Brand new mutations are helping scientists figure out what is going on in autism.

Autism is incredibly frustrating from a genetic point of view. Every study clearly shows that genetics plays an important role in this disease. But when these studies try to find a cause, they keep coming up short.

And this isn’t because scientists aren’t trying hard. They are. In most of the recent studies they are comparing thousands of people’s DNA at millions of different spots. If there was a simple explanation, they would have found it.

One thing they have managed to find from all of these studies is that a minority of cases result from brand new mutations that most likely happen in either the sperm or the egg before fertilization. While these are not going to be that useful as a diagnostic test, they may prove useful as a way of figuring out which genes to focus on. And maybe even for coming up with new ways to treat autism.

With that in mind, a whole slew of researchers set out to find more of these sorts of de novo mutations (as they are called). They reported their findings in the following three back to back to back reports in the journal Nature:

Study 1
Study 2
Study 3

These researchers took on the herculean task of looking at every letter of every gene of over two thousand people. Basically they compared the genes of parents to the genes of their autistic children (and a few of their unaffected siblings). They were able to confirm that some previously identified genes were important in autism and they identified a few new ones.

They were also able to confirm that older dads pass on more of these sorts of mutations than younger dads or moms of any age. Which makes sense if you think about sperm production.

Each time a sperm is made, its DNA needs to get copied. And each time DNA is copied, there is a chance for a mistake to creep in. So it makes sense that the older the dad, the more mutations he’ll have in his sperm.

Frustratingly, this was the most solid finding in the study. But fret not. They also learned some important things about how autism happens too.

The most important thing they found was that many children with autism shared mutations in related genes. Their mutations affected different genes that all impacted the same or related biochemical pathways.

An fMRI scan of an autistic brain.

This is what we might expect from something as complicated as brain development. To pull off something like this, various genes are going to need to fire off at the right time in the right order. If any one of the genes in a similar pathway misfires, you can end up with similar problems. And this is undoubtedly happening in some cases of autism.

This is a very important finding for identifying where to focus research so new treatments can be found for this disease. Isolated genes can be hard to target because sometimes scientists don’t know what they are doing or how they fit into the grand scheme of things. But researchers can identify a pathway, then they can identify chemicals that can tweak that pathway that can one day become medicines.

These studies also highlight yet again what a hideously complex disease autism is. Your risk depends on what versions of lots of different genes you have. Some versions will increase your risk and some will decrease it. Your chances are a summation of all of these risks.

As if this wasn’t complicated enough, autism is more than genes. Something in the environment has to trigger the disease and we know very little about these triggers (except that vaccines aren’t one). Now add to this the fact that different genetic combinations are going to be susceptible to different triggers and you begin to see why this has been such a challenge to geneticists.

Figuring out why a particular person ended up with autism is really hard. But even if we can’t figure it out for a particular person, these studies are important for finding what is happening in the brains of people with autism. And hopefully by knowing that, we can find new treatments.

A long video about the biology of autism. Well worth your time.

Environment may play a bigger role in autism than genetics. Photo courtesy of SeRVe Photography

Autism has long been considered among the most heritable of developmental brain disorders. But a new study of autistic twins indicates that shared environment has a larger impact on the development of autism and autism spectrum disorders than previously thought, and is in fact more important than genetics.

Researchers from Stanford and UC San Francisco examined the prevalence of autism among both identical and non-identical twin pairs. The frequency of identical twins both being diagnosed with autism was lower than would be predicted from statistical models of heritability. The scientists estimate that environmental factors common to twins explains 55% of susceptibility to autism, whereas genetics accounts for only 37%.

Another study published in the same issue of Archives of General Psychiatry suggests that the use of antidepressants by mothers doubles the risk of a child developing autism. Other environmental factors that could be important in autism risk include diet, pollution, parental age, birthweight and maternal infections during pregnancy.

Scientists studied twins like these to figure out that genetics accounts for about 37% of autism. Image courtesy of Jeff Balke.

