Nobel Laureate Dr. Phillip A. Sharp told the New York Times January 21 that recent research on micro RNAs – tiny pieces of genetic material that appear to regulate DNA gene expression, among other actions – is a "gift from heaven" because these snippets of RNA play an extremely important, previously overlooked role in many disease processes.

"As research continues, scientists wonder how the small RNA's eluded them for so long," Andrew Pollack reported in the Times. "One explanation is that genes that code for RNA are easy to overlook in computer scans of genomes. But another reason, scientists say, is simply that no one thought to look."

"This work could have been done 20 years ago," Dr. Sharp said. "There's nothing new in it in terms of technology. We just missed it."

One of the small RNAs overlooked by researchers for the past 20 years that may be implicated in diseases such as chronic lymphocytic leukemia, as well as two syndromes that lead to mental retardation (Fragile X and Prader-Willi syndromes) and others, is called RNA interference, or RNAi for short. RNAi "interferes" with the actions of specific genes by simply turning them off.

Does the action of RNAi – or other micro RNAs, new types of which are being discovered weekly – explain why some people develop serious, even fatal, reactions to vaccines while others do not? Viral vaccines, in particular, contain a veritable soup of DNA and RNA from not only the virus against which the vaccine is created, but also the host cells (human or animal) in which the virus was grown.

Is some of that RNA regulatory genetic material, like RNAi, that "turns off" natural processes and leads to the development of autism and other vaccine adverse effects in vulnerable individuals?

This is a critical question that must be answered as soon as possible, since the United States has already begun inoculating 500,000 military personnel and 500,000 civilian "first responders" with the smallpox vaccine, which is acknowledged by government health officials as the most dangerous vaccine ever developed.

Smallpox Vaccine: Is the Preventative Worse Than the Disease?

The last outbreak of smallpox in the United States occurred in New York City in 1947. Three days after the diagnosis of smallpox was made for a hospitalized Mexican businessman, health officials decided to vaccinate everyone in the city. Schools, firehouses, and police stations were turned into inoculation centers. Within a month, approximately 6.4 million New Yorkers—and a visiting President Harry Truman—were vaccinated against smallpox. Two people subsequently died from smallpox. The smallpox vaccine killed nine.

Although smallpox is considered a dangerous, highly contagious disease that can kill as many as 30% of affected individuals, the smallpox vaccine is, according to a report from the National Academy of Medicine, the least safe vaccine ever used on a large scale. As the Centers for Disease Control and Prevention (CDC) prepares to implement the smallpox vaccination program that is part of the CDC Smallpox Response Plan and Guidelines designed in anticipation of and response to a biological terrorist attack using smallpox virus, an increasing number of questions are being raised about advisability of vaccinating the nation.

The Smallpox Response Plan, announced by the White House December 13, 2002, will be carried out under the auspices of the new Homeland Security Act (in effect as of 1/24/03). The Plan calls for immediate vaccination of some 500,000 civilian "first responders," including health care workers, police, firemen, and other law enforcement personnel. (Immunization of 500,000 troops has already begun.) Most of the 74 acute-care hospitals in New York City were expected to participate in the vaccination program, but, by mid-January, a number had already expressed reservations, quickly followed by hospitals across the country. One major concern is the possibility that newly-vaccinated health care providers will inadvertently inoculate hospital patients with suppressed immune systems, which could be deadly.

"Do you furlough staff that have agreed to be vaccinated?" Dr. Robert C. Rothberg at New York University Medical Center in Manhattan asked Newsday reporter Margaret Ramirez January 14. "And is it safe for someone who just received the vaccine to work in a neo-natal [newborn] or oncology [cancer] unit?"

By January 21, more than 80 hospitals all over the country had told the CDC that they will not participate in the smallpox vaccination program because of its danger to hospital staff, patients, and family members, according to a page-one story in USA Today.

Concern about the impact of the vaccine on the health of hospital workers is at the top of most administrators' lists. Should immunized employees be furloughed for the amount of time they are considered to be contagious from the vaccination? What if they become seriously ill as a result of the vaccination? In these cases and others, the biggest unanswered question is: Who pays? If a hospital has to furlough employees after vaccination so they don't harm seriously ill patients, who covers their salary costs? Who pays to replace staff who become ill from the vaccine? If a doctor or nurse goes blind from the vaccine (a "serious" but not "life-threatening" side effect) and is unable to work, to whom does he or she turn for recompense? If a patient or family member of a vaccinated health care worker has an unrecognized immune problem (like cancer or AIDS) and becomes ill from exposure to the worker, who is financially responsible?

