Every organism is unique, but we all become unique in the same way

We've just run across a 2004 Nature paper by André Pires-daSilva and Ralf Sommer about the evolution of signaling in animal development. This paper, of which we were not aware but should have been, is highly related to some main themes of our book The Mermaid's Tale, which deals with fundamental aspects of how life works including, but not focused on, how it evolved.

The authors write that only seven signaling pathways are responsible for most of the cell-cell interactions that control the development of a single cell into the organism it becomes. They are used repeatedly at every stage of development, and have been co-opted through evolutionary time in the development of new morphological traits and systems.

After millions of years of evolution, signalling pathways have evolved into complex networks of interactions. Surprisingly, genetic and biochemical studies revealed that only a few classes of signalling pathways are sufficient to pattern a wide variety of cells, tissues and morphologies. The specificity of these pathways is based on the history of the cell (referred to as the 'cell's competence'), the intensity of the signal and the cross-regulatory interactions with other signalling cascades.

These ubiquitous pathways are the Hedgehog, Wnt, transforming growth factor-, receptor tyrosine kinase, Notch, JAK/STAT and nuclear hormone pathways. How can the wide diversity of life around us be produced by so few ways for cells to communicate with each other?

Given the flexibility of signalling pathways, research in the past decade has concentrated on the question of how specificity is achieved in any signalling response. There is now clear evidence that the specificity of cellular responses can be achieved by at least five mechanisms, which in some cases act in combination, highlighting the network properties of signalling pathways in living cells.

First, the same receptor can activate different intracellular transducers in different tissues.

Second, differences in the kinetics of the ligand or receptor might generate distinct cellular outcomes.

Third, combinatorial activation by signalling pathways might result in the regulation of specific genes. Several signalling pathways can be integrated either at signalling proteins or at enhancers of target genes.

Fourth, cells that express distinct transcription factors might respond differently when exposed to the same signals.

Fifth, compartmentalization of the signal in the cell can contribute to specificity. The recruitment of components into protein complexes prevents cross signalling between unrelated signalling molecules or targets multifunctional molecules to specific functions.

The idea that a handful of networks can be responsible for most of the cellular 'decision-making' that is development is a beautiful example of core principles of life that we write about. The different ways that cells respond, the different developmental cascades that can be triggered by the same signaling networks, the interaction of different signaling pathways to trigger specific responses, and so forth all demonstrate the importance of modularity, signaling, contingency, sequestration and chance over and over again. How the components of these signaling pathways have evolved -- co-evolved -- is not yet well-understood, but it has to be that the interactions are tolerant of imprecision, and indeed, that tolerance (variation in the affinity of receptor/ligand binding) has been built into the system and leads to the evolutionary novelty.

The keys to this are partial sequestration of components of an organism so that local cells in different parts of the plant or animal can behave in different ways, so they can sense and respond to their environment (by signalling), and the arbitrary combinatorial codes by which signalling systems -- like the ones discussed in the 2004 paper -- work. That the same systems can produce diverse organisms reflects the logic of development, that is, the relational principles by which life is organized. Notch signaling is about the code specified by Notch, its receptor and related proteins, in combination with other such systems--and not by any particular property of the Notch proteins per se.

Every organism is unique, but we all become unique in the same way. It is basically the open-ended use of these very simple processes involving a limited number of components that enables this essentially unlimited diversity of living Nature.

Kissing cousins

Well, the latest episode of Our European Cousins has aired. Svante Paabo, who if anything knows how to play each side of the street as long as there are cameras there, has announced now that 1-4% of the modern human genome is derived by admixture with Neanderthals. In the past, he was comparably insistent in headlining that Neandertals had not admixed and were a dead lineage.

The paper reported in the news (on the BBC website, e.g.) appears in Science's new issue. Make no mistake, it's a good and important piece of work, long promised and finally arrived. It is a sequence of roughly the entire Neandertal genome compared to five available whole-genome sequences from modern humans. Getting and assembling anything close to a whole genome sequence from fragmentary bits in fossils, contaminated with DNA from other things such as bacteria in the earth where the individual fell thousands of years ago, is no easy task and Paabo's group has been one of the global leaders. Studies of ancient DNA are important because they provide direct evidence of the past, so where DNA is preserved it will remain valuable to sequence and interpret it.

One thing to note, that seems like double-think, but is not relevant to the points we want to make here, is that this Neandertal whole genome sequence is not the whole genome sequence of a Neandertal. This sequence is a composite assembled from ancient DNA extracted from three different individual Neandertals' remains. But 'the' human genome sequence online at GenBank is also a composite. Some technical issues are affected by this, but they aren't relevant here.

