Information below is from my book "We All Operate in the Same Way." (Virginia Smith Books. 2017.) The Wisconsin State Journal's lead reporter on most of the paper's articles about this line of research is aware of the problems discussed below. Unfortunately, the paper's readers remain in the dark.
Chapter 15. Biosafety
Programs of biosafety and security at UW-Madison
"are among the most rigorous in the world." --
William S Mellon, Ph.D.
Senior Associate Dean, Academic Affairs,
and, Associate Dean for Research Policy,
and, the responsible official for the University's
Select Agent Program.
Jan. 10, 2012.(1)
The University of Wisconsin-Madison's secrecy about its use of animals and its misleading and often false public statements about its use of animals and its biological research cause various kinds of harm. Members of the public cannot form intelligent opinions because they do not have the facts; the pertinent facts are generally kept secret. Animals are hurt and killed in the public's name without the public's knowledge.(2) Americans cannot effectively participate in our form of democracy unless we are reasonably well informed. And of course, public pressure that might be brought to bear out of some concern for the animals used by an institution like the university is less likely to develop when the situation is misrepresented by hiding the details and misstating the facts. The hidden nature of the enterprise means that the harm to the animals is inordinately hard to address by the tiny number of people who take the time to dig for and demand information.
The secrecy that surrounds the use of animals in the nation's publicly-funded government and university laboratories also puts the public at serious risk. Some of the research occurring in these labs has involved the transportation and handling of highly infectious, very dangerous disease-causing agents and using them to infect animals, who in turn become infectious vectors. Whenever the issue is mentioned by media it invariably includes strong assertions by the parties involved that their bio-containment methods are state-of-the-art and that strict regulations guarantee the public's safety. The actual history of research using dangerous and infectious agents is not nearly so reassuring.
The regulation of such agents is the responsibility of the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC). The regulation of agents studied in laboratories entails the assignment of various levels of risk; these are termed, in order of risk, biosafety levels 1, 2, 3, or 4 and are referred to as BSL-1, BSL-2, etc.
The Department of Homeland Security offers this quick characterization:
BSL-1: Microorganisms not known to cause disease in healthy adult human beings.These classifications carry with them recommendations and requirements for the safety procedures used by laboratory personnel and sometimes even the physical design of the lab, particularly in the case of the BSL-3 and BSL-4 labs. Workers in a BSL-3 lab commonly wear some sort of disposable coverall, eye protection, and sometimes a respirator that filters the air they breathe. Workers in a BSL-4 lab wear spacesuits and have air hoses attached to an isolated air delivery system. Workers in a BSL-4 lab must shower prior to leaving the lab. BSL-4 labs are essentially a building isolated within another larger building. All air, water, and materials leaving the unit are collected, decontaminated, and often incinerated. BSL-4 labs have been the setting for scenes in the movies Outbreak (1995) and Contagion (2011).
BSL-2: Microorganisms of moderate potential hazard to personnel and the environment.
BSL-3: Microorganisms present in the United States, and foreign and emerging agents that may cause serious consequences in livestock but are not harmful to human beings because of available protective measures.
BSL-4: Microorganisms that pose a high risk of life-threatening disease and for which there is no known vaccine or therapy.
A common feature in many BSL-2 and BSL-3 labs are containment or aerosol cabinets or chambers; the two terms are interchangeable. These are essentially mini-BSL-3 labs that have special venting requirements. Some are completely sealed and have rubber gloves built into them that allow workers to manipulate items or animals in the chamber without actually reaching inside, others are hoods with controlled air flows. Workers wearing gloves reach under the hood to access and handle the materials or animals.
In 2005, it came to light that leaky aerosol chambers manufactured by the UW-Madison were responsible for a number of laboratory accidents around the U.S. According to an investigation by the Sunshine Project:
The Madison aerosol chamber is a specialized type of lab equipment. The chamber is used to infect animals with disease through their lungs. Cultures of organisms causing tuberculosis or the bioweapons agents anthrax, Q fever, or brucella [sic] and others are placed in a part of the device called a nebulizer, which mixes the agents with air. The resulting aerosol is directed into a metal chamber in which animals have been placed on racks. The animals then breathe in the agent. The integrity of the complicated device's "O rings," seals, and other fittings is critical to preventing the aerosols from escaping the chamber and causing accidental infections.(4)The Madison Chamber was responsible for three laboratory-acquired tuberculosis infections in a Seattle BSL-3 lab at the Infectious Disease Research Institute (IRDI) in 2004. In a report from IRDI, the inventor of the device is quoted as saying that "the chamber was so safe that there was no need to even locate it in a BSL-3 environment," that it was "foolproof," and that "respirator use was not necessary."
In 2006, a Madison aerosol chamber mishap at Texas A&M University caused an accidental infection of a researcher with the bioweapons agent Brucella. The journal Science reported that the CDC suspended all research on dangerous pathogens known as select agents(5) at Texas A&M University after the school failed to report two exposures.(6)
In 2007, Madison Chambers were still being touted for their safety, but people were beginning to
ask questions
The Madison Chamber is used for animals ranging from mice to rabbits and the dual-sided unit is used for small animals and non-human primates.In 2009, the Associated Press reported that UW-Madison had "quietly decided to stop manufacturing its signature aerosol chambers" due to the units having caused dangerous lab accidents and the risk of "huge liability costs" if more accidents occurred.(8)
The Madison aerosol exposure chamber was developed by the University of Wisconsin in 1970 as a stand-alone system designed for total body exposure of animals as small as mice or as large as rabbits. The chamber, which can hold up to 90 mice, allows researchers to simultaneously infect large numbers of animals. ...The chamber, designed for specialized BSL-3 and BSL-4 labs, is being used today to study tuberculosis, bioterrorism agents, anthrax, and any research that requires the infection of a large number of animals.
As a stand-alone system, the chamber poses potential exposure risks to researchers working with pathogens. ...
“There are only about 40 or 50 of the Madison Chambers being used in the world today and there have been reported cases of researchers being infected when they opened the stand-alone chamber,” says Mark Zarembo, custom products division manager at the Baker Co.(7)
What We Don't Know
Laboratory workers are presumably informed about the risks inherent in working with and around infectious agents and then weigh them and decide that the benefits -- financial, scientific, and/or otherwise -- outweigh them. People living near such labs, or even on the other side of the planet, do not have the same choice. Accidents in a BSL-2 or even a BSL-3 lab may pose serious consequences to the lab workers and the community, but accidents associated with the agents that are mandated to be studied only in BSL-4 labs carry an altogether different level of risk. In 2007, the Associated Press reported that:
University of Wisconsin-Madison research on the deadly Ebola virus was conducted for year in a less-secure laboratory than required, until the National Institutes of Health alerted the school to the problem....
The university approved [Yoshihiro] Kawaoka's study initially for a Biosafety Level 3. Several of UW-Madison's laboratories are Level 3 labs, but none are Level 4, where the most stringent guidelines to contain the most dangerous pathogens are applied.
[UW-Madison biological safety officer Jan] Klein said Kawaoka was pressing to conduct the research in a less restrictive Level 2 lab. When the university asked the NIH for guidance, it learned the material was restricted to a Level 4 lab.(9)
The public could reasonably expect that the university would have had a clear understanding of the federal regulations and would have known that they unequivocally required Ebola research to be conducted in a BSL-4 lab. If they did know, they were deceiving federal regulators by conducting the work in an unapproved lab. If they were not knowingly deceiving the federal authorities responsible for safe-guarding the public from potentially devastating accidental exposures, then there is cause for alarm because research involving select agents is common at the university and at other similar institutions; not understanding and diligently complying with the rules places everyone at serious and unnecessary risk. University officials ought to know the rules for studying deadly diseases like Ebola before allowing such research to take place.
Mutant Diseases
Today's biologists can insert genes directly into germs' genetic codes and give them characteristics that do not occur in nature. One of the characteristics that can be and is sometimes inserted is resistance to the antibiotics used to control the germ. Research involving the creation of such antibiotic resistant germs is (rightly) termed a "Major Action" under the "NIH Guidelines," and requires written permission from the NIH Recombinant DNA Advisory Committee (RAC) and the NIH Director before doing so. This makes good sense. A disease easily controlled with a specific antibiotic could quickly become a world-wide scourge if it was no longer able to be controlled by that antibiotic. But in spite of having biosafety standards that are among "most rigorous in the world," according to the responsible official for the university's Select Agent Program, from sometime in 2004 until late in 2007, the lab manager, researchers, research assistants, and graduate students in Dr. Gary Splitter's lab were genetically modifying strains of Brucella, a select agent, that were resistant to various antibiotics, or knew that others in the Splitter lab were doing so. From August 2003 until February 2006, Gary Splitter served on the university's Institutional Biosafety Committee (IBC) and approved Kawaoka's Ebola research.
