Dr. Catherine Shanahan On Dietary Epigenetics and Mutations

Dr. Catherine Shanahan is a board-certified family physician with an undergraduate degree in biology, along with training in biochemistry and genetics. She has also studied ethno-botany, culinary traditions, and ancestral health. Besides regularly appearing in and writing for national media, she has worked as director and nutrition consultant for the Los Angeles Lakers. On High Intensity Health, she was interviewed by nutritionist Mike Mutzel (Fat Adapted Athletes Perform Better). At the 31:55 mark in that video, she discussed diet (in particular, industrial vegetable oils or simply seed oils), epigenetic inheritance, de novo genetic mutations, and autism. This can be found in the show notes (#172) where it is stated that,

“In 1909 we consumed 1/3 of an ounce of soy oil per year. Now we consume about 22 pounds per year. In the amounts that we consume seed oils, it breaks down into some of the worst toxins ever discovered. They are also capable of damaging our DNA. Many diseases are due to mutations that children have that their parents did not have. This means that mothers and fathers with poor diets have eggs/sperm that have mutated DNA. Children with autism have 10 times the number of usual mutations in their genes. Getting off of seed oils is one of the most impactful things prospective parents can do. The sperm has more mutations than the egg.”

These seed oils didn’t exist in the human diet until the industrial era. Our bodies are designed to use and incorporate the PUFAs from natural sources, but the processing into oils through high pressure and chemicals denatures the structure of the oil and destroys the antioxidants. The oxidative stress that follows from adding them to the diet is precisely because these altered oils act as trojan horses in being treated by the body like natural fats. This is magnified by a general increase of PUFAs, specifically omega-6 fatty acids, with a simultaneous decrease of omega-3 fatty acids and saturated fats. It isn’t any difference in overall fat intake, as the 40% we get in the diet now is about the same as seen in the diet at the beginning of last century. What is different is these oxidized PUFAs combined with massive loads of sugar and starches like never seen before.

Dr. Shanahan sees these industrial plant oils as the single greatest harm, such that she doesn’t consider them to be a food but a toxin, originally discovered as an industrial byproduct. She is less worried about any given category of food or macronutrient, as long as you first and foremost remove this specific source of toxins.** She goes into greater detail in a talk from Ancestry Foundation (AHS16 – Cate Shanahan – Bad Diet, Bad DNA?). And her book, Deep Nutrition, is a great resource on this topic. I’ll leave that for you to further explore, if you so desire. Let me quickly and simply note an implication of this.

Genetic mutations demonstrates how serious of a situation this is. The harm we are causing ourselves might go beyond merely punishment for our personal sins but the sins of the father and mother genetically passing onto their children, grandchildren, and further on (one generation of starvation or smoking among grandparents leads to generations of smaller birth weight and underdevelopment among the grandchildren and maybe beyond, no matter if the intervening generation of parents was healthy).

It might not be limited to a temporary transgenerational harm as seen with epigenetics. This could be permanent harm to our entire civilization, fundamentally altering our collective gene pool. We could recover from epigenetics within a few generations, assuming we took the problem seriously and acted immediately (Dietary Health Across Generations), but with genetic mutations we may never be able to undo the damage. These mutations have been accumulating and will continue to accumulate, until we return to an ancestral diet of healthy foods as part of an overall healthy lifestyle and environment. Even mutations can be moderated by epigenetics, as the body is designed to deal with them.

This further undermines genetic determinism and biological essentialism. We aren’t mere victims doomed to a fate beyond our control. This dire situation is being created by all of us, individually and collectively. There is no better place to begin than with your own health, but we better also treat this as a societal crisis verging on catastrophe. It was public policies and an international food system that created the conditions that enacted and enforced this failed mass experiment of dietary dogma and capitalist realist profiteering. Maybe we could try something different, something  less psychopathically authoritarian, less psychotically disconnected from reality, less collectively suicidal. Heck, it’s worth a try.

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** I’d slightly disagree with her emphasis. She thinks what matters most is the changes over the past century. There is a good point made in this focus on late modernity. But I’d note that industrialization and modern agriculture began in the prior centuries.

It was in the colonial era that pasta was introduced to Italy, potatoes to Ireland, and sugar throughout the Western world. It wasn’t until the late 1700s and more clearly in the early 1800s that there were regular grain surpluses that made grains available for feeding/fattening both humans and cattle. In particular, it was around this time that agricultural methods improved for wheat crops, allowing it to be affordable to the general public for the first time in human existence and hence causing white bread to become common during the ensuing generations.

I don’t know about diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis. But I do know that the most major diseases of civilization (obesity, diabetes, cancer, and mental illness) were first noticed to be on the rise during the 1700s and 1800s or sometimes earlier, long before industrial oils or the industrial revolution that made these oils possible. The high-carb diet appeared gradually with colonial trade and spread across numerous societies, first hitting the wealthiest before eventually being made possible for the dirty masses. During this time, it was observed by doctors, scientists, missionaries and explorers that obesity, diabetes, cancer, mental illness and moral decline quickly followed on the heels of this modern diet.

Seed oils were simply the final Jenga block pulled out from the ever growing and ever more wobbly tower, in replacing healthy nutrient-dense animal fats (full of fat-soluble vitamins, choline, omega-3 fatty acids, etc) that were counterbalancing some of the worst effects of the high-carb diet. But seed oils, as with farm chemicals such as glyphosate, never would never have had as severe and dramatic of an impact if not for the previous centuries of worsening diet and health. It had been building up over a long time and it was doomed to topple right from the start. We are simply now at the tipping point that is bringing us to the culmination point, the inevitable conclusion of a sad trajectory.

Still, it’s never too late… or let us hope. Dr. Shanahan prefers to end on an optimistic note. And I’d rather not disagree with her about that. I’ll assume she is right or that she is at least in the general ballpark. Let us do as she suggests. We need more and better research, but somehow industrial seed oils have slipped past the notice of autism researchers.

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On Deep Nutrition and Genetic Expression
interview by Kristen Michaelis CNC

Dr. Cate: Genetic Wealth is the idea that if your parents or grandparents ate traditional and nutrient-rich foods, then you came into the world with genes that could express in an optimal way, and this makes you more likely to look like a supermodel and be an extraordinary athlete. Take Angelina Jolie or Michael Jordan, for instance. They’ve got loads of genetic wealth.

Genetic Momentum
 describes the fact that, once you have that extraordinary genetic wealth, you don’t have to eat so great to be healthier than the average person. It’s like being born into a kind of royalty. You always have that inheritance around and you don’t need to work at your health in the same way other people do.

These days, for most of us, it was our grandparents or great grandparents who were the last in our line to grow up on a farm or get a nutrient-rich diet. In my case, I have to go back 4 generations to the Irish and Russian farmers who immigrated to NYC where my grandparents on both sides could only eat cheap food; sometimes good things like chopped liver and beef tongue, but often preserves and crackers and other junk. So my grandparents were far healthier than my brother and sisters and I.

The Standard American Diet (SAD) has accelerated the processes of genetic wealth being spent down, genetic momentum petering out, and the current generation getting sick earlier than their parents and grandparents. This is a real, extreme tragedy on the order of end-of-the-world level losses of natural resources. Genetic wealth is a kind of natural resource. And loss of genetic wealth is a more urgent problem than peak oil or the bursting of the housing bubble. But of course nobody is talking about it directly, only indirectly, in terms of increased rates of chronic disease.

Take autism, for example. Why is autism so common? I don’t think vaccines are the reason for the vast vast majority of cases, since subtle signs of autism can be seen before vaccination in the majority. I think the reason has to do with loss of genetic wealth. We know that children with autism exhibit DNA mutations that their parents and grandparents did not have. Why? Because in the absence of necessary nutrients, DNA cannot even duplicate itself properly and permanent mutations develop.

(Here’s an article on one kind of genetic mutation (DNA deletions) associated with autism.)