Whatever the details of the assembly, or whether variation among Neandertals was observed, the issue here is the origin of modern human sequences: did any of it descend directly from Neandertals, or were they an entirely separate group (or species, even) that separated from the common human stock and had no subsequent inter-breeding. That is, we today would have no descent directly from the Neandertals. Or was there some inter-group hanky-panky?

The new paper suggests that there was, but there are two major problems with that. The 1-4% are in segments that seem to have a different ancestry from the rest of the Neandertal genome, less divergent from us. The rest diverges from us by about the amount you'd expect given our joint time of separation from our common ancestry with chimpanzees.

The first problem is one we harp on regularly, the playing to the media and exaggeration of the results. In this case, the exaggeration was the definitive way the admixture issue was made melodramatic and definitive. It suggests that interbreeding was something exotic or immoral, like a human mating with a chimp, rather than what at the time would have been considered routine mate choice among individuals from neighboring groups.

They would probably have coexisted together in times when nobody moved very far, and would have differed from each other far less than, say, Africans and Europeans do today, and between whom mating is thankfully no longer a big deal in our society. In fact, the evidence reported is that this interbreeding occurred after both groups were part of the Eurasian population after its expansion out of Africa. In that sense, the groups may have diverged somewhat, and come in contact again later, and became good neighbors for a while. Whatever happened way back then involves our ancestry which is certainly interesting and worth knowing. But when the evidence is tentative so should be the claims.

But there is a second and much more important problem. It is a subtle issue, that in essence is that whether or not any direct human genetic ancestry traces back through Neanderthals basically doesn't matter related to how 'different' we are from them. In round numbers, here's why:

A copy of your genome and a copy of a chimp's (our nearest living relative) differ by about 2 to 5% in terms of DNA sequence. Two copies of the human genome today differ by about 0.1 to 2% depending on the comparison one makes.

We've been separated from our common ancestor by 7-10 million years. Corresponding to that, the paper shows that the Neandertals differ from modern humans by about 7% which is about what you'd expect given that (regardless of admixture issues) the Neandertal split happened only after about 90-95% of the time had passed since we and chimps split.

By that time, basically everybody was human, and in turn that means that overall we are essentially as similar to Neandertals as we are to each other (crudely speaking, we're 95% closer to them than to chimps). And of course the vast majority of sequence differences generally, and hence in this case, will have little if any function. If humans are virtually identical to each other then we are virtually identical to Neanderthals whether there was any inter-mixing or not.

But consider how much functionally meaningful (as opposed to evolutionary clock-meaningful) variation there is in modern humans around the world. Within our single species, there's plenty of room for differences, and they can be important. They can protect you in very important ways from the environment (as skin pigmentation does in the tropics), they can protect you from disease (as immunological differences among us do), and there is a lot of variation in behavioral abilities of all sorts. As many diseases show, even just one single DNA change can be lethal.

The point is that whatever important functional differences or similarities there were between us and Neanderthals need have nothing to do with whether there was any admixture between their populations and populations of our other direct ancestors. Natural selection will purge bad variation, favor sterling advantages, and ignore most of the rest wherever it comes from.

If there is major functional difference between us and our burly cousins, it is to be found in the relevant genes, not in the score card (or dance card) of our sequence differences. And they could have existed in them then, but not us now, even if there was inter-breeding.

This means that Dr Paabo is right to treat this as a story for publicity. Its scientific impact is far less than its human interest value. To portray the inter-mixing question as an important one about human function is to misrepresent (or misunderstand?) how genes and evolution work. But to understand that takes more than a sound byte, and of course that means not many people will be interested.

At the same time, there's nothing wrong with trying to find out, especially from direct genetic data when it's available, what we can about our closest, if dearly departed, ancestors.

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]

Rounded up? No, the varmints got away!

It seems there really is no free lunch....except perhaps for weeds. That's because it turns out that genetically modified crops don't defy evolution after all! The laws of Nature stand, and weren't superseded by agribusiness scientists.

A story in the New York Times this week tells about the increasing resistance of weeds to Roundup, or glyphosate, the weedkiller originally introduced by Monsanto but now sold by a number of other companies. The weedkiller was made for use with 'Roundup Ready' crops, grown from seeds genetically modified to be resistant to the herbicide. Many farmers who planted these seeds were very happy with how easily weeds could be controlled as well as the kind of no-till agriculture, and the reduction in top soil erosion that that brought, that then became possible. (Though there was, and still is, controversy over Roundup Ready crop yields, the safety of the chemical, Monsanto's legal right to insist that farmers can't save seed to plant the following year, and so on, but those issues are not for this post.)

