Posts in: science

January lectures of note

The calendar is full again. Rejoice?

I tend to add “to all who celebrate” because the Serbian Orthodox Church is still on the Julian calendar, which is off by 13 days. Most orthodox churches are aligned with the Gregorian calendar and have been so for the last 100 years thanks to a revision proposed by — drumroll please — the Serbian Orthodox Church. Having a good idea and not following through because Russia isn’t on board is a typical Serbian thing to do, so points for consistency I guess.

Today’s Washington Post has a good write-up on how genetic engineering of the near-extinct American chestnut tree to make it more resistant to infection went wrong:

After he enlisted the help of Ek Han Tan, a geneticist at the University of Maine, to analyze the chestnut’s genome, they made their discovery this fall: The plants they were working on were, in fact, not Darling 58 trees.

Instead, they found they were working with a different chestnut line — called the Darling 54 — where the gene was inserted in another chromosome entirely, potentially corrupting one of the tree’s existing genes.

…

In a phone interview, Newhouse, the SUNY ESF director, acknowledged the mix-up but said he wasn’t sure what transpired.

“As far as exactly how it happened, we don’t know,” he said. “It must have been a label swap between these two trees that we were working with at the same time” in or around 2016.

The brilliant minds who think engineering mosquitos is a good idea can’t foresee that even a seemingly innocuous clerical error can lead to disaster, never mind the second-order effects to nature if your project succeeds. Whoever’s read Taleb’s Incerto (or some of his tweets) knows better.

If you think yourself a scientist or physician-scientist, please stop what you are doing and dedicate 5 minutes to reading Darren Dahly’s tip for recording data in a spreadsheet. Your future self, your statistician, and the general scientific community will thank you.

Adam Mastroianni is out with another long essay about science and how statistics are not the be-all and end-all of finding the truth, because:

… the whole ritual of “run study, apply statistical test, report significance” is only about 100 years old, and the people who invented it were probably drunk.

So a bunch of drunks built modern statistics on the foundations of probability theory created by a bunch of gamblers. Sweet.

Last year we showed that “better” cancer drugs don’t necessarily cost more. In a follow-up analysis just out in JAMA Network Open, it looks like novelty doesn’t have much to do with the price either. Then what does? To paraphrase № 46: drugs cost whatever the market will bear.

If you’ve haven’t heard of Big Biology until today, well, welcome to the club. It’s a podcast, and it describes itself thusly:

Scientists talking to scientists, but accessible to anyone. We are living in a golden age of biology research. Big Biology is a podcast that tells the stories of scientists tackling some of the biggest unanswered questions in biology.

Right up my alley! I started with the latest episode, on invasive species, and the intro seems a bit too scripted, but the focus is on the interviews, and those delivered. It’s already on my Overcast list of regulars. (ᔥRobin Sloan)

December lectures of note

Not too much this month, for understandable reasons:

There is both a science and an art to medicine. The “art” part usually comes into play when we talk about bedside manner and the doctor-patient relationship, but recognizing and naming diseases — diagnosis — is also up there. José Luis Ricón wrote recently about a fairly discrete entity, Alzheimer’s disease, and how several different paths may lead to a similar phenotype. This is true for most diseases.

But take something like “cytokine release syndrome”, or “HLH”, or any other syndromic disease that is more of a suitcase phrase than anything, and that can present as a spectrum of symptoms. Different paths to different phenotypes, with only a sleigh of molecular storytelling to tie them together. Yet somehow it (mostly) works. It’s quite an art.

No one is hiding the miracle cures

So, who wants to dismantle the FDA, you ask? Some patient advocacy groups, among others, aided by a few senators:

We need the FDA to be more insulated from these forces. Instead, every few years, legislators offer bills that amount to death by a thousand cuts for the agency. The latest is the Promising Pathways Act, which offers “conditional approval” of new drugs, without even the need for the preliminary evidence that accelerated approval requires (i.e., some indication that biomarkers associated with real outcomes like disease progression or survival are moving in the right direction in early drug studies).

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This bill is being pushed by powerful patient groups and has the support of Democratic senators like Kristin Gillibrand and Raphael Warnock, who should know better.

The bill would codify using “real-world data” and unvalidated surrogate endpoints for something called “provisional approval”, a level below the already tenuous accelerated approval.

I can see how it may appeal to patients: you may get a promising new drug for your life-threatening, debilitating disease sooner via this pathway. On the other hand, there are already mechanisms in place that enable access to these: a clinical trial, for one. Or expanded access (a.k.a. “compassionate use”) for those who may not be eligible for a trial.

So how would “provisional approval” help? If anything, wouldn’t it transfer the risks and — importantly — costs of drug development from the drug manufacturer/sponsor/study investigator to the patient?

Ultimately, the reason why there aren’t many cures for rare, terminal diseases is not because the big bad FDA is keeping the already developed drugs away from patients but rather because they are devilishly difficult to develop at our current level of technology. Wouldn’t it then make more sense to work on advancing the technology The careful reader will note that the opposite is being done, and I write this as no great fan of AI. that would lead to those new cures? I worry that the Promising Pathways Act would solve a problem that doesn’t exist by adding to the already skyrocketing costs of American health care. But that could be just me.

(↬Derek Lowe)