About the Banner
The banner above is intended to represent the nexus of three broad areas of current research into the causes and treatments of autism spectrum disorders (ASD).
The left photo represents chromatin, massively folded and bundled strands of RNA, DNA and proteins present in the nucleus of each of our cells, that guide the cell's growth, function, and death. It is here, where our genes are housed, that researchers are detecting patterns of genetic mutations that are related to an individual's risk of developing ASD. There are estimated to be at least 500 genes related to autism risk. What's more, these genes appear to be in areas of our genome that are both highly mutable and essential to human evolution.
The center photo alludes to research revealing that, for some children, a distinct physical pattern of brain development associated with autism is forming even during the second and third trimesters of pregnancy. The photo also alludes to the influence of the environment in which the potentially autistic child is immersed, beginning at conception and perhaps continuing through early life.
The rightmost photo brings us to one of the most important conclusions of recent clinical research. Namely that now, based on the above two points, early detection of ASD is of prime importance. For the autistic child, an earlier age of first detection is crucial to administering treatments that might arrest, or at least mitigate, the further development of ASD conditions.
Autism: A Lesson in Anthropogeny?
Mid last year (2012) CARTA1, the Center for Academic Research and Training in Anthropogeny, announced an upcoming symposium entitled "Human Origins: Lessons from Autism Spectrum Disorders."
The Oct 5, 2012 symposium brought together an international group of researchers noted for their work in autism and other closely related areas. What's new is the approach that autism researchers are now using. It is part of a growing trend, since at least the early 90's, of applying the principles of biological evolution directly to the study and treatment of human diseases. This new trend in medical research is called evolutionary medicine2.
In other words, autism is being studied with respect to things like genetic mutations and the affects of environment on the growth and development of the human fetus and child. However, in this symposium as the title implies, these researchers came not so much to report on autism itself, but rather specifically to illuminate an understanding of human evolution in the light of autism research. This is very exciting stuff for those absorbed with the questions of where we humans came from and how we got here.
What is Autism?
In a nutshell, autism is not a disease. Clinically, according to researchers Daniel Geschwind and Jonathan Sebat, it's a neurodevelopmental syndrome. It's defined by onset prior to age 3 and involves difficulty in social interaction, impaired ability to communicate, and the presence of repetitive and restricted behavior. These are the core behaviors diagnostic of autism.
But, besides the core behaviors, there are other impairments and effects in varying degrees and combinations that may or may not also be present. These show, importantly, the extreme heterogeneity of the syndrome that must have confounded early researchers. A more full discussion can be found on many autism Internet sites such as Autism Speaks which states "ASD can be associated with intellectual disability, difficulties in motor coordination and attention and physical health issues such as sleep and gastrointestinal disturbances. Some persons with ASD excel in visual skills, music, math and art."
The Early Diagnosis of Autism: Examinations of Behavior and Brain
Karen Pierce, Director of Clinical Research and Functional Brain Imaging at the UCSD Autism Center of Excellence, is focusing her research efforts on identifying and detecting the early signs of autism in children from 1 to 3 years old.
Because autism is presently diagnosed through observing a child's behavior, says Pierce, 40% of cases of autism, according to a recent CDC study, aren't being diagnosed until age four. This is too late in terms of brain development. As Pierce explains, we're all born with about all the neurons in our brains that we're ever going to have. During the first years of life the brain is busy selectively building the necessary mass of connections between our neurons for our brains to function normally. If these connections are not being arranged in the normal patterns, then the time for treatment is during the building of these connections while the patterns of connections might still be influenced by experience.
Dr. Pierce employs a fascinating technique that relies on advanced technology and involves the precise tracking of eye gaze. In eye gaze measurements, scenes are presented to a child and the child's eye movements are tracked as he or she looks over the scene. Both the exact spot in a scene that a child is looking at and the time he looks at it can be measured. Although this is still diagnosis by observation of behavior, it can be applied to children at one year of age.