The IBC was required by NIH guidelines that had gone into effect in 2002, to approve any and every project involving recombinant genetics (rDNA) prior to the research commencing. That same year a graduate student in Splitter's lab created a "library" of 2,880 vials of trimethoprim-resistant Brucella. Trimethoprim is a commonly used antibiotic for the treatment of brucellosis, the name of the disease caused by the bacteria Brucella ssp.
In March 2005, the regulations governing the use of select agents and rDNA were tightened, and the NIH began requiring prior approval from them before any such research could be started. In May of 2007, a graduate assistant in the Splitter lab created spectinomycin-resistant Brucella without approval from NIH. The gene responsible for spectinomycin resistance also confers resistance to streptomycin, another antibiotic commonly used to treat brucellosis.
An inspection of the Splitter lab by inspectors from the U.S. Public Health Service Centers for Disease Control (CDC) and USDA-APHIS from August 27 to August 30, 2007, discovered that the experiments with select agents had been and were being conducted without the knowledge of the NIH or its approval. The guidelines are clear: A “Major Action” cannot be undertaken without prior submission of the proposed modification to the Office of Biotechnology Activities, publication of the proposal in the Federal Register for public comment, review by the NIH Recombinant DNA Advisory Committee, and specific approval by the NIH director. Missing from the record available to me is correspondence leading up to mention of specific January 2008 correspondence -- a letter and later email -- from the university to the NIH notifying the Office of Biotechnology that a violation of NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) had occurred.
In response, the NIH Office of Biotechnology wrote in April 2008, that it was “extremely concerned” about the experiments because of the “serious potential consequences to public health.”(10) Multiple investigations followed. The letter states that the investigator (referring to Splitter) agreed to stop the research with the unapproved strains "immediately." But the violations had been discovered in August of 2007, the university wrote to the NIH about the violations in January 2008, and the NIH then thanked them in April for doing so.
One investigator(11) reported that Splitter had lied to them about knowing what was occurring in his lab. Splitter was guilty of either not knowing what was occurring in his BSL-3 laboratory or else he did know and then lied about it afterwards. He was either negligent or a liar, and perhaps both. A problem even more serious than these violations in the Splitter lab was that the Splitter lab probably was not an anomaly. That investigator reported on the Institutional Biosafety Committee: "Of the senior people I talked with, not one said that the campus biosafety system was working well, or even acceptably. One senior individual characterized the organization and functioning of the system as 'nuts'." (Emphasis in original.) He also said he believed that “a large share of that blame" was the university's because of "the serious deficiencies in its biosafety system."
Another investigator wrote, "I found no consistent communication or outreach effort to engage the research community and increase awareness of their responsibility under the NIH rDNA Guidelines and the Select Agent regulations." That investigator reported that there seemed to be "some reluctance" on the part of the university's small Biosafety Office staff to discuss "regulatory issues" with lab staff.(12)
A November 26, 2008, letter to William Mellon from the Office of Council to the Inspector General, Department of Health and Human Services, informed the university that as a result of Splitter's violations the Office of the Inspector General was authorized "under 42 C.F.R. § 73.21 to impose civil monetary penalties of up to $250,000 per violation against an individual and up to $500,000 per violation against an individual, including any entity, that is in violation of any of the requirements...".(13)
Given the multiple violations, the university was at some, perhaps slight, risk of significant monetary penalties and of losing income by having its research program curtailed by NIH. It disciplined Splitter much more severely than it had previously or has done since with any other staff member. Provost Paul DeLuca, Jr. spelled out the final determination in a "Letter of Suspension and Research Privileges"(14) but did not acknowledge any institutional culpability. The university imposed a five-year-long sanction that took away Splitter's access to use or work with select agents, to have access to a lab designated as BSL-2 or higher, to supervise lab staff working in those labs, and ordered that he could not be named as the principal investigator on any project involving research occurring in such an environment. DeLuca stated in the "Letter of Suspension and Research Privileges" that Splitter's claim of not knowing what was going on in his lab "lacked credibility." The university was fined only $40,000 for the Major Action violation by NIH. A student and another worker in Splitter's lab contracted the disease and one developed cysts on their brain. Both recovered.(15) The university blamed Splitter and claimed that he had simply refused to follow the Major Action guidelines. Splitter in turn, said that the situation demonstrated the deep flaws in how UW-Madison handles biological agents.(16) The university claims that oversight has been tightened.(17)
The Splitter case is an example of the problems that can occur in spite of regulations, no matter how stringent. If the modified Brucella escaped or had been released, it could have put the public at significant risk. Normally, brucellosis is not a very serious disease because it can be readily treated with antibiotics. According to the CDC, it is usually caused by eating or drinking unpasteurized/raw dairy products from sheep, goats, cows, or camels when their milk becomes contaminated with the Brucella bacteria, but slaughterhouse workers, farm hands, and veterinarians are also at risk if they have open sores and come into contact with infected animals. If the antibiotic-resistant strains had gained a foothold in the environment, the results could have been catastrophic. That is exactly why intentionally creating antibiotic resistant germs is called a Major Action by the NIH.
It Gets Worse
The most dangerous diseases -- the select agents that can usually be studied only in a BSL-4 lab -- are those that are difficult to treat, often fatal, are caused by airborne organisms, and are spread easily and rapidly. These are frequently zoonotic diseases (non-host specific germs that can jump from species to species.) One such disease is influenza.
One type of influenza, a strain of H1N1, known colloquially as the 1918 Spanish flu, is the most
deadly disease ever encountered. John M. Barry, in his book The Great Influenza, says:
Although the influenza pandemic stretched over two years, perhaps two-thirds of the deaths occurred in a period of twenty-four weeks, and more than half of those deaths occurred in even less time, from mid-September to early December 1918. Influenza killed more people in a year than the Black Death killed in a century; it killed more people in twenty-four weeks than AIDS has killed in twenty-four years(18)Over half of those who died in the 1918 pandemic were in their 20s and 30s, in the prime of life, not the elderly.
One of the characteristics that makes H1N1 so dangerous is its relatively long incubation period of 1 to 4 days (some sources say up to 10 days.) This means that if someone is infected, they may not know it for a while, and while they still feel healthy, they may be spreading the virus. This is one of the reasons that H1N1 spread so very rapidly and killed so many people in 1918/19. Estimates vary, but everyone agrees that it killed tens of millions of people, maybe even 100 million.
If someone in a lab studying H1N1 is accidentally infected, they may not know it for a few days. When they stop to buy a loaf of bread on the way home from the lab, the store clerk and everyone in the store is at risk of infection. If someone there is infected, they take it home to their families, and their kids take it to school.
This version of the flu is the most dangerous disease in the world. It spreads rapidly and has a very high death rate. People spread the disease before they even know they are sick. It was virtually extinct until 2005 when scientists dug up a victim's body in the Canadian permafrost. Yoshihiro Kawaoka and others were able to reconstruct the virus from influenza genes left behind in the frozen tissues of its deceased victim. They began testing the virus in animals very soon afterwards. In Kawaoka's report on the effect of the virus on monkeys, he and his coauthors wrote:
Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome...A 2007 story from the Associated Press gives a little more detail in plain talk:
All 1918-virus-infected animals became symptomatic within 24 h post-infection. They appeared depressed, were hesitant to eat or drink normal food items, and showed respiratory complications such as nasal discharge and non-productive cough. They became progressively more debilitated and eventually developed an acute respiratory distress syndrome. Two macaques infected with the 1918 virus and one with K173 were euthanized on each of days 3 and 6 for analysis. Of these, one 1918-virus-infected animal had reached the predetermined score for euthanasia on day 6. The remaining animals, originally scheduled for euthanasia on day 21 post-infection, were euthanized on day 8 owing to severity of symptoms in 1918-virus-infected animals.(19)
"Essentially people are drowned by themselves," said University of Wisconsin virology professor Yoshihiro Kawaoka, lead author of a study being published Thursday in the journal Nature.The university says that the public should not be concerned that the virus is being studied in Madison, because they built Kawaoka a new BSL-3 lab. In an article from 2004, D. A. Henderson of the University of Pittsburgh, a leading biosecurity expert, commented about Kawaoka studying the disease at UW-Madison: "The potential implications of an infected lab worker – and spread beyond the lab – are terrifying." Ronald Voorhees, chief medical officer at the New Mexico Department of Health, is quoted saying that: "I experienced disbelief… regarding the decision to relocate the reconstructed 1918 influenza strain from a BSL-4 facility to a BSL-3 facility...".(21) Conducting the research in the BSL-3 lab was approved by the university's IBC, which at the time included Gary Splitter as a member.
Scientists believe the results open a window into what could happen if the current bird flu in Asia morphs into a highly lethal strain that spreads easily among people.
The 1918 virus was reconstructed with reverse genetics, relying on tissue from victims of the early-day flu pandemic. The virus is kept only in two labs where scientists are studying it: the U.S. Centers for Disease Control and Prevention in Atlanta and the Public Health Agency of Canada's lab in Winnipeg where the monkey experiment was done.
