A Personal Aside
I have been thinking a lot lately about why it was exactly I got into science and have been pursuing an academic career. I thought I would take the effort to collect my thoughts here in case my ramblings prove helpful for anyone else.
It is actually rather simple to explain why I am in science. To be perfectly blunt, it is the culminated experiences I have had with my late twin brother Kyle who was autistic. My future scientific directions and decisions in life are shaped by what time I had with Kyle, and particularly by his death.
Reader’s Digest Intro to Kyle
Despite the world telling me different, I never felt that Kyle was broken. We watched Monty Python’s Flying Circus and Mr. Bean together, we went to movies together, he was my partner in crime whenever I wanted to misbehave as a child-and always willing to take the blame. In short, he was my little brother and best friend, nothing less than an integral part of me.
Important for this discussion, Kyle was never developed spoken language, he first learned to sign, then he got a facilitated communication device, basically a large keyboard with a speaker that would either let him spell things out or else he could push preprogrammed keys to speak phrases. Very rapidly he progressed beyond the canned functions and the touch talker-as we called it-was just set so Kyle could type. In fact, Kyle was such a good typist that in high school he showed an aptitude for medical transcription, since he could type fast enough to keep up with the tape, but also never misspelled words.
Relatively early in life we learned another thing about Kyle. Like me and my father, Kyle was a voracious reader. We always thought he was just scanning through pages of magazines and newspapers to look at the pictures or else stim (visually self stimulate), but he was in fact reading them. We found this out one day when there was an interesting article and we caught him slowing down just enough we could see his eyes scanning the page as he was reading. Basically, we caught him being just like the rest of us. He was clearly intelligent, just not able to speak.
When it came to school, Kyle was actually better than the normal kid. He sat in class with his laptop taking notes. He actually loved school and loved learning. He enjoyed his history classes and was easily able to pull B+’s and A’s in classes that were known as valedictorian killers. To be frank, I never saw him happier than he was walking in the hallways and heading into his classroom for another session.
This love for education was so profound, that when I left for college Kyle had a very hard time because he was not allowed to come attend school with me (We withheld 1 grade unit so he did not officially graduate from high school-this was the only way he would remain eligible for adult school from ages 18-22). Since he could not go to college, Kyle developed an interesting learning strategy: he watched educational TV all day on the local PBS station. He also started to start typing entire chapters of Utah and US history textbooks we had around the house, and then answer the questions at the end of each chapter. He found a way to keep learning regardless. To this day I regret Kyle not going to college with me. I feel that we forcibly held him back and never let him achieve his potential-and it haunts me, I think it always will.
Fast forward 14 years. Out of nowhere Kyle was admitted to the hospital with acute kidney failure and dangerously variable blood pressure. His lungs aspirated. Long story short, his last few days were spent on dialysis and Propofol/Morphine anesthesia surrounded by family as we impatiently awaited results from the pathology lab that would only finally arrive a month after his death. The doctors kept recommending we let him linger, just in case something was learned from the pathology report that never arrived, but we knew it would have only protracted Kyle’s Purgatory. So we let him go…
While in the hospital, behind my family’s back I contacted the lab I was going to do postdoctoral work in to donate Kyle’s brain. My only thoughts were that he was highly functional, no history of long term epilepsy aside from two seizures we knew about, and really intelligent. In the end, his organs were shot as they were highly infected, but his brain and his eyes went to scientific research with people I trust.
Kyle’s final gift to the world was the knowledge we can gain from studying his eyes and his brain. This is the only comfort that came from his untimely death.
Experience Guides my Life Choices
One of my early memories was having a research team from UCLA and the University of Utah come to my house to administer the autism questionnaires to Kyle and me, give all the members of my family some cognitive assessments, and take blood samples for genetic testing. The early results of these studies are collected in these papers, as well as Here, Here, Here, and Here. The most tragic to me is this one because Kyle died while it was in press. His datapoint is in the wrong column, by less than a month. This paper suggested that individuals with autism die early, of at best poorly understood reasons.
Obviously, having early experiences with a bunch of researchers playing brain games with me, letting me watch and ask annoying questions as the phlebotomist collect blood samples, and being able to read science papers in which I was a research subject was nothing short of spectacular. By the ripe old age of 10, I had made it through the two banker’s boxes of research papers my mother kept in the basement about autism. To be sure I did not understand it fully, but I was hooked. It was also about this time I decided wanted to become a neurobiologist; primarily because that was the term that the team leader of this research (Dr. Edward Ritvo) used to describe himself in one of his editorials in which he proposed studying the “neurobiology” of autism rather than as a purely psychological disorder.
At the same time as I was learning about autism from reading these papers, I was spending a lot of time immersed within the autism community in Utah. My brother was attending what was then called the Children’s Behavioral Therapy Unit (CBTU; Now the Carmen B. Pingree Center for Children with Autism) in Salt Lake City and my mother was working there. I had the opportunity to go in at times for “peer” and “sibling” training so I could learn how to help my family manage my brother’s behavioral outbursts as well as so they could learn about how autism in the family affected the nonautistic siblings. My mother also took charge of numerous summer programs to help the local autism community. This generally meant that I got to play with autistic kids and teens in the summer. In doing all of this, I spent a lot of time with kids with autism and their families. As a result, I have an odd sort of kinship with the autism population.
