Comment by alextheparrot | Hacker News Reader

Comment by alextheparrot | Hacker News Reader

There was an interesting comment made on the recent "Bio Eats World" episode [0] that genetic tests are not aligned with health care reimbursement cycles.

Jorge Conda [0] cited two reasons that genome sequencing (Different from 23andMe's GWAS, for example). First he cited the high upfront cost to buy the machines (Usually meaning you need to be a big hospital). The second fact was a bit more interesting, which is that doing one expensive test (Genome sequencing) which then your health care provider could do cheap queries against ("Which other users have your symptoms and similar mutations in key genes" for example) does not align with the current billing model.

I think that's the "What's next". Finding a way to effectively bring genomic care to the general population, to allow for better research into genetic conditions. If you're interested in how "big" this can be, here's a case where "This American Life" covered how just a few genetic differences was the difference between an olympic athlete and a muscular dystrophy patient [2].

There's also the bio-terrorism and pandemic response angle, which is why the DoD is investing in third-generation sequencing systems where portability has finally become more of a priority.

[0] https://en.wikipedia.org/wiki/Knome [1] https://a16z.com/bio-eats-world-podcast/ (About 13 minutes in) [2] https://www.propublica.org/article/muscular-dystrophy-patien...

There are a handful of sequencing-based genetic tests that have achieved fairly wide penetration; NIPT and cancer panels are probably the best examples.

However, if the question is why whole-genome sequencing has not gained wider clinical usage, I think the answer is less about reimbursement, and more the fact that there are just very few clinically compelling reasons to sequence a whole human genome.

Then there is the fact that although we have ostensibly achieved the fabled "$1000 whole genome" that was touted as the tipping point for clinical acceptance, that was really more of a publicity stunt by Illumina. In reality a clinical-grade WGS still costs a multiple of $1000 (see, e.g., https://bmchealthservres.biomedcentral.com/articles/10.1186/...). The Moore's Law-like cost reductions of genome sequencing are a bit of a myth at the present time; in practice Illumina has a monopoly on the technology used for clinical WGS, and therefore they have a great deal of influence over the effective cost of sequencing.

If I want to sequence my own genome are there any services that do it already today with any reliability?

I think about the best you can manage (with or without having a doctor order the test for you) is a Whole Exome Sequence[1]

1: https://www.verywellhealth.com/whole-exome-sequencing-458268...

Nebula Genomics: https://nebula.org/whole-genome-sequencing/

A lot of that cost is due to inefficiencies by the institutions doing the sequencing. My current employer spends much more than my previous employer spends in order to sequence & analyze a single sample and the only substantive difference is in the process itself.

very few clinically compelling reasons to sequence a whole human genome.

Isn't that a bit of a self-reinforcing problem, where the reasons to do something can't be developed until the thing has been done enough to find more reasons?

It is. That's why much of the WGS action these days is not is sequencing individuals in the clinic, but rather in large-scale population studies like UK Biobank. These are aimed at identifying interesting genotype-phenotype relationships, for which you need massive sample sizes. This approach probably will bear fruit eventually, but the outcome won't necessarily be that everyone gets their whole genome sequenced; rather, the discoveries will be translated into the clinic via either (1) targeted tests that assay specific variants discovered via the population-level studies, or (2) drugs developed on the basis of gene-disease associations.

This chicken-and-egg problem is also the reason why Illumina has invested massive amounts of money in companies like Helix and Grail, which are basically highly speculative attempts to find a problem for which loads of Illumina sequencing is the solution.

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