Fortunately, most disease is not due to permanent letter mutations and therefore a good diet can rehabilitate a lot of genetic disease that is only a result of altered genetic expression. To put your high-school biology to work, it’s the idea of genotype versus phenotype. You might have the genes that make you prone to, for example, breast cancer (the BRCA1 mutation), but you might not get the disease if you eat right because the gene expression can revert back to normal.

Deep Nutrition: Why Your Genes Need Traditional Food
by Dr. Catherine Shanahan
pp. 55-57

Guided Evolution?

In 2007, a consortium of geneticists investigating autism boldly announced that the disease was not genetic in the typical sense of the word, meaning that you inherit a gene for autism from one or both of your parents. New gene sequencing technologies had revealed that many children with autism had new gene mutations, never before expressed in their family line.

An article published in the prestigious journal Proceedings of the National Academy of Sciences states, “The majority of autisms are a result of de novo mutations, occurring first in the parental germ line.” 42 The reasons behind this will be discussed in Chapter 9.

In 2012, a group investigating these new, spontaneous mutations discovered evidence that randomness was not the sole driving force behind them. Their study, published in the journal Cell, revealed an unexpected pattern of mutations occurring 100 times more often in specific “hotspots,” regions of the human genome where the DNA strand is tightly coiled around organizing proteins called histones that function much like spools in a sewing kit, which organize different colors and types of threads. 43

The consequences of these mutations seem specifically designed to toggle up or down specific character traits. Jonathan Sebat, lead author on the 2012 article, suggests that the hotspots are engineered to “mutate in ways that will influence human traits” by toggling up or down the development of specific behaviors. For example, when a certain gene located at a hotspot on chromosome 7 is duplicated, children develop autism, a developmental delay characterized by near total lack of interest in social interaction. When the same chromosome is deleted, children develop Williams Syndrome, a developmental delay characterized by an exuberant gregariousness, where children talk a lot, and talk with pretty much anyone. The phenomenon wherein specific traits are toggled up and down by variations in gene expression has recently been recognized as a result of the built-in architecture of DNA and dubbed “active adaptive evolution.” 44

As further evidence of an underlying logic driving the development of these new autism-related mutations, it appears that epigenetic factors activate the hotspot, particularly a kind of epigenetic tagging called methylation. 45 In the absence of adequate B vitamins, specific areas of the gene lose these methylation tags, exposing sections of DNA to the factors that generate new mutations. In other words, factors missing from a parent’s diet trigger the genome to respond in ways that will hopefully enable the offspring to cope with the new nutritional environment. It doesn’t always work out, of course, but that seems to be the intent.

You could almost see it as the attempt to adjust character traits in a way that will engineer different kinds of creative minds, so that hopefully one will give us a new capacity to adapt.

pp. 221-228

What Is Autism?

The very first diagnostic manual for psychiatric disorders published in 1954 described autism simply as “schizophrenic reaction, childhood type.” 391 The next manual, released in 1980, listed more specific criteria, including “pervasive lack of responsiveness to other people” and “if speech is present, peculiar speech patterns such as immediate and delayed echolalia, metaphorical language, pronominal reversal (using you when meaning me, for instance).” 392 Of course, the terse language of a diagnostic manual can never convey the real experience of living with a child on the spectrum, or living on the spectrum yourself.

When I graduated from medical school, autism was so rarely diagnosed that none of my psychiatry exams even covered it and I and my classmates were made aware of autism more from watching the movie Rain Man than from studying course material. The question of whether autism (now commonly referred to as ASD) is more common now than it was then or whether we are simply recognizing it more often is still controversial. Some literature suggests that it is a diagnostic issue, and that language disorders are being diagnosed less often as autism is being diagnosed more. However, according to new CDC statistics, it appears that autism rates have risen 30 percent between 2008 and 2012. Considering that diagnostic criteria had been stable by that point in time for over a decade, increased diagnosis is unlikely to be a major factor in this 30 percent figure. 393

Given these chilling statistics, it’s little wonder that so many research dollars have been dedicated to exploring possible connections between exposure to various environmental factors and development of the disorder. Investigators have received grants to look into a possible link between autism and vaccines, 394 smoking, 395 maternal drug use (prescription and illicit), 396 , 397 , 398 organophosphates, 399 and other pesticides, 400 BPA, 401 lead, 402 mercury, 403 cell phones, 404 IVF and infertility treatments, 405 induced labor, 406 high-powered electric wires, 407 flame retardants, 408 ultrasound, 409 —and just about any other environmental factor you can name. You might be wondering if they’ve also looked into diet. But of course: alcohol, 410 cow’s milk, 411 milk protein, 412 soy formula, 413 gluten, 414 and food colorings 415 have all been investigated. Guess what they’ve never dedicated a single study to investigating? Here’s a hint: it’s known to be pro-oxidative and pro-inflammatory and contains 4-HNE, 4-HHE, and MDA, along with a number of other equally potent mutagens. 416 Still haven’t guessed? Okay, one last hint: it’s so ubiquitous in our food supply that for many Americans it makes up as much as 60 percent of their daily caloric intake, 417 a consumption rate that has increased in parallel with rising rates of autism.

Of course, I’m talking about vegetable oil. In Chapter 2 , I discussed in some detail how and why gene transcription, maintenance, and expression are necessarily imperiled in the context of a pro-inflammatory, pro-oxidative environment, so I won’t go further into that here. But I do want to better acquaint you with the three PUFA-derived mutagens I just named because when they make it to the part of your cell that houses DNA, they can bind to DNA and create new, “de novo,” mutations. DNA mutations affecting a woman’s ovaries, a man’s sperm, or a fertilized embryo can have a devastating impact on subsequent generations.

First, let’s revisit 4-HNE (4-hydroxynonanol), which you may recall meeting in the above section on firebombing the highways. This is perhaps the most notorious of all the toxic fats derived from oxidation of omega-6 fatty acids, whose diversity of toxic effects requires that entire chemistry journals be devoted to 4-HNE alone. When the mutagenicity (ability to mutate DNA) of 4-HNE was first described in 1985, the cytotoxicity (ability to kill cells) had already been established for decades. The authors of a 2009 review article explain that the reason it had taken so long to recognize that HNE was such an effective carcinogen was largely due to the fact that “the cytotoxicity [cell-killing ability] of 4-HNE masked its genotoxicity [DNA-mutating effect].” 419 In other words, it kills cells so readily that they don’t have a chance to divide and mutate. How potently does 4-HNE damage human DNA? After interacting with DNA, 4-HNE forms a compound called an HNE-adduct, and that adduct prevents DNA from copying itself accurately. Every time 4-HNE binds to a guanosine (the G of the four-letter ACGT DNA alphabet), there is somewhere between a 0.5 and 5 percent chance that G will not be copied correctly, and that the enzyme trying to make a perfect copy of DNA will accidentally turn G into T. 420 Without 4-HNE, the chance of error is about a millionth of a percent. 421 In other words, 4-HNE increases the chances of a DNA mutation rate roughly a million times!

Second, 4-HHE (4-hydroxy-hexanal), which is very much like 4-HNE, his more notorious bigger brother derived from omega-6, but 4-HHE is derived instead from omega-3. If bad guys had sidekicks, 4-NHE’s would be 4-HHE. Because 4-HHE does many of the same things to DNA as 4-HNE, but has only been discovered recently. 422 You see, when omega-6 reacts with oxygen, it breaks apart into two major end products, whereas omega-3, being more explosive, flies apart into four different molecules. This means each one is present in smaller amounts, and that makes them a little more difficult to study. But it doesn’t make 4-HHE any less dangerous. 4-HHE specializes in burning through your glutathione peroxidase antioxidant defense system. 423 This selenium-based antioxidant enzyme is one of the three major enzymatic antioxidant defense systems, and it may be the most important player defending your DNA against oxidative stress. 424 , 425

Finally, there is malonaldehyde (MDA), proven to be a mutagen in 1984, but presumed to only come from consumption of cooked and cured meats. 426 Only in the past few decades have we had the technology to determine that MDA can be generated in our bodies as well. 427 And unlike the previous two chemicals, MDA is generated by oxidation of both omega-3 and omega-6. It may be the most common endogenously derived oxidation product. Dr. J. L. Marnett, who directs a cancer research lab at Vanderbuit University School of Medicine, Nashville, Tennessee, and who has published over 400 articles on the subject of DNA mutation, summarized his final article on MDA with the definitive statement that MDA “appears to be a major source of endogenous DNA damage [endogenous, here, meaning due to internal, metabolic factors rather than, say, radiation] in humans that may contribute significantly to cancer and other genetic diseases.” 428

There’s one more thing I need to add about vegetable-oil-derived toxic breakdown products, particularly given the long list of toxins now being investigated as potential causes of autism spectrum disorders. Not only do they directly mutate DNA, they also make DNA more susceptible to mutations induced by other environmental pollutants. 429 , 430 This means that if you start reading labels and taking vegetable oil out of your diet, your body will more readily deal with the thousands of contaminating toxins not listed on the labels which are nearly impossible to avoid.

