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Biological Weapons, Bioterrorism, and Vaccines

Biological Weapons, Bioterrorism, and Vaccines

A biological attack by terrorists or a national power may seem more like a plot element in an action film than a realistic threat. And indeed, the possibility of such an attack may be very remote. Biological attacks, however, have occurred in the past, one as recently at 2001. Accordingly, a collection of U.S. government agencies are involved in planning responses to potential biological attacks.

Bioweapon threats could include the deliberate release by attackers of an agent that causes one or more of a variety of different diseases. Public health authorities have developed a system to prioritize biological agents according to their risk to national security. Category A agents are the highest priority, and these are disease agents that pose a risk to national security because they can be transmitted from person to person and/or result in high mortality, and/or have high potential to cause social disruption. These are anthrax, botulism (via botulinum toxin, which is not passable from person to person), plague, smallpox, tularemia, and a collection of viruses that cause hemorrhagic fevers, such as Ebola, Marburg, Lassa, and Machupo. These disease agents exist in nature (with the exception of smallpox, which has been eradicated in the wild), but they could be manipulated to make them more dangerous.

Category B agents are moderately easy to disseminate and result in low mortality. These include brucellosis, glanders, Q fever, ricin toxin, typhus fever, and other agents. Category C agents include emerging disease agents that could be engineered for mass dissemination in the future, such as Nipah virus. (This index of possible threats from the CDC lists all Category A, B, and C agents. Note that chemical weapons, such as those involving nonbiological substances such as chlorine gas, are not included.)

The use of effective vaccines would likely protect lives and limit disease spread in a biological weapons emergency. Licensed vaccines are currently available for a few threats, such as anthrax and smallpox, and research is underway to develop and produce vaccines for other threats, such as tularemia, Ebola virus, and Marburg virus. Many bioweapon disease threats, however, lack a corresponding vaccine, and for those that do, significant challenges exist to their successful use in an emergency situation.

What Is a Bioterror Threat?

The draft Model State Emergency Health Powers Act of 2001, which is a document designed to guide legislative bodies as they draft laws regarding public health emergencies, has defined bioterrorism as “the intentional use of any microorganism, virus, infectious substance, or biological product that may be engineered as a result of biotechnology, or any naturally occurring or bioengineered component of any such microorganism, virus, infectious substance, or biological product, to cause death, disease, or other biological malfunction in a human, an animal, a plant, or another living organism in order to influence the conduct of government or to intimidate or coerce a civilian population.” Biological warfare and bioterrorism are often used interchangeably, but bioterrorism usually refers to acts committed by a sub-national entity, rather than a country.

How Likely Is a Biological Attack to Happen?

Expert opinions differ on the plausibility of a biological attack. The U.S. Office of the Director of National Intelligence and the National Intelligence Council stated in 2008 that bioterrorism is a more likely threat than nuclear terrorism. That same year, U.S. Director of National Intelligence Mike McConnell revealed that of all weapons of mass destruction, biological weapons were his personal greatest worry (McConnell, 2008). Other defense experts and scientists insist that the possibility of any attack, especially a large-scale one, is small, given the immense challenges to cultivating, weaponizing, and deploying biological agents. For example, the technical difficulties in aerosolizing a disease agent and dispersing it accurately and widely while maintaining its virulence are immense. Regardless, most biosecurity experts acknowledge that the potential of an attack should not be ignored. Moreover, preparations for a biological attack will likely benefit the response to other kinds of public health emergencies.

History

Biological Weapons                  Biological weapons are not just a 21st century concern: humans have used infectious agents in conflicts for hundreds of years. Below are a few examples.

  • In a 1336 attempt to infect besieged city dwellers, Mongol attackers in what is now the Ukraine used catapults to hurl the bodies of bubonic plague victims over the city walls of Caffa.
  • Tunisian forces used plague-tainted clothing as a weapon in the 1785 siege of La Calle.
  • British officers discussed plans to intentionally transmit smallpox to Native Americans during Pontiac’s Rebellion near Fort Pitt (present-day Pittsburgh, Pennsylvania) in 1763. It is not clear whether they actually carried out these plans. But, whatever its source, smallpox did spread among Natives Americans in the area during and after that rebellion.
  • The Japanese used plague as a biological weapon during the Sino-Japanese War in the late 1930s and 1940s. They filled bombs with plague-infected fleas and dropped them from airplanes onto two Chinese cities; they also used cholera and shigella as weapons in other attacks. An estimated 580,000 Chinese people died as a result of the Japanese bioweapons program (Martin et al., 2007).

