Science Daily reports that a new study has zeroed in on a specific problem in the brains of people with autism and mental retardation (also called intellectual challenge) which may be at least partially responsibility for problems with learning and memory. According to the article:
According to neuroscientists at Tufts University School of Medicine, with students from the Sackler School of Graduate Biomedical Sciences at Tufts, a protein called APC (adenomatous polyposis coli) plays a key role in synapse maturation, and APC dysfunction prevents the synapse function required for typical learning and memory.
This issue, apparently, is of genetic origin - and researchers have found that individuals with autism and MR are more likely to have mutations in the genes responsible for the production of the critical proteins.
As of right now, while the findings are intriguing, it is unclear what impact this difference actually has in the real world. To find out, the researchers have developed a mouse model for study:
The research team's next step is to examine the behavioral and cognitive changes that occur when APC is deleted in neurons of the mammalian brain. They have developed a new mouse model that will allow them to investigate how the loss of APC function leads to synaptic changes and impaired learning and memory.
More Articles on Autism and the Brain:
I see an important study such as the recent vaccinated vs unvaccinated monkey one pushed back by the powers that be, and then I see another regurgitated autism is genetic let’s look at some mice “soon”promoted by NIH and am just sickened.
Barbaraj – the main difference between this study and the recent Hewitson one is that this is good well researched science that adds to the body of science about autism. The Hewitson paper is poorly performed science that adds absolutely nothing to the body of science about autism.
There are several reasons why the Hewitson studies are so bad. One example – in this latest paper she appears to have lost a monkey. Shoddy.
No, this study is not new, this study does NOT address the current epidemic of autism, if you continue to believe autism is genetic that is your right, however, even the old naysayers are against the possibility. The monkey study was correct in recognizing the basic causality of this epidemic and studying same. Soon, we will have to face the facts that vaccines, environmental mercury exposures, including pesticides and amalgam fillings all play a major part in the development of autism, with vaccines being the cause of the current explosion of cases. The studies are coming, and no political force is going to be able to keep their combat line in place for much longer.
Barbaraj, not sure I understand where you’re going with your thoughts.
Are you saying that the structural differences in the brain and other issues related to brain function that are currently being found are not real issues at all?
Or are you sayingthat they are real issues but they are unrelated to autism?
Or are you saying that they may be real and they may be related to autism but they are not genetic in nature and in fact are caused by vaccines?
Or are you saying something completely different here?
Lisa
Barbaraj – so as I understand it, unless a study addresses the FACT that vaccines cause autism, its invalid? Is that your stance?
I don’t have a stance, I believe that these little side studies are designed to take the focus off of the real cause of autism. It’s not unlike finding a reason for cancer clusters, you find what the common factor is and you LOOK, no one says, oh well isn’t it a coincidence that so many genetically susceptible people live on that block. It’s perhaps time we look at individual chemicals taken into cells before and after birth through exposures.
http://library2.usask.ca/theses/available/etd-07022007-140223/unrestricted/Yole_m.pdf
Barbara, am I right in understanding that you believe studies like this one are being conducted solely for the purpose of distracting the world from vaccines as a cause of autism? That is – the researchers, the research institution, the funder and the subjects are all engaged in an elaborate ruse to turn attention to the brain rather than to environmental chemicals?
What would be the purpose of spending all that time and money on such a ruse – and why would all those people agree to it? Isn’t it more likely that there are multiple issues and causes to consider, many of which lead to interesting findings?
The present study is unrelated in any way to vaccines, biomedical interventions or DAN protocols. It’s a finding related to proteins and brain synapses!
Lisa
A thesis or dissertation is not a peer-reviewed journal article, though most become articles in some form. My dissertation was only approved by a panel of four or five professors at Minnesota, which would be considered a potential bias. I’ll be the first to admit not one faculty member on my committee was specifically an autism expert.
I have written at length on the various monkey research, including the funding provided by “Thoughtful House” for several of these published projects. That the research appears in places like Medical Veritas or obscure Polish journals is also a problem.
I’ve started the process of switching academic careers and hope to be in an entirely different field by the end of 2011. I also tabled my plans to write an autism-related book; it isn’t worth the frustrations at the moment.