When seven macaques were given the virus at the high-level biosafety lab there,scientists were struck by how suddenly and overwhelmingly the flu struck. The virus spread faster than a normal flu bug and triggered a "storm" response in the animal's immune systems.
Their bodies' defenses went haywire, not knowing when to stop, researchers said. The lungs became inflamed and filled with blood and other fluids.(20)
Holes in the Safety Net
BSL-4 labs are not common. According the Federation of American Scientists, as of 2011, there were seven operational BSL-4 labs in the U.S., with five more planned, under construction, or suspected. There are many thousands of BSL-3-capable labs worldwide; the number of BSL-3 labs has been rising rapidly.(22)
A 2007 report from the U.S. Government Accountability Office reported a total of 1,356 registered BSL-3 facilities in the U.S, and fifteen BSL-4 labs. The GAO reports that no one actually knows how many of these labs are operating in the U.S. (let alone the world.) The report came in response to a widespread concern about the proliferation of such labs and the increased risk to the public's health.(23)
It seems likely that a brand new lab is relatively safe. But BSL-3 and BSL-4 labs incorporate complicated engineering designs. The Madison Chambers, though complex in design were fairly simple machines, and yet they failed and caused many accidental infections of lab workers. In the case of diseases like the 1918 Spanish flu, a single accident could trigger a pandemic that could kill many millions of people and other animals in a short period of time. In 1918/19 the disease spread rapidly, even without commercial air travel.
Evidence from the USDA's agricultural BSL-3 lab at Plum Island, New York is not reassuring with regard to a lab's long-term safety. Rubber seals dry out and become worn, dust accumulates on air filters, fan and pump motors become worn and ever less effective. It has been called "creeping degradation" by some observers. Staff inevitably take shortcuts, become complacent and less concerned with seemingly small problems. Those in charge of oversight become defensive and continue to make public claims about a facility's safety while failing to note problems in their official reports. People are only human. Maybe staff really do not see the problems. Accidents happen. Unforeseeable events are inevitable.
In what was a potentially catastrophic accident in July of 2009, tissues and blood samples from dead pigs mistakenly thought to have have died from “blue ear disease” in the Philippines were mailed to Plum Island. The tissues were actually harboring a rare and (very luckily) not-so-dangerous-to-humans strain of Ebola.(24) The not-so-dangerous strain is called Reston Ebola. That version of Ebola got its name from another near miss that occurred when monkeys from the Philippines unknowingly infected with Ebola were shipped to Reston, Virginia.(25)
Things that should not happen do happen. No matter how secure a lab is, what procedures are in
place, there is always the human factor. Rumors abound as to why animal lab assistant Raymond Clark III murdered Yale University pharmacology student researcher Annie Le in 2009, but it is no rumor that Mr. Clark had complete access to the research building.(26) If Mr. Clark had been mad at his university or the owner of a nearby bicycle store instead of Ms. Le, what would have stopped him from putting a few vials of some deadly germs into his pocket and exposing the public? Apparently nothing.
Also in 2009, an audit of the BSL-4 lab at Fort Detrick in Frederick, Maryland, turned up 9,220 vials of Ebola, anthrax, botulinum, equine encephalitis virus, and other deadly germs that had been stored away and forgotten. No one knew the vials existed; no one can say whether any are missing.(27)
The risk of a sweeping pandemic resulting from an accident or from an intentional act by a lab worker has led to some trepidation among some infectious disease experts and public health officials; one of the most dangerous methodologies has recently been curtailed, at the time of this writing.(28) The funding for “gain-of-function” research has been paused; whether it will resume is yet to be decided. "Gain-of-function” at the university research is discussed later in this chapter. [I had some hope but never much doubt. RB 3-13-19]
The real risk of a sweeping pandemic has not been sufficiently motivating to the university; it remains a stalwart proponent of the most dangerous infectious disease research and conducting it in a populated area. In spite of a history of equipment and laboratory mishaps, university experts and officials continue to claim that the work would be safe and would lead to great medical advancement. Second thoughts are probably quieted by the potential financial rewards if the NIH decided to resume its funding. While potential riches are sufficiently motivating to the university, potential pandemic does not seem to be a significant deterrent.
The National Bio and Agro-Defense Facility
Ranchers and dairymen may fear foot and mouth disease above all other potential diseases that might infect their animals. Because the disease spreads so rapidly and there is no ready medical remedy for the disease, the standard reaction by officials is to order the complete destruction and incineration of entire herds if even a single case is discovered. An outbreak of the disease in 2001 in the United Kingdom resulted in more than six million animals being destroyed and economic losses estimated to have been about $13 billion (£8 billion).(29) In spite of this, in 2011 another outbreak occurred, this time it was caused by "leaking drains, heavy rain and building work" at the very secure government owned Pirbright Laboratory, where research on a the disease is conducted and a library of hoof-and-mouth viruses is stored. That outbreak cost the government about $70 million (£47 million) and the livestock industry about $160 million (£100 million).(30)
On November 30, 2006, I attended a presentation by the Dean of the UW-Madison School of Veterinary Medicine, Daryl Buss and other university representatives at a Town of Dunn town hall meeting. The Town of Dunn is a twenty minute drive from Madison. The Town of Dunn is known nationally for the innovative land use plan it initiated in 1979 which has successfully preserved the town's rural nature by protecting the surrounding environment and maintaining strict controls on growth and development; the town has focused its resources on improving the health of local wetlands, lakes and farmland. The select group of purported university experts were there to explain to the residents exactly why the university was offering the U.S. Department of Homeland Security its 160-acre parcel located in the township as a site for a 500,000-square-foot BSL-3 and BSL-4 laboratory, the National Bio and Agro-Defense Facility (NBAF). I have read that the average Wal-Mart is about 100,000 square feet in size.
During the Dunn town hall meeting, Dean Buss told the overflowing audience of area residents that the new facility would be a replacement for Plum Island just off the New York coast. He explained that Plum Island was an exemplary laboratory, but that it was deemed too old to renovate fully, so Homeland Security was trying to find a location to build a new laboratory. When asked why the university had invited the government to build its new lab in the Town of Dunn and begin shipping in deadly diseases prior to discussing the matter with the citizens of Dunn, university Provost Patrick Farrell said that the university submits so many letters of interest to the federal government that it just did not seem important. But according to statements made during the meeting by a resident of the nearby town of Appleton, the university claimed at least three times in its 90-page application, that local officials supported the idea of having the lab in their community. When asked to name those officials, the university representatives at the town hall meeting could not name one and said that they had been in a hurry to get their application in on time.
When asked about worse case scenarios, one of the university experts said that if a lab technician dropped a beaker with some dangerous germs inside, that they were trained to hold their breath. Few questions were answered substantively.
During the meeting, an elderly woman stood and asked the panel whether any of them had read the book she was holding, Lab 257, an exposé written in 2004 that brought to light many of the problems that had occurred at Plum Island over the years. None of them were familiar with the book. Former New York Governor Mario Cuomo may have been prescient when he worried that if someone did not force the government to do something about Plum Island, that the author’s “brilliant work will have been wasted and we may be the victims, once again, of government inadvertence."(31) The meeting ended in some disarray. The residents were clearly angry that the university was working to have the giant germ lab build in Dunn without talking about it with the town. The university came across as uniformed and arrogant.
A January 31, 2007, press release from the university announced that Thomas McKenna, director of the Foreign Animal Disease Diagnostic Laboratory at Plum Island, where he had worked since 1995, had been chosen to head the Wisconsin Veterinary Diagnostic Laboratory, a university based facility, which includes a self-contained BSL-3 laboratory, where work with highly infectious organisms and other potential bioterrorism agents is performed.
The release quoted Buss: “We are highly impressed with Tom's leadership skills, his scientific credentials and his ability to manage a resource that is vitally important to Wisconsin citizens.”(32) As I mentioned above, during the Dunn town hall meeting, Buss had claimed that Plum Island was an exemplary laboratory. Buss’s praise for Thomas McKenna’s leadership during his twelve years at Plum Island does not line up with the problems at Plum Island revealed by Michael C. Carroll’s Lab 257, the book Buss and the other university representatives had been asked about. Buss was claiming that McKenna leadership was impressive without first having familiarized himself with well researched criticisms of Plum Island’s history of germ research. The university tried to convince the Town of Dunn that it had nothing to worry about if Homeland Security built a BSL-4 lab replacement for Plum Island in its back yard. One of the experts at the town hall meeting had said that they would be happy to let their grand daughter play just outside the facility's walls. Now, another expert would be able to say that he had worked at Plum Island. The people of Dunn and nearby Madison should feel perfectly safe.