The U.S. military developed biological weapons and investigated their effects in the 20th century. The U.S. Army’s Biological Warfare Laboratories was based at Camp (later Fort) Detrick, Maryland, from 1949 to 1969. The program produced and weaponized several biological agents, including anthrax and botulinum toxin, though the biological weapons were never used in conflicts. President Richard Nixon ended the biological weapons program 1969, and U.S. biological weapons were destroyed. U.S. research into biological weapons since that time has focused on defensive measures, such as immunization and response.

In 1975, the Biological and Toxin Weapons Convention (BTWC) came into force. More than 100 nations, including the United States, have ratified this international treaty, which aims to end the development and production of bioweapons. In spite of the agreement, bioweapon threats from fringe groups, terrorists, and nations not committed to or observing the convention continue to worry public health authorities.

The former Soviet Union is known to have produced large quantities of smallpox virus and many other disease agents in its bioweapons program long after it signed the BTWC. In the 1970s, it stockpiled tons of smallpox virus and maintained production capability at least until 1990. The Soviet Union also sponsored an anthrax weapon program; an accidental release of a small amount of weaponized anthrax from a military research facility in 1979 led to at least 70 deaths. The U.S.S.R. claimed that it destroyed its bioweapons stock and dismantled the bioweapons program in the late 1980s, but most experts are skeptical that all stocks, equipment, and records were destroyed. They regard it as possible that illicit transfer of biological materials or knowledge has occurred. So, while only two known sources of smallpox virus exist, both in World Health Organization reference laboratories, many suspect that other groups—whether national or subnational—may have unknown quantities of smallpox virus as well as other remnants of the Soviet biological weapons program.

On a similar note, in the 1990s Iraq admitted to United Nations inspectors that it had produced thousands of tons of concentrated botulinum toxin and had developed bombs to deploy large quantities of botulinum toxin and anthrax. Though the Iraqi government abandoned its bioweapons program after the first Iraq war, the status and whereabouts of the large quantities of infectious material they developed are not known.

Other groups of current concern to biosecurity experts include Al Qaeda, which had a large-scale bioweapons effort in Afghanistan. This was destroyed when the U.S. bombed its facilities and training camps in 2001. Al Qaeda’s program today is likely to be much smaller in scale because so much of its material and intellectual capital was destroyed. Most experts think that Al Qaeda’s current attempts to reconstitute the weapons are focused on chemical weapons rather than on biological ones. At a national level, a 2007 U.S. military assessment of biological threats included the following overview of bioweapons programs, “According to an unclassified U.S. Department of State report in 2005, nations suspected of continued offensive biological warfare programs in violation of the BWC [Biological Weapons Convention] include China, Iran, North Korea, Russia, Syria, and possibly Cuba” (Martin et al., 2007).

Contemporary U.S. Attacks                  Oregon followers of Indian guru Bhagwan Shree Rajneesh mounted an attack that sickened nearly 800 people with typhoid fever in 1984. Cult members introduced bacteria into salad bars and other restaurant food receptacles after their attempts to contaminate the local water supply failed. They hoped to influence local election results by preventing residents from voting. Though 43 people were hospitalized, no one was killed, and the wrongdoers were prosecuted.

A more recent U.S. biological attack occurred just after the Al Qaeda attacks of September 11, 2001, on the World Trade Center and the Pentagon. An unknown actor mailed a powder containing infectious anthrax spores to two U.S. senators and several media outlets. Five people died from anthrax after exposure to the material in the letters, and 17 became ill. Medical personnel offered the anthrax vaccine as post-exposure prophylaxis (PEP) to 1,727 potentially exposed people who were also taking antibiotics to counter anthrax. Of those people, 199 agreed to take the vaccine and received all doses of it.

Law enforcement investigators reached the conclusion that a U.S. biodefense researcher who worked for a military laboratory at Fort Detrick conducted the attacks. The researcher, Bruce Ivins, killed himself in 2008 during the investigation. Ivins, however, was never formally charged with a crime, and no direct evidence links him to the attacks. Speculation about his motives centers on Ivins’s investment in maintaining national interest in an anthrax vaccine he worked on and also on his apparent mental instability. In fact, one might argue that these attacks should be considered a biocrime rather than bioterror incident if the motive was not an attempt to influence the conduct of government or to intimidate a civilian population.

