The looming crisis in human genetics

[orcenio]

@athelas

To those, like orcenio, who post glib content-free assurances that absence of proof is proof of absence, remember that the same logic applies to heritable traits like baldness or developing Alzheimers. The heritability of psychometric traits is not up for debate; it’s only a matter of finding the genetic markers.

Glib my arse, I think I accurately painted that crap article right from the start; I definitely put more thought into my summation then it ever deserved.

For you, I’ll give you this:

1. Absence of proof is not proof of absence, but it is absence of proof
2. Read up on the differences between “heritability” and “genetic.” For instance even accents are heritable, but they are not genetic.

[orcenio]

@Belowjob2.0

Yeah, pretty much.

Claims that genetics will one day prove the inferiority of certain ethnic groups have been made for decades. The hard evidence never actually arrives, and geneticists themselves tend to avoid the debates because the noise dwarfs the signal by orders of magnitude. The proof, the racialists say, is just around the corner. We’ll get there, just have faith.

Geneticists (like Anthropologists [1, 2, 3, 4] and Psychologists) have repeatedly stepped into this debate, all against the “race realists;” who in turn fall back to claims of a gigantic conspiracy, careful misrepresentations of mainstream scientific consensus, or simple assertions and brute willpower.

[orcenio]

@xtisme

At any rate, I’m going to start digging my bomb shelter, since I want to protect myself from the looming genetics crisis…

-XT

You win this thread.

[mswas]

Orcenio Well I am not going to argue with you, as I am not even in your league. My comments were just top of my head lay examples. In otherwords the point I was making is that intelligence is a combination of multiple benefits.

When I referred to conduction velocity, what I meant was say if someone just grew good neurons that increased their speed by .05%, that would translate into a quicker thought-action response time, which wouldn’t seem very significant on its face but when taken over time and when coupled with other aspects, it leads to a greater level of intelligence overall.

I am not sure I can buy being so quick to dismiss the article in the OP, because I do think that genetics will ask us to question a whole lot of our assumptions. It’s going to be as controversial for the racists who want to find simplistic confirmations of their biases, but it will also be controversial for multiculturalists who will have trouble accepting that cohorts have common genetic potentials that are measurable. Sure, race is one of the least granular categories of human cohorts, and as such very little can be accurately stated about race overall, but within that, certain tribes and clans will have different aptitudes. That won’t sit well with those people who think that egalitarianism is the highest of all ideals.

As I see it, saying that a greater understanding of genetics will lead to controversy should be an uncontroversial statement to make. He’s very much discussing it directly as it relates to his field, which is a prediction of how it will impact political behavior.

I hope this point doesn’t get lost in my ham-fisted attempts to make a point about neurological feature-sets. I’m trying to learn neurology, but I’m a noob.

[Belowjob2.0]

@orcenio

Geneticists (like Anthropologists [1, 2, 3, 4] and Psychologists) have repeatedly stepped into this debate, all against the “race realists;” who in turn fall back to claims of a gigantic conspiracy, careful misrepresentations of mainstream scientific consensus, or simple assertions and brute willpower.

I stand corrected. I’m familiar with geneticists who want nothing to do with the whole “race and intelligence” debate because they say it has nothing to do with their research.

[Chen019]

through the axonal wall by increasing the insulation of the axon by the myelin sheath. Both of these factors don’t different from person to person (unless it’s due to a neuropathological disease like Multiple sclerosis) but from neuron type to neuron type.

orcenio,

But myelination integrity apparently does vary from person to person?

http://www.technologyreview.com/biomedicine/22333/

Geneticists (like Anthropologists [1, 2, 3, 4] and Psychologists) have repeatedly stepped into this debate

Some of those statements by the Anthropologists appear heavily political. If you read a book like Steven Pinker’s ‘The Blank Slate’ this political slant will not surprise you. I’d recommend it.

For another great example of a political statement by scientists see:

Seville Statement on Violence

In fact University of Chicago geneticist Bruce Lahn wrote an article for Nature a few months ago, suggesting people need to ‘celebrate human genetic diversity’.

