Short answers to big questions

John Brockman's Edge World Question Center has been an inspiration.
Below are some of the questions posed in recent years, and my answers.

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1998
What is the most important invention in the past two thousand years?...and why?
Text is special

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1999
What is today's most unreported story?
Is the Market on Prozac? (This was reported in hundreds of news sources just before the crash. The idea has been reinvented by others several times early in 2009. No one has tested the idea yet.)

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2001
What questions have disappeared?
Why is life so full of suffering- I ?

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2002
What is your question...and why?
Why is life so full of suffering- II

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2003
"What are the pressing scientific issues for the nation and the world, and what
is your advice on how I can begin to deal with them?" GW Bush
Finding out how relationships work

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2004
What's your law?
Nesse's Laws for deciding when it is safe to use drugs

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2005
What Do You Believe Is True Even Though You Cannot Prove It?
People gain a selective advantage from believing in things they can't prove

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2006
What is your dangerous idea?
Unspeakable Ideas

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2007
What are you optimistic about?
We will find new ways to block pessimism

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2008
What have you changed your mind about? Why?
Truth does not reside with smart university experts

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2009
What will change everything?
Recognizing that the body is not a machine

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Nature-Nurture, No Nonsense

As often noted, it is senseless to ask whether a trait is caused more by genes or more by environment. Like the length and width of a rectangle, both genes and environment are essential to the development of any trait. However, if the task is to explain variations in a trait, then the same analogy holds--the area of the rectangle changes only if its width or length (or both) changes. Variations among individuals can result only from differences in genes, differences in environments, and the interactions between them.

The proportions of variance attributable to each component obviously will differ depending on 1) the variability of the environment and 2) the range of genotypes in the population under consideration. If all individuals are clones, then all variation is environmental. If environmental variation is relatively low, such as in Scandinavian societies compared to the USA, then the proportion of variation from genetic factors will increase. Interactions between genetic and environmental factors are, of course, important. In short, it is senseless to estimate the heritability of a trait; heritability reflects the proportion of variation in a trait that can be attributed to genetic variations given a particular environment.

Less recognized is the possibility that there may be many different routes to a disorder, so the responsible factors may be mainly genetic in one individual and mainly environmental in another. One person may get atherosclerosis or depression because of a strong family predisposition in the absence of special environmental risk factors, while another with no predisposition may get the condition mainly because of environmental exposures. An evolutionary approach fosters simultaneous consideration of the many factors that may explain individual variation in a trait.

Some sources of individual differences include:

1. Additive genetic differences among individuals that result in phenotypic differences (in this environment). The differences are additive if the simultaneous effects of multiple genes on a trait can be predicted by adding the effects of each individual genes. The “narrow sense heritability” refers to effects of additive genetic effects and is estimated by h2 = Vadditive genetic effects/Vphenotype
2. Non-additive variation resulting from Gene x Environment interactions
3. Non-additive variation resulting from Gene x Gene interactions
4. Assortative mating—nonrandom mating can increase trait variance
5. Random factors in development, such as the stochastic nature of neuron migration or different exposure to trace elements in the diet or happenstance social experiences
6. Effects of cues that influence development via facultative mechanisms shaped by natural selection to a trajectory suited to the particular environment, such as early heat exposure influencing the number of adult sweat glands
7. Effects of trauma, toxins and other environmental exposures outside the range of “normal” that damage the organism or distort its development
8. Effects of environmental factors that influence the organism “top-down” via perceptual experience without resulting in damage or acting via a specific facultative mechanism.
9. Effects of environmental factors that influence the organism from the “bottom-up” that are neither damaging nor mediated via facultative adaptations.
10. Effects of individual learning that facilitate flexible coping with current aspects of the environment.
11. Experiences shared within a culture and whose effects are incorporated into values and emotional proclivities that may be difficult to change later (such as values or attitudes about sex)
12. Experiences shared within a culture whose effects account for variation, but these effects are not mediated by enduring influences on individuals.

