I’d feel schadenfreude, except that it’s such a damn sad waste

Alternative medicines: they claim to cure all kinds of ailments, or at best they promise that they’re harmless supplements. Now here comes the data that says some herbal remedies are correlated with increased cancer risk.

According to a study published Wednesday in Science Translational Medicine, traditional components of herbal remedies used throughout Asia are widely implicated in liver cancers there. In Taiwan, for instance, 78 percent of 98 liver tumors sampled displayed a pattern of mutations consistent with exposure to herbs containing aristolochic acids (AAs). These are carcinogenic components found in a variety of centuries-old herbal remedies said to treat everything from snakebites to gout, asthma, and pain.

Because of their toxicity, some (but not all) of the herbs and plants known to contain AAs have been banned in Taiwan and other places. These flora tend to come from the genera Aristolochia (e.g., birthwort, pipevine) and Asarum (wild gingers). The Food and Drug Administration has also issued several warnings and advisories over AA-containing remedies.

Also relevant: patients who replace tested medicines with alternative crap have a 5x higher death rate within 5 years.

There’s a reason there are tested guidelines in place for careful, controlled studies of medicines, and why side-effects and long-term consequences are scrutinized thoroughly. What’s the point of a treatment for gout that works, hypothetically, if it increases your risk of liver cancer?

There are also reasons for ethical guidelines. Take, for example, this experimental vaccine for herpes that was designed by William Halford and backed by Peter Thiel. They bypassed IRB review; they ignored FDA guidelines; they carried out the tests on an island in the Caribbean, St Kitts, to bypass US oversight requirements. They injected 20 patients who really were suffering with serious, chronic herpes infections with a weakened virus, and got mixed results — for some it changed how subsequent expressed themselves, for others, it made the symptoms worse. The researchers failed to demonstrate either safety or efficacy.

And then, to make it even worse, Halford died, leaving the patients and the study in the hands of…who? No one. By abandoning responsible oversight, he’d left the legitimate biomedical authorities free of any obligation.

Maybe Peter Thiel will step forward and take responsibility for this botched and poorly designed experiment.

I can laugh at that idea, at least. But not at the desperate people who take bizarre alternative medicines or leap at terrible forlorn hope therapies.

The continuing saga of the scientific implosion of the Wansink lab

How can anyone be this sloppy?

Originally published in JAMA Pediatrics in 2012, the study found that children were more likely to choose apples over cookies during lunch when the apples had a sticker of Elmo. Both the original and the replacement claimed that the study included 208 students “ranging from 8 to 11 years old” at seven schools in upstate New York.

But, as confirmed to BuzzFeed News by the leader of the study, Cornell University professor Brian Wansink, the data was actually collected while observing kids 3 to 5 years old.

“We made a mistake in the age group we described in the JAMA article. We mistakenly reported children ranging from 8 to 11 years old; however, the children were actually 3 to 5 years old,” Wansink told BuzzFeed News by email.

As the “leader of the study”, you’d expect someone to have some vague idea of the approximate ages of the subject…you’d at least know whether the school you were testing at was a pre-school or an elementary school. This is what you’d expect of a guy who is great at churning out papers and grant proposals, but is a bumbling incompetent at the science. Unfortunately, most of the rewards of science go to those who excel at the first set of skills, while the second has a low priority.

Anti-vaxxers behaving badly

Another study has come out claiming a link between vaccinations and autism — and it has been retracted. The paper was deeply flawed in a lot of ways, but we can ignore the poor experimental design, the bad statistics, the cherry-picking of the data, and the funding from dubious sources, and focus entirely on one crystal clear concern: they faked their data. One of their figures is a jiggery-pokery jigsaw assemblage of gel bands copy-pasted into an image that bears little relationship to reality.

The principal investigator, Christopher Shaw, was confronted with these obvious, irrefutable facts of faked data, and he goes into an unconvincing song-and-dance of denial. He doesn’t know who could have done this or why, he says.

We don’t know how some images in the manuscript came to be altered. We investigated when the first suggestions came out in Pubpeer and confirmed that some of the images had indeed been manipulated. We don’t know by whom or why. The first author, Dr. Dan Li, denies doing anything wrong, but has not provided any information about this in spite of repeated questions from us. We are continuing to pursue these questions, but as she is now at another institution, we can’t force her to comply.

Those are outright lies. He knows. The figures for a paper do not simply manifest out of thin air — Shaw had to have discussed this illustration with Li. If he didn’t contribute directly to the paper himself, he is responsible for delegating the work. It’s got 4 authors on it; they had to have talked about the data, worked to interpret it, decided how these data supported their hypothesis, and put together a publishable story. The person who put so much remarkable effort into cobbling together a totally fake image had to have done so consciously — you don’t ‘accidentally’ make at least a dozen edits and reorganize the contents of an image in Photoshop.

Shaw also claims that the figures were not significant anyway. Then why publish it? This is another lie. They thought it was worth including in the paper, and someone went to considerable effort to mangle the data — why would they risk compromising their scientific integrity for a figure that they think doesn’t matter?

Faking data is the second most serious crime you can commit against science (the first would be ethics violations that do harm, which includes faking data). It is unforgivable. Retracting this paper is an inadequate response — the perpetrators ought to be fired, any grants rescinded, and there ought to be an asterisk, at least, on all of their published papers because their data is clearly untrustworthy. Two of the authors, Shaw and Tomljenovic, have a history of dubious work and past retractions. They still get published. The University of British Columbia is still defending them, which is unfortunate since it taints all the legitimate research done there.

Shaw is blaming others for his problems.

“Anti-vaccine” researcher is an ad hominem term tossed around rather loosely at anyone who questions any aspect of vaccine safety. It comes often from blogs and trolls, some of which/whom are thinly disguised platforms for the pharmaceutical industry… Anyone who questions vaccine safety to whatever degree gets this epithet.

This is nonsense. Imagine it’s true that there is a conspiracy against you, and swarming trolls are trying to destroy your reputation. What would you do? Would you be particularly careful to make your work above criticism, consulting with colleagues to get a thorough inspection of your data and interpretations before publishing them, or would you get so sloppy that you would eagerly publish an easily detectable manipulated figure?

Fire the lot of ’em. Forging data is such an egregious crime in science that it ought to warrant retraction of tenure.

This chart is a lie

Serial cables are neutral? No way. Chaotic evil. I had to make too many of them. DB9 or DB25, or some ghastly custom pinout some manufacturer saw fit to stick on their device? I’ve encountered lots where all you need is 3 pins — ground, transmit, and receive — but even then you have to worry about whether this is a straight pass-through cable or a null modem cable. Some devices require one or several of the handshaking lines to be enabled — but different machines require different handshakes. Do you need DTR or DCD? Sometimes yes, sometimes no. Then some of those handshake lines are completely redundant, and you can make it work just fine by shorting out the line to one of the other pins.

I remember the bad old days when you’d buy laboratory devices and they’d have some odd connector hanging off the back and there’d be a cryptic pinout diagram in the specs, and you’d have to solder up your own cable for it. It was not a happy time.

A science video about gonad development

A bit about the early development of human gonads.

A few useful sources:
Sadler TW. 2014. Langman’s Medical Embryology. LWW. ISBN: 1451191642.

Everyone needs to have a copy of Langman’s around. Diagrams in the video were taken from this text.

Sajjad Y. 2010. Development of the genital ducts and external genitalia in the early human embryo. J Obstet Gynaecol Res. 36(5):929-37. doi: 10.1111/j.1447-0756.2010.01272.x.

A good review of the embryonic plumbing.

Zhao F, Franco HL, Rodriguez KF, Brown PR, Tsai MJ, Tsai SY, Yao HH. 2017. Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science 357(6352):717-720. doi: 10.1126/science.aai9136.

New stuff: a nice example of a female gene product that actively suppresses a male developmental feature.

I could use bigger muscles, but I’m not going to get them with biotech in my garage

Josiah Zayner is a self-proclaimed bio-hacker. He sells CRISPR/CAS9 home gene editing kits, and he goes to conferences where he publicly injects himself with chemicals to modify his own genes. For instance, at a biotech conference, he got up on stage and injected himself with a cocktail to knock out the myostatin gene, to give himself “bigger muscles”.

If you want to genetically modify yourself, it turns out, it’s not necessarily complicated. As he offered samples in small baggies to the crowd, Zayner explained that it took him about five minutes to make the DNA that he brought to the presentation. The vial held Cas9, an enzyme that snips DNA at a particular location targeted by guide RNA, in the gene-editing system known as CRISPR. In this case, it was designed to knock out the myostatin gene, which produces a hormone that limits muscle growth and lets muscles atrophy. In a study in China, dogs with the edited gene had double the muscle mass of normal dogs. If anyone in the audience wanted to try it, they could take a vial home and inject it later. Even rubbing it on skin, Zayner said, would have some effect on cells, albeit limited.

He does not look particularly muscular in his photos.

He’s a snake-oil salesman. He’s doing this demonstration, confident that nothing will go wrong, because he must know that this is a spectacularly inefficient way to use CRISPR/CAS9. I looked over his website, and there’s no information on the frequency of incorporation of his edited sequence into cells, or even on whether they’ve seen any phenotypic effects with this approach. I suspect there’s little effect, which is a good thing. Even if he does get incorporation into some cells, he’s not going to get much of a result — myostatin affects the growth and differentiation of myocytes (it’s not going to do a lot for an adult), and regulates protein synthesis in muscle cells, which could, in fact, promote more ‘bulking up’ of existing muscle mass.

That’s not necessarily a good thing. Cardiac hypertrophy is not something you want to have, and Zayner isn’t exactly controlling delivery of his reagents to specific subsets of muscle cells.

But again, he’s almost certainly not getting enough DNA modification to have either his desired result or a deleterious result. He’s just gambling that the injections will be innocuous enough that they won’t actually do anything except look impressive to the rubes. Here’s hoping he doesn’t get erroneous editing of random cells so that basically, all he’s doing is giving himself a low-dose mutagen.

George Church is the voice of reason on this one.

If you modify your DNA, it’s possible to then sequence your DNA to see if you made the targeted change. But a garage experiment also can’t provide as much information as more conventional methods. “You can confirm that you’ve altered the DNA, but that doesn’t mean that it’s safe and effective,” says George Church, professor of genetics at Harvard Medical School (who also serves as an advisor to Zayner’s tamer kit company, recognizing the value of a biology-literate public in what’s being called the century of biology). “All it does is tells you that you’ve molecularly done the right thing, but it could be unsafe because you’ve also done something off-target. It could be ineffective in the sense that not enough cells were altered, or it’s too late in life and the damage has already been done.” If a baby is born with microcephaly, for example, changing the genes in its body likely won’t be able to change the effects of the condition on its brain.

Zayner’s vial of CAS9 myostatin knock-out juice is really cheap, at only $20. It also makes me wonder about quality control and safety at his workplace, though. I’d worry more about contaminants in a random vial of fluids that I’m expected to inject into my bloodstream than that it contains the latest biotech buzzword.