Doug Axe published a good paper in 1996

I just found this paper, and it’s very surprising. I’ll get to it at the end…

And one must be even more careful to distinguish between what someone says and what has been demonstrated to be true empirically. Go on…

A quote, even if correct, is not “what has been demonstrated to be true empirically.” Where’s the evidence? Not just some of it.

And where’s the quote in the video?

No theory or speculation is necessary. Abzymes, which are enzymes, show that enzymatic activity is common in random sequences.

Ignoring the implications of the hard data from abzymes, and from studies like this:

…in which the authors started with a single random sequence,

is like a trial lawyer ignoring video footage of a crime in favor of the testimony of his client’s imaginary friends, wouldn’t you say?

It’s not complicated at all; one of my graduate students could have done it in a couple of weeks.

I don’t have any trouble understanding that it is an extraordinarily weak paper, since he started with an unstable temperature-sensitive mutant, not a wild-type protein, and he did neither structural nor enzymatic assays.

It’s fascinating that you mention expertise, as I have far more experience in relating changes in protein sequence to structure and function than Doug Axe has, while AFAIK you have zero. If you’re going to invoke appeals to authority, isn’t it more than a bit hypocritical for you to be here lecturing?

This is an amazing bit of cherry picking. Why wouldn’t you cite Doug Axe’s very own paper?

Completely random!
Doesn’t that contradict everything you’ve claimed here?

D D Axe, N W Foster, and A R Fersht found that they could change all 13 of the core residues of barnase to other random hydrophobic residues. That change corresponds to a 12% alteration in the initial sequence! That’s more than a 10-fold difference from the experiment you cherry picked. Do you not believe in his data? How could you work at the DI and not be familiar with this paper?

What’s more, this was a pretty good paper, because Axe and his colleagues devised a very sensitive, yet simple assay to measure very low barnase activities. Given this, Axe’s solo 2004 paper looks even more contrived, since it did not include a single structural or biochemical assay.


That is interesting. I would be interesting to see of Doug Axe ever cites this paper in his ID work or if it was lost down a memory hole.

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It’s pretty surprising that one can replace the entire hydrophobic core.

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