Preparation for Biological Attacks

In 2001, before the 9/11 attacks, several U.S. agencies and academic groups conducted a simulated biological attack, codenamed Dark Winter, in which smallpox virus was the weapon. The exercise, which operated on an assumption of about 12 million available doses of smallpox vaccine, based on the then-available stores of smallpox vaccine, “demonstrated serious weaknesses in the public health system that could prevent an effective response to bioterrorism or severe naturally occurring infectious diseases” (“Overview of Potential Agents of Biological Terrorism,” Southern Illinois University School of Medicine).

One key weakness exposed in the exercise was a shortage of vaccine; this has since been addressed, at least in the case of smallpox, with the addition of hundreds of millions of doses of smallpox vaccine to U.S. vaccine reserves. Other difficulties exposed were the conflicts between federal and state priorities in managing resources, a shortage of medical infrastructure to deal with mass casualties, and the crucial need for U.S. citizens to trust and cooperate with leaders. The reaction of those exposed to anthrax in the post-9/11 attacks illustrates the challenges embedded in the latter issue: a study published in 2008 suggested that the reticence of many exposed individuals to take the anthrax vaccine reflected their fear of the vaccine’s side effects and distrust of medical personnel (Quinn, 2008). In any large-scale bioterror incident, this distrust may be a major hurdle to effective containment of an infectious agent.

Authorities hope that disaster planning and the devising of effective medical countermeasures for biological attacks will both minimize the impact of any such attack and also act as deterrent to those who might consider such an attack. If the attack could be easily contained and addressed, then a terrorist or unfriendly nation might have less incentive to initiate one.

Agencies Involved in Bioweapon Response

A variety of U.S. federal, state, and local agencies are involved in public health emergency preparedness and response. The U.S. Congress funds the Centers for Disease Control and Prevention’s Office of Public Health Preparedness and Response (PHPR) to build and strengthen national preparedness for public health emergencies caused by natural, accidental, or intentional events. Part of the funding supports the Strategic National Stockpile, which manages stores of vaccines, drugs, and medical supplies that may be deployed in national emergencies. (See below for more on the SNS.)

The U.S. Department of Health and Human Services (HHS) houses several offices involved in public health emergency response. The Office of the Assistant Secretary for Preparedness and Response (ASPR) was created after Hurricane Katrina and is responsible for leadership in prevention, preparation, and response to the adverse health effects of public health emergencies and disasters. ASPR conducts research and builds federal emergency medical operational capabilities. Within ASPR, the Biomedical Advanced Research and Development Authority (BARDA) is responsible for the development and purchase of the necessary vaccines, drugs, therapies, and diagnostic tools for public health medical emergencies.

The U.S. Department of Homeland Security includes several groups that address bioweapon threats. The National Biodefense Analysis and Countermeasures Center (NBACC) examines the scientific basis of the risks posed by biological threats. NBACC’s National Biological Threat Characterization Center (NBTCC) conducts studies and experiments on current and future biological threats, assesses vulnerabilities and conducts risk assessments, and determines potential impacts to guide the development of countermeasures such as detectors, drugs, vaccines, and decontamination technologies. Other offices are responsible for responding to and analyzing bioweapon attacks after they occur to help investigators identify perpetrators and determine the origin and method of attack.

State and local health departments, as well as public and private hospitals and local law enforcement agencies, would also be involved in responding to a bioweapon public health emergency. Their roles are outlined in national response plans and are addressed in detail by organization-specific plans.

Role of the Food and Drug Administration

The U.S. FDA controls the pathway to licensure for vaccines, treatments, diagnostic tests, and other tools for responding to biological threats. The regulatory requirements for licensure of a vaccine are complex and apply to a multi-step process of safety, immunogenicity, and efficacy testing, and post-licensure surveillance. (See the article Vaccine Development, Testing, and Regulation to read about this non-emergency approval process.) A typical vaccine might be in development and clinical trials for 10 to 20 years before licensure.

In situations when a new vaccine is needed quickly, the FDA has developed rapid alternative pathways to licensure. One option is an accelerated approval path that might apply in the case of a life-threatening disease with an unlicensed vaccine that has meaningful therapeutic benefit over existing options. Second, in other, more drastic threats, the so-called animal rule may be invoked—if research toward a vaccine or treatment would necessitate exposing humans to a toxic threat, then animal studies, rather than previously conducted studies in humans, may be sufficient for approval. To date, these two rapid pathways have not been invoked for vaccines. More information is available at the FDA’s Critical Path Initiative.

