Like many parents they had delved into the science of the disease when Clay was first born.  But there weren’t many answers and so much to do on a daily basis they never really got back to it.

“Most parents read what they can about autism in the beginning, when their child is first diagnosed.  Then you forget about the disease and just figure out how to deal with your child,” Marshall Bassett says.  “The causes of the disease had nothing to do with his daily reality.  We buried our heads in the sand.”

Last summer Clay Bassett died tragically and unexpectedly at age 14 and his parents did something they never imagined they would do: they donated their son’s brain to a tissue bank and became key players in the emerging field of brain research. 

“For all these years Clay was trapped by his brain, this brain that had failed him,” Marshall said.  “Maybe by donating the tissue we might be able to find out what was wrong.”

Clay was first diagnosed with autism at age 2 and a half.  The beautiful, seemingly healthy child had started life precociously, his first words coming early.  Then he lapsed into an eerie silence and developed an overpowering interest in flicking the lights on and off and holding his hands under a faucet to savor the sensation of water running over his fingers.

The parents were not, by nature, “head in the sand” types.  Marshall, a portfolio manager, had gone back to graduate school to prepare for a career in advanced finance.  Mary Clay Bassett is a pharmacist.  “Our goal was to make him functional,” Marshall said.  “The root of the disease didn’t seem connected to our daily struggles.” 

The couple embarked on a multi-state search for the best programs, the best teachers and the best therapists.  They focused on the how rather than the why.

“The only way we could deal with Clay was through education and therapy,” Marshall said.

They followed a routine familiar to parents of autistic kids: move away from a bad school district, fight with a new one and romance a third, their dreams haunted by dueling ghosts named “Miracle Cure” and “Irreversible Disintegrative Disorder.”

The hard work paid off.  Clay began to talk.  He overcame a morbid fear of getting his face wet and learned to swim.  Recently he learned to play the piano and sight read sheet music.  He had a special curriculum in the neighborhood middle school.

“He was different from many autistics,” Marshall said.  “He was extremely outgoing, liked people and people liked him.  He was a good kind person who sought very hard to please.  I can’t even begin to recount the joy he gave.”

He liked television and football and had recently converted to a fat free diet, ritually reciting the ingredients of every prepared foodstuff in the house. 

“He was normal in so many ways,” said his father, with a knowing chuckle.  “He loved football.  He had gotten interested in girls.  I don’t think he understood anything about sex, but we’d get these Victoria Secrets catalogue in the mail and he’d cut out pictures of the models and pin them on his bulletin board.  I don’t think he knew why he liked them, but he did like them.”

In August the family took a vacation in Algonquin National Park in Ontario and one day Clay and Marshall set off on a six-mile hike.  “The first half was uphill, the second half down, it wasn’t particularly exerting,” Marshall said.  “We were almost back to the car and he got dizzy and collapsed and went almost immediately into coma and died some hours later.”

Because of Clay’s age and the unusual nature of his death, an autopsy was ordered.  A final finding on the cause of death—which is believed to be linked to hyperthermia, despite the fact it was only 75 degrees the day of the hike—still hasn’t been reached.  The pathologist in Ontario retained a large amount of tissue, including the child’s brain.

Days later a friend gave the Bassetts a copy of a magazine story about NAAR and Marshall decided to get involved.  “I contacted them immediately to get the tissue donated,” Marshall said, “I hadn’t realized before just how valuable Clay’s brain might be.”
 

The Bassetts donated Clay’s brain tissue to the newly founded Autism Tissue Program, a joint effort between NAAR and the Autism Society of America (ASA) Foundation, designed to go to the core of the mystery disease. 

“Gross anatomy findings have been reported on less than about forty postmortem brains of people with autism, and the diagnosis is often in question.  Even fewer brain specimens have been studied with modern microscopic techniques,” said Jane Pickett, Ph.D. who heads the Autism Tissue Program.  “Compared with at least 3500 Alzheimer brains that number is low and hasn’t allowed for studies controlled for age and sex.”

The Unknown Disease
Clay’s brain, like that of all people with autism, is vitally important in the search for a cause and a cure.  Prior autism research has focused on behavior, and on genetic causes of the disorder.  But very little work has been done on postmortem tissue.  The early research is promising, uncovering fascinating signposts on the horizon that might point a way to an understanding of the how, why and wherefore of the disease that afflicts an estimated 400,000 Americans.
 

Scientists don’t understand the disorder.  Isabelle Rapin, MD, Department of Pediatric Neurology at the Albert Einstein College of Medicine and one of the premier physician-researchers in the field, watched my son Daniel bounce around her office seven years ago.  He ignored the toys, tugged at the venetian blind as his eyes drifted in and out of focus.  I had hoped she would say that an initial diagnosis from a doctor at Yale was wrong, that it wasn’t autism.  I hoped she would say his condition was something else that she could fix with a pill or a needle.

It was, of course, autism, and when I asked how and why this happened, she shrugged, with an apologetic look on her face.  “We don’t understand much about the brain,” she said in as soothing a tone as possible.