The task of accounting for individual differences should not be reduced to arguing about the relative importance of one factor compared to another. It is, instead, the challenge of explicating how each contributes to individual differences in a particular trait, and how their contributions to a particular trait may be different not only between families, populations, or cultures, but even between individuals within a family, population, or culture. This is has practical implications, especially for mental health research. For instance, we need to take seriously the possibility that many different genes contribute to depression vulnerability by many different routes

Why Constructive Engagement is Rare

Constructive engagement is rare, not just in political seasons, not just in our society, but always and everywhere, for good evolutionary reasons. Understanding those reasons gives us a fighting chance to avoid useless fighting and begin constructive engagement.

By constructive engagement, I mean people trying as hard as they can to express their own ideas clearly, to understand other people’s beliefs and their reasons for those beliefs, to understand the exact differences between the beliefs, and to specify and search out information that would resolve any differences. Far more common are two patterns of unconstructive engagement, which can be caricatured as the mutual admiration society and the war of the clans.

In the mutual admiration society, members flatter and congratulate each other, falling all over their own ideas in order to show that there are not any real, or at least any serious disagreements, and that the other people’s ideas, and the people themselves, are wonderful and superior to others. Good ideas and areas of agreement are emphasized, while errors, contradictions, and disagreements are ignored, excused, or actively suppressed. This is the norm in most public settings, including academia.

In the war of the clans, participants perceive and describe the beliefs of others as negatively as possible, and they attack whatever is most vulnerable, including the people, their abilities, motives, and moral standing. Good ideas and areas of agreement are ignored or actively suppressed, while errors, contradictions, and disagreements are emphasized. The participants in clan wars usually seek allies who will join them to support a shared ideology that uncritically accepts and glorifies the beliefs of the in-group, and that rejects and ridicules the beliefs and members of the out-group.

These modes of engagement are intimately related. It is dangerous to attempt to try to tell a friend or colleague that you think he or she is wrong about something because the expectation for mutual support in the in-group is so strong that any deviation, even the most careful and respectful attempt to explore areas of disagreement, is experienced as a defection, as a social attack that indicates opposition. Most people want friends and they don’t want enemies, so they mostly say what others want to hear. Muddled ideas and vagueness triumph.

This is why politics is so difficult despite being ubiquitous, and perhaps why its difficulty may have led to the rapid evolution of the human brain. The politician must simultaneously convince people that he or she will advance the interests of the in-group, usually by opposing an out-group, while ensuring that the out-group is small and powerless enough to not be a threat. Coalitions are built on common interests, but if the interests are too broad, people will not identify with the group, while if too narrow, the group will be small. The solution is to say little of substance, appearing always to support the agendas of those who are listening, while attacking ill-defined outsiders. To speak clearly about specific beliefs and plans is suicidal for a politician. To speak clearly with our friends and colleagues about areas of disagreement is dangerous for any of us.

What is evolutionary about all of this? Our ancestors have lived in complex social settings for well over a million years. People who have a tendency to engage in mutual admiration behavior with in-group members, who conform to, believe in, and advocate and work for the ideology of the in-group against the interests of other groups, have almost certainly have had a selective advantage over people who tend to be more objective. Subjectivity and the emotions that fuel it are not flaws, but adaptations.

In academia, we highly value constructive engagement, but we don’t do it very often. Far more often, we politely engage in mutual admiration, letting crucial disagreements persist for the sake of social alliances. Less often, but even more unconstructively, we engage in clan wars, where opposing sides define group boundaries and then distort and derogate the out-group’s members and their ideas and beliefs. Examples of such wars are endless: post-modernists vs. scientists, behaviorists vs. Freudians, Marxists vs. free-marketers, social scientists vs. biological scientists, evolutionists vs. creationists, geneticists vs. whole organism biologists, adaptationists vs. Gouldians, conservatives vs. liberals, pro-liferes vs. abortion rights advocates, theoreticians vs. experimentalists, and all the proponents of various theories of literary criticism against each other. These examples are not anomalies, they are what humans do, and how human societies are organized. Worse yet, people have an intrinsic tendency to attend to a person who is passionately dedicated to a simple, vivid, unusual position. So leaders tend to polarize. Mass media bring instant attention to the most extreme positions, amplifying the phenomenon.

