Thursday, January 31, 2008

Autism and Paternal Age

Paternal age is emerging as a potential cause or causal factor giving rise to autism. On this site, (as a father whose autistic son was conceived when I was 41), I have received several posts from a blogger/poster who has focussed on this issue . In Australia, couriermail.com.au reports that researchers at the Queensland Centre for Mental Health Research have found:

"adult mice born to older fathers have differently shaped brains and are generally more anxious and less adventurous than those fathered by younger animals. ... brain scans of the mice showed those born to older fathers had thicker cerebral cortexes."

The research team's senior investigator, John McGrath explains that "What we've found in the mice is reminiscent of autism because there's some reasonable evidence about early brain overgrowth in autism". McGrath also stated that the results need to be replicated before they are given scientific validity.

The couriermail.com.au article by reporter Janelle Niles states that previous population studies have found a six-times increased likelihood of autism than those born to dads in their 20's. Unlike my friends at Autism Street I am no statistician but on a common sense level, if the article information is correct, a six-times increased likelihood of autism in offspring for Dad's in their 40's compared to Dads in their 20's would seem to be .... statistically significant ... one which should be the focus of further research.

Wednesday, January 30, 2008

FMR4 - New Gene Link to Fragile X and Autism

The Autism Knowledge Revolution is continuing at such an explosive pace that it barely makes the news when an important new research development provides new insights into the biological structures and process of autism disorder. More of the genes associated with autism and related conditions, Fragile X, in the report that follows, are becoming known. At times it seems on a daily basis.

PLoS ONE has published a report - A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome of a study by researchers Ahmad M. Khalil, Mohammad Ali Faghihi, Farzaneh Modarresi, Shaun P. Brothers, Claes Wahlestedt of the Molecular and Integrative Neurosciences Department (MIND), The Scripps Research Institute, Jupiter, Florida which identifies a new gene FMR4 involved with Fragile X syndrome and potentially many cases of autism.

In New Gene Linked To Fragile X Syndrome -- Suggests Potential Targets For Autism And Other Neurological Disorders Science Daily translates from science into layperson the article published in PLoS ONE :


ScienceDaily (Jan. 30, 2008) — Scientists at The Scripps Research Institute have discovered a new gene involved in fragile X syndrome, a condition that often shares many symptoms of autism. The discovery may lead to new tests or treatments for several neurological disorders.

...

Fragile X syndrome affects thousands of patients worldwide with severe learning disabilities, often accompanied by anxiety disorders, obsessive-compulsive behavior, and attention deficit hyperactivity disorder. There are currently no therapeutic treatments available for fragile X syndrome. Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism, according to The National Fragile X Foundation, including such behaviors as social anxiety, poor eye contact, and hand biting.

More than 16 years ago, scientists linked fragile X syndrome to inactivation of FMR1 gene expression, leading to the lack of a protein known as the fragile X mental retardation protein, now considered to be critical for neuronal function. Until the current study, no other functional gene other than FMR1 had been shown to be inactivated in the disorder.

However, Wahlestedt knew the FMR1 gene locus-a specific point on a chromosome-was not well mapped. Wahlestedt and his colleagues hypothesized that unknown regulatory genes might be transcribed from the region.

The new study shows at least one other functional gene-FMR4-from this genetic region is linked to fragile X syndrome, although the gene's exact role in the intact brain remains uncharacterized.......

For anyone wondering, as I was, what the term anti-apoptic means, it relates to apoptosis for which I found some definitions on-line:

MedicineNet.com:

Apoptosis:

A form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area. Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells, unnecessary cells, and unhealthy cells. The human body replaces perhaps a million cells a second. Too little or too much apoptosis plays a role in a great many diseases. When programmed cell death does not work right, cells that should be eliminated may hang around and become immortal. For example, in cancer and leukemia. When apoptosis works overly well, it kills too many cells and inflicts grave tissue damage. This is the case in strokes and neurodegenerative disorders such as Alzheimer, Huntington and Parkinson diseases. Apoptosis is also called programmed cell death or cell suicide. Strictly speaking, the term apoptosis refers only to the structural changes cells go through, and programmed cell death refers to the complete underlying process, but the terms are often used interchangeably.

Merriam-Webster OnLine

apoptosis

Main Entry:
ap·o·pto·sis Listen to the pronunciation of apoptosis
Pronunciation:
\ˌa-pəp-ˈtō-səs, -pə-ˈtō-\
Function:
noun
Inflected Form(s):
plural ap·o·pto·ses Listen to the pronunciation of apoptoses \-ˌsēz\
Etymology:
New Latin, from Greek apoptōsis a falling off, from apopiptein to fall off, from apo- + piptein to fall — more at feather
Date:
1972
: a genetically directed process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or removal of a suppressing agent or stimulus, and is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells —called also programmed cell death
ap·o·pto·tic Listen to the pronunciation of apoptotic \-ˈtä-tik\ adjective

Monday, January 28, 2008

Autism and Censorship


I do not subscribe to the vaccine/thimerosal causes autism theory. It is necessary to state that at the outset because of the often heated, sometimes irrational nature of internet discussions of autism issues.

There exists a group of people, often called "neurodiversity" comprised of some high functioning autistic persons, some parents and professionals who share their view, who tend to promote a view of autism as a non-medical disability, a socially created disability which, from their perspective is simply different wiring of the brain. In the neurodiversity belief system autism is just a different way of thinking which, by their self identification with historical geniuses, can even be seen as superior to neurotypical thought. Positive views of autism are promoted. Negative realities of autism are suppressed. And now, in the American Academy of Pediatrics, the neurodiversity movement has a powerful new ally as it seeks to censor a work of fiction - the Eli Stone television series episode which apparently suggests a link between vaccines and autism.

The neurodiversity group is so rigid in its perspective that its adherents react with intense hostility to any negative portrayal of autism disorders such as that shown in the Autism Every Day video or the Ransom Notes campaign. The AED video presented the realities of autism from the perspective of caring parents. The Ransom Notes campaign was an attempt to create public awareness of some of the harsher realities of disabilities includig autism. While they have not been able to silence Autism Speaks, or the parents who created the Autism Every Day video, it is not for want of trying. And the "autism is beautiful" movement was a prime player in the successful effort to censor the Ransom Notes campaign, a campaign which was designed to focus attention on the harsher realities of various disabilities including autism disorders. Even Ph.D's, academics, presumably committed to the free exchange of ideas, bragged on the internet that they were doing "happy dances" over their success in shutting down the Ransom Notes campaign.