Scientists have known that autism is a combination of genes and the environment for a long time. But the focus has been on genes because early twin studies suggested that autism was mostly genetic.

Scientists looked at sets of identical and fraternal twins to see how often both twins in a pair had autism. Remember, identical twins have the exact same DNA whereas fraternal twins only share as much DNA as any other siblings.

If autism were purely genetic, then both identical twins in a pair should either have it or not. It should be very rare for one twin in a pair to have autism and the other to not have autism. Fraternal twins should have it at about the same rate as any other siblings.

But if autism were purely environmental, then both twins in an identical or fraternal twin pair should get it at about the same rate. Depending on what part of the environment is causing the problem, this rate might be higher than that of siblings.

A study back in the 1970’s found that both twins in an identical pair had autism 72% of the time and that both fraternal twins never had it at the same time. This is where the 90% heritability for autism number came from.

The fact that fraternal twins never both had autism was weird from the start. Scientists knew that if one sibling had autism, the risk for the other siblings was anywhere from 3-14% which is higher than the general risk. Fraternal twins are siblings and so there should probably be some increased risk too.

In a new study, scientists did a more extensive study on 192 twin pairs and arrived at very different results. In this study, male identical twins both had autism 58% of the time and male fraternal twins both had autism 21% of the time. (Female numbers were similar.) These numbers suggest that genetics accounts for about 37% of autism. Still significant but nowhere near 90%!

If this study holds up, it means is that scientists can start looking at environmental effects. They’ve ruled out vaccines as a cause but there are lots of other possibilities. And many of these may happen before the child is even born.

For example, it may be that like Down syndrome or schizophrenia, parents’ age is a factor. Or it may be that diseases mom might have had or chemicals she might have been exposed to while pregnant could increase chances for autism. Or a host of other possibilities might be responsible.

What is important to keep in mind is that if scientists can identify an environmental cause, they can try to keep expectant mothers away. Or try to ameliorate the effects. In many cases, this will be much easier to deal with than genes.

For more, read

Sometimes autism that looks environmental can be genetic from Undestanding Genetics.

Meet author Seth Mnookin at Down to a Science tonight.

Down to a Science, one of San Francisco's best monthly science events (run by our very own Kishore Hari), is back tonight to tackle the topic of vaccines and autism. Hari's events always bring together scientific experts and an engaged audience to foster an atmosphere of scientific learning.

Tonight's event features Seth Mnookin, author of The Panic Virus. From Down to a Science's website:

"In 1998 Andrew Wakefield, a British gastroenterologist with a history of self-promotion, published a paper with a shocking allegation: the measles-mumps-rubella vaccine might cause autism. The media seized hold of the story and, in the process, helped to launch one of the most devastating health scares ever. In the years to come Wakefield would be revealed as a profiteer in league with class-action lawyers, and he would eventually lose his medical license. Meanwhile one study after another failed to find any link between childhood vaccines and autism.

Yet the myth that vaccines somehow cause developmental disorders lives on. Despite the lack of corroborating evidence, it has been popularized by media personalities such as Oprah Winfrey and Jenny McCarthy.

In The Panic Virus, Seth Mnookin draws on interviews with parents, public-health advocates, scientists, and anti-vaccine activists to tackle a fundamental question: How do we decide what the truth is? The fascinating answer helps explain everything from the persistence of conspiracy theories about 9/11 to the appeal of talk-show hosts who demand that President Obama “prove” he was born in America."

Tonight's event is at the Atlas Cafe, 3049 20th St @ Alabama St. in the Mission District and runs from 7 – 9pm.

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Public health officials in the Bay Area are concerned that not enough children are starting kindergarten with all their immunizations. (Credit: CDC/ Judy Schmidt)

Reported for KQEDnews.org

Concerned by the steady increase in the number of children who are starting kindergarten without proof of updated vaccinations, public health officials in the Bay Area will meet in November to look into the possibility of tightening the system that allows parents to opt out from mandatory immunizations.