As the autism community looks for drugs to help, the pharmaceutical companies ask which part we want to fix.  We tell them we need to stop the tantrums, but we don’t know what causes them; we want them to restart the speech, but we don’t know why it stopped.  We want to stop the compulsions, the repetitive behavior, the self-stimulation, the retreat into a world our autistic relatives occupy alone.  The drug companies say politely that if we don’t know which part is broken, they can’t be of much help fixing the problem.

The Autism Tissue Program
A National Institutes of Health hearing in 1995 ratified what the autism community already knew: not only were there few answers about the cause of the disease, there was little or no hope in getting more answers because of the scarcity of ongoing or proposed research, and of funding.  Three parent-run groups, NAAR, ASA and CAN each tried to jump start the scientific community with money, political pressure and sheer force of will.

The key to brain research starts with examination of brain tissue.  Over the last several decades, researchers have made extraordinary progress in figuring out how the brain works, how neurons shoot messages from one part of the brain to the another, delivering instructions and retrieving memories.  Almost everything we know about the normal function of the brain has come from the “natural experiments” that occur when people suffer brain injury.  When a brain-injured person loses a particular function, researchers assume that the damaged area is involved in the lost function.  Then they can test this hypothesis by creating the same injury in an animal brain to see whether the same function is lost.

Less money is invested in autism research than in a variety of other diseases that occur with far less frequency.  Only recently did we grasp just how low it was. 

“After the 1995 NIH conference on autism, we realized the desperate need for tissue to drive research,” said John Maltby, chairman of the ASA Foundation.  “We started pursuing the possibility of getting involved.  At the same time NAAR was doing the same thing for the same reasons and last year we started a partnership.  What NAAR brings is scientific expertise.  What we bring is a membership list of more than 25,000.”

The collaboration, called the Autism Tissue Program, is being run out of New Jersey by a former Princeton researcher, Jane Pickett, Ph.D.  The goal is to develop a steady flow of new tissue to allow researchers to test hypotheses and embark on new ones.  The program has joined with the renowned Harvard Brain Tissue Resource Center, which will receive, process and store tissue and pass on samples to qualified researchers.

Researchers say that by dissecting and studying the brains of autistic people they may be able to find physical clues to unlock the mystery.  Is it a physical deficit in an area that controls speech?  Is there miswiring in the elemental brain stem that would indicate the condition develops soon after conception? Are there links to seizures and other conditions common to people with autism or are they merely coincidental?  Do the changes that take place in the brain over time help plot a course to a cause?

New state of the art breakthroughs allow scientists to peer directly into the brain and to study tissue for minute defects that have only been identified in the past several years.  These new techniques make the need for tissue all that much more pressing.

“If we had started a national awareness campaign 10 years ago, we’d be a lot farther along the road,” said Pickett.  “And to have so little brain tissue to study today is heartbreaking because of the new technology.  We have the tools, we just need the tissue.”

Researchers hope to link biological findings to behaviors.  “What we want to do, over a long period of time is bring to the study of the brain a clearer picture of what the person was like in life so we can relate the anatomy to the symptoms,” said Maltby. 

In other words, there is hope that the Tissue Program will allow researchers to identify not just specific genes or pathological conditions present deep inside the brains of people with autism, but which conditions create each specific type of abnormality.

Beyond linking anatomy and behavior, doctors are also interested in younger specimens that might exhibit evidence that becomes lost or hidden in later years.  Researchers can make discoveries like Margaret Bauman’s finding that the brains of autistic adults are different from the brains of autistic children only if they have brain tissue from children to examine.  Children like Clay Bassett.

The Problem
The program is discovering the most difficult challenge is acquiring tissue.  While other organ donation programs can tug heartstrings with a promise of a life for a life because they involve transplants, the tissue program offers only the hope of unspecified scientific breakthrough in the distant future.

“It’s a difficult thing, but what we are asking parents is, when the worst imaginable thing has happened, to make a phone call for that donation,” said Pickett.  “We are talking with parent groups and just now formulating the most effective way to make that plea.”

There is no polite way to say it: the only place to get brain tissue is from someone who has died.  And because of the nature of the disease, chances are the patient will have died an untimely death.

“In other kinds of tissue research, we’d be starting out with a population aged 50 or 60 and up,” said ASAF’s Maltby.  “With autism we are starting with a population mostly under 40.  Diagnosis of older individuals may never have been properly made, the syndrome itself having only been isolated 50 years ago and not widely used until much more recently.”  While middle-aged and elderly people with autism are out there, we don’t know who or where they are.

Because most diagnosed autistics are young, the request for donations must focus on parents, who might have more difficulty making such a monumental decision than other relatives.

“We were able to donate only because Clay’s tissue had been preserved by the medical examiner,” Bassett said.  “After the death, we weren’t thinking about research, we were thinking about boxing him up and taking him home to be buried.”

Magnifying the suddenness of the process is the need to move quickly.

Harvard says that the ideal transfer time—post mortem interval or PMI—is 18 hours for fresh specimens that will reveal the most information.  Samples that take slightly longer, or that have been properly preserved like Clay’s, are also important.  Pickett said prolonging life support, which is sometimes done to preserve other “donateable” organs, doesn’t work because those techniques do not preserve brain tissue.
 