The Eli Stone episode is, on the surface, objectionable to the neurodiversity autism censors because it portrays a link between vaccines and autism. The episode features a family attorney who wins a court decision in which he successfully argues that a mercury-containing flu vaccine caused autism in a child. This alleged causal link enjoys little support in the medical and scientific communities and the AAP is presumably acting with good intentions when it seeks to censor the episode in question. But the same can not be said of the neurodiversity censors.

To be sure their criticisms of the vaccine autism link are consistent with accepted medical and scientific opinion but they want the episode and such discussion censored for another reason. They are offended by a medical model of autism disability. To them autism is a disability only because society imposes conditions on autistic persons which make it a disability. Even discussion of potential environmental bases for autism, anything other than a purely genetic model, is met with intense hostility by neurodiversity bloggers.

I have never been a fan of David Kirby, or his promotion of the vaccine causes autism theories. But I would not want to silence his voice, his opinion on this or any other subject. And I believe he has a point when he expresses alarm about the attempt to censor a television series episode in Scarier Than Fiction: Pediatricians Try To Censor ABC.

Autism Disorder is a medical disorder. Censorship is a severe social disorder which poses a threat to the health of a democratic society.


Autism Waiting Lists In Alberta


The disparity in funding for autism treatment in Canada has, in the past, led some families with autistic children to move to oil rich Alberta, which has substantial government funding available for autistic children. But the availability of better funding has not translated into better services in all cases as children are stuck on lengthy waiting lists awaiting assessment. In Situation critical for autistic children Nicki Thomas of Sun Media reports on the critical shortage of staff and funding threatening the futures of autistic children in Edmonton. Terri Duncan of Children's Autism Services of Edmonton indicates that there are staffing shortages everywhere in Alberta and children are waiting up to a year for assessment. That year is a critically important year lost for autistic children in need of treatment:

Duncan said if autism isn't detected and treated early on, disruptive behaviour - like hitting, kicking and biting - develop from an inability to communicate effectively.

"Those behaviours can make lives really difficult and hard to deal with," she said.

"We would be able to take a lot more children off the waiting list if we had more qualified, trained staff," Duncan said.

Many credible studies and reviews of professional literature have confirmed that early ABA intervention is critically important for achieving the best possible outcome for autistic children. Lengthy waiting lists for assessment deprive autistic children of a better future.

In New Brunswick many, including me, have thought that a medical doctor is the only professional who can diagnose autism disorders. I was informed though that Psychologists can also make the initial autism diagnosis.

New Brunswick, Alberta, or anywhere else in Canada, it would seem that an important step in addressing the autism crisis, a crisis which is very real for families of children with autism, is to take steps to educate GP's in diagnosing autism. The tools being made available now by the American Academy of Pediatrics and similar organizations should be used by all doctors and psychologists to ensure autistic children receive early ABA treatment during the important early years without time being squandered.

Sunday, January 27, 2008

Tragic Autism Reality In North Carolina - Autistic Child Dies After Going Missing

A casual reader of "autism" blogs on the internet might think that the most pressing autism problems were largely literary in nature, the right metaphor or nuance to use, whether it is proper to refer to "a person with autism" or "an autistic person". Attempts by concerned parents to discuss the hard realities of autism are often met with condemnation - until tragedy strikes as it has in Cabarrus County North Carolina where an autistic child died hours after going missing from a care center, only to be found near a pond and rushed to Intensive Care. I feel for the family members, and for the care givers at the center who were apparently very close to the boy.

I lived through a "gone missing" situation with Conor which thankfully ended well, in large part because of the efforts of a Good Samaritan who took him into a nearby store, and away from the busy street he had wandered onto, but the intense fear and guilt I felt will always be with me. I can only imagine the grief of those who loved the unfortunate child in Cabarrus County for whom things ended so badly.

The world needs autism treatments and cures, so that all children with autism have the opportunity to grow into adults and live as full a life as possible.

Psychoanalysis Allegedly Helps Kids With Autism, No Evidence To Back Up Claim


In Psychoanalysis Helps Kids With Autism CBS quotes Susan P. Sherkow, MD, a New York City psychoanalyst who works with autistic children and their families and describes how, in her opinion, psychoanalysis helps autistic children:

"The therapist focuses on the behavior, mood, or emotion of the child and then translates it to the child and waits for a sign that the child feels understood, such as a furtive glance. And from there, the therapist enters the child's world," she explains. Sometimes this translation is putting the child's actions into words, such as saying "you are picking up a cup." "Psychoanalysis should be part of the package because unless you have a really gifted specialist, you are not going to get at the meaning of what these children are trying to convey," she says.

The article cites only Dr. Sherkow's opinion in support of its headline proposition that psychoanalysis helps kids with autism. No credible studies, no studies of any kind, are offered in support of the proposition. Fortunately Denise Mann, the author of the article, also spoke with Andy Shih, PhD, vice president of scientific affairs at Autism Speaks, who stated:

"Very little is known about effective treatments for autism. The only approach that has evidence behind it is ABA. In many cases, this approach has been helpful in allowing children to lead a healthy and more normal life."

Saturday, January 26, 2008

Conor Shows Off His Basketball Skills For Dad



Conor showing off his ball handling skills at the gym for Dad while Education Aide Brad Daniels looks on. Brad has done some great work with Conor in the gym this year. It was a real thrill for me to be able to attend at the school gym yesterday and see Conor having so much fun.

It is a large field house style gym and there were many other children making lots of noise which didn't seem to bother Conor at all. A huge plus!