Six percent of the state’s kindergartens – up from 2 percent a decade ago – have so many unvaccinated children that public health officials consider them “sites of concentrated vaccine-preventable disease risk,” according to a 2009 report by the California Department of Public Health. At these schools, more than 10 percent of the students were exempted from providing proof that they’re up to date with all their vaccines.

Ten percent may seem like a small number, but it’s enough to “put a school at risk of an outbreak of a vaccine-preventable disease if the disease was introduced,” said Dr. Robert Schechter, chief of the immunization branch of the state Department of Public Health, located in Richmond.

The issue is of increasing concern to medical leaders in California, where a whooping cough outbreak this year has made more than 5,000 people sick and resulted in the deaths of nine babies.

“Increases in the numbers of children whose parents choose not to immunize them are concerning,” said Kathleen Harriman, an epidemiologist with the department’s immunization branch. “In Europe, it was a drop in childhood immunization rates that allowed previously controlled diseases to become endemic again.”

Officials strive to keep immunization rates high enough to confer “herd immunity,” or “community immunity,” to the population. Herd immunity occurs when the vaccination of a portion of the population provides protection to unvaccinated people.

Depending on the disease and the community in which it might occur, in order for unvaccinated people to be protected against communicable diseases, approximately 75 to 95 percent of the population has to be vaccinated against them, medical experts say.

“For example, the level of vaccine coverage necessary to retain herd immunity to measles, a vaccine preventable disease that has recently caused outbreaks in schools, is estimated to be 83 percent to 94 percent,” said Schechter.

The 20 states that appear in green – California among them – allow parents to get a personal belief exemption for their child. The states highlighted in pink allow parents to opt out of vaccination only for religious reasons. (Credit: Institute for Vaccine Safety, Johns Hopkins University). Enlarge this map.

California is one of 20 states that allow parents to opt out from providing proof that their children have received mandatory vaccinations by stating that they are philosophically opposed to their child being vaccinated.

All states except for Mississippi and West Virginia allow parents to opt out because of their religious beliefs. And every state allows for children who have a medical reason to opt out.

In California, children starting kindergarten must show proof that they have had five doses of the whooping cough vaccine, four of the polio, three of the hepatitis B, two of the combined measles-mumps-rubella and one of the chickenpox vaccine, or that they have been sick with the chickenpox instead.

California’s vaccine exemption system is among the easiest in the country, said Dr. Saad Omer, of the Emory Vaccine Center at Emory University in Atlanta, who has compared exemptions around the country. California law requires only that a parent sign a form called a personal belief affidavit – also known as a personal belief exemption – stating that immunizations are contrary to his or her beliefs.

In total, 10,280 kindergartners in California had personal belief exemptions in 2009. That’s 2 percent of all the state’s kindergartners.

Omer found that in states where getting an exemption is easy, such as in California, the rate of whooping cough was at least 50 percent higher than in states that made it more difficult for parents to opt out.

“It’s not just an abstract legal requirement,” Omer said. “It has an impact on disease rates.”

California is in the midst of a whooping cough epidemic that has made roughly 5,300 people sick in 2010 – the most cases reported in 60 years. Nine people have died, all of them babies. Eight of them were under two months of age, too young to be vaccinated against the disease. The ninth baby had received the first dose of the vaccine two weeks before getting sick, according to the California Department of Public Health.

Whooping cough is the common name for pertussis, a bacterial respiratory infection that causes a persistent, fitful cough that can be life-threatening for infants. Highly infectious, it gets its name from the characteristic “whoop” sound that happens as people gasp for breath, although many babies under six months of age don’t develop the whoop.

In California, some counties where the rates of personal exemptions are high have suffered more cases of whooping cough. In Marin, for example, 7 percent of kindergarten students had personal exemptions – the highest rate in the Bay Area. The county has been particularly hard hit by whooping cough, with more than 300 cases so far this year. But other counties that have been hard hit by the disease, such as the Central California county of Madera, don’t have particularly high rates of vaccine exemptions, said Catherine Martin, executive director of the California Immunization Coalition, a non-profit group in Sacramento.