Constructive engagement always involves risk and often requires sacrifice. Even to advocate it may be seen as an indication that one can not be counted on for unswerving loyalty to the in-group. Constructive engagement is rare for good reasons, but it is nonetheless wonderful.

On reading Schopenhauer in Berlin

I have spent much of this year trying to understand why natural selection shaped a capacity for low mood. The evolutionary perspective is new, but the core idea is ancient—despair comes from unsatisfied desires. Schopenhauer (1788-1860) was preoccupied with the connection between desires and despair. Like many aging philosophers, he wrote a late essay giving advice on how to live: The Wisdom of Life (1851, translation by T. Bailey Saunders, Echo Library, 2006). The essay has much to say about the goals humans pursue.Schopenhauer begins by citing Aristotle’s three blessings (from the body, the soul and from without) and proceeds by saying he will “keep nothing from the distinction but the number.” Instead his lists three remarkably modern categories:

1. What a man is: health, personality, beauty and intelligence
2. What a man has: property and possessions
3. How a man stands in the estimation of others

His categories 1, 2, and 6 are the standard categories 1, 2 and 6, from behavioral ecology:

Somatic
1. Personal
2. Material
Reproductive
3. Mates
4. Offspring and kin
Social
5. Allies
6. Status

Schopenhauer leaves out partners, children, and friends (3, 4 and 5). This is, I suspect, why he was so unhappy. Modern research finds that those who pursue money and status are less happy than those who invest in friends and family (see work by Jennifer Crocker on “contingencies of self-esteem”). As an evolutionist I think the main question is not whether some goals are better than others, but the data is nonetheless important.

Schopenhauer’s recommendations are an expanded commentary on a chapter title from Epictetus: “The happiness we receive from ourselves is greater than that which we obtain from our surroundings.” However, his larger framework is a thoroughly modern version of cognitive therapy: “Everything confirms the fact that the subjective element in life is incomparably more important for out happiness and pleasure than the objective.” He devotes a chapter to each of his three resources for life.

The chapter on Personal resources begins with the importance of health, and the eternal and valid advice—exercise. He then jumps to what he describes as the inevitable trade-off between pain and boredom. He panders shamelessly to academics. Or is he writing to assuage his own despair? The rich, he says, are bored, because external amusements can never satisfy. They are inferior, so intellectually dull they can never savor the deeper and more enduring pleasures of the mind. He also has contempt for extraverts: “As a rule, it will be found that a man is sociable just in the degree in which his is intellectually poor and generally vulgar.” The chapter goes on to disparage “ordinary men” further, especially the value they place on external things.

Only the genius, he says, can be truly happy. “The man of inner wealth wants nothing from outside but the negative gift of undisturbed leisure, to develop and mature his intellectual faculties, that is, to enjoy his wealth; in short, he wants permission to be himself, his whole life long, every day and every hour.” In support, he cites Socrates, Aristotle, and Goethe.

The next chapter, on Property, is only five pages. It emphasizes the trap of the majority, working to get their bread, and the trap of the rich, striving to have more than others. “For what everyone most aims at in ordinary contact with his fellows is to prove them inferior to himself.” (p28)

The final chapter, on Position, goes on for 37 pages, making careful distinctions among Reputation, Pride, Rank, Honor and Fame. Once again, Schopenhauer provides salve for the damaged self-esteem. “In all we do, almost he first thing we think about it, what will people say; and nearly half the troubles and bothers of life may be traced to our anxiety on this score.” (p32) His solution? “A retired form of life has an exceedingly beneficial influence on our peace of mind, and this is mainly because we thus escape having to life constantly in the sight of others, and pay everlasting regard to their casual opinions; in a word, we are able to return upon ourselves.” (p34) Predictably, he continues on to belittle worldly honors and social rank, and the tradition of settling matters of honor with a duel.

