Richard C. Francis' "Epigenetics: The Ultimate Mystery of Inheritance"

This is an exciting topic and I had high hopes for this book. The book does include some wonderful "attention grabbing" stories of some biological facts that don't fit the traditional genetics story. It did introduce me to several areas of research where epigenetics his giving new insight into biology. But I felt the author could have provided more detail on the science and more a "lay of the land" review. The specific examples were interesting but without more background it is hard to appreciate them in the overall context of epigenetics as a scientific theory.

My lament may not be a fault of the author. I notice than when I look through the Wikipedia article on epigenetics I find much detail but not a solid sense of an over-arching scientific theory. I see many mechanisms discussed, but I feel the glue is missing, the stuff that makes these mechanisms all part of a coherent scientific theory. Maybe I'm asking for too much. But it feels as if "physics" is introduced as statics, dynamics, kinematics, etc. An assortment of subfields grouped under "physics". But what is the rational for physics as a scientific field and how do these subfields fit together into a whole? Presumably the glue and the coherent overarching theory is "epigenesis" but Francis' book doesn't make me comfortable that I understand this theory. I'm left seeing the trees but not the forest.

The author goes to great pains to make clear that epigenetics isn't just a new development in genetics. He wants to emphasize that the "genetics" in epigenetics derives from "genesis" and not "genes". It is a story of developmental biology. I especially enjoyed the section where he discussed "preformationism" and "epigenesis". I found this an excellent motivation for understanding why epigenetics as a new science is so important. It provides the scientific mechanisms to support epigenesis.

I found the material on "genetic imprinting" murky. He did labour mightily to make it clear, but I think I'm a victim of terminology. The word "imprinting" kept throwing me for a loop. There was nothing to imprint with imprinting. And it certainly has nothing to do with ethology's "imprinting". It is simply a deplorable lack of imagination in coming up with a technical term that adequately captures the concept.

The chapter on cancer and epigenetics was exciting. I can see great hope in dealing with cancer by changing the paradigm from genetics and disease to inter-cellular communication and control over gene expression.

He makes it very clear that the traditional story of genes are the blueprint and proteins are the resulting organism is far too shallow a story. The book makes it clear that something quite exciting is happening with discoveries of how inter-cellular communication is controlling gene expression through epigenetics and that the story of epigenetics is quite complex. I just wish he has expanded the book to cover more of the story.

I was disappointed in the book because it was written with a whiff of dry academic style. He needs to put more effort into using words to paint pictures and build up a story that can carry the average reader along. I found myself having to refer to the index far too often to keep straight terminology. Only specialists want to learn the opaque terminology of modern science. I'm happy to be acquainted with the words, but I need something more descriptive to hang my hat on. I need more of "tell me what you are going to say, say it, and then tell me what you just said to me" storyline so that I can get comfortable with new concepts and get confidence that I understand them.

You can get a sense of the dryness of the text from the postscript where he is reviewing the "themes" that his book covered:

The first theme concerns the nature of epigenetic processes: a form of gene regulation. Epigenetic gene regulation is long-term gene regulation, hence epigenetic alterations have long-term effects on gene behavior. Indeed, epigenetic alterations of gene behavior can be longer lasting than mutational alterations of gene behavior, epigenetic alterations of gene behavior are generally reversible.

I can vouch that the book supports the factual truth of all of the above, but you can see how turgid the style can be. That's a lot of dense prose that will put most readers to sleep with too much repetition of fairly opaque terms. You have to be motivated to want to wade through that kind of writing to understand what the author is trying to tell you. Sure, from an insider's viewpoint, all of that is obvious. But from an outsider's view there is that deadly repetition of $100 words labouring a point that is hard to discern.

I do recommend this book. It is an important field. You will find some interesting examples of epigenetics and get an appreciation of how it works. But it will mostly leave you desperate for a better text to more properly introduce you to the field. Something that goes beyond examples and presents a well rounded theory with all the examples safely embedded into a structure that makes sense of the field.

Sex and Ancient Humans

It was only a few years ago that the idea that Homo sapiens sapiens interbred with Neanderthals became thinkable. Now genetics no only demonstrates it but claims it delivered benefits.

Here is a bit from a Yahoo! News report:

Sexual encounters with archaic humans like the Neanderthals produced children who inherited key genes that have helped modern humans fight illness and disease, said a US study published Thursday.

"The cross-breeding wasn't just a random event that happened, it gave something useful to the gene pool of the modern human," said Stanford University's Peter Parham, senior author of the study in the journal Science.

Equipped with knowledge of the genome of the Neanderthals and the Denisovans, of whom a tooth and a finger bone were discovered in a Russian cave last year, researchers scoured the data for hints of what genes crossed over.

Scientists already knew that about four percent of Neanderthal DNA and up to six percent of Denisovan DNA are present in some modern humans.

This study took a close look at a group called HLA class I genes which help the immune system adapt to fight off new pathogens that could cause various infections, viruses and diseases.

Researchers traced the origin of one type, HLA-B*73, to the Denisovans, who likely mated with humans arriving in West Asia on their way out of Africa. The variant is rare in modern African populations but is common in people in west Asia.

"We think this had a lot to do with the pathogenic environment in different parts of the world," said Laurent Abi-Rached, a French researcher and lead author of the study.

"When modern humans came out of Africa, they were going into a new environment. This gave them an advantage. It was a rapid way of acquiring defense," he told AFP.

These ancient HLA genes have multiplied among modern populations and are seen in more than half of Eurasians today, said the study.

I love the way science slowly advances human knowledge. The world is a very interesting place and facts, for me, are far more fascinating than fiction.

I don't get excited about hyped "science" like the Ivanov experiments. But I enjoy sound science which breaks new ground such as the new genetics which allows hybridization with Neanderthals to come out of the murky world of speculation into the world of hard facts.

Zimmer Talks about Viruses

Carl Zimmer write articles and books on biological topics. His latest book is titled A Planet of Viruses. Here is a recent talk he gave on that subject and is available as a video from FORA.tv:



Elsewhere Zimmer points out that we are more bacteria than human, i.e. we carry ten times the number of baterial cells in and on our bodies than we carry human cells. In this talk he astounds me with a new fact. We have roughly tens times as much endogenous retroviruses embedded in our genome than we have human genes in our genome! (This article by Zimmer gives examples of embedded viruses.)

To call yourself "human" is to be charitable. We are more bacteria than human and more virus than human. Who would have thought!

Interesting Research Result on Autism

The NeuroLogica blog has an interesting post on ASD (Autism Spectrum Disorder). Here is the bit I found most interesting because it cites an interesting phenomenon of copy number variation which can act to turn up or down sociability:

Sanders et al studied 1124 families with one affected child with ASD and one unaffected child, with unaffected parents. They found that 6-8% of them could be explained by changes in copy number variants – how many copies of specific genes were present. Most intriguing, they found:

We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality.

In other words – at one gene location where a deletion causes a syndrome characterized by a highly social personality, they found duplications associated with a decrease in sociability. This strongly suggests that the gene in question has a strong influence on sociability, and can be either turned up or down depending on the genetic change.

And this:

In another study in the same issue researchers find that large networks of genes are responsible for the ASD phenotype. Further they provide evidence that could explain the fact that males are at higher risk of ASD than females. They find that a much greater perterbation in the gene network is required for ASD to manifest in girls than in boys.

And it interesting that they are eliminating epigenetics as an explanation:

Genes evolve to respond to the environment, and increasingly scientists are identifying important epigenetic factors in disease. But the research to date suggests a highly dominant role for genetics in autism, and this recent research adds to the growing body of research supporting this.

Go read the original article to get the embedded links.

