Does phlebotomy 'work'?

There's a discussion in a nice book about the history of Islamic science (Ehsan Masood, Science and Islam: A History) of a man named al-Razi, who in about AD 900 was said to have done a carefully controlled experiment to test whether phlebotomy (blood-letting) worked as a treatment for meningitis. Some patients were given the treatment and others were untreated 'controls'. Al-Razi found that the bloodletting worked, in that more of the treated patients than controls recovered.

This therapy was part of the ancient and revered view of life upon which the classical medical approach codified by Galen was based. The humoral theory, that existence and hence life and health are based on balance of four basic properties (earth, air, fire, water), that in humans corresponded to blood, black bile, yellow bile, and phlegm.

Everything could be explained in terms of disease as the state in which these are out of balance. Blood-letting was done when the patient was deemed to have an imbalance by an excess of blood. Galenic medicine lasted for many centuries and it was verboten even to question it. And why question it? It worked! That is, some patients got better and the belief in the system led everyone to accept its sometime success as supportive evidence (and indeed, it's possible that even when assessed by modern scientific standards, bloodletting may sometimes have done some good, as this story describes).

Why don't we accept it today? In fact, even al-Razi himself wrote a book casting doubt about the degree to which Galenic medicine was true. After all, we accept modern medicine even though it fails to cure everyone. We have to ask what causation really is. After all, placebos work. If you know people are praying for you, it apparently works -- although prayer doesn't work if you don't know people are praying for you.

We dismiss that as 'only' psychological, even if that is purely physical and molecular, by involving neurotransmitters that affect other cell behavior, such as by the immune system and who knows what else, eventually leading to improvement in the disease. Blood-letting apparently has a measurable, replicable physiological rebound effect that makes people feel better a few hours later. We say these things don't really cure the disease, or if they're just psychosomatic, somehow that doesn't count. But if the brain is a material rather than immaterial structure, and the effect is thus material, why doesn't it count?

We want higher percentages of success. We want therapy to be direct, rather than indirect. If the treatment is believed by the patient, it boosts his immune system in some way, etc. Somehow, targeting the true pathology indirectly, rather than by targeting the proximate molecular cause, is not considered 'real'.

But that's our own culturally derived way to define medicine and its efficacy. It's similar with diseases like AIDS and HIV. As the South Africans said for a decade or more, poverty is the true 'cause' of AIDS, not the virus. Unfortunately, many thousands died as a result. Yet poverty is still causally associated with HIV infection. South Africa has finally accepted that HIV is also a cause of AIDS, and thousands or millions of lives may now be saved as a result.

Empirically, the desired explanation can be chosen to be some net result -- 'cure' in the case of disease. Science in the west, at present, wants reductionist molecular explanations, about proximate cause. Causes higher up the material chain -- like poverty and poor education cause poor neighborhoods with no good grocery stores cause reliance on McFastFood causes obesity causes high blood pressure or glucose causes retinal and peripheral neuropathy causes blindness and loss of extremeties. So what causes blindness? Even in our molecular, reductionist, technical age, diabetics still become blind.

There is no one answer. If removing poverty greatly reduced blindness, isn't poverty a cause? Or McBurgers? The prevailing view is that if we identify some ultimate cause -- the preferred target for many in science these days is your 'personalized' genome -- we will get to the 'real' cause and will then live forever. But the focus on genes is part and parcel of the structure of our current society.

Whether one approach to causation will ever, by itself, lead to miraculously high levels of efficacy nobody can say. Galenic physicians thought they had the ultimate answer. Collinsian medicine (Francis Collins, Director of NIH and the chief spokesperson for personalized genomic medicine) is having its day today. What about tomorrow?

The same kinds of questions arise in evolutionary and developmental biology. We've recently posted on phenogenetic drift-- the idea that essentially the same trait can come to be due to different genetic bases even while being conserved by natural selection -- which suggests that genes contribute but are not 'the' cause of the trait. This is related to the entire concept of complex causation.

So was al-Razi right that phlebotomy cured meningitis? Perhaps it is inappropriate to ask whether Galenic medicine 'works'. It is more interesting, to us at least, to ask what we mean by 'works'.

[p.s., al-Razi, known in the west as Rhazi, wrote critically about Galenic medicine in a book Doubts About Galen]

The way to a man's heart is .... through simpler nutrition labeling?