With slower diseases, the process is somewhat easier.  Take Alzheimer’s patients, for example.  They are involved in a long degenerative process that allows guardians time to carefully consider the donation procedure.  The success of Alzheimer’s tissue programs is starting to pay off: scientists believe they are close to discovering methods to slow or block the ravaging progress of the disease (unfortunately the type of damage discovered does not match that found in autism).

The spiritual nature of the human brain also makes potential donors skittish.

“For reasons I can’t quite articulate donating the brain is much more sensitive than other organs,” said Nancy Richardson, Executive Director of COSAC (the New Jersey Center for Outreach and Services for the Autism Community) and the mother of a 26 year old autistic.  “I know that I will participate and I know it is important; we are dedicated to discovering the cause.  I am just not comfortable.  It may be that the brain is the seed of life.  The heart is essential, but that’s different.  It’s horrible to think about, but it is important to donate.”

Pickett has scheduled focus group sessions at COSAC to understand better how to minimize parents’ unease about donation.  They will discuss religious tenets and taboos as well as superstitions and practical questions like whether an open casket is possible after brain tissue donation (the answer is yes).

“We offer technical information, explaining how and why procedures are done,” she said.  “We have a brochure entitled ‘Research Takes Brains’ that spells it out.  I suppose there is a bit of superstition involved.  By not considering things like post mortem donation maybe we lull ourselves into forgetting about the inevitability of death.”

NAAR and ASAF will decide how best to contact the families of potential donors early on.  One proposal is to have them sign up much like the uniform organ donor donation program run by many state motor vehicle departments (Pickett says that the Autism Tissue Program requires that brains be the primary donation rather than part of multiple organ donation because, while other organs can be kept functioning and “alive” after death, the brain starts to deteriorate immediately).

Since there is no central registry, the closest thing to a reliable census of autism patients are the rolls of the Autism Society of America.  “Initially we didn’t have much money to donate to this research, but we do have a membership list of 25,000,” said ASAF’s Maltby.  “We can provide access.  Hopefully we will be able to increase the research 10 fold in a matter of years.”

Cause or Cure
Obviously the long-term goal is to identify the cause or causes of the disease and then turn attention to finding a cure or mitigation.  “We don’t know how long it will take to understand autism in a biomedical sense.  Research takes time,” said Pickett.  “But there are possible short-term benefits if genes are identified or neurodevelopment is better understood.  We hope that the combined efforts of neuroimaging, genetic and tissue research will guide us to more effective treatments for individuals with autism now and for generations to come.”

Given the genetic nature of the disease, there is a personal motive to donate brain tissue for most parents of autistics, who hope to be able to block the disease in their grandchildren, nieces and nephews.

Beyond that, knowing the cause is personally important.  All parents of autistic people suffer periods of self-blame and guilt.  Specific information will better allow us to confront those feelings head on.

“If Clay had been 10 years older some bastard would have told me it was my fault he was autistic because we were uptight, anal retentive types who didn’t nurture him enough or that Mary had one glass of wine during pregnancy and that was the cause,” said Marshall Bassett.

All parents who have spent countless midnight hours reciting the mantra “why, why, why,” staring at the bedroom ceilings or licking their wounds after yet another explosive tantrum, will benefit from solid information.

“I donated his brain because I wanted something to come out of this horrible experience of having my 14-year-old son die in my arms,” Bassett said.  “I hope that in five years I get a call from somebody in NAAR who says we’ve made some breakthroughs and Clay’s brain tissue was instrumental.  That would be good.  If the study of his brain helps spare parents and children what you and I and others have gone through, that would be a wonderful thing.”

Like with most people with autism, a large portion of my son Danny’s brain works fine.  He was multi-lingual until nearly four-years-old, fluent in English, Spanish and the Philippine language Tagalog.  He had a smattering of Cantonese and had picked up a string of embarrassing English language epithets his war correspondent father brought home from the jungles.  We would show him off like a sideshow display, switching effortlessly from language to language like a United Nations translator.  Then, it went away and he no longer speaks anything.  He will follow instructions in any of those languages, but does not verbally respond.

Several years later we were at a swimming pool with friends when Danny dragged himself out of the water.  His bathing suit was drooping and I shouted, “Hey Danny, you’ve got plumbers butt.”

He turned and smiled, then pulled up his suit.

A friend, who had long said he believed our claims that autism was a communication rather than cognitive problem, was amazed.  “That was a complicated transaction,” my friend said.  “Danny just translated an enormous amount of information and acted on it.  He recognized his name, he got the joke and responded appropriately.  There really is a lot of stuff going on in that brain of his.”

Yes, there is.  And we all hope that research studies made possible by the Autism Tissue Project will help get that “stuff” out.

Jim Mulvaney headed a team of reporters at the Orange County Register who won the 1996 Pulitzer Prize for Investigative Reporting for their year long probe of a California fertility clinic.  Mulvaney, a former foreign correspondent who has reported on wars, elections, coups and crises from more than three dozen countries on four continents, is currently completing a novel.  He lives with his wife, the author Barbara Fischkin, and their sons, Danny and Jack in Long Beach, NY.