Why Identical Twins Are Not Always Identical

I found this post by Kevin Mitchell in his blog Wiring the Brain to be fascinating. It explains why identical twins are not always identical:

... these studies also highlight the limits of genetic determinism, which is especially evident in comparisons of monozygotic (identical) twins, who share all their genetic inheritance in common. Though they are obviously much more like each other in psychological traits than people who are not related to each other, they are clearly NOT identical to each other for these traits. For example, if one twin has a diagnosis of schizophrenia, the chance that the other one will also suffer from the disorder is about 50% - massively higher than the population prevalence of the disorder (around 1%), but also clearly much less than 100%.

What is the source of this extra variance? What forces make monozygotic twins less identical? I have argued previously that random variation in the course of development is a major contributor. The developmental programme that specifies brain connectivity is less like a blueprint than a recipe (a recipe without a cook) – an incredibly complicated set of processes carried out by mindless biochemical algorithms mediated by local interactions between billions of individual components. As each of these processes is subject to some level of “noise” at the molecular level, it is not surprising that the outcome of this process varies considerably, even between monozygotic twins.

While such developmental variation can be referred to as “non-genetic”, a new study suggests that one important component of this variation may be genetic after all, just not inherited. Mutations can be passed on from parents to offspring or arise during generation of sperm or eggs and thus be inherited, but they can also arise any time DNA is replicated. So, each time a cell divides as an embryo grows and develops, there is a very small chance of new mutations being introduced. These “somatic” mutations (meaning ones that happen in the body and not in the germline) will be inherited by all the cells that are descendants of that new cell and so will be present in some fraction of the final cells of the individual. Mutations arising earlier in development will be inherited by more cells than those arising later.

Each person will therefore be a mosaic of cells with slightly different genetic make-up. The vast majority of such mutations will not have any effect of course (with the obvious exception of those that cause dysregulation of cellular differentiation and result in cancer). But sometimes a new mutation will affect a trait and cause a detectable difference. The most obvious examples are in genes affecting hair or eye colour – where a patch of hair may be a different colour, or the two eyes may be different colours.

But what if the mutations in question are linked to a psychiatric disorder? If such a mutation arises early in the development of the brain and is therefore inherited by many of the cells in the brain then this could lead to the psychiatric disorder, just as if the mutation had been inherited in a germ cell.

A new study adds to the evidence that such mutations do indeed occur at an appreciable frequency and may help explain the discordance in phenotype between pairs of twins where one has schizophrenia and the other does not. The authors analysed the DNA from blood cells of pairs of twins discordant for schizophrenia and their parents. They were looking for two different kinds of mutation: ones that changes the identity of a single base of DNA (one letter of the genetic code to another), called point mutations, and ones that delete or duplicate whole chunks of chromosomes, called copy number variants, or CNVs.

As expected, they were able to detect both inherited mutations (present in one of the parents) and de novo mutations (present in both twins but not in the blood cells of either parent). What is more remarkable though, is that they also detected de novo mutations present in the blood cells of one twin but not the other – lots of them. About 1,000 point mutations and 2-3 new CNVs not shared by the other twin. The implication is that these mutations arose during the somatic development of one twin. They identify a couple CNVs in the twins affected by schizophrenia, raising the (very speculative) possibility that those mutations may contribute to the development of the disorder. It will obviously require a lot more work to test that specific hypothesis.

All of this is fascinating, but especially interesting is that this effect is visible at the macro level. You can see it with the condition heterochromia iridum (the two eyes having different colours).

Click to Enlarge

Psychopaths

Here is a bit from an article by Jon Ronson in the UK's Guardian newspaper entitled "How to Spot a Psychopath". Ronson has just written a book about psychopaths entitled The Psychopath Test. I would guess that this article is excerpted from the book:

...how could psychopaths be cured?

In the late 1960s, a young Canadian psychiatrist believed he had the answer. His name was Elliott Barker and he had visited radical therapeutic communities around the world, including nude psychotherapy sessions occurring under the tutelage of an American psychotherapist named Paul Bindrim. Clients, mostly California free-thinkers and movie stars, would sit naked in a circle and dive headlong into a 24-hour emotional and mystical rollercoaster during which participants would scream and yell and sob and confess their innermost fears. Barker worked at a unit for psychopaths inside the Oak Ridge hospital for the criminally insane in Ontario. Although the inmates were undoubtedly insane, they seemed perfectly ordinary. This, Barker deduced, was because they were burying their insanity deep beneath a facade of normality. If the madness could only, somehow, be brought to the surface, maybe it would work itself through and they could be reborn as empathetic human beings.

And so he successfully sought permission from the Canadian government to obtain a large batch of LSD, hand-picked a group of psychopaths, led them into what he named the "total encounter capsule", a small room painted bright green, and asked them to remove their clothes. This was truly to be a radical milestone: the world's first ever marathon nude LSD-fuelled psychotherapy session for criminal psychopaths.

Barker's sessions lasted for epic 11-day stretches. There were no distractions – no television, no clothes, no clocks, no calendars, only a perpetual discussion (at least 100 hours every week) of their feelings. Much like Bindrim's sessions, the psychopaths were encouraged to go to their rawest emotional places by screaming and clawing at the walls and confessing fantasies of forbidden sexual longing for each other, even if they were, in the words of an internal Oak Ridge report of the time, "in a state of arousal while doing so".

My guess is that this would have been a more enjoyable experience within the context of a Palm Springs resort hotel than in a secure facility for psychopathic murderers.

Barker watched it all from behind a one-way mirror and his early reports were gloomy. The atmosphere inside the capsule was tense. Psychopaths would stare angrily at each other. Days would go by when nobody would exchange a word. But then, as the weeks turned into months, something unexpected began to happen.

The transformation was captured in an incredibly moving film. These tough young prisoners are, before our eyes, changing. They are learning to care for one another inside the capsule.

We see Barker in his office, and the look of delight on his face is quite heartbreaking. His psychopaths have become gentle. Some are even telling their parole boards not to consider them for release until after they've completed their therapy. The authorities are astonished.

Back home in London, I felt terribly sorry for Tony. So many psychopathic murderers – fortunate to have been under Barker's radical tutelage – had been declared cured and freed. Why couldn't Broadmoor adopt some of his ideas? Of course, they seemed dated and naive and perhaps overly reliant on hallucinogenics, but they were surely preferable to locking someone up for ever because he happened to score badly on some personality checklist.

Then I learned that two researchers had in the early 90s undertaken a detailed study of the long-term recidivism rates of psychopaths who'd been through Barker's programme and let out into society. In regular circumstances, 60% of criminal psychopaths released into the outside world go on to reoffend. What percentage of their psychopaths had? As it turned out: 80%.

The capsule had made the psychopaths worse.

I very much agree with Hare that you can't "rehabilitate" a psychopath and that they are very different from normal humans. They are a variant. I'm a variant in that I have red-green colour-blindness. You can't "rehabilitate" me to remove that abnormality. There is no prison program or psychological therapy that is going to turn a psychopath into a normal person. They are different. They need to be designated "dangerous offenders" and be kept locked up even with their prison sentence comes to an end. This may mean transferring them to a psychiatric facility. But they need to be segregated from the rest of society.

And after reading Hare's book Snakes in Suits it is clear to me that corporations need to test their management and weed out the psychopaths. I very much believe that the 2008 financial crisis could have been avoided if the psychopaths on Wall Street and the big banks could be weeded out.

Viewing People Inside Out

Here is a snippet from an interesting film done by a person with autism entitled Normal People Scare Me:



I remember first becoming fascinated with this disorder back in the early 1970s when I wrote a review of a book on autism. Like most books back then, that author took seriously that this was a psychological "disorder" caused by refrigerator moms. This was especially cruel because the poor mothers of autistic kids are overwhelmed by the problems that this condition creates, the additional burdens of mothering, and to then turn and blame the mother! Sadly this was from the idiotic "Freudian" interpretation of disorders as all arising from problems in relationships and not from genetics or disease.

