the notion of net neutrality, and exemplified by the open access movement.

It can be argued too that it’s a stance that anticipates the structure of today’s information economy, predicating the concepts of freemium services or advertisers offsetting the costs of free access that underpin so many apps. Despite this philosophy winning out, it’s also deeply ironic that despite our heightened awareness of privacy intrusion and the need to maintain the security of personal medical data, we now glibly give up that same privacy in exchange for the free usage of online platforms such as Facebook.

Facebook, social media, the internet, are all facets of the information age. Computers predate the age, but one could argue that when we digitised ourselves, when we read our own code, was the point when it began. Sulston’s career straddled these epochs, and played a key role in the transition. That’s some legacy.

Posting suggested by Catarina Gadelha (University of Nottingham).

One thought on “Gone to the worms

  1. I could teach an entire undergraduate course on his contributions to science; the man was a prince (by which I mean genuinely helpful and not at all wrapped up in his own ego). Oh, and brilliant too.

    Liked by 1 person

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