In the actual eye gazing measurements diagnostic of autism, the child sees two images side by side. One image is of another child who is shown moving about a bit and looking into the camera. It has been well known since the 70's that even newborn babies have a preference for looking at the human face. It's something we're born with, usually.
The other image presented is of a developing geometric pattern like many screen-savers we've all seen and probably have stared at vacantly. The bottom line is that what we would call normal children spend the majority of time staring at the images of children while autistic children, not all but some, spend most of their time staring at the changing geometric patterns. And so this is potentially a very powerful way to detect at least some cases of autism early in life when something might be done about it.
The other technical advance measures patterns of brain activity in young children, even in newborns. Functional magnetic resonance imaging, or fMRI, is a non-invasive safe way to peek in on a sleeping baby and produce a map of brain activity that is in response to language stimulus.
Simply put, a sleeping child is placed in the fMRI machine and is fitted with a presumably comfortable headset. At times a story is told to the baby in native language words and at other times nonsense, non-word, verbal sounds, such as a recorded story played backwards, are presented to the baby's ears.
The brain's response to these sounds is found to be in the side lobes of the brain known as the superior temporal gyri (one gyrus on each side of the head). Not surprisingly, this is the part of the brain near the ears. The human brain normally uses the left gyrus, on the left side of the brain, for language, and so when the baby is hearing actual language, as opposed to nonsense sounds, the left language area is active, and this is detected in images of the typical brain. In the ASD brain, however, the left right laterality is not the usual. Autistic children can show a markedly different pattern of activity in response to language.
Nature, Nurture and Psychoanalysis
Before getting into the details of autism's place in human origins and evolution, it's worth a look at the history of the diagnosis and treatment of ASD, which has had its share of controversy. If, as Jonathan Sebat says, autism has been with us from the beginning, then our modern awareness of autism symptoms is some kind of re-discovery, or perhaps some kind of cultural reclassification, or, as is the case with the increase in cases of adult onset diabetes, a cultural shift in how we live.
How did the ancients regard autism and what, if anything, did they do about it? These things we must continue to wonder.
The modern study of autism got off to a conflicted start. Leo Kanner, who is credited with being the world's first child psychologist, in his seminal 1943 paper3, described autism as a syndrome, a set of identifiable specific behaviors (alluded to above) that occur together. To his credit, he didn't assign these children to nondescript categories, such as retarded or disturbed, but rather recognized ASD as a unique condition with perhaps specific causes. His was a modern approach.
Kanner concluded in this paper, "We must, then, assume that these children have come into the world with innate inability to form the usual, biologically provided affective contact with people, just as other children come into the world with innate physical or intellectual handcaps [sic]." Clearly he anticipated a biological, as opposed to a simple environmental, basis for ASD. For an interesting review, see Fischback, SFARI.
On the other hand, Kanner also stated his observation that often the parents were cold and preoccupied. He wrote, "One other fact stands out prominently. In the whole group there are very few really warm hearted fathers and mothers." Eventually, Kanner went on to develop this parental aspect of the situation even to using the term 'refrigerator mother'. He appeared to blame parents for at least not being able to care about their affected child. This second, refrigerator mother4, hypothesis is the really hurtful part and perhaps the first blunder in the modern story of ASD.
Is ASD hard-wired or acquired?
And so what ensued was a nature-versus-nurture debate of the type popular at the time. A related debate I remember as I entered college was whether humans had any instincts at all or were we all born as clean slates, the 'tabula rasa' hypothesis. Were we born with preconceived ideas and goals, or were we taught everything, from language to sexual orientation, only after being nurtured in the real world of experience?
With regard to the origin of autism, the 'nature' side began arguing for an innate deficiency, as Kanner put it, while the 'nurture' side of the debate began arguing for a so-called psychogenic origin. That is, under the psychogenic hypothesis, ASD was supposed to be a behavioral disturbance of psychological origin (e.g. caused by bad parenting) rather than of organic or genetic, that is to say biological, origin. And, given this psychogenic origin, it was supposedly treatable using the then very popular Freudian psychoanalysis5.