Why all this focus on genes when we’re talking about autism? Nearly every day a new study comes out that further consolidates the consensus among scientists that autism is commonly a genetic disorder. The latest research is focusing on de novo mutations, meaning mutations neither parent had themselves but that arose spontaneously in their egg, sperm, or during fertilization. These mutations may affect single genes, or they may manifest as copy number variations, in which entire stretches of DNA containing multiple genes are deleted or duplicated. Geneticists have already identified a staggering number of genes that appear to be associated with autism. In one report summarizing results of examining 900 children, scientists identified 1,000 potential genes: “exome sequencing of over 900 individuals provided an estimate of nearly 1,000 contributing genes.” 431

All of these 1,000 genes are involved with proper development of the part of the brain most identified with the human intellect: our cortical gray matter. This is the stuff that enables us to master human skills: the spoken language, reading, writing, dancing, playing music, and, most important, the social interaction that drives the desire to do all of the above. One need only have a few of these 1,000 genes involved in building a brain get miscopied, or in some cases just one, in order for altered brain development to lead to one’s inclusion in the ASD spectrum.

So just a few troublemaker genes can obstruct the entire brain development program. But for things to go right, all the genes for brain development need to be fully functional.

Given that humans are thought to have only around 20,000 genes, and already 1,000 are known to be essential for building brain, that means geneticists have already labeled 5 percent of the totality of our genetic database as crucial to the development of a healthy brain—and we’ve just started looking. At what point does it become a foolish enterprise to continue to look for genes that, when mutated, are associated with autism? When we’ve identified 5,000? Or 10,000? The entire human genome? At what point do we stop focusing myopically only on those genes thought to play a role in autism?

I’ll tell you when: when you learn that the average autistic child’s genome carries de novo mutations not just in genes thought to be associated with autism, but across the board, throughout the entirety of the chromosomal landscape. Because once you’ve learned this, you can’t help but consider that autism might be better characterized as a symptom of a larger disease—a disease that results in an overall increase in de novo mutations.

Almost buried by the avalanche of journal articles on genes associated with autism is the finding that autistic children exhibit roughly ten times the number of de novo mutations compared to their typically developing siblings. 432 An international working group on autism pronounced this startling finding in a 2013 article entitled: “Global Increases in Both Common and Rare Copy Number Load Associated With Autism.” 433 ( Copy number load refers to mutations wherein large segments of genes are duplicated too often.) What the article says is that yes, children with autism have a larger number of de novo mutations, but the majority of their new mutations are not statistically associated with autism because other kids have them, too. The typically developing kids just don’t have nearly as many.

These new mutations are not only affecting genes associated with brain development. They are affecting all genes seemingly universally. What is more, there is a dose response relationship between the total number of de novo mutations and the severity of autism such that the more gene mutations a child has (the bigger the dose of mutation), the worse their autism (the larger the response). And it doesn’t matter where the mutations are located—even in genes that have no obvious connection to the brain. 434 This finding suggests that autism does not originate in the brain, as has been assumed. The real problem—at least for many children—may actually be coming from the genes. If this is so, then when we look at a child with autism, what we’re seeing is a child manifesting a global genetic breakdown. Among the many possible outcomes of this genetic breakdown, autism may simply be the most conspicuous, as the cognitive and social hallmarks of autism are easy to recognize.

As the authors of the 2013 article state, “Given the large genetic target of neurodevelopmental disorders, estimated in the hundreds or even thousands of genomic loci, it stands to reason that anything that increases genomic instability could contribute to the genesis of these disorders.” 435 Genomic instability —now they’re on to something. Because framing the problem this way helps us to ask the more fundamental question, What is behind the “genomic instability” that’s causing all these new gene mutations?

In the section titled “What Makes DNA Forget” in Chapter 2 , I touched upon the idea that an optimal nutritional environment is required to ensure the accurate transcription of genetic material and communication of epigenetic bookmarking, and how a pro-oxidative, pro-inflammatory diet can sabotage this delicate operation in ways that can lead to mutation and alter normal growth. There I focused on mistakes made in epigenetic programming, what you could call de novo epigenetic abnormalities. The same prerequisites that support proper epigenetic data communication, I submit, apply equally to the proper transcription of genetic data.

What’s the opposite of a supportive nutritional environment? A steady intake of pro-inflammatory, pro-oxidative vegetable oil that brings with it the known mutagenic compounds of the kind I’ve just described. Furthermore, if exposure to these vegetable oil-derived mutagens causes a breakdown in the systems for accurately duplicating genes, then you might expect to find other detrimental effects from this generalized defect of gene replication. Indeed we do. Researchers in Finland have found that children anywhere on the ASD spectrum have between 1.5 and 2.7 times the risk of being born with a serious birth defect, most commonly a life-threatening heart defect or neural tube (brain and spinal cord) defect that impairs the child’s ability to walk. 436 Another group, in Nova Scotia, identified a similarly increased rate of minor malformations, such as abnormally rotated ears, small feet, or closely spaced eyes. 437

What I’ve laid out here is the argument that the increasing prevalence of autism is best understood as a symptom of De Novo Gene Mutation Syndrome brought on by oxidative damage, and that vegetable oil is the number-one culprit in creating these new mutations. These claims emerge from a point-by-point deduction based on the best available chemical, genetic, and physiologic science. To test the validity of this hypothesis, we need more research.

Does De Novo Gene Mutation Syndrome Affect Just the Brain?

Nothing would redirect the trajectory of autism research in a more productive fashion than reframing autism as a symptom of the larger underlying disease, which we are provisionally calling de novo gene-mutation syndrome, or DiNGS. (Here’s a mnemonic: vegetable oil toxins “ding” your DNA, like hailstones pockmarking your car.)

If you accept my thesis that the expanding epidemic of autism is a symptom of an epidemic of new gene mutations, then you may wonder why the only identified syndrome of DiNGS is autism. Why don’t we see all manner of new diseases associated with gene mutations affecting organs other than the brain? We do. According to the most recent CDC report on birth defect incidence in the United States, twenty-nine of the thirty-eight organ malformations tracked have increased. 438

However, these are rare events, occurring far less frequently than autism. The reason for the difference derives from the fact that the brain of a developing baby can be damaged to a greater degree than other organs can, while still allowing the pregnancy to carry to term. Though the complex nature of the brain makes it the most vulnerable in terms of being affected by mutation, this aberration of development does not make the child more vulnerable in terms of survival in utero. The fact that autism affects the most evolutionarily novel portion of the brain means that as far as viability of an embryo is concerned, it’s almost irrelevant. If the kinds of severely damaging mutations leading to autism were to occur in organs such as the heart, lungs, or kidneys, fetal survival would be imperiled, leading to spontaneous miscarriage. Since these organs begin developing as early as four to six weeks of in-utero life, failure of a pregnancy this early might occur without any symptoms other than bleeding, which might be mistaken for a heavy or late period, and before a mother has even realized she’s conceived.

Dietary Health Across Generations

It’s common to blame individuals for the old Christian sins of sloth and gluttony. But that has never made much sense, at least not scientifically. Gary Taubes has discussed this extensively, and so look to his several books for more info about why applying Christian theology to diet, nutrition, and health is not a wise strategy for evidence-based medicine and public health policy.