Towards the end, he tells us that true greatness can be identified because it is unappreciated in its time. Excellence, he says, is opposed strenuously by the “common lot” of mediocrity. (p61) Fame he values, but he quickly tries to convince us that contemporary fame is but “trumpeted forth by a clique of admiring undergraduates—the resounding echo of empty heads.” (p62) What counts is enduring fame, and that comes most often, he says, to those unappreciated in their time. “It is easy to see why contemporary fame so seldom develops into posthumous fame” (p65). “”The truest fame, the fame that comes after death, is never heard of by its recipient; and yet he is called a happy man.”

Some of these opinions echo an event in Schopenhauer’s life 30 years before. In 1820, shortly after the publication of his masterpiece, The World as Will and Idea, Schopenhauer challenged the dominant, already famous, and highly popular Hegel to a duel by student popularity. He scheduled his lectures at the University of Berlin at exactly the same time as Hegel's. Only five students came. Schopenhauer dropped out of academia, and never taught at a university again. He did, however, keep writing. Over 150 years later, many continue to read what he wrote.

Yesterday, I saw a plaque on a house in Berlin at Kupfergraben 5, near Museumsinsel, placed to honor Hegel by Berlin (now Humboldt) University. A quick Google search finds Hegel listed in the history of the University. But there is no plaque to remember Schopenhauer, and no mention of him on the University website.

Schopenhauer’s brilliant musings are an extraordinarily sophisticated set of intellectualized defenses that salved and salvaged the ego of a brilliant narcissist, eclipsed in his time by more popular figures. The defenses are as useful today as they were then to give hope and succor not only to unappreciated philosophers, but to anyone who feels unappreciated for pursuing a life of the mind. However, the obvious psychological functions of Schopenhauer’s writings should not undermine their truth and wisdom. His core point could have come from Ecclesiastes; all human endeavors are vanities. But Schopenhauer makes one exception, efforts to find out what is true.

This does not take us far towards understanding the evolutionary origins of depression, but it is a valiant and interesting attempt to understand the exigencies of human efforts in pursuit of universal goals.

Evolutionary pharmacogenomics

Articles about evolution and medicine are spread so widely over the scientific landscape that no matter how much you read, you know you are missing things. The pleasure on finding them is, however, like finding a diamond in the sand. Such is the case with evolutionary pharmacogenomics (a phrase that turns up not one hit on Goggle!). At our seminar yesterday, Mark Thomas put us onto work by Daniel Nebert. A long-time leaders in pharmacogenomics, he has written several papers offering an evolutionary framework for thinking about genes that influence drug metabolism. Suddenly, all kinds of things make sense. Why 57 genes in the Cytochrome P450 super-gene family? Because they are products of co-evolution between plants trying to defend themselves and herbivores looking for a meal. All the genes can be traced back to a common ancestor about 2 billion years ago, but the fast differentiation, espcecially in the CYP2 family, came about 400 million years ago as animals moved onto land to be come a problem for plants.

The implications are profound:

The entire field of pharmacology and drug development represents the discovery and characterization of naturally occurring plant metabolites, followed by synthesis of analogs that are found to do a better job with fewer side effects (2006, p4)

His perspective gets us away from thinking about drug metabolizing enzymes-they evolved to deal with endogenous and exogenous substances long before there were drugs, and they are active not only in liver, but in every cell in the body. He also notes that we should not ony expect to find major differences between species depending on their diet, we should expect to find that these systems are inducable by exposure, as of course, they are.

