But they’re too complicated!

That dirty open secret in biomedical research: bias gets built into the study design.

For decades, scientists have embarked on the long journey toward a medical breakthrough by first experimenting on laboratory animals. Mice or rats, pigs or dogs, they were usually male: Researchers avoided using female animals for fear that their reproductive cycles and hormone fluctuations would confound the results of delicately calibrated experiments.

“Delicately calibrated” seems to be used as a synonym for “not robust”. If your results are so finicky that they don’t hold true in translation from male to female rats, why would you expect them to hold up in translation from rats to people? There are detectable differences in male and female physiology that turn out to matter, so this business of ‘simplifying’ by focusing entirely on one sex means women’s medicine suffers.

There is good news. Now the NIH is cracking down and telling researchers that they must test mixed sexes, or no money for you. That’s an effective incentive.

It also turns out that the decision to ‘simplify’ by studying only male experimental animals is a bad one, borne of a bias that women are hypervariable because of their menstrual cycle — other studies find that male animals tend to be more variable.

Bias in mammalian test subjects was evident in eight of 10 scientific disciplines in an analysis of published research conducted by Irving Zucker, a professor of psychology and integrative biology at the University of California, Berkeley. The most lopsided was neuroscience, where single-sex studies of male animals outnumbered those of females by 5.5 to 1.

Contrary to the conventional wisdom in laboratories, there is far more variability among males than among females on a number of traits and behaviors, Dr. Zucker has found. Yet even when researchers study diseases that are more prevalent in women — anxiety, depression, thyroid disease and multiple sclerosis among them — they often rely on male animals, according to another analysis led by Dr. Zucker, who has written extensively on gender bias in scientific research.

At least I can say I’m safely innocent of this bias: all my work is on zebrafish embryos between fertilization and about 48 hours, and they don’t have sexes yet. I couldn’t sort out male and female embryos if I wanted to.

The danger of correlational studies

My doctor had me on fish oil pills for quite a while — they were a popular supplement that was supposed to reduce the incidence of heart disease. She told me not to bother any more about a year ago, as more information was coming out that they didn’t really do anything. Now it looks like the original study that started the fish oil fad is falling apart.

The original study, by Danish physicians H.O. Bang and D.J. Dyerburg, claimed Inuit in Greenland had low rates of heart disease because of their diet, which is rich in fish oil and omega-3 fatty acids from eating fish and blubber from whales and seals.

"I reviewed this original paper and it turned out to be that they actually never measured the frequency of heart disease in [Inuit]," said Dr. George Fodor, the new study’s lead researcher.

If you’re going to do a correlational study, you have to be fairly rigorous in exactly what you’re measuring: if you’re going to claim that Substance X has an effect on Disease Y, it’s kind of important that you’re actually measuring Disease Y. In this case, the correlation wasn’t what they claimed it was: it was more like, poverty-stricken indigenous populations with limited access to public health facilities poorly document their incidence of disease.

Fodor and his team of three other researchers found that the chief medical officer’s annual records were likely deficient because the inaccessible, rural nature of Greenland made it difficult to keep accurate records, and also because many people didn’t have access to doctors.

The 2014 study has found that Inuit do have similar rates of heart disease compared to non-Inuit populations, and that death rates due to stroke are “very high.”

The study also shows that the Greenland Inuit overall mortality is twice as high as non-Inuit populations.

This is almost as bad as the claim that the paleo diet must be good for you, because public health records from the paleolithic are even scantier than those for the Inuit.

#PLOSGenetics: The Case for Junk DNA

This is the paper to read: Palazzo & Gregory’s The Case for Junk DNA. It clearly and logically lays out the complete argument from evidence and theory for the thesis that most of the genome is junk. It’s not revolutionary or radical, though: the whole story is based on very fundamental population genetics and molecular biology, and many decades of accumulated observations. And once you know a little bit of those disciplines — you don’t need to be a genius with a great depth of understanding — the conclusion is both obvious and in some ways, rather trivial.

Here’s that conclusion:

For decades, there has been considerable interest in determining what role, if any, the majority of the DNA in eukaryotic genomes plays in organismal development and physiology. The ENCODE data are only the most recent contribution to a long-standing research program that has sought to address this issue. However, evidence casting doubt that most of the human genome possesses a functional role has existed for some time. This is not to say that none of the nonprotein-coding majority of the genome is functional—examples of functional noncoding sequences have been known for more than half a century, and even the earliest proponents of “junk DNA” and “selfish DNA” predicted that further examples would be found. Nevertheless, they also pointed out that evolutionary considerations, information regarding genome size diversity, and knowledge about the origins and features of genomic components do not support the notion that all of the DNA must have a function by virtue of its mere existence. Nothing in the recent research or commentary on the subject has challenged these observations.