This map shows the rate of personal belief exemptions in California counties in 2009. (Credit: California Department of Public Health) Enlarge this map.

In Marin, two private schools have the county’s highest rates of personal belief exemptions. At the Marin Waldorf School, in San Rafael, 31 of the 49 kindergartners had personal belief exemptions in 2009, a rate of 63 percent. So did eight of the 19 kindergartners at Mill Valley’s Greenwood School.

Among Marin’s public school districts, the two schools with the largest number of kindergartners with personal belief exemptions are in the Ross Valley School District. At Brookside Elementary, 15 out of 126 kindergartners have exemptions this year, a rate of 12 percent, and at Manor Elementary, 16 kindergartners – or 25 percent of the school’s 58 kindergartners – have exemptions.

“I think it is very easy for parents to sign the waiver,” said the school district’s nurse, Laurel Yrun.

As for why Marin County parents seem more likely to sign a waiver than parents in other California counties, she said, “It’s a good question. We’re a wealthy county; this is a community of fairly well-educated people, probably with good access to medical care. It’s interesting. I don’t know.”

Yrun said most of the parents who are signing exemptions in her district are doing so because they have opted not to give their children a particular vaccine. Only a minority of parents are opting out of vaccines altogether, she said. The most popular vaccine to skip in her district is the hepatitis B, followed by polio and the measles-mumps-rubella, she said. The whooping cough vaccine was the least likely to be skipped in her district, she said.

Nonetheless, the district was hard hit by whooping cough during the past school year. In Marin, only 87 percent of kindergartners had been vaccinated against whooping cough in 2009, compared to 93 percent statewide.

The California Department of Public Health hasn’t studied the characteristics of the parents who obtain exemptions. But research by Omer and his colleagues in Colorado, Massachusetts, Missouri and Washington confirms Yrun’s experience. They found that only 25 percent of exempted children didn’t receive any vaccines at all.

In the case of whooping cough, other factors in addition to personal belief exemptions have contributed to the epidemic in California, said Martin, of the California Immunization Coalition. For example, immunity to the bacterium that causes the disease wanes over time, so a large number of teenagers and adults are currently unprotected.

A whooping cough booster shot will become mandatory for middle schoolers in July 2011. (Credit: Gabriela Quiros)

Children receive the fifth dose of the DTap vaccine that protects against whooping cough at age four or five. But by the time they’re 10 or 11, they need a booster shot called Tdap, which only became available in 2005. In September, Gov. Arnold Schwarzenegger signed into law an update to the health code that will require schools to check that children starting middle school have received the Tdap booster shot, starting in July of 2011.

Public health officials in the Bay Area have been concerned about the increase in the number of parents choosing to opt out of mandatory vaccinations since before this year’s whooping cough epidemic. They trace the change to what Emory University’s Omer refers to as “the Wakefield affair.”

In 1998, English doctor Andrew Wakefield published a study of 12 children linking the measles-mumps-rubella vaccine to autism. The paper caused rates of vaccination to fall and cases of measles to climb in the United Kingdom. Wakefield’s research has since been discredited. In February, the medical journal the Lancet retracted his paper, saying that its authors had made false claims about how the study was conducted.

Nonetheless, the paper’s effects are still being felt, said nurse Yrun.

“That’s been refuted, but once it’s been out in the media, parents hang onto it,” she said.

Concerns were also raised about thimerosal, a mercury derivative used as a preservative in some pediatric vaccines. It was eliminated in the United States from all but some flu vaccines in 2001. And numerous studies have found no connection between thimerosal and autism, the most recent of which was a Centers for Disease Control paper published in September.

“While we still need to find out the cause of autism, it seems quite clear that vaccinations are not one of them,” said Dr. Robert Benjamin, public health officer of Alameda County.

