[Note: Shared for #AutisticHistory archive purposes. This is NOT An Autistic Ally.]
Autism a test case for genome research
By Faye Flam, INQUIRER STAFF WRITER
The Inquirer, philly.com
Tuesday, February 20, 2001
If all the hoopla is to be believed, the mapping of the human genome will lead to cures for everything from cancer to heart disease, diabetes, Alzheimer’s, schizophrenia and autism.
Indeed, the $3 billion Human Genome Project was promoted to the public with the promise that it would eventually help families like the Rizzos of Yardley.
The Rizzos have three sons affected with relatively mild versions of autism. John, 14, and 12-year-old twins Vincent and Danny all have experienced periods of odd preoccupation and isolation.
If the Human Genome Project (and its private competitor) is to fulfill the promise to alleviate human suffering, autism could be a test case – it’s a disease that strikes children and robs them of much of an entire life, rather than shaving a few years off the end.
It won’t be as easy as originally thought.
That’s because autism – like cancer, heart disease and most of the other big killers – is a so-called complex disease. It is caused by a complicated mix of multiple genes and environmental triggers.
It is theorized that autism, for instance, may be triggered by a type of food, a drug, exposure to a chemical, or an infection – all working in tandem with various genes.
Unlike single-gene diseases such as cystic fibrosis, hemophilia and sickle-cell anemia, there may be hundreds of ways to become autistic.
No cure has been found for even the simple genetic diseases. The challenges for curing complex ones such as autism are far greater.
Autism is a mysterious condition that many people first glimpsed in the movie Rain Man. The character played by Dustin Hoffman – like the Rizzo boys – had a level of autism that allowed him to function. Many others with the disease fare much worse: They are locked in an isolated world, unable to speak, compelled to flap their arms or endlessly repeat jingles from the radio.
With her children facing an uncertain future, Regina Rizzo wonders whether genetic research will eventually help – perhaps by leading to new drugs.
“My hope is that they’ll find something,” she said.
In fact, autism has attracted many researchers because it seems more clearly genetic than, say, cancer or heart disease. It ravages families, often striking two or three siblings.
“Scientists are driven by what they think they can tackle,” said Joseph Buxbaum, a geneticist at New York’s Mount Sinai School of Medicine who has moved on from Alzheimer’s to autism. Of the complex diseases, he said, “autism might be the easiest one to address.”
To connect genes to diseases, scientists undertake a kind of detective work, rounding up hundreds of families, drawing their blood, and looking for patterns of disease inheritance that match similarities they can read in DNA.
The Rizzo family in Yardley is part of the investigation, having given blood to a database of more than 300 families known as the Autism Genetic Resources Exchange. Researchers use the database to try to determine which genes are linked to autism.
What the genome projects did was to spell out most of the three billion characters of chemical code in the DNA of a small sample of humans.
Monumental as those efforts were, they did not figure out what each gene does. And because they analyzed the DNA of healthy people, the results by themselves say nothing specific about disease.
Autism runs in families, but not in the way it would if it were caused by a single-gene defect such as cystic fibrosis. In identical twins, about 60 percent share their autism, which scientists take as evidence of a genetic influence. And yet, in about 40 percent of cases where one twin has autism, the other, while sharing the exact same genetic blueprint, does not.
It is striking proof that genes do not determine everything.
Mount Sinai’s Buxbaum has scrutinized the DNA from members of several hundred families with two or more siblings who have autism, trying to figure out what genes the autistic children inherited that the others did not.
The human genome is broken into 23 chromosomes, each identified by a number except for the sex chromosomes, X and Y. Different researchers are focusing on different chromosomes.
Buxbaum is interested in a region on Chromosome 2. After a few years of investigation, he has found a stretch of DNA that appears to be inherited by autistic siblings more often than non-autistic ones.
In Toronto, geneticist Steve Scherer at the Hospital for Sick Children has identified another pattern on Chromosome 7.
To figure out which chromosome to start with, Scherer decided to examine unusual cases of autism – people who had a defect so obvious he could see it in a microscope. In some, he saw a chunk of DNA from one chromosome stuck on another.
Studying such special cases led him to look for more subtle genetic differences in that same region of DNA in other autistic people.
With a more detailed look at the DNA in his database of families, Scherer has narrowed the suspicious stretch on Chromosome 7 down to a region with 30 to 40 million characters of chemical code.
That’s where the genome projects come in. Only certain stretches of the huge lengths of DNA contain genes, and the genome mapping shows where these are. So Scherer can refer to a database to find which genes reside in his hot zone.