Given these geographically differentiated polymorphisms, it is possible to group humans on the basis of their genetic make-up. Such grouping largely confirms historical separation of global populations by geography5. Indeed, a person’s major geographic group identity can be assigned with near certaintly on the basis of his or her DNA alone (now an accepted practice in forensics). There is growing evidence that some of the geographically differentiated polymorphisms are functional, meaning that they can lead to different biological outcomes (just how many is the subject of ongoing research). These polymorphisms can affect traits such as pigmentation, dietary adaptation and pathogen resistance (where evidence is rather convincing)10, 11, 12, and metabolism, physical development and brain biology (where evidence is more preliminary)6, 8, 13, 14.

For most biological traits, genetically based differentiation among groups is probably negligible compared with the variation within the group. For other traits, such as pigmentation and lactose intolerance, differences among groups are so substantial that the trait displays an inter-group difference that is non-trivial compared with the variance within groups, and the extreme end of a trait may be significantly over-represented in a group.

http://www.nature.com/nature/journal/v461/n7265/box/461726a_BX1.html

[Belowjob2.0]

http://foreigndispatches.typepad.com/dispatches/2005/09/brain_evolution.html

The truth about the way genes work is that other than in the case of simple mendelian traits of the kind which geneticists have had most success studying during the last century, it is almost unheard of in genetics research to discover single genes which are able to account for more than a minute fraction of variation in any given trait; furthermore, the very reason why so many traits in any given population happen to abide by a normal distribution is because to the extent said traits aren’t determined by environmental differences, they must be under the influence of very many genes, and the smoother the curve, the greater the number of underlying genes must be - this is nothing more than a generalization of the binomial theorem with which we are all familiar. In the case of the human brain, we know that about half of all genes - or some 15,000 of the total - are expressed in the brain during the course of development, and there is no a priori reason to believe that variations in any of them, or even in whatever regulatory regions might govern their behavior, will have no impact on how said organ functions. In light of all the foregoing, anybody who thinks we will find 20 or even 50 genes which rigorously account for, say, 90% of all “genetic” variation in “IQ” or whatever nebulous measure of intellect we decide upon is a fool at best.

Having discussed the “one trait -> one or a few genes” fallacy, let me turn now to its counterpart, namely the belief that a gene’s only or main function must be to determine any single particular trait (hence all the idiotic talk of genes “for” IQ, homosexuality, jazz improvisation, etc.). Genes code for proteins, not explicit traits, and it is part of the blind genius of evolution that individual proteins are co-opted to serve multiple roles all the time, so much so that there is even a technical name for the phenomenon, to whit, pleiotropy.

http://foreigndispatches.typepad.com/dispatches/2006/12/the_iq_genes_th.html

Time has a funny way of working, and as the months have gone by, my words of caution have subsequently been completely borne out by the research, which has thus far failed to uncover any association whatsoever between variation in the ASPM and MCPH1 genes and standardized measures of intelligence.

http://foreigndispatches.typepad.com/dispatches/2006/02/mapping_quantit.html

Anyone who expects things to be easier with humans than they are with short-lived organisms for which no restrictions on experimentation exist is living in a dream world. It will likely take several decades to unravel the genetic basis for variation in such amorphous traits as “IQ” or personality, assuming it ever becomes possible at all, and anyone who claims otherwise is a charlatan selling snake oil.

http://foreigndispatches.typepad.com/dispatches/2005/12/genes_iq_and_ma.html

Jirtle predicts that about 25 percent of Caucasians carry the variant gene. An international database that catalogs genetic variation states that the variant gene was found in 28 percent of Japanese living in Tokyo and 24 percent of Han Chinese living in Beijing. The variant gene was not found in a population of Yoruba people living in Ibadan, Nigeria.

At this point the “race realists” leap up into the air shouting “YES!!! OMGWTFBBQ!!!”; the thing is, though, that the absent variant in the Yoruba is the one that supposedly lowers IQ in Caucasians … Bow down before the brilliant Yoruba, ye mighty, and despair!