Yes, Americans in particular would be wise to do something about their health in a society where 88% of the adult population has one or more symptoms of metabolic syndrome with about three-quarters being overweight and about half diabetic or prediabetic (Joana Araújo, Jianwen Cai, June Stevens. “Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016”; for more info, see The University of North Carolina at Chapel Hill or Science Daily). Consider, these statistics are even worse for the younger generations. But let’s put this in even greater context. It’s not only that each generation is unhealthier than the last for this declining health is being inherited from before birth. There is now an obesity epidemic among 6 month old babies. I doubt anyone thinks it’s reasonable to blame babies. Should babies eat less and exercise more?

This goes back a while. European immigrants in the early 1900s noticed how American children were much chubbier than their European counterparts. By the 1950s, there was already a discussion of an obesity epidemic, as it was becoming noticeable with the younger generations. We are several generations into this modern industrialized diet of highly processed starchy carbs, added sugar, and seed oils. Much of this is caused by worsening environmental conditions, from harmful chemicals to industrial food system. The effects would begin in the womb, but the causality can actually extend across numerous generations.

This is called epigenetics, what determines which genes get expressed and how. And this epigenetic effect is magnified by the microbiome we inherit as well, since microbes help determine some of the epigenetic effect, involving short-chain fatty acids that can be obtained either through plant or animal foods (Fiber or Not: Short-Chain Fatty Acids and the Microbiome). This is important, as it is easier and more straightforward to manipulate our microbiome than our epigenetics, or at least our knowledge is more clear about the former. By changing our diet, we can change our microbiome. And by changing our microbiome, we can change our epigenetics and that of our children and grandchildren.

The dietary aspect is the most basic component, in that some diets seem to have an effect directly on the epigenome itself, however the microbiome may or may not be involved — for example, there is “recent evidence that KD [ketogenic diet] influences the epigenome through modulation of adenosine metabolism as a plausible antiepileptogenic mechanism of the diet” (Theresa A. Lusardi & Detlev Boison, Ketogenic Diet, Adenosine, Epigenetics, and Antiepileptogenesis). It’s been proven for about a century now that the ketogenic diet is the most effective treatment for epileptic seizures, but there has been much debate about why. Now we might know the reason. The mechanism appears to be epigenetic.

This is not exactly new knowledge (Health From Generation To Generation). Such cross-generational influences have been known since earlier last century, but sadly such knowledge is not epigenetically inherited by each succeeding generation. Francis M. Pottenger Jr studied the health of cats on severely malnourished and well-nourished diets — by the third generation the malnourished cats were no longer capable of breeding and so there was no fourth generation. This doesn’t perfectly translate to the present human diet, although it does make one wonder. Many of our diseases of civilization seem to be at least partly caused by malnourishment. This is a public health epidemic as national security crisis.

Here is the question that comes to mind: In this modern industrialized diet, what generation of malnourishment are we at now? And if as a society we changed public health policies and medical practice right now, how many generations would it take to reverse the trend and fully undo the damage? To end on a positive note, we could potentially turn it around within this century: “Dr. Pottenger’s research also showed that the health of the cats could be recovered if the diet were returned to a healthy one by the second generation; however, even then it took four generations for some of the cats to show no symptoms of allergies” (Carolyn Biggerstaff, Pottenger’s Cats – an early window on epigenetics).

So, what are we waiting for?

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To give you some idea of how long our society has experienced declining health, check out some of my earlier posts:

Malnourished Americans
Ancient Atherosclerosis?
The Agricultural Mind

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Videos, podcasts, and articles on epigenetics as related to diet, nutrition, microbiome, health, etc with some emphasis on paleo and ketogenic viewpoints:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nutriepigenomics
from Wikipedia

Changes in the diet affect epigenetics via the microbiota
from EurekAlert!

Diet and the epigenome
Yi Zhang and Tatiana G. Kutateladze

Dietary Epigenetics: New Frontiers
by Austin Perlmutter

RHR: The Latest Discoveries in Evolutionary Biology, Genetics, and Epigenetics
by Chris Kresser

Epigenetics, Methylation, and Gene Expression
by Kevin Cann

Epigenetics: Will It Change the Way We Treat Disease?
by Kissairis Munoz

Hacking Your Genes Through Epigenetics and Targeted Nutrigenomics
by Daniel Rash

The Promise of Paleo-Epigenetics
by Jennifer Raff

Dawn of Paleoepigenomics
by Zachary Cofran

37: Robb Wolf – Diets, Epigenetics, Longevity, and Going Foodless for 9 Days
by Andy Petranek

Epigenetics and the Paleo Diet
from The Paleo Diet

Paleo, Epigenetics, and Your Weight
from Paleo Leap

EP157: Improving Mental Health with Epigenetics, Diet & Exercise with Alex Swanson
from Paleo Valley

Epigenetics Warning: Are You Wrecking Your Kids’ Health?
by Louise Hendon

EPISODE 64: Epigenetics 101 with Bailey Kirkpatrick
from Phoenix Helix

Episode 90 – Dr. Lucia Aronica studies keto and epigenetics
by Brian Williamson

Can Keto Affect Your Genes?
from KetoNutrition

Energy & Epigenetics 1: The Infant Brain is Unique
by Jack Kruse

Dr. David Perlmutter: Intermittent Fasting, Epigenetics & What Sugar Really Does To Your Brain
by Abel James

Epigenetic Explanations For Why Cutting Sugar May Make You Feel Smarter
by Caitlin Aamodt

Eating Sweet, Fatty Foods During Pregnancy is Linked to ADHD in Children
by Bailey Kirkpatrick

High Fat, Low Carb Diet Might Epigenetically Open Up DNA and Improve Mental Ability
by Bailey Kirkpatrick

A Child’s Mental Fitness Could Be Epigenetically Influenced by Dad’s Diet
by Bailey Kirkpatrick

Dad’s Drinking Could Epigenetically Affect Son’s Sensitivity and Preference for Alcohol
by Bailey Kirkpatrick

B Vitamins Protect Against Harmful Epigenetic Effects of Air Pollution
by Bailey Kirkpatrick

Vitamin D Adjusts Epigenetic Marks That Could Hinder A Baby’s Health
by Bailey Kirkpatrick

Could We Use Epigenetics and Diet to Fix Binge Eating?
by Bailey Kirkpatrick

Early Epigenetic Nutrition ‘Memory’ Could Program You for Obesity Later in Life
by Bailey Kirkpatrick

The Consequences of a Poor Diet Could Epigenetically Persist Despite Improving Eating Habits
by Bailey Kirkpatrick

Epigenetic Transfer of Nutrition ‘Memory’ Ends Before Great-Grandchildren
by Bailey Kirkpatrick

How your grandparents’ life could have changed your genes
by Tim Spector

Nutrition & the Epigenome
from University of Utah

The epigenetics diet: A barrier against environmental pollution
from University of Alabama at Birmingham

How Epigenetics May Help Explain the Complexity of Autism Spectrum Disorder
from Zymo Research

Epigenetics, Health and the Mind
from PBS with John Denu

Eating for two risks harm to the baby
by Laura Donnelly and Leah Farrar

Micronutrients in Psychiatry: Sound Science or Just Hype?
by Seth J. Gillihan

Epigenetics: A New Bridge between Nutrition and Health
by Sang-Woon Choi and Simonetta Friso

Role of diet in epigenetics: a review
by Abhina Mohanan and Raji Kanakkaparambil

The science behind the Dutch Hunger Winter
from Youth Voices

Epigenetic Marks From Parents Could Influence Embryo Development and Future Health
by Tim Barry

Can Your Diet Epigenetically Shape Your Child’s Health?
by Janeth Santiago Rios

Epigenetic Insights on Nutrition, Hormones and Eating Behavior
by Janeth Santiago Rios

Paternal Environmental and Lifestyle Factors Influence Epigenetic Inheritance
by Estephany Ferrufino