As stated above, I never saw these kids as broken, but rather as just different. Some of them, admittedly, did have crippling behavioral problems and epilepsy, but these seemed to be trivial to their potential, which was rarely achieved. What I did come to notice at these times was the culture of doctors trying their hardest to help these kids be normal by giving them experimental drug treatments. Kyle was even briefly on Pondimin, but my parents decided to discontinued treatment when he became thin as a rail and had a personality change-having Kyle be the Kyle we loved was more important than normal or typical social behavior. This lesson stuck. I wanted MY Kyle, not a perfectly behaved little robot for a brother. Over the years I have interacted with autistic children on lithium, other antipsychotics, barbiturates, steroids, among many other unproven off-label drug regimens. Every time I see this I want to grab the families and shake some sense into them and then go smack the doctors. I don’t do it because I truly understand the sense of helplessness these families feel, they do not see anyone helping, so they see grasping at straws (in this case experimental therapy) as the only logical move.
Why I Do What I Do
So, primarily because of my life experiences with Kyle, I specialize in the experimental analysis of behavior in animal models. More to the point, I develop experiments and collections of experiments that are specifically intended to be used as preclinical drug screens. This is explicitly so the mouse can become sufficiently useful that it never again becomes necessary for doctors to be required to use antipsychotics, barbiturates, or diet drugs as potential off label cures or treatments for autism, or any other disorder for that matter. I want to help give the families and doctors legitimate options.
It is my sincere hope that some of these behavioral outcome measures are useful not to help drug companies make the new miracle drug, but to remove the ineffective ones from reaching clinical trials. If a drug does not show a cognitive benefit that outweighs any side effects using a battery of tests specifically designed to be clinically relevant, then the rationale for moving forward with the compound is removed. Then we can all move on and design a better option.
I have avoided autism as a model in which to do this work for a few reasons 1) I am too close. I cannot be dispassionate or impartial to the results, so I may skew them unintentionally or get invested in a particular outcome. And 2) there is a new best or more complete mouse model for autism every 30 seconds it feels like. I don’t like moving targets so I have avoided that one. However, these reasons do not keep me from studying everything around autism. I have spent a lot of time studying Fragile X and related disorders as well as Down Syndrome, and I have worked at the MIND institute in Sacramento. What I have been noticing is that increasingly, the Fragile X field and the autism field are using each other’s outcome measures, so perhaps my early experiments in Fragile X may prove useful for autism work moving forward.
I also have chosen an additional focus in neuropathology. This was partially by accident, but I have always wanted to know what was different about Kyle’s brain and mine, and this seemed a good enough reason as any to move into this field. One of my first forays into neuropathology was actually a research rotation wherein I did a pilot experiment to assess any differences in microglia in the hippocampus of post mortem autism cases compared to no autistic control cases. I later moved more toward the Fragile X direction, but always keeping my periphery open to autism related cases.
After Kyle’s death I have become angry. I am angry at the researchers trying to cash in and overhype whatever incremental “breakthrough” they have made. I am tired of advocate groups trying to shove useless bullshit and pseudoscience down the throats of families that have so little hope that they will follow any advice from an authority figure. And I am angry at the medical profession for forgetting that autism is something they have to consider in designing treatment options, both for brain or non-brain related disease. And I am sick and tired of society treating people like my brother as if they are broken. They aren’t, we are just too stupid to understand them, so we are unable to extend them the olive branch they so desperately need…
And I am furious with science in general for missing the point. We are not in science to cure anything. I say this because we cannot actually cure autism without knowing about it first. We have to uncover some of the essential truths at the heart of autism before we can even presume to treat it. We have to study both verbal and nonverbal autistics, low and high functioning autistics, and we have to study the entire population, not just a few select individuals that are easy to study and will sit still for a half hour during an fMRI experiment.
Honestly, it has been some time since I have actually seen a true basic science paper studying autism. Basic characterizations are spun as revolutionary ideas begging for therapeutic application. Experimental results are patented before publication and spun off into companies on nothing more than a whim and a prayer. Controversial theories entirely unsupported by fact are announced as gospel truths on the gravitas of authority; and are subsequently used to do cause harm to autistics under the guise of compassion.
And then all I do is I sit by and watch it happen. Right now thinking of this is frankly pissing me off. If all I have the power to do is to emphasize the good autism-related science on this blog and try to kill and discredit overblown, poorly interpreted studies via twitter, that is what I am going to do. I am done with sitting on the sidelines like an enraged fan screaming at the top of my lungs at a team that has long since stopped listening…
Now is the time for me to get involved…It is time for me to make the difference I have always felt compelled to make…My first step is to figure out how I am going to do it.