Friday, January 25, 2008

Autism, Genetics and Environment - Study Finds Autism Immune System Link


A study reported in the January 2008 issue of Genomics, Gene expression changes in children with autism, has found that a group of genes with known links to natural-killer cells, that attack viruses, bacteria and malignancies, are expressed at high levels in the blood of children with autism when compared to children without the disorder. The study also found gene expression distinctions in children with early onset and regressive autism. The study is summarized in a digestible format on the UC Newsroom article Researchers identify gene expression profile distinctions in children with autism. Comments by the senior researcher Frank Sharp M.D. clinical neurologist, neuroscientist, and professor, department of neurology, school of medicine, indicate that the findings suggest a possible environmental role in the development of autism disorders:

"What we found were 11 specific genes with expression levels that were significantly higher in the blood of children with autism when compared to the blood of typically developing children," said Frank Sharp, senior author of the study and professor of neurology with the M.I.N.D. Institute.

"Those 11 genes are all known to be expressed by natural-killer cells, which are cells in the immune system necessary for mounting a defense against infected cells. We were surprised by our results because we were not looking for these particular genes. And while a number of studies have shown immune system dysregulation to be an important factor in autism, ours is one of the first to implicate these particular cells."

...

"What we are seeing can reflect something in the environment that is triggering the activation of these genes or something genetic that the children have from the time they were conceived," Sharp explained. "Such an immune response could be caused by exposure to a virus, another infectious agent or even a toxin.

Another possibility is that these changes represent a genetic susceptibility factor that predisposes children to autism when they are exposed to some environmental factor."
He added that the current study also does not identify whether or not the natural-killer cells are functioning abnormally, which further work by M.I.N.D. Institute immunologists will reveal. "If the natural-killer cells are dysfunctional, this might mean that they cannot rid a pregnant mother, fetus or newborn of an infection, which could contribute to autism."

The study is also featured in an article by Carrie Peyton Dahlberg at sacbee.com which features several interesting comments by Dr. Jeffrey Gregg, director of molecular diagnostics for the UC Davis Medical Center who was also involved in the study. It is pointed out that both similarities and differences were found between the early onset and regression autism cases:

Children with that "regressive" autism had nearly 500 genes that were activated differently than children with "early onset" autism, Gregg and his colleagues found after examining blood samples from 61 children.

"That would suggest that those two groups are very different … and may have totally different underlying pathology," Gregg said.

Both groups, though, as well as other children with a range of symptoms called autism spectrum disorder, shared the 11 strongly expressed genes that control natural killer immune cells.

Dr. David Amaral, the UC Davis MIND Institute's research director suggested that much remains to be learned about how the genetic and environmental factors giving rise to autism interact:

It is still unclear how early those differences emerge, but other MIND Institute researchers are looking at immune differences in mothers' bloodstreams that might be predictive for having a child with autism, said Dr. David Amaral, the institute's research director.

"Things are moving really, really fast now," Amaral said, with scientists around the country working to understand the relationship of genetic and environmental factors that may underlie autism.

It seems clear from this study that environmental factors can not be ruled out in trying to understand the causes -- and potential treatments for autism. Some of the rhetoric which dismisses all genetic or all environmental factors appears to be ill founded. The Autism Knowledge Revolution is being carried out by researchers and scientists in relevant medical fields and the knowledge they are gaining appears to point to both genetics and environment as being involved in the development of autism.

Thursday, January 24, 2008

Autism Resources Miramichi Gets A Boost


Lila Barry accepts a cheque for $30,000 from MLA Bill Fraser. They
are joined by ARM board members Dianne Pineau and Linda Robichaud.
Photo and caption from Miramichi Leader Online Edition
© 2007 CanadaEast Interactive, Brunswick News Inc.

In Autism centre receives government funding the Miramichi Leader reports on a positive autism development in Miramichi, New Brunswick as Autism Resources Miramichi receives funding to get started. New Brunswick has seen its share of advocates of alternative non evidence based treatments for autism. Lila Barry, Dianne Pineau and Linda Robichaud at ARM will ensure that parents receive reliable information about evidence based interventions for their autistic children - and strong moral support through the tough times:

Barry and other parents of ASD children were at the office of Miramichi-Bay du Vin MLA Bill Fraser last Monday, Jan. 7 for the official funding presentation. She said the centre will especially help parents who are struggling to deal with affected children.

"As a parent you're actually trying to reach out to other parents. Parents often when they first get the diagnosis; they're always in a state of anxiety and overwhelmed with the diagnosis. They don't necessarily have anyone to turn to or don't know who to turn to once their child is diagnosed," she said.

Barry also said stress levels are very high for parents of ASD children and family separation and divorce often result. She said many parents are often desperate to get help for their children and turn to the wrong sources of information.

"It's difficult obtaining reliable, accurate information on best practices, treatment and research," she said. "So often there is some much out there on the Internet that is just garbage."

She said parents will often spend large amounts of time and money chasing worthless therapies and miracle treatments. She wants the centre to provide these parents with the right information needed to help.

Autism Communication Deficit At The CIHR



The Canadian Institutes of Health Research have played an important role in fostering autism research. The CIHR quite properly promotes its role in funding the recently reported study on the association of certain chromosomes with some instances of autism. The CIHR also professes to be committed to partnering with relevant "stakeholders" and community interest groups in an open, transparent manner:

Freedom of Inquiry CIHR recognizes that the primary purpose of all research in the public domain is the creation of new knowledge in an environment that embodies the principles of freedom of inquiry and unrestricted dissemination of research results.
Transparency and Accountability Decision-making processes should ensure that all decisions are fair, open, reputable and able to bear close public scrutiny. Honest and cost-effective accountability mechanisms will be in place for all aspects of the work undertaken by CIHR.
Collaboration CIHR values positive and mutually respectful relationships with partners and stakeholders who are committed to openness, responsibility and fairness and are mutually respectful of each other's priorities and objectives.


Measured against the noble principles espoused by the CIHR are the realities of the CIHR organized national autism symposium which was held, according to rumour at least, November 8 and 9 2007 in Toronto. The symposium was supposed to be a key element in the Stephen Harper- Tony Clement "national autism strategy" such as it is.

Invitees to the symposium were told that the symposium would be an exercise in community building, an odd goal for such a secretive event. No program, list of speakers or list of invitees to the event were ever published. The invitation also indicated that the symposium would be conducted by professional facilitators, which is a PR way of saying that the discussion would not be open and dissent or criticism would not be permitted. The hand picked delegates were selected not by the community organizations they were supposed to represent but by CIHR officials.

