The Autism Cases, and What's Next

The fight to get recognition of a link between autism and childhood vaccines took a heavy blow in February when the U.S. Court of Federal Claims found no such connection in the three test cases before it. Results of recent studies certainly portended these outcomes, but hope remained that the so-called Vaccine Court ' the Office of Special Masters of the U.S. Court of Federal Claims ' might side with the claimants.

The claimants were seeking compensation from the National Vaccine Injury Compensation Program (VICP) (See 42 U.S.C. ' 300aa-10, et. seq.), a program set up in 1988 by the U.S. Department of Health and Human Services to compensate those who are injured by certain vaccines. In order to collect on a VICP claim, petitioning parents must generally show that: 1) their child received a vaccine covered by VICP; 2) the vaccine was given in the United States; 3) the child suffered a serious and long-term injury because of the vaccination; and 4) there has been no previous award or settlement concerning that injury. (In certain cases, if an injury is a well-known side-effect of a particular vaccine, and it is listed in what is called the “Vaccine Injury Table,” the petitioners need show only that the victim received the vaccine and that he or she suffered the injury listed in the table in order to recover.)

Many more claims brought by parents of children who began showing signs of autism soon after they received the MMR (measles, mumps and rubella) vaccination are in the pipeline. The three cases decided in February, however, were considered some of the strongest for the claimant side. Looking at one of these cases and at the special master's reasoning for rejecting petitioners' claims gives some indication of where the Vaccine Court can be expected to go with the remainder of these cases.

The Cedillo Case

Theresa and Michael Cedillo, parents of Michelle Cedillo, claimed that their daughter developed autism, immune system dysfunction and gastrointestinal problems following administration of an MMR vaccine, as well as other vaccines containing the mercury-containing preservative agent thimerosal. They said the multiple thimerisol-containing inoculations harmed their daughter's immune system, and then the MMR shot further damaged it. Because her immune system was compromised, the measles virus contained within the MMR vaccine was able to replicate and cause inflammation in her brain and digestive system, leading to autism and inflammatory bowel disease (IBD).

Because these conditions were not listed in the Vaccine Injury Table as being known reactions to the MMR vaccine, the Cedillos were required to demonstrate their right to receive compensation by resort to the four-element test for receiving compensation through the VICP. The sticking point for them was in the third element ' proving that their child's serious injuries were caused by the MMR vaccine. In order to prove this, the court, quoting Althen v. Secretary of HHS, 418 F.3d 1274 (Fed. Cri. 2005), said the Cedillos would have to: “1) put forward a medical theory causally connecting the vaccination and the injury; 2) demonstrate a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and 3) prove [] a proximate temporal relationship between vaccination and injury.”

The Cedillos' daughter Michelle was born in August 1994. She seemed to develop normally, although she was consistently large for her age. During her early months, she received about a dozen inoculations, including shots for hepatitis B, chicken pox and other diseases. Many of these preparations contained thimerosal. On Dec. 20, 1995, she got her first MMR shot. One week after that, Michelle became ill with a high fever and rash, which subsided. She became ill again, however, and returned to her pediatrician's office on Jan. 6, 1996. According to her parents' report to the doctor, her temperature was at one point above 105 degrees. The doctor diagnosed sinusitis, for which he prescribed antibiotics. Michelle received a second MMR shot in March 1996, apparently without incident. However, in the pediatrician's notes from that visit, he noted that Michelle was “talking less since ill in Jan.”

A year later, in March of 1997, Michelle's parents took her to a new pediatrician, Dr. Emilia Matos, who noted that Michelle's development was behind schedule and that she had apparently suffered some neurological damage following her fevers of late 1995 and early 1996. Whether this was a post-immunization phenomenon or a separate occurrence, would be very difficult to say,” the doctor's notes from that visit stated. In July 1997, developmental psychologist Dr. Karlsson Roth, examined Michelle and diagnosed her with severe autism and “profound mental retardation.”

