Brave New World?

There has been a lot of yammering but very little explanation or understanding of the baby recently born to a Jordanian couple which is purported to have "three parents." The technique which made this possible is illegal in the United States and apparently for some reason offensive to many people.

The baby does not have three parents, he has two. What he also does not have is Leigh's disease, which is the whole reason the procedure was done. But in order to really understand what happened, you need to understand something about the history of life on earth, which was not created in seven days 10,000 years ago.

Some time around 2 billion years ago (no way to be at all exact) one cell absorbed a smaller one, which survived and reproduced inside it and so the smaller cell's descendants continued to inhabit the larger cells descendants after the larger cell divided. The two cell types then evolved together as a symbiotic community. The smaller cell gradually lost most of its genetic material (some of it may have migrated to the nucleus of the larger cell) and was reduced to specialty functions, most notably as the manufacturer of Adenosine Triphosphate, the cell's energy source. The DNA that remains in the mitochondrion is only what is needed for mitochondrial functioning. It has not influence on the development or characteristics of the organism beyond any effect of defective mitochondrial functioning, an example of which is Leigh's disease.

The nuclear DNA is the DNA that combines chromosomes from the mother and father, and determines everything else about our genetic inheritance. The mitochondria are inherited exclusively from the mother through the cytoplasm of the ovum. You could vacuum out all the healthy mitochondria from a fertilized ovum (gamete) and replace them with equally healthy mitochondria from a different, completely unrelated person and the resulting human would be completely unaffected.

In this case, the mother had some healthy mitochondria and others that had a fatal mutation. She had enough healthy ones that she was not ill, at least not seriously; but there's no telling what the proportion of functional and non-functional mitochondria will be in any of her ova. Unfortunately, she'd had the bad luck to have two babies who were severely affected and who died young. What the doctors did in this case was simply to transplant the nucleus from one of her ova into another woman's ovum from which the nucleus had been removed, and fertilize it with her husband's sperm. Result: baby with two parents and no mitochondrial disease.

It had to be done in Mexico because it's illegal in the U.S. I await an explanation of why this is unethical.

Social Psychology vs. Parapsychology

Hard to say nowadays which is less credible as science. Here's a lengthy post by Andrew Gelman about the so-called "replication crisis," which is a fancy way of saying that the entire field of social psychology is looking like mostly bunkum.

The defensiveness of its practitioners is to be expected, but let's check our own walls for glass before throwing stones. The main problems in the field of social psychology are not ones to which other social sciences or for that matter biomedical research are immune. It's a bit hard to explain if you haven't taken much in the way of statistics or research methods generally, but the keystone issue is the worship and misunderstanding of the concept of "statistical significance."

If I compare two samples from a given population, with an equal (or at least known) probability of being selected at random, and some with characteristic A are more likely to have characteristic X than are those without A, I want to know how likely this is to just be a coincidence. If the observed difference is expected to occur less than 5% of the time when there isn't really a difference in the total population, we say the "p value" is less than .05 and we declare the observation "statistically significant" which is presumed to be more or less synonymous with "true." If the probability is 6% we declare the observation "not statistically significant" which is presumed to be synonymous with "false."

This is so wrong for so many reasons it makes one feel foolish to point them out. One is that the p value depends on sample size as much as it does on the magnitude of the effect. If my sample is too small, I will be likely to get an insignificant p value even if a meaningfully large effect exists. If the sample is large, I will likely get a "significant" p value for an meaninglessly small effect. A bigger problem is that if I make multiple comparisons I will likely find a "significant" value in there just by chance, because you have to multiply the values by the number of comparisons. Cherry picking the ones that are "significant" is basically fraudulent, although it seems most people who do it don't know that.

Other problems are that in social psychology, dependent variables are typically quite subjectively measured and it may be difficult to detect observer bias; independent variables may be associated with other, unmeasured variables that are actually responsible for any effect; there are all sorts of rationales for excluding cases selectively after the fact; and samples are rarely representative of any broader group than (quite typically) undergraduates at a selective university from which they are drawn -- who, by the way, are quite likely to divine the research question and consciously or unconsciously alter their behavior in response.