But farmers are growing increasingly unhappy. Roundup resistant weeds -- superweeds -- were first found flexing their new-found muscles in Delaware, but now crop up all over the country (so to speak), with insidious and expensive effects.

To fight them, Mr. Anderson and farmers throughout the East, Midwest and South are being forced to spray fields with more toxic herbicides, pull weeds by hand and return to more labor-intensive methods like regular plowing.

“We’re back to where we were 20 years ago,” said Mr. Anderson, who will plow about one-third of his 3,000 acres of soybean fields this spring, more than he has in years. “We’re trying to find out what works.”

Farm experts say that such efforts could lead to higher food prices, lower crop yields, rising farm costs and more pollution of land and water.

“It is the single largest threat to production agriculture that we have ever seen,” said Andrew Wargo III, the president of the Arkansas Association of Conservation Districts.

Oddly enough, Monsanto originally promised that herbicide resistance would be insignificant. Why? They must have believed they were dealing with so fundamental a vulnerability on the weedy pests' part that they couldn't evolve a way around their assassin.

Monsanto is still saying that the problem is containable -- but they would, since they stand to lose a lot if farmers no longer have reason to buy Monsanto's Roundup resistant seeds. Did Monsanto think that, as one of the largest agricultural companies in the world, that they could make evolution stand still? And of course it's not just glyphosate resistance that's the problem. The International Survey of Herbicide Resistant Weeds lists "347 Resistant Biotypes, 195 Species (115 dicots and 80 monocots) and over 340,000 fields". The additional problem with Roundup is that farmers (and Monsanto) have become dependent on GM seeds, and the cultivation methods they've used to grow them.

The story is of course reminiscent of the increasingly widespread antibiotic resistance in bacteria, though there we had 50 good years, while with Roundup it was only several decades -- neither even a blink of the eye in evolutionary terms, of course. But, we've known for millennia that artificial selection is a fast and powerful force for change -- it was Darwin's very model for how natural selection works in the wild, after all. Farmers have chosen their best animals for breeding probably since they were first domesticated 10,000 years ago.

So, it shouldn't be surprising that in effect artificially selecting for herbicide resistant weeds, or antibiotic resistant bacteria, is fast and effective as well. The idea that we might be headed for the last roundup is naive. Nope, the truth is, pardner, that the varmints are still out there, eluding all the posses we send after them.

First 2010 Misrepresentation of the Year Award Goes to Nature

The first 2010 Misrepresentation of the Year Award goes to Nature magazine for last week's cover story. The caption on the cover is "The MS Genome" and is accompanied by silhouettes of one person standing and her twin in a wheelchair. But is the story about 'the multiple sclerosis genome' (whatever that would be)? No.

Compare the authors' actual title of their report to the cover's:
"Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis."

This is a representative, scientifically responsible title for the paper. There is a difference between genomes from MS patients and 'the MS genome.' What the  authors report is the complete sequencing of the genomes of one discordant pair of identical twins (where one twin has MS and the other doesn't), and gene expression differences between 3 sets of discordant identical twins. They discuss issues of data accuracy and replicability, and they find no genetic signature that can explain the discordance.

• Is the story well-done work? Yes, we're not experts but it seems to be
• Is the science valid? Yes, it seems to be
• Have the authors explained MS? No, but they don't claim to have done so
• Have they found the MS genome? No and they don't claim that either
• Have they identified which genome is 'the' MS genome? No
• Have they shown that there is such a thing as 'the' MS genome? No
• Is the story an important contribution to the understanding of MS? That's debatable

Genetic differences between the two twins in each pair were found, presumably the result of somatic mutations that occurred during or after embryogenesis, but none were associated with MS. Because MS has a curious relationship to climate and has sometimes been attributed to viral infection, sequences that weren't identifiable as human from each set of twins were aligned with viral genomes. That was a clever thing to try, and might have identified an MS 'infectome', but unfortunately no differences were found between the viral load of affected vs. unaffected twins.

The twins did not show replicable discordance at the immune system (HLA) genes, or other genes, that previous mapping and other studies had shown are likely contributors to MS risk. The twins varied a lot in terms of DNA sequence (presumably, somatic mutation) and gene expression levels--but in a way that could be attributable to their MS discordance.