Getting information from Plum Island seems to have been as difficult for Carroll as getting information from the university has proven to be. What has emerged from Caroll's efforts is a large body of evidence, circumstantial and factual, that demonstrates the likelihood that Plum Island is responsible for a number of disease outbreaks that have proven to be national public health and agricultural nightmares. Carroll’s Lab 257 presents compelling evidence that Plum Island is responsible for the introduction into the United States of Lyme disease, West Nile virus, Dutch duck plague, and the reintroduction hoof-and-mouth disease. Plum Island’s biocontainment mechanisms were allowed to deteriorate and remained non-functional for many years. Security was lax. Accidents were common. Plum Island’s apparent catastrophic failure to protect the public must be borne in part by Thomas McKenna. Naming McKenna to lead a BSL- 3 laboratory – without fully understanding the history of Plum Island – appears to have been a violation of the public’s trust.
On March 8, 2007, three representatives from the university made a presentation to the Dane County Board of Supervisors on the proposed NBAF in Dunn. I attended that meeting. On the day of the meeting, the Wisconsin State Journal ran an article ostensibly discussing the controversy that had erupted between the citizens of Dunn and the university.
Irwin Goldman, Associate Dean for Research in the College of Agricultural and Life Sciences was the primary university spokesperson at the March 8 presentation; he was interviewed for the
Wisconsin State Journal article:
Goldman said one of the things that struck him at the November town meeting was the level of misinformation about the facility. A number of people were concerned the facility would develop biological weapons, which university and federal officials say is simply not true. Goldman isn't bothered by the politics.Goldman’s opinion regarding the “level of misinformation” among those at the Dunn town hall meeting was ironic and telling. I mentioned above that the panel was asked whether any of them had read Michael C. Carroll’s Lab 257: The Disturbing Story of the Government’s Secret Plum Island Germ Laboratory. At the March 8 meeting, over three months after the town hall meeting, the three-man university delegation was again asked by a Dunn resident whether any of them could comment on the information in Lab 257, but they still had not read the book, even though many people in Dunn had. The delegation was still unable to address concerns raised by the book's author. Not one university representative had taken the time to familiarize themselves with the book.
"It's just like science," Goldman said. "You've got to lay it on the table and then let people pick it apart."(33)
During the Dunn town hall meeting, it was clear that the panel’s information had come from the Department of Homeland Security’s website, and that not one of them had spent any time looking into the history of Plum Island or doing any independent investigating. Throughout the NBAF fiasco, the university remained quiet about the laboratory accidents that it knew were occurring across the country because of its faulty aerosol chambers, there was never mention made of Kawaoka's and the university IBC's Ebola safety errors, and no one from the university mentioned the half-decade of the Gary Splitter lab's Major Action violations with select agents. The public was misinformed, but the misinformation was largely the result of the university keeping quiet about the chronic problems with its biosafety program.
The university’s decision to use Irwin Goldman as a spokesperson for its efforts to host the NABF is curious. Goldman claimed that he understood the nature of the risk associated with the research that would be occurring at the proposed NBAF, but his smooth-talking-you-have-nothing-to-worry-about-trust-me-I'm-an-expert assertion was at odds with his professional background. Irwin Goldman is an expert in the genetics of carrots, onions, and beets. His ten most recent publications at the time he was acting as the university spokesperson on matters of BSL-4 security were:
Horticulture, horticultural science, and 100 years of ASHS. HortScience.
Corn and vegetable yield trends, 1900-present. HortScience.
Temporal aspects of onion-induced antiplatelet activity. Plant Foods for Human Nutrition.
Trends in productivity of US crops and long term selection. Plant Breeding Reviews.
Evaluation of long-day onions for resistance to white rot infection using greenhouse and
laboratory techniques. Journal of the American Society for Horticultural Science.
Recognition of fruits and vegetables as healthful: vitamins, minerals, fiber, and phytonutrients.
HortTechnology.
Back to the future of food: phytonutrients and quality in vegetable crops for the 21st century.
Acta Horticulturae.
Relationship of white rot resistance to pyruvate and S-alk(en)yl-L-cysteine sulfoxides in onion
roots. Acta Horticulturae.
Flavor precursor (S-alk(en)yl-l-cysteine sulfoxide) concentration and composition in onion plant
organs and predictability of field white rot reaction of onions. Journal of the American Society
for Horticultural Science.
A one-pass semi-quantitative method for extraction and analysis of carotenoids and tocopherols
in carrot. HortScience.
Goldman told the Dane County Supervisors that he understood the risks associated with biological research because he was familiar with the use of pesticides and herbicides. In his opinion, based on his own expertise in horticulture, he found nothing to be concerned with in having a BSL-4 lab in town.
I do not know why the university choose an onion expert rather than a member of the university's Institutional Biosafety Committee (IBC) to address the County Board. Missing altogether was the Director of the university's Safety Department, a permanent member of the IBC who had been at the previous meeting. He was the person who had told the people of Dunn that lab personnel were trained to hold their breath in the event that a vial holding some deadly virus was broken.
Onion-expert Irwin Goldman was accompanied at the Dane County Supervisor’s meeting by Dean Buss and James Tracy, Associate Dean for Research of the School of Veterinary Medicine. One of the concerns raised at both meetings was the likelihood of biowarfare agents being studied at the proposed lab. This was one of the “misinformed” concerns raised during the Dunn meeting commented on by onion-expert Goldman in the Wisconsin State Journal.
Dean Buss said that because the United States had signed the 1972 Biological and Toxin Weapons Convention, such concerns were unfounded. He said he knew from visiting the Department of Homeland Security website that the lab would not be involved with germ warfare. But the U.S. government does not hide the fact that it conducts work on biowarfare agents. The National Institute of Acquired and Infectious Disease says:
Even before the current emphasis on biodefense, NIAID scientists had been studying organisms that cause a variety of infectious diseases. Examples of diseases caused by these organisms include plague, rabies, tick-borne encephalitis, West Nile virus disease, influenza, anthrax infection, Ebola virus hemorrhagic fever, HIV, tuberculosis, transmissible spongiform encephalopathies, and Q fever. Potentially, some of these microbes also could be used as agents of bioterrorism. All of this work has been carried out in either the Maryland or Montana laboratories with required safety measures in place.(34)The Public Health Research Institute Center (a Plum island affiliate) wrote on its website:
PHRI has received a $2 million grant from the National Institutes of Health (NIH) to perform biodefense-related research as part of an award to the Northeast Biodefense Center for a Regional Center of Excellence in Biodefense and Emerging Infectious Diseases. Announced by HHS Secretary Tommy G. Thompson, the PHRI award is part of a $350 million NIH initiative to protect the world against the threat of bioterrorism by funding eight regional research centers throughout the USA.(35)
The GAO reported to Congress that the lab at Plumb Island that NBAF was intended to replace is also involved in this sort of work:
PLUM ISLAND ANIMAL DISEASE CENTER: DHS and USDA Are Successfully"It's just like science," Goldman said. "You've got to lay it on the table and then let people pick it apart."(37) Except, in the case of animal-based sciences at the university, secrecy is the name of the game.
Coordinating Current Work, but Long-Term Plans Are Being Assessed. [T]he information DHS provided about its role at Plum Island has emphasized deliberate introductions. For example, the Joint Strategy emphasizes the bioterrorism focus of DHS work at Plum Island in describing the agency’s mission "to conduct, stimulate, and enable research and development to prevent or mitigate the effects of catastrophic terrorism."(36)
On Thursday, April 3, 2007, the Dane County Board of Supervisors voted 19-7 in support of a resolution opposing the university's bid to host the Department of Homeland Security’s proposed gigantic BSL-4 infectious disease lab. In July, the university learned it had been eliminated from the list of possible sites by Homeland Security. Community opposition was the main reason.(38)
An odd post mortem conducted by three UW-Madison professors and a Ph.D. candidate from
North Carolina University (part of a local consortium there that was also vying for the giant germ lab), resulted in a 2011 paper titled "Interpersonal Amplification of Risk? Citizen Discussions And Their Impact On Perceptions Of Risks And Benefits Of A Biological Research Facility."(39) The authors explained away the problems -- that were at least in part due to the university's dismissal of residents' concerns -- with the claim that like-minded people who were against the facility spoke primarily to others who agreed with them, and that no matter how much information the universities that were trying to snare the project might have provided to them, it was unlikely to have changed their minds. Their report begs the question of whether or not the opposite would have been true. If the universities had been worried about the risks and had communicated that concern along with substantiating data, would the supporters have remained steadfast in their support? The report's chilling conclusion was paraphrased by a science blogger in a post titled: "Forget Consensus - More Telling, Less Discussing, Recommends NC State Paper."(40)
The Government Accounting Office published a report at the end of 2007 titled: High-Containment Biosafety Laboratories: Preliminary Observations on the Oversight of the Proliferation of BSL-3 and BSL-4 Laboratories in the United States.(41) The authors of the paper cited above must not have read or perhaps simply ignored the GAO's report. It provides strong substantiation for the residents' fears that having a BSL-3 or -4 lab in ones backyard may not be prudent:
According to the experts, there is a baseline risk associated with any high-containment. With expansion, the aggregate risks will increase. However, the associated safety and security risks will be greater for new labs with less experience. In addition, high-containment labs have health risks for individual lab workers as well as the surrounding community. According to a CDC official, the risks due to accidental exposure or release can never be completely eliminated, and even labs within sophisticated biological research programs--including those most extensively regulated--have had and will continue to have safety failures.