U.S. Emergency Use Authorization (EUA) is an option in pandemic and bioweapon response for both civilian and military populations. After a declaration of emergency by the Department of Health and Human Services secretary, this program allows for use of an unapproved medical product (or a product that has been approved but not for the specific use applicable to the situation at hand) that is the best available treatment or prevention for the threat in question. EUAs were issued for antiviral treatments, a respirator, and a PCR diagnostic test during the 2009 A/H1N1 pandemic.

One challenge to licensing vaccines for response to bioweapon threats is the absence of some of these disease agents in the natural world. Vaccine efficacy is more difficult to establish when natural exposure to a pathogen is impossible (as with smallpox and other threats) and when human challenge studies are not feasible. The FDA accepts animal testing for proof of efficacy in these cases.

In the fall of 2011, national debate focused on the issue of emergency use of bioweapon vaccines. A simulated anthrax attack code named Dark Zephyr was conducted in February 2011 and raised the questions about the use of anthrax vaccine for post-exposure prophylaxis in children. Researchers have never tested the anthrax vaccine for safety and efficacy in children, though it has been extensively studied in adults and has been given to millions of U.S. servicepeople. After considering the issue in the wake of Dark Zephyr, the National Biodefense Science Board, a federal advisory panel to HHS, decided that testing the vaccine in children is ethically justifiable, given that it would provide information important to the health and well-being of any child victims of an attack. Critics have disputed that thinking, stating that the possibility of an anthrax attack is too remote to justify exposing children to any risk at all. HHS has not established a timeline for further action on studying anthrax vaccine in children.

In the meantime, if a bioweapon incident involving anthrax were to occur, adults would be given three doses of the vaccine, along with oral antibiotics, as post-exposure prophylaxis (PEP) under Emergency Use Authorization, as the vaccine is not currently licensed for PEP nor for use in a three-dose regimen. Children might receive the vaccine under FDA approval of an investigation new drug protocol (IND). Use of anthrax vaccine in children under an IND protocol is not ideal, as the protocol is more suited to clinical trials or to an emergency situation for a single patient.

Vaccine Response to Bioweapon Threats

In a wide-scale emergency in which a vaccine is available or potentially available, a large supply of vaccine would be necessary and would be needed quickly. Currently, the U.S. Strategic National Stockpile (SNS) has enough smallpox vaccine to vaccinate every person in the country in the event of a bioweapon attack. The stockpile also holds millions of doses of anthrax vaccine, other vaccines, antiviral medications, and other medical supplies. Quick deployment of a vaccine is essential to its success in preventing disease: for some diseases, vaccinating after exposure may have no effect on preventing disease, and for others, vaccination must occur very quickly after exposure for prophylaxis to work. In the case of smallpox, PEP is most likely to be effective when given within four days of exposure to the virus. Plans provide for smallpox vaccine to be shipped starting on the first day of an attack, and it would continue to be shipped from the stockpile to the rest of the country as needed in the five to six days following the attack.

Biosecurity experts have suggested that the use of agents for passive immunization could play a role in response to certain bioweapon attacks. (Passive immunization is the introduction of antibodies taken from immune donors into nonimmune individuals. The “borrowed” antibodies offer short-lived protection from certain diseases. See our article on Passive Immunization for more information.) The advantage of using antibodies rather than vaccines to respond to a bioterror event is that antibodies provide immediate protection, whereas a protective response generated by a vaccine is not immediate and in some cases may depend on a booster dose given at a later date.

Candidates for this potential application of passive immunization include botulinum toxin, tularemia, anthrax, and plague. For most of these targets, only animal studies have been conducted, and so the use of passive immunization in potential bioweapon events is still in experimental stages.

Conclusion

A biological attack by terrorists or an unfriendly nation is a remote possibility that nevertheless demands public health emergency response planning. Several multi-agency simulations have exposed weaknesses in systems designed to respond to biological emergencies. These exercises have helped to focus planning efforts on the need for emergency plans to address the potential for a large bioweapons event to overwhelm medical capabilities, cause widespread illness and death, and lead to economic and social disruption. The successful deployment of vaccines, antibodies, and other medications in a bioweapon event will depend on a number factors, such as how many people the attack has the potential to harm, the stability of the transportation system in an emergency, the availability of viable vaccine and drugs, and the ability of the public health system to communicate with the public and get the vaccines and medications into the people who need them.