From Wikipedia:

Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by rare mutations, or by rare combinations of common genetic variants.

The good news is that intense intervention early in development gives these kids a much better life. They will never be "normal" but many of them can have reasonable lives. In the past, most were "institutionalized" which is just another name for warehousing until they die. And if you put a person in an institution with little loving interaction, many die fairly quickly. So the "solution" in the past was a kind of euthanasia. I have no problem with people choosing this option. It should be the decision of the family. But the good news is that for families with the strength to meet the challenges of raising an autisitic kid, there are much more positive outcomes today than there were 30 or 50 years ago.

One of my favourite science writers, Stephen Jay Gould, had a son with autism who was a calendar calculator like the twins Flo & Kate. I also enjoy books by autistics. Some that quickly come to mind are Temple Grandin's books Thinking in Pictures and Animals in Translation and Daniel Tammet's Born on a Blue Day (a savant with synesthesia).

Watch this talk given by Temple Grandin at a TED conference:

Why is there World Hunger?

Superstitious, anti-science thinking is the simple answer. Here's a bit from a UK Guardian newspaper article:

Food prices worldwide were up by a whopping 25% in 2010, according to the UN's Food and Agriculture Organisation, and February marked the eighth consecutive month of rising global food prices. Within the past two months, food riots helped to trigger the ousting of ruling regimes in Tunisia and Egypt. (It is noteworthy that food prices increased 17% last year in Egypt, and the price of wheat, a critical staple there, soared by more than 50%.) For poor countries that are net importers of food, even small increases in food prices can be catastrophic, and recent bumps have been anything but small.

There are several causes of rising prices. First, large-scale disasters have precipitated localised crop failures, some of which have had broad ripple effects – for example, Russia's ban on grain exports through at least the end of this calendar year resulted from fires and drought. Second, deadly strains of an evolving wheat pathogen (a rust) named Ug99 are increasingly threatening yields in the major wheat-growing areas of southern and eastern Africa, the central Asian Republics, the Caucasus, the Indian subcontinent, South America, Australia and North America. Third, rising incomes in emerging markets like China and India have increased the ability of an expanding middle class to shift from a grain-based diet to one that contains more meat.

And fourth, against this backdrop of lessened supply and heightened demand, private investment in R&D on innovative practices and technologies has been discouraged by arbitrary and unscientific national and international regulatory barriers – against, in particular, new varieties of plants produced with modern genetic engineering (aka recombinant DNA technology or genetic modification, or GM). Genetic engineering offers plant breeders the tools to make crops do spectacular new things. In more than two dozen countries, farmers are using genetically engineered crop varieties to produce higher yields, with lower inputs and reduced impact on the environment.

And this:

In fact, the United States and Europe are diverting vast and increasing amounts of land and agricultural production into making ethanol. The United States is approaching the diversion of 40% of the corn harvest for fuel and the EU has a goal of 10% biofuel use by 2020. The implications are worrisome. On 9 February, the US department of agriculture reported that the ethanol industry's projected orders for 2011 rose 8.4%, to 13.01bn bushels, leaving the United States with about 675m bushels of corn left at the end of the year. That is the lowest surplus level since 1996.

So, what do we know? Bad weather and a virulent new plant pathogen. The weather will change. And science can help develop resistent strains to deal with the new pathogen.

Rising incomes is not a problem. It makes it tough for the world's poor, but rising incomes also gives them hopes that they too will earn more and eat better some day.

Anti-GM quackery is a real problem. This is anti-science at its worst. Mumbo jumbo about what is "natural" and how it goes "against God's will to move genes from one species to another" is nutty. And the lies these fanatics tell! They claim that new breeding programs based on GM need special scrutiny is the same nonsense as the belief that the tomato was a "poisonous food" back in 1590.

Worst of all are the doom-and-gloom crowd so worried about "global warming" that they are willing to sacrifice the poorest billion people so that the "global warming" crowd can tool around in their SUV's using ethanol. That's right. The "global warming" crowd burns food so they can enjoy their yuppie lifestyle and continue to spread malicious rumours about "global warming" while letting a billion or so people starve to death. Talk about misplaced values and skewed ethics! And these hypocrites dare to preach to the rest of the world and spread their vile propaganda, a lie about climate that isn't going to kill anybody. But they are willing to condemn a billion to painful starvation. Hypocrites!

Autism

I worked with a guy who had Asperger syndrome. He was brilliant but strange. He never looked you in the eye and he had no social skills. Sadly his company was always nearly broke despite his brilliance because he couldn't find people to surround himself with the necessary skills.

I've been interested in autism since the early 1970s when I reviewed a book on it that claimed it was caused by a "refrigerator mom". Thankfully that era is long gone.

Here's a bit from a nice piece about current research at Stanford from the alumni magazine:

[Autism is] a disorder that affects 1 in every 110 kids. (The rate is 1 in 70 for boys and 1 in 315 for girls.)

Autism is a spectrum of disorders that share three core features—language deficits, social deficits, and repetitive interests and movements. On one end of the spectrum are people with Asperger's syndrome, who are socially awkward but who often have above-average intelligence. Dolmetsch's son has this diagnosis: He was late to speak and when he did speak, he talked in a stilted and peculiar way—more like a little adult than a child; and he has problems socializing. The most serious autism cases involve severe mental disabilities (about 40 percent of children with autism have IQs below 70) and behavioral problems. Between these two extremes, children may have normal intelligence but pronounced language and social impairments.

This is fascinating because it uses identical twins -- the gold standard for separating genetic versus environment -- who show different traits:

J.C. Flores, '87, has 15-year-old identical twins with autism. Lomasi can speak, but she avoids talking and gives mostly one-word answers. Marielle can say only a few words and has no functional communication system. "They're sweet and they like to hang around people," Flores says. "But they don't really feel the need to communicate. They don't see why you have to." ...

Studies of twins have shown that autism has a large genetic component, but it's not all genes. Identical twins have the same DNA, but sometimes only one twin gets autism. In other cases, as with Flores's daughters, Lomasi and Marielle, the severity of the disorder differs. The genetics are also complex. Different genes may be involved in different people; and, in any given individual, the disease may arise from changes in one gene, changes in several genes, or a combination of genetic and environmental factors. (Though no specific environmental triggers have been identified, researchers are testing everything from exposure to heavy metals and pesticides to TV watching.) Tackling this complexity requires large studies.

I'm amazed at the progress in identification and understanding "the disease", but research is nowhere near understanding what causes "it":

One of the biggest challenges is that autism is not one thing: It's a catchall diagnosis that likely includes a host of biologically distinct disorders. Though children with autism share a set of symptoms, these symptoms are quite varied and may have many, diverse biological origins. "Autism is incredibly heterogeneous. We've been lumping everyone together under this name autism, and unfortunately it makes it very difficult to study the biological features when we are treating multiple groups as one," says Sophia Colamarino, '90, vice president of research for Autism Speaks—a science and advocacy group—and consulting associate professor of psychiatry and behavioral science. To get a toehold into the biology, researchers will need to identify unique subgroups of autism, she says. Researchers across the globe are defining subgroups based on genes, molecular pathways, or signatures in the brain and blood.

Another impediment: access to the brain. Scientists can slice cancer cells out of a tumor and study them directly, but they can't just scoop cells out of the brain. Stanford is on the forefront of solving this problem...

This bit about the advances in genetic understanding is fascinating:

In the past decade, geneticists have discovered a handful of genes that when mutated or missing can cause autism. Though rare, these genes have given scientists some of their best clues about the disease's biological underpinnings. "I think it's very exciting, even if it's rare cases. We can at least get a better understanding of one piece of the puzzle and then we can branch out from there," Hallmayer says. For example, several of these genes are involved in communication between neurons. In a 2010 paper in Nature, Hallmayer and his colleagues from the Autism Genome Project greatly expanded this list of genes—reporting hundreds of rare genetic events that may be involved in autism.