Gellman points to all sorts of other design flaws but the overall lesson is that it's just too easy to find what you are looking for. These studies get a lot of press because they seem relatable and often directly relevant to our own lives and supposed behavioral predispositions and those of the people around us. But they're largely gahrbahzh. So sad.

Too many emergencies

Yes, the Trump Foundation and the border wall and birtherism and all of the dreck that spews from Ronald T. Dump should get news coverage.

However, there is shit happening in the world that is like, really, really important and probably ought to be discussed by the candidates. You know, that little climate change problem, nucular weapons, mass extinction . . .

There is also this. When antibiotics stop working, it's not just those poor dusky-hued people in distant lands currently dying of tuberculosis who will be shit out of luck. It's you. Not only might you die from an infected scratch on your hand, common surgical procedures will be far too risky, women will die in childbirth and children will die from strep throats. Gonorrhea and syphilis will be incurable.

Of course, avoiding this fate requires paying a few cents more a pound for pork, beef and chicken, so we can't possibly afford it.

What are the chances it will come up in the debate on Monday?

San Quintin

Many years ago, I visited the small town of San Quintin in Baja California Norte with my then-girlfriend. There is, or was, a small resort there catering to United Statesian surfer bums and retirees. Pensioners would live there because it's cheap and the weather is always sunny and warm. They never bothered to learn Spanish and would order the staff around arrogantly. (Of course.)

We visited the town which consisted of a few cinder block shacks, a Pemex station, and a fly-infested general store. The people had a few wilting cabbages and starving cows. One guy owned the whole place, he had a farm down the road where the women and old men who hadn't gone north labored in the dust to fill trucks with tomatoes for the journey up the peninsular highway. He had all the water rights so the peasants couldn't irrigate their pathetic gardens. There was a big field with a fence around it and a sign saying "no cazar." (No hunting.) There was a guy sitting on a horse with a rifle to make sure nobody did. Mostly though there was nothing to hunt. More than a mile or so from the ocean was high desert, just coarse sand and the meanest cacti you ever saw.

Oh yeah. The farm had pumped out so much groundwater that salt water was intruding into the aquifer and the water in the resort was spoiled, so they had to use bottled water. It hardly ever rains there. It looks like that's about to change:

The storm is taking dead aim at San Quintin. When we were there I found some old cattle bones sticking out of the sand. The people told me the beast had drowned in a storm some years ago. So, once every thirty years or so they get a tropical storm. I imagine the desert blooms.

ClinicalTrials.gov (wonky)

Krugman does the "wonky" trigger warning on his blog so I figured I should too. A major problem with biomedical research is what's called "publication bias." This takes a couple of forms. One is that negative findings -- i.e. "A does not cause B" or "is not associated with B" -- are unlikely to be published. Journal editors and reviewers just don't think they're exciting. However, if there are three trials that show that A does not cause B and one that does, and the last one is the only one that gets published, we wind up with a false view of reality.

A second form is that -- oh, did I ever mention that drug companies are evil? They choose not to publish studies that are unfavorable to their products. Same result, we come to believe that drugs are much more effective than they really are.

Another problem is post hoc analysis. If your initial hypothesis isn't borne out, dredge through the data to find some sort of significant association, say with a sub-group or a variable that you originally intended as a covariate rather than an outcome. The problem with this is that the p values are spurious, because if you make a large number of comparisons some associations will appear significant just by chance, when nothing is really going on.

Recognizing these problems, the FDA requires that all clinical trials for drugs be registered in advance, so that a) we'll know what the original hypotheses and protocols were and b)  we'll know about trials that aren't published. The penalty for not reporting your results within a year is supposed to be $10,000 a day.

Surprise! It isn't happening, and the law is not being enforced. We know that results aren't being reported in many cases, but we don't know how many trials aren't even being registered in the first place. Things appear to be getting a bit better, but there are still a lot of drugs being prescribed that probably should not be. This is a huge scandal that is almost completely ignored while we obsess over Hillary's e-mails.