Sources

Arnon, S.A., et al. Botulinum as a biological weapon: Medical and public health management. JAMA 2001;285(8):1059-1070. Accessed 04/19/2017.

BARDA Strategic Plan. (337 KB). Accessed 04/19/2017.

Ben Ouagrham, S. Biological weapons threats from the former Soviet Union. Working Paper Series on Russia and the Former Soviet States. Liechtenstein Institute on Self-Determination at Princeton University. August 2003.

Centers for Disease Control and Prevention. Questions and answers about smallpox vaccine storage and distribution. Accessed 04/19/2017.

Challenges in the use of anthrax vaccine adsorbed (AVA) in the pediatric population as a component of post-exposure prophylaxis (PEP). A Report of the National Biodefense Science Board. October 2011. (1.3 MB). Accessed 04/19/2017.

Fenn, E.A. Biological Warfare in eighteenth-century North America: beyond Jeffery Amherst. Politics and the Life Sciences. Accessed 04/19/2017.

Henderson, D.A., Inglesby, T.V., Jr. O’Toole, T., Mortimer, P.P. Can postexposure vaccination against smallpox succeed? Clin In Dis. (2003) 36 (5); 622-629. Accessed 04/19/2017.

Global Trends 2030: Alternative Worlds. A publication of the National Intelligence Council. December 2012. (20.5 MB). Accessed 04/19/2017.

Martin, J.W., Christropher, G.W., Eitzen, E.M., Jr. History of biological weapons: from poisoned darts to intentional epidemics. In: Dembek, Z.F., ed. Medical Aspects of Biological Warfare, Office of the Surgeon General, Borden Institute, 2007. Accessed 04/19/2017.

McConnell, M. Remarks and Q&A by the Director of National Intelligence. December 2, 2008. (111 KB). Accessed 04/19/2017.

McIsaac, J.H. Preparing hospitals for bioterror: a medical and biomedical systems approach. Burlington, Mass.: Academic Press, 2006.

Model State Emergency Health Powers Act. A Draft for Discussion Prepared by The Center for Law and the Public’s Health at Georgetown and Johns Hopkins Universities. (88.8 KB). Accessed 04/19/2017.

Nightingale, S.L., Prasher, J.M., Simonson, S. Emergency Use Authorization (EUA) to enable use of needed products in civilian and military emergencies, United States. Emerg Infect Dis [serial on the Internet]. 2007 Jul. Accessed 04/19/2017.

O’Tool, T., Michael, M., Inglesby, T.V. Shining light on “Dark Winter.” CID 34:7, 972-983. Accessed 04/19/2017.

Quinn, S.C., Thomas, T., Kumar, K. The anthrax vaccine and research: reactions from postal workers and public health professionals. Biosecur Bioterror. 2008 December; 6(4): 321–333. Accessed 04/19/2017.

Southern Illinois University School of Medicine. Overview of potential agents of biological terrorism. Accessed 04/19/2017.

Stein, R. Possible study of anthrax vaccine’s effectiveness in children stirs debate. Washington Post, 10/13/11.  Accessed 04/19/2017.

Tucker, J.B. Scourge: the once and future threat of smallpox. New York: Grove Press, 1992.

Wheelis, M. Biological warfare at the 1346 siege of Caffa. Emerg Infect Dis [serial online] 2002 Sep. Accessed 04/19/2017.

Wilkening, D.A. Sverdlovsk revisited: Modeling human inhalation anthrax. PNAS 103;20:7589-7594. Accessed 04/19/2017.

Last update 19 April 2017

Do Vaccines Cause Autism?

Do Vaccines Cause Autism?

Autism rates in developing countries have risen remarkably in the past 20 years. For children born in 1992, according to the U.S. CDC, about 1 in 150 would be diagnosed with an autism spectrum disorder (ASD). For children born in 2004, about 1 in 68 children would receive an ASD diagnosis.[1] It is difficult to compare autism rates from the 1990s and later with rates from the 1940s through the 1980s: in earlier years, autism was associated primarily with very severely affected individuals and the rate of autism was estimated to be only about 1 in 10,000 people.[2] Beginning in the 1990s, our understanding of the spectrum of autism has expanded greatly, and now individuals who would most likely previously not have been thought of as having autism may be classified with one of a variety of ASDs.[3]

Whether the high rates of autism today are due to increased diagnosis and reporting, changing definitions of autism, or an actual increase in development of ASD is unknown.[4],[5] Regardless, researchers and worried parents alike have speculated about causes of autism, and the issue has been widely studied. The role of vaccines has been questioned, along with other possible risk factors for ASD, such as genetic predisposition, advanced parental age, and other environmental factors. Vaccines have perhaps received more scrutiny that any other speculated cause of ASD, and the great majority of scientists, physicians, and public health researchers have come to the conclusion that there is no association between vaccines and autism.[6] Some, however, still question whether vaccines play a role in ASD development, and so the public health and medical establishments continue to address these concerns.

