All of Ben Podgursky's Comments + Replies

I haven't read much at all about the Iterated Meiosis proposal but I'd be pretty concerned based on the current state of polygenic models that you end up selecting for a bunch of non-causal sites which were only selected as markers due to linkage disequlibrum (and iterated recombination makes the PRS a weaker and weaker predictor of the phenotype).

Hey @GeneSmith, really appreciate you putting this together.  I wanted to throw in a few thoughts regarding monogenic disease (the disclaimer/context here is I lead engineering at Orchid, and we've put a lot of thought into our monogenic embryo screening).

The 1% risk of monogenic disease you cite above is pretty misaligned with most estimates of monogenic disease.  It may be an old reference, or filtering for only catastrophic disease, but common estimates for monogenic screening yield in adults are between 3.5% and 18%:

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5GeneSmith
Thanks a lot for the comment. I'll amend the post with some of this information in the next week. If your numbers are correct (and I have no current reason to doubt them, that substantially increases my estimate of the effectiveness of whole genome embryo sequencing. I've been meaning to write a whole post about the different screening companies but a combination of little time due to starting a new company and a lack of clear data have preventing me from doing so thus far. With this information I might reconsider. One more thing I'd like to ask at some point is whether you're going to publish the AUCs of all the predictors in your panel within some reference population. That would be extremely helpful for patients trying to compare Orchid vs Genomic Prediction or any other company.

"My real answer to what went wrong is that our civilization is profoundly inadequate. We have lost our ability to do things."

This is the only conclusion I would challenge — we actually did do things, for a while. We locked down (almost) completely for a month. But the emerging consensus as the numbers resolved was that the disease wasn't catastrophic enough to shut down society over for a year, or two, or three.

Does this mean that we couldn't lock down and quarantine for a disease with a CFR of 20%? I don't know. Maybe, ... (read more)

I think on the whole the US' lockdown was pretty weak and had low compliance; I think compliance was to a large extent dependent on things already looking bad enough locally to feel dangerous, at which point it's too late to get case levels low with the duration and severity of lockdown people have been up for. ('Compliance' might even be the wrong word for it, since I think people were mostly just avoiding things based on how dangerous things looked to them personally, not based on any top-down rules or guidelines.)