These concerns may seem somewhat foolish to those of us who were routinely vaccinated against smallpox as children and, at the time, were told nothing of the vaccine's risks. Even before AIDS existed, however, before organ transplantation became semi-routine and before an aging population produced a higher-than-ever percentage of people with cancer or undergoing cancer treatment, the smallpox vaccine was extremely risky.

What’s In the Smallpox Vaccine?

Unlike most vaccines, the smallpox vaccine is not made from pieces of DNA identified as being from the smallpox (variola) virus. Instead, it is made from cells containing the vaccinia virus, a related "pox" virus. As the CDC web site that discusses the smallpox vaccine explains, "The smallpox vaccine helps the body to develop immunity to smallpox…. The vaccine does not contain smallpox virus and cannot give you smallpox."

Because it is a "live virus" vaccine – meaning that the cells and all the DNA and RNA they contain, host and viral, are not killed during incorporation into the vaccine – the smallpox vaccine can cause serious, even life-threatening, adverse effects not only in the vaccinee but in people exposed to the vaccinee.

According to the CDC, 1000 out of every million individuals who are vaccinated (in other words, one in 1,000) will develop "serious" reactions, including: (1) an allergic or toxic reaction (swelling, soreness, pain, and rash or sores) at the vaccination site ("erythema multiforme"); (2) development of a rash or outbreak of open sores in one area of the body, caused by touching the vaccination site and then touching another part of the body or an unvaccinated individual ("inadvertent inoculation"). While not considered a life-threatening reaction, one of the most serious outcomes of inadvertent vaccination can be blindness; and, (3) a widespread rash all over the body, in which sores break out in areas removed from the vaccination site due to spread of the infectious agent through the blood ("generalized vaccinia").

Between 14 and 52 people per one million vaccinated will experience "potentially life-threatening" effects from the smallpox vaccine, and 1 or 2 people will die from the vaccine, according to the CDC.

Life-threatening effects of the smallpox vaccine are: (1) Serious skin rashes caused by widespread infection of the skin in people with skin conditions such as eczema or atopic dermatitis ("eczema vaccinatum"); (2) ongoing infection of skin leading to tissue destruction (necrosis) that is frequently deadly ("progressive vaccinia" or "vaccinia necrosum"); and (3) inflammation of the brain, also called encephalitis, which can also be fatal ("postvaccinal encephalitis").

Those who are at increased risk for life-threatening reactions to the smallpox vaccine who should not be vaccinated include, according to the CDC: People who have had, even once, certain skin conditions (especially eczema or atopic dermatitis) and people with weakened immune systems, such as those who have received a transplant, are HIV positive, are receiving treatment for cancer, or are currently taking medications (like steroids) that suppress the immune system. Pregnant women should not get the vaccine because of the risk it poses to the fetus. Women who are breastfeeding should not get the vaccine. Children younger than 12 months of age should not get the vaccine. According to the CDC's Advisory Committee on Immunization Practices (ACIP), there should be no "non-emergency use of smallpox vaccine" in children younger than 18 years of age. In addition, those allergic to the vaccine or any of its components—specifically, the antibiotics tetracycline, neomycin, streptomycin, or polymixin—should not receive the vaccine.

It is important to note that, as the CDC points out, these statistics on rates of adverse reactions originate from two studies performed in 1968. Nearly 40 years later, it's likely that a considerably higher proportion of the population will be vulnerable to adverse effects of the vaccine, because of rates of immunosuppression due to cancer, cancer treatment (radiation and/or chemotherapy), eczema, AIDS, organ transplantation, and pregnancy.

Taking all of this information into account, along with what some experts consider to be an extremely small chance that it's even possible to use smallpox as a biological weapon, the National Academy of Sciences' Institute of Medicine issued a report on January 17 suggesting that the CDC slow down and re-think the CDC Smallpox Response Plan and Guidelines.