No ,I’m not saying these types of studies are deliberately set up to negate the very possibility that toxins such as mercury are responsible for autism however, they are funded to provide for very narrow research to occur, where-in a set of circumstances such as this one can be proven, yet the root cause , the event that set off those circumstances is not part of the designed process. I am certain these findings are as accurate as any provided, they are not new, the question remains, what changed ,modified or mutated to cause this APC dysfunction. Of course it’s genetic, but not in the sense of mom and pops genes, in the sense that something is destroying the very basic genetic makeup in a large portion of our children. Had one in sixty-six boys been born without an arm, perhaps the cry for better research would be made and we wouldn’t care so much about the process of an arm bud not forming, we would care more about identifying the toxin.
Barbara – of course most biological research studies do look at frustratingly tiny questions, because that’s the nature of the scientific method.
I would agree that it’s easy to confuse “heredity” with “genetics,” and from what I’ve read both inherited AND spontaneous mutations are likely to be responsible for autistic differences.
Since spontaneous mutation would happen prior to birth, though, it wouldn’t be caused by toxins experienced AFTER birth. Of course, it’s possible that spontaneous mutations occur as the result of toxic encounters during gestation.
Oddly, though, few people seem to feel that maternal exposure to toxins is the issue…
It really should be more simple than this. Autism may be caused by a set of circumstances where epidemiology could and should take precedance over scientific method. Something as routine as applying weed killer to one’s lawn could set off an induced mitochondrial disorder awaiting the next circumstance that could set off a reaction. Amalgams in mom’s mouth, rhogam shots, etc. could provide an embryo with toxic amounts of mercury to set off a chain of events that are exponentially accelerated at the time of the child’s own intake of mercury, where increased dosages could be responsible. Let the scientists describe the biological chain of events, but let the medical detectives start the effort by applying evidence based logic. Too often ,and in reference to autism,this area of medical science is being shunned as anecdotal and dismissed, when it’s place in science should be valued as most important.
Not trying to be difficult, but it seems to me that trying to find associations between autism and X and then assuming those associations are causations has already led to a lot of myth-making.
Remember the hype around the rainy day theory of autism? “there are lots of kids with autism in Seattle. It rains a lot in Seattle. When it rains people watch cable TV. Thus watching cable TV causes autism.”
We’ve had similar hype around pet shampoo, contrails, being wealthy, living in New Jersey, you name it!
I know and agree that the scientific method is dreadfully slow – and in individual cases trial and error when choosing treatments seems to be justified. But I don’t think we’ll find a single cause for most cases of autism by looking for general commonalities in exposures among 1% of American families.
Lisa
I see you ,too, are discounting the value of epidemiology. I believe that is part of the propaganda pushed by pharmaceuticals, to devalue an important arm of science. Many mysteries have been solved by putting these medical detectives to work.
Making light of theories doesn’t always pay, either. Interesting things happen on rainy days, many chemicals are re-wetted only to be picked up later by the sun and volatilized. Jersey has a pretty terrible chemical past, one that included activities such as loading up tractor trailers with chemicals that needed to be dumped, and driving them on rainy days up and down the turnpike letting the poisons drip onto the highway. ..it was a mafia run dumping system. New Jersey ,once higher in compliance , has slipped to a low in vaccinations, likely because the citizens believe them as a cause. No I don’t make light of the suggestions that seem outrageous, because I know the outrageous exists. Likely there will be a much more reasonable explanation for the explosion of autism we’ve experienced these last few years,one that may corelate to the addition of hepb at birth and other additions to the vaccine program, this may well include exposures to this generation of moms who kept their teeth ,and most of us have, due to “better” dental care that included mercury fillings and flouride treatments. Meanwhile, yes, the findings of dysfunction is interesting, but not an explanation.
But it was epidemiology that found no link between autism and vaccines… and it’s individual, anecdotal evidence that suggests that in some cases there IS a link…
IMO there are flaws and strengths to be found in each type of study – but it’s hard to imagine that any individual study of any type will provide a definitive answer to the question of “what causes autism.” In part, I believe, that’s because “autism” is no more a single disorder than is “headache” or “fever.”
Lisa
Epidemiologists are professionally constrained from stating that “X causes Y.” They can offer correlation, probability, and other measures of statistical significance, but they are not experts in causation.
In fact, the U.S. Code prohibits the use of epidemiology as the sole or even primary evidence in a case relating to causation. The British and Canadian courts have similar restrictions on epidemiologists.