This is another installment in the Life is Complex Department. We said above that this may not be an important contribution, because there are so many possible reasons why the authors didn't find what they hoped to find. That would not be their fault, and indeed, their work shows some of the many reasons why these kinds of data are problematic (sequencing errors, difficulty replicating expression levels, and so on). Perhaps they should have known this would have been the case from other similar kinds of studies (such as comparing genomes of cancer and normal tissue from the same person).

They confined their gene expression comparisons to a very confined set of sites -- necessarily, given current sequencing methods -- but that means that in no sense was this study exhaustive. It could be said that this was a premature use of new technology. But that's not our issue here!

The idea was a clever one, but perhaps built too much on hope against what we know about disease complexity. In general, one would be surprised if a clear result had been found, because these twins did not even have the suggested risk genotypes at those candidate genes, and because a genetic signature for MS has been so elusive before now.

Perhaps identical twins are not as good a comparison as they seem on the surface, since we know that stochastic and somatic changes can be responsible for many differences during life (that's what the cancer studies show).

Perhaps twins that did carry the suspected HLA or other risk genotypes, but who are nonetheless discordant for MS, would provide a more cogent comparison. Discordance in them would suggest that something else--perhaps environmental pathogen exposure or somatic mutation in other genes in one of the twins--was responsible.

The etiology of MS remains mysterious and this was one way to take a shot at a discovery.

But multiple sclerosis is no joking matter. The Nature cover is a kind of cruel disservice to those who suffer from MS, or their loved ones, by suggesting that the genetic cause had been found, with the obvious innuendo that a cure is just round the corner. Why else the cover story in Nature??

Their kind of misrepresentation is what diverts resources to inefficient or even lost causes. In fact, in no way has 'the' MS genome been found, nor is it defensible to suggest that there is such a singular thing. And only half the studied people were affected. Maybe the affected twin experienced somatic genetic changes, while the unaffected twin reflected the inherited 'resistant' or 'normal' genome of the pair?

It's not the authors but the journal that is responsible for the misrepresentation. It was a shot in the dark, perhaps, that had no business as a cover story. We hope that research will not be discouraged as a result--that is, that the authors' lack of positive findings does not lead to their work being thought of as 'negative' (if the bait-and-switch of the journal cover leaves hopeful readers deflated when they see the real story).

Nature has been quite successful at its attempt to match the quality standard of People magazine, and we assume that will continue, as they're pros and they know how to reach their market. Their naked savage and 'ancient' Khoisan genome cover of a couple of months ago ran this one a close second, and we wrote about that at the time. Though we're sure they would deserve it, we want to keep these Misrepresentation Awards one per customer per year, so we hope Nature (but not People) will wait for its next one til 2011.

Plus c'est la même chose, plus ça change??

Nothing ever really changes, or so goes the old French saying 'plus ça change, plus c'est la même chose.' The more things change, the more they're the same thing. But is that how life really is?

An interesting new paper in Genome Research on this subject is getting some notice, but in fact the results should not be surprising, given what is known about evolution and development.

The blurb in Nature says:

The earliest stages of embryo development [as shown in the photo above, taken from the paper] seem to be almost identical among mammals. However, Sheng Zhong at the University of Illinois at Urbana-Champaign and his team have found that 40.2% of the genes shared by humans, mice and cows are expressed differently at this point.

Their analysis of gene-expression patterns in embryos at various stages early in development showed that differences result from altered gene regulation. In some cases, mutations affected the binding of regulatory proteins. In others, transposons or 'jumping genes' had hopped in front of the genes, changing their regulation.

This variation among species suggests that multiple gene networks can guide embryo development, and could be harnessed to generate embryonic stem cells.

This may have significant implications for stem cell research, but it also says a lot about evolution and development (EvoDevo). People are often surprised to learn that traits that are similar between species can have very different genetic architecture -- it's more usual to hear about homologous or orthologous genes, similar genes for similar traits (the iconic example is Hox genes, which play a major role in body patterning in fruit flies and humans, and every species in between).

Alternatively, a story in the New York Times last week described the usefulness of yeast or plants or worms for finding genes for human diseases. The genes described belong to clusters that do completely unrelated things in different organisms (one example was of a cluster of genes that repair damage to the cell wall in yeast but that is involved in blood vessel formation in humans). These clusters have been conserved through evolutionary time.

