Information on the Rabies Research Protocol Violation
Rabies Researcher Violated Institutional Protocols
CDC found through an in-depth investigation that a principal investigator (PI or research scientist) violated institutional safeguards in place to ensure humane animal research and laboratory worker safety. CDC does not condone or tolerate any violation of institutional protections.
The investigation found that no laboratory workers have become ill and there was no exposure to the broader employee population or community. CDC has taken additional steps to reinforce systems that oversee and ensure compliance with established research protocols and procedures.
In August 2012, the possible breach in a research protocol was reported by CDC employees to management. Managers immediately reported the possible breach in research protocol to the CDC Institutional Official (IO) who oversees animal research. The IO immediately: 1) notified leadership; 2) consulted with the Office of Laboratory Animal Welfare (OLAW) at the National Institutes of Health; and, 3) requested that CDC's Atlanta Institutional Animal Care and Use Committee (IACUC) launch an investigation into the alleged violations.
The Atlanta IACUC promptly and fully investigated allegations raised and proposed specific actions to be taken immediately. The IACUC had access to related records and interviewed staff for the relevant period.
Allegations and the findings of the IACUC investigation included the following:
- Allegation 1: Conducting an experiment(s) on non-human primates (NHP) without a CDC IACUC approved animal protocol: specifically, inoculating (challenging) NHP with non-rabies lyssaviruses not authorized on the CDC IACUC-approved animal protocols conducted in the rabies laboratory.
- Finding 1: NHP studies were conducted by the principal investigator that were not authorized in the applicable CDC IACUC-approved protocols.
- Allegation 2: Failing to promptly apply necessary humane euthanasia at appropriate times upon NHP exhibiting clinical signs of infection (as specified by the euthanasia criteria in the CDC IACUC approved animal protocol).
- Finding 2: Insufficient evidence is available to support the allegation that Rabies Team staff allowed NHP to progress through clinical signs that exceeded the euthanasia criteria specified in the applicable CDC IACUC-approved protocols.
- Allegation 3: Endangering health of staff who handle lyssavirus-challenged NHP by failing to inform staff that the current rabies vaccine may not provide protection (immunity) against the lyssaviruses used in the NHP studies.
- Finding 3: Experiments using NHP did include the use of non-rabies lyssaviruses for which the conventional rabies vaccine and the post-exposure prophylaxis is apparently inadequate and this information was not explicitly communicated to Rabies Team staff and Animal Resources Branch (ARB) staff.
The IACUC recommended that CDC remove the researcher from all animal protocols and permanently ban the PI from being a principal investigator or associate on animal protocols and from access to animal facilities.
CDC supported this investigation and ensured corrective steps were implemented right away.
Following the investigation, CDC instituted all recommended actions including the following:
- permanently banned the PI from any involvement with animal activities.
- conducted a thorough management review
- enhanced record keeping
- improved specimen management and storage
- developed a post-exposure treatment and prophylaxis regimen for non-rabies lyssaviruses
The CDC IO immediately notified proper oversight authorities (OLAW) about the outcome of the investigation. The OLAW develops and monitors, as well as exercises compliance oversight, relative to the Public Health Service Policy on Humane Care and Use of Laboratory Animals. Subsequently, the IO has informed OLAW that corrective steps were taken and completed. OLAW concurred with CDC's actions and determined that no further action by OLAW was necessary. The PI left the agency last year.
In addition to the IACUC review, CDC’s Office of Safety, Health and Environment conducted an investigation regarding the well-being of involved staff. The safety officials conducted a safety risk assessment and developed a post-exposure treatment and prophylaxis regimen for non-rabies lyssaviruses. The officials concluded the research carried out within the laboratories did not pose any additional hazard to the research staff.
Details of the IACUC Investigation
During the course of the investigation, the IACUC confirmed that between 2006 and 2009, rabies researchers were approved to study “rabies virus street isolates” (or canine rabies) in non-human primates. The PI challenged (inoculated) the non-human primates with two non-rabies lyssaviruses (Lagos bat virus and West Caucasian bat virus), which the IACUC determined was not covered by the approved protocol. During the investigation, the PI reported to IACUC his belief that these viruses were encompassed in the language of the protocol. The IACUC disagreed.
The IACUC further found that, contrary to allegation #2, staff consistently indicated during interviews that non-human primates were euthanized when clinical signs of rabies infection were observed. The IACUC did note that between 2005 and 2010, two non-human primates were found dead in their cages. However, the IACUC pointed out that the time between observable signs of illness and death could be as short as 6 hours and could occur between observational periods. Ultimately, the IACUC found there was insufficient evidence available to support the allegation that the non-human primates were allowed to progress in their disease to exceed euthanasia criteria specified in the protocols.
Finally, the IACUC found that CDC staff were reportedly unaware that non-rabies lyssaviruses were used in some of the studies. These could be life-threatening viruses for which no vaccine is known to be protective. Staff reported wearing appropriate protective equipment while working with the animals; however, the IACUC found that animal protocol PIs are required to communicate safety-related issues associated with the pathogens used in animal studies and that this information was shared incompletely with the staff.
In addition to measures taken to address this situation, CDC continually strives to strengthen systems and provides support and training for its scientists so that essential animal research at CDC is conducted in a safe and ethical manner.
Follow up: On March 12, 2013, CDC received a letter from the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) with continued full accreditation with no suggested findings for improvement. In the letter CDC was commended for maintaining an excellent animal care and use program.