To date, no information has been released of the proceedings of the invisible National Autism Symposium of November 8 and 9 2007. In relation to autism, it seems reasonable to say that the CIHR has failed miserably in its goal of community building. It is not clear what the CIHR is so afraid of although it seems that parents advocating for a national autism strategy to actually help Canadian children are high on its "do not invite" list. Perhaps the CIHR scientists/bureaucrats are simply trying to ensure maximum compliance with their marching orders from Prime Minister Harper and Health Minister Clement.

What the CIHR is not doing is community building. What the CIHR is not doing is communicating with Canadians about autism, autism research or effective evidence based autism interventions. When it comes to autism the CIHR suffers from a massive communication deficit.

Wednesday, January 23, 2008

Autism Research - Hopkins Team Comments on CNTNAP2 Gene Autism Study


The John Hopkins research study, one of three reported in the January 2008 issue of the American Journal of Human Genetics that confirmed the CNTNAP2 gene as an important genetic link to autism susceptibility, is commented on by some of the study's lead researchers in Hopkins Team Identifies Autism Susceptibility Gene. Aravinda Chakravarti, Ph.D., professor of medicine, pediatrics and molecular biology and genetics and member of the McKusick-Nathans Institute of Genetic Medicine at Hopkins and Dan Arking Ph.D., an assistant professor at the McKusick-Nathans Institute explain the methodology the followed in the study and some interesting findings. Some interesting findings in the study - that autistic individuals are more likely to get the T allele, a key genetic variant associated with autism, from mothers than fathers, and more likely to be boys than girls.

Using genome-wide analysis, the team first analyzed DNA from 292 individuals, including 148 affected offspring. They compared single nucleotide polymorphisms, or SNPs, the differences in single chemical’s building blocks of the DNA at the same point across many people. They found that autistic individuals tend to inherit the DNA letter T from their parents much more often than expected by chance at one particular place on the chromosome.

To validate their finding, the team then repeated their approach with a separate group of samples consisting of 1,295 parent-child trios. They again found an over representation of T, confirming that inheritance of the T genetic variant is associated with increased risk of developing autism.

The T genetic variant is found in the middle of the CNTNAP2 gene, short for contactin-associated protein-like 2, which codes for a protein that’s thought to mediate cell communication in the nervous system.

The researchers then looked at the same data to see if there were differences in which parent the T allele is inherited from and the gender of the child. They found that autistic individuals are more likely to get the T allele from mothers than fathers, and more likely to be boys than girls.

“We know that boys are four times as likely as girls to be autistic,” says Chakravarti. “And now we have some intriguing evidence suggesting that the gene may show a parent-of-origin effect.”

Autism and the Criminal Law

Should an 18 year old man with autism and an IQ measured between 43 and 62, who a psychiatrist has testified functions on the level of a 3-4 year old be found competent to stand trial for criminal charges of assaulting a teacher and a room mate in separate incidents? The question is not one that Michelle Dawson, Jim Sinclair or Amanda Baggs have offered much enlightenment on but it is one that is undoubtedly of great concern to many parents of low functioning autistic children, both out of love for their children and concern for themselves, siblings and other caregivers. It is a question that is under deliberation by a judge in an Athens, Georgia court proceeding as reported in Judge considers whether to put mentally disabled man on trial for assaults by Athens News Senior Writer Jim Phillips. The Defendant is being tried in juvenile court.

The young man involved requires 24 hour supervision and has difficulty following the context of a discussion according to the psychiatric evidence. A caseworker though has testified that he understands that it is wrong to hit. I would not presume to assess the evidence from afar, as summarized in a newspaper article, of a matter under deliberation by a judge in a proceeding. The court's decision will be of interest to many parents of severely autistic children.

Tuesday, January 22, 2008

Translating Autism: An Autism Research Blog - Check It Out


A member of the Autism Awareness Facebook group posted about this autism resource blog Translating Autism: An Autism Research Blog. It is an informational blog intended to rapidly disseminate the latest scientific findings related to the nature, causes, & treatments of autism spectrum disorders.

The host of the blog claims to be a clinical psychologist and neuroscience researcher working at a large Midwest child psychiatric institute but is not an autism specialist. His/her name is not published on the site although it is available by email. The host also indicates that he/she is not a proponent of one cause over another, one treatment over another, one philosophy over another and takes no philosophical position simply translating research findings into applicable and useful information that could help parents, teachers, clinicians, and consumers make better informed decisions.

Looks like Translating Autism could be a valuable resource for anyone with an interest in autism.

I urge everyone to check it out.

Facing Autism Didn' t Make It to Round 2 of the Canadian Blog Awards

Well it was nice to be nominated for a Canadian Blog Award, Best Personal Blog, but Facing Autism in New Brunswick did not make the cut to advance to Round 2 of the voting. Congratulations to those blogs that did. Here are the blogs advancing to Round 2 in the Personal Blog category:

Don Mills Diva
And She Knits Too!
Raymi the Minx
Schmutzie’s Milk Money or Not
Meg Fowler

Autism and Affection - Conor Waits Anxiously For Dad

Last evening I got home late after finishing work at 8 pm local time. When I pulled in the driveway I could see Conor though the window in our side door .... waiting anxiously for Dad. His mom said he had been asking for me since 5:30 pm and had gotten a bit upset, asking for me almost non stop, with some wall banging. He was happy to see Dad and insisted (Daddy help) that I help put him to bed.

Obviously I wish Conor had not gotten upset but at the same time I would be lying if his expressed desire to see his old Dad at the end of the day did not lift my spirits considerably. Although I have trouble with the concept of finding joy in autism, I have no trouble accepting Conor for who he is, a fun loving, caring boy who loves his mom, dad, brother, Nanny, Grammy, Grampy and whoever shares his life with him in a caring way. That is who Conor is ... with or without autism.

Sunday, January 20, 2008

Facing Autism in New Brunswick Nominated For A 2007 Canadian Blog Award


Facing Autism in New Brunswick has been nominated for recognition in the Best Personal Blog category of the Canadian Blog Awards 2007 . It really is an honour and I thank Scott Tribe for the nomination. There are a number of excellent blogs nominated in the Personal Blog category and I feel good about just being included in that list.

