We like simple things in the modern, digital world, white or black, 0 or 1! Autism is either the fault of the mother or poor genetics. But both are false! the idea of the mother’s fault was born in the mind of a twisted psychologist, which has no scientific basis, if only because the syndrome “is born” during pregnancy. It is interesting to note that this aberration still has sme influence in countries with a Vatican Catholic tradition; among Protestants and other Anglicans, she did not live long; we will have to examine the relationships between politics, religion, the extreme right and paternalism to understand this aberration!
For genetics, the facts are just as stubborn. Despite hundreds of mutations identified and suggested to be linked to autism, in most centers there are very few autistic children with a genetic mutation. To decide that X% have a genetic cause – ranging from 15 to 80% depending on the mood of the moment – our geneticists rely on a false statistical approach, a combination of analysis of DNA fragments and/or homo or di-zygotes. These 2 approaches are valid if and only if certain conditions are met, but they are not. Just an example – to combine DNA fragments and analyze them (known as GWAS technique) and decree that X% of children are of genetic origin, the fragments must be independent of each other (we cannot mix in one statistical analysis of interconnected elements). However, we have no idea if these elements are connected or not, not knowing what they encode, we cannot therefore decree that they are independent. Furthermore, these elements must be independent of the environment. However, we can only control the environment in animals raised in batteries or plantations, not in humans. As a result, the conclusions are subject to important limitations. Therefore, the clinical predictive values of genetics in autism are very limited.
Let us repeat it out loud once again, man is a social animal, very influenced by the environment. Autism is born in utero and elsewhere; as we have shown recently, we can identify 96% and approximately half of babies from birth who will not be autistic or will be autistic later, based solely on maternity parameters normally collected in all maternity wards in France and from Navarre, without any genetic information. A plethora of extra or intra-environmental factors increase the incidence of autism – intrauterine inflammation, bacterial or viral infections, pollution, pesticides, acute stress, obesity, and heart problems etc. Furthermore, saying that DNA is everything is outdated since epigenesis – this mechanism which controls the actual expression (or silencing) of genes – plays a major role and is also transmitted over several generations. In other words, a pathological event occurring during pregnancy can be transmitted over several generations without any modification of the DNA! In summary, forgetting that man is above all a societal animal leads us to ignore the importance of parental relationships, of school, in short everything that attenuates and corrects the misfortunes of nature and makes everything depend on bad luck. genetic, without possibility of correction. All this fits well with the policy, it is the fault of bad chances and not of pollution or the conditions of maternity.
Therapeutically, saying that autism is genes and synapses is a bit short. Almost all brain diseases involve synaptic alterations and a synapse consisting of hundreds of proteins and complex regulatory mechanisms, this is not an exploitable precise target for developing a treatment. To treat, we need to identify precise targets and we are far from that. Out of 289 clinical trials listed in US.Trials.gouv – the Mecca of clinical trials – we learn that there are 289 clinical trials on autism underway, none of which has a genetic basis. And for good reason, because the major criticism of genetics for treating patients is that it is a rigid vision, one (or more) mutations directly linked to the syndrome as if nothing else was happening in utero. However, the characteristic of the brain is its extraordinary dynamism and plasticity. An image of the brain at time T is no longer valid a few minutes later and even more so when it comes to an embryo, where everything changes at great speed. We and many others have shown that an event pathological produces a cascade of modifications which are ultimately the final cause of the disease and a potential target for treatments – and not the inaugural event. There is no direct link between the initial cause (the mutation for example) and its consequences.
The treatment must concern these modifications and therefore on the therapeutic level, the mutation is of little interest, it just allows us to test hypotheses in animals which will or may not be validated in humans and which in any case, knowing the extraordinary heterogeneity of the autistic syndrome, will only concern a few children at best. We must return to developmental biology, and rather than still looking for mutations, try to understand what these modifications are that are generated by the inaugural pathological, environmental, or genetic event. Developmental biology, the main approach that will help us understand and treat Autism.
