I never get more hate mail than when I discuss Autism and Asperger’s syndrome in my blog articles. For some reason people really get upset at the suggestion that these are not real diseases. Before you start raging at me, let’s be clear what I mean by “real disease”. I mean a disease that has an identifiable genetic and/or physiological manifestation. Being born without an arm is a real condition, being born with Down Syndrome is a real genetic condition. There are a huge range of conditions that we name because they share some related symptoms but we can’t figure out what causes them. Autism, Asperger’s, depression, allergies, asthma, obesity and many other conditions fall into the category of conditions we generally “treat” the same way but we actually have little or no idea what causes them, if they have a common cause or if some of them are even really diseases other than that we believe they are undesirable conditions. I have a few of them myself and I’d be happy to have them cured. Given that they all have in common a certain intractability to treating or discovering their causes, I personally believe that discussing them is a good idea.
These conditions have another interesting property in common, we are being diagnosed with them at an accelerating rate. One school of thought holds that we’ve always had these conditions in the same proportions but advances in medicine have made us more aware of them and ways of treating them. Another school of thought holds that environmental conditions, vaccines, pesticides, bacteria, viruses, or diet are exacerbating these conditions. Because of the complex nature of these conditions there is likely to be an element of truth to many of these ideas. But what if there is a more fundamental common cause?
An absence of natural selection on the human genome over time. It wasn’t long ago that infants died of mysterious causes with over a 50% probability. Autism has the weird property of being genetically heritable but not necessarily arising from parents with any family history of the condition. Suppose you have two genetically “healthy” adults in every known way with no family history on either side of Autism and they have an autistic child? The autistic child is found to have genetic mutations that differ from BOTH parents. How does this happen?
“One remarkable discovery made by Michael Wigler’s group while trying to understand the genetic basis of autism is that a fraction of the mutations associated with autism are not actually inherited from either parent. They are NEW mutations in the autistic child that arose in the sperm or the oocyte prior to fertilization. Identical monozygotic twins that separate after fertilization will both have the trait, the classical definition of heritability. Moreover, once the mutation arises, the affected child has a trait that can be passed on to his or her children, so it is indeed a heritable trait. However, classical genetic linkage studies rely on the assumption that virtually all disease-causing mutations are preexisting mutations inherited across many generations, and the finding of new mutations in autism violate that expectation. Human biology is a constant source of surprises.”
-Principals of Neural Science, 5th edition
The common wisdom on genetic mutations is that germline mutations between two healthy parents occur on average 1.5 times per infant. At this low rate of germline mutation the idea that modern healthcare is preventing natural selection from culling genetically defective “mutant” people is implausible, however as human life expectancy increases the germline mutation rate of male sperm has also been increasing dramatically.
““When we first reported that older age of fathers increases risk for autism, we suggested that mutations might be the cause,” notes co-author Abraham Reichenberg. “Genetic research later showed that this hypothesis was correct. In this study, we show for the first time that autism risk is associated with disparately aged parents. Future research should look into this in order to understand the mechanisms.” Dr. Reichenberg is a neuropsychologist and epidemiologist with the Icahn School of Medicine at Mount Sinai, in New York City.”
So for anybody who doesn’t try to stay current on the latest revelations in genetic research, this is a HUGE statement. Increasing human longevity combined with reduced infant mortality may be mutating the human germline at an accelerating rate! This is a fascinating new idea. If we comb the research in other areas of mysterious accelerating human medical conditions can we find any similar kinds of claims?
“We and others have reported that mutations in MC4R are found in 5%–6% of patients with severe early-onset obesity (55) and at a frequency of approximately 1/1,000 in the general UK population (56), making this one of the most common human monogenic diseases”
“Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder resulting from germline mutations in GNAS1 that decrease expression or function of Gsα protein. Maternal transmission of GNAS1 mutations leads to AHO (characterized by short stature, obesity, skeletal defects, and impaired olfaction) plus resistance to several hormones (e.g., parathyroid hormone) that activate Gs in their target tissues; paternal transmission leads only to the AHO phenotype (89).”
“Classical FPLD results from mutations in LMNA encoding nuclear lamin A/C (FPLD2), but recently some families with partial lipodystrophy and normal LMNA sequence were found to have germline mutations in PPAR (FPLD3).”
So here we have two entirely different genetic sources of obesity that result from germline mutations. But how common are these kinds of mutations?
” Furthermore, while the total number of DNMs increases at a constant rate for paternal age, the contribution from the mother increases at an accelerated rate with age. These observations have implications related to the incidence of de novo mutations relating to maternal age.”
So as we age our rate of germline mutations… those are mutations that become PERMANENT and HERITABLE to our children, is accelerating while the rate at which infant mortality may have formally culled genetic defects has declined 500% in 60 years resulting in an accelerating rate of heritable human genetic maladies concentrating in the population over time. That’s a crazy epigenicy sounding theory, let’s see if we can find some research on causes of crib death also known as SIDS to see what science tells us about WHY infant mortality has declined.