Benjamin is one of the public health officers who will be attending a meeting organized by the California Immunization Coalition in mid-November. The meeting will bring together a small group of private doctors, public health officials and representatives of medical associations interested in discussing possible changes to the personal belief exemptions, said the coalition’s Catherine Martin.

Benjamin said that in Alameda County, 11 percent of the people who have contracted pertussis had a personal belief exemption.

“While it doesn’t sound like a large percentage, it’s significant not only in that these kids are acquiring pertussis, but they’re also transmitting it,” he said. “This is where the personal belief exemption is an individual decision which has large societal and community ramifications.”

Benjamin said he would like to change the exemption’s wording so that it makes parents reflect on the impact their decision might have on the community. Or he would like to make it more difficult to obtain.

After studying personal belief exemptions around the country, Emory University’s Omer has come up with a guideline for those designing exemptions.

“It shouldn’t be easier to have your child exempted than to have your child immunized,” he said.

Omer has found that replacing a pre-printed form with a letter crafted by the parents in which they explain why they want the exemption could be an effective way to curtail the number of exemptions. Some states even require the letter to be notarized. A counseling session, viewing a video, or visiting the health department are some of the educational measures that have also been effective, he said. His team didn’t study the language of the exemptions in detail, he said. So he said he couldn’t comment on whether adding new wording to California’s form might help.

When the California group meets, the biggest challenge they might face is deciding who should be given the job of educating parents, if an educational component is agreed upon as the solution.

“To be honest, everybody is challenged budget-wise and everyone wants others to do the job,” said the immunization coalition’s Martin. “Some may feel it’s the schools’ job to educate the parents. Other people believe it’s the doctors’ and public health departments’ job. But the doctors and health departments are feeling stressed because of reimbursements and budgets.”

In fact, the state Legislature, facing record deficits, reduced the budget of the Department of Public Health’s infectious disease branch immunization program by $18 million last week, Martin said.

In Marin County, nurse Yrun said she’s curious to see how the efforts to change the exemptions system will pan out.

“It’s a huge issue to tackle,” she said. “Even though they’re a minority (parents who exempt their children), they have some pretty strong beliefs.”

But the whooping cough epidemic has raised concern among parents who are giving their children all their vaccines.

“Some people in the district were very angry,” she said. “We had parents calling and asking what the district was doing about the un-immunized children. I reassured them that the county is trying to reduce it. The public health department has gone out and had physicians talk to parents. But when you have events like that you usually have the people who believe in vaccinations who show up. The department has advertisements, they have a campaign – they’re using cows to depict herd immunity. It’s just now starting.”

To find out how many children might be under-vaccinated at your school, download the 2009 Immunization Status of Kindergarten Students in California (.pdf, 676 KB).

Watch our QUEST story about Northern California researchers searching for the causes of autism.

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Why aren’t more parents vaccinating their kids?

Whooping cough has reached epidemic proportions in the state of California. And it is hard to know who to be the maddest at.

Should we be mad at the parents who refuse to have their children vaccinated? Or the scientists who have failed to communicate the safety of vaccines to these parents? Or the bacterium itself since it tends to follow a cycle and get worse every 2-5 years? Or the state of California for being too cheap to provide booster shots for 11 and 12 year olds? Or the insurance companies for refusing to adequately reimburse the cost of a vaccine? As you can see, there is plenty of blame to go around.

I can’t do anything about the bacterium itself and little or nothing about the last two. Penny-wise and pound-foolish seems to be the modus operandi of government and the insurance industry. But it seems like other scientists and I should be able to do something about the first two. The question is what…

The facts are out there. Vaccines are very safe and they do not cause autism. All the follow up studies have failed to find a link between autism and vaccines. And the doctor in the U.K. who published the original paper on the subject has had his license taken away because of the unethical way he did the original study.

There is some risk of adverse side effects from a vaccine but they tend to be small. For example, the whooping cough or pertussis vaccine can sometimes lead to severe side effects like shock or brain inflammation. These only happen 1 in 10,000 and less than I in one million respectively. These are much better odds than the 1 in 200 kids who died from whooping cough before the vaccine.

