I agree with you about significant financial support from the government if that support is financial and given to smaller groups.

I disagree about societal acceptance though. I feel like your point of view may be missing clinical trials and treatments in the USA. The laws we have are written in blood, and the laws more sophisticated than I think you appreciate.

There are various options for fast-tracking drug development if the conditions are serious enough or the drugs promising enough. I suggest actually reading about how these processes work, and the history of what happens when we don't have these protections, before deciding that approvals are overly cautious.

But some think our attitude

Should be one of gratitude

Like the widows and cripples in old London town

Who owe their large pensions to Wernher von Braun.

Because of this initial trials consume lots of medical staff to deal with the potential side effects. Normal side effects for cancer treatments include:

  * Your gut lining dissolves, your shit leaks into your body cavity, and you get sepsis.

  * Your heart stops during the infusion.

  * Cumulative poisoning that nobody understands. (E.g. some agents have lifetime limits, and if you go beyond that, then you die. Guess how we found out.)

  * Your immune system, and you get things like disseminated fungal infections.

This puts a limit on how many patients you can put into a trial. I'm under the impression that cancer trials are pretty much always full.

My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing drugs. Some of the side effects included:

  * Her heart stopping during a drug infusion. This happened multiple times over the 18 months of treatment.

  * Disseminated fungal infections.

  * Sepis because holes were developing in her GI tract.

This was a good response. Other patients just died from the drug combination.

This is what going slowly looks like in the world of cancer treatment.

It was biased in some sense towards those things that could be crystalized, but but at that time we were already seeing the same sorts of recurring motifs with cryo-em which is much less restrictive in the required preparations. (Purify it and flash freeze it.)

In the last 30 years there's nothing that has overturned the recurrence of motifs in protein structure. It's just become more and more established.

This paper confirms that.

The methods they're using are interesting, but the fundamental result isn't surprising.

There's a great book on the subject called "Merchants of Doubt" by Naomi Oreskes and Erik M. Conway.

The only lesson is that, to a biochemist, the result is not surprising.

The result also fits in with the rest of biochemistry. While there are a vast variety of interesting chemicals in living things, and they do all sorts of amazing stuff, there are really only a handful of classes of chemicals.

The variety of classes of chemicals that can exist dwarfs what gets used in biochemistry. Why would we expect structure to be different?

We're in agreement though, that it would be interesting to understand what the constraints are.

An enzymatic reaction center is also known as an "active size". It's the location within an enzyme's 3D structure where catalysis happens.

We have broken our world for the greed of a few. History will not be kind to us.

1) Only handful of amino acids in a enzyme structures were highly conserved. (Out of hundreds, generally less than ten.)

2) Those were generally in the reaction center.

3) Almost all single sequence replacements had no measurable effect on protein structure and function.

4) Across species the "same" protein can diverge in sequence by up to 40%, while keeping the same structure. Sometimes this goes as far as 80%.

Given these basic facts, the findings in the paper aren't really surprising to anyone who studies proteins.

[Note: As with everything in biology, you can find counter examples. The histone proteins involved in DNA packing have an incredibly conserved sequence.]

If you don't have f(n * 0) == n * f(0), then all sorts of weird stuff happens. Compare these two:

  For f(x) -> [0, 255] then f(0) + f(0) + f(0) = 3 * 0 = 0

  For f(x) -> [0.5/8,7.5/8] then f(0) + f(0) + f(0) = 3 * 0.5/8 = 1.5/8

Choosing f(x) -> [0.5/8,7.5/8] breaks the algebraic correspondence.