The whole ENCODE debacle, in which hundreds of millions of dollars was sunk into an effort to identify the function of every bit of the genome, was a PR disaster. Larry Moran asks how Nature magazine dealt with the errors; the answer seems to be with denial. Authors of the ENCODE report are claiming they were “misunderstood & misreported” and that they aren’t “backing away from anything”.

I’m not too dismayed that science journalists didn’t understand how the claims of ENCODE conflicted with evolutionary biology, since I don’t expect journalists to have the same focus on the science (this is not a knock on science journalism; I have a lot of respect for the good practitioners of the art, but just that they have different priorities than the working scientists who have to deal with the background details). But what really shocks me is that big-name genomics researchers, people who get awarded lots of money to study the structure of the genome, don’t understand the fundamentals laid out for them in the Palazzo & Gregory paper. It’s not that I expect every scientist to know the entirety of a gigantic field — heck, I get confused and lost every time I read a bioinformatics paper — but these are scientists paid in big money and prestige to study genome function who don’t have a grasp on the evolutionary constraints on genome function, which seems to be a rather critical omission. And these scientists without a clue get elected to the Fellowship of the Royal Society.

How does that happen? I had this fantasy that science was a meritocracy and that great scientists advanced by having deep knowledge and doing great work, but it seems another way to succeed is leap into a new field and bamboozle everyone with technology.

I am so disillusioned.

That’s how to do a debate on a settled issue

John Oliver shows how it’s done. It’s a televised debate between a couple of deniers and 97 scientists.

I also learn that any time you see Nye engaged against someone on a talk show, the other guy is an idiot.

I also have an idea how to deal with those frequent debate requests on evolution that I get: I’ll agree, as long as I get to bring 40 or 50 friends to share the stage against the one loon.

The right wing’s new/old strategy for dealing with an uncomfortable reality

Declare that they are smarter than scientists. Simple!

George Will and Charles Krauthammer are right wing hacks who have an air of cultivated superciliousness that passes for intelligence in the smugly self-serving atmosphere of the Sunday morning talk shows…but they have no other talent or ability to justify their existence. The two got together on Fox News to pontificate on the usual conspiracy theories about how scientists are all lying. Here’s Will:

Now, there is, as Charles says, the policy question is how much wealth do we want to spend directly or in lost production in order to have no discernible measurable effect on the climate? People say, well, what about this report? There is a sociology of science. Scientists are not saints in white laboratory smocks. They have got interests like everybody else. If you want a tenure-track position in academia, don’t question the reigning orthodoxy on climate change. If you want money from the biggest source of direct research in this country, the federal government, don’t question its orthodoxy. If you want to get along with your peers, conform to peer pressure. This is what’s happening.

Krauthammer doubles down by claiming that all of science is subjective and simply made up by the eggheads.

99 percent of physicists convinced that space and time were fixed until Einstein working in a patent office wrote a paper in which he showed that they are not. I’m not impressed by numbers. I’m not impressed by consensus. When I was a psychiatrist, I participated in consensus conferences on how to define depression and mania. These are things that people negotiate in the way you would negotiate a bill, because the science is unstable, because in the case of climate, the models are changeable, and because climate is so complicated.

And then he declares that the conclusions of science are equivalent to superstition.

And you always see that no matter what happens, whether it’s a flood or it’s a drought, whether it’s one — it’s warming or cooling, it’s always a result of what is ultimately what we’re talking about here, human sin with the pollution of carbon. It’s the oldest superstition around. It was in the Old Testament. It’s in the rain dance of the Native Americans. If you sin, the skies will not cooperate. This is quite superstitious, and I’m waiting for science which doesn’t declare itself definitive but is otherwise convincing.

Do either of these guys have any knowledge of how science actually works? No. That doesn’t stop pundits from declaring it all invalid when it produces answers different from their ideological presuppositions, though. Isn’t it nice that the news media has become a haven for propagandists? It pays them a cushy salary and bolsters their prestige so they can go on air every week and engage in that exercise in projection in which they declare scientists to be scum-sucking shills who’ll say anything for money.

And now watch Marco Rubio. Oh, he’s pandering to the Tea Bagger vote.