An epidemiologic study published in a medical or scientific journal, is legally “hearsay.” An epidemiologic study that is performed by the government, or funded by and subject to oversight bodies, such as one performed by/for the Centers for Disease Control (CDC), may be admissible based on the hearsay exception for government records contained in Fed. R. Evid. 803(8)©.
Epidemiology is, at least legally, only evidentiary in rare instances. Usually, authors of university studies are not permitted to testify as paid experts (COI regulations), and the CDC/NIH have even more restrictive policies.
Quoting from the Federal Judicial Center (fjc.gov): “A final caveat is that employing the results of group-based studies of risk to make a causal determination for an individual plaintiff is beyond the limits of epidemiology.”
Epidemiology is, at best, able to recommend what other fields study and test. That’s extremely important, undoubtedly, but epidemiologists are not research scientists — they are statistical experts from fields such as bioinfomatics and empirical sociology.
I doubt the explanation matters, though. I have heard “epidemiologists” working for private groups make claims beyond what the professional organization allows.
The Association for Professionals in Infection Control and Epidemiology is the main body, followed by the American College of Epidemiology. APIC doesn’t even include the “E” in their official logo, though — epidemiology is not viewed as existing within the medical field, but as an advisory field.
Epidemiologists have no state boards, no licensing requirement, and are not regulated as medical professionals would be. You can call yourself an “epidemiologist” with any degree specializing in statistical analysis of infection and/or disease.
Seriously, these are the ACE requirements:
Doctoral degree, or doctoral equivalent, as follows:
In epidemiology or in any field relevant to epidemiology, with specific formal training in epidemiology of at least one year’s duration.
I admire many epidemiologists, including one I worked with during the start of the AIDS crisis in the 1980s, but I also know the risk of including epidemiological data in a paper. Such data are almost always challenged as “not also considering factors X, Y, and Z.” Correlation is not causation. Not in science.
Yes, and there is no place in science for “epidemiologists” to be providing studies proving vaccines don’t cause autism. A lot of lines have been crossed in the quest for the causation of autism,and while scrutiny has been applied heavily here and there it’s often missed it’s mark. In the case of autism, politics and greed , power and propaganda seem to collide with medicine and science. It seems the government programs and the pharms are being protected, and not the future victims. It’s reminiscent of the untouchable big chemical companies and the greed associated gangs written about in the early eighties, “A Bitter Fog”, “Poison for Profit”. A history lesson on how little our lives are worth in corporate or gangland America.
Some of these discussions do raise the fur a bit..I find it outrageous that we are allowing our beliefs to be swayed by court systems and the press..headlines such as these…imo have no place in science.
“court rules that vaccines do not cause autism”
“court rules that thimerosal does not cause autism”
However toxicology is science and we aren’t allowing that it??
..mercury can cause inactivation of various enzymes, structural proteins, transport proteins and alteration of cell membrane permeability by the formation of mercaptides. In addition mercury may induce one or more of the following effects..increased oxidative stress, mitochondrial dysfunction,changes in heme metabolism, glutathione depletion increreased permeability of the blood brain barrier, and disruption of microtubule formation, protein synthesis, DNA replication, DNA polymerase activity, calcium homeostasis, synaptic transmission, and immune response.
from.. Toxicology:basic and clinical principles ..Ramesh Gupta
Perhaps within this is an explanation for the dysfunction of proteins in the development of autism…possibly more important why is there omission of evidence..is that not lying ?
It seems the issue is covered by lobbyists and well paid spokespeople, who most often aren’t scientists..studies are signed off by researchers who hadn’t read a word or been involved…such as Thorson..the very basic system needs to be reworked..
1972…Can you understand the frustration?
The Pathologic Physiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Received 13 March 1972
The synthesis of proteins was more sensitive to mercury than nucleic acids. Total ribosome content and their distribution among their functional cytoplasmic compartments varied with alterations in protein synthesis activity, suggesting disturbances at the level of gene translation. The capacity to synthesize DNA was conserved in the liver and kidneys at elevated tissue mercury levels. The evidence presented advances the hypothesis that disturbances in protein synthesis is a fundamental aspect of alkylmercury poisoning.