The MMR Hypothesis

The story of how vaccines came to be questioned as a cause of autism dates back to the 1990s. In 1995, a group of British researchers published a cohort study in theLancet showing that individuals who had been vaccinated with the measles-mumps-rubella vaccine (MMR) were more likely to have bowel disease than individuals who had not received MMR.[7] One of these researchers was gastroenterologist Andrew Wakefield, MD, who went on to further study a possible link between the vaccine and bowel disease by speculating that persistent infection with vaccine virus caused disruption of the intestinal tissue that in turn led to bowel disease and neuropsychiatric disease (specifically, autism). Part of this hypothesis – that vaccination was associated with autism – had been suggested previously a few researchers. For example, Fudenberg, in a small pilot study published in a non-mainstream journal, posited this relationship[8], as did Gupta in a review of possible treatments for autism.[9] This hypothesis had not been systematically investigated when Wakefield began to interrogate it.

In 1998, Wakefield, along with 12 co-authors, published a case series study in The Lancet claiming that they found evidence, in many of the 12 cases they studied, of measles virus in the digestive systems of children who had exhibited autism symptoms after MMR vaccination.[10] Though in the paper they stated that they could not demonstrate a causal relationship between MMR vaccination and autism, Wakefield suggested in a video released to coincide with the paper’s publication that a causal relationship existed between the MMR and autism: “…the risk of this particular syndrome [what Wakefield termed autistic enterocolitis] developing is related to the combined vaccine, the MMR, rather than the single vaccines.”[11] He then recommended that the combination MMR vaccine be suspended in favor of single-antigen vaccinations given separately over time. (Wakefield himself had filed for a patent for a single-antigen measles vaccine in 1997 and so would seem to have a potential financial interest in promoting this view.[12])

Reaction to the Wakefield publication was immediate. Press outlets covered the news widely and frightened parents began to delay or completely refuse vaccination for their children, both in Britain and the United States. MMR vaccination rates in Britain plummeted.[13]

Over the next twelve years, the possibility of a link between MMR and autism was studied exhaustively. No reputable, relevant study confirmed Wakefield’s findings; instead, many well-designed studies have found no link between MMR and bowel disease or MMR and autism.[6],[14]

In 2004, then-editor Dr. Richard Horton of The Lancet wrote that Wakefield should had revealed to the journal that he had been paid by attorneys seeking to file lawsuits against vaccine manufacturers.[15] In television interviews, Horton claimed that Wakefield’s research was “fatally flawed.”[16] Most of the co-authors of the study retracted the interpretation in the paper[17], and in 2010, The Lancet formally retracted the paper itself.[18]

Three months after the retraction, in May 2010, Britain’s General Medical Council banned Wakefield from practicing medicine in Britain, stating that he had shown “callous disregard” for children in the course of his research. The council also cited previously uncovered information about the extent to which Wakefield’s research was funded by lawyers hoping to sue vaccine manufacturers on behalf of parents of children with autism.[19]

On January 6, 2011, the BMJ published a report by Brian Deer, a British journalist who had previously reported on flaws in Wakefield’s work. For this new report, Deer spoke with parents of children from the retracted study and found evidence that Wakefield committed research fraud by falsifying data about the children’s conditions.[20]

Specifically, Deer reported that while the paper claimed that eight of the study’s twelve children showed either gastrointestinal or autism-like symptoms days after vaccination, records instead show that at most two children experienced these symptoms in this time frame. Additionally, while the paper claimed that all twelve of the children were “previously normal” before vaccination with MMR, at least two had developmental delays that were noted in their records before the vaccination took place.

After examining the records for all twelve children, Deer noted that the statements made in the paper did not match numbers from the records in any category: the children having regressive autism; non-specific colitis; or first symptoms within days after receiving the MMR vaccine. The Lancet paper claimed that six of the children had all three of these conditions; according to the records, not a single child actually did. (See a table entitled “Comparison of three features of the 12 children in The Lancet paper with features apparent in the NHS records, including those from the Royal Free hospital” that breaks down the comparison between The Lancet numbers and the medical records in the Deer article here.)