The report looked at three specific cases of high-containment laboratory safety violations and accidents: the multiple accidents and violations at Texas A&M University, a system-wide biocontainment failure at the Centers for Disease Control in Atlanta, and the Pilbright laboratory-caused hoof and mouth epidemic in the United Kingdom. The GAO concluded that significant risks to the public heath and environment are inherent and a near certainty. All three of the facilities tended to operate in the same way, just as does every other similar facility in the U.S. and around the world.
While the Select Agent Program and the rDNA Guidelines have reporting requirements, institutions sometimes fail to report incidents. According to CDC, there were three specific types of incidents that TAMU [Texas A&M University] officials failed to report to CDC: (1) multiple incidents of exposure, including illness; (2) specific types of experiments being conducted by researchers; and (3) missing vials and animals.
In addition, in November 2006, during our first visit to TAMU--a meeting in which all key officials who knew about these incidents were present--we asked if there had been any incident in which a lab worker was exposed to a select agent. TAMU officials did not disclose any of these incidents. Moreover, in August 2007, during our second visit, the biosafety officer said that he had conducted an investigation of the incident, in which the lab worker was exposed to Brucella, and wrote a report. However, the report that was provided to us was dated June 17, 2006, but discussed other incidents that had occurred in 2007, a discrepancy that TAMU failed to explain to us.
According to the literature and discussion with federal officials and experts, accidents in labs are expected, mostly as a result of human error due to carelessness, inadequate training, or poor judgment. In the case of theft, loss, occupational exposure, or release of the select agent, the lab must immediately report certain information to CDC or USDA. However, there is a paucity of information on barriers to reporting by institutions. It has been suggested that there is a disincentive to report acquired infections and other mishaps at research institutions because of (1) negative publicity for the institution or (2) the scrutiny from a granting agency, which might result in the suspension of research or an adverse effect on future funding. Further, it is generally believed that when a worker acquires an infection in the lab, it is almost always his or her fault, and neither the worker nor the lab is interested in negative publicity.
...
The lab worker at TAMU who was exposed was not authorized to work with Brucella but was, we were told, being escorted in the lab only to help out with the operating of the aerosolization chamber. [A Madison chamber.]
Severe consequences for the worker can result from delays in (1) recognizing when an exposure has occurred or (2) medical providers' accurately diagnosing any resulting infection. Further, if the worker acquires a disease that is easily spread through contact, there can also be severe consequences for the surrounding community.
In the Brucella incident at TAMU, at the time of the exposure on February 9, 2006, the lab worker did not know she was infected nor did anyone else in the lab. In fact, the CDC conducted a routine inspection of TAMU on February 22, 2006--13 days after the exposure--but had no way of knowing that it had happened. According to the exposed worker, it was more than 6 weeks after the exposure that she first fell ill.
According to BMBL [Biosafety in Microbiological and Biomedical Laboratories, CDC], the causative incident for most laboratory-acquired infections is often unknown. It can only be concluded that an exposure took place after a worker reports illness--with symptoms suggestive of a disease caused by the relevant agent--some time later. Since clinical symptoms can take weeks to become apparent, during which time an infected person may be contagious...
...
An hour-long power outage, in June 2007, at the CDC's newest BSL-4 facility raised questions about safety and security, as well as the backup power system design. The incident showed that, even in the hands of experienced owners and operators, safety and security of high-containment labs can still be compromised. The incident also raises concerns about the security of other similar labs being built around the nation.
On June 8, 2007, the CDC campus in Atlanta experienced lightning strikes in and around its new BSL-4 facility, and both primary and backup power to that facility were unavailable. The facility was left with only battery power--a condition that provides limited power for functions such as emergency lighting to aid in evacuation. Among other things, the outage shut down the negative air pressure system, one of the important components in place to keep dangerous agents from escaping the containment areas. In looking into the power outage, the CDC determined that, some time earlier, a critical grounding cable buried in the ground outside the building had been cut by construction workers digging at an adjacent site. The cutting of the grounding cable, which had gone unnoticed by CDC facility managers, compromised the electrical system of the facility that housed the BSL-4 lab.
According to CDC officials, the new BSL-4 facility is still in preparation to become fully operational and no live agents were inside the facility at the time of the power outage. However, given that the cable was cut, it is apparent that the construction was not supervised to ensure the integrity of necessary safeguards that had been put in place.
Gain-of-Function
Yoshihiro Kawaoka, the university scientist who was caught experimenting with Ebola in a lab with safety precautions much less stringent than those required by federal regulations, and who experimented with the resurrected 1918 Spanish flu in a lab that caused infectious disease experts much worry, sprang into the news again at the end of 2011, when he and Ron Fouchier of Erasmus Medical Center in the Netherlands independently published papers that explained how they were able to induce a mutation of the avian H5N1 version of influenza that transformed it into a lethal air borne virus that was able to infect not only birds, but mammals as well. This relatively new area of biological research is commonly called “gain-of-function.” During most of the ensuing international controversy, local Madison media outlets carried very little news about the situation. Madison is essentially a company town; news that might be damaging to the university's reputation is reported with something less than investigative vigor. The Vilas monkey scandal discussed in Chapter 9 stands out as a notable exception.
Over the course of a little more than a year, NIH imposed a blackout on publishing details of Kawaoka's and Fouchier's research. The controversy stimulated much heated discussion; more than 40 news articles about Kawaoka and Fouchier's research appeared in the journal Nature or on its news blog. Over the same period of time more than 20 editorials on the research and the risks were published Nature. Scientific American included the controversial decision to publish Kawaoka and Fouchier's research as one of the "Top 10 Science Stories of 2012."(42) The situation was a topic of discussion just about everywhere except Madison; in 2012, the daily Wisconsin State Journal published 8 very mild articles about the controversy.
An opinion by the editors of the Sunday Review in the New York Times from January 7, 2012 was titled: "An Engineered Doomsday." They wrote:
We nearly always champion unfettered scientific research and open publication of the results. In this case it looks like the research should never have been undertaken because the potential harm is so catastrophic and the potential benefits from studying the virus so speculative.(43)British newspaper The Independent reported on the controversy in a January 23, 2013 article:
Sir Richard Roberts, who won the Nobel Prize in medicine in 1993 and is an expert in genetic engineering, said there has not been enough public consultation about the work. “The decision to lift the moratorium, which seems to have been made a small group of self-interested scientists, makes a mockery of the concept of informed consent,” Sir Richard said.The Independent followed up with another report on December 20, 2013:
The ending of the voluntary moratorium was announced last night in the form of a letter signed by 40 flu scientists to the journals Science and Nature, which published the original H5N1 transmissions studies by Ron Fouchier of the Erasmus Medical Centre in Rotterdam and Yoshihiro Kawaoka of the University of Wisconsin-Madison.
The scientists independently discovered that they could mutate the H5N1 strain of birdflu so that it could be transmitted through the air between laboratory ferrets, the standard animal model used to study influenza in humans.(44)
Some of the world's most eminent scientists have severely criticised the arguments used by some influenza researchers who are trying to make the H5N1 bird-flu virus more dangerous to humans by repeatedly infecting laboratory ferrets.The Wisconsin State Journal's coverage of the controversy and the reasons behind it was thin dismissive gruel. Questions about public safety raised by experts around the world were mentioned, but there was little substantive coverage. Concerns raised by international experts about public safety were infrequently reported, and when they were mentioned were not the subject of the reporting. To the degree anything about safety was mentioned, the focus was on the possibility of terrorists being able to use the research as a blueprint for making bio-weapons rather than the university's history of violations or the accidental infection of lab workers and the possibility of subsequent infection of others. Local reporters and editors offered no opinions, and to the degree that the paper covered the story, it consistently showcased Kawaoka's claim that the experiments would benefit mankind. Given the history of the 1918 Spanish flu killing so many people in such a short time, the university's and other local media's resistance to public discussion about turning more or less benign influenza viruses into potentially species-eliminating super germs should be disturbing to everyone.
More than 50 senior scientists from 14 countries, including three Nobel laureates and several fellows of the Royal Society, have written to the European Commission denouncing claims that the ferret experiments are necessary for the development of new flu vaccines and anti-viral drugs.