The Institute of Medicine (IOM) Report

The Institute of Medicine's "Review of the Centers for Disease Control and Prevention's Smallpox Vaccination Program Implementation—Letter Report #1" summarized a study requested by the CDC. It was released publicly on the IOM's web site on January 17, following a leak of its conclusions in the January 16 New York Times. The most striking and contentious recommendation made by the 15 member IOM panel urged the CDC to slow implementation of the vaccination policy "to ensure that the campaign is carried out as safely as possible."

The 54-page IOM report (which is available free on its web site) notes that the panel examined the CDC's "pre-event" vaccination strategy—i.e., the precautionary vaccination of smallpox response teams, first responders (police, firefighters, doctors, nurses), and the general public before a biological attack occurs.

In addition to slowing the pace of the immunization campaign, the panel called for increased "clarity" in all stages of the CDC's plan, including clarification of the "rounds" or "phases" in which immunization is to proceed. The panel also requested greater clarity concerning how reported frequency of adverse effects in phase I will be used to re-evaluate implementation (or cancellation) of secondary and tertiary vaccination phases (i.e., vaccinating the general public). Some selected examples of the 23 specific recommendations included in the IOM report are:

(i) The committee's main concern was to slow the entire immunization process, recommending that the CDC "proceed cautiously, allowing continuous opportunity for adequate and thoughtful deliberation, analysis, and evaluation. Embark on phase II only after adequate evaluation of phase I has occurred."

(ii) To address the committee's concern that consent to vaccination might be neither truly informed nor voluntary, it suggested that "all consent documents include a statement that the risks of the smallpox vaccine, while very low, are predictably higher than the risks associated with most other vaccines, but that the benefit is presently unknown—possibly very low (absent exposure to smallpox) or very high (in the event of exposure)."

(iii) To address the committee's concern about compensation for individuals who are injured or killed by the vaccine, it "further recommends that informed consent forms include explicit notification of the availability, or lack thereof, of compensation for adverse reactions."

(iv) The committee recommended that "CDC collect data on the reasons why potential vaccinees choose not to be vaccinated," and that those data be evaluated after the completion of phase I of the vaccination program before phase II is launched.

(v) So that no adverse reactions to the vaccine go unrecognized, the committee "strongly recommends that active surveillance for adverse reactions be employed, rather than relying exclusively on the passive surveillance systems that already exist (e.g., VAERS [the Vaccine Adverse Event Reporting System]). The committee recommends that CDC use the Pre-Event Vaccination System (PVS) as the primary data collection system for adverse reactions."

(vi) To study long-term effects of the smallpox vaccine and protect against inadvertent exposure of household contacts in phase II (and population-wide inoculation, if necessary), the committee recommended "a follow-up on a subset of individuals in PVS [Pre-Event Vaccination System] rather than a telephone survey of vaccine recipients. The follow-up survey could be used to gather information on long-term effects from the vaccine, as well as information on cases of accidental vaccinia infection in household members of vaccinees, rather than focusing on obtaining data on common adverse reactions."

(vii) To make certain that all individuals at risk of developing serious or life-threatening reactions to the vaccine can and will be identified, the committee "strongly recommends analysis of the phase I PVS [Pre-Event Vaccination System] data as a series of nested case-control studies, with results available before moving on to phase II of the vaccination program."

When asked by New York Times reporter Denise Grady to comment on the IOM study's recommendations before the study was publicly released in its entirety, CDC director Dr. Julie L. Gerberding said she had not yet seen the report (New York Times, January 17). She added, however, "We have enormous respect for the IOM. The credibility of their input is always taken very seriously by CDC, and we look forward to seeing the final report. That's why we wanted to take this issue to the IOM."

Times reporter Grady also interviewed an unidentified IOM panel member who said of the report, "I think it's saying the decision to vaccinate was essentially a political one, and there are a lot of scientific reservations about it. We were not asked to talk about the policy, but we're saying there are a lot of reservations and safeguards that need to be put in place." The IOM report estimated that 30 percent of the US population should not receive the smallpox vaccine because of risk of life-threatening adverse effects (including people with cancer, AIDS, eczema, and other conditions, including pregnancy, because of potential damage to the fetus).

