Sunday, 9 March 2014

Why so many huge sequencing projects?

In the United Kingdom, a project to sequence 100,000 whole genomes is under way. Saudi Arabia has started another 100,000 genome sequencing project. And a few days ago, bioentrepreneur Craig Venter announced a new company called Human Longevity, which is going to initially sequence 40,000 genomes, followed by hundreds of thousands later. Most likely, additional projects on a similar scale will be kicked off over the next months and years.

All this sequencing is not going to be cheap. For example, the British government has put aside £100 million (around $170 million) for its project. How can these costs be justified to taxpayers and investors?


One reason for government-funded projects like the one in Saudi Arabia and the UK is that they are going to directly benefit the sequenced patients. The other and probably more significant reason is that the resulting data will impact the development of new cures.

Genetic variants protecting against common diseases such as Alzheimer's and diabetes have already been discovered. Any drug that mimics the effect of those variants would be likely to also protect against the disease whilst at the same time being safe. The caveat is that rare protective variants can only be detected by studies involving tens or hundreds of thousands of people. Hence the need for sequencing-megaprojects.

Given the potential impact on drug discovery, it may seem puzzling that the initiative comes from governments and startups, rather than from established pharmaceutical companies, whose core competency is, after all, drug discovery.This is probably due to both the relatively conservative nature of most pharmaceutical companies, as well as the so far unproven nature of the approach.

3 comments:

  1. No, not puzzling at all, for a few reasons:

    1) In order to understand the polygenic nature of common disease (think T2D or Altzheimers or atherosclerosis) it is necessary to have millions of genomes (or exomes) and many thousands of well-phenotyped samples

    2) Even at $1k for the WGS pricepoint (or $200 for the WES) the costs are still in the multi-million dollars, only affordable by a few entities (think government is really the only entity to be able to take this on)

    3) For a 'moonshot', someone once estimated the Apollo cost the US about $24B in 1973. Only a government has the resources to tackle it, later private industry will eventually (perhaps) follow suit (certainly for near orbit spaceflight)

    Of course the HLI (Venter) and Calico (Google) other entities starting to look at the genetics of longetivity have budgets in the eight-figure range, which is fund-able from a venture capital point of view but as you point out too risky for conservative Big Pharma.

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    1. Hi Dale,

      As always, your comment is at least as interesting as my original post. I agree that for the time being sequencing projects on this scale are only feasible for governments.

      However, given that it costs billions to develop a single drug, it may well be worth for pharmaceuticals to go down the same route if and when the megasequencing approach proves its worth.

      I assume that one reason why Venter convinced his investors to part with their money is that he's going to look into multiple age-related diseases. That way, he can re-use the data, which would be difficult for a standard case-control study. All this is pure conjecture on my part of course.

      Best wishes,

      Art

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  2. Hello,

    IMO most large pharma companies with the resources necessary for these kinds of projects have shifted those resources away from early drug discovery and re-focused their resources and core competencies on licensing, clinical trials, sales, and marketing.

    As a result, comparatively little of the total cost of drug development by "big" pharma is spent on this kind of research. There are exceptions, Regeneron's exome sequencing project with Geisinger Health springs to mind.

    Brendan

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