In fairness to Kanner, notwithstanding his coinage 'refrigerator mother', he likely did not mean that parents caused ASD but that their lack of bonding with the child contributed to the child's condition. In retrospect, he may simply have been observing the inevitable confusion, hurt and emotional withdrawal of some parents and their inability to deal with it. I would bet that if he were alive today he would say, "God, I wish I hadn't said that!."
Enter, now, Bruno Bettleheim who popularized the refrigerator mother hypothesis and made it the basis of his treatment program for autism. A regrettably severe aspect of Bettleheim's treatment was the complete separation of the ASD child from the parents, whom he blamed for the child's autism. He applied his therapies in his institutional setting where the children then lived in complete separation from their parents.
Bettleheim was enormously popular in his time in child psychology and well respected despite the presence of low level grumbling and misgiving especially on the part of parents and siblings. But, he was supposedly the expert. My wife, who studied early childhood education in the early 70's, remembers his theories being taught in her classes.
The psychogenic interpretation was eventually rejected, as was Bettleheim's work and theories. Meanwhile, the pain caused to parents by the refrigerator hypothesis was enormous and unjustified. Bettleheim's methods were eventually exposed as unscientific and not founded on real data.
In 1964, Bernard Rimland, founder of the Autism Research Institute and the Autism Society, wrote a book6 that debunked the refrigerator mother hypothesis and argued that ASD was in fact a neurodevelopmental disorder. His book contained a supportive foreword by Leo Kanner who sounded very relieved that some one had finally constructed a solid theory in which progress could be made. A side conclusion that one could draw without it having been said was that Bettleheim had been a quack. For a heart breaking exposé on this aspect see the documentary video Refrigerator Mothers.
And what of the great nature-vs-nurture debates? Clearly Bernard Rimland's showing ASD to be a neurodevelopmental disorder means that ASD may have a genetic basis, as researchers are finding, and at the same time may also be related to environmental influences, perhaps even chemical exposure such as to maternal medications or infant immunizations. And that seems to be the level of debate in society at large today.
In modern terms the more correct paradigm is not nature-vs-nurture but something more like nature-and-nurture. Or, more to the point, the whole nature/nurture conceptual dichotomy simply may not make sense anymore. Geschwind's concept, as we will see, is of a still more complex system that integrates genetics and environment into a functional whole. Fortunately, complexity is something that we are increasingly able to deal with given modern methods, computational power and a growing research literature.
So, what is it about human evolution that autism should have something to do with it? To understand this relationship, we need an overview of human evolution and an overview of the relevant points of our genetics. This section discusses some of what I think is understood about our origins and in the next section I'll give my impression of genes and how they work.
Three Time Scales
Behaviorally Modern Humans
When anthropologists talk about human origins, they may be talking bout a time going back some 200,000 years. This is thought to be around the time when anatomically modern humans, Homo sapiens that look like us, began to evolve. It's back when other humans, different from us, like the Neanderthals, Homo neanderthalensis, lived in Europe and West Asia.
Within this, the period from 100,000 to 13,000 years ago is particularly interesting as it offered very severe challenges to our survival due to rapid and wide changes in climate. These climate changes are thought to be big drivers of our evolution, an evolution that was played out in terms of the natural selection of genetic endowments that survived and were passed down the generations to us.
It also contains the disappearance in the fossil record of the Neanderthals, at about 30,000 to 40,000 years ago, and the subsequent rise of our species as the only remaining kind of human save some now extinct populations of Homo erectus and Homo floresiensis in East Asia.
This period is also very important with regard to autism. Anthropologists look at this time as the one in which behaviorally modern humans evolved. That is, the times when humans began to act and think like us moderns, and to develop modern languages and display our human psychology especially with regard to social skills.
