Friday, June 29, 2007

Vaccines and autism: stop betting on the horse that always loses

Many people believe in things for which there is no evidence. A smaller, but still large, number of people believe in things for which there is not only no evidence, but for which there is great evidence to the contrary. Immunization as a cause for autism is one of those things ...
Why there's no dispelling the vaccines-cause-autism myth. - By Arthur Allen - Slate Magazine

.... People who study irrational beliefs have a variety of ways of explaining why we cling to them. In rational choice theory, what appear to be crazy choices are actually rational, in that they maximize an individual's benefit—or at least make him or her feel good.

Blaming vaccines can promise benefits. Victory in a lawsuit is an obvious one, especially for middle-class parents struggling to care for and educate their unruly and unresponsive kids. Another apparent benefit is the notion, espoused by a network of alternative-medical practitioners and supplement pushers, that if vaccines are the cause, the damage can be repaired, the child made whole. In the homes of autistic children it is not unusual to find cabinets filled with 40 different vitamins and supplements, along with casein-free, gluten-free foods, antibiotics, and other drugs and potions. Each is designed to fix an aspect of the "damage" that vaccines or other "toxins" caused.

"Hope is a powerful drug," says Jim Laidler, a Portland scientist and father of two autistic boys who jumped ship from the vaccine conspiracy a few years ago. In reality, autism has no cure, nor even a clearly defined cause. Science takes its time and often provides no definitive answers. That isn't medicine that's easy to swallow.

Another explanation for the refusal to face facts is what cognitive scientists call confirmation bias. Years ago, when writing an article for the Washington Post Magazine about the Tailwind affair, a screwy piece of journalism about a nonexistent attack on American POWs with sarin gas, I concluded that the story's CNN producers had become wedded to the thesis after interviewing a few unreliable sources. After that, they unconsciously discounted any facts that interfered with their juicy story. They weren't lying—except, perhaps, to themselves. They had brain blindness—confirmation bias.

The same might be said of crusading journalists like David Kirby, author of Evidence of Harm, a book that seemed to corroborate the beliefs of hundreds of parents of autistic children, and UPI reporters Dan Olmsted and Mark Benjamin (the latter now with Salon).

Systems of belief such as religion and even scientific paradigms can lock their adherents into confirmation biases. And then tidbits of fact or gossip appear over the Internet to shore them up. There's a point of no return beyond which it's very hard to change one's views about an important subject.

Then, too, the material in discussion is highly technical and specialized, and most parents aren't truly able to determine which conclusions are reasonable. So they go with their gut, or the zeitgeist message that it makes more sense to trust the "little guy"—the maverick scientist, the alt-med practitioner—than established medicine and public health. "History tells us that a lot of ground-breaking discoveries are made by mavericks who don't follow the mainstream," says Laidler. "What is often left out is that most of the mavericks are just plain wrong. They laughed at Galileo and Edison, but they also laughed at Bozo the Clown and Don Knotts."

And to be sure, there was some basis for suspecting vaccines several years ago, before definitive studies had discounted a link. When the first vaccine theory was proposed in 1998, it appeared in the prestigious British medical journal Lancet and was published by an established London gastroenterologist, Andrew Wakefield. Two years later at a congressional hearing, Wakefield and an Irish virologist, John O'Leary, announced they had found measles viral RNA in the guts of autistic kids with severe bowel problems.

The air of respectability fell away over the years as we learned that Wakefield had serious conflicts of interest (including a 1997 patent application on a measles vaccine to replace the potentially soon-to-be-avoided MMR shot) and that a subsequent publication on measles RNA was probably an artifact of false positives, a common problem in polymerase chain-reaction technology.

The thimerosal theory emerged in a different context. The Centers for Disease Control and Prevention, concerned about cumulative mercury exposures in young children, asked manufacturers in 1999 to phase out thimerosal-containing vaccines. In other countries, such as Denmark and Canada, thimerosal was removed because of new vaccine combinations that either didn't require thimerosal or would be damaged by it. Nowhere was thimerosal removed because of evidence of harm.

