September 7, 2022 - Southern Illinois University

Dear Dr. Kruse,

Thank you for the information provided by you and others at your institution regarding the Office for Human Research Protections’ (OHRP) requests for information about a former Southern Illinois University (SIU) employee’s experimental use of a herpes simplex 2 vaccine (HSV-2) in humans.

On September 1, 2017, OHRP learned from a reporter’s inquiry that a researcher at SIU allegedly conducted research involving the experimental use of an HSV-2 vaccine on humans during 2016, without IRB approval and oversight. On October 6, 2017, SIU informed OHRP by letter that this researcher conducted human experiments with an HSV-2 vaccine without IRB oversight or FDA approval from March through August 2016 in St. Kitts, as part of his work with Rational Vaccines, Incorporated (hereinafter referred to as RV, Inc.), a company he co-founded in 2015. SIU characterized these experiments as an “outside activity” with RV, Inc., and not related to the researcher’s work at SIU. SIU also included information about an ongoing investigation regarding other experiments conducted by this researcher that did not involve RV, Inc., stating that SIU would file a formal report about that non-compliance with both OHRP and the FDA.

On October 16, 2017, SIU sent OHRP a formal report of serious non-compliance pertaining to human experiments by the same researcher, conducted between 2011 and 2014. This report did not discuss RV, Inc. experiments because SIU asserted that SIU was not involved in those experiments. After multiple communications to assess the 2011-2014 allegations, OHRP received a letter dated August 3, 2018, from legal counsel to SIU asserting that SIU was not responsible for the 2011-2014 human experiments because they were conducted outside the scope of the researcher’s SIU employment.

The research conducted by this researcher during 2011-2014 was not funded by the Department of Health of and Human Research (HHS). However, the Federalwide Assurance on file with OHRP for SIU at the time those experiments were conducted indicated that SIU extended HHS regulations at 45 CFR part 46 to apply to all research, regardless of funding source. The researcher (who died in June 2017) was an associate professor of microbiology and immunity, hired by SIU in 2007. He was the recipient of an NIH grant for animal studies for development of an HSV-2 vaccine in 2009-2010.

The purpose of this letter is to inform you that OHRP is closing our assessment of whether SIU violated the HHS regulations at 45 CFR part 46 related to the above allegations.

I. BACKGROUND

During fiscal year 2009 to 2010, the researcher and SIU School of Medicine became the recipients of an NIH grant, project number 5R21AI081072-02, titled, “Development of an effective genital herpes vaccine.” This grant funded preclinical research until the end of 2010 and was intended only for experiments in animals. During 2011-2014, this researcher allegedly conducted herpes vaccine experiments in humans, without IRB or FDA approval, and concealed his activities from SIU. As legal counsel for SIU stated in the August 3, 2018, letter to OHRP, “[o]n February 20, 2012, this researcher wrote to one subject, ‘[a]s we have discussed before, all this research conflicts with the laws about how human subjects research should be conducted so please maintain strict confidentiality about all of this. If I did not believe that the FDA system is a hopelessly broken quagmire when it comes to human vaccines, I would not be doing any of this.’”

When this researcher co-founded RV, Inc. in 2015, the company noted its plan to manufacture and conduct clinical trials using the HSV-2 vaccine. On May 8, 2015, SIU licensed two patents stemming from the researcher’s experiments on animals, the “109 patent,” as well as a prior related patent, the “605 patent,” to RV, Inc.

According to SIU officials, they first learned about the 2016 human experiments which took place in St. Kitts at an SIU technology expo in Chicago on October 13, 2016, where this researcher presented information about those experiments, which had been conducted through RV, Inc. The researcher had not previously shared information with SIU about these human experiments nor the content of what was presented during the 2016 expo.

On July 31, 2017, SIU’s IRB Chair met with a former SIU faculty member who worked with the researcher and with the Chief Executive Officer (CEO) of RV, Inc., at their request. The SIU IRB chair was advised by RV, Inc.’s CEO that this researcher had engaged in human subjects research activities prior to the researcher’s 2016 human studies with RV, Inc. The CEO stated that this researcher injected himself and others with the HSV-2 vaccine.

The SIU IRB Chair expressed concerns about these allegations, because according to him, the IRB members thought the researcher’s SIU HSV-2 herpes vaccine experiments had been performed only on animals, specifically mice and guinea pigs, and was overseen by the SIU Institutional Animal Care and Use Committee. The IRB was not aware that human subjects had ever been part of the researcher’s work.