So why aren’t more parents vaccinating their kids? I have always thought that if people have the facts, then they will come to the “right” conclusion. But this is only true if someone can tell good facts from bad. And without training, this can be very difficult which means most folks need to trust the authorities who are reporting the facts. Unfortunately, as our UK doctor and countless others have shown, not all authorities can be trusted.

Chris Mooney is someone who thinks an awful lot about this stuff and in a recent Washington Post op-ed he concluded that, “…based upon my observation, vaccine skepticism seems closely connected to distrust of the pharmaceutical industry and of the federal government's medical research establishment.” What this means is that the facts are out there and the people who don’t vaccinate their kids know about them, they just don’t trust the folks who did the work.

So we don’t necessarily need more facts or getting the facts out there more comprehensively. We need some out-of-the-box thinking to get around this impasse. Here are three possibilities off the top of my head (note that I didn’t even try to come up with a way to gain trust in the pharmaceutical industry):

1) Build up trust in government agencies

2) Circumvent government agencies by creating new scientifically reliable nongovernmental study groups

3) Increase the public’s scientific literacy

Of the three, the best short term solution is probably to create some reliable alternative to government agencies on controversial sorts of issues like vaccinations. Perhaps something like the Bill and Melinda Gates Foundation could fund a group who would try to build consensus on the need for vaccinations and their relative safety compared to the diseases they protect us from. The group would include people opposed to vaccines like Jenny McCarthy, parents whose children have died from whooping cough, scientists with no stake in the discussion, etc.

Maybe these people get together and start the discussion with the fact that, “In 1920 prior to the development of the ‘DPT’ vaccine, one in 200 children died of whooping cough.” Then they propose ways to solve this problem.

Most likely the solution will be vaccines but who knows, maybe people can come up with something better. If vaccines end up as the solution, then the next step is to figure out how to get more buy in for vaccination. Find out why people aren’t getting vaccinated and then build studies or policy suggestions around that.

If people think kids get too many vaccines too close together, then maybe alternative vaccination strategies should be made available. Maybe some people just get vaccines to the real killers and vaccines like chicken pox and maybe even the measles become optional. Would this get more people on board? Would this provide adequate safety for the public?

Also find out what scientific studies this group wants done and by whom to show that vaccines do not cause autism. Then fund those studies and have people that Jenny McCarthy trusts to do the studies. The study would obviously need to be done by someone qualified to conduct such a study but still, get everyone as involved as possible.

Maybe we could push the pharmaceutical industry to create even safer vaccines. Or maybe have nongovernmental organization make the vaccine instead. If we have Pharma do it, then we’ll have to give them incentives. More profits (since profits on vaccines tend to be mighty low) or maybe some protection from lawsuits.

Anyway, the take home message here is that unlike Joe Friday, most people need more than just the facts. They need for the facts to come from someone they trust.

Here's a recent Forum discussion of the whooping cough epidemic.

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Is there a link between childhood vaccines and
autism? Recent news says no. Credit: James Gathany

February was a big month in the debate about the possible role of vaccines in causing autism, a subject we covered in last year's TV story, Autism: Searching for Causes, and several blog posts. The claim-–that there might be a link between the immunizations children receive and the onset of autism–-has recently taken some hard hits.

First, on February 1, two Philadelphia researchers published a scientific literature review that summarized a number of studies from around the world, all of which refuted the claim that there was a vaccine-autism link.

Then on February 8, the news came out that the doctor whose 1998 research had sparked the initial autism-vaccine scare had manipulated his data. Finally, on February 12, a special federal court ruled against three families who argued that the measles, mumps and rubella vaccine had caused autism in their children, saying that the evidence was "overwhelmingly contrary" to the claims.

No doubt there will be more debate about this issue in the future, as families and researchers continue the search for the cause.

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It's challenging to report on an illness such as autism, which scientists and doctors are only beginning to understand (the disease was described in the 1940s) and over which there is so much debate.