The Cedillos filed a claim asserting that: 1) Michelle contracted autism through exposure to thimerosal; 2) Michelle contracted autism through exposure to the measles virus in the MMR vaccine; and 3) Michelle developed gastrointestinal dysfunction due to exposure to the measles virus in the MMR vaccine. The decision on her claims was issued by Special Master George L. Hastings Jr., in Cedillo v. Sec'y of HHS, No. 98-916V (Spec. Mstr.. Feb. 12, 2009).

Failure to Prove Harm from Thimerosal

The special master determined that the Cedillos had not shown either: 1) that thimerosal-containing vaccines can harm recipients, or 2) that the ones Michelle received actually harmed her. With respect to harm to the general population, the court credited the respondent's expert over the petitioners' experts. This was due in large part to the fact that the petitioners' primary expert relied on evidence of mercury harm involving mercury in a different form or in much higher amounts than that found in childhood vaccines. He also relied on in vitro studies rather than on studies in living creatures, and the results of such studies are known to be less reliably applicable to humans. As the defense expert testified, in vitro studies can provide the basis for a hypothesis, but until their results are shown to apply to humans, they must be treated as purely speculative.

Petitioner's expert Dr. H. Vasken Aposhian, Ph.D, surmised that the reason some children developed autism after vaccination might be attributable to a genetic hypersusceptibility in those children. However, he could not point to any medical literature supporting the contention that any such hypersusceptibilty exists within the general population, despite multiple studies of those with autism. (The court emphasized that the existence of such literature was not a prerequisite to its acceptance of a theory of causation. Its absence, however, weighed against the petitioners.)

Dr. Aposhian also speculated that Michelle might have what he termed a “mercury efflux disorder.” He described the disorder as one in which a person is less able than most to excrete mercury from the system, leading to cell damage. However, no such disorder is recognized in the medical community, and the court was not persuaded that Dr. Aposhian's sources for this theory used sound scientific methods in coming to the conclusion that autistic children or those with immune disorders retained more mercury in their systems following vaccinations with thimerosal-containing agents.

Failure to Prove Harm Through Exposure to the Measles Virus

The Cedillos relied on the results of a diagnostic test Michelle underwent in 2002 as proof that her autism and gastrointestinal disease could be traced to the MMR vaccine. That test, a biopsy of tissue from Michelle's small intestine, detected the lingering presence of the measles virus. The testing was performed by the Unigenetics Ltd. Laboratory operated by Dr. John J. O'Leary and others, located in Dublin, Ireland.

The Unigenetics Laboratory had also tested other autistic and non-autistic children for the presence of the measles virus, and the results of those tests were reported in an article in Molecular Pathology. See V. Uhlmann et al., Potential Viral Pathogenic Mechanixm for New Variant Inflammatory Bowel Disease, 55 Molecular Pathology 84 (2002). The Uhlmann article's primary author was Dr. Andrew Wakefield, a British physician, although 11 other researchers, including the Unigenetics Laboratory's Dr. O'Leary, co-authored it. The Uhlmann study found that most of a group of developmentally disabled children with intestinal problems had the measles virus in their intestines, while the non-disabled children with intestinal problems generally did not.

The assumption that some made from these results was that the live measles virus in the MMR shot might be implicated in causing developmental deficits, including autism. Later tests done by others, however, debunked the Uhlmann study's findings, showing that those authors' testing methodology was faulty and that none of the children in the test likely had the measles virus in their systems.

Two of the Cedillos's experts testified as to the validity of the Uhlmann findings. Respondent's experts disagreed, however, pointing out that the type of testing the Uhlmann authors conducted is very tricky to conduct and lends itself to the production of false positive results. They also faulted the Unigenetics Laboratory's quality control methods and advised that the results of their testing in this instance were unreliable.

The court credited the testimony of the respondent's experts and found that it was unlikely that the Unigenetics Laboratory had truly detected the presence of the measles virus in Michelle's intestines, or indeed in the intestines of the developmentally disabled children discussed in the Uhlmann article. And, even if such a virus was detected, the Unigenetics Laboratory's results did not prove that what the children had was a vaccine-strain virus, versus the “wild” measles virus that they could have been exposed to in their daily lives.