It's long been known that about 5 percent of autistic kids have a chromosomal abnormality that can be seen under a microscope —part of a chromosome is missing, duplicated or in the wrong place. Because these changes affect a large number of genes, the children often have many problems in addition to autism. What wasn't known until recently is that we all have slight imperfections in our chromosomes—small regions of DNA that are duplicated or deleted. When these stretches of DNA contain genes, people can end up with one or three copies of the genes instead of the standard two. Technological advances have made it possible to detect these "copy-number variants," or CNVs. And it turns out they're important in autism and some psychiatric disorders. For example, a region of chromosome 16—containing about 25 genes, some involved in brain function and development—is deleted or duplicated in 1 to 2 percent of people with autism (and some with schizophrenia). Scientists are beginning to study these patients as an autism subgroup. ...

They identified disruptions in hundreds of genes that occurred only in autism cases, never in controls. Not all of the genes will turn out to be relevant to autism, but the ones that are could explain maybe 10 to 15 percent of cases, Hallmayer says.

This article is full of bits of information, hints about various things that cause autism. It is quite complex. There are lots of possibilities. It is easy to agree that this is a "spectrum" disorder because there are so many different areas where an autistic brain differs from a normal brain. This bit is surprising:

It's long been known that children with autism have larger-than-normal brains early in their development. Hardan has refined this observation, showing that some (but not all) children with autism have an increase in the thickness of the cortex —the part of the brain responsible for complex functions such as language and social behavior—that disappears as they grow. It might be possible to link this back to genetics, says Hardan, who frequently collaborates with Hallmayer. We know some of the genes that contribute to cortical thickness, he says.

Hardan is exploring new brain imaging technologies that offer an unprecedented level of detail. For example, diffusion tensor imaging (DTI) shows the individual axons (the elongated parts of neurons) that connect different parts of the brain. And MRI spectroscopy measures the levels of specific chemicals in various parts of the brain. DTI studies from several universities suggest that autistic children have abnormal long-distance brain connections, an observation that dovetails with Dolmetsch's studies in neurons. Using MRI spectroscopy, Hardan also has detected specific chemical imbalances in the brains of children with autism. He's looking for treatments that can normalize these imbalances.

Hardan's team is involved in about 15 different clinical studies. Whenever possible, he tries to link treatment responses to changes in brain images and to a subgroup of people with autism.

I expect as neuroscience becomes more advanced there will be more splitting and the autistic spectrum will hive off new diseases. Unfortunately, because of ignorance, the disease is "diagnosed" by symptoms. But that really is backwards. If you understand the mechanism then you can identify the disease. Multiple diseases can confuse you by appearing to be one disease.

One researcher that I've followed for years is Simon Baron-Cohen at the Autistic Research Centre in the UK. He may be the modern equivalent of the "refrigerator mom" diagnostician. But I do like his "extreme male brain" approach to understanding autism.

Epigenetics

From an article by Lizzie Buchen in Nature magazine, a story about an example of behavioural epigentics:

After dropping a pair of male and female adult rats into a rectangular Plexiglas container, Frances Champagne can expect one of a few scenarios to ensue. The male will definitely try to mate with the female — but the female is less predictable. She might approach him, appraise his scents and arch her back to allow him to mount her. Should a second male enter the cage after she's mated with the first, she may be similarly hospitable.

Some females play it coy, however, evading the male, requiring more courtship and, if mating does occur, avoiding another go. A number of factors can influence what the female does, but to Champagne, a behavioural scientist at Columbia University in New York, one is particularly beguiling: how often the female rat's mother licked and groomed her during her first week of life. Doting mothers have prudish daughters, whereas the daughters of inattentive rats cavort around like mini Mae Wests. At the heart of these differences lies the sex hormone oestrogen, which drives female sexual behaviour. Champagne says that neglected rats might respond to it more strongly than those raised by attentive mums.

The phenomenon is just one example of how experiences early in life can shape behaviour, and it may apply to humans. It is known, for example, that children who grow up in poverty are at greater risk as adults for problems such as drug addiction and depression than those with more comfortable upbringings, regardless of their socioeconomic situation later in life. But what is it about early experiences that has such a lasting effect? For Champagne and many of her colleagues, the answer has been apparent for nearly a decade. Life experiences alter DNA; not necessarily its sequence but rather its form and structure, including the chemicals that decorate it and how tightly it winds and packs around proteins inside the cell. These changes, often referred to as epigenetic modifications, make genes easier or more difficult for the cell's protein-making machinery to read.

Genetics by itself is infinitely more complex than we would think. Here is an interesting article by Dorothy Bishop on how misleading the idea of one-gene-one-trait is.

People's understanding of genetic effects is heavily influenced by the way genetics is taught in schools. Mendel and his wrinkly and smooth peas make a nice introduction to genetic transmission, but the downside is that we go away with the idea that genes have an all-or-nothing effect on a binary trait. Some characteristics are inherited this way (more or less), and they tend to be the ones that textbooks focus on: for example eye colour, colour-blindness, Huntington's disease. But most genetic effects are far more subtle and complex than this. Take height, for instance. Genes are important in determining how tall you are, but this is not down to one gene: instead, there is a host of genes, each of which nudges height up or down by a small amount.

Furthermore, genetic influences may interact in complicated ways. For instance, coat colour in mice is affected by combinations of genes, so that one cannot predict whether a mouse is black, white or agouti (mouse coloured!) just by knowing the status of one gene. The expression of a gene may also depend crucially on the environment; for instance, obesity relates both to calorie intake and genetic predisposition, but the effects are not just additive: some people can eat a great deal without gaining weight, whereas in others, body mass depends substantially on food intake. And a genetic predisposition to obesity can be counteracted by exercise.

Technology Advances, Costs Fall

Here is a bit from a post on the Progress Daily blog:

Eric Lander, calculates that the cost of DNA sequencing has fallen to a hundred-thousandth of what it was a decade ago. The genome sequenced by the International Human Genome Sequencing Consortium took 13 years and cost $3 billion. Now, using sequencers from Illumina, a human genome can be read in eight days at a cost of about $10,000. Pacific Biosciences has a technology that can read genomes from single DNA molecules, and thinks that in three years’ time this will be able to map a human genome in 15 minutes for less than $1,000.

The falling cost of computers created a huge new industry and affected all parts of society. The new genetics will do the same. How? I don't know. But I'm guessing one area will be energy. Most big oil companies are busy with research to produce fuel from algae, see here and here.

Nature vs. Nurture

Life is complex. But people tend to look for simply explanations. When it comes to the debate between genetics and environment, people tend to line up on one side or the other. But in fact, life is more muddled. Some genetics is straightforward: if you have the gene then you have to trait. But a lot of genetics is much more convoluted. If you have the gene, then if some environmental conditions occur, the trait will be expressed. In other words, you get nature only through nurture. It isn't an exclusive either/or. It is both.

Here's a bit from an article in New Scientist giving an excellent example:

Our tale begins two decades ago, when a group of Dutch women set out to find an explanation for the antisocial behaviour of the males in their family. As well as having learning difficulties, these men and boys were prone to outbursts of aggression and were racking up a list of serious offences, including arson, attempted rape and murder. Suspecting that the behaviour might be hereditary, the women approached geneticist Hans Brunner at the University Hospital in Nijmegen, the Netherlands. Eventually, in 1993, he tracked down the culprit: a defunct variant of a gene called monoamine oxidase A, or MAOA, located on the X chromosome.