Epidemiologists can “disprove the null hypothesis” — a basic tenet in mathematical modeling. They cannot prove specific causation. It’s confusing outside research statistics, sadly. So, yes, a respected epidemiologist can disprove something, but can never prove — problems a semester-long course in empirical statistics can’t even explain to many students.
It is clear some people have beliefs and biases that go far beyond the science. I’ve never seen the evil plots discussed, never had anyone control what I researched, never had any colleague pressured to research or not research a particular matter.
But, some will always imagine the black helicopters, owned by Halliburton and backed by a secret union of George Soros and Rupert Murdoch, are spreading chemicals at night to test the effects on mankind.
Seriously, when we had malathion sprays during the “Med Fly” years in California, people on radio in San Francisco said it was really an experiment. Last week, I heard someone say that’s why there’s so much autism in the Bay Area and cited a study linking ADHD to pesticides — it was a conspiracy.
I happen to believe pesticides are never a good idea, but the conspiracy theories strain all credibility. But, government stupidity in the past can be cited proving experiments were done decades ago. The problem with conspiracy nonsense: always an element of truth.
There’s just enough ignorance of science in our culture that its easy to persuade people that evil plots are widespread in scientific research.
It breaks my heart on so many levels.
Often it is stupidity and yes pesticides are rarely good for us, but…those risk benefit ratios were always stacked..still are. Organophosphates have been proven to cause behavioral deficits as well as being identified as a group of chemicals proven to lower IQ. Malathion if I recall caused heart and lung problems as well. Yes, pretty much stupidity, but where does it stop?
This malathion issue is important, it’s a great example of a program ,designed to be helpful, yet all of the serious potential for health risks were overlooked . Decades of information pointing toward the dangers of this chemical were ignored.
http://www.chem-tox.com/malathion/research/
Where is the line drawn? How much stupidity can we allow while having such blind faith ?
Another thing, while I’m on my soap box, my child suffers from an array of physical problems, he has exzema, he has gi problems, he has growth issues, including the large head, and runs fevers with colds exceeding 105..why ..why on earth is autism considered a psychiatrically defined syndrome. Perhaps we’d have better luck uncovering root causes if we addressed what caused the health problems that caused the physical damage, that caused the brain damage…that caused the sensory issues..and on..like “swallowed a fly”.. IMO and in other’s I’m sure, autism is improperly assigned as a mental health issue.
Barbara – I’m sorry to hear of your son’s many physical issues. The reality is, though, that by no means all people with autism have these issues, and many who don’t have your son’s issues have different physical issues or none at all.
IMO, autism is NOT a single disorder, and that’s why we wind up disagreeing so much. Your son’s constellation of issues is representative of a group, for sure, but it’s not representative of the large group called “people with autism spectrum disorders.”
If autism were defined as a disorder that included GI issues, skin issues, growth problems, sleep problems and high fevers, very very few of the people now diagnosed with autism spectrum disorders would have that diagnosis. But all people with the ASD diagnosis do have speech/communication/social delays – the only areas of commonality.
Lisa
Very few have eczema? gi issues? bigger than normal heads?gi problems? I don’t believe this at all, I see most regressive autism is accompanied by these issues. The”speech/communication/social delays – the only areas of commonality” represents only the purely psychiatric approach which is exactly representative of my point.
We are ignoring the disease process that brought about these “delays”..which aren’t really delays they are deficits.
Barbaraj, you just confirmed my point when you said that “I see most regressive autism is accompanied by these issues.”
Of course, I have no idea whether, in fact, most regressive autism IS accompanied by these issues, but assuming that such is the case, it is a sub-group of people with autism. I don’t disagree that there MUST be sub-groups with specific physical issues – but if we confound “autism spectrum disorders” with “regressive autism with X Y and Z physical issues” I think we’ll end up even more befuddled.
My son and and many people I know on the spectrum are essentially quite physically healthy and strong (though with some muscle tone and sensory issues). Most of those people are NOT what you’d probably term “regressive autistics,” but rather are people who developed differently from an early age.
I would guess that we are looking at very distinct disorders that happen to have “language and social/communications delays” as a common symptom. Of course, this is just a guess – not a scientifically proven statement! But logic suggests that we parents are looking at different disorders.
Lisa
barbaraj is correct- the majority of children with ASD have sleep disorders, and GI issues…many also have skin problems (ezcema, or hives, or other rashes;many also have allergies, sensitivities, intolerances to foods or pollens, grasses, etc.). In my experiences as a public school teacher, advocate, and parent of young adult w/ASD, who has spoken with countless numbers of others parents, I’m not sure if I even know ONE person on the spectrum who has not had serious issues with sleep problems!