"While we recognize that CDC has been asked to initiate the immunization campaign rapidly, it's important to remember that recipients of the vaccine are voluntarily assuming its risks for the greater public good. We agree with CDC and President Bush that safety is paramount, and we support efforts to minimize those risks," commented Dr. Brian L. Strom of the University of Pennsylvania School of Medicine (Philadelphia), chair of the IOM study committee, upon the release of the report. "Learning from experience, making midcourse corrections on every aspect of the program, and maintaining constant communication with the public are integral to developing the safest program possible."

After the IOM study's recommendations and reservations were publicly released, Dr. Gerberding appeared to dismiss them, contrary to her previous statements. On January 18, Dr. Gerberding told Newsday, "We are not going to delay this program because of concerns about compensation," referring to one of the reasons the IOM panel suggested slowing the pace of the immunization program (see item [iii] above). "…The president's decision to recommend this vaccination program…is based on the fact that we need urgent and immediate action because we live in a dangerous world," she added.

And in the January 18 New York Times, Dr. Gerberding told Grady, "We intend to make this program happen on time. We live in a dangerous world these days where a terrorist attack with smallpox is possible. We must be prepared….We will do what we need to do, to get the show on the road here."

Meanwhile, the Service Employees International Union (which has 750,000 health care workers among its members) and the 153,000-member American Nurses Association both wrote to President George W. Bush asking that the smallpox vaccination program be delayed, according to the January 18 New York Times. By January 21, 80 hospitals in 22 states had informed CDC they would not participate in the smallpox vaccination plan, according to USA Today. "Show me one case of smallpox anywhere in the world, and I would change my mind immediately," Dr. Richard Wenzel of the Virginia Medical College, one of those refusing to participate in the vaccination program, told USA Today. "Or come up with new evidence that the threat is more serious and imminent."

Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, who played a key role in creating the CDC smallpox vaccination plan, told USA Today, "Nobody has a foolproof answer in an area of uncertainty like this. But the federal government had to make a decision. The threat of bioterrorism is real. If you guess wrong, and say there is no chance of an attack, then you've been irresponsible to the American public."

In their rush to implement President Bush's wish to vaccinate health care workers and other first responders against a possible biological attack using smallpox, are federal health officials like Fauci and Gerberding ignoring evidence that could lead to serious, even life-threatening, consequences? Is Dr. Gerberding's determination to "make this program happen on time" just a little too parallel to NASA scientists' ignoring evidence that O-rings in the space shuttle Challenger were faulty, placing on-time launch ahead of the astronauts' safety and, ultimately, their lives?

What else might scientists have missed in their rush to vaccinate people against admittedly deadly diseases? Are RNAi’s – or other micro-RNAs – involved in the toxicity found in all vaccines against organisms that grow in cells, i.e., all viral vaccines? Are these undefined, complicated biologic fluids called "vaccines" responsible for the inexplicable rise in conditions like autism and the development of Gulf War Syndrome?

The smallpox vaccine was last routinely administered in the United States more than 30 years ago, during the presidency of Richard M. Nixon. The smallpox vaccine to be administered today, like some aspects of the plan being developed to dispense it, has been frozen since 1972. Much has changed since then, most specifically the immune status of a considerable segment of the American public. If the federal smallpox immunization program blows up like the space shuttle Challenger did because sticking to an arbitrary timetable is more important than carefully evaluating risk, the lives of many more than seven brave Americans will almost certainly be lost.

More information about smallpox and the smallpox vaccine is available on the Centers for Disease Control and Prevention web site, http://www.cdc.gov. The Institute of Medicine report is available for free on its web site, at http://www.nap.edu/catalog/10601.html?onpi_newsdoc01172003.


References

Grady, Denise. "Medical Panel Has Doubts About Plan for Smallpox." New York Times, January 16, 2003.
National Academy of Sciences Office of News and Public Information. "IOM Report Supports a Cautious and Deliberate Approach to Implementing the Smallpox Immunization Program." January 17, 2003.
Manning, Anita. "Armed Against Smallpox." USA Today, January 6, 2003.
Parker, Laura. "Hospitals Balk at Smallpox Vaccine." USA Today, January 21, 2003.
Ramirez, Margaret. "Smallpox Shot Worries." Newsday, January 13, 2003.
Utley, Garrick and Sanjay Gupta. "NY Faced Last U.S. Smallpox Outbreak." CNN.com, January 18, 2003.