Understandably, the announcement created a sensation. It was the first time a gene had been linked to human aggression - and MAOA seemed to be responsible for a history of violence stretching back five generations.

In the following years, evidence poured in to bolster the connection between MAOA and aggression. Then, in 2004, journalist Ann Gibbons sealed the link by giving MAOA the headline-friendly label "warrior gene". The moniker stuck, raising the profile of MAOA, and at the same time fuelling misconceptions about how our behaviour is affected by our genetic make-up.

...

Genes simply make proteins. So for behavioural geneticists the question is how, when and why they influence our behaviour. Clearly, this involves a complex tango between genes and environments. Working out the exact steps is devilishly difficult, and conveying the findings to those without a scientific background is just as problematic. The mis-selling of MAOA is a salutary lesson in what can go wrong.

...

The so-called "warrior gene" is actually just a molecular garbage collector. It encodes a protein that breaks down some of the brain's signalling molecules when they have outlived their usefulness - including serotonin, noradrenalin and dopamine. If it slacks on the job, the build-up of these neurotransmitters leads to abnormal moods and behaviour. The gene comes in several varieties, distinguished primarily by their levels of activity. Because it is found on the X chromosome, females may have two different forms, while males have just one. Brunner's aggressive Dutchmen had a rare and completely inactive variant. The so-called low-activity variant, or MAOA-L, has a slightly shorter than usual promoter - the region that controls the gene's activity - and so produces less protein. Another common variant, MAOA-H, is more active.

Like the defunct version of MAOA found in the Dutch family, MAOA-L, is associated with violence and aggression. Last year, Kevin Beaver from Florida State University, Tallahassee, found that boys who carry MAOA-L were more likely to join gangs, and those who did were four times more likely to use weapons in a fight (Comprehensive Psychiatry, vol 51, p 130). Headlines proclaimed that "gang culture may be due to warrior gene" and that "boys who carry the gene are likely to be dangerous, violent and carry weapons". But this kind of deterministic thinking is wrong-headed. MAOA-L is actually very common: a third of white people have this version and most of them have nothing to do with gangs.

...

The discovery that MAOA-L-related aggression appears mostly as a reaction to certain circumstances is perhaps not surprising, since this is how most aggression manifests itself. However, the clearest sign yet that the gene is no ruthless determinant of behaviour came in 2002 when Avshalom Caspi and Terrie Moffitt of Duke University in Durham, North Carolina, published their findings about a sample of 442 men from New Zealand who they had followed from birth. A third of these men carried the MAOA-L variant. Now, aged 26, this group was indeed more likely than the others to have developed antisocial disorders and violent behaviour - but only if they had been poorly treated or abused as children. Moffitt and Caspi concluded that the so-called "warrior gene" affects a child's sensitivity to stress and trauma at an early age. Childhood trauma "activates" bad behaviour, but in a caring environment its effect is quashed.

This complexity of indirect effect gets even more complex with epigenetics where an effect of an environmental condition on a gene can show up as a trait a generation or two later:

Marcus Pembrey and colleagues also observed in the Överkalix study that the paternal (but not maternal) grandsons of Swedish boys who were exposed during preadolescence to famine in the 19th century were less likely to die of cardiovascular disease; if food was plentiful then diabetes mortality in the grandchildren increased, suggesting that this was a transgenerational epigenetic inheritance. The opposite effect was observed for females -- the paternal (but not maternal) granddaughters of women who experienced famine while in the womb (and their eggs were being formed) lived shorter lives on average.

Go read the Wikipedia article for more details on epigenetics.

Pondering the Direction of Science

Freeman Dyson has a review of Richard Holmes' history of early science in Britain, The Age of Wonder. Here is a key bit where he speculates that an earlier age of amateurs might return during the first half of the 21st century:

The Age of Wonder, according to Holmes, ended with the first meeting of the British Association for the Advancement of Science (BAAS) in York in 1831. By that time the three giants, Joseph Banks, William Herschel, and Humphry Davy, had grown old and feeble and finally died. The three young leaders who took their places were the mathematician Charles Babbage, the astronomer John Herschel, and the physicist David Brewster. Babbage led the attack on the old regime in 1830 with a book, Reflections on the Decline of Science in England. He attacked the dignitaries of the Royal Society in London as a group of idle and incompetent snobs, out of touch with the modern world of science and industry. The professional scientists of France and Germany were leaving the English amateurs far behind. England needed a new organization of scientists, based in the growing industrial cities of the north rather than in London, run by active professionals rather than by gentleman amateurs. The BAAS was set up according to Babbage's specifications, with annual meetings held in various provincial cities but never in London. Membership grew rapidly. At the third meeting in Cambridge in 1833, the word "scientist" was used for the first time instead of "natural philosopher," to emphasize the break with the past. Victoria was not yet queen, but the Victorian Age had begun.

Holmes's history of the Age of Wonder raises an intriguing question about the present age. Is it possible that we are now entering a new Romantic Age, extending over the first half of the twenty-first century, with the technological billionaires of today playing roles similar to the enlightened aristocrats of the eighteenth century? It is too soon now to answer this question, but it is not too soon to begin examining the evidence. The evidence for a new Age of Wonder would be a shift backward in the culture of science, from organizations to individuals, from professionals to amateurs, from programs of research to works of art.

If the new Romantic Age is real, it will be centered on biology and computers, as the old one was centered on chemistry and poetry. Candidates for leadership of the modern Romantic Age are the biology wizards Kary Mullis, Dean Kamen, and Craig Venter, and the computer wizards Larry Page, Sergey Brin, and Charles Simonyi. Craig Venter is the entrepreneur who taught the world how to read genomes fast; Kary Mullis is the surfer who taught the world how to multiply genomes fast; Dean Kamen is the medical engineer who taught the world how to make artificial hands that really work.

Each achievement of our modern pioneers resonates with echoes from the past. Venter sailed around the world on his yacht collecting genomes of microbes from the ocean and sequencing them wholesale, like Banks who sailed around the world collecting plants. Mullis invented the polymerase chain reaction, which allows biologists to multiply a single molecule of DNA into a bucketful of identical molecules within a few hours, and after that spent most of his time surfing the beaches of California, like Davy who invented the miners' lamp and after that spent much of his time fly-fishing along the rivers of Scotland.

Dean Kamen builds linkages between living human brains and mechanical fingers and thumbs, like Victor Frankenstein, who sewed dead brains and hands together and brought them to life. Page and Brin built the giant Google search engine that reaches out to the furthest limits of human knowledge, like William Herschel, who built his giant forty-foot telescope to reach out to the limits of the universe. Simonyi was chief architect of software systems for Microsoft and later flew twice as a cosmonaut on the International Space Station, like the intrepid aeronauts Blanchard and Jeffries, who made the first aerial voyage from England to France by balloon in 1795.

There are obvious differences between the modern age and the Age of Wonder. Now we have a standing army of many thousands of professional scientists. Then we had only a handful. Now science has become an organized professional activity with big budgets and big payrolls. Then science was a mixture of private hobbies and public entertainments. In spite of the differences, there are many similarities. Holmes remarks that in 1812 "Portable Chemical Chests" began to go on sale in Piccadilly, priced between six and twenty guineas. These contained equipment and materials for serious amateur chemists.

Their existence proves that some of the fashionable ladies and gentlemen who swarmed to Davy's public lectures at the Royal Institution either did real chemical experiments in their homes or encouraged their children to do such experiments. Last year I received as a Christmas present a "Portable Genome Chest," a compact disc containing a substantial amount of information about my genome. My children and grandchildren, and our spouses, got their compact discs too. By comparing our genomes, we can measure quantitatively how much each grandchild inherited from each grandparent.

I love the popular writing of Freeman Dyson. He is a smart guy with wide interests. I find him fascinating. It helps that he connects with my favourite physicist: Richard Feynman. The two shared a car trip across the US shortly after WWII.