In an accompanying editorial, BMJ editor in chief Fiona Godlee and co-authors Jane Smith and Harvey Marcovitch examine the damage to public health caused by a tiny study based on parental recall with no control group – a study that turned out to be almost entirely fraudulent, but whose impact continues to this day.[21]

Although the findings of Wakefield’s paper have long been discredited by scientists, the evidence that the data itself was falsified makes this report by the BMJ a landmark moment in the history of vaccines. Evidence is strong that the original study should not have been published not merely because it was poorly conducted, but instead because it was a product of research fraud.

The Thimerosal Hypothesis

MMR is not the only vaccine or vaccine component that has been targeted for scrutiny by those who suspect vaccination might be related to autism. After the MMR controversy died down, critics turned their questions to thimerosal, a mercury-containing preservative used in some vaccines. (Thimerosal had never been used in MMR, as antimicrobial agents are not used in live vaccines.[22])

In the late 1990s lawmakers, environmentalists, and medical and public health workers became concerned about environmental exposures to mercury, particularly from consumption of fish. With heightened attention to known and potential harmful effects of such exposures, the U.S. Food and Drug Administration (FDA) in 1999 requested that drug companies report on amounts of mercury in their products. The results for mercury in vaccines, in the form of thimerosal, exceeded FDA guidelines for exposures to the kind of mercury found in fish. Mercury in fish appears in the form of methylmercury, which is not readily metabolized and excreted in the human body. It is known to cause, at certain levels of high exposure, harmful neurological effects. The mercury in thimerosal metabolizes in the body to ethylmercury, a compound that, while not widely studied at the time, was thought to be much less harmful than methylmercury.[23]

The FDA had a dilemma: there were no recommendations for exposure to levels of ethylmercury. Should they apply the methylmercury guidelines to ethylmercury? Was there cause for concern about exposure to mercury in childhood vaccines? Unable to answer these questions immediately, together with the American Academy of Pediatrics and other groups, they called for vaccine companies to reduce or eliminate the use of thimerosal in vaccines. Additionally, studies were planned to investigate whether there were harmful effects in children exposed to the amount of mercury in vaccines.

Activists and others became concerned about the safety of thimerosal at this point, and they posited that autism could be an outcome of exposure to mercury in vaccines. The Institute of Medicine undertook a comprehensive safety review of the issue. Their preliminary report, published in 2001, stated that the committee did not find enough evidence to support or reject a causal relationship between mercury in vaccines and neurodevelopmental disorders.[24] However, their final report, published in 2004, came to the conclusion that the large body of evidence gathered on the question since 2001 favored rejecting the hypothesis that mercury in vaccines was associated with neurodevelopmental disorders.[6] Since then, evidence from many studies has continued to support rejecting an association between thimerosal and autism.[25], [26]

Today, thimerosal is no longer used in most childhood vaccines, though some forms of influenza vaccine available in multi-dose vials may contain the preservative.[23]

Other Hypotheses

After thimerosal was removed from most vaccines, autism rates did not drop. Rather, they continued to rise.[1] Some vaccine critics shifted their attention from a hypothesized mercury exposure/autism connection to other targets. One such target is the number of vaccines given to children. Many vaccines have been added to the childhood immunization schedule since the 1980s, and some critics have voiced concern that this increase in vaccine exposure results in autism. However, no evidence of an association between increased exposure to vaccines and autism has appeared.[27] Others have focused on the aluminum adjuvant in some vaccines as a potential cause of autism. Yet the amounts of aluminum used in vaccines are small in comparison to other exposures to aluminum, such as in breast milk and infant formula. Aluminum in vaccines has not been implicated in any infant or childhood health problems.[28]

Conclusion

Most scientific and medical experts are satisfied that no connection exists between vaccines and autism and other neurodevelopmental disorders. Still, critics continue to question the issue. Not only do they question the relationship between MMR and thimerosal and autism, they bring up further culprits they believe might play a role in development of autism. Researchers continue to examine these questions, but there is no evidence that these factors play a role in autism development. Most autism researchers hold that the causes of autism are many and include genetic and environmental factors, but do not involve vaccines.[4],[5]