Sen. Marco Rubio (R-FL) asserted recently that there was nothing that humans could do to stop climate change because it was not caused by humans, and that any new laws would only destroy our economy.

In an interview that aired on Sunday, ABC’s Jonathan Karl asked the Florida Republican if he agreed with scientists who said that two of the cities in his state were being threatened by climate change.

I don’t agree with the notion that some are putting out there — including scientists — that somehow, there are actions we can take today that would actually have an impact on what’s happening in our climate, Rubio insisted. Our climate is always changing. And what they have chosen to do is take a handful of decades of research, and say that this is now evidence of a longer-term trend that’s directly and almost solely attributable to manmade activity.

Don’t try to tell me these frauds aren’t science deniers.

The hbd delusion

A confession: I have long disliked Nicholas Wade’s science journalism. He has often written about biology in the NY Times, and every time he seems to make a botch of the reporting, because he actually doesn’t understand biology very well. For example, in his very last article for the NYT, he described some work that identified 12 genes found on the Y chromosome that are globally expressed — they aren’t just involved in testis development, for instance. This is no surprise. There are genes required for sperm differentiation found on autosomes, for instance, and the Y chromosome is not a gentleman’s club with “No Girls Allowed” tacked on the door. But Wade turned it into a phenomenon that explained the differences between men and women.

Differences between male and female tissues are often attributed to the powerful influence of sex hormones. But now that the 12 regulatory genes are known to be active throughout the body, there is clearly an intrinsic difference in male and female cells even before the sex hormones are brought into play.

I can sort of see his thinking: if there are genes that are found only on the Y chromosome that are expressed in all the cells of the body, then maybe they confer a non-sexual difference on only male behavior and physiology.

But that’s all nonsense. Those genes aren’t found only on the Y chromosome: they have homologs on the X chromosome. They aren’t “male” genes at all! As Sarah Richardson explains:

The 12 genes residing on the Y chromosome exist to ensure sexual similarity. The genes are “dosage-sensitive,” meaning that two copies are needed for them to function properly. We’ve long known that those 12 genes exist on X chromosomes. Females have the 12 genes active on both of their X chromosomes. If males, who have just one X, didn’t have them on the Y, they would not have a sufficient dosage of those genes. Now we know they do. Just like women.

You see what I mean? I’ve never trusted Wade’s science reporting, because it’s always been grossly wrong on the subjects I know well. I wouldn’t want Wade defending evolution education, either, especially since he argues for an evolutionary ladder. I’m not very interested in his ideas about the origin of life, which are rather bogus.

So you can imagine how I groaned when I heard that Wade was coming out with a new book, A Troublesome Inheritance: Genes, Race and Human History. Wade doesn’t understand genes, so now he’s going to misapply his incomprehension to a hot-button issue like race? Great. Expect all the ‘scientific racists’ to come out cheering. Steve Sailer, the racist ignoramus who likes to cloak himself in pseudoscience, considers it another shot in Wade’s long-running war with liberals. John Derbyshire, the guy who was too racist for the National Review because he wrote a grossly bigoted screed (published on the same site that published Sailer’s review!), who also serves up large dollops of sexism, thinks it is a significant step for race realism.

Oh, a hot tip: these new racists really hate being called racists, so they’ve been struggling for years to come up with a new label. “Scientific Racism” and “Academic Racism” didn’t test well; they’ve still got “racism” in the name. For a long time they called themselves “Race Realists”, which I always read as “really racist”. That’s gone by the wayside now, mostly. The term of art you’re looking for now is “Human Biodiversity”, or “hbd” for short. Notice — “race” isn’t in the label any more. But don’t be fooled, hbd really is just the slick new marketing term for modern racism.

A good (but too generous) review of Wade’s book by Andrew Gelman notes that racism never really seems to change — it’s just that the targets always shift to reflect current stereotypes.

I suspect that had this book been written 100 years ago, it would have featured strong views not on the genetic similarities but on the racial divides that explained the difference between the warlike Japanese and the decadent Chinese, as well as the differences between the German and French races. Nicholas Wade in 2014 includes Italy within the main European grouping, but the racial theorists of 100 years ago had strong opinions on the differences between northern and southern Europeans.

We don’t even have to go back a century — racial presuppositions have changed within my lifetime.