This article by Dyson is filled with interesting bits. Here's something about the human genome:

An important step toward an understanding of the genome is the recent work of David Haussler and his colleagues at the University of California at Santa Cruz, published in the online edition of Nature, August 16, 2006. Haussler is a professional computer expert who switched his interest to biology. He never dissected a cadaver of mouse or human. His experimental tool is an ordinary computer, which he and his students use to make precise comparisons of genomes of different species. They discovered a small patch of DNA in the genome of vertebrates that has been strictly conserved in the genomes of chickens, mice, rats, and chimpanzees, but strongly modified in humans. The patch is called HAR1, short for Human Accelerated Region 1. It evolved hardly at all in three hundred million years from the common ancestor of chickens and mice to the common ancestor of chimpanzees and humans, and then evolved rapidly in six million years from the common ancestor of chimpanzees and humans to modern humans.

During the last six million years, eighteen changes became fixed in this patch of the human germ line. Some major reorganization must have occurred in the developmental program that this patch helps to regulate. Another crucial fact is known about HAR1. It is active in the developing cortex of the embryo brain during the second trimester of the mother's pregnancy, the time when the detailed structure of the brain is organized. Haussman's team found another similar patch of DNA in the vertebrate genome which they call HAR2. It is active in the developing wrist of the human embryo hand. The brain and the hand are the two organs that most sharply differentiate humans from our vertebrate cousins.

The discovery of HAR1 and HAR2 is probably an event of seminal importance, comparable with the discovery of the nucleus of the atom by Ernest Rutherford in 1909 or the discovery of the double helix in the nucleus of the cell by Francis Crick and James Watson in 1953. It opens the door to a new science, the study of human nature at the molecular level. This new science will profoundly change the possible applications of biological knowledge for good or evil. It may give us the key to control the evolution of our own species.

Go read the article. It is fun and filled with facts that will dazzle you. And... he presents you with a wondrous vision of a better future. This is something that is sorely missing today: a story with a happy ending. It is only a conjecture, but it is profoundly satisfying to me. We need more hope. We need to look to the future.

To the Rescue! Another Doomsday Scenario

It seems there is no end to people willing to weave worries for us with stories of doom and gloom. Here's one from Carl Zimmer's blog The Loom:

...the evolutionary biologist Michael Lynch has published a provocative paper (to mark his inauguration into the National Academy of Sciences) in which he makes another kind of forecast. Our future evolution, he warns, is going to lead to a devastating decline in our health.

The idea is not new. Hermann Muller, who won the Nobel Prize for his work on mutations, first raised the specter of evolutionary decline in 1950. He pointed out that many mutations that arise in a population are harmful. They can cause various diseases, cutting lives short or making it harder for organisms to reproduce. Left to themselves, these mutations can drive down the reproductive rate of a population. But their harmful effects can be balanced by natural selection. If individuals with harmful mutations have fewer offspring than other individuals, the mutations become less common. Overall, the population can continue to reproduce at a healthy rate.

As Lynch points out, Muller’s argument depended on the actual rate of mutations and other vital statistics that no one in the 1950s could know with much precision. But in his new paper, Lynch surveys recent studies that make it possible to know the mutation rate quite well. Lynch concludes that every gamete (a sperm or egg) acquires the following:

–38 base-substitution mutations (a single “letter” of DNA changes to another one).

–3 small insertions or deletions of a stretch of DNA

–1 splicing mutation (which changes the combination of segments of a gene that cells use to build proteins)

–Plus some assorted other mutations (gene duplications, insertions of DNA copied by transposable elements, and so on).

All told, Lynch estimates a total of 50 to 100 mutations.

Compared to other species, Lynch points out, we mutate a lot. Any base in our DNA is twice as likely to mutate as a base in a fruit fly’s DNA, for example. Part of our special burden is our long life. As sperm divide rapidly during a man’s life, they pick up lots of new mutations. We are also left prone to cancer, as our skin, intestines, and other tissues continue to divide and sometimes pick up new mutations.

A lot of the new mutations in every new baby are harmless. But each baby may acquire a few harmful ones. These mutations rarely cause a swift death. Instead, in their totality, they slice off a tiny fraction of the total offspring an entire population can produce. Lynch estimates that mutations to protein-coding DNA cause the fitness of a population to decline by 1%. That’s assuming natural selection does not favor other mutations over these harmful ones.

Lynch acknowledges that natural selection is still in effect in humans, particularly in places where people never see doctors, let alone get clean drinking water. But as the world’s standard of living goes up, he argues, more and more people are being shielded from natural selection’s most intense effects–and harmful mutations are piling up.

In a matter of a few centuries, Lynch predicts, industrialized societies may experience a huge increase in harmful genes–”with significant incapacitation at the morphological, physiological, and neurobiological levels,” he writes.

Battling this decline won’t be easy, says Lynch. Rather than a few big mutations causing the trouble, the decline will be brought about by a vast number of mutations, each with a very small effect. The fantasies of selective breeding dreamed of by eugenicists aren’t just loathesome–they’re also useless. Instead, Lynch argues for something that would make the eugenicists crazy. “Ironically, the genetic future of mankind may reside predominantly in the gene pools of the least industrialized segments of society,” he writes.

Why am I not ready to go into a froth and bay at the moon with the other doomsters? Well... even if the above is correct it totally ignores clever human's ability to tinker with Nature and interrupt a "natural decline" in our viability from accumulating genetic decay. While many are probably ready to form loud protest groups and demand that we all lay in the streets and bay to the moon about our dismal decline, I just don't believe it. We won't go down without a fight. I really doubt that the wretched primitives in far corners of the globe are poised to take over as the elites of the developed world keel over and die a sudden death from being "overwhelmed" with genetic abnormalities. That is nutty. It won't happen. Medical intervention will come sooner rather than later.

Remember the horror story retailed about 20 years ago about the "imminent decline of the human species because the Y chromosome was losing genes and shrinking"? I haven't noticed males gathering in alleyways sobbing on each other's shoulders about this soon-to-be disaster scenario.

Nope... humans have an uncanny fascination with weaving stories of horror and decline and a future that menaces us. Nutty.

Lies, Damn Lies, and Statistics

Greg Mankiw, an economist at Harvard, is busy proving that people with high salaries and high test results are that way because they are just plain smart, i.e. high IQs. Not because wealth buys better education. Nope. He firmly believes that cream rises to the top, so good test results and big incomes just naturally come to those who are "smart".

In his blog, he presents this graph:


Then he makes the statement:

It would be interesting to see the above graph reproduced for adopted children only. I bet that the curve would be a lot flatter.

David Cesarini, an economics professor at MIT, provides him with the desired graph:


Which Mankiw takes as evidence of his claim.

But if Mankiw were truly honest with himself, he would expect the line for the adopted children to be absolutely flat, i.e. completely uncorrelated with income because adopting is about as close to a fair lottery as you can get.

Instead, where he sees a "lot flatter" curve, I see a curve that looks pretty highly correlated with wealth. Yeah, it is kind of flat for the middle 4 deciles, but the overall curve is very strongly correlated with the level of wealth and has the same shape as the ordinary children.

So where I see evidence that wealth buys you good test results, Mankiw sees confirmatory evidence that the smart are just naturally rich and get good test results. Funny.

They say "beauty is in the eye of the beholder" but I think this proves that economic "truths" are also in the eye of the beholder.

There is more info on at Wikipedia on nature versus nurture. And it gets more complicated because of epigenetics where experience changes gene expression. From my perspective, the best approach is probably "nature through nurture" as in...


In other words, the two factors are inextricably intertwined.

Update 2009sep02: In the comments you will find that I am caught out on too quickly reviewing the graphs and not getting the details straight. So look at the comments to see what went wrong.