Carol, this is me raising my hand as the parent of a child with autism who has never had eczema or significant sleep issues.
where are you getting your information about “most” people with autism? I am unaware of ANY study looking at eczema, seasonal allergies and the like.
while it’s perfectly possible that you know a lot of kids with these issues, I don’t think it’s accurate to make a blanket statement based on your experience.
If I were to do the same, I’d say “I’ve met a few people with kids on the spectrum who have mentioned allergies and skin issues, and many more who have mentioned food intolerances. On the other hand, I’ve met plenty of parents of kids withOUT autism who have skin issues, allergies, and seem to get sick all the time. My personal experience is that my child prefers certain foods, but has no apparent allergies or intolerances. In addition, I have read no studies that even address the question of whether most kids with autism have seasonal allergies or are more prone to ordinary illness than the typical child.”
Lisa
I just did a few searches at googlescholar.com, and have found many interesting studies connecting illness, allergy,yeast,eczema , gi disturbances surrounding regressive autism. Perhaps because regressive autism is somewhat different than the autism experienced in earlier decades, the host of physical symptoms are newer,as well , and aren’t represented in older literature. It does seem as though regressive autism is the most represented in this epidemic. Even the well sponsored Journal of Pediatrics offers a free, detailed study, with open conclusions, saying more study needs to be done on the issues of autism /leaky gut connections.
huh – I actually put “autism eczema” and “autism allergies” into pubmed (the NIH database) and came up with bupkus.
http://scholar.google.com/scholar?q=eczema+regressive+autism&hl=en&as_sdt=20000001&as_sdtp=on
yep..that’s what I put in on scholar..
http://pediatrics.aappublications.org/cgi/reprint/125/Supplement_1/S1
this is the does it doesn’t it from JP
BTW- barbara, you say that “regressive autism is different than the autism experienced in earlier decades,” and I’m not sure I understand why you say that.
Are you suggesting that there is a new form of autism characterized by later, more sudden onset and a host of physical problems, which you’re terming “regressive autism?” Am I right in thinking that you believe this new form of autism is different from Kanner’s autism or from the autism that existed prior to, say, the late 1980’s – and that it was caused by a specific toxin?
This is an idea that’s new to me, though it actually seems to fit some of the anecdotes most common on sites like AofA. Parents on that site and other similar sites seem to have in common that their children regressed, that they have serious physical problems, that they are generally quite profoundly autistic, and that they (anecdotally) seem to respond well to changes in diet and related treatments.
The problem is, while all this sounds reasonable and logical, it really has very little basis in research so far. I would LOVE to see more studies looking at different autistic cohorts to see what those groups have in common in terms of symptoms, exposures, and effective treatments!
Lisa
I find it has nothing to do whatsoever with aoa or anyone’s opinion, it does however seem to be getting the most attention because whatever it is, likely Kanner’s autism, it’s attacking in a more agressive manner in a more malignant form to many more susceptibles. Possibly caused by larger doses of “whatever” triggers it.
I believe that one article from JP addresses the issue of dietary adjustments. That entire piece is a what if ,maybe, no real conclusions, but at least it opens up a dialogue perhaps for some future studies.
I have no idea why my words are cut
off on the right, so I’m putting in the
other link again, and shortening the
right side.
http://pediatrics.aappublications.org/cgi/
reprint/125/Supplement_1/S1
Just putting my hand up too – my 8 yo son has had no sleep issues, no food allergies, never even really had an ear infection . . . pretty healthy kid overall, who also happens to be autistic.
http://archneur.ama-assn.org/cgi/content/abstract/38/3/191
maybe thirty years ago they made a distinction and lost it …
Having done a bit of Googling, I see a whole lot of anecdotal mention of eczema and autism, but I don’t see a study on what percentage of kids with autism have eczema.