A headline today from the BBC: "Lower IQ 'a heart disease risk'". This is a report of a paper in the European Heart Journal in which researchers looked at the life experience of more than 4000 US Vietnam vets and concluded that IQ alone explains 20% of the risk of heart disease. They controlled for known risk factors such as smoking, diet, exercise and socioeconomic status (heart disease risk is already well-known to be higher among people with lower income and education levels, and smoking, diet and exercise are associated with SES as well), and still found an IQ effect.

Clearly, however, if this association is real, low IQ is not the direct 'cause' of heart disease--unless someone truly believes that 'brain' genes affect heart function such as clogging of arteries! Instead, IQ is a confounder, a measured variable that is not directly causal but is correlated in the sample with some unmeasured truly causal exposure factor, be it genetic or otherwise.

But confounder for what? The lead researcher suggests that the problem may be that people with low IQ may have trouble heeding health advice. It needs to be simpler and easier to understand.

"For instance, we often read about how some types of alcohol are good for you while others, or even the same ones, are not. The messages can be difficult to interpret, even by knowledgeable people."

This is an interesting quote because it (presumably unwittingly) points out that health advice is often contradictory, not to mention highly cultural. And thus impossible to interpret meaningfully, no matter your IQ. Some alcohol is good for you--except when it's not. Hard to think how you could make that into advice that's easier to follow. The other interesting bit about this quote is that the alcohol he's talking about is red wine, more generally the drink of choice among the middle and upper classes.

That aside, what could IQ be a marker of? Many people suspect IQ scores to be nothing but cultural markers--indeed, it's well-known that they vary by race, and have been changing rapidly over recent time, for largely cultural reasons. So IQ would be a marker of race, but the BBC story doesn't mention race, because the paper itself doesn't, either. Unbelievable!

One can hardly imagine an aware US epidemiologist who would not think right off the bat that race may well be the real risk factor here, for which IQ is a correlated marker. Heart disease risk is higher among African Americans, and presumably, if this particular study group follows known trends in IQ scores, African Americans would be more heavily represented in the lower IQ scoring/higher heart disease risk group. Thus, IQ is merely a marker for race here, and the risk associated with race.

But, let's run with the idea that intelligence might actually be a risk factor for heart disease. Numerous studies have been done to try to identify genes 'for' IQ, but with little replicable success. But let's suppose there are genes 'for' intelligence--indeed, if the IQ/heart disease association is real, mapping studies looking for genes associated with heart disease should have at least identified IQ genes. (But determining whether genes are IQ genes or not would be difficult because 70-80% of genes, no matter where else they are expressed or what their known function(s), are expressed in the brain--are they all 'brain genes' or genes for intelligence?). Indeed, genes 'for' poor circulatory function may affect ability to study and learn, so the reverse should also occur: IQ mapping should pick up cardiovascular genes!

Further, if this association is real, it raises the question of causality. But what 'causes' AIDS? Is it the HIV virus? But, HIV/AIDS rates are highest among the poor, so was Thabo Mbeki, the former president of South Africa, at least partly correct when he insisted that HIV/AIDS is caused by poverty? So if low IQ is a marker of race, and SES, do poverty and racial discrimination cause heart disease?

This study was carried out by British researchers. One wonders if their less nuanced understanding of American race and class issues erroneously led them to conclude that an effective way to lower heart disease is to make nutrition labeling easier to understand. Or could they be from such a middle-class environment as to be insensitive to these kinds of issues?

Or could it be that the general operating notions of causation, based as they are on stereotypical study designs that look for statistical associations, are a barrier to understanding?

As usual, genetic causation today and genetic causation as the result of evolution are similar. If natural selection favors some trait, then any genetic variation that gets the favored state will be favored. If variation in IQ genes led our ancestors to pick low-fat fruit (say), then those genotypes would be favored by selection just as fat-metabolizing genes would. If they could be detected by the kinds of searches for evidence of selection that many are doing these days, much experimental effort could be wasted trying to show how those genes were involved in lipid metabolism.

This is a subtle world today, and it's been that way throughout our ancestry.

Science is based on cause and effect, which is not identical to correlation and effect. The meaning of 'cause' has been central to philosophical thinking since Aristotle. Perhaps we should be less driven by methodology and pay more careful attention to that in science today.