Sources

  1. Centers for Disease Control and Prevention. Autism Spectrum Disorder: Data & Statistics. Accessed 04/05/2017.
  2. Rice, C.E., Rosanoff, M., Dawson, G., Durkin, M., Croen, L.A., Singer, A., Yeargin-Allsopp, M. Evaluating changes in the prevalence of the autism spectrum disorders (ASDs).Public Health Reviews. 2012; 34(2): 1.
  3. Hertz-Picciotto, I., Delwiche, L. The rise in autism and the role of age at diagnosis. Epidemiology. 2009; 20(1): 84.
  4. Centers for Disease Control and Prevention. Autism spectrum disorder (ASD). Research. Accessed 04/05/2107.
  5. National Institutes of Health. National Institute of Neurological Disorders and Stroke. Autism spectrum disorder fact sheet. Accessed 04/05/2017.
  6. Immunization Safety Review Committee, Institute of Medicine. Immunization safety review: vaccines and autism. National Academies Press, 2004. Accessed 04/05/2017.
  7. Thompson, N.P., Pounder, R.E., Wakefield, A.J., & Montgomery, S.M. Is measles vaccination a risk factor for inflammatory bowel disease? The Lancet. 1995; 345(8957): 1071-1074.
  8. Fudenberg, H.H. Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot study. Biotherapy. 1996; 9(1-3): 143-147.
  9. Gupta, S. Immunology and immunologic treatment of autism. Proc Natl Autism Assn Chicago.1996;455–460
  10.  Wakefield A, et al. RETRACTED:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998; 351(9103): 637-641.
  11. Deer, B. Royal free facilitates attack on MMR in medical school single shots videotape. No date. Accessed 04/05/2017.
  12. Deer, B. Revealed: Wakefield’s secret first MMR patent claims “safer measles vaccine.” No date. Accessed 04/05/2017.
  13. Offit, P.A. Autism’s False Profits. New York: Columbia University Press; 2008. See Chapters 2 and 3.
  14. See a list of such studies in this Children’s Hospital of Philadelphia Vaccine Education Center document.
  15. Horton, R. A statement by the editors of The LancetThe Lancet. 2004; 363(9411): 820-821.
  16. Laurance, J. How was the MMR scare sustained for so long when the evidence showed that it was unfounded? The Independent. September 19, 2004. Accessed 04/05/2017.
  17. Murch, S.H., Anthony, A., Casson, D.H., Malik, M., Berelowitz, M., Dhillon, A.P., … Walker-Smith, J.A. Retraction of an interpretation. Lancet. 2004; 363(9411): 750.
  18. The Editors of The Lancet. Comment: RETRACTION:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet. 2010; 375(9713): 445. Accessed 04/05/2017.
  19. Meikle, J., Boseley, S. MMR row doctor Andrew Wakefield struck off register. May 24, 2010. Accessed 04/05/2017.
  20. Deer, B. How the case against the MMR vaccine was fixed. BMJ. 2011; 342: c5347. Accessed 04/05/2017.
  21. Godlee, F., Smith, J., Marcovitch, H. Wakefield’s article linking MMR vaccine and autism was fraudulent. BMJ. 2011; 342: c7452. Accessed 04/05/2017.
  22. World Health Organization. Thimerosal in vaccines. July 2006. Accessed 04/05/2017.
  23. Most of this narrative refers to the facts and chronology outlined in the Food and Drug Administration’s Publication Thimerosal in Vaccines.
  24. Immunization Safety Review Committee, Institute of Medicine. (2001). Immunization safety review: measles-mumps-rubella vaccine and autism. National Academies Press. Accessed 04/05/2017.
  25. Centers for Disease Control and Prevention. Science summary: CDC studies on vaccines and autism. Accessed 04/05/2017.
  26. American Academy of Pediatrics. Vaccine safety: examine the evidence. (122KB). Updated April 2013. Accessed 04/05/2017.
  27. DeStefano, F., Price, C.S., Weintraub, E.S. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism. The Journal of Pediatrics. 2013; 163(2): 561-567.
  28. Children’s Hospital of Philadelphia. Vaccine Education Center. Vaccines ingredients: aluminum. Accessed 04/05/2017.
  29. Centers for Disease Control and Prevention. Autism spectrum disorder (ASD). Research. Accessed 04/05/2017.
  30. National Institutes of Health. National Institute of Neurological Disorders and Stroke. Autism spectrum disorder fact sheet. Accessed 04/05/2017.

Last update 05 April 2017