There are a lot of studies on immune dysfunction and autism. Here’s just a few:
CHILDREN WITH AUTISM HAVE DISTINCTLY DIFFERENT IMMUNE SYSTEM REACTIONS COMPARED TO TYPICAL CHILDREN
Immunologists from UC Davis M.I.N.D. Institute find clear biological component to perplexing childhood neurological disorder
May 5, 2005
w w w . ucdmc.ucdavis.edu/newsroom/releases/archives/mind/2005/immune_sys5-2005.html
h t t p : / / pn.psychiatryonline.org/content/40/11/26.full
The University Record, November 16, 1998
Immune system response may cause autism
By Nancy Ross-Flanigan
w w w .ur.umich.edu/9899/Nov16_98/9.htm
February 1, 2008
AUTISM LINKED TO HYPERACTIVE IMMUNE SYSTEM
“A new study has found a group of genes which control vital immune cells are more active in children with autism, providing more evidence of immune system involvement in the disorder… The researchers found that children with that “regressive” form of autism had nearly 500 genes that were activated differently than children with “early onset” autism.”
w w w .ei-resource.org/news/autism-news/autism-linked-to-hyperactive-immune-system/
The immune response in autism: a new frontier for autism research
Paul Ashwood*,1, Sharifia Wills and Judy Van de Water
May 12, 2006
w w w .jleukbio.org/cgi/content/full/80/1/1
a review of current research linking immune dysfunction to autism
P.S. – one stat on sleep issues –
“Sleep problems occur in about 40% to 70% of people with autism”
w w w .webmd.com/brain/autism/autism-symptoms?page=2
Hi, folks. Just wrote a longish new blog post on the question of “autism and physical illness,” and linked to an existing poll about kids’ symptoms. Thought that might facilitate the conversation a bit.
Here’s the link: http://autism.about.com/b/2010/08/31/physical-illness-and-autism-whats-the-connection.htm (it’s just the newest blog post on the site!).
Lisa
In my experience, many kids without autism also have the long list of medical conditions. And about those sleep disorders, there’s not a study out there that depicts the majority with autism suffer from that, and even if there was, it would be statistical only, meaning they have a set number in the study, and they come up with a statistical number. In my own experience with my son who has a diagnosed sleep disorder; sleep onset and sustained sleep via a sleep study, he was the first in our school district that special ed ever had. I had met quite a few autism parents in my state and never once met another child who also had a sleep disorder. The only ones I have met were on-line.
My son has ezcema, but so does my mom and a my sons cousin on his dads side, neither have autism. My son does have IBS, but so does my older sister. Stress alone can trigger GI issues. My son used to be sick all the time but actually was tested for autoimmune disorders, which is a general term for over 80 conditions. He didn’t have any such disorder, his behaviors of mouthing everything got him sick all the time. Every time my son runs a fever, it’s way up there. His highest was 105.8. Can I relate that or connect it to anything? No. My son has no allergies, but my sisters have severe allergies to pollens. The only thing I can some what connect to autism is the sleep issue. My son can ignore the need for sleep as he can ignore pain. However, medical issues aside, autism alone is more difficult than all his medical issues put together.
As for the study itself, it is interesting to me since my nephew was born with a known protein issue which is genetic. Both parents had the genes and the other 5 kids including me have no idea if we also carry this gene. The protein defect could have something to do with how the body then relates to other exposures, and result in more allergies and so on. Who knows, but we will never know unless these studies are conducted.
I am the Aspergeric mom of a three year old ASD diagnosed son and find it at least personally implausible that there is no hereditary function to ASD–in my son’s family there are numerous individuals diagnosed with Autism, Asperger’s, ADHD, and OCD.
To wit: My son is a light sleeper. So am I. So is my mother. My mom is not autistic; I show signs of mild autism w/o language delay (hence, Asperger’s); my son is diagnosed ASD. I had eczema as a child; my son has it. My son does have a large head, but then, so does his father and it is a common trait in his family, which is plagued with multiple cases of ADHD and Bipolar disorder. My son has some mild constipation–not unusual given that I do as well and my father (not autistic) has Crohn’s disease. Most, if not all, of my son’s classic “autism” traits are VERY noticeable in other members of my family. One nephew (14) has classic autism. My son is atypical in being very social and very motivated by external approval (his therapists, my husband and I, etc.).
My son showed no sign of autism until roughly a year, when, in retrospect, I observed his inconsistent responses to his name. His behavior was still normal until nearing two, when development slowed and we aggressively pursued treatment.
I personally find a genetic component and a compromised immune system the most compelling theory, but don’t feel that my personal experience=expert opinion.