The discussion inspired a new idea. Our ancestors routinely ate somewhat toxic plants until just the past 5-10,000 years. Agriculture and plant breeding now allow us to eat mild tasting foods. I wonder if the resulting inadequate stimulation of "drug" metabolising enzymes may be responsible for some diseases of civilization. This should certainly be testable in rats. Probably it has already be done. If you know about such studies, please leave a comment below.

Nebert DW, Dieter MZ (2000) The evolution of drug metabolism. Pharmacology 61: 124-135

Nebert DW (2006) Drug metabolism: Evolution. Encyclopedia of Life Sciences: Wiley Press (online). pp. 1-6.

No genes for schizophrenia--What gives?

Ten years ago, most of us paying attention were exhilarated about the prospects for psychiatric genetics. Heritability is high for many disorders--80% of the variation in vulnerability to bipolar disorder and schizophrenia can be attributed to genetic variations. We thought we would soon find the responsible abnormal genes, and this would quickly reveal the biochemical defects that cause these disorders, and this would quickly lead to ways to cure, or at least dramatically alleviate, these terrible scourges.

Candidate genes were examined by the best researchers using larger and larger samples and sophisticated statistics; a few were identified as prime suspects. Most results could not be replicated, but a few loci were very suspicious based on multiple studies.

Now, in an article by in this month's American Journal of Psychiatry, Saunderset al. report on 433 SNPs associated with 14 candidate genes that were prime suspects for schizophrenia in about 1900 cases and 2000 controls of European ancestry. The results? Not one of the genes was significantly associated with schizophrenia prevalence. Even a 25% increase would have been detected with high probability.

An editorial by Steven Hamilton doi: http://dx.doi.org/10.1176/appi.ajp.2008.08020218 tries to put the best possible face on the results by noting that studies of tens of thousands of subjects were required to find genes that contribute to real but small (<25%) increases in risk for Type II diabetes. But that is not the point. Sanders, et al. deserve commendation for stating their conclusion clearly:

Our results suggest that, taken together, common DNA variants in these 14 genes are unlikely to explain a large proportion of the genetic risk for schizophrenia in populations of European ancestry. More robust findings are likely to be discovered using genome-wide association methods and, as our knowledge of the biology of mental illness continues to improve, focused studies of genes based on more precise mechanistic hypotheses. Nevertheless, although larger samples could possibly detect small genetic effects that were missed in this experiment, our findings suggest it is unlikely that true associations exist at the population level for the alleles that have formed the basis for the large candidate gene literature for these 14 postulated schizophrenia candidate genes.

Now what? Should we just do larger and larger studies with fancier and fancier bioinformatics? We have been looking for abnormal genes--mutations that cause diseases. But what if that is not the right model? That presumes that there is a normal genome and if all is in order all works fine, but when a part breaks, disease results.

A clue comes from Craig Ventner's genome. The human genome project provided sequences for haploid genomes. But the chromosomes from both Ventner's father and mother have now been sequenced. The results are a big surprise. Variation between human individuals is five times higher than we thought: 0.5% instead of 0.1%. Much of the difference is in the number of copies of a gene, and their locations. DOI: 10.1126/science.317.5843.1311

Copy number variations look likely to explain a lot. They are invisible to genetic testing that just looks for the presence of certain sequences. But they are important. Especially for mental disorders.

In this week's Science,Walsh, et al. report big differences in CNVs in people with schizophrenia: "Novel deletionsand duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases" DOI: 10.1126/science.1155174 In previous work they have found similar differences in autism.

This may well explain why we have not been able to find the genes for schizophrenia--schizophrenics don't have different genes from other people, just different numbers of certain genes. This also fits with paternal age effects on schizophrenia -- the risk of schizophrenia increases as the father's --but not the mother's--age increases. (Male gamtes keep dividing throughout out life, increasing the risk of errors, while the eggs of females are all formed by birth)

So, myriads of different genetic variations may contribute to schizophrenia, many involving micro insertions and deletions. This tells us where to look.