One of Wade’s key data points is the rapid economic growth of East Asia in the past half-century: “In the early 1950s Ghana and South Korea had similar economies and levels of gross national product per capita. Some 30 years later, South Korea had become the 14th largest economy in the world, exporting sophisticated manufactures. Ghana had stagnated.” Wade approvingly quotes political scientist Samuel Huntington’s statement, “South Koreans valued thrift, investment, hard work, education, organization, and discipline. Ghanaians had different values.” And Wade attributes these attitudes toward thrift, investment, etc., to the Koreans’ East Asian genes.

This all fits together and could well be true. But … what if Wade had been writing his book in 1954 rather than 2014? Would we still be hearing about the Korean values of thrift, organization, and discipline? A more logical position, given the economic history up to that time, would be to consider the poverty of East Asia to be never-changing, perhaps an inevitable result of their genes for conformity and the lack of useful evolution after thousands of years of relative peace. We might also be hearing a lot about Japan’s genetic exclusion from the rest of Asia, along with a patient explanation of why we should not expect China and Korea to attain any rapid economic success.

Isn’t that convenient? Somehow, the reality of race realists — excuse me, hbd proponents — always seems to mirror our prejudices. And most strangely, when asked for evidence, they always simply point to current trends or current sweeping characterizations of whole groups as supporting their contentions…never mind that we see rapid shifts in the overall behavior or status of those cultures that cannot be explained by genetics.

Noah Smith has an excellent explanation of the pseudo-scientific strategem of the hbd crowd. It’s all about overfitting.

Here’s how academic racism generally works. Suppose you see two groups that have an observable difference: for example, suppose you note that Hungary has a higher per capita income than Romania. Now you have a data point. To explain that data point, you come up with a theory: the Hungarian race is more industrious than the Romanian race. But suppose you notice that Romanians generally do better at gymnastics than Hungarians. To explain that second data point, you come up with a new piece of theory: The Romanian race must have some genes for gymnastics that the Hungarian race lacks.

You can keep doing this. Any time you see different average outcomes between two different groups, you can assume that there is a genetic basis for the difference. You can also tell "just-so stories" to back up each new assumption – for example, you might talk about how Hungarians are descended from steppe nomads who had to be industrious to survive, etc. etc. As new data arrive, you make more assumptions and more stories to explain them. Irish people used to be poor and are now rich? They must have been breeding for richness genes! Korea used to be poorer than Japan and is now just as rich? Their genes must be more suited to the modern economy! For every racial outcome, there is a just-so story about why it happened. Read an academic-racist blog, like Steve Sailer’s, and you will very quickly see that this kind of thinking is pervasive and rampant.

There’s just one little problem with this strategy. Each new assumption that you make adds a parameter to your model. You’re overfitting the data – building a theory that can explain everything but predict nothing. Another way to put this is that your model has a "K=N" problem – the number of parameters in your model is equal to the number of observations. If you use some sort of goodness-of-fit criterion that penalizes you for adding more parameters, you’ll find that your model is useless (no matter how true or false it happens to be!). This is one form of a more general scientific error known as "testing hypotheses suggested by the data", or "post-hoc reasoning". It’s a mistake that is by no means unique to academic racism, but instead is common in many scientific disciplines (cough cough, sociobiology, cough cough).

Wade continues in this fine tradition. I considered reading his book, just to tear it up, but I don’t think it’s worth the effort, from the reviews — it’s just another collection of anecdotes dressed up with Wade’s sloppy understanding of genes.

The truth only bullies liars

Gah. SE Cupp. She is the worst: a right-wing atheist who fully supports the dishonesty of the Fox News types, and who has no regard for reality. Atheists who bury themselves in a new set of delusions sicken me.

She got into an argument with Bill Nye — that’s a bad sign, since the last loon he had to put down was Ken Ham. She was really peeved that those “science guys” keep confronting climate change denialists with facts. Science bullies her ideological cronies!

“Isn’t it a problem when science guys attempt to bully other people?” Cupp asked Nye. “Nick here had to say, ‘I’m not a denier.’ He had to get it out: ‘I’m not a denier.’ Because really, the science group has tried to shame anyone who dares question this, and the point I’m trying to make is, it’s not working with the public.”

This was after she threw up some statistics, that only 36% of the American public think global warming is a serious threat to their way of life. I’d have two replies to that: 1) polling data on what a deluded public thinks is not a measure of the truth, and 2) the problem here isn’t scientists explaining the science, it’s propagandists like Cupp using dishonest media like Fox News or Heritage Foundation tracts to cast fear, uncertainty, and doubt over the evidence.

Watch the encounter and see Cupp hopelessly outclassed.

Best part of the interview? This exchange:

nyenamite