But the first CDC study of children's exposures to thimerosal-containing vaccines was difficult to interpret. And anti-mercury activists jumped on the transcript of a 2000 meeting at which the study was scrutinized to argue that something improper was going on. The transcript shows no such thing. But the activists unleashed a public-relations campaign alleging a government and "big pharma" coverup.

That, in turn, proved to be eye candy for environmental groups already enraged by the Bush administration's enlistment of former industry officials in the squashing of environmental regulations. Anti-pollution lawyer Robert F. Kennedy zealously jumped on the thimerosal bandwagon in an "expose" published in Salon and Rolling Stone.

No surprise there. What editor or writer doesn't want to "reveal" that drugmakers and the government conspired to poison a generation of innocent kids. (Kirby's book won a 2005 Investigative Reporters and Editors award.) Where's the passion in the story that some public-health bureaucrats quietly moved to blunt a danger that turned out to be nonexistent?

In the pre-Internet days, the parents of an autistic child living in a small city might have found a handful of other parents in their predicament. Now, they instantly find thousands online. The denominator—healthy children—has disappeared. This is a good thing if you're looking for answers. But the answers may not be good ones. Joined together on the Internet, these actors create a climate of opinion that functions as an echo chamber for conspiracy dittoheads. Even the women's division of the Methodist Church has gotten in on the act, presumably on the grounds that it is fighting for social justice by decrying mercury poisoning, although there was no mercury poisoning, and social justice would be better met by promoting confidence in vaccines.

Kennedy, who wrote blithely in the Huffington Post during the trial that "overwhelming science" had confirmed the link, continues to believe it. So does Rep. Dan Burton, R-Ind., whose circuslike hearing room aired many such claims. Neither cites any solid studies, because they do not exist...
It makes no sense to keep doubling down on the three legged horse that's finished last in the past twenty races. It's long past time for the hard core loyalists to bet on a a new nag.

Years ago it was arguably reasonable to look for a connection between thimerasol and autism, or immunization and autism, but those days have passed. Now it's a waste of precious time and precious energy. Every week brings new insights into cognitive disorders of every kind, including parts of the diverse collection currently labeled "autism" -- that's where we should put our effort.

Wednesday, June 27, 2007

A treatment for Fragile X syndrome?

Even if this were a perfect treatment, which is very unlikely, it would ordinarily be 10 years away from being available for human use. It's also not a treatment for "autism" (a term of limited clinical value), but the news is still quite exciting. If the results hold up it represents a breakthrough in our understanding of Fragile X syndrome, a relatively common cognitive disorder.
BBC NEWS | Health | Autism symptoms reversed in lab

... US scientists created mice that showed symptoms of Fragile X Syndrome - a leading cause of mental retardation and autism in humans.

They then reversed symptoms of the condition by inhibiting the action of an enzyme in the brain.

The study, by Massachusetts Institute of Technology, appears in Proceedings of the National Academy of Sciences.

Fragile X Syndrome is linked to mutation in a gene carried on the X chromosome called FMR1.

It can cause symptoms ranging from mild learning disabilities to severe autism.

The researchers, based at MIT's Picower Institute for Learning and Memory, targeted an enzyme called PAK which affects the number, size and shape of connection between brain cells.

They found that inhibiting the enzyme stopped mice with Fragile X Syndrome behaving in erratic ways.

Prior to treatment they showed signs of hyperactivity, purposeless and repetitive movements.

Further analysis showed that not only were structural abnormalities in connections between brain cells righted, proper electrical communication was restored between the cells....

...People with Fragile X Syndrome have more dendritic spines than usual, but each is longer and thinner, and transmits weaker electric signals.

Blocking PAK activity in the lab mice corrected these abnormalities.

Researcher Dr Susumu Tonegawa stressed that the mice were not treated until a few weeks after symptoms of disease first appeared.