There is even disagreement around the question of whether or not there has been a real increase in the number of children being diagnosed with autism in California. In our TV segment, we interview psychologist Ron Huff, director of clinical services at the Alta California Regional Center in Sacramento. In the mid-1990s, Huff sounded the alarm about an increase in the number of reported cases of autism in California. (Through California's 21 regional centers the state's Department of Developmental Services offers services to children and adults with developmental disabilities).

"In 1996 I asked the Department of Developmental Services to pull some raw data off of their statewide electronic information system. And when I saw that data it was obvious that there were a lot more kids in our system with autism than anyone else had expected,"Huff told QUEST. "By 1999 the (California) legislature decided to have the department do a formal study of the number of people who were entering the system with autism. So we looked at about 11 years of data and recognized that there was a 300 plus percent increase in the number of kids coming in with autism."

Since then, researchers have vigorously been debating whether or not there is a true increase in the number of cases. Huff believes that at least part of the increase is a true increase, in other words, that not all of the increase can be explained by factors such as more accurate diagnosis of autism, increased awareness or better availability of services. But other researchers like Kaiser Permanente epidemiologist Lisa Croen feel there isn’t enough information to conclude that even part of the cases are due to a true increase.

"Unfortunately, I don't think we really have the data, and no one really has the data right now to answer that question adequately," she told QUEST. But in her view, whether or not there's a true increase, there is indeed a crisis afoot. "It goes without question that there are definitely more people being diagnosed with autism today than ever before and that is a really big public health crisis. Estimates across the country are that one in 150 children at about 8 years of age will have a diagnosis of autism. So whether or not the increase, or how much of this increase, is really due to a true increase in occurrence, the question now is what’s causing this and what are the risk factors and that’s what we really have to concentrate on."

The research looking into factors other than genes is just beginning. The Centers for Disease Control have launched a large epidemiological study called SEED that seeks to answer the question of what the environmental causes of autism are. When researchers talk about "environmental factors" they mean this very broadly. These factors include, for example, the age of the parents. For our TV story we filmed Meghan Wallace, a four-year-old with an autism diagnosis who is participating in SEED. In Northern California, Kaiser Permanente is overseeing the research. Both children with and without autism are being enrolled. "There really has never been a large, robust, well-designed epidemiologic study that can adequately study the many possible risk factors for autism spectrum disorders," said Lisa Croen, who is one of the principal investigators on SEED.

At the same time, U.C. Davis' M.I.N.D. Institute is carrying out a smaller study into the causes of autism. It's called MARBLES and it’s funded by the EPA and the National Institute of Environmental Health Sciences. By studying pregnant women, MARBLES principal investigator Irva Hertz-Picciotto hopes to find out if there are any risk factors for autism that happen during pregnancy. In our TV story, we followed M.I.N.D. Institute personnel as they visited one of the families in the study. They had followed the mother through her pregnancy and delivery and were now taking samples from her six-month-old boy. The researchers collected everything from his dirty diapers to dust from the family's rug. In between, they asked the mom about her family's use of pesticides and cleaning products.

Hertz-Picciotto's research stemming from another M.I.N.D. Institute study has already pointed to a connection between autism and pesticides. In May of 2008, she and her colleagues reported at the International Meeting for Autism Research in London that mothers of autistic children were twice as likely as mothers of children who didn't develop autism to report that they had used household insecticides and pet shampoos for fleas or ticks. They reported using these products during a period between three months before conception and the first year of the child’s life. Other risk factors are also starting to emerge. A study by Lisa Croen and colleagues reported that paternal and maternal age are risk factors for autism. "What we found was for every 10 years of increase in the age of a mother or a father, the risk of autism went up by about 20 or 30%," Croen told QUEST.