A big piece of the puzzle remains missing, however. Why can so many different genetic variations all cause schizophrenia? Part of the answer is heterogeneity of the phenotypes--we should talk about the schizophrenias, in the plural. Nonetheless, it is remarkably that the brain fails so often in the same general ways. Why are bipolar disorder and schizophrenia so common compared to any number of other disorders, and the myriads of disorders that could exist but don't? The answer will come, I think, when we quit thinking of the body as a machine designed by engineers in which problems are caused by broken single parts. Bodies are fundamentally different from machines. Genes that make traits that on average tend to Darwinian fitness become more common. They form networks and modules, but in ways that often do not correspond to anything a sensible engineer would do. They create robust networks that are resistant to damage, until, that is, some slight variation wrecks the whole system. This may be why certain cognitive system are so vulnerable.

My best guess is that a cliff-edge effect is involved. Some trait has given such a large advantage that it has been pushed rapidly by selection to a value that is close to a cliff-edge, where the system is prone to fail catastrophically. Levels of uric acid in humans are a good example. Uric acid levels have increased in humans relative to other primates, probably because the antioxidant effects of uric acid are selected for in a a species with a long life span, despite the risk of gout. The strong correlation between uric acid levels and life span in primates is supportive evidence. For schizophrenia, Crespi summarize relevant evidence for signals of positive selection on candidate genes.

There are many other ideas out there. Bernie Crespi's work on the possibility that autism and schizophrenia are flip sides of conditions resulting from imprinted genes that advance maternal and paternal genetic interests is particularly intriguing.

We are getting there. But it is increasingly clear that it is a serious mitake to think of the brain as a machine with parts that break. The brain is, instead, an organ in an evolved soma whose information code is nothing like anything a any human programmer would write. It is not irreducibly complex, but it may well be incomprehensibly complex at the molecular level. Deeper evolutionary thinking about genomics may prove essential to understanding schizophrenia and autism.

Balancing selection--no answer for schizophrenia

Many have asked why genes that cause such a serious disease persist, and a number of evolutionary hypotheses have been inspired by the kind of balancing selection that explains the persistence of genes that cause sickle cell disease. A new article by Adriaens debunks such hypotheses. He offers a nice review of studies about the reproductive success of people with schizophrenia, although I think he discounts excessively the evolutionary significance of a 50% fitness decrease for male schizophrenics.

It seems to me that he is absolutely right, however, to point out data that undermine hypotheses based on covert benefits of schizophrenia genes. He generalizes about evolutionary psychiatrists as if they are not only all in one category, but as if they all think the same things. This is especially surprizing given his emphasis on the mistake of assuming that schizophrenia is a natural category. It is so important to criticize hypotheses, not people or groups.

There is much additional useful in his paper, especially his outline of evolutionary reasons why the genetic factors in schizophrenia will be much more complex than we have imagined. This all fits very nicely with other reports this week about the genetics of schizophrenia I do think, however, that we do need to ask why such a highly heritable devastating disorder persists. Balancing selection is not likely. It could be just that new mutations happen. But I think that the high heritability has kept attention focused on the level of the gene, when the problem may well be in constraints and trade-offs at a higher level. See a previous post for more on this.

Why are humans such lousy dog trainers?

Training Lucy has taught me so much. Mostly it has taught me what a lousy dog trainer I am. I started off confident that my knowledge of psychology and learning theory would make me a superior dog trainer. Besides, humans have been training dogs for thousands of years, and, we have had a few hundred thousand years to learn how to influence each other. So, it shouldn't be hard to train an eager, smart, poodle puppy.

Not so! Over and over again, I discover that my innate dog training inclinations are exactly wrong.

I say, Lucy, Come! She runs away. Annoyed, I call her name in a harsh commanding tone: LUCY! She looks toward me, then runs further away.

I come in the door at home. Lucy jumps up on me eagerly. I say firmly, NO! Down!, all the while looking at her and touching her to try to get her to sit down. Every time I come home, she jumps a bit more wildly.