In its list of "UW Animal Research Achievements" discussed in Chapter 10, the university says that:
With heavy reliance on animals, UW–Madison researchers are studying influenza viruses and have made major advances related to the deadly 1918 influenza epidemic, the threatened H5N1 bird flu, and the current H1N1 pandemic. UW–Madison research is contributing to new methods for making vaccines and developing antiviral drugs as a first line of defense against the next pandemic.(46)That is about as far fetched as it gets. No one anywhere has made any "major advances related to the deadly 1918 influenza epidemic" if the term advancement is taken to mean better ways of treating or preventing the disease. Until Kawaoka and others brought the virus back to life, it had been essentially extinct. The university's invention of a mutant H5N1 has resulted in a lethal virus that has created the very real potential of a pandemic that many experts fear could kill millions in very short order. The seasonal influenza outbreaks are of greatest risk to the very young and very old, while the efficacy of the flu vaccines is controversial.(47) The value and need for flu shots is hyped by vaccine makers who want the U.S. government to stockpile and subsidize their products.(48) In November 2013, the university was still cultivating the illusion of public safety:
Dear Editor: The letter from Gerard Schultz regarding avian influenza studies at UWMadison asks important questions. In short, is the work done safely and securely? The answer is yes, of course. Otherwise, we would not be doing it.
.... The laboratory, which is far from an open environment, is among the most regulated on our campus and experiences both routine and unannounced inspections from campus biosafety officials and the federal agencies that regulate such research, including the Centers for Disease Control and the Animal and Plant Health Inspection Service. We also have an excellent working relationship with the UW-Madison Police Department and the Federal Bureau of Investigation. Both agencies are familiar with the work conducted at the lab and play a continuous and significant role in ensuring its security.
William S Mellon, Ph.D. Senior Associate Dean, Academic Affairs and Associate Dean for Research Policy, and the responsible official for the university's Select Agent Program(49)
Lies, Secrets, and Cover-ups
I had a guest column published in the July 8, 2014, The Capital Times newspaper titled "Millions Dead Within Weeks."(50) It started out like this:
A June 25 editorial in the journal Nature should give Madisonians pause. The editors voiced serious concern over influenza research at the University of Wisconsin-Madison. The editors and senior disease researchers in the U.S. and abroad are making public statements about how dangerous they believe this research is.On June 11, the university fired back with a letter to the editor from Timothy Yoshino, the so-called "responsible official" for the university's Select Agent Program and Susan West, then chair of the Institutional Biosafety Committee.(51) Most of what they wrote was intended to disparage me; shooting the messenger seemed like a good move to them. They made only a couple substantive claims:
The work he criticizes as a public health threat is in reality an identified priority of the world’s major health organizations, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the World Health Organization.On the first point, as I write this, the NIH has stopped funding for gain-of-function studies over the concerns raised worldwide. The work is not so important that it might not be severely curtailed. More about this below. [I was hopeful. RB 3-19]
Research on influenza on the University of Wisconsin-Madison campus and at the Influenza Research Institute has been conducted safely for years under the strict regulations set forth by federal authorities. While research with serious human pathogens always carries some element of risk, it can be and is carried out safely and responsibly.
On their second point, that Kawaoka's lab had conducted its research safely for years, I could only worry to myself that time was not on their side. I was unaware that they were lying [Maybe they just didn't have all the facts. RB 3-19]; even today, with so many examples of their dishonesty so well known to me, I still find myself occasionally accepting what they say; our obedience and trust in authorities is a very hard behavior to break.
The implication that the work is safe because the lab had been operating safely "for years" was misleading. The university built Kawaoka his new lab, with much fanfare(52), in 2006 after the CDC raised concerns over his Ebola research. In 2014, the lab had been operating for less than a decade; the rubber seals, air pumps, and filters were probably still reasonable functional. But that massage of the facts, though obviously intended to quell public concern was not clearly a lie. The lie was their claim that the lab had operated safely during that time. But I did not know that when they wrote their letter.
The Influenza Research Institute
USA Today published an extensive investigative report on biosafety in U.S. laboratories in May, 2015. It was subtitled "Investigation reveals hundreds of accidents, safety violations and near misses put people at risk."(53) The report included a database of the records they had received in response to their public records requests. Included in the database were 420 pages of documents related to the university's use of hazardous pathogenic organisms. Among those was correspondence between the university and the NIH related to two accidents that occurred in the Influenza Research Institute's most secure space, its Enhanced BSL-3-Ag lab, where Kawaoka and his staff tinker with some of the most dangerous diseases known to science and in some cases try to make them even more deadly. The first accident occurred on November 9, 2013, and the second just a week later on November 16. The issues were not resolved until early February 2014, and only after the NIH threatened to immediately cancel Kawaoka's funding if the university did not fix its biosafety procedures, just five months before my op-ed was published and the university spokespersons wrote: "Research on influenza on the University of Wisconsin- Madison campus and at the Influenza Research Institute has been conducted safely for years under the strict regulations set forth by federal authorities."
The accidents were never reported by local media; it is likely that the university kept them secret.
Jacqueline Corrigan-Curay, M.D., J.D., Acting Director of the NIH Office of Biotechnology Activities [OBA] responded in writing to the university's report on the two accidents in two separate letters, both dated December 16, 2013, and both directed to Daniel Ulrich, PhD., Associate Vice Chancellor for Research Policy. She recounts the details provided by the university in a series of teleconferences between the university and her office. She gave the university until December 23, to explain how they would correct the problems.
A third letter from the NIH, dated December 17, signed by Amy P. Patterson, M.D. Associate Director for Science Policy and Sally Rockey, Ph.D., Deputy Director for Extramural Research, was sent to Martin Cadwallader, PhD., Vice Chancellor for Research and Dean of the Graduate School. Copies of the two December 16 letters were included. The letter to Cadwallader summarizes the issues and makes the concerns very clear. The emphasis is in the original.
US. Public Health ServiceThe letter was Signed by Patterson and Rockey and cced to Kawaoka and multiple university officials and the CDC, USDA, and Corrigan-Curay.
Bethesda, Maryland 20892
Office of Biotechnology Activities [OBA]
National Institutes of Health
December 17, 2013
Dear Dr. Cadwallader:
We are writing in regard to two incidents involving recombinant research with highly pathogenic avian influenza (HPAI) H5N1 that have occurred recently in the laboratory of Dr. Yoshihiro Kawaoka. After reviewing the details of these two incidents, NIH has significant concerns relating to the University of Wisconsin's apparent lack of a dedicated quarantine facility other than the researcher's home. We also have concerns relating to the biosafety practices associated with these incidents. Our concerns are detailed below.
Lack of a dedicated quarantine facility
In the needlestick incident that occurred on November 16, 2013, a decision was made to home quarantine the individual because the route of exposure (needlestick) was not expected to place the researcher at high risk for infection and this influenza strain, which contained the HA gene from H5N1, was determined not to be a mammalian-transmissible strain. However, in conversations with the University of Wisconsin Alternate Responsible Official, Ms. Rebecca Moritz, regarding this incident, Ms. Moritz informed us that all researchers exposed to H5N1 would be quarantined at home, regardless of the risk of infection or whether the strain was mammalian-transmissible or not.
In a subsequent phone conversation with the University of Wisconsin Senior Associate Dean for Research, Dr. William Mellon and Ms. Moritz, the policy for home isolation for all incidents was reiterated to us. We were told by Dr. Mellon and Ms. Moritz that the decision was based upon consultation with University of Wisconsin infectious disease experts and the state health department. We were also informed that the use of a hospital room for quarantine was rejected due to the stress it would place on the laboratory worker.
The University of Wisconsin's policy on home quarantine communicated to us by Dr. Mellon and Ms. Moritz is not in keeping with what was communicated to us in Dr. Kawaoka's application to the Department of Health and Human Services to perform research with mammalian transmissible strains of HPAI [Highly Pathogenic Avian Influenza] H5N1. In a May 6, 2013, plan provided to NIH, Dr. Kawaoka indicated that he had access to a "designated quarantine apartment" in which researchers could be placed for 10-14 days in the event of an accidental exposure (Attachment A). Dr. Mellon and Ms. Moritz have indicated to OBA that there was a miscommunication between the PI and the University of Wisconsin administration regarding the availability and appropriateness of such a quarantine apartment.
The University of Wisconsin's policy on home quarantine is inconsistent with the requirements for this research under the NIH Guidelines for Research Involving Recombinant or Nucleic Acid Molecules (NIH Guidelines), and under the terms agreed to by the University as a condition of funding this project. The University of Wisconsin must find a dedicated facility outside of the individual's permanent residence (1) in which an individual exposed to mammalian-transmissible HPAI H5N1can be safely isolated for up to 10 days, and (2) that can be decontaminated easily after the individual's departure. An isolation room in a hospital would also be appropriate. An individual's permanent residence is not appropriate when the risk of infection is high. For high risk exposures, it is critical to isolate the individual in a structure that does not have shared air exchange and can be quickly and efficiently decontaminated in the case of infection. In addition, if this structure is outside of a health care facility, there needs to be a plan in place regarding how this researcher could be safely transported to an isolation room in a health care facility, should he or she develop clinical without the risk of exposure to other individuals.