But the idea that different genes can underlay homologous traits is perhaps more counter-intuitive. Ken and his then post-doc, Malia Fullerton, published a paper in Theoretical Population Biology in 2000 describing just this. The effect is called 'phenogenetic drift' to indicate that the trait's genetic basis, the genetic effects that generate the phenotype, changes. This is not the same as genetic drift, when genetic variation that has no effect on a trait, or at least on reproductive success ('fitness') changes over the generations, nor that of phenotypic drift, when traits vary over generations to the extent that the variation doesn't affect reproductive success. Phenogenetic drift can be these things, but also, and perhaps most importantly, it occurs even when there is selection affecting the trait, even strong selection.

Thus, in the example above, the very early and hence very fundamentally important, stages in mammalian embryos are quite similar among different species, but the usage of genes to make it so is considerably different. Phenogenetic drift is easy to see all over the place -- even within species, when different people can have the same trait -- even including disease -- for different genetic reasons. Relative to each other these genotypes are equivalent in fitness terms, and their contributing alleles will change frequency over time by drift. It's no surprise to see it when we know that duplicate genes and many contributing genes together generate lots of redundancy and alternative genetic pathways to get the same trait.

However the dogma about selection and adaptive evolution has been gene- rather than trait-centered. But when many different genotypes can generate effectively the same phenotype, then perhaps genes really aren't the most important things to consider when we try to understand evolution. In this sense, perhaps because genes weren't understood at the time and perhaps because he had it right, Darwin developed his ideas about phenotypes -- the traits of organisms -- rather than genotypes. After all, he didn't need his idea of genetics to explain the historical nature of life's variation (indeed, evolution as he saw it wouldn't work under his idea of inheritance, and he knew it).

It often seems that the longer a trait is maintained, the more likely it is to have changed its genetic basis. Kazu Kawasaki in our lab, for example, has written a number of papers about the different genetic architecture for bone and tooth mineralization that has evolved in different lineages. In that case, the gene pathways share a common ancestor, a single gene that duplicated in different lineages to create gene families involved in mineralization -- he calls these the SCPP gene family. The original founding gene was apparently involved in the development of the first vertebrate mineralized skeletal tissue (probably, external skeletal protective plates or scales, even before there were calcified bones).

The final composition and structure of mineralized bone may vary, but it's the same trait, and serves essentially the same purpose (strength) in different lineages. Same trait, different genes. Whether this is usually true with conservation of form within lineages (such as the ants in amber that we wrote about last week), we can't know, because we have no way to know the original genetic basis. However, among other things, phenogenetic drift or alternative genomic pathways to the same trait, has interesting implications for notions of homology, the sharing of traits today because they have descended from the same ancestor. Traits can be homologous, but their genetic basis may not be. When selection is on the phenotype, it gets maintained however works!

School's Out! (But is my joy based in biology?)

It’s the last day of the semester. Students are submitting their final exams to me today and it’s only fitting that I submit my final thoughts to them (and to you) about what I learned this semester about the Biology of Behavior (Anthropology 261).

First of all, it’s mind boggling that after spending an entire semester studying the subject there are students on one hand…

Here’s me with arms outstretched to the sides, palms up.

… who believe that behavior is mostly determined by genes and that one day we’ll be able to explain it all with genetics, and then there are students on the other hand who are super critical of science and also think that behavior is entirely learned.

You’re wondering what this “behavior” is that I’m talking about.

Me too.

Here’s me wincing vulnerably with blushing cheeks.

That’s problem number one. What is behavior? It’s not really clear. Not after a course like this. Maybe my students will illuminate this for me in their final essay in which they categorize human behaviors according to their own taxonomies. But I haven’t read their essays yet.

Here’s me feeling fight-or-flight grading anxiety with tingly palms and armpits.

Problem number two. Everybody, even the most extreme, was on board with Nature PLUS Nurture (as opposed to Nature VERSUS Nurture). So, many of the class discussions boiled down to popular debates, as opposed to more nuanced debates that would have been more productive. But because we couldn’t become experts at this introductory level, it was difficult to get to the nitty-gritty. What we concluded was that the debate about human behavior in the popular media is full of false dichotomies, irrational fears of improbable/impossible future science, and irrelevant debates as a result of both.

Problem number three has to do with normal versus abnormal behavior. People seem to think that because a behavioral disorder can be traced back to genes, then therefore variation in that behavior at the normal level in unaffected people can also be explained by genes.

Here’s me making a wrong answer buzzer sound. Errrrrrr!

So did we figure out why humans do what they do? Well, considering the two choices [(A) It’s instinct. It evolved by natural selection or (B) We learned it. It’s a product of our environment.] The question of why becomes obscured by the possibility that we may not have a choice.