How Diet Can Change Your DNA
by Renee Morad

Food that shapes you: how diet can change your epigenome
by Cristina Florean

The Unknown Link: Epigenetics, Metabolism, and Nutrition
by Nafiah Enayet

Obesity, Epigenetics, and Gene Regulation
by Jill U. Adams

Epigenetics and Epigenomics: Implications for Diabetes and Obesity
by Evan D. Rosen et al

Epigenetic switch for obesity
from Science Daily

Epigenetics between the generations: We inherit more than just genes
from Science Daily

Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes
by R. Lambrot et al

Diet-Induced Obesity in Female Mice Leads to Offspring Hyperphagia, Adiposity, Hypertension, and Insulin Resistance
by Anne-Maj Samuelsson et al

Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring
by Sarah J. Glastras

Transgenerational Epigenetic Mechanisms in Adipose Tissue Development
by Simon Lecoutre et al

Your Grandma’s Diet Could Have Made You Obese, Mouse Study Suggests
by Kashmira Gandery

Your Diet Affects Your Grandchildren’s DNA, Scientists Say
by Christopher Wanjek

You Are What Your Grandparents Ate
by Maria Rodale

People who eat too much fast food could cause heart disease in their great grandchildren by Jasper Hamill

Eating Badly When Pregnant Might Make Your Kid Fat
by Zak Stone

Perinatal Western Diet Consumption Leads to Profound Plasticity and GABAergic Phenotype Changes within Hypothalamus and Reward Pathway from Birth to Sexual Maturity in Rat
by Julie Paradis et al

A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring
by S. A. M. Bayol et al

Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring
by María Teresa Ramírez-López et al

A maternal junk food diet alters development of opioid pathway in the offspring
from Science Daily

‘Junk food’ moms have ‘junk food’ babies
from Science Daily

Born to Be Junk Food Junkies
by Linda Wasmer Andrews

Reality check: Do babies inherit junk food addictions from their moms?
by Carmen Chai

Bad Eating Habits Start in the Womb
by Kristin Wartman

Could Over-Snacking While Pregnant Predispose Children to Be Obese?
by Natasha Geiling

Overeating in pregnancy could lead to child obesity
by John von Radowitz

Eating for two puts unborn child at risk of junk addiction
by James Randerson

Craving for junk food ‘inherited’
from BBC

Craving for junk food ‘begins in the womb’
by Fran Yeoman

Hooked on junk food in the womb
by Fiona MacRae

How pregnant mums who ‘eat for 2’ can make their babies fat
by Victoria Fletcher

 

Inherited Learned Behavior

There is what we inherit from our parents and there is what we learn from our own experience. The two are distinct, right? Well, actually no they are not separate. This was further demonstrated by a Princeton study (Danger avoidance can be genetically encoded for four generations, biologists say):

“Moore and her colleagues investigated whether C. elegans can convey this learned avoidance behavior to their progeny. They found that when mother worms learned to avoid pathogenic P. aeruginosa, their progeny also knew to avoid the bacteria. The natural attraction of offspring to Pseudomonas was overridden even though they had never previously encountered the pathogen. Remarkably, this inherited aversive behavior lasted for four generations, but in the fifth generation the worms were once again attracted to Pseudomonas.”

This is not an entirely new understanding. Earlier research has found similar results in other species. The study that always fascinates me had to do with rodents. The scent of cherry blossoms was emitted in their cage and immediately following that the bottom of the cage was electrified. Unsurprisingly, the rodents jumped around trying to avoid the pain. The rodents learned to begin jumping merely at the presence of the scent, whether or not any electric shock followed. The interesting part is that their rodent descendants, even though never shocked, would also jump when they smelled cherry blossoms. And this lasted for multiple generations. A very specific learned behavior was passed on.

Of course, this isn’t limited to worms and rodents. Humans are harder to study, partly because of our longer lives. But researchers have been able to observe multiple living generations to discover patterns. I’m not sure if this exactly fits into learned behavior, except in how the body learns to respond to the environment. It’s similar enough. This other research found that the children and grandchildren of famine survivors had higher rates of obesity that had nothing to do wasn’t caused by genetics or diet. It is what is called epigenetics, how the genes get set for expression. The same genes can be switched on or off in numerous ways in relation to other genes.

I find that fascinating. It also makes for much complication. Almost no research ever controls for multigenerational confounding factors. Epigenetics has been largely a black box, until quite recently. To be certain that a particular behavior was directly related to specific genetics in a population, you would have to be able to follow that population for many generations. To fully control for confounders, that would require a study that lasted more than a century. It might turn out that much of what we call ‘culture’ might more correctly be explained as population-wide epigenetics.

* * *

As a side note, this would have immense significance to dietary and nutritional research. Many of the dietary changes that have happened in modern society are well within the range of epigenetic involvement. And the epigenetic effects likely would be cumulative.

We have an ongoing and uncontrolled experiment going on. No one knows the long-term consequences of the modern industrial diet of refined carbohydrates, added sugars, highly processed vegetable oils, food additives, farm chemicals, microplastic, etc. It’s a mass experiment and the subjects never chose to participate.

Definitely, we have reasons to be concerned. Francis M. Pottenger Jr. studied the dietary impact on feline health. He fed some cats a raw food diet, others a cooked food diet, and a third group with a diet mixed of raw and cooked. The cats on the cooked food diet became sickly in the first generation and were entirely infertile after a number of generations.

This is not exactly similar to the human diet of industrial foods. But it points to how results play out across generations. The worst effects aren’t necessarily seen in the immediate generation(s). It’s future generations that have to deal with what those before them caused, as true for epigenetics as it is for national debt and environmental destruction.

Epigenetics, the Good and the Bad

Epignetics is what determines which genes express and how they express. Research on epigenetics for some reason has often focused on negative consequences.

In rodent research, scientists were able to induce a Pavlovian response to a smell that preceded a shock. The rodents would jump when the smell was present, even when no shock followed. And generations of rodents kept jumping, despite their never having been shocked at all. The Pavlovian response was inherited. In human research, scientists studied populations that had experienced famine. They looked at multiple generations where only the older generation had been alive during the famine. Yet all the generations following had higher rates of obesity. They inherited the biological preparation for famine.

One might start to think that epigenetics is a bad thing, almost like a disease. But that would be a mistake. Everything about who we are, good and bad, is shaped by epigenetics. To balance things out, I just came across some a more positive example. Health benefits get passed on as well. I would note, however, that this is what exacerbates inequality. This is why oppression and privilege get inherited not only through social conditions but in biology itself. This is all the more reason we should intervene to create the most optimal conditions for everyone, not merely the fortunate few.

This is why the political left emphasizes equality of results, beyond theoretical equality of opportunity. Opportunity is meaningless if it remains an abstract ideal disconnected from lived reality for most of the population. Telling people to get over the past is cruel and ignorant. The past is never past and, in fact, becomes imprinted upon the bodies of many generations, maybe across centuries. Historical injustices and transgenerational trauma are what our society are built upon, and much of it is within living memory, from the Indian Wars to Jim Crow.

It will require direct action to undo the damage and to promote the public good. That is the only path toward a free and fair society.

* * *

Intergenerational transmission of the positive effects of physical exercise on brain and cognition
by Kerry R. McGreevy et al

Significance

Physical exercise is well known for its positive effects on general health (specifically, on brain function and health), and some mediating mechanisms are also known. A few reports have addressed intergenerational inheritance of some of these positive effects from exercised mothers or fathers to the progeny, but with scarce results in cognition. We report here the inheritance of moderate exercise-induced paternal traits in offspring’s cognition, neurogenesis, and enhanced mitochondrial activity. These changes were accompanied by specific gene expression changes, including gene sets regulated by microRNAs, as potential mediating mechanisms. We have also demonstrated a direct transmission of the exercise-induced effects through the fathers’ sperm, thus showing that paternal physical activity is a direct factor driving offspring’s brain physiology and cognitive behavior.

