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mjewkes | 11 months ago | on: A small violin part highlights bigger problems for the global economy

Sure, they can build it here—but protectionism doesn’t deliver long-term success.

In the short term, it drives up prices and makes consumers poorer. In the long run, tariffs shield companies from global competition and limit their ability to scale. Without that pressure or opportunity, businesses grow weaker—not stronger.

That weakens U.S. industry, not strengthens it.

mjewkes | 1 year ago | on: A primer on the next generation of antibodies

The FDA approves new modalities that do things “in their own way” all of the time!

Yescarta, Kymriah, the mRNA vaccines, the approved VHH, scVF and “mimetics” in the article. Here’s a whole page of cell/gene therapies, many of these were produced “in their own way” or in ways that didn’t exist at all 10 years ago. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-t...

Warp speed did accelerate review of COVID vaccines, but it didn’t change trial design nor manufacturing requirements - I’m not sure that supports your argument. I have seen the FDA be quite receptive to innovative trial design - baysean protocols, conditional endpoints, genetic diagnostics in inclusion criteria, etc

If you think there is a whole wave of innovation being held back by the FDA - can you point to examples of drugs it rejected or innovations happening in any other country that should be happening here?

Lots of stem cell “medicine” is happening in Korea where the requirements on cellular medicine are more lax… none of that is translating to effective medicine here afaik.

As you say, biology is hard and messy! And it is the job of the FDA to prevent five 20 year olds in a garage from injecting desperate cancer patients with some hacked together MVP. We’re agreed on that.

But I just don’t see any evidence of a giant pool of untapped innovation at the preclinical level that the FDA is blocking.

mjewkes | 1 year ago | on: A primer on the next generation of antibodies

>I can say this with pretty strong confidence: had the FDA not being so strict about its trials, lots of these experimental type of antibodies would have already received massived research and commercialization

If the FDA was not so strict in requiring evidence, medicine would look like the supplement aisle, and the incentive to actually do the stupidly hard work of developing effective drugs & proving their efficacy would disappear.

Why even bother investing in developing a complex new antibody if you can sell some mushroom powder from a beach and claim whatever you want about it, ala Tim Ferris & "BrainQUICKEN".

There are plently of valid "incremental" critiques about the FDA. IMO, their devices and diagnostics divisions are weaker than CDER and CBER. Even those two (drug focused) divisions can be too slow moving and occasionally capricious about when they want more evidence. But their final decisions are generally pretty good, with a few exceptions. And most of those exceptions are drugs that they approved that they shouldn't have (e.g. Aduhelm) - not vice versa.

Can you point at a promising drug candidate with statistically solid efficacy data that CDER or CBER has rejected?

Also - note that there are approved scFVs and VHHs and mimetics - as stated in the article. Each is useful in particular situations, but none is some sort of wild medical breakthrough. There is just no evidence that any of these modalities would be attracting extraordinary investment "if only it weren't for the FDA".

mjewkes | 1 year ago | on: Why YC went to DC

If you are truly netflix-to-be, you should be able to affordably incentivize your 12 key employees with equity.

An exit for Employee < 50 at a netflix-to be will be in the hundreds of millions.

mjewkes | 1 year ago | on: Zephyr 141B, a Mixtral 8x22B fine-tune, is now available in Hugging Chat

For sure. It's not a fair prompt at all. I'm super bullish on LLMs and am using GPT-4 in production right now. This stuff is magic.

It's actually hard to find short, simple, "plain english" failure cases like the above.

The "chain of reasoning" that the modern models deploy before the fail is funny too. This is GPT-4:

---

To determine the relationship between cherries and bananas based on your statements, let's break it down:

  1. Apples are better than bananas.
  2. Cherries are worse than apples.
From statement 1, we know apples rank higher than bananas. Statement 2 tells us cherries rank lower than apples. By this logic, since cherries are lower than apples, which are higher than bananas, it follows that cherries are also lower than bananas.

Therefore, based on these comparisons, cherries are not better than bananas.

mjewkes | 2 years ago | on: Arthropod head problem

Worth checking out the talk page. Looks like this whole article is out of date and that much of the problem is resolved.

mjewkes | 3 years ago | on: Ask HN: What good sources of information on ovarian cancer treatments?

As fabiancook mentions, credible sources all end up on pubmed within a year or two of publication, so it's an excellent resource.

That said, Pubmed is an aggregator, not a curator. So you'll find a fair amount of crap there too. Also, there are ~600 results per year related to ovarian cancer, which is likely too much to meaningfully sift through.

The things that come to mind for me are:

- Try to get second, third, fourth opinions from well regarded oncologists at well regarded hospitals, ideally who specialize in ovarian cancer. There is a pretty big gap, especially in cancer treatment, between those who keep up with the latest recommendations, and those who use "still ok" recommendations from 5-10-20-30 years ago

- ASCO is the major scientific conference for oncologists. In terms of understanding what is cutting edge, looking through their material is useful. I would suggest reading what has been presented at ASCO and then taking that to your doctors / second opinions.

- If there are specific biomarkers associated with her cancer, understand those, and make sure you understand if there are latest recommendations specific to those biomarkers. These are the types of specific case information that a generalist oncologist might miss (e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998656/)

- Another place you might be able to complement / compensate your oncologist's care is understanding options for "cancer support" (chemotherapy support as fabian says). Basically, the faster you can recover between treatment sessions, the more drug you can be given faster, and the more cancer gets killed. Oncologists are often (but not always) more up to date with the latest chemo/immuno/surgery/radiological interventions than with the options for chemo support.

mjewkes | 3 years ago | on: High cost of cancer care in the U.S. doesn’t reduce mortality rates

Hey biorach - I would suggest: https://www.rand.org/pubs/research_briefs/RB9412.html and The Great American Drug Deal, by Peter Kolchinsky.

Specific claims:

- The US pays more for new drugs than the rest of the world

- The US contribution is disproportionate, and is major driver of the drug development industry.

-If the US paid less for new drugs, the entire industry would slow, and we would have fewer more effective treatments.

...

Routine medical procedures being crazy expensive is unrelated and pathological.

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