Concerns relating to biosafety practices
In addition to the quarantine issue, NIH has significant concerns regarding the biosafety practices associated with both of the recent incidents.
The November 16, 2013, needlestick incident occurred when the researcher used a needle to collect tissue culture supernatant in violation of the University of Wisconsin's own policies, which only permits needles to be used in the ABSL3+ laboratory to anesthetize research animals, draw blood from research animals, or inoculate eggs. It was unclear from the University's response why this individual was using a needle for this type of procedure.
The University of Wisconsin report regarding the November 9, 2013, HPAI H5N1 spill described the researcher as having two to three inches of exposed skin between where [redacted] tyvek suit ended and [redacted] shoe covers began. While it was reported that none of the spilled material landed on the researcher's bare skin, we made it clear in our letter (Attachment A) and in a phone conversation with Ms. Moritz and Dr. Mellon that having bare skin in the ABSL3+ laboratory was unacceptable under the containment requirements for this research specified in the NIH Guidelines. During that phone conversation, Ms. Moritz and Dr. Mellon stated that the laboratory had recently undergone a Select Agent inspection and the report from that inspection did not specifically mention a prohibition against working in the ABSL3+ laboratory with bare skin. We have discussed the issue of bare skin in the laboratory with the United States Department of Agriculture (USDA) Select Agent Program, and they are in agreement that bare skin is unacceptable at this level of containment.
Attachments B and Attachment C to this letter contain the NIH response to both H5N1 incidents. These letters contain requests for action regarding the quarantine situation and our biosafety concerns. We would appreciate any assistance you can provide to ensure that these requests are answered by December 23, 2013.
Finally, if your response is not received by this date or if does not fully address the issues we have described regarding a dedicated quarantine facility and inappropriate biosafety practices, as required by the terms and conditions of grant award, NIH will institute enforcement action(s) for the NIH grant 2 R01 AI069274-06A1, Transmissibility of Avian Influenza Viruses in Mammals, Yoshihiro Kawaoka, DVM, Principal Investigator. Such actions could include disallowance of costs, suspension, or termination of the grant award.
If you have any questions, please feel free to contact us.
Since 2006, and as of 2016, Kawaoka's grant, AI069274, has received $6,045,121 in NIH funding.
Uhlrich reached out immediately to the executive director of University Health Services, who, in turn it seems, received a commitment from the University of Wisconsin Hospital to provide quarantine facilities in the event of another accident in the lab. University Health Services responded in writing in a letter dated December 20. Worth noting is that in the letter they list reasons they believed that quarantine in the hospital would not be a good idea. Secrecy seemed to be one of their chief concerns:
There are a significant number of people who work in and visit hospitals on a daily basis. Due to sheer number of individuals it would be much harder to control the spread of information and as a result there would be a higher probability of incorrect information being told to general public and potentially members of the media.Uhlrich answered each of Corrigan-Curay's letters the same day, December 20. He had probably been waiting to get the promise of a quarantine room from the hospital. In response to the needle stick accident, he said that their procedures had been improved and that sharp needles would be used only for drawing blood or injecting animals, and that whenever a reconstructed version of the 1918 Spanish flu was involved, that two people would be present. He also said that they had decided that her recommended isolation room at a hospital was the "best option." He also noted that the then just-imposed international ban on this line of work made it unlikely that such experiments would be occurring again very soon.
He also stated that people working in the ABSL3+ laboratory would start covering their lower legs and ankles with booties, but he complained that they could not find mention of this precaution in the NIH regulations cited by Corrigan-Curay. More worrisome, he also said something that is hopefully inaccurate, but if not, then seriously dangerous. He wrote:
As you know, many PAPRs [Powered Air Purifying Respirator] lack shrouds and leave the researcher’s neck exposed. Does the no-bare-skin requirement apply for all RG3 influenza viruses including wild type viruses or just mutant/reassortant viruses? The reason we ask is we would like to be consistent across all RG3 influenza virus laboratories at our institution.RG3 is shorthand for Risk Group 3. RG3 influenza viruses are members of a family of viruses called the Orthomyxoviruses. They include the 1918-1919 H1N1 (1918 H1N1), human H2N2 (1957-1968), and highly pathogenic avian influenza H5N1 strains within the Goose/Guangdong/96-like H5 lineage (HPAI H5N1).(54) These are the viruses studied in the Kawaoka lab. His special lab was designed with the enhancements required by NIH for labs studying RG3 viruses. There is, according to all newspaper accounts, university announcements, and articles in the Alumni magazine, only one such laboratory at the university. Yet, the Associate Vice Chancellor for Research Policy alludes to others.
The NIH and CDC use various names for this level of biosecurity: ABSL-3+, ABSL-3 Plus, Enhanced BSL-3-Ag, and others. The Wisconsin State Journal tells readers that the security in the Kawaoka is only a "half a notch" below the top level BSL-4 in its safety precautions, but that half notch appears to be a public relations ploy. In fact, as I mentioned earlier, in a BSL-3 setting, even an Enhanced BSL-3-Ag lab like Kawaoka's, the level of safety is much lower than in a BSL-4 lab.
One of the important differences between a BSL-3 and BSL-4 lab is that work with the infectious agents occurs under a hood, a biosafety cabinet (like the defunct and dangerous Madison Cabinets) or in other containment in the BSL-3 environment, but the room itself is not considered nor is it required to provide primary containment as it is in a BSL-4 setting. One of the enhancements required for working with the RG3 influenza viruses in a BSL-3 lab is the use of a PAPRs [Powered Air Purifying Respirator], a self-contained unit that covers a workers head. Some include a shroud that coves the neck and upper torso.
In answer to the university's question about covering the skin of the neck, NIH replied that they thought it was not absolutely necessary, but also pointed to a recommendation by the CDC that workers in labs handling RG3 influenza viruses not have any exposed skin. It remains to be seen whether the university has adopted the CDC recommendation or just the minimum required by NIH.
In its mandatory report to the NIH, the university explained what happened during the November 9, 2013 accident:
The spill occurred during the collection of supernatant samples from the infected cultures at the 24 h time point (on the morning of November 9th, 2013). To collect the virus culture supernatant samples, three 6-well tissue culture plates were transferred by the researcher from the tissue culture incubator into a biosafety cabinet (BSC), and a sample was harvested from each well into 2 ml screw-cap tubes. Following sample collection, the researcher removed all three plates from the BSC (stacked on top of each other) for transfer back into the tissue culture incubator. After opening the external door and the internal glass door of the incubator, the lower half of the tissue culture plate on the bottom of the 3-plate stack slipped from the researcher’s hand and fell to the floor. Four wells of this plate were infected (2 wells each with two different virus mutants: [CENSORED] and [CENSORED])(55),so approximately 8 ml of virus containing media spilled onto the floor.(56)When the plates shattered, the virus-infected material splashed onto the researcher's pants leg and possibly also onto his or her bare ankle. In a BSL-4 lab, they would have been wearing a full spacesuit.
There was disagreement about what to do. The researcher wanted Tamiflu, the standard antiinfluenza drug, but the university expert, an unnamed infectious disease doctor at the university hospital, did not think it was warranted. In spite of that, the unnamed Alternate Responsible Official (ARO) insisted, and a Tamiflu prescription was provided to the researcher who was sent home and told to monitor himself for symptoms. They did not report the incident to state or local public health officials.
The second accident seems to have been what really caught the attention of the NIH. In the event of a possible exposure and infection from a highly pathogenic, highly contagious, very dangerous, experimentally mutated influenza virus, the university's emergency procedure was to drive the victim home and ask them not to leave their house or apartment for ten days. And a few months later the university called me irresponsible for voicing some concern about the public health risks associated with the work going on in the lab.
The university and local media continue to promote these labs' work and to downplay the risk to the public. The Wisconsin State Journal's "Top Story" on September 2, 2015 was a long article titled "Controversial UW-Madison flu research yields new vaccine model."(57)
A controversial technique to create flu viruses, now effectively banned, led to the discovery of a flu vaccine model that could be more reliable than today’s main method using chicken eggs, according to a study by UW-Madison scientist Yoshihiro Kawaoka.The article is primarily a lament that his gain-of-function studies have been halted. Apparently, he wants to grow flu vaccine in dog and monkey cells rather than hens' eggs. The driving force behind the university's steadfast promotion of his work is explained near the end of the article:
The finding, reported Wednesday in the journal Nature Communications, stems from virus engineering research Kawaoka did prior to last October, when the government told him to stop such work during a review of its risks and benefits, he said.
The Wisconsin Alumni Research Foundation is seeking a patent on Kawoaka’s high-yield vaccine technology. Commercialization could fuel a switch from egg-based vaccines, said Kawaoka, founder of FluGen, a Madison company developing flu vaccines.Most of what I have written above is about the university putting the public at risk. The people involved nearly all use animals in their experiments or else they are in administrative positions that lead them to promote and defend the use of animals. Hype and obfuscation are common elements of that culture.