Between August 2017 and early October 2017, the SIU IRB conducted a review of the researcher’s computers, laboratory notebooks and other data, obtaining information about the researcher experiments between 2011 and 2014. The following key points were noted in SIU’s investigations and provided to the IRB:

1. The researcher tested his unapproved HSV-2 vaccine on himself in 2011 outside the context of an approved clinical trial. There was also evidence suggesting that the HSV-2 vaccine was injected into the researcher’s family members, but the IRB could not confirm this. Based on the timing, it appeared that activities may have occurred at SIU, or with the use of SIU assets. The SIU IRB never received or approved a protocol for the testing of this HSV-2 vaccine in human subjects.
2. The researcher apparently tested his unapproved HSV-2 vaccine on at least 15 people (in addition to himself). These individuals do not appear to be members of the researcher’s family and potentially are not members of the research team.
3. It appeared that no physician was involved in the activities related to the HSV-2 vaccine at SIU.
4. Several doses of the HSV-2 vaccine were found in the researcher’s freezer at SIU.
5. No protocol document, consent documents, or HIPAA documents were found during the review of the researcher’s records at SIU.
6. Many communications were found at SIU between the researcher and individuals who took part in these experiments, including the researcher’s instructions that they should discontinue certain medications.

On October 11, 2017, the convened SIU IRB discussed the investigative evidence related to these allegations, including the six issues set forth above. The IRB concluded that the researcher willfully conducted the 2011-2014 human experiments without the approval and oversight of the IRB, in contravention of SIU’s policies, applicable laws, and regulations. This conclusion is contained in the October 16, 2017, report of serious non-compliance to OHRP.

II. CONCLUSION

OHRP has direct compliance oversight authority over the IRBs that review HHS-funded or -conducted human subjects research, and institutions engaged in HHS-funded or -conducted human subjects research. Institutions can agree to voluntarily extend OHRP oversight authority to human subjects research in which the institution is engaged that is not HHS-funded or -conducted, when submitting a Federalwide Assurance.

The issue of an institution being engaged in research in turn requires an examination of the actions of the individuals conducting the research and determining when and to what extent they might constitute the actions of the institution. In OHRP’s 2008 guidance document, “Engagement of Institutions in Human Subjects Research,” OHRP provides the following guidance regarding how OHRP interprets the concept of an institution’s employees or agents for purposes of determining whether the institution is engaged in research:

“For purposes of this document, an institution’s employees or agents refers to individuals who: (1) act on behalf of the institution; (2) exercise institutional authority or responsibility; or (3) perform institutionally designated activities. ‘Employees and agents can include staff, students, contractors, and volunteers, among others, regardless of whether the individual is receiving compensation”.

As explained above, legal counsel to SIU asserted that OHRP does not have regulatory compliance authority over SIU for the researcher’s experiments conducted during 2011 through 2014. Referring to the OHRP 2008 engagement guidance, quoted above, the attorney stated that events between 2011-2014 indicate that the researcher was acting on his own, in a clandestine manner, and outside the scope of his SIU employment. While we do not necessarily agree with SIU’s conclusions on this issue, we do acknowledge that it is far from clear that it could be demonstrated, under the appropriate legal standards relating to OHRP’s authority, that SIU was responsible for the actions of this researcher while he was conducting the described experiments during that time period.

As for research that took place during 2016, under the oversight of RV, Inc., those activities were likely not under OHRP’s authority because that work had been specifically designed to constitute an “outside activity” of the researcher in relation to his employment by SIU. It was conducted through work by RV, Inc., an entity that did not receive Federal funding for human subjects research.

In addition, OHRP does not foresee a future risk for individuals becoming research subjects, without required IRB approval, because of actions by an SIU employee. Furthermore, it would be quite difficult to obtain additional information regarding the alleged activities conducted by this researcher. As noted above, the researcher died in 2017. The staff associated with the researcher left SIU shortly after the researcher died.

At this time, there should be no need for further involvement by our office in this matter. Please notify us if you identify new information which might alter this assessment.

We appreciate your institution’s continued commitment to the protection of human research subjects.

Sincerely,

Lisa Buchanan, MAOM
Director
Division of Compliance Oversight

cc:
Ms. Alisha Mirabile, Human Protections Administrator, SIU
Ms. Winifred Meeker-O’Connell, Director, Office of Clinical Policy, Food and Drug Administration (FDA)
Dr. Quynh-Van Tran, Center for Drug Evaluation and Research, FDA
Dr. David Glasgow, Office of Regulatory Affairs, FDA
Dr. Michelle Bulls, Director, OPERA, Office of Extramural Research, National Institutes of Health NIH
Dr. Pamela Kearney, Director, Division of Human Subjects Research, Office of Extramural Research, NIH
Dr. Adam Berger, Director, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Ms. Lydia Kline, Team Lead, Clinical Research Policy, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH