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Another study has come out claiming a link between vaccinations and autism — and it has been retracted.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.

Evolutionary Psychology poisons everything

This study comes to a happy conclusion, and then wrecks it all with EP bullshit. What the researchers did was to email requests for either a pdf of a paper or copies of the raw data to researchers, and what they found was a high degree of cooperativity: 80% were willing to send a pdf, 60% were willing to send data. They seem to think this is surprisingly prosocial, but actually, I was a little surprised the numbers were so low. I was brought up to consider this to be expected — back in my old-timey days, when you published a paper, you also ordered a great big box of reprints, because people would send you postcards asking for a copy, and you’d mail it to them. Now you just push a button on a computer, and only 80% oblige? OK, I guess that’s an alright result.

They analyzed further, though, and also found a sex difference. If you were a man requesting a paper from a man, you were 15% more likely to get a positive response. That’s troubling. I’d say that that could be interpreted as indicating a continuing sexism in science. But that’s not enough for these authors.

There is no evolutionary analysis involved in this study, but of course, the reason for their result is…evolution.

Massen and his colleagues say that one possible explanation for their results “may be that among male academics there is a network at play, in which they favor each other much like ‘Old Boy’ networks”. They also suggest that this imbalance might have evolutionary roots and point to an idea called the male-warrior hypothesis, which states that men have evolved to form strong bonds with other males in their group because in the past this enabled them to defend territory from hostile attackers.

“Men are more ready to cooperate with genetic-stranger males to form these fighting coalitions,” says Mark van Vugt, an evolutionary psychologist at the Free University of Amsterdam who first suggested the theory in 2007. Some of the evidence for this idea comes from lab-based tasks such as public-goods games (in which volunteers choose how many tokens to keep or share), but there are some real-world hints too, he says. Boys tend to play in larger groups than girls, van Vugt says, and in sports such as tennis and boxing, men make more effort to bond with their opponent after a match or fight than women do. However cultural factors are also thought to be at work.

Jebus. Can I just say the words “US Women’s Soccer Team” and see this whole bogus line of reasoning vanish in a spray of flop sweat and tears from the men’s team?

Biology is going to put a crimp in the space program

Scott Kelly served on the International Space Station for 340 days, partly as an experiment to see how the human body held up in long term weightlessness. Not well, it turns out. Kelly writes about his experience on finally returning to Earth.

I struggle to get up. Find the edge of the bed. Feet down. Sit up. Stand up. At every stage I feel like I’m fighting through quicksand. When I’m finally vertical, the pain in my legs is awful, and on top of that pain I feel a sensation that’s even more alarming: it feels as though all the blood in my body is rushing to my legs, like the sensation of the blood rushing to your head when you do a handstand, but in reverse.

I can feel the tissue in my legs swelling. I shuffle my way to the bath room, moving my weight from one foot to the other with deliberate effort. Left. Right. Left. Right. I make it to the bathroom, flip on the light, and look down at my legs. They are swollen and alien stumps, not legs at all. “Oh shit,” I say. “Amiko, come look at this.” She kneels down and squeezes one ankle, and it squishes like a water balloon. She looks up at me with worried eyes. “I can’t even feel your ankle bones,” she says.

“My skin is burning, too,” I tell her. Amiko frantically examines me. I have a strange rash all over my back, the backs of my legs, the back of my head and neck – everywhere I was in contact with the bed. I can feel her cool hands moving over my inflamed skin. “It looks like an allergic rash,” she says. “Like hives.”

I’m rather appalled that this experiment was done at all — we’ve known about the deleterious effects of shorter periods of weightlessness for a long time, so it’s bizarre that they pushed for longer and longer exposures. Were they hoping everything would just get better, that the human body would adjust to living in space? Because if they did, they’d have made returning home even more traumatic.

Face it, if we’re going to have people working in space for months or years, the hardware is going to have to provide some kind of substitute for gravity — great big spinning wheels, ala 2001, or built-in central centrifuges. I would hope that our space agencies would stop wrecking human bodies in pointless exercises in endurance.

I can think of more productive experiments. How much gravity is enough? Do we need a full 1G to be healthy, or would, for instance, .38G, as found on Mars, be enough? Of course, to do that kind of experiment they would need to build one of those rotating space stations, so we’re talking big money and a reset of the ISS.

We’re also ignoring the effects of prolonged radiation exposure. It’s not just the weightlessness. I have the feeling that there are a lot of ghoulish doctors working for NASA who are going to be ticking off symptoms and writing papers on the deterioration of human bodies in space,
which will be ignored by the administrators and politicians who will make speeches about the heroic sacrifices our brave astronauts are making.

An alternative strategy: let’s train tardigrades to crew space ships, if we must have biological entities aboard.

Newsweek, peddling tabloid bunk

I can’t believe they went down this road…LAS VEGAS SHOOTING: WHAT CONTROVERSIAL GENETICS THEORIES SUGGEST ABOUT THE MOTIVE. What controversial “theory” do they have? That his genes made him do it.

The suspect behind the mass shooting in Las Vegas on Sunday might have been at higher risk for criminal behavior because his father was apparently once on the FBI’s most-wanted list, according to controversial theories about links between crime and genetics.

That’s it. That’s all of their “evidence”: his father was a criminal, therefore he might have inherited genes that caused criminality. There’s no consideration of the likelihood that growing up in a family where the father was on the lam from the FBI, was robbing banks, and who was never around the kids. So you’ve got kids from a broken family, and one of them commits a criminal act in life, therefore it’s genes? Weak. They bring in an Authority to help back up their claim.

“I was really blown away by the fact that his father had this history, and it’s really hard to argue that this would have nothing to do with Stephen Paddock’s behavior,” says Deborah Denno, a professor and the founding director of the Neuroscience and Law Center at the Fordham University School of Law in New York City. “He may have inherited certain attributes from his father that would lead to greater impulsivity.”

Deborah Denno is a lawyer, not a neuroscientist, and definitely not a geneticist. Despite that handicap, I wonder what her legal training would say about trying a suspect, not on the evidence of his behavior, but on the criminal history of his father?

The article does bring in a few voices of reason, like J.C. Barnes and Art Caplan, trying to argue that you can’t defend this argument, but too late, the damage is done. Newsweek published a garbage article promoting an indefensible, fact free claim of the genetic determination of behavior. Shame.