I remember the early days of the International Society for Autism Research (INSAR). Back then the congress had only a few hundred people in attendance. Participants seated at a table for lunch usually knew each other. It was that time of the year when I had the opportunity to catch up with old friends. Now, I miss not being able to see again my congress buddies Isabelle Rapin and Hans Bogte. They are sorely missed. Without them, INSAR has lost part of its luster.
INSAR’s early meetings were attended by a high ratio of senior researchers as compared to junior ones. Over the years the meeting has grown, emphasizing international participation and bringing on-board a new group of young investigators. Now, at Montreal (2019) there are over 2,000 participants, most of them young and making their first presentation in what hopefully will be a budding academic career. Accommodating so many researchers has provided for a breathtaking view of autism from many different perspectives. Practically anything has been the object of study. However, although bringing knowledge to the field and looking at problems from different perspectives is generally a good thing, there is a dark side to the story.
People at INSAR are generally drawn to the large plenary presentations. Indeed, a few speakers are given the opportunity to publicize their findings to the larger audience. In these cases, a big auditorium is provided so that people can attend and receive some pearls of wisdom. I had the opportunity to attend a few of these presentations. Contrary to many attendees that were seemingly in rapture with the lectures, I was thoroughly depressed and concerned about the direction research is taking in regards to autism.
One of the plenary presentations discussed the speaker’s efforts in using animal models and neuroimaging as a way of parceling subtypes within the autism population. The speaker did a good job in cautiously expressing himself and being receptive to the sensitivities of autistic individuals. The science involved a large swab of collaborating institutions, fellows, animal work, and MRI time. I think the series of studies that he presented accounted for several million dollars worth of research money. The pity for me, is that I considered the efforts not more than a high school science fair project. It reminds me of the joke about the drunkard looking for his car keys under a lamp post even when he had lost the same blocks away. “Did you lose your car keys here?” No, but the light is much better here”.
This particular study cherry picked the regions of interest that were measured in the study. It eliminated some areas for which there are no homologies when comparing mice and human brains. Indeed, in humans the main area involved in autism research has been the dorsolateral prefrontal cortex. There is no similar cortical area in the brain of a mouse. Similarly, many of the cells that have been incriminated in the pathophysiology of autism (e.g., double bouquet cells, mirror neurons) are absent in rodents. It seems that this research project started by eliminating the areas that we would like to target in autism research! I have to believe that the investigator, like the drunkard looking for his car keys, pursued this line of inquiry because he could conveniently study mice in the laboratory setting. Unfortunately, this was not the only deficiency of the studies he presented. It appears that a “ground truth” had never been established in their studies. Different anatomical areas are measured with varying sensitivities. The cerebral cortex being quite thin and having shadowy borders may be more difficult to measure than the bulbous protrusion of the basal ganglia that has excellent contrast with its surroundings. This being the case, we could expect a lot of variability in measurements of the cerebral cortex that could wash away differences as compared to the basal ganglia. Lastly, I don’t like research that ends in a period. I prefer a question mark. By this I mean, that research should give rise to questions to be pursued by the investigator. If there are areas of the brain that the investigator claims may be abnormal, I would like to know the nature of this abnormality. Unfortunately, this would require using techniques outside the zone of comfort of the researcher. After many years of publishing his results, the researcher had yet to report on a single study that could clarify the nature of his findings. I have to guess that pursuing a line of research that could disprove his precious findings would not be a profitable endeavor for his laboratory.
Another researcher of international reputation directed a panel of presentations studying transcriptomics in postmortem research. The researcher was looking for genetic markers in autopsied tissue. After a few years of studies, and lot of invested money, the researcher was keen in publicizing his results: the pathology of autism resides in the microglia! This cell type, the microglia, plays a supportive role within the central nervous system. It has a role in tissue repair and forms part of the immune defense of the brain. Microglia are usually activated after the brain has suffered an insult (e.g., lack of oxygen, deprivation of glucose). However, in autism these cells are activated, not because of the primary diagnosis (i.e., autism), but because of a common comorbidity; that is, seizures. This has been the object of many studies and debates which were not taken into account by this panel of investigators. It appears that knowledge in one field (i.e., neuropathology) does not migrate to others (i.e., genetics). History turns on a dime! Genetics has just discovered a well known artifact of neuropathology. Researchers appear to work in silos, applying their own technique regardless of adequacy. Indeed, the investigators in the panel, and in recent publications in prestigious journals, have not controlled for seizures and other preagonal/agonal conditions that could account for the findings. It is well known that about one third of autistic individuals suffer from seizures and about two thirds of them have EEG abnormalities. In many cases, the autistic patient may not even know he/she suffers from seizures!
Each of these lines of research will drag forwards spending an ever-increasing amount of money. This expenditure is wasteful and misleading. It confuses the literature, gives support to more useless research, and may even mislead researchers into ill-thought therapeutic attempts. It is a pity that funding organizations emphasize primarily publicity driven research, large multi-institutional endeavors, and costly ventures at the expense of good science. I follow a dictum that research worthy topics are those that make a difference in the quality of life of patients and parents- in the now, not in generations to come. This is our responsibility. Present research is becoming a burden on our future generations. Even if looking for a cause or a cure is presently beyond our reach, how about tackling those problems that are likely to snowball through the lifetime of autistic individuals? Why not target dental hygiene, the importance of exercising, the need for adding fiber to the diet, or literacy? These are problems that can change the lives of patients. But alas, I did not see this happening at INSAR this year. What I did perceive is that it is a good time to be a mouse! INSAR researchers will spend countless time and money trying to rescue deficits in mice regardless of how generalizable the results may be to humans. I am sure that mice appreciate all of INSAR’s research efforts.
Those interested in more insights into autism research can read:
Also, please read my personal perspective on Autism Speaks and the value of its research efforts: Autism Speaks, Redefining Initiatives and the Zika Virus
Let me know your opinion in the comment section. Thanks!