I am happy to see that some people appreciate the realistic approach that I have taken in describing Autism Disorders and my son's life as a person with Autism Disorder and profound developmental delays. There are many blog sites on the internet which paint a rosy picture, a joyful picture of autism. Some of these sites are hosted by people who condemn any attempt to describe autism realistically.

I have always believed that I would be doing a great disservice to Conor by bowing to pressure to paint autism as something other than what it is for him and so many other autistic persons - a debilitating neurological disorder which severely limits their life prospects. I include happy stories, and happy pictures, of life with Conor on this site. He is my buddy. And he makes me very happy. But daily life with Conor's autism is a real challenge and sometimes he hurts himself and others. His long term prospects - after his mom and dad have departed as we all must do - are not pretty. I feel obligated to tell the world the complete truth, good and bad, about Autism Disorder.

For now there is little in the way of evidence based treatments or interventions available to help autistic children. Applied Behavior Analysis, ABA, is the only intervention which has consistently, based on decades of research, been found to be effective in making gains in all domains for autistic children but even ABA is not a cure.

There is, however, an incredible explosion of research now taking place in various areas of autism. The neurological structures and processes of autism, causes and possible treatments are all being explored. We truly are living in the era of the Autism Knowledge Revolution. Hope for treatments to improve the lives for autistic persons is more realistic today than ever before.

Long live the revolution. Long live the Autism Knowledge Revolution.

Saturday, January 19, 2008

Autism, Environment and Genetic Mutations: Hamilton Steel Mills and Conor's Autism Disorder


The dark smokestacks and olive green buildings on the left are part of the Stelco steel mill, the mint green ones in front of that and to the right are Dofasco. The skyway bridge (8 lanes wide!) that runs between connects east Hamilton to west Burlington over the Hamilton Habour (the western end of Lake Ontario.)

Photo and information above from skyway-ingenia, Lisa Shadforth


Genetic Mutation has been a hot topic in the autism news with several studies pointing to genetic mutations as indicating increased autism susceptibility. Genetic mutation can occur as a result of a number of different factors including chemical and radioactive insults. A story in today's Toronto Star dealing with genetic mutation in Hamilton Ontario mice really made me sit up and take notice.

Mice breathing the air downwind from Hamilton's two big steel mills were found to have significantly higher mutation rates in their sperm, a new Health Canada-led study says.

While there's no evidence that residents of the area are experiencing the same genetic changes, the project's lead author says the findings do raise that question.

"We need to do that experiment and find out," said Carole Yauk, a research scientist with Health Canada.

A future study will look at "DNA damage in the sperm of people living in those areas."

...

Dr. Rod McInnes, director of genetics at Canadian Institutes of Health Research, said the mice could be "the canary in the coal mine" signalling the genetic risks to humans of breathing toxic air. ... While genetic changes in sperm would not affect a male directly, they'd get passed on to the offspring that receive his DNA.



The story reports on a study indicating that the mice living under the Burlington skyway downwind from 2 Hamilton steel mills and breathing the air from those mills for a period as short as 10 weeks were found to have significant sperm mutations. The study Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location is published in this weeks edition of PNAS.

Why did this particular story grab MY attention? We lived on Leominster Drive, in the westerly area of Burlington adjacent to Hamilton for 12 months prior to Conor's conception and a further 9 months until he was born at the Joseph Brant Memorial Hospital in Burlington. Two years later he was diagnosed with PDD-NOS, later changed to Autism Disorder with profound developmental delays.

Enough information to jump to rash conclusions? No. Pause for thought? Yes.

Autism's "Royal We"

Autism discussions are often marked by the use of the "Royal We" (or its variation the "Royal Us") in which some persons with either Aspergers or high functioning Autism implicitly speak on behalf of all persons with autism. Wikipedia explains the Royal We:

Pluralis majestatis

From Wikipedia, the free encyclopedia

Jump to: navigation, search

Pluralis majestatis ("majestic plural") is the plural pronoun where it is used to refer to a single person holding a high office, such as a monarch, bishop, pope, or university rector. It is also called the "Royal 'we'" or the "Victorian 'we'." The more general word for the use of we to refer to oneself is nosism.[1]

The idea behind the pluralis majestatis is that a monarch or other high official always speaks for his or her people.[citation needed] For example, the Basic Law of the Sultanate of Oman opens thus:

On the Issue of the Basic Law of the State We, Qaboos bin Said, Sultan of Oman…[2]

Famous examples of purported instances:

  • We are not amused. — Queen Victoria (in at least one account of this quotation, though, she was not speaking for herself alone, but for the ladies of the court.[citation needed])
  • The abdication statement of Nicholas II of Russia uses the pluralis majestatis liberally, as in "In agreement with the Imperial Duma We have thought it well to renounce the Throne of the Russian Empire and to lay down the supreme power."[3]

Arguably the most famous use of the Royal We is the essay by Jim Sinclair "Don't Mourn For Us". Apart from the title Don't Mourn For Us is rich in Royal We declarations"


I invite you to look at our autism, and look at your grief, from our perspective:

This is what we hear when you mourn over our existence.

This is what we hear when you pray for a cure.

This is what we know, when you tell us of your fondest hopes and dreams for us: that your greatest wish is that one day we will cease to be, and strangers you can love will move in behind our faces.

But don't mourn for us. We are alive. We are real. And we're here waiting for you.


"King Jim" Sinclair went well beyond the Royal We in presuming to speak on behalf of all autistic children including those with Autism Disorder, some of whom lack his considerable intellectual and communication gifts. He also used his Royal Insight to tell parents of children newly diagnosed with autism what they were thinking and feeling in responding to the realities of their children's diagnoses. "We" were in fact mourning the child we should have had, wishing we could replace the people behind our children's faces with entirely new non-autistic people. Bad, bad parents, we should all be banished to the stocks. And if you can believe some of essays by parents of autistic children praising autism as a different perhaps better way of thinking and living, praising the joy of autism, it appears they at least heard the Royal message. Treatment bad, cure bad, ABA bad, autism good, autism joyful.

Of course no mention of Autism's Royal We would be adequate if it made no reference to another very high functioning autistic adult, diagnosed as an adult, who also uses the Royal We in her relentless anti-ABA campaigns before courts, Parliament and the media in Canada. In The Word Is Out About Autism, Canada In The Era Of Autism Advocacy Michelle Dawson also made extensive use of the Royal We, "Queen Michelle" told the Canadian Senate Standing Committee
on Social Affairs, Science, and Technology that:


There is no consideration of who autistics might be and what we might need. Either we are horribly sick or we aren’t, depending on what non-autistics need.