The former choice, A, implies that we can’t help our behavior…We have excuses for behaving badly and we can’t take moral credit for behaving nicely either.

The latter, B, puts the emphasis on culture and its importance…either at the individual level or beyond. Our bad behavior is our own fault or due to our parents, friends, environment, circumstances. Our good behavior is our own doing or it is shaped by parents, friends, environment, circumstances, and by government laws and religion.

So no matter what the answer is, it’s probably going to offend somebody.

Then there are all the behaviors that are neither “bad” nor “good.” The ones that are just what folks do or do not do at various times of their lives, in various circumstances, under various conditions, according to various individual biologies and histories.

Here’s me shrugging my shoulders and throwing my hands up in the air.

The bottom line that everyone agreed on (I hope) is that all behavior is biological even if it’s learned because we are biological beings. Everything we do, learn, say, feel, think is a biological process. Our genes don’t have to determine it for it to be biological. And, it’s all biological unless you invoke supernatural explanations. Human behavior is biological and this goes for whether or not we intend to do what we do.

So what are the determinants of human behavior that all somehow derive from biological processes?

We made a flow chart over the course of the semester and this is the result. Because there are no arrows pointing to any behaviors, this is not a chart of the determinants of human behavior. Instead it is the “Determinants of the determinants of human behavior.” Smart alecs will notice that there are no quantum variables on here and that’s because we didn’t get that small/big this semester.

Hey, at least it’s better than the flow chart for the American strategy in Afghanistan.

Now could you say that explaining human behavior is easier than explaining the American strategy in Afghanistan? That's a good question! But this flow chart may have caused you to wonder, what’s the point of trying to explain human behavior if it’s at least this complex?

Well, there are behavioral disorders we can hope to treat or cure. And there are evolutionary puzzles that we want to solve!

So how’s the treatment of disorders going? One recent example is the search for the genes for stuttering. That the genes linked to stuttering are involved in metabolism is, first of all, surprising to most until they think about how metabolic processes are linked to neurological development. Okay. So what’s the gene? There are three genes where stutterers in the study population had mutations: GNPTAB, GNPTG , NAGPA. So they found the genes for stuttering? Not exactly. Only 6% of stutterers in the sample had these mutations. Only 6%! The other 94% of stutterers are stuttering with perfectly normal versions of these genes. Plus, there are some people in the sample of non-stutterers (albeit a very few, <0.5%). style="">At least for the 6% who do have known mutations, they could see drug treatments soon.

Now, about those evolutionary riddles we’re all dying to solve…

That’s where maternal effects come into play. This is when mom’s genotype or phenotype influences her offspring’s phenotype and maternal effects are known for things like body size, immune function, predator resistant morphology (like spikes or wings). Known triggers are things like resources, density of conspecifics, temperature, parasites, and predators. And these are adaptive! Relatively little is known about maternal effects on behavior, however, it has been reported recently that mother crickets, just by their being around wolf spiders, influence how their offspring react to predators.

Here’s me crouching down and imitating a cricket immobilizing itself as predator-defense.

Mothers who have been exposed to predators have offspring that are better at surviving in the presence of predators than offspring of mothers who have not been exposed to predators.

Here’s me spit-taking my morning coffee because this is just so incredibly mind-blowing.

So if Nature VERSUS Nurture is so passé. And if it all does boil down to biological underpinnings and genes even if the genes don’t dictate things. Then why the rage and the frustration over explaining human behavior? Why the fears that we’re going down the horrific eugenics path by continuing to search for genes for behavior when we probably can’t find genes that determine variation in any of the behaviors that we find especially interesting in normal people?

I think that what offends people most about biological studies of behavior is the simple fear that it might be explained. Learning about human nature and coming up with the explanations for ourselves, by ourselves, is one of the thrills of being a human. It’s something that we want to experience over our lifetimes, not learn from someone else’s simple rules. It’s the idiosyncrasies and the surprises along the way that can be so beautiful and meaningful and those moments are threatened if a scientist tells us how to size up a person with an equation.

What I learned this semester is that people are defensive about science explaining our personalities, our selves. But what I also learned is that no matter how hard it tries, science cannot explain even the average Joe’s behavior or personality with genes or otherwise.

So what’s the big deal? Relax. You’ll always be somewhat of an enigma. And so will I.

Here’s me lifting my arms behind my head, leaning back, grinning, and sighing contently.

School’s Out!