[Chief_Pedant]

The battle line between those who advocate nature over nurture will not be won by identifying every gene set and proving its exact consequent phenotypic expression. As you with the face pointed out earlier, a given trait might be gene A in this population and gene B in that population, and how does one determine which gene is better?

Instead, two things will occur.

The first nurture shibboleth to fall will be that we are all sort of the same, roughly homogeneous mix. Currently the protestations focus on “race” as being a poor identifier. And it is definitely a crude one; it would have fallen out of favor long ago were it not for the social ramifications, propelled in great measure currently by those for whom it is a social benefit under current law (race-based admission and job-diversity efforts, for instance). As we more accurately and more cheaply identify the genome, we’ll find more accurate ways to identify population heritages–in effect, we’ll better-define the branches of the family of man.

The second shibboleth to fall will be the notion that nurture cannot be perfectly accounted for and that therefore nature versus nurture is permanently undefinable. Elucidating the genome will provide more and more examples of ordinary non-controversial population-level differences in gene distribution (the gene set coding for cystic fibrosis, for example); next will be marginally more socially-controversial gene sets associated with physical abilities; and finally gene sets associated with personalities or intellect. It won’t be argued that a given gene set coding for something good is the only possible gene set coding for that, or that the population which has it more frequently must be superior to a different population in which it appears less frequently–such an approach is a non-starter. It will simply be demonstrated that for that particular gene set, there is a fundamental difference in outcome between those who have Gene A and those who have Gene B, even within what would otherwise be considered the same population (all females, say).

And when that happens–when we identify the variant gene distributions themselves–a single population can be studied for outcomes without layering on any sensitive issues around “superior” populations–it will be the same population/ethnic group/race…whatever. With the racist/nazi hot-buttons disabled by studying the same population, we’ll see studies which clarify the effect nature v. nurture on everyday abilities, not just disease states.

[Blake]

As with every post Chief Pedant has made in this thread, that last one contains a lot of assertions and absolutely no facts or evidence to back up any of them.

Absolute ignorant nonsense from start to finish.

[Chen019]

Blake,

Which of the following do you disagree with.

As we more accurately and more cheaply identify the genome, we’ll find more accurate ways to identify population heritages–in effect, we’ll better-define the branches of the family of man.

This doesn’t seem that controversial? For instance, in this recent paper the resolution of the study is sufficiently high that Swedes and Norwegians can be distinguished with 90 percent accuracy.

http://www.nature.com/ejhg/journal/v16/n12/fig_tab/ejhg2008210t4.html#figure-title

It will simply be demonstrated that for that particular gene set, there is a fundamental difference in outcome between those who have Gene A and those who have Gene B, even within what would otherwise be considered the same population (all females, say).

In terms of increased risk of crime from early maltreatment, this is the case with some MAO-A variants.

'Warrior Gene' Linked To Gang Membership, Weapon Use

[Chief_Pedant]

@Blake

As with every post Chief Pedant has made in this thread, that last one contains a lot of assertions and absolutely no facts or evidence to back up any of them.

Absolute ignorant nonsense from start to finish.

I have left you, in an earlier post, with a specific example of genes triumphing over nurturing (underperformance of whites in the NBA) , and a number of specific examples of nurturing failing to overcome genes (underperformance of blacks with similar educational exposure on MCAT and post-Medical School exams).

Your entire response was, “Dude, none of those cites supports what you claimed. Care to try again?”

I submit that “Absolute ignorant nonsense from start to finish” as a response to my comments is as unlikely to be found to be persuasive as is the complaint of racism from others.

When I have a reasoned argument from you why the under-representation of US whites in the NBA is not an example of nurture being beaten by nature, I may consider responding. In the meantime please do me a favor and stop threadshitting. Surely we can keep some debates above the level of name-calling and idle, vapid editorializing.

