Ancestors

Written by Dan Goodman on 2025-01-27 at 18:08

Thinking about big science, the human genome project looms large. I'm not an expert so: did this project fulfil its potential? From what I've seen, it seems the major achievement was development of sequencing tech and a focus on open data. Otherwise, people still talking in terms of potential value?

Apologies in advance if this comes across as ignorant, I really don't know much about genetics.

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Written by Ricardo Segurado on 2025-01-27 at 20:08

@neuralreckoning

As the HGP was being completed, we saw the same sort of personalities and competition and certain invective that we see with all big-money projects. We saw the same sort of promises being used to secure the money, and then those promises being forwarded to the public (by governments) or shareholders (by the privates) to justify the expense.

So that is interesting.

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Written by Ricardo Segurado on 2025-01-27 at 20:09

@neuralreckoning

The project itself was a very humdrum piece of science, very boring. Hence much of the hype was about speeding it up, who would finish first. I never quite understood how you could then justify speed of sequencing as one of the pluses to emerge from it.

Maybe it is a plus in the long run, but pending actual benefit from knowing the genome sequence, that is sort of putting the cartbefore the horses

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Written by Ricardo Segurado on 2025-01-27 at 20:13

@neuralreckoning

In terms of the benefit of the data, and all the hype around the medical advances, not a lot has planned out IMHO.

Rare and monogenic diseases have certainly been mapped, but you can often enough do that without full sequence.

Common and chronic disease (where you can get real bang for your buck in terms of population health) has turned out to largely not be dependent on one or two or even a few genes. Largely as expected, really. Clinical benefit has been slow for all..

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Toot

Written by Ricardo Segurado on 2025-01-27 at 20:17

@neuralreckoning

What's striking is that the volume of data, the development of molecular genetic tools, of computational tools has put innovative, mechanistic work in the shadow. There hasn't really been any "great leap forward" in terms of new insights, new laws of life, and so (am I right on this, happy to be corrected) no Nobel prizes for such stuff, that could be attributed to the HGP.

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Descendants

Written by Ricardo Segurado on 2025-01-27 at 20:18

@neuralreckoning

There's been utility of the sequence in archeological genetics, comparative genetics (across species, insights into evolution), and in the (slightly more interesting) slog of annotating the sequence (where are the genes, how are they different, what types are there, how do they seem to work).

Some of this matches the pre-2000 hype and promises, but not on the most impactful fronts.

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Written by Ricardo Segurado on 2025-01-27 at 20:21

@neuralreckoning

Of course a negative result in science is still a result. It's interesting that diabetes is so complicated genetically, and yet turns up as quite heritable in family studies. Psychiatric disease even more so. There might be general high level insights there, but no one has grasped it, or operationalised it.

Also. Some areas of human medical genetics are out of my field, so e.g. cancer genetics has advanced faster, and maybe I don't have a sense of that....

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Written by Ricardo Segurado on 2025-01-27 at 20:25

@neuralreckoning

Cancers and some other diseases had relatively well-charecterised molecular bases, independently of the HGP, and that was boosted. But who is to say by how much -would advances in those diseases have been made anyway, without whole-sequence data or tools?

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Written by Ricardo Segurado on 2025-01-27 at 20:30

@neuralreckoning

I would support your hunch on the outputs from the genome project.

You get plenty of people who are believers, though! I've been shouted down (on 'other platforms') on occasion, I admit.

But the promises now touted are still in the future, usually hooked onto new analytic methods etc which have yet to materialise. Always the next best thing....

That said, I am a believer! I think it has all that potential for human health, and more! Just no clear path towards that, yet.

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Written by Dan Goodman on 2025-01-27 at 22:34

@red_concrete thanks for that! It's really interesting to see different scientists' impressions of the impact. Very eye opening to me, a non-specialist.

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