The more important point is that the debate goes on. There is a very interesting blog by Alex Tabarrok on the Marginal Revolution site. It has this graph:


That appears to be the graph that Greg Mankiw should have presented because it has the "flat line" for adoptees.

Here's some of Alex's commentary:

The graph shows how parent income at the time of adoption relates to child income for the adopted and "biological" (non-adopted) children. The income of biological children increases strongly with parental income but the income of adoptive children is flat in parent income. What does this mean?

The graph does not say that adopted children necessarily have low income. On the contrary, some have high and some have low income and the same is true of biological children. What the graph says is that higher parental income predicts higher child income but only for biological children and not for adoptees.

Now what about education? Sacerdote looks at that as well. He doesn't have a child SAT-score, parent-income correlation but he does find:

Having a college educated mother increases an adoptee's probability of graduating from college by 7 percentage points, but raises a biological child's probability of graduating from college by 26 percentage points.

The effect for father's years of education is even larger; about a ten times larger effect on biological children than on adoptees. Similarly, parent income has a negligible effect, small and not statistically significant, on an adoptee completing college but an 8 times larger and statistically significant effect on a biological child completing college (Table 4, column 3).

So... is the debate over? No.

• Not if you look carefully at Tabarrok's comments. Note that he doesn't have the SAT or IQ scores that Mankiw really wants. But he does have data about scholastic achievement, and it isn't a flat line. In other words, wealth of the family translates into better academic success. That is not what Greg Mankiw wants the data to say.


• Not if you look at the comments to Alex's posting. A lot of people jump all over him with alternative interpretations of "the" data. That's what makes science so interesting. The facts don't "speak for themselves". You have to interpret them. And your theory is your filter through which you see the facts.

This debate of nature/nurture is very old. It won't go away quickly. But it is an interesting debate that merits time looking at it and understanding your own position/prejudice.

Update 2009sep21: There is a very interesting discussion of the shortcomings of Mankiw's interpretation of the data in a posting by Mike Konczal on his blog Rortybomb. Go read the posting!

Peering into the Future

I find it amusing to find people predicting the future. Most people simply do a linear extrapolation. More sophisticated people, like Ray Kurzweil (author of The Singularity is Near) argue that innovation is increasing at an exponential rate so any linear extrapolation falls far short of reality. (Funny thing, most ordinary predictions -- at least to my estimate -- don't fall short but over-estimate the future. Where they fall short is "seeing" the unexpected discoveries.)

Here is a posting on BoingBoing by Mark Frauenfelder that discusses a new wager by scientists predicting the future:

Professor Lewis Wolpert and Dr Rupert Sheldrake, have set up a wager on the predictive value of the genome.

The wager will be decided on May 1, 2029, and if the outcome is not obvious, the Royal Society, the world's most venerable scientific organization, will be asked to adjudicate. The winner will receive a case of fine port, Quinta do Vesuvio, 2005, which should have reached perfect maturity by 2029 and is being stored in the cellars of The Wine Society.

Prof Wolpert bets that the following will happen. Dr Sheldrake bets it will not: By May 1, 2029, given the genome of a fertilized egg of an animal or plant, we will be able to predict in at least one case all the details of the organism that develops from it, including any abnormalities.
Prof Wolpert and Dr Sheldrake agree that at present, given the genome of an egg, no one can predict the way an embryo will develop. The wager arose from a debate on the nature of life between Wolpert and Sheldrake at the 2009 Cambridge University Science Festival.

Prof Wolpert believes that all biological phenomena can in principle be explained in terms of DNA, proteins and other molecules, together with their interactions. He is convinced that it is only a matter of time before all the details of an organism can be predicted on the basis of the genome.

Dr Sheldrake believes that the predictive value of genes is grossly over-rated. Genes enable organisms make proteins, but they do not contain programs or blueprints. Instead, he thinks that the development of organisms depends on organizing fields called morphogenetic fields, which are not inherited through the genes.

I find several things that are odd about this "bet":

• Wolpert was born in 1929, to live to 2029 to "win" this bet he would have to be 100. The odds of that are very low (unless he is also "predicting" that lifespans will be dramatically increased in the future, but lifespans from 1800 to 2060 were dramatically increased by avoiding early deaths, not by extending the age of death).


• The nature/nurture debate was settled long ago as far as I can tell. Sure the genes are the blueprint, but just like you will get different results if you hand the blueprint to a skilled craftsman versus a raw apprentice versus a complete novice, genes under different environments will create different results. The raging new field of epigenetics shows how the central dogma of molecular biology (that DNA -> RNA -> protein) is not true, i.e. the environment can control into gene expression.

The post by Frauenfelder is interesting because he mentions a number of other famous scientific bets and their results:

• Richard Feynman's bet of$1000 that no-one could construct a motor no bigger than 1/64 of an inch on a side. He lost.


• Stephen Hawking bet fellow cosmologist Kip Thorne that Cygnus X-1 would turn out not to be a black hole (Hawking lost).


• In 1980 biologist Paul Erlich bet economist Julian Simon that the price of five mineral commodities would rise over the next ten years. In fact they fell.

So the track record of scientists in predicting the future is pretty dismal.

I would add that Ray Kurzweil is "betting" that he can live long enough that the science of life extension will advance fast enough to keep death in his future and he will in effect live forever. I believe he will lose this bet. But there are new scientific developments which may prove that my jaded outlook is wrong. Resveritrol seems very promising to provide significant life extension. Maybe for a middle aged guy like Kurzweil (now 61 years old) this will be just enough to allow him to hang in there until the next big advance in life extension will arrive to keep that appointment with the Grim Reaper indefinitely postponed.

And I need to add one other note: While I back Rupert Sheldrake in this "bet", I find him to be a fraud. Over twenty years ago I read his book The Presence of the Past about "morphic resonance" and found it to be pure quackery. At that time he presented himself as a bio-chemist studying plants. He has now gone over to the dark side as a researcher in "parasychology", pure nonsense.

The Real Garden of Eden?

The NY Times has an intersting article by Nicholas Wade that uses genetics and linguistics to locate the most likely point from which modern humans dispersed. Here's the initial bit:

Locations for the Garden of Eden have been offered many times before, but seldom in the somewhat inhospitable borderland where Angola and Namibia meet.

A new genetic survey of people in Africa, the largest of its kind, suggests, however, that the region in southwest Africa seems, on the present evidence, to be the origin of modern humans. The authors have also identified some 14 ancestral populations.

The new data goes far toward equalizing the genetic picture of the world, given that most genetic information has come from European and Asian populations. But because it comes from Africa, the continent on which the human lineage evolved, it also sheds light on the origins of human life.

click to enlarge

Nature/Nurture of What?

The Olivia Judson blog at the NY Times is a great source of interesting biological science. She's been having guest bloggers, this week Sandra Aamodt and Sam Wang take on genes and environment and the strange interactions between them in an article entitled "Mugged by Our Genes?". Read the whole thing, but for me the key bit was...

Major depression arises from a vicious cycle between genes and environment. Let’s start with genetics: a particular gene influences the sensitivity of individuals to bad experiences. One famous paper demonstrated a complex interaction between the serotonin transporter gene and negative events. (The gene encodes a protein that removes the neurotransmitter serotonin from the synapse after a neuron releases it. The action of this protein is inhibited by antidepressants like Prozac.) People with two copies of the high-risk variant of the gene are likely to develop depression in response to multiple stressful experiences like divorce or assault, but they are fine if their environment remains benign.

In contrast, people with two copies of the low-risk form of the gene are resilient against depression, even when they experience environmental stressors. People with one copy of each variant fall somewhere in between, as you might expect.