[Honesty]

@orcenio

Learning and memory are theoretical concepts (but much more useful then “quick thinking”) used to explain that experience influences behaviour; they are not directly observable entities. Most Neuroscientists (including me) believe that there is a physical basis in the brain for the function of these concepts. Which leads to studies of synaptic plasticity (Long-term Potentiation/Depresstion) of things like the gill withdrawal reflex of Aplysia (a sea slug with a simple nervous system). However, this all has nothing to do with the “ability to grow neural maps” nor do Neuroscientists have any strong idea to how Learning/memory work in animal/humans other then “it has something to do with the Hippocampus.”

Good post. From what I’ve learned and gathered, the mechanistic differences between the storage of short and long-term memories in the hippocampus have been established. My professor seemed to espouse the view that there were associative maps where new memories and experiences are “attached” to existing memories rather than remade. He explained it more clearly than that though.

• Honesty

[Belowjob2.0]

Your NBA example doesn’t work, because it fails entirely to explain why there are a number of standout white players in the NBA, but almost none of them are Americans. Is there something unique to white Americans’ DNA which makes them unable to compete at the level of Canadians like Steve Nash, and Spaniards like Pau Gasol? If not, then we have to acknowledge that non genetic factors play an enormous role in plays in the NBA.

a number of specific examples of nurturing failing to overcome genes (underperformance of blacks with similar educational exposure on MCAT and post-Medical School exams).

Again, no. Similar educational exposure does not equal nurture. The effects of nurture on brain development are most profound in utero, infancy and early childhood.

We’ve already had testimony from people who work in the field of neuroscience, pointing out that your arguments are weak, your claims unfounded.

[Belowjob2.0]

@Honesty

Good post. From what I’ve learned and gathered, the mechanistic differences between the storage of short and long-term memories in the hippocampus have been established. My professor seemed to espouse the view that there were associative maps where new memories and experiences are “attached” to existing memories rather than remade. He explained it more clearly than that though.

• Honesty

My layman’s understanding is that the hippocampus can be strongly affected by environmental stress, and this plays a big role in learning and memory.

http://www.fi.edu/learn/brain/stress.html

Stress and Memory

Chronic over-secretion of stress hormones adversely affects brain function, especially memory. Too much cortisol can prevent the brain from laying down a new memory, or from accessing already existing memories.

The renowned brain researcher, Robert M. Sapolsky, has shown that sustained stress can damage the hippocampus , the part of the limbic brain which is central to learning and memory. The culprits are “glucocorticoids,” a class of steroid hormones secreted from the adrenal glands during stress. They are more commonly know as corticosteroids or cortisol .

During a perceived threat, the adrenal glands immediately release adrenalin. If the threat is severe or still persists after a couple of minutes, the adrenals then release cortisol. Once in the brain cortisol remains much longer than adrenalin, where it continues to affect brain cells.

topics
Cortisol Affects Memory Formation and Retrieval

Have you ever forgotten something during a stressful situation that you should have remembered? Cortisol also interferes with the function of neurotransmitters, the chemicals that brain cells use to communicate with each other.

Excessive cortisol can make it difficult to think or retrieve long-term memories. That’s why people get befuddled and confused in a severe crisis. Their mind goes blank because “the lines are down.” They can’t remember where the fire exit is, for example.

topics
Why We Lose Our Memory

Stress hormones divert blood glucose to exercising muscles, therefore the amount of glucose – hence energy – that reaches the brain’s hippocampus is diminished. This creates an energy crisis in the hippocampus which compromises its ability to create new memories.

That may be why some people can’t remember a very traumatic event, and why short-term memory is usually the first casualty of age-related memory loss resulting from a lifetime of stress.

topics
Cortisol and Temporary Memory Loss-Study

In an animal study, rats were stressed by an electrical shock, and then made to go through a maze that they were already familiar with. When the shock was given either four hours before or two minutes before navigating the maze, the rats had no problem. But, when they were stressed by a shock 30 minutes before, the rats were unable to remember their way through the maze.

This time-dependent effect on memory performance correlates with the levels of circulating cortisol, which are highest at 30 minutes. The same thing happened when non-stressed rats were injected with cortisol. In contrast, when cortisol production was chemically suppressed, then there were no stress-induced effects on memory retrieval.