Science for Sale

As my 2 1/2 long time readers have probably noticed, nothing frosts my pumpkin more than corrupt science. Well the gourd has a thick layer of ice right now. Stanton Glantz - a major figure in exposing corruption of science by the tobacco industry, has turned his guns on the sugar industry. They too were paying scientists to say that sugar is good for you.

You may recall that we had a consensus for a couple of decades that the way to avoid heart disease was a low fat diet. It's taken a couple of decades more to eradicate that falsehood and it's still clinging to life. Food manufacturers touted their "low fat" products as healthful while they were full of toxic sugar. What we're finally getting around to understanding is that dietary fat -- other than transfats -- and dietary cholesterol do not cause atherosclerosis. But sugar does, and it also causes a glycemic spike in the blood which contributes to diabetes. Plus it makes you fat. The entire edifice of nutrition science from the late sixties right into the nineties was a fraud erected by the sugar industry and its scientific prostitutes in academia.

That's really evil.

Celebrity Jeopardy

So one way I dispose of 1/2 hour of unneeded consciousness from time to time is by watching Jeopardy! For those of you who aren't familiar with the program, they have special tournaments for categories such as high school students, college students, teachers and what not. They also do a celebrity tournament every year which features people who for one reason or another are famous. As it turns out famous people tend not to be very smart so they make the questions really easy.

This year many of the players as it turns out are "journalists," among them Chuck Todd and Anderson Cooper. Apparently the only reason they agreed to go on the show is because of the Dunning-Kruger effect. As it turns out they are both astonishingly ignorant of the most basic facts of history (e.g., Cooper thought that Alexander the Great presided over the golden age of Athens, and also couldn't figure out that "tank" is a word that means both an aquarium and a war fighting machine) and incapable of the simplest deductive thought. They revealed themselves to be total airheads. Louis C.K., on the show with Jonathan Capehart and Kate Bolduan -- who are maybe a small notch above Cooper and Todd but not much when it comes to gray matter -- destroyed them both. I will venture to say that comedians in general are probably much smarter and better informed than journalists.

The way you get to be a talking head on TV is by being pretty and having good diction. Being an idiot who will read whatever drivel and propaganda your corporate overlords put in front of you is how you rise to the top and make millions of dollars.

Rapid Testing

Reading between the lines -- and not very far between them -- it appears the whole Theranos corporation thing was never anything but a scam, although as with most cons it is likely that CEO Elizabeth Holmes on some level believed her own bullshit.

For those who don't know, this was a silicon valley start up that promised to do a whole suite of medical tests from a drop or two of blood. No more getting the needle and giving up vials. The company attracted billions in venture capital and Holmes was briefly recognized as the world's wealthiest female entrepreneur. Turns out, the technology doesn't work and the billions have melted away like the snows of March.

What you may not know is that this probably didn't seem preposterous to investors because in fact you can get some reliable test results from a fingerstick, in just a few minutes. Many large practice now have on-site rapid testing for blood lipids -- i.e. cholesterol -- and what is called the HbA1c,* which is an indicator of what your blood sugar has been over the past few weeks and is the standard for monitoring diabetes control.

When practices have these things, it makes diabetes care better, easier and cheaper. You come in for your visit, the medical assistant pricks your finger and gets a drop of blood for the HbA1c and a small pipette for the lipid test. Then she (yeah, usually it's she, that's the real world) goes down the hall, sticks them in a machine, and in a few minutes has the numbers to give your doc before the visit. The alternative is for the doctor to give you a test order and for you to make a second visit to a lab, in which case the doctor won't have your test until after the visit when obviously it's much less useful. Plus which you might not bother to get the test at all.

Unfortunately, other than simple blood glucose that's all we've got right now. Other tests require more blood and can't all be run by one machine either. It is probably impossible even in principle. But what the Theranos story tells us is that with sufficient audacity and a convincing act, even smart rich people can be conned. Viz. Bernie Madoff and Ken Lay, among too many others to name.

* Stands for hemoglobin A1c, and the way it works is that the glucose in your blood gets attached to the hemoglobin in your red blood cells. The more glucose, the more of it is attached. This is also called "glycolated hemoglobin."