Either we are horribly sick or we aren’t, depending on what non-autistics need.

we are most reliably defined by our strengths, our innate autistic strengths, which exist in all autistics regardless of how our level of functioning is judged.

1. That this Committee, and the Senate as a whole, apologize to autistic Canadians, for using your power and resources to promote and distribute false and pejorative information about autistics which is likely to be damaging and dangerous to us.

3. That the above-mentioned final report make it clear that autism is not a mental illness; that autism is receiving a great deal of attention due to the efforts of autism advocates; and that this attention, because it arises from factually false and ethically indefensible portrayals of autistic people, has harmed and damaged us.


Apparently though, not all higher functioning autistic persons reside in the Royal Autism Courts of King Jim or Queen Michelle. In Autistic Blogger Jonathan Mitchell Says NO To Neurodiversity I commented on a blog, NEURODIVERSITY: JUST SAY NO , by Jonathan Mitchell, an autistic person who rejects the anti-cure, anti-treatment, ideology promoted by Sinclair and Dawson and who asserts that some autistic persons DO wish to be cured. That post prompted some hostile, personal attacks on Mr. Mitchell which prompted my follow up commentary "House Autistic" Or More Neurodiversity Trash Talk.

Mr. Mitchell challenged the assumption that the anti-cure ideologies of some autistic persons represented the views of all autistic persons and for that was decried as a "liar":

A number of high functioning autistics claim that there is a consensus among all autistic persons that finding a cure for autism would be a horrible thing. Autism is a part of who they are and to take away the autism is to take away the person. They go further to claim that autism is not really a disorder but just a different form of brain wiring--some call this philosophy "neurodiversity".

Some of them do acknowledge that autism is a disability. However, there is a distinction between a medical model of disability-wherein the person has a disease state and the social model of disability--the disabled person would not be at a disadvantage if society made accommdoations for them.

I am a diagnosed autistic, nonverbal, feces smearing at age 3, 8 year veteran of special education yet I do not share this view. I long for a cure for autism though a cure at age 52 is not the same as at age 3, even in the unlikely event of a cure being found in my lifetime. Somehow I got missed when they took the census. So they are incorrect about all autistics.

Mr. Mitchell is not the only autistic person who rejects the anti-cure ideologies of King Jim and Queen Michelle. There are in fact other high functioning autistic persons for whom they do not speak. And it is difficult to see how they speak at all on behalf of those autistic persons with whom they have very little in common.

People as eloquent as Jim Sinclair or as intelligent as Michelle Dawson do not share the same realities of life as a much lower functioning autistic person with limited communication skills and limited understanding of the world, someone like my son Conor. Like Ms Dawson I once worked for Canada Post, albeit as a lawyer. It can be a complex and challenging work environment regardless of one's position. To be a letter carrier or postal clerk requires signficant command of language. My son does not know what Canada Post is, he does not know what a PO Box or postal code is, or what it represents.

Jim Sinclair and Michelle Dawson are free, in democratic societies, to use the Royal We in presuming to speak on behalf of all persons with Autism. But my son Conor Doherty, diagnosed at age 2, with Autism Disorder, with profound developmental delays does not sit as a subject in their courts. If safe, effective, treatments and cures are found for him then I will not hesitate to seek their application for Conor's benefit, to improve his life, to help him experience life to the fullest.

Autism Disorder and Impulse Control

There are many puzzling features of autism. Hence the puzzle symbol for autism. Some of the mystery is being removed as our daily news brings us reports of new studies mapping the genetic and biological basis of autism. But even those areas are just beginning to be explored and while we are living through an Autism Knowledge Revolution there is much which remains unexplained and mysterious. Impulse control is one of those unexplained mysteries.

Even 10 years after Conor was diagnosed with Autism Disorder I am still startled by the impulses which suddenly seize Conor, and I mean seize literally, turning gentle acts of affection into potentially injurious and even dangerous acts of violence. Conor is very affectionate, tactile and observant. He likes to place his hands on either side of Dad's scruffy bearded face and study my face. But some times, suddenly, his hands dig painfully into my face. Sometimes he will grab my throat. Conor has also suddenly grabbed his mother by the hair and snapped her head and neck. Walking arm in arm downtown Fredericton, as we often do on weekends, he will occasionally grab by arm forcefully.

We have never thought for even a second that Conor intentionally tries to injure. I do not believe he has control during these instances. An impulse appears to overcome him suddenly and often is not preceded by any apparent triggering environmental stimuli. Conor simply appears physically seized by a powerful impulse.

I do not know what causes these seizure like impulses. I realize that my description of these events may sound like they are epileptic seizures and Conor's pediatrician may well confirm that lay person's guess. I know that there are many articles commenting on comorbidity of autism and epilepsy. Putting a new name on them may well be helpful in leading to other literature and understanding but I suspect that the behavior itself when it happens will always be startling and mysterious.

Friday, January 18, 2008

Healthy 29 Year Old Man Suffers Taser Death In Minnesota

Mark Backlund, a 29 year old man, reported by his family to be in good health, has died after being tasered by Minnesota police for failing to cooperate after crashing his vehicle. The official line is that "more study" is needed to determine the cause of death. No word on whether officials will consider the remote possibility that the taser blast might have had something to do with it.

Thursday, January 17, 2008

Autism and AutismPro - Buzzwords Aplenty But Where Is The Evidence???

AutismPro is a commercial internet based software package available from VEC Inc. VEC is undeniably expert at self promotion. It's latest of many Press Releases is "evidence" of VEC's very substantial self promotional skills. In an earlier commentary, AutismPro - "Somewhat" Evidence Based Internet Autism Intervention or Not Evidence Based At All?, I questioned the evidence basis of AutismPro. Apparently I needn't have worried. After all, highlighted in the latest Thomas Mitchell/VEC Inc. Press Release is information which appears to address my concerns:

The rich content represents evidence-based best practices for children within the autism spectrum of disorders as defined by the US National Research Council in 2001

The above quote is from renowned autism expert Kathleen A. Quill. That should be the end of any questions about the evidence bases of AutismPro right? Well no it isn't. Dr. Quill, as the Press Release acknowledges, is a professional advisor to AutismPro and has been since its inception. It is difficult to view her as a detached, objective source for assessing the merits of AutismPro.