Abstract

Physical exercise has positive effects on cognition, but very little is known about the inheritance of these effects to sedentary offspring and the mechanisms involved. Here, we use a patrilineal design in mice to test the transmission of effects from the same father (before or after training) and from different fathers to compare sedentary- and runner-father progenies. Behavioral, stereological, and whole-genome sequence analyses reveal that paternal cognition improvement is inherited by the offspring, along with increased adult neurogenesis, greater mitochondrial citrate synthase activity, and modulation of the adult hippocampal gene expression profile. These results demonstrate the inheritance of exercise-induced cognition enhancement through the germline, pointing to paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.

What is a gene?

Now: The Rest of the Genome
by Carl Zimmer

In this jungle of invading viruses, undead pseudogenes, shuffled exons and epigenetic marks, can the classical concept of the gene survive? It is an open question, one that Dr. Prohaska hopes to address at a meeting she is organizing at the Santa Fe Institute in New Mexico next March.

In the current issue of American Scientist, Dr. Gerstein and his former graduate student Michael Seringhaus argue that in order to define a gene, scientists must start with the RNA transcript and trace it back to the DNA. Whatever exons are used to make that transcript would constitute a gene. Dr. Prohaska argues that a gene should be the smallest unit underlying inherited traits. It may include not just a collection of exons, but the epigenetic marks on them that are inherited as well.

These new concepts are moving the gene away from a physical snippet of DNA and back to a more abstract definition. “It’s almost a recapture of what the term was originally meant to convey,” Dr. Gingeras said.

A hundred years after it was born, the gene is coming home.

Genome 2.0: Mountains Of New Data Are Challenging Old Views
by Patrick Barry

This complex interweaving of genes, transcripts, and regulation makes the net effect of a single mutation on an organism much more difficult to predict, Gingeras says.

More fundamentally, it muddies scientists’ conception of just what constitutes a gene. In the established definition, a gene is a discrete region of DNA that produces a single, identifiable protein in a cell. But the functioning of a protein often depends on a host of RNAs that control its activity. If a stretch of DNA known to be a protein-coding gene also produces regulatory RNAs essential for several other genes, is it somehow a part of all those other genes as well?

To make things even messier, the genetic code for a protein can be scattered far and wide around the genome. The ENCODE project revealed that about 90 percent of protein-coding genes possessed previously unknown coding fragments that were located far from the main gene, sometimes on other chromosomes. Many scientists now argue that this overlapping and dispersal of genes, along with the swelling ranks of functional RNAs, renders the standard gene concept of the central dogma obsolete.

Long Live The Gene

Offering a radical new conception of the genome, Gingeras proposes shifting the focus away from protein-coding genes. Instead, he suggests that the fundamental units of the genome could be defined as functional RNA transcripts.

Since some of these transcripts ferry code for proteins as dutiful mRNAs, this new perspective would encompass traditional genes. But it would also accommodate new classes of functional RNAs as they’re discovered, while avoiding the confusion caused by several overlapping genes laying claim to a single stretch of DNA. The emerging picture of the genome “definitely shifts the emphasis from genes to transcripts,” agrees Mark B. Gerstein, a bioinformaticist at Yale University.

Scientists’ definition of a gene has evolved several times since Gregor Mendel first deduced the idea in the 1860s from his work with pea plants. Now, about 50 years after its last major revision, the gene concept is once again being called into question.

Theory Suggests That All Genes Affect Every Complex Trait
by Veronique Greenwood

Over the years, however, what scientists might consider “a lot” in this context has quietly inflated. Last June, Pritchard and his Stanford colleagues Evan Boyle and Yang Li (now at the University of Chicago) published a paper about this in Cell that immediately sparked controversy, although it also had many people nodding in cautious agreement. The authors described what they called the “omnigenic” model of complex traits. Drawing on GWAS analyses of three diseases, they concluded that in the cell types that are relevant to a disease, it appears that not 15, not 100, but essentially all genes contribute to the condition. The authors suggested that for some traits, “multiple” loci could mean more than 100,000. […]

For most complex conditions and diseases, however, she thinks that the idea of a tiny coterie of identifiable core genes is a red herring because the effects might truly stem from disturbances at innumerable loci — and from the environment — working in concert. In a new paper out in Cell this week, Wray and her colleagues argue that the core gene idea amounts to an unwarranted assumption, and that researchers should simply let the experimental data about particular traits or conditions lead their thinking. (In their paper proposing omnigenics, Pritchard and his co-authors also asked whether the distinction between core and peripheral genes was useful and acknowledged that some diseases might not have them.)

Epigenetic Memory and the Mind

Epigenetics is fascinating, even bizarre by conventional thought. Some worry that it’s another variety of determinism, just not located in the genes. I have other worries, if not that particular one.

How epigenetics work is that a gene gets switched on or off. The key point is that it’s not permanently set. Some later incident, conditions, behavior, or whatever can switch it back the other way again. Genes in your body are switched on and off throughout your lifetime. But presumably if no significant changes occur in one’s life some epigenetic expressions remain permanently set for your entire life.

Where it gets fascinating is that it’s been proven that epigenetics gets passed on across multiple generations and no one is certain how many generations. In mice, it can extend at least upwards of 7 generations or so, as I recall. Humans, of course, haven’t been studied for that many generations. But present evidence indicates it operates similarly in humans.

Potentially, all of the major tragedies in modern history (violence of colonialism all around the world, major famines in places like Ireland and China, genocides in places like the United States and Rwanda, international conflicts like the world wars, etc), all of that is within the range of epigenetis. It’s been shown that famine, for example, switches genes for a few generations that causes increased fat retention and in the modern world that means higher obesity rates.

I’m not sure what is the precise mechanism that causes genes to switch on and off (e.g., precisely how does starvation get imprinted on biology and become set that way for multiple generations). All I know is it has to do with the proteins that encase the DNA. The main interest is that, once we do understand the mechanism, we will be able to control the process. This might be a way of preventing or managing numerous physical and psychiatric health conditions. So, it really will mean the opposite of determinism.

This research reminds me of other scientific and anecdotal evidence. Consider the recipients of organ transplants, blood and bone marrow transfusions, and microbiome transference. This involves the exchange of cells from one body to another. The results have shown changes in mood, behavior, biological functioning, etc

For example, introducing a new microbiome can make a skinny rodent fat or a fat rodent skinny. But also observed are shifts in fairly specific memories, such as an organ transplant recipient craving something the organ donor craved. Furthermore, research has shown that genetics can jump from the introduced cells to the already present cells, which is how a baby can potentially end up with the cells of two fathers if a previous pregnancy was by a different father, and actually it’s rather common for people to have multiple DNAs in their body.

It intuitively makes sense that epigenetics would be behind memory. It’s easy to argue that there is no other function in the body that has this kind and degree of capacity. And that possibility would blow up our ideas of the human mind. In that case, some element of memories would get passed on multiple generations, explaining certain similarities seen in families and larger populations with shared epigenetic backgrounds.

This gives new meaning to the theories of both the embodied mind and the extended mind. There might also having some interesting implications for the bundle theory of mind. I wonder too about something like enactivism which is about the human mind’s relation to the world. Of course, there are obvious connections of this specific research with neurological plasticity and of epigenetics more generally with intergenerational trauma.

So, it wouldn’t only be the symptoms of trauma or else the benefits of privilege (or whatever other conditions that shape individuals, generational cohorts, and sub-populations) being inherited but some of the memory itself. This puts bodily memory in a much larger context, maybe even something along the lines of Jungian thought, in terms of collective memory and archetypes (depending on how long-lasting some epigenetic effects might be). Also, much of what people think of as cultural, ethnic, and racial differences might simply be epigenetics. This would puncture an even larger hole in genetic determinism and race realism. Unlike genetics, epigenetics can be changed.

Our understanding of so much is going to be completely altered. What once seemed crazy or unthinkable will become the new dominant paradigm. This is both promising and scary. Imagine what authoritarian governments could do with this scientific knowledge. The Nazis could only dream of creating a superman. But between genetic engineering and epigenetic manipulations, the possibilities are wide open. And right now, we have no clue what we are doing. The early experimentation, specifically research done covertly, is going to be of the mad scientist variety.