According to James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine, "This effect only lasts for a couple of hours, so that the impairing effect in this case is a temporary impairment of retrieval. The memory is not lost. It is just inaccessible or less accessible for a period of time."12

topics

Cortisol and the Degenerative Cascade

Normally, in response to stress, the brain’s hypothalamus secretes a hormone that causes the pituitary gland to secrete another hormone that causes the adrenals to secrete cortisol. When levels of cortisol rise to a certain level, several areas of the brain – especially the hippocampus – tell the hypothalamus to turn off the cortisol-producing mechanism. This is the proper feedback response.

The hippocampus, however, is the area most damaged by cortisol. In his book Brain Longevity, Dharma Singh Khalsa, M.D., describes how older people often have lost 20-25% of the cells in their hippocampus, so it cannot provide proper feedback to the hypothalamus, so cortisol continues to be secreted. This, in turn, causes more damage to the hippocampus, and even more cortisol production. Thus, a Catch-22 “degenerative cascade” begins, which can be very difficult to stop.

topics
Cortisol and Brain Degeneration-Study

Studies done by Dr. Robert M. Sapolsky, Professor of Neurology and Neurological Sciences at Stanford University, showed that lots of stress or exposure to cortisol accelerates the degeneration of the aging hippocampus.

And, because the hippocampus is part of the feedback mechanism that signals when to stop cortisol production, a damaged hippocampus causes cortisol levels to get out of control – further compromising memory and cognitive function. The cycle of degeneration then continues. (Perhaps similar to the deterioration of the pancreas-insulin feedback system.)

topics

Cortisol Levels During Human Aging-Study

The study was titled “Cortisol levels during human aging predict hippocampal atrophy and memory deficits”. A third of the 60 volunteers, who were between ages 60 and 85, had chronically high cortisol levels, a problem that seems to be fairly common in older people.13

The size of the hippocampus averaged 14% smaller in one group and showed high and rising cortisol levels, compared to a group with moderate and decreasing levels. The small hippocampus group also did worse at remembering a path through a human maze and pictures they’d seen 24 hours earlier and – two tasks that use the hippocampus.

topics

Shrinking Hippocampus, Memory Loss, and Alzheimer’s-Study

Using magnetic resonance imaging, Mayo Clinic researchers found that specific changes in the hippocampus were linked to changes in behavior associated with aging and Alzheimer’s disease. “When certain parts of the hippocampus shrink or deteriorate, specific, related memory abilities are affected,” says neurologist Ronald C. Petersen, the principal author of the study.

Furthermore, individuals with a shrunken hippocampus tend to progress more rapidly towards Alzheimer’s.

“In earlier studies we were able to show that the volume of the hippocampus could help diagnose early Alzheimer’s disease or help predict which patients may develop Alzheimer’s disease in the future. Now we can look specifically at which part or parts of the hippocampus are affected and match that with particular memory functions which are impaired in that particular patient,” says Dr. Petersen.14

[heatmiserfl]

@Chief_Pedant

We are, primarily, our genes.

Chief Pedant, you may find this NOVA episode on Epigenetics informative. It focuses mostly on DNA methylation but there are many, many epigenetic mechanism at play in our cells.

Epigenetics

Google epigenetics and you’ll get a nice surprise. Pay special attention to things like DNA methylation, non-coding RNAs and histone modifications. Even more amazing is that these epigenetic marks, once acquired from environmental stimuli, may be passed on to progeny if the marks or small RNAs are present in sperm. Sort of Lamarckian, eh?

But really, we are products of our environment as much as we are products of our DNA sequence. That includes intelligence (whatever that is).

Epigenetics: 100 Reasons To Change The Way We Think About Genetics

Oh, forgot to say thanks to orcenio for the informative post.

[Belowjob2.0]

@heatmiserfl

Chief Pedant, you may find this NOVA episode on Epigenetics informative. It focuses mostly on DNA methylation but there are many, many epigenetic mechanism at play in our cells.

Epigenetics | NOVA | PBS

Google epigenetics and you’ll get a nice surprise. Pay special attention to things like DNA methylation, non-coding RNAs and histone modifications. Even more amazing is that these epigenetic marks, once acquired from environmental stimuli, may be passed on to progeny if the marks or small RNAs are present in sperm. Sort of Lamarckian, eh?