More importantly the quote from Dr. Quill addresses none of the issues I raised in my earlier commentary. The various interventions offered in the AutismPro package vary in the strength of evidence in support. Further, when various interventions are offered in combination they become a new, eclectic, intervention for which new evidence is required in order to be able to claim that the intervention is "evidence-based". Presumably the qualifications, experience and skills of the person using the program would affect the results achieved.

Autism is a perplexing neurological disorder. The delivery of any autism intervention by a pre-packaged program far from the time and place of the challenges involved in educating or treating an autistic child introduces a new element to any intervention used. AutismPro is unquestionably innovative, a buzzword that will undoubtedly help sell it to Education Departments and School Districts but it is very much open to debate as to whether it is "evidence based".

None of which is meant to detract from the admirable job done by Mr. Mitchell and the VEC Inc. PR team in selling AutismPro. The latest Press Release includes an impressive list of buzz words and phrases some of which are set out below:

autism software solution
innovative software program
intelligent software systems
state-of-the-art Internet technologies
impressive collection of seasoned special educators
world-renown autism specialists
enable educators
educational achievement
collective brainpower of leading autism experts
comprehensive web-based special education case management system
robust reporting capabilities
comprehensive end-to-end instructional management system

The buzz words and phrases in this latest VEC release are impressive. But where is the evidence that AutismPro itself is an evidence based effective intervention for educating or treating autistic children? In a 2006 Press Release VEC Inc. stated that:

"Dr Holden is currently undertaking a research trial consisting of 46 families across Ontario, including 63 adult care providers and 52 children aged 2 to 9, using AutismPro. The study is being done in partnership with Autism Ontario and Autism Spectrum Disorder - Canadian American Research Consortium (ASD - CARC) out of Queen's University. Participants have been provided with a one year subscription to the program."

http://ww1.prweb.com/releases/2006/12/prweb489594.htm#

I had some concerns about the objective value of research trials being conducted by Dr Holden who was also an AutismPro consultant. But that being said, what were the results of the studies which were being conducted in 2006?

If AutismPro is an evidence based effective intervention for autistic children where is the evidence?

Wednesday, January 16, 2008

Why I Find No Joy In Autism - Biting and Other Self Injurious Behavior



Above are two pictures taken a short while ago. Conor came home from a great day at school. He sat at a computer as he often does to view some of his favorite sites which he has bookmarked. For some reason, slow loading pages perhaps, I am not sure, Conor became very frustrated with the computer, suffered a meltdown and began biting his hand.

There are those who argue we should find joy in autism, we should view our child's autism as part of who he is and not try to cure him of his autism or change his true autistic nature. To me such reasoning is absurd. Not just wrong but absurd. Self injurious behavior, such as the biting shown above is one major reason why I feel that the joy of autism philosophy is perverse nonsense.

My son is beautiful, in Conor I find great joy, but not in his autism, not in his self injurious behavior.

Capilano College ABA For Autism And Related Disorders Program


Capilano psychology instructor, Ellen Domm, was motivated by her seven-year-old son, Levi, to start a bachelor's degree program at the college that will teach professionals to treat children with autism and related developmental disorders, such as Asperger's syndrome. (CNW Group/Capilano College)

Parents of newly diagnosed autistic children will face tremendous challenges as they strive to help their children. They will receive a bewildering range of advice when responding to the reality of their child's autism. They will read essays by some, not all, but some, high functioning autistic persons and persons with Aspergers telling them that they should not try to cure or treat their autistic children. Even some parents of autistic children will advise them to surrender, to accept their child's autism as a blessing; they will be counseled to find the joy of autism.

For those who move past such side alleys and try to help their children through treatment and cure they will be confronted with a further bewildering array of quack treatments from NAET to swimming with dolphins. If they are lucky they will be pointed in the direction of the only substantially evidence backed treatment option currently available - Applied Behavior Analysis. In Canada though our federal governments have shown no serious interest in ensuring that funding for ABA treatment be made available to all autistic Canadian children regardless of which province they live in. But even then, if they live in a province that makes at least some contribution towards the cost of autism treatment and even if they have the independent finances to obtain treatment they find a shortage of capable ABA practitioners.

In New Brunswick local autism advocacy groups worked with the University of New Brunswick to establish an autism intervention training program to provide interventions to pre-school autistic children and in recent years we have enjoyed some success in pushing the program and the training into the school system with teacher aides and resource teachers receiving autism intervention training through the UNB-CEL Autism Intervention Training program. We are far short of the levels of trained personnel we need in these areas but we have made significant progress.

In British Columbia a mother has taken a similar route. The attached CNW news release, and photo above, tell the story of Ellen Domm a psychology instructor and mother of a seven year old boy diagnosed with autism at the age of three and the applied behavior analysis (ABA) bachelor's degree program that will commence in 2009 and which she helped establish:


Instructor's experience inspires new autism therapy degree program at Capilano College


NORTH VANCOUVER, Jan. 10 /CNW/ - Ellen Domm knows intimately how thousands of families in B.C. suffer due to a scarcity of qualified professionals to treat children with autism and related developmental disorders such as Asperger's syndrome. And the Capilano psychology instructor hopes a unique applied behavior analysis (ABA) bachelor's degree program inspired by her family's experience, which the college is launching in 2009, will help alleviate what she says is clearly a staffing crisis. When Domm's seven-year-old son, Levi, was diagnosed at age three with autism, a condition affecting the brain's normal development of social and communication skills, she and her husband Perri immediately decided on an ABA
treatment program.


Although the scientifically validated therapy would be expensive - as much as three times the province's $20,000 annual subsidy for autistic children up to age six, after which it drops to $6,000 - it was their son's best hope for improvement. But when they tried to assemble a behaviour interventionist team to implement the program, Domm said they quickly found out how difficult that was.