Both the SEED and the MARBLES studies are looking at the question of whether or not childhood vaccination is a risk factor for autism. This is another issue that we talk about in our TV story. Concerned about guaranteeing that infectious diseases don't reemerge, public health officials at agencies like the CDCs state that research doesn't bear out an autism-vaccine connection. But UC Davis' M.I.N.D. Institute is taking a more nuanced approach to the question. Based on new findings by their researchers showing that the immune systems of autistic children are different than those of typically developing children, the Institute suggests that a small number of children may respond to vaccines in an atypical way. They quickly add that there isn't yet a way to determine who those children might be. Studies like SEED and MARBLES might help elucidate this and other questions about what remains a mysterious disease.

Watch the "Autism: Searching for Causes" TV Story online, as well as find additional links and resources.

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You're as likely to be struck by lightning
as to have a severe reaction to a vaccine.

I was reading an article in Time last week about parents not vaccinating their children. The story was about how this phenomenon is becoming more widespread.

These kinds of stories are weird to me because vaccines are pretty safe. The risk of an adverse side effect is incredibly small. For example, the risk for anaphylaxis from the Hepatitis B Virus vaccination is around 1 in 600,000. This is about the same risk as being struck by lightning (1 in 700,000).

Of course, the article wasn't talking about known risks. Instead, it was referring to a hypothesized link between vaccines and autism.

People proposed this link when they noticed that cases of autism and the number of vaccinations were rising at the same time. Of course, just because two things happen to occur at the same time, this does not mean they are causally linked. For example, the increase in global temperature is not related to the decrease in the world's populations of pirates (despite what the Pastafarians say).

So how could an increased number of vaccinations cause an increase in the number of cases of autism? I have seen two ideas put forth. The first is that thimerosal is to blame. The second is that there are so many vaccinations now that we are stressing out the body's immune system. Most likely neither idea is valid.

Thimerosal is a mercury-based preservative that used to be used in vaccines. Even though there haven't been any good studies on the effects of thimerosal on brain development, everyone knows mercury is bad for the brain. So the idea behind thimerosal makes some sense.

Back in 2001, vaccine manufacturers decided to eliminate thimerosal from their vaccines. We would predict, then, that cases of autism should go down significantly if thimerosal was linked to autism. They haven't. In fact, in one California study, cases have continued to climb. So thimerosal is most likely not to blame.

Another point that has been made is that there are so many vaccines now that we are stressing out our bodies' immune systems. Again, this concern is unfounded.

Vaccines are injections of viral proteins. Our bodies see the proteins and raise antibodies to them. Then when a virus invades, we have antibodies that recognize the virus and target it for destruction.

It is the number of viral proteins that matter in terms of taxing the body's immune system and not the number of vaccinations. All of the current vaccines put together do not have as many viral proteins as the old smallpox vaccine (150 vs. 200). So the number of vaccines is unlikely to be the issue.

What all of this means is that vaccines are probably not responsible for the significant increase in the number of cases of autism. What is responsible? No one knows for sure.

It may be that the rise just comes from all of us recognizing the symptoms more. Or it could be due to some cause we don't know about or understand.

What we do know is that vaccines save many lives. I assume no one wants to go back to the early 20th century when polio epidemics swept the country. For example, 2,500 cases of polio ended up at one Los Angeles hospital between May and November of 1934. And in 1952, the U.S. had 21,000 cases of paralytic polio.

We can prevent this sort of thing from happening by making sure everyone is vaccinated. And yet there are people who choose to hide behind the people who take the miniscule risk of getting vaccinated.

Is this a matter of free choice? Should parents be allowed to opt out of vaccinating their children even if it risks society at large?

One idea, I suppose, is to have people who choose not to be vaccinated to sign a waiver saying they accept full responsibility for their actions. In practice this would mean that health insurance and the government would not be responsible for their children's health care bills if they become ill with one of the diseases they refused to be vaccinated against.

And if your infant, grandma, or immuno-suppressed cousin came down with a disease these folks refused to be vaccinated against, then you could sue the un-vaccinated for damages. The common good isn't enough to encourage these folks. Perhaps threats to their pocketbook will be.

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