These interesting times are going to get way more interesting.

* * *

Could Memory Traces Exist in Cell Bodies?
by Susan Cosier

The finding is surprising because it suggests that a nerve cell body “knows” how many synapses it is supposed to form, meaning it is encoding a crucial part of memory. The researchers also ran a similar experiment on live sea slugs, in which they found that a long-term memory could be totally erased (as gauged by its synapses being destroyed) and then re-formed with only a small reminder stimulus—again suggesting that some information was being stored in a neuron’s body.

Synapses may be like a concert pianist’s fingers, explains principal investigator David Glanzman, a neurologist at U.C.L.A. Even if Chopin did not have his fingers, he would still know how to play his sonatas. “This is a radical idea, and I don’t deny it: memory really isn’t stored in synapses,” Glanzman says.

Other memory experts are intrigued by the findings but cautious about interpreting the results. Even if neurons retain information about how many synapses to form, it is unclear how the cells could know where to put the synapses or how strong they should be—which are crucial components of memory storage. Yet the work indeed suggests that synapses might not be set in stone as they encode memory: they may wither and re-form as a memory waxes and wanes. “The results are really just kind of surprising,” says Todd Sacktor, a neurologist at SUNY Downstate Medical Center. “It has always been this assumption that it’s the same synapses that are storing the memory,” he says. “And the essence of what [Glanzman] is saying is that it’s far more dynamic.”

Memory Transferred Between Snails, Challenging Standard Theory of How the Brain Remembers
by Usha Lee McFarling

Glanzman’s experiments—funded by the National Institutes of Health and the National Science Foundation—involved giving mild electrical shocks to the marine snail Aplysia californica. Shocked snails learn to withdraw their delicate siphons and gills for nearly a minute as a defense when they subsequently receive a weak touch; snails that have not been shocked withdraw only briefly.

The researchers extracted RNA from the nervous systems of snails that had been shocked and injected the material into unshocked snails. RNA’s primary role is to serve as a messenger inside cells, carrying protein-making instructions from its cousin DNA. But when this RNA was injected, these naive snails withdrew their siphons for extended periods of time after a soft touch. Control snails that received injections of RNA from snails that had not received shocks did not withdraw their siphons for as long.

“It’s as if we transferred a memory,” Glanzman said.

Glanzman’s group went further, showing that Aplysia sensory neurons in Petri dishes were more excitable, as they tend to be after being shocked, if they were exposed to RNA from shocked snails. Exposure to RNA from snails that had never been shocked did not cause the cells to become more excitable.

The results, said Glanzman, suggest that memories may be stored within the nucleus of neurons, where RNA is synthesized and can act on DNA to turn genes on and off. He said he thought memory storage involved these epigenetic changes—changes in the activity of genes and not in the DNA sequences that make up those genes—that are mediated by RNA.

This view challenges the widely held notion that memories are stored by enhancing synaptic connections between neurons. Rather, Glanzman sees synaptic changes that occur during memory formation as flowing from the information that the RNA is carrying.

What is inheritance?

The original meaning of a gene was simply a heritable unit. This was long before the discovery of DNA. The theory was based on phenotype, i.e., observable characteristics. What they didn’t know and what still doesn’t often get acknowledged is that much gets inherited from parents, especially from the mother. This includes everything from epigenetics to microbiome, the former determining which genes express and how they express while the latter consists of the majority of genetics in the human body. The fetus will also inherit health conditions from the mother, such as malnutrition and stress, viruses and parasites — all of those surely having epigenetic effects and microbiome changes that could get passed on for generations.

Even more interestingly, DNA itself gets passed on in diverse ways. Viruses will snip out sections of DNA and then put them into the DNA of new hosts. Mothers, including surrogate mothers, can gain DNA from the fetuses they carry. And then those mothers can pass that DNA to any fetus she carries after that, which could cause a fetus to have DNA from two fathers. Fetuses can also absorb the DNA from fraternal twins or even entirely absorb the other fetus, forming what is called a chimera. Bone marrow transplantees also become chimeras because they inherit the stem cells for blood cells from the donor, along with inheriting epigentics from the donor. These chimeras could pass this on during a transplantee’s pregnancy.

We hardly know what all that might mean. There is no single heritable unit that by itself does anything. That is not the direct source of causation. A gene only acts as part of DNA within a specific cell and all of that within the entire biological system existing within specific environmental conditions. The most important causal factors are various. What is in DNA only matters to the degree it is expressed, but what determines its expression will also determine how it expresses. Evelyn Keller Fox writes that, “the causal interactions between DNA, proteins, and trait development are so entangled, so dynamic, and so dependent on context that the very question of what genes do no longer makes much sense. Indeed, biologists are no longer confident that it is possible to provide an unambiguous answer to the question of what a gene is. The particulate gene is a concept that has become increasingly ambiguous and unstable, and some scientists have begun to argue that the concept has outlived its productive prime” (The Mirage of a Space between Nature and Nurture, p. 50). Gene expression as seen in phenotype is determined by a complex system of overlapping factors. Talk of genes doesn’t help us much, if at all. And heritability rates tells us absolutely nothing about the details, such as distinguishing what exactly is a gene as a heritable unit and causal factor, much less differentiating that from everything else. As Fox further explains:

“It is true that many authors continue to refer to genes, but I suspect that this is largely due to the lack of a better terminology. In any case, continuing reference to “genes” does not obscure the fact that the early notion of clearly identifiable, particulate units of inheritance— which not only can be associated with particular traits, but also serve as agents whose actions produce those traits— has become hopelessly confounded by what we have learned about the intricacies of genetic processes. Furthermore, recent experimental focus has shifted away from the structural composition of DNA to the variety of sequences on DNA that can be made available for (or blocked from) transcription— in other words, the focus is now on gene expression. Finally, and relatedly, it has become evident that nucleotide sequences are used not only to provide transcripts for protein synthesis, but also for multilevel systems of regulation at the level of transcription, translation, and posttranslational dynamics. None of this need impede our ability to correlate differences in sequence with phenotypic differences, but it does give us a picture of such an immensely complex causal dynamic between DNA, RNA, and protein molecules as to definitely put to rest all hopes of a simple parsing of causal factors. Because of this, today’s biologists are far less likely than their predecessors were to attribute causal agency either to genes or to DNA itself— recognizing that, however crucial the role of DNA in development and evolution, by itself, DNA doesn’t do anything. It does not make a trait; it does not even encode a program for development. Rather, it is more accurate to think of DNA as a standing resource on which a cell can draw for survival and reproduction, a resource it can deploy in many different ways, a resource so rich as to enable the cell to respond to its changing environment with immense subtlety and variety. As a resource, DNA is indispensable; it can even be said to be a primary resource. But a cell’s DNA is always and necessarily embedded in an immensely complex and entangled system of interacting resources that are, collectively, what give rise to the development of traits. Not surprisingly, the causal dynamics of the process by which development unfolds are also complex and entangled, involving causal influences that extend upward, downward, and sideways.” (pp. 50-52)

Even something seemingly as simple as gender is far from simple. Claire Ainsworth has a fascinating piece, Sex redefined (nature.com), where she describes the new understanding that has developed. She writes that, “Sex can be much more complicated than it at first seems. According to the simple scenario, the presence or absence of a Y chromosome is what counts: with it, you are male, and without it, you are female. But doctors have long known that some people straddle the boundary — their sex chromosomes say one thing, but their gonads (ovaries or testes) or sexual anatomy say another. Parents of children with these kinds of conditions — known as intersex conditions, or differences or disorders of sex development (DSDs) — often face difficult decisions about whether to bring up their child as a boy or a girl.”

This isn’t all that rare considering that, “Some researchers now say that as many as 1 person in 100 has some form of DSD.” And, “What’s more, new technologies in DNA sequencing and cell biology are revealing that almost everyone is, to varying degrees, a patchwork of genetically distinct cells, some with a sex that might not match that of the rest of their body. Some studies even suggest that the sex of each cell drives its behaviour, through a complicated network of molecular interactions. Gender should be one of the most obvious areas to prove genetic determinism, if it could be proven. But clearly there is more going on here. The inheritance and expression of traits is a messy process. And we are barely scratching the surface. I haven’t seen any research that explores how epigenetics, microbiome, etc could influence gender or similar developmental results.