Tools Using Humans
Sometimes paleoanthropologists talk about human origins as going back to the earliest members of the genus Homo, which is about 2.3 million years ago. In this period, our ancestors were walking fully upright and, as early as 2.5 million years ago were using stone tools. At least about a million years ago, they were using fire to cook food and then went on to develop the heat-treatment of rocks and wood for better tools. (I think it probable that the heat treating of rocks led to the discovery of smelting metal ore and eventually led to the metal ages of history.)
Presumably they were also sitting around campfires and creating new and increasingly complex ways of socializing, like story-telling and myth making. Today, we regard humans as hypersocial, meaning that this is one of our most specialized and radical adaptations. (Consider, for example, my favorite comedian Lewis Black telling jokes to an audience of thousands at Carnegie Hall. Almost 3,000 people are listening to just one man talk. At various times they all convulse and slam their hands together in synchrony. This just does not happen elsewhere in the animal kingdom.)
The early humans during this period were also working out better and better models of how nature works and how to develop and use knowledge. They were also beginning to spread themselves far and wide creating networks of communication and trade. The social and analytical parts of brains were expanding over the generations.
The Big Split
And other paleoanthropologists study the period going back to the separation of the line of animals that leads to us from the line that has led to modern Chimps and Bonobos. That's about 6.5 million years ago. Our line, for whatever reasons, began to walk more upright, freeing the hands and allowing their use for more things. Let's speculate; less tree swinging and more tool using and gathering, less toothy, more brainy. But pretty much the mark of our new line is upright walking and more time on the ground. Somehow, perhaps as a result of these changes, and most importantly, it meant growing brain size with growing mental abilities, especially sociality.
For two good books on paleoanthropology see first Origins, Human Evolution Revealed7, for a well written and spectacularly illustrated introduction to all the relatives you never new you had. Next a textbook Introduction to Physical Anthropology8 is for a more rigorous and professional orientation.
It's In Our Genes: People Really Do Need People
Andrew Meltzoff said in his presentation The Puzzle of Social Cognition: The Other Minds Problem, "In the typical developmental case, there is a fundamental connection between people, a social connection that already exists at birth." This "like me" theory, as Meltzoff calls it, sometimes goes by the name of Theory of Mind9. It refers to the ability of each of us, from birth, to recognize others as being "like me" with thoughts, feelings, beliefs, intentions and so on.
We are born with the beginnings of a "theory", as it were, of other people's minds. Even at 1 year old, says Meltzoff, babies understand "when others act like me, they have inner states like me."
Babies are then quick to imitate others. If you have children, you know that a child's capacity for imitation is almost unlimited. We imitate others and, as we grow, put that imitation along with our own experience to arrive at our own behavior.
Children with ASD show a lack of ability for imitation, perhaps indicating that the autistic child is not using others as a model of self to accelerate learning, according to Meltzoff.
What Do Genes Actually Do?
I remember being taught in school that genes were a kind of blueprint, a set of plans for building an organism. But that was a gross over-simplification and not really accurate. (Who was it who said, "We think we explain it better when we get it a little bit wrong"?) Genes are made of Deoxyribonucleic acid, DNA, and make up only some of the genetic message that we pass down from generation to generation. It's much more accurate to say that DNA determines the response of the biological cell to its environment, a less specific but truer statement.
To my way of thinking, the fundamental unit of life is the cell. According to paleontologists, life in the form of bacteria was present on earth by about 3.5 billion years ago10. Bacteria are small single cells with a limited repertoire of behavior. By about 1.5 billion years ago, another more complex and more talented type of cell evolved from bacteria11. These were the eukaryotes, the type of cell that makes up our bodies. We are eukaryotes. The special thing about the eukaryotic cell is that it has a nucleus where the DNA is housed and attended to by the nuclear machinery of the cell. Eukaryotic cells are the building blocks of all multi-celled animals and plants.
Each cell of our body contains the same genetic message. We are, in effect, a giant colony of 100 trillion eukaryotic cells all with the same DNA message12. Our cells are so very smart that they can become any one of about 200 cell types: liver cells, nerve cells, skin cells, bone cells, and so on. How do cells with identical DNA decide what kind of cell each of them will become?