STAY! I say, giving the hand signal as well. Lucy sits, and looks at me. Wonderful! I give a reward. Immediately, she jumps up and runs ahead. No, Lucy, stay staying, please!

We are at the dog park, and it is time to go home. COME! Lucy, I yell. She immediately runs to the far corner of the dog park. I chase her. She runs faster. Much faster than I can.

Thanks to help from several experienced dog trainers, I have gradually overcome the worst of my natural dog as training habits, but only very gradually and with constant inhibition of my natural impulses. Gradually, I learn that her name must only be used in a positive setting. I discipline myself to completely ignore her jumping behavior. I gradually figured out for myself, that to get her to stay, I need to give her not just one, but a series of treats at random times during the stay. And, at the dog park, I began calling her every few minutes, leash in one hand, treat in the other, until COME! at the dog park no longer signals that she will soon be separated from her happy pack.

If natural selection is so great, why aren't we better dog trainers? It seems that we humans are lousy at using rewards and punishments to influence the behavior of all others, not just dogs, but people as well. In my work as a psychiatrist, I am constantly amazed at spouses who angrily demand love from a partner. Then there are parents who fear a daughter will be promiscuous, so they make wild angry accusations whenever she stays out too late; they are not surprised when she fulfills their expectations. Neither am I, but for different reasons. Then, there are parents who yell at their infants, telling them to stop crying; when the baby does not obey, they get enraged. How can we are so poor at the most basic skill of influencing others?

Another possibility to explain our specific deficit in dog training abilities is that we use strategies that tend to work to influence adult humans. Anger and commands can influence others, especially if they’re dependent or lower in social rank. In the long run it creates enemies looking for opportunities for revenge, but in the short run it works. Words work to influence humans. For dogs, hand signals are far better, words are far less influential and the tone is as important as the phonemes.

Why don’t we all have better innate dog (and person) training skills? This is worth more thought.

Can we ever be sure about what happened long ago?

Often when I lecture about evolutionary biology, a member of the audience will say, "You don't have a time machine, so you can never be sure about what happened long ago, this is all this speculation."

Well, it is hard work, and often no experiment can conclusively differentiate the hypotheses. However, sometimes one can be as sure as sure can be.

Paleontologists have long recognized a major decline inlarge mammals about 35,000 years ago in the vicinity of the land bridge between Alaska and Siberia. The cause has now been identified.

Firestone and colleagues at Berkeley hypothesized that a meteor impact killed off the mammals. To test this, they examined 8000 mammoth tusks for the presence of metal particles. Seven tusks and a bison skull had magnetic particles embedded, and the levels of nickel and titanium were substantially different from those found in terrestrial iron samples. One more remarkable observation is the clincher. In all of the tusks with multiple particles, the particles were all on the same side of the tusk.

So, can we be sure? I find it convincing. But let's see the publication and give it a year for comments.

Ten Ways to Apply Evolution in Medicine

I have always found it somewhat confusing that evolutionary principles can be applied to medicine in so many ways. From the start of my work with George Williams, it has seemed clear that our attempts to ask why natural selection left the body vulnerable to so many diseases are fundamentally different from applications of population genetics or phylogenetic trees. Finally, in preparing an article with Stephen Stearns, I came up with a framework that seems helpful.

First it is essential to be clear about the kind of question:
1. What is the phylogeny of the trait?
2. How has the trait given a selective advantage?

Second, it is important to distinguish five different objects of explanation:
1. Human (or other focus species) phenotypic trait
2. Human (or other focus species) gene
3. Pathogen phenotypic trait
4. Pathogen gene
5. Somatic cell lines such as cancer or immune cells

This fleshes out into a rather nice table that defines ten ways evolutionary biology can be applied to medicine.

The full article is available free from Evolutionary Applications.

Nesse, R. M., & Stearns, S. C. (2008). The great opportunity: Evolutionary applications to medicine and public health. Evolutionary Applications 1(1), 28-48.