What and where is memory?

Memories May Not Live in Neurons’ Synapses
By Roni Jacobson, Scientific American

“If memory is not located in the synapse, then where is it? When the neuroscientists took a closer look at the brain cells, they found that even when the synapse was erased, molecular and chemical changes persisted after the initial firing within the cell itself. The engram, or memory trace, could be preserved by these permanent changes. Alternatively, it could be encoded in modifications to the cell’s DNA that alter how particular genes are expressed. Glanzman and others favor this reasoning.”

Mice Inherit the Fears of Their Fathers
By Virginia Hughes

“Now a fascinating new study reveals that it’s not just nurture. Traumatic experiences can actually work themselves into the germ line. When a male mouse becomes afraid of a specific smell, this fear is somehow transmitted into his sperm, the study found. His pups will also be afraid of the odor, and will pass that fear down to their pups.”

 

What do we inherit? And from whom?

Our parents don’t just give us our genetics. They also give us microbes. Add on top of that the factors of epigenetics and environment that our parents give us and it makes one wonder about the complexity of it all.

Microbes are fascinating. Our entire life is dependent on them. And they make up a large part of our body mass. They don’t just impact our health but also our moods and who knows what else.

Or consider parasites. There is the toxoplasmosis gondii parasite which can have major impact on mammalian psychology, at least for rats and humans. Like rabies, toxoplasmosis changes behavior of the infected in order to spread the infection to others. These little buggers literally control your mind. Conniving clever creatures!

This gives a whole other perspective to parasite load. Parasites are more common in warm regions. It isn’t accidental that some of the poorest countries are also the warmest, as their populations have higher parasite loads. This effects both physical and mental health, stunting development and lowering IQ, among much else.

We’ve barely even researched this area. Most microbes and parasites remain unstudied. We have no clue what they do, good or bad. Most of the genetic material we carry in our bodies isn’t human, and that isn’t even including RNA with its bacterial origins. That should give you pause.

Anyway, genetics are only around 2% of the human genome, the rest being so-called Junk DNA, but scientists have come to realize it serves other purposes. By the way, viruses living in us like to snip out pieces of our DNA and mix them up, just for shits and giggles.

What all of this might mean genetically and epigenetically (i.e., across generations) is entirely up in the air. We live in a fascinating time of ignroance and discovery. Genetic determinists can put that in their pipe and smoke it.

On a positive note, this inheritance isn’t fatalism, as much of it can be changed as an adult. In particular, it should be relatively easy to improve gut health. Just introduce new microbes. And new foods that they like. Be sure your microbes are happy!

‘The Diet Myth,’ ‘The Good Gut’ and ‘The Hidden Half of Nature’
By Sonia Shah, NYT

“Using the improved detection capacity of genetic sequencing techniques, scientists have discovered that 100 trillion microscopic creatures live in and on the body, influencing everything from the intensity of our immune responses and our moods to our dietary preferences and propensity to gain weight.”

‘Infectious Madness,’ by Harriet A. Washington
By Meghan O’Rourke, NYT

“Indeed, a handful of researchers are wondering whether mental illnesses are really caused by our immune system’s response to powerful microbial infections. As Harriet A. Washington reports in her new book, “Infectious Madness: The Surprising Science of How We ‘Catch’ Mental Illness,” some researchers in the field believe microbes may be responsible not only for clear-cut diseases like typhoid and tuberculosis, but also for mental illnesses such as anorexia, obsessive-­compulsive disorder and schizophrenia — but in a less tidy manner. As she reports, research has found that 10 to 20 percent of mental illnesses, including autism, are partly caused by pathogens.”

The Bouncing Basketball of Race Realism

There is a blog, Occidentalist, I’ve been occasionally commenting at this past month or so. The blogger, Chuck, is a race realist. He is fairly typical in holding a human biodiversity perspective, a semi-deterministic model of genetics. He is somewhat of true believer, but he occasionally expresses some niggling doubts about standard race realist beliefs. It is too bad he doesn’t take his own doubts seriously.

He also doesn’t take seriously some of the most interesting recent data. That is the strangest thing about this type of person. They are intellectual and knowledgeable to an extent, but they are committed to a particular worldview in a quite unscientific way. Science is used merely to express their certainty and so used selectively, instead of as a pathway of curiosity and learning.

I shared an analysis of some recent research that is paradigm-shattering (which I’ve previously posted about in my blog). None of the old theories can explain much of it, partly because it isn’t clear exactly what is in need of explanation, the unknowns being unknown. I highlighted one study in particular:

“Somehow, though, invisible influences intervened. With the scientists controlling for nearly everything they could control, mice with the exact same genes behaved differently depending on where they lived. And even more surprising: the differences were not consistent, but zigged and zagged across different genetic strains and different locations. In Portland, one strain was especially sensitive to cocaine and one especially insensitive , compared to the same strains in other cities. In Albany, one particular strain— just the one— was especially lazy. In Edmonton , the genetically altered mice tended to be just as active as the wild mice, whereas they were more active than the wild mice in Portland and less active than the wild mice in Albany. It was a major hodgepodge”

I made three basic points about this and the other studies:

1) We can no longer honestly claim percentage estimates about genetic vs environmental influence. It isn’t just that past research wasn’t controlling for all confounding factors. Genetic researchers are beginning to realize they don’t even know how to control for all confounding factors because quite a few apparently are unknown at present. We don’t even know how to attempt to disentangle these factors so as to isolate them all. More importantly, we can’t figure out how to separate genetics from the environmental background of this complex web of confounding factors.

2) It has typically been assumed that if researchers controlled for all obvious genetic and environmental factors it should lead to the same basic results. Slight variances are to be expected, but nothing to the extreme differences as found in that mouse study. It demonstrates possibly very minor differences, so small as to be presently undetectable, can lead to major alterations in end results. It demonstrates how powerful environmental conditions can be, even when they are being controlled for with the best methods researchers know how to use.

3) In the uncontrolled conditions of human lives, the environmental influences would be even more powerful. No human study of genetics has come even close to how well controlled this mouse study was done. Even most animal studies aren’t that well controlled. This relates to the issue of the poor quality of much medical research, specifically in terms of race realism.

His response was dismissal, as if it meant very little, just a mild curiosity at best:

“None of this is to say that epigenetics isn’t marginally interesting.”

Ho-hum… *yawn*… nothing interesting here, folks… just move along.

It was like he couldn’t even see it, not really. In his mind, it wasn’t there in some basic sense. He assumed he had seen it all before and so he didn’t need to look at this new data in order to take it seriously, because if he had seen it all before how could new data show him something he hadn’t already seen, right?

It wasn’t just about epigenetics. The study I highlighted brought up other issues about environmental conditions, confounding factors, and scientific controls. It challenges Chuck’s assumptions and conclusions at a fundamental level, and yet he could barely acknowledge what I had shared. He just went on repeating his same basic argument, like he has done a thousand times before.

I’m reminded of a social experiments about inattentional blindness, where focusing one thing makes people unaware of other things. One study had the subjects count the number of times a basketball was dribbled. While they were preoccupied, a person in a gorilla costume came out and began dancing where he was easily seen. When asked about it, most people didn’t remember a dancing gorilla, despite the extreme oddness of such an intrusion. It simply didn’t fit into the parameters of their focus of concern, the bounding basketball. Even if the subject was right about their claim of how many times the basketball bounced, they still missed the most interesting thing that was happening.

Race realists such as Chuck are like this. They share a lot of data that is correct, but the obsession about certain data disallows them from appreciating other data. They know what they know in great detail, and they often love to swamp discussions with a ton of data. The failure is that their knowledge lacks a larger context of understanding. Their opinions can never change, no matter the data, as long as they continue to narrowly focus on that bouncing basketball of race realism.