But really, we are products of our environment as much as we are products of our DNA sequence. That includes intelligence (whatever that is).

Epigenetics: 100 Reasons To Change The Way We Think About Genetics | ScienceDaily

Oh, forgot to say thanks to orcenio for the informative post.

Ignorance fought on this end.

It’s even more complicated than I’d imagined. I don’t see the likelihood of it getting simpler, either. The kind of certainty Cheif Pedant hopes for is probably now as far out of reach as the nearest stars.

[mswas]

Hmm, I hope I don’t forget to watch heatmiserfl’s video later when I have the opportunity.

[Chen019]

Your NBA example doesn’t work, because it fails entirely to explain why there are a number of standout white players in the NBA, but almost none of them are Americans. Is there something unique to white Americans’ DNA which makes them unable to compete at the level of Canadians like Steve Nash, and Spaniards like Pau Gasol? If not, then we have to acknowledge that non genetic factors play an enormous role in plays in the NBA.

The existence of non-genetic factors does not mean that genetic factors aren’t a necessary condition for success in this competition. Or that there are not different distributions of abilities across populations.

If you are going to use sporting examples, the most obvious is the 100 metre sprint. Only those of west african ancestry have managed to go under 10 seconds in this event.

http://www.jonentine.com/reviews/straw_man_of_race.htm

[Chief_Pedant]

@Belowjob2.0

Ignorance fought on this end.

It’s even more complicated than I’d imagined. I don’t see the likelihood of it getting simpler, either. The kind of certainty Cheif Pedant hopes for is probably now as far out of reach as the nearest stars.

The problem of sorting out nature versus nurture is actually much more simple than identifying putative genesets and proving they are responsible. One simply need take two cohorts, expose them to similar nurturing and observe whether there is a difference.

We don’t need to identify the gene set that distinguishes male from female to prove within a reasonable certainty that males are superior to females at basketball (as a cohort average), for example.

But there is another bridge that will be crossed first, laying the groundwork for acceptance that our genes do separate us: identifying the marked variability among populations, and the lineages of those populations, and the fact that there are reasonably-definable branches in the family of man, sortable by genetic lineage and within those lineages, disproportionate representations of all sorts of genes.

No sociobiologist would get by in today’s academia arguing for relative superiority of any human group–genetically or phenotypically–in any area. It’s entirely against current dogma for the family of man (though not for animals, of course, where there is no sensitivity around the topic). So the first step is simply to find out whether or not there are populations and whether or not gene set (mal-)distribution exists, or not (with the exception of diseases, which is already accepted).

I have made my personal opinion clear, for the reasons elucidated above, and it’s my observation that there is so much tenderness around the topic that no debate is likely to resolve the issue. In particular, the demand for perfect amelioration of nurturing differences and perfect elaboration of specific genesets down to the level of “What SNP are you proposing that you can show definitively makes a difference?” will carry the doubters for some time.

Unfortunately, practical efforts to eliminate nurturing differences have not (and will not, in my personal opinion) overcome our genetically pre-determined maximum potentials, and so differences among us even at a group cohort level will persist.

It’s a bit tedious to make the same points over and over, but the author of a book I recommended earlier (Taboo, by Jon Entine) has written a summary article that interested readers can find here: The official site of the NBA for the latest NBA Scores, Stats & News. | NBA.com

[Chief_Pedant]

@heatmiserfl

But really, we are products of our environment as much as we are products of our DNA sequence. That includes intelligence (whatever that is).

In my opinion, while genetic egalitarians are busy hoping this is true, whole commercial enterprises will be built upon the opposite premise: that our maximum potential is determined by our genes. Of course environment is layered upon our genes. But if it were an equal proposition we would not see the practical disparity that we see today among a broad range of people exposed to approximately similar circumstances, and a child with Down’s would have little more intellectual disadvantage than any other child–we’d simply overcome his genetic disadvantage with some solid nurturing.