"Even though we had a pool of Capilano students to draw from and train, the turnover rate is quite high," she said, "and we went through 14 therapists in two years." Autism is now the most common childhood developmental or neurological disorder in the country, affecting more than 4,300 children in B.C."But we have only a handful of board certified behaviour analysts," said Domm, "and they have lengthy waiting lists." So, she thought, why not offer an ABA course at Capilano with a practical component so families can count on steady pool of motivated students to work with their kids.


She pursued the idea with fellow Capilano psychologist Cara Zaskow and with her help, and input from autism families and professionals, the course has mushroomed into Canada's first ABA bachelor's degree program. Scheduled to begin next January, it will operate as a cohort program, accepting about 20 students with associate degrees in psychology to train for work with autism cases, among others.


"They'll be qualified to become board certified associate behavior analysts, earning at least $40 an hour to start," said Domm. "Or they can pursue a master's degree in ABA, special education or psychology." Thanks in large part to his therapy, Levi, a high-functioning autistic, is now an attentive, affectionate boy. He attends a mainstream Grade 2 class and receives 12 hours a week of academic and behavioral therapy at home. "I still worry about his future," Domm said, "but what mother doesn't? And I'm pleased that Capilano will soon be producing the professionals the autism community so desperately needs so other families won't be left in the lurch like we were."

Monday, January 14, 2008

Autism, De Novo Genetic Mutation and Environmental Mutagens

The genetic bases of autism dominated autism news the previous week with the publication of the Chromosome 16p11.2 study in the New England Journal of Medicine and three CNTNAP2 gene study reports, Alarcón et al., Arking et al.,and Bakkaloglu et al., in the American Journal of Human Genetics respectively. Various ideological, literary, anthropological and cultural perspectives on autism make for interesting chat, and occasionally heated debate, but add little to our real understanding of autism. It is very encouraging to see our science based understanding of autism growing in such dramatic fashion.

As a lay person heavily dependent upon credible interpretations of the science though I was struck by the references to genetic mutations and de novo genetic mutations. I tried to Google my way to a basic understanding of some of these concepts and some of the references that I found helpful follow:

The Genetics Home Reference web page provides some basic helpful information that indicates that environmental factors can play a role in some genetic mutations:

Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body.

Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder.

Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation.

At Learn. Genetics page of the Genetic Science Learning Center of the University of Utah an explanation is provided for how mutations occur:

There are two ways in which DNA can become mutated:

  1. Mutations can be inherited. This means that if a parent has a mutation in his or her DNA, then the mutation is passed on to his or her children.
  2. Mutations can be acquired. This happens when environmental agents damage DNA, or when mistakes occur when a cell copies its DNA prior to cell division.
The Learn. Genetics site indicates that environmental agents that can damage DNA include ultra violet radiation and certain chemicals. On the What Causes DNA Mutations page of the site the Center provides diagrams and further explanation of both the environmentally caused mutation process and the cell copying mistake process.

1. DNA damage from environmental agents

normal DNA structure

Modifying nucleotide bases

Ultraviolet light, nuclear radiation, and certain chemicals can damage DNA by altering nucleotide bases so that they look like other nucleotide bases.

environmental DNA damage

When the DNA strands are separated and copied, the altered base will pair with an incorrect base and cause a mutation. In the example below a "modified" G now pairs with T, instead of forming a normal pair with C.

incorporating DNA mistakes

Breaking the phosphate backbone

Environmental agents such as nuclear radiation can damage DNA by breaking the bonds between oxygens (O) and phosphate groups (P).

breaking the phosphate backbone

Breaking the phosphate backbone of DNA within a gene creates a mutated form of the gene. It is possible that the mutated gene will produce a protein that functions differently.

Cells with broken DNA will attempt to fix the broken ends by joining these free ends to other pieces of DNA within the cell. This creates a type of mutation called "translocation." If a translocation breakpoint occurs within or near a gene, that gene's function may be affected.

In Mutation, Mutagens, and DNA Repair Beth A. Montelone, Ph. D., Division of Biology, Kansas State University, defined mutagen as "a natural or human-made agent (physical or chemical) which can alter the structure or sequence of DNA." In addition to radiation Dr. Montelone describes four categories of chemical mutagens and provides examples of some of the better known chemical mutagens in each category:

1. Base analogs

These chemicals structurally resemble purines and pyrimidines and may be incorporated into DNA in place of the normal bases during DNA replication:
  • bromouracil (BU)--artificially created compound extensively used in research. Resembles thymine (has Br atom instead of methyl group) and will be incorporated into DNA and pair with A like thymine. It has a higher likelihood for tautomerization to the enol form (BU*)
  • aminopurine --adenine analog which can pair with T or (less well) with C; causes A:T to G:C or G:C to A:T transitions. Base analogs cause transitions, as do spontaneous tautomerization events.

2. Chemicals which alter structure and pairing properties of bases

There are many such mutagens; some well-known examples are:
  • nitrous acid--formed by digestion of nitrites (preservatives) in foods. It causes C to U, meC to T, and A to hypoxanthine deaminations. [See above for the consequences of the first two events; hypoxanthine in DNA pairs with C and causes transitions. Deamination by nitrous acid, like spontaneous deamination, causes transitions.
  • nitrosoguanidine, methyl methanesulfonate, ethyl methanesulfonate--chemical mutagens that react with bases and add methyl or ethyl groups. Depending on the affected atom, the alkylated base may then degrade to yield a baseless site, which is mutagenic and recombinogenic, or mispair to result in mutations upon DNA replication.

3. Intercalating agents

acridine orange, proflavin, ethidium bromide (used in labs as dyes and mutagens)

All are flat, multiple ring molecules which interact with bases of DNA and insert between them. This insertion causes a "stretching" of the DNA duplex and the DNA polymerase is "fooled" into inserting an extra base opposite an intercalated molecule. The result is that intercalating agents cause frameshifts.

4. Agents altering DNA structure

We are using this as a "catch-all" category which includes a variety of different kinds of agents. These may be:
  • --large molecules which bind to bases in DNA and cause them to be noncoding--we refer to these as "bulky" lesions (eg. NAAAF)
  • --agents causing intra- and inter-strand crosslinks (eg. psoralens--found in some vegetables and used in treatments of some skin conditions)
  • --chemicals causing DNA strand breaks (eg. peroxides)
What these agents have in common is that they probably cause mutations not directly but by induction of mutagenic repair processes .