In addition, the petitioners presented preliminary results of an ongoing study being done by another researcher, which showed vaccine-strain measles virus in the guts of autistic children. Their effort was to no avail, however, as the court considered such preliminary findings as just that: preliminary.

The court also determined that the testimony of the Cedillos pediatric neurologist expert, Dr. Marcel Kinsbourne, failed to prove either that the MMR vaccine can cause autism in the general public, or that it did so in Michelle's case. Dr. Kinsbourne credited the tests that showed Michelle had the measles virus in her system and he opined that this persisting virus had invaded Michelle's brain, prompting her immune system to respond and cause inflammation in her brain. This inflammation, in turn, disorganized certain circuits in her brain, causing the autism. He testified that children who have caught the “wild” version of the measles virus have been known to suffer neurological and intestinal damage therefrom. Similarly, since Michelle had suffered both neurological damage (as evidenced by her autism) and intestinal damage, these must have been caused by the same agent: the vaccine-strain measles virus.

The Response

The special master's response to these arguments focused primarily on the lack of proven scientific evidence that could support Dr. Kinsbourne's and the Cedillos's theories. First, as discussed here previously, the court was unconvinced of the reliability of the tests that found the measles virus in Michelle's system. Second, even if such a test did exist, there were no good studies to show that the presence of the measles virus in the brain could result in autism. Third, the fact that the “wild” measles virus had never been shown to cause autism weighed against drawing any such conclusions in the case of the vaccine-strain measles virus. In addition, there is strong evidence that autism may be caused, at least in part, by genetic factors, and autopsies of autistic people have shown that abnormalities in their brains can be traced to the prenatal period, long before vaccines are administered.

Timing was also an issue for the Cedillos's case. Under Althen, a petitioner, in order to recover for a vaccine-related injury, must be able to show that the injury suffered occurred during a time period following the vaccination in which it has been scientifically proven that such injuries will manifest if vaccine-related. Dr. Kinsbourne, however, was unable to pinpoint a specific period of time following an MMR vaccine in which signs of autism should show up, and no other reliable evidence of such a temporal proximity was proffered. These and other factors led the special master to conclude not only that the link between the MMR inoculation and autism had not been proven in the general population, but also that no such link could be shown between Michelle's MMR shot and the onset of her autism symptoms.

MMR Vaccine and Gastrointestinal Diseases

The Cedillos's sole witness on the issue of Michelle's gastrointestinal complaints and their cause was pediatric gastroenterologist Dr. Arthur Krigsman. He based his opinion that the MMR vaccine caused the child's IBS and other intestinal problems primarily on the facts that the Unigenetics Lab's tests found the measles virus in Michelles gut, and her symptoms apparently began soon after she received her first MMR inoculation. However, the respondents' experts, who disagreed with Dr. Krigsman's opinion that Michelle suffered from inflammation in her intestinal tract, also gave no credence to the theory that the measles virus could cause ongoing gastrointestinal problems. In addition, the special master had already found that the Unigenetics Laboratory's tests were faulty and not to be relied upon.

After the Decision

After all the evidence was in, Special Master Hastings sided with the respondents, stating, “I feel deep sympathy and admiration for the Cedillo family ' . However, I must decide this case not on sentiment, but by analyzing the evidence. Congress designed the [National Vaccine Injury Compensation] Program to compensate only the families of those individuals whose injuries or deaths can be linked causally, either by a Table Injury presumption or by a preponderance of causation-in-fact evidence, to a listed vaccination. In this case the evidence advanced by the petitioners has fallen far short of demonstrating such a link. Accordingly, I conclude that the petitioners in this case are not entitled to a Program award on Michelle's behalf.”

The Cedillos are seeking appellate review of the decision. In next month's issue, we'll look at the arguments advanced in their memorandum in support of review of the special master's decision.

Janice G. Inman is Editor-in-Chief of this newsletter.