Cells talk to each other and essentially decide amongst themselves which will do what. Each gets the message somehow about which genes to turn on and which to turn off. The environment in which a cell finds itself determines what the job of that cell will be. Throughout development, cells are responding to each other through chemicals and proteins that they make and exchange. They may also respond, sometimes with tragic results, to substances that come to them from the wider environment. The bottom line is that development from a fertilized egg to an individual is a process in which cells are both producing and receiving chemical messages. It's a cell-community development responding to the environment. It's not a building to blueprint.
The cell nucleus is, essentially, a reading and writing machine, among other things. It reads strands of DNA to get the basic recipes for what the cell is supposed to do in life. And it can, when ready to reproduce itself, write out a whole copy of its DNA to pass on to the next generation. Thus, DNA is a kind of writing, a record of recipes, that gets copied and passed on. The catch is that the copying is not perfect. An offspring can have too many or too few copies of one or another gene or genes. These are called copy number variations, or CNVs. Also, changes can be made to a single point in the DNA message. These are called single point mutations, or SNPs (for single nucleotide polymorphism, pronounced 'snip'). Furthermore, a SNP or CNV can arise for the first time in one of the parents sex cells, the sperm or egg. These are called de novo mutations because the parents body cells do not have this mutation. It's brand new. These DNA changes can be useful, neutral, or harmful. Furthermore, de novo CNV's are prevalent in cases of autism and schizophrenia.
All life that we know of on Earth is based on essentially the same system of genetics and inheritance. Presumably we therefore inherited our DNA from the earliest forms modified through a long series of adaptations and innovations, that is, evolution. You may have heard that humans and chimpanzees have 98.8% the same DNA. We also share about 60% of our DNA with bananas. (I don't know which sounds more discouraging.)
A Higher Level or Organization: Cells Build Humans
It's seems miraculous indeed that these tiny cells, though brilliant and talented as they are, can come together and make a vastly more complex animal like me. My cells, through their development according to my DNA and environment, can construct in particular my brain. But do they determine my thoughts? I think not. I have legs too, that developed in due course, but I'm sure my DNA does not decide where I will walk on any particular day. The complex process of development, as describe above, decides the shape and use of my legs, the fact that I walk upright like a human, and all the physical capabilities I have inherited, but not where I shall walk.
I think it's the same with my brain. The structures and workings of my brain was decided upon by my brain cells interacting with each other and their environment. Those structures determine the capability for all kinds of typical human thoughts, emotions, and desires. But DNA does not determine which particular thoughts I will have in response to, say, a solar eclipse. Just as my physical legs determine how I must walk, my structured brain determines how I will think.
I think it is possible to see now, given a little reflection, how it is that people are different from one another. Our cells have slightly different DNA to start with, and we have been immersed in different environments. Also, there can be changes in our DNA that our parents didn't have. And some people can be noticeably different, as in autism.
Both thinking and running, and all other human actions, are at a level distinct from that of the cell. As smart as cells are, not one of them is "aware" of what I'm thinking or where I'm going, though their actions are indeed the very substance of my thought. Our lives emerge from the lives of our cells. We have DNA only because each of our cells have "our" DNA.
There's another level that should be mentioned to complete the picture that I'm trying to paint. As a human being emerges out of the lives of trillions of cells, a population of humans emerges from the lives of individual humans. And again there are emergent properties that don't exist in any individual but are characteristic of only groups. For humans this next level of organization is society, social thinking supported by evolved brain structures. We are hyper-social beings because, over all our past generations, changes to our DNA have been selected for, through a long evolution, that has brought more and more involuntary unconscious functions into consciousness and social control.
Looking at the spectrum of human behavior, it's easy to conceive of a spectrum of social behavior in which autism, the faltering of social interest and function, is but one extreme. Another extreme of sociality might be an over-active social nature such as hearing voices that aren't there, or uncontrollably fearing beyond reason imagined evil plots by others.
