The Sunshine Project
19 September 2007
Ebola Error in Wisconsin Shows Lax Federal Biodefense Oversight
Similar Violations May be Undetected Elsewhere
In 2005 and into the summer of 2006, researchers at the University of Wisconsin at Madison (UW) made and manipulated copies of the entire Ebola virus genome without proper safety precautions. Although federal safety rules required a maximum protection Biosafety Level Four (BSL-4) lab for the research, UW allowed it to proceed at the much less safe and secure BSL-3 level. The rules that UW broke are intended to ensure that agents that are easily transmissible and usually incurable don't escape maximum containment. They prohibit working at BSL-3 with Ebola (and similarly dangerous) virus material that has not been rendered irreversibly incapable of reproducing. UW does not have a BSL-4 lab suitable for handling Ebola virus, which is one of the most dangerous pathogens in the world.
Despite the contrary provisions of the NIH Guidelines for Research Involving Recombinant DNA Molecules, permission for UW scientist Yoshihiro Kawaoka to perform the Ebola genome work at BSL-3 was granted by the University of Wisconsin Institutional Biosafety Committee (IBC). This significant violation of NIH Guidelines was not detected in a timely manner by the National Institutes of Health (NIH) or, apparently, by the CDC Select Agent Program staff that inspect the Kawaoka lab.
Ebola virus was first recognized in 1976 in Africa. It is one of the more dangerous pathogens on earth. It is transmitted from person to person and causes a deadly hemorrhagic fever. Most people who contract Ebola quickly die from the disease. Its gruesome progression has provided horrific grist for innumerable popular books and movies, such as "The Hot Zone". An Ebola outbreak currently underway in the Democratic Republic of Congo has claimed an estimated 170 lives.
(A sources section a the bottom of this news release provides links to more information.)
KEEPING EBOLA IN THE BSL-4: The degree of danger posed by the work at UW, which involved manipulation of full-length Ebola cDNAs (see "The Science" below) is scientifically debatable. Some might argue the work was not terribly unsafe, because the Ebola constructs were not used together with two critical proteins whose presence would trigger growth of virulent virus. Others would argue that it was irresponsible to handle complete DNA copies of a virus as deadly as Ebola at less than BSL-4 when the copies were capable of producing virulent virus. From a security standpoint, it may also be argued that it is inadvisable to facilitate access to the Ebola virus by distributing the means to produce it (i.e. the cDNAs) to facilities other than BSL-4 labs, which are fewer and have the strongest security measures in place.
OVERSIGHT FAILURE: The research was not halted until Kawaoka remarkably repeatedly pushed for permission to lower it to biosafety level two (BSL-2), which is used for diseases that are comparatively mild and easy to treat. Kawaoka's persistence in requesting the even lower BSL-2 standard prompted a UW official to consult with the National Institutes of Health, whereupon it was determined that UW did not have appropriate facilities and should never have approved the studies at all.
But the organization that was funding the research, which explicitly included precisely the activity that violated NIH rules, was none other than NIH itself. "NIH disapproved its own project," says Sunshine Project Director Edward Hammond, "but it wasn't stopped because NIH's left hand knew what the right was doing, it was essentially by chance and long after the project started." Says Hammond, "After of years of studying NIH's toothless enforcement of its own Guidelines, it is dismaying but not surprising that NIH's biodefense program was funding work that violates NIH's safety rules. The Guidelines have been an unenforced afterthought for years."
There are several troubling questions that remain:
1) Why did the Madison IBC approve the project in the first place?
2) Why doesn't the National Institutes of Health Office of Biotechnology Activities, which is supposed to oversee this work, have a system in place that detects such violations, especially when NIH is funding the work?
3) Why did the Centers for Disease Control apparently fail to identify the problem? The Kawaoka lab handles select agents and is thus subject to registry and inspection by CDC. Is not an inadequate lab experimenting with the complete means to produce Ebola something that CDC's Select Agent Program should identify and act upon?
Says Hammond, "NIH's Office of Biotechnology Activities has no idea what's going on in the labs it allegedly oversees. It is well-established that there is practically zero oversight NIH under the NIH Guidelines and common knowledge that there is never any penalty for disobeying them."
CELEBRITY STANDARDS? The Kawaoka Lab is known for work on the bleeding edge of virology. It is a world of dangerous experiments with dangerous diseases, such as infecting monkeys with deadly agents. Daring lab workers frequently deal with diseases like 1918 influenza and - by protocol - preemptively pop Tamiflu like it was breath mint. Engineering controls clearly don't seem to themselves inspire complete confidence. It is doubtful that many other virologists would gain institutional approval for some of the lab's practices or, for that matter, would be willing to routinely subject themselves to some of the lab's risks.
The lab is well funded with biodefense grants and is at once admired and controversial. In late 2004, UW and the University of Pittsburgh got into an unseemly bidding war over the scientist, offering up tens of millions of dollars in salaries, labs, people, and other public resources in packages more reminiscent of a MTV pop music star's concert rider than a college professor's salary contract.
"Pecking order means a lot in biology, in Madison and elsewhere, and Kawaoka is a big bird," says Hammond. The Sunshine Project would like to know if celebrity status caused UW to disregard the NIH Guidelines and lower safety and security standards: "If it had wanted to, was the IBC even realistically able to veto Kawaoka's research plans after the University had spent millions to keep him, blowing cash and political capital all the way to the governor's office? That these imbalanced situations exist at all is one good reason to make IBC compliance a matter of law instead of guideline."
Wednesday, September 19, 2007
Ebola Error in Wisconsin
at 12:34 PM