The fight to get recognition of a link between autism and childhood vaccines took a heavy blow in February when the U.S. Court of Federal Claims found no such connection in the three test cases before it. Results of recent studies certainly portended these outcomes, but hope remained that the so-called Vaccine Court ' the Office of Special Masters of the U.S. Court of Federal Claims ' might side with the claimants.

The claimants were seeking compensation from the National Vaccine Injury Compensation Program (VICP) (See 42 U.S.C. ' 300aa-10, et. seq.), a program set up in 1988 by the U.S. Department of Health and Human Services to compensate those who are injured by certain vaccines. In order to collect on a VICP claim, petitioning parents must generally show that: 1) their child received a vaccine covered by VICP; 2) the vaccine was given in the United States; 3) the child suffered a serious and long-term injury because of the vaccination; and 4) there has been no previous award or settlement concerning that injury. (In certain cases, if an injury is a well-known side-effect of a particular vaccine, and it is listed in what is called the “Vaccine Injury Table,” the petitioners need show only that the victim received the vaccine and that he or she suffered the injury listed in the table in order to recover.)

Many more claims brought by parents of children who began showing signs of autism soon after they received the MMR (measles, mumps and rubella) vaccination are in the pipeline. The three cases decided in February, however, were considered some of the strongest for the claimant side. Looking at one of these cases and at the special master's reasoning for rejecting petitioners' claims gives some indication of where the Vaccine Court can be expected to go with the remainder of these cases.

The Cedillo Case

Theresa and Michael Cedillo, parents of Michelle Cedillo, claimed that their daughter developed autism, immune system dysfunction and gastrointestinal problems following administration of an MMR vaccine, as well as other vaccines containing the mercury-containing preservative agent thimerosal. They said the multiple thimerisol-containing inoculations harmed their daughter's immune system, and then the MMR shot further damaged it. Because her immune system was compromised, the measles virus contained within the MMR vaccine was able to replicate and cause inflammation in her brain and digestive system, leading to autism and inflammatory bowel disease (IBD).

Because these conditions were not listed in the Vaccine Injury Table as being known reactions to the MMR vaccine, the Cedillos were required to demonstrate their right to receive compensation by resort to the four-element test for receiving compensation through the VICP. The sticking point for them was in the third element ' proving that their child's serious injuries were caused by the MMR vaccine. In order to prove this, the court, quoting Althen v. Secretary of HHS , 418 F.3d 1274 (Fed. Cri. 2005), said the Cedillos would have to: “1) put forward a medical theory causally connecting the vaccination and the injury; 2) demonstrate a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and 3) prove [] a proximate temporal relationship between vaccination and injury.”

The Cedillos' daughter Michelle was born in August 1994. She seemed to develop normally, although she was consistently large for her age. During her early months, she received about a dozen inoculations, including shots for hepatitis B, chicken pox and other diseases. Many of these preparations contained thimerosal. On Dec. 20, 1995, she got her first MMR shot. One week after that, Michelle became ill with a high fever and rash, which subsided. She became ill again, however, and returned to her pediatrician's office on Jan. 6, 1996. According to her parents' report to the doctor, her temperature was at one point above 105 degrees. The doctor diagnosed sinusitis, for which he prescribed antibiotics. Michelle received a second MMR shot in March 1996, apparently without incident. However, in the pediatrician's notes from that visit, he noted that Michelle was “talking less since ill in Jan.”

A year later, in March of 1997, Michelle's parents took her to a new pediatrician, Dr. Emilia Matos, who noted that Michelle's development was behind schedule and that she had apparently suffered some neurological damage following her fevers of late 1995 and early 1996. Whether this was a post-immunization phenomenon or a separate occurrence, would be very difficult to say,” the doctor's notes from that visit stated. In July 1997, developmental psychologist Dr. Karlsson Roth, examined Michelle and diagnosed her with severe autism and “profound mental retardation.”

The Cedillos filed a claim asserting that: 1) Michelle contracted autism through exposure to thimerosal; 2) Michelle contracted autism through exposure to the measles virus in the MMR vaccine; and 3) Michelle developed gastrointestinal dysfunction due to exposure to the measles virus in the MMR vaccine. The decision on her claims was issued by Special Master George L. Hastings Jr., in Cedillo v. Sec'y of HHS, No. 98-916V (Spec. Mstr.. Feb. 12, 2009).

Failure to Prove Harm from Thimerosal

The special master determined that the Cedillos had not shown either: 1) that thimerosal-containing vaccines can harm recipients, or 2) that the ones Michelle received actually harmed her. With respect to harm to the general population, the court credited the respondent's expert over the petitioners' experts. This was due in large part to the fact that the petitioners' primary expert relied on evidence of mercury harm involving mercury in a different form or in much higher amounts than that found in childhood vaccines. He also relied on in vitro studies rather than on studies in living creatures, and the results of such studies are known to be less reliably applicable to humans. As the defense expert testified, in vitro studies can provide the basis for a hypothesis, but until their results are shown to apply to humans, they must be treated as purely speculative.

Petitioner's expert Dr. H. Vasken Aposhian, Ph.D, surmised that the reason some children developed autism after vaccination might be attributable to a genetic hypersusceptibility in those children. However, he could not point to any medical literature supporting the contention that any such hypersusceptibilty exists within the general population, despite multiple studies of those with autism. (The court emphasized that the existence of such literature was not a prerequisite to its acceptance of a theory of causation. Its absence, however, weighed against the petitioners.)

Dr. Aposhian also speculated that Michelle might have what he termed a “mercury efflux disorder.” He described the disorder as one in which a person is less able than most to excrete mercury from the system, leading to cell damage. However, no such disorder is recognized in the medical community, and the court was not persuaded that Dr. Aposhian's sources for this theory used sound scientific methods in coming to the conclusion that autistic children or those with immune disorders retained more mercury in their systems following vaccinations with thimerosal-containing agents.

Failure to Prove Harm Through Exposure to the Measles Virus

The Cedillos relied on the results of a diagnostic test Michelle underwent in 2002 as proof that her autism and gastrointestinal disease could be traced to the MMR vaccine. That test, a biopsy of tissue from Michelle's small intestine, detected the lingering presence of the measles virus. The testing was performed by the Unigenetics Ltd. Laboratory operated by Dr. John J. O'Leary and others, located in Dublin, Ireland.

The Unigenetics Laboratory had also tested other autistic and non-autistic children for the presence of the measles virus, and the results of those tests were reported in an article in Molecular Pathology. See V. Uhlmann et al., Potential Viral Pathogenic Mechanixm for New Variant Inflammatory Bowel Disease, 55 Molecular Pathology 84 (2002). The Uhlmann article's primary author was Dr. Andrew Wakefield, a British physician, although 11 other researchers, including the Unigenetics Laboratory's Dr. O'Leary, co-authored it. The Uhlmann study found that most of a group of developmentally disabled children with intestinal problems had the measles virus in their intestines, while the non-disabled children with intestinal problems generally did not.

The assumption that some made from these results was that the live measles virus in the MMR shot might be implicated in causing developmental deficits, including autism. Later tests done by others, however, debunked the Uhlmann study's findings, showing that those authors' testing methodology was faulty and that none of the children in the test likely had the measles virus in their systems.

Two of the Cedillos's experts testified as to the validity of the Uhlmann findings. Respondent's experts disagreed, however, pointing out that the type of testing the Uhlmann authors conducted is very tricky to conduct and lends itself to the production of false positive results. They also faulted the Unigenetics Laboratory's quality control methods and advised that the results of their testing in this instance were unreliable.

The court credited the testimony of the respondent's experts and found that it was unlikely that the Unigenetics Laboratory had truly detected the presence of the measles virus in Michelle's intestines, or indeed in the intestines of the developmentally disabled children discussed in the Uhlmann article. And, even if such a virus was detected, the Unigenetics Laboratory's results did not prove that what the children had was a vaccine-strain virus, versus the “wild” measles virus that they could have been exposed to in their daily lives.

In addition, the petitioners presented preliminary results of an ongoing study being done by another researcher, which showed vaccine-strain measles virus in the guts of autistic children. Their effort was to no avail, however, as the court considered such preliminary findings as just that: preliminary.

The court also determined that the testimony of the Cedillos pediatric neurologist expert, Dr. Marcel Kinsbourne, failed to prove either that the MMR vaccine can cause autism in the general public, or that it did so in Michelle's case. Dr. Kinsbourne credited the tests that showed Michelle had the measles virus in her system and he opined that this persisting virus had invaded Michelle's brain, prompting her immune system to respond and cause inflammation in her brain. This inflammation, in turn, disorganized certain circuits in her brain, causing the autism. He testified that children who have caught the “wild” version of the measles virus have been known to suffer neurological and intestinal damage therefrom. Similarly, since Michelle had suffered both neurological damage (as evidenced by her autism) and intestinal damage, these must have been caused by the same agent: the vaccine-strain measles virus.

The Response

The special master's response to these arguments focused primarily on the lack of proven scientific evidence that could support Dr. Kinsbourne's and the Cedillos's theories. First, as discussed here previously, the court was unconvinced of the reliability of the tests that found the measles virus in Michelle's system. Second, even if such a test did exist, there were no good studies to show that the presence of the measles virus in the brain could result in autism. Third, the fact that the “wild” measles virus had never been shown to cause autism weighed against drawing any such conclusions in the case of the vaccine-strain measles virus. In addition, there is strong evidence that autism may be caused, at least in part, by genetic factors, and autopsies of autistic people have shown that abnormalities in their brains can be traced to the prenatal period, long before vaccines are administered.

Timing was also an issue for the Cedillos's case. Under Althen, a petitioner, in order to recover for a vaccine-related injury, must be able to show that the injury suffered occurred during a time period following the vaccination in which it has been scientifically proven that such injuries will manifest if vaccine-related. Dr. Kinsbourne, however, was unable to pinpoint a specific period of time following an MMR vaccine in which signs of autism should show up, and no other reliable evidence of such a temporal proximity was proffered. These and other factors led the special master to conclude not only that the link between the MMR inoculation and autism had not been proven in the general population, but also that no such link could be shown between Michelle's MMR shot and the onset of her autism symptoms.

MMR Vaccine and Gastrointestinal Diseases

The Cedillos's sole witness on the issue of Michelle's gastrointestinal complaints and their cause was pediatric gastroenterologist Dr. Arthur Krigsman. He based his opinion that the MMR vaccine caused the child's IBS and other intestinal problems primarily on the facts that the Unigenetics Lab's tests found the measles virus in Michelles gut, and her symptoms apparently began soon after she received her first MMR inoculation. However, the respondents' experts, who disagreed with Dr. Krigsman's opinion that Michelle suffered from inflammation in her intestinal tract, also gave no credence to the theory that the measles virus could cause ongoing gastrointestinal problems. In addition, the special master had already found that the Unigenetics Laboratory's tests were faulty and not to be relied upon.

After the Decision

After all the evidence was in, Special Master Hastings sided with the respondents, stating, “I feel deep sympathy and admiration for the Cedillo family ' . However, I must decide this case not on sentiment, but by analyzing the evidence. Congress designed the [National Vaccine Injury Compensation] Program to compensate only the families of those individuals whose injuries or deaths can be linked causally, either by a Table Injury presumption or by a preponderance of causation-in-fact evidence, to a listed vaccination. In this case the evidence advanced by the petitioners has fallen far short of demonstrating such a link. Accordingly, I conclude that the petitioners in this case are not entitled to a Program award on Michelle's behalf.”

The Cedillos are seeking appellate review of the decision. In next month's issue, we'll look at the arguments advanced in their memorandum in support of review of the special master's decision.

Janice G. Inman is Editor-in-Chief of this newsletter.