Next in Part II
In the second part of this article, we'll get further into some specific genetic mutations as Jonathan Sebat talks about the genetic etiology of autism and points out its relationships to human evolution. From there we'll look at the systems approach to understanding the interplay of genetics, environment and even behavior and culture, presented by Daniel Geschwind. And finally, I'll attempt to present the ideas of Bernard Crespi who presents a spectrum of human behavior that makes sense in terms of our underlying genetics so that we can begin to perceive the deeper meaning of our differences and of human evolution.
CARTA is located at the University of California,
San Diego, UCSD. I recommend visiting the CARTA site for the
best in videos of seminars on important and fascinating topics in anthropogeny.
These seminars are always presented by many of the world's
best known and prolific scientists. You can also find these videos and many more on
CARTA's primary academic focus is to "explore and explain the origins of the human phenomenon" by answering two questions. First, where do we come from? And, second, how did we get here? These two themes are not very far from the three questions posed by French artist Paul Gauguin in the title to his painting, "Where do we come from? What are we? Where are we going?" I imagine this painting was done on the island of Moorea looking across Cook bay at Mt. Rotui.
2. Probably the best known example of evolutionary medicine concerns the increasing anti-biotic resistance of important disease causing bacteria, such as the newer drug-resistant strains of tuberculosis. Another example: Scientists are now studying the roots of dental and gum diseases by following the evolution of the bacterial communities inhabiting the human mouth since the beginnings of agriculture 10,000 years ago.
- Stearns, S. C. (2012). Evolutionary medicine: its scope, interest and potential. Proceedings of the Royal Society B. 279: 4305-4321. Read it
- Adler, C. J., Dobney, K., Weyrich, L. S., Kaidonis, J., Walker, A. W., Haak, W., ... i Cooper, A. (2013). Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions. Nature Genetics. Doi: 10.1038/ng.2536. Read it
3. Kanner L., Autistic disturbances of affective contact, Nervous Child 2, 217-250 (1943) Read it
4. "Refrigerator Mothers paints an intimate portrait of an entire generation of mothers, already laden with the challenge of raising profoundly disordered children, who lived for years under the dehumanizing shadow of professionally promoted 'mother blame'." Quoting from the linked Website.
5. It would be difficult to overstate the popularity of psychoanalysis and Freud's influence in society at large. Freud's theory was thought of as a great scientific achievement, perhaps as great as Einstein's theory of relativity. See, for example the 1945 Hitchcock movie Spellbound, which begins with "Our story deals with psychoanalysis, the method by which modern science treats the emotional problems of the sane." Eventually much of psychoanalysis was debunked as unscientific by the philosopher of science Karl Popper. Popper showed that much of the clinical application of psychoanalysis was in fact meaningless.
6. Rimland, B., (Kanner, L., M.D., Forward), Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior, Prentice-Hall 1964
7. Palmer, Douglas, Origns: Human Evolution Revealed, Mitchell Beazley, 2010
8. Jurmain, Robert, Kilgore, L., Trevathan W., Introduction to Physical Anthropology, Eleventh Edition, Thomson Wadsworth, 2008
9. The first use of the term "theory of mind" is credited to David Premack and Guy Woodruff who used the term to describe the ability to impute the state of mind of oneself and others. Nowadays people loosely call this mind-reading, understanding what's in some one else's mind.
- David Premack, Guy Woodruff, Does the Chimpanzee have a theory of mind? Behavioral and Brain Sciences, Vol 1, Issue 04, Dec 1978
- Josep Call, Michael Tomasello, Does the chimpanzee have a theory of mind? 30 years later, Trends in Cognitive Sciences Vol. 12 No. 5, Cell Press
10. Schopf, William J., Major Events in the History of Life, Jones and Bartlett, Boston 1992
11. Margulis, Lynn, Origin of Eukaryotic Cells: Evidence and Research Implications for a Theory of the Origin and Evolution of Microbial, Plant, and Animal Cells on the Precambrian Earth, Yale University Press, New Haven, 1970
12. 10 Facts about cells on About.com. Read the Article
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