"This implies that future treatment may still be effective even after symptoms are already pronounced," he said.

Professor Eric Klann, of New York University's Center for Neural Science, agreed that the research was potentially significant.

He said: "This is very exciting because it suggests that PAK inhibitors could be used for therapeutic purposes to reverse already established mental impairments in fragile X children."
If it does work in humans with Fragile X, it may be that it has to be used quite early for substantial benefit. The absence of any other treatment, and the theoretical potential to alter the course of the disease, means researchers will push this along faster than a typical drug candidate.

Saturday, June 23, 2007

Configuring a simplified OS X computing environment

Gordon's Tech: OS X and Mac Mini tutorial and configuration guide is about an update to a guide I published a while back. It may be of use to anyone configuring a system for a user with visual or other disabilities.

Wednesday, June 20, 2007

Some varieties of "autism" may be related to neuroligins

This is quite preliminary, but it smells like something worth tracking. Note that some neuroligin mutations have also been associated with schizophrenia.
BBC NEWS | Health | Protein mutations link to autism

Scientists have discovered how mutations in two key proteins may lead to autism.

They have shown one protein increases the excitability of nerve cells, while the other inhibits cell activity.

The University of Texas team found that in normal circumstances the proteins balance each other out.

But the study, published in Neuron, suggests that in people with autism the balance between the proteins is knocked out of kilter.

The findings back the theory that autism involves an imbalance between excitatory and inhibitory connections between nerve cells...

...The proteins - neuroligin-1 and neuroligin-2 - create a physical bridge at the junction - or synapse - of nerve cells, enabling them to make connections with others...

...Neuroligin-1 was associated with excitatory connections and neuroligin-2 with inhibitory connections.

When they introduced a mutant form of neuroligin-1 thought to be carried by some people with autism the number of synapses fell dramatically - and the cells became significantly less excitable...

... carrying a mutant form of neuroligin-1 may depress the number of synapses that make it into adulthood....
The neuroligins are very likely to tell an interesting story ...

Sunday, June 17, 2007

Perverse incentives in education, youth baseball and health care

I help coach my older son's baseball team. He's been able to do pretty well in this relatively laid back mainstream league; he's not a star but he is a competent performer. It's been a great experience, but now we've moved up a level.

In this level there's real competition, including a "championship series". So what's the best way to coach a team to contention? Teams are supposed to be relatively balanced, though experienced coaches can game the system. Assume, however, that players really are randomly assigned. Every player has to go up to bat, and every player must play in the field roughly the same number of times a game (though positions are not rotated - the best players go to pitching, catching, 1st base, etc).

There are two approaches, the hard way and the easy way.

The hard way is to focus on each child's strengths and weaknesses and make them the best ball player they can be. Teach them to play as a team and have fun. Teach the fundamentals and develop strategies to work around fixed weaknesses, such as the child who can't field or throw.

The easy way, of course, is to eliminate the weaker players. There are numerous ways to do this, and most of them don't require any conscious effort. The easiest by far is to simply pay less attention to the weaker players, and not to make any extra efforts to help them work past frustrating circumstances. Focus resources instead on keeping the stronger players happy...

In no time at all, the weaker players will be gone, and the stronger will survive. Since every player bats, this can have a dramatic impact on scoring. Eliminating 1-2 players can make a team much stronger.

This is, of course, the method that Texas school districts used to meet their educational mandates when George Bush was governor. They eliminated the weakest students and raised their academic averages.

This behavior is not limited to youth baseball coaches or school teachers. Physicians will soon become expert at it. Medicare is shifting physician reimbursement to be based on "performance". There are several ways to "perform". The hard way is to improve the quality of care. The easy way is to encourage non-performers to move to someone else's practice. There will usually be some naive idealist who can be encouraged to collect all the non-performing patients.

Oh well, in about ten years we'll figure out what we've done wrong and change direction. Ten years after that we'll forget everything and start over again ...