“When a sudden infant death does occur, it is important to search for genetic mutations;
Even though it is unlikely that one defective gene predisposes a baby to SIDS, genes may act in combination with environmental risk factors to result in SIDS.5 Predisposing factors could include polymorphisms in genes involved in metabolism and the immune system, as well as conditions that affect the brain stem and cause neurochemical imbalances in the brain“
…so crib death is often caused by mutations in genes involved with metabolism (Obesity) and the immune system (Asthma & Allergies) and genes that can cause neurochemical imbalances in the brain (Autism)? Now that kids with those new germline mutations are five times more likely to survive infanthood, they live to pass those mutations on to their kids. We appear to be in the process of producing generations of GMO children.
Before we continue let’s check the literature on Asthma to see if germline mutations play a role here?
“Genetics also fail to explain the sudden rise in allergies and asthma as even with significant selection pressure, any change in population genetics would necessitate multiple generations to occur. Epigenetic changes on the other hand can be induced much more rapidly with various environmental exposures and, like with genetics, these changes can be passed down from parents to offspring. There are several ways in which epigenetics can influence phenotype inheritance, including gene imprinting, in utero modifications and transgenerational inheritance.”
Hang on what are epigenetic changes? Those are a class of mutations that permanently affect the way a gene expresses itself. Chimps and humans are genetically 1% different but most of those differences are epigenetic mutations. Dogs and wolves are almost exactly the same species save for epigenetic differences. Note the statement that epigenetic changes can be INDUCED much more rapidly. What they are saying is that GERMLINE epigenetic mutations can be deliberately caused by environment pressures. Without digressing too much, specifically they have found that starving animals are more likely to pass on a germline mutation for obesity (increased fat storage) to their offspring. So not only can germline genetic mutations occur with age, germline epigenetic changes can be induced through environmental pressures and most remarkably… we have evidence the the organism can control them!
We’re all scientists here so let’s perform an amateur test on our crazy hypothesis. If germline mutations are at least party responsible for Autism, Obesity and Asthma… then they should have a high correlation to one another right? Let’s see what we can find in the literature!
“Asthma is approximately 35 % more common in autistic children; screening may be an efficient approach to reduce risk of morbidity due to asthma.“
…and ironically the author of this article hasn’t made the connection between germline mutations and Autism so the purpose of the research is to find ways to reduce the death rate for these individuals to increase their chances of passing their newly minted mutant genes on to their children.
Now let’s try Autism + Obesity.
“In children age 2 to 17 years, 33.6% were overweight and 18% were obese. Compared with a general US population sample, rates of unhealthy weight were significantly higher among children with ASDs ages 2 to 5 years“
It’s almost as though they are born fat!
Let’s pretend for the sake of discussion that all of this very formal scientifical analysis turns out to be true over time. In the absence of selective pressures our genomes are HERITABLY mutating at an accelerating rate causing us to suffer an accelerating rate of ambiguous hard to treat maladies. What does that mean for the human species?
- Do we need to increase infant mortality?
- Do we need to breed more with people from undeveloped countries with high mortality rates?
- Do we need to decide if it’s ethical to genetically screen our potential offspring?
- Do we need to decide if it’s ethical to correct germline mutations?
- Are germline mutations progress and should we just leave it alone and just buy more medications to treat it all?
- Are Autism, Asthma and Obesity now all really the same disease?
- Can I officially name the new disease Autobasthma?
- Where can I get an X-Men flight suit?
All thought provoking questions guaranteed to generate maximum hate comments on this blog piece. One last question… if it turns out that genetic mutations including germline mutations are DELIBERATE biological responses to stress then why would our bodies deliberately mutate to give us adverse diseases? In the scenario where genetic mutations are deliberate and biologically guided it would follow that mutation rates increase with age because as we age our immune systems have LEARNED more about how to survive in the current environment and can pass on that genetic wisdom to our offspring. We already know that the fundamental machinery of the human immune system is based on highly controlled systematic biologically governed mutation.
So why wouldn’t an immune system that is a genetic engineering machine try to mutate germline reproductive cells to pass on immunities learned by the parent? Knowing what we know now about how our immune system works it should almost be surprising to find that it didn’t pass on genetic mutations to our offspring to try to improve their survival. If conditions like asthma and allergies are the result of our immune systems getting hyper-sensitized to harmless environmental pathogens then a desirable systematic evolutionary process may simply be running amok in the absence of natural selective pressures to constrain it. Just as a bubble can’t be stable in a vacuum a species can’t remain genetically stable in the absence of selective pressures.
“Autistic Boy With Higher IQ Than Einstein Discovers His Gift After Removal From State-Run Therapy”
…and we have our first “autistic X-Man”
I got a call from a friend who founded a real-time genomics sequencing software company. He’s seen thousands of human genomes sequenced. He read my blog and reports that he sees 600-700 germline mutations per infant on average much higher than my text books reported 1.5. He says that he believes that many of the germline mutations appear to be the result of viral DNA contamination our cells accumulate with age. As we get older we get more viral debris in our genes and some of it gets passed on to our kids as germline mutations.