Using the genome project’s government database to supplement gene maps developed in his own lab, he estimates there are between 10 and 50 genes in that region.
Some of these genes may have a known function, perhaps production of a brain chemical. Others are unknown.
The next step will be to tie a variant of one of the genes that Scherer identifies to at least some cases of autism.
It is clear there will not be just one autism gene.
“Early estimates were that there were three or four genes involved with autism,” Buxbaum said. “If it were that few, we would have found them by now.”
Optimists say there are six to eight; pessimists, as many as 20.
Even if the scientists nab their autism genes, there is no certainty they can turn that into a treatment.
A genetic diagnosis at birth could, however, help children get special therapy early.
In one of the best-case scenarios, scientists could identify problem genes and develop a reliable genetic test – and find key environmental triggers. Then, babies testing positive could avoid whatever food, medicine, or other factors are linked to the disease.
But the real promise behind the genome is in new drugs, perhaps something that could make it easier for autistic people to cope. If that’s possible, it could take years.
Genes merely hold the code to make proteins. It is those proteins that actually operate the body – digesting food, fighting infections, sending signals through the brain.
Gene-based drugs work, in theory, by imitating the normal version of an abnormal protein. Gene therapy goes further, adding an engineered version of the gene so the body can make the protein itself.
In Bucks County, Regina Rizzo said that other parents of autistic children consider her lucky because her boys are less severely handicapped than most.
The oldest, John, now 14, was talkative and inquisitive at 9 months. He seemed precocious at first but started falling behind in kindergarten, both socially and academically. In grade school, he became so absorbed in various interests – fish, oceanography, weather, the planets – that other children lost patience with him. He is diagnosed with Asperger Syndrome, a mild version of autism.
The younger twins showed unusual symptoms earlier, especially Vincent, who was withdrawn, distant, and preoccupied as an infant.
Their academic performance has been spotty, although all three are now in regular classes.
Still, Rizzo is uncertain what the future will bring, and whether the genome projects will make a difference.
“If I peel away the layers between them and the world, there is some kind of gift – John with his creativity and Danny with his sense of humor and physical strength, and Vince has a way of bringing out the best in people,” she said.
“I don’t know what they’re going to do . . . but my hope is they’ll be able to take care of themselves, be happy and have someone to share life with.”
More With Cure Autism Now
Autistic people have fought the inclusion of ABA in therapy for us since before Autism Speaks, and other non-Autistic-led autism organizations, started lobbying legislation to get it covered by insurances and Medicaid.
ABA is a myth originally sold to parents that it would keep their Autistic child out of an institution. Today, parents are told that with early intervention therapy their child will either be less Autistic or no longer Autistic by elementary school, and can be mainstreamed in typical education classes. ABA is very expensive to pay out of pocket. Essentially, Autism Speaks has justified the big price tag up front will offset the overall burden on resources for an Autistic’s lifetime. The recommendation for this therapy is 40 hours a week for children and toddlers.
The original study that showed the success rate of ABA to be at 50% has never been replicated. In fact, the study of ABA by United States Department of Defense was denounced as a failure. Not just once, but multiple times. Simply stated: ABA doesn’t work. In study after repeated study: ABA (conversion therapy) doesn’t work.
What more recent studies do show: Autistics who experienced ABA therapy are at high risk to develop PTSD and other lifelong trauma-related conditions. Historically, the autism organizations promoting ABA as a cure or solution have silenced Autistic advocates’ opposition. ABA is also known as gay conversion therapy.
The ‘cure’ for Autistics not born yet is the prevention of birth.
The ‘cure’ is a choice to terminate a pregnancy based on ‘autism risk.’ The cure is abortion. This is the same ‘cure’ society has for Down Syndrome.
This is eugenics 2021. Instead of killing Autistics and disabled children in gas chambers or ‘mercy killings’ like in Aktion T4, it’ll happen at the doctor’s office, quietly, one Autistic baby at a time. Different approaches yes, but still eugenics and the extinction of an entire minority group of people.
Fact: You can’t cure Autistics from being Autistic.
Fact: You can’t recover an Autistic from being Autistic.
Fact: You can groom an Autistic to mask and hide their traits. Somewhat. … however, this comes at the expense of the Autistic child, promotes Autistic Burnout (this should not be confused with typical burnout, Autistic Burnout can kill Autistics), and places the Autistic child at high risk for PTSD and other lifelong trauma-related conditions.
[Note: Autism is NOT a disease, but a neurodevelopmental difference and disability.]
Fact: Vaccines Do Not Cause Autism.