Genes that predispose people to depression, though, also influence their risk of experiencing negative environmental events. In one study, women whose identical twin suffered from depression were significantly more likely to have been assaulted, lost a job, divorced, or had a serious illness or major financial problems than people whose fraternal twin was depressed. (It’s not known which genes are responsible for this effect.) These bad events did not occur because the women were depressed, as the correlations persisted even when women who were currently depressed were excluded from the study. Thus, genes can act on the same disorder by making people more sensitive to stressful environmental events and by making these events more likely to occur.

The interaction between genetic tendencies and life experiences may explain another puzzling finding: the heritability of many psychological traits — from intelligence to anxiety — increases as people mature. This result seems odd at first glance, since genes are most important in brain development in babies and children. But children also have less control over their environment than adults. As people get older, they become more able to determine their own circumstances, and they may be able to choose environments that reinforce their natural personality tendencies. Apparently those of us who suspect we are turning into our parents as we get older may have a valid point.

After all this, you may wonder if your genes are ultimately to blame for your fortunes, good or ill. That’s hardly the case: only one-fourth of the variation in life events is heritable, which means that three-fourths is not. So you have plenty of opportunity to influence your circumstances. Whether that’s better than turning into your parents, we’ll leave to your judgment.

I remember as a kid the excitement of the early decoding of DNA. The central dogma was that one gene codes for one protein and all information flowed one way. Now there is epigenetics which puts this on its head and creates a much more complex palette for development.

Nifty Tool to look at Human Y Genome

Wikipedia is set up with a page that lets you see the evolution of the Y chromosome and "point & click" to get information about specific variants of Y. What a great tool for "navigating" through human history.

I was annoyed by the The Genographic Project (funded by National Geographic) is a bit heavy handed with graphics & gadgets and forces you to traverse their (admittedly gorgeously illustrated) data in a structured manner. I prefer the anarchistic possibilities of the Wikipedia approach.

Here's the Wikipedia view of the Y chromosome distribution as of 1500 AD:

Nicholas Wade's "Before the Dawn"

Before the Dawn by Nicholas Wade is a delightful romp through the application of current research in genetics to the last 50,000 years of human evolution.


Some of the delightful insights of the book:

• The genetics of body lice help to date the first human clothing to 72,000 years ago.
• Human body hair as decoration dates back 200,000 years ago with inactivation of genes that control the growth & quiescence cycle of normal fur.
• Truly modern human behaviour (culture) dates back only 50,000 years ago and is coincident with the achievement of fully modern speech.
• The discovery of that a defective FOXP2 gene inhibits normal speech and that this gene is highly conserved over 70 million years, but over the last 5 million years as the human line diverged from the ape line it has undergone two changes indicating that it is under strong evolutionary pressure.
• The roots of modern humans are in the sub-Saharan as small tribes of hunter gatherers who probably spoke a click language related to Khoisan.
• The earliest exodus of modern humans was via the sea's edge and followed the cost of south Asia all the way to Australia (the continent of Sahul). It requires rafting/boating to pass from the horn of Africa via the 12 mile sea at the Gates of Grief to southern Yemen and it required more substantial boats to cover the 60 miles of open water between the lost continents of Sunda and Sahul.
• The relict Homo Erectus hindered penetration of east Asia and the relict Neanderthal hindered penetration of western Asia/Europe.
• The Upper Paleolithic saw a number of modern human cultures flourish as climate change brought bouts of Ice Age extension that pushed survivors into southern redoubts: Aurignacian, Gravettian, Solutrean, and Magdalenian. Each cycle of isolation and then expansion allowed population bottlenecks to drive genetic differentiation.
• The dog was domesticated 15,000 years ago.
• Humans drove the Neanderthals to extinction around 30,000 years ago, entered the Americas 14,000 years ago and the last expansion in the Pacific was to New Zealand in 1200 AD.
• It was evolution of our mitochondrial DNA that fitted us to penetrate the cold Eurasian landmass.
• Settlement preceded agriculture in the earliest switch from hunter gatherer to agricultural lifestyle. There was a genetic accomodation required to reduce the level of hostility to allow larger groups to live a settled life.
• Cattle herding dates back to 6,000 years ago with the Funnel Beak culture and required a genetic accommodation via lactose tolerance to take advantage of the new food source. Genetics puts the centre of cattle domestication in north-central Europe. The highest lactose tolerance is among human populations centred in north-central Europe reaching 100%.
• The Romantic picture of peaceful, in-tune-with-nature primitives is a myth. Primitive humans suffered higher violent deaths than civilized people despite the carnage of modern wars. Primitive battles typically resulted in 30% casualties, more than what were experienced at Gettysberg. Typically 65% of all primitive societies are at war at any given time and primitives suffer an annual 0.5% death rate from violence.
  
• Kinship ties spell life over death. In the Mayflower 51% of the colonists died in the first year. Those who had no kin were more likely to die than those who had kin. In the Donner party stranded in the Sierra Nevada, only 3 of 15 single men survived while the typical survivor had 8.4 family members with him.
• Human evolved the levels of oxytocin and vasopressin to allow living in larger units. Our behaviour evolution included the development of a trust to act as social glue. In order to minimize "freeloaders" we developed religion as a belief system requiring commitment and those who broke the trust were shunned or exiled.
• Humans are "domesticated". Our skeletons are gracilized as we have lowered the level of violence and come to live in larger societies.
• Settled societies depend on the strengthening of two traits in hunter gatherer societies: reciprocity and leadership.
• Race is a natural result of differentiation based on genetic isolation. It has a genetic basis. There is a clustering of human DNA into 5 groups: Africans, Caucasians, Asians, Pacific Islanders, and Native Americans. (Modern medicine is starting to take note of racial differences because drug responses can vary by racial group.)
  
• Language correlates with modern human dispersion patterns. The linguist Joseph Greenberg has developed a universal classification of linguistic evolution. Using statistical techniques similar to genetic studies, historical dating of the evolution of languages is becoming possible. Indo-European languages date back to 8,700 years ago and correlate with the spread of agriculture out of the Middle East. (The alternative hypothesis was that Indo-European dates from the Kurgan warrior expansion of 6,000 years ago from the steppe area north of the Black Sea.)
• Men seek power to get reproductive access, and it works: (a) 8% of all Asian men in the lands rules by the Mongols carry Genghis Khan's Y chromosome that dates back to 1200. (b) 1.6 million Asian have the Y chromosome of Giocangga, the patriarch of the Manchu dynasty, dating back to 1644.
• Genetics can solve some mysteries. Thomas Jefferson sired a family with the slave mistress Sally Hemmings. His affair started when he brought the 13 year old Sally to France while he was posted as American ambassador there. She was free in France, but he persuaded her to return as his slave by promising to free his children by her, and he did. But he never spent any time with his black offspring (i.e. showed no "fatherly affection"). They would not have learned to read except some of the white children in the Jefferson household taught them. The reason why Jefferson took Sally Hemmings as his mistress was that she was his wife Martha's half sister since she was the offspring of the slaveholder John Wayles. Apparantly Sally Hemmings had a strong resemblance to her half-sister Martha Wayles who became Jefferson's wife. It is odd that the author of the Declaration of Independence who wrote the ringing words "we hold these truths to be self-evident that all men are created equal" would be a slaveholder who used his position to have sex with his slaves.
• There is strong evidence of on-going human genetic evolution, especially in our response to deadly diseases: malaria, black plague, small pox, etc. Apparantly the Caucassian response on the CCR5 receptor, in response to small pox, has made this population resistent to AIDS.
• Wade speculates that the European environment put selective pressure on the European population to accommodate ideas of individualism, freedom, consensual government, and an open economy. He sees the Chinese civilization with its organization favoured conformism. (These are speculations for which he offers no real scientific evidence, but are meant to encourage thinking about how evolution is on-going and how our environment is shaping human populations.)