Notes.
(1) William S Mellon, Ph.D. Senior Associate Dean, Academic Affairs and Associate Dean for Research Policy, and the responsible official for the university's Select Agent Program quoted in the Milwaukee Journal Sentinel. "Professor defends safety of UW's bird flu research." Jan. 10, 2012.
(2) UW-Madison Associate Professor of Bioethics and Philosophy, Robert Streiffer has argued that laws are evidence that that "society has already taken a stand" on an issue; but you cannot take a stand on something unless you know about it. The history of the long grueling efforts to change existing laws runs counter to Streffer's claim; the simple fact is that moneyed interests often circumvent democracy through their bought access to lawmakers. Streiffer's claim is from his prepared remarks in response to a request that the university consider the ethics of conducting
harmful experiments on monkeys. University of Wisconsin, Madison, All Campus Institutional Animal Care and Use Committee Minutes. 1-8-2010.
(3) "Reference for National Bio and Agro-Defense Facility." Department of Homeland Security.
http://www.dhs.gov/reference-nbaf. Web retrieved 5-19-1013.
(4) Faulty BioLab Aerosol Chamber Infects Three With TB: NIAID Encourages Use of Leaky Device in Biodefense. Patricia Doyle. The Sunshine Project. (News Release.) 4-20-2005. Web retrieved 12-31-2014. http://www.rense.com/general64/fe.htm.
(5) Select agents, as the term implies, are agents -- disease-causing organisms, prions, or poisons -- that have been identified and selected by the U.S. Department of Health and Human Services or the U.S. Department of Agriculture as being so dangerous that laboratories handling any of these agents must take special precautions to ensure that the agents are not released into the environment. The list of select agents include things like: Eastern Equine Encephalitis virus; Rift Valley fever virus; Ebola virus; Venezuelan equine encephalitis virus; Francisella tularensis; Lassa fever virus; Lujo virus; Marburg virus; African horse sickness virus; Monkeypox virus; African swine fever virus; Reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments (Reconstructed 1918 Influenza virus); Foot and mouth disease virus; Goat pox virus; Ricin; Lumpy skin disease virus; Rickettsia prowazekii; Mycoplasma capricolum; and SARS-associated coronavirus (SARS-CoV), to list but a few. HHS and USDA Select Agents And Toxins. 7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73. Web retrieved 12-31-2013. http://www.selectagents.gov/resources/List_of_Select_Agents_and_Toxins_2013-09-10.pdf.
(
6) "Pathogen Work at Texas A&M Suspended." Jocelyn Kaiser. 7-2-2007. Science Now. Science. American Association for the Advancement of Science. http://news.sciencemag.org/2007/07/pathogen-work-texas-amsuspended.
(7) "Selecting the Most Suitable Aerosolization Equipment." 7-31-2007. Tradeline Inc. Web retrieved 12-31-2014. http://www.tradelineinc.com/reports/2007-7/selecting-most-suitable-aerosolization-equipment.
(8) "U. of Wis. Quietly Scraps Risky Lab Equipment." Ryan J. Foley. Associated Press. 1-9-09. Reported in The Seattle Times: http://seattletimes.com/html/localnews/2008610233_apwiriskydiseasechambers1stldwritethru.html.
(9)"Security Concern Halted Wis. Ebola Study." Ryan J. Foley. Associated Press. 9-20-2007. Reported in USA Today. Web retrieved 12-31-2014. http://usatoday30.usatoday.com/news/health/2007-09-20-2834756754_x.htm. "Wisconsin Lab Broke Ebola Rules, Watchdog Group Says." Lisa Schnirring. 9-25-2007. CIDRAP - Center for Infectious Disease Research and Policy. Academic Health Center, University of Minnesota, Minneapolis, MN. Web retrieved 1-27-2014. http://www.cidrap.umn.edu/news-perspective/2007/09/wisconsin-lab-broke-ebola-ruleswatchdog-group-says.
(10) Letter of April 9, 2008, from Amy Patterson, M.D., Director. Office of Biotechnology Activities, National Institutes of Health, addressed to Jan Klein, Ph.D., Biolgical Safety Officer. Office of Biological Safety. University of Wisconsin-Madison.
(11) "Report of Investigation." Stephen Robinson 5-27-2009. pg 10.
(12) "Review and Assessment of Biolgigical Oversight Program: Biosafety Office, Institutional Biosafety Committee, Select Agent Program University of Wisconsin-Madison, July 28 and 29, 2008." Claudia Mickelson, PhD., Consultant. See too: "Suspended UW-Madison Researcher Served On Key Safety Committee." Ryan J. Foley. Associated Press. 5-18-2010. http://host.madison.com/news/local/education/university/suspended-uw-madison-researcher-served-onkey-safety-committee/article_fa2f976e-629b-11df-9bac-001cc4c03286.html.
(13) Letter to William Mellon, Responsible Official, University of Wisconsin-Madison. (Via Federal Express). From John W. O'Brien, Senior Counsel. Office of the Inspector General. Office of Council to the Inspector General. Department of Health and Human Services. 11-26-2008.
(14) Letter to Professor Gary Splitter. Re: Letter of Suspension of Laboratory and Research Privileges (FPP Ch. 9 investigation) [sic] from Paul M. DeLuca, Jr. 1-29-2010.
(15) "Reports Find UW Lab Oversight Weak." Deborah Zif. Wisconsin State Journal. 5-29-2010. Web retrieved 1-31-2014. http://host.madison.com/news/local/education/university/reports-find-uw-lab-oversightweak/article_2cc80c47-83ad-55a1-abad-8510c034647b.html
(16) "Scientist, Banned From Lab, Blames U. of Wisconsin for Biosafety Lapse." Paul Basken. The Chronicle of Higher Education. 5-19-2010.
(17) "UW Steps Up Bio Research Safety." David Wahlberg. Wisconsin State Journal. 2-21-2012. Web Retrieved 1-30-2014. http://host.madison.com/news/local/education/university/uw-steps-up-bio-research-safety/article_3320c7cd-0cda-5fbc-9b9a-f3921231705c.html.
(18) The Great Influenza: The Epic Story of the Deadliest Plague in History [Paperback]. John M. Barry. (Also published as The Great Influenza: The Story of the Deadliest Epidemic in History.) New York: Penguin Books. 2004. p 4.
(19) Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Kobasa D, Jones SM, Shinya K, Kash JC, Copps J, Ebihara H, Hatta Y, Kim JH, Halfmann P, Hatta M, Feldmann F, Alimonti JB, Fernando L, Li Y, Katze MG, Feldmann H, Kawaoka Y. Nature. 2007 Jan 18;445(7125):319-23.
(20) "1918 Killer Flu Tested on Monkeys." AP Online. 2007. HighBeam Research. (January 30, 2014). http://www.highbeam.com/doc/1Y1-102256235.html.
(21) "Experts Fear Escape of 1918 Flu From Lab. Debora MacKenzie." New Scientist. 10-21-2004. Web retrieved 12-31-2013. http://www.newscientist.com/article/dn6554-experts-fear-escape-of-1918-flu-from-lab.html.
(22) "BSL-4 Laboratories in the United States." Federation of American Scientists. Web retrieved 1-31-2014. http://www.fas.org/programs/bio/research.html#USBSL4.
(23 "High-Containment Biosafety Laboratories: Preliminary Observations on the Oversight of the Proliferation of BSL-3 and BSL-4 Laboratories in the United States. GAO-08-108T. 10-4-2007. http://www.gao.gov/products/GAO-08-108T. See too: BSL-4 Laboratories as of 2010-2011. Federation of American Scientists. https://www.google.com/fusiontables/DataSource?snapid=S567513UnBn.
(24) "If Swine Flu Weren't Enough, Now There's Swine Ebola: Scientists report that domestic pigs harbor Reston ebolavirus, the only Ebola species that has not caused disease in humans." Brendan Borrell. Scientific American. 7-9-2009. http://www.scientificamerican.com/article.cfm?id=swine-ebola-discovered.
(25) "Ebola Reston Outbreaks." Thesis. Tara Waterman. 2-25-1998; revised 3-1-1999. http://www.stanford.edu/group/virus/filo/filo.html.
(26) "Demanding Job in a Divided Lab, Then a Murder." Javier C. Hernandez and Serge F. Kovaleski. The New York Times. 9-17-2009.
(27) "Fort Detrick Inventory Turns Up 9,220 More Vials of Pathogens." Nelson Hernandez. Washington Post. 6-18-2009.
(28) "State Incidents Highlight Bioterror Lab Concerns." Science. 10-3-2015. http://news.sciencemag.org/biology/2015/10/u-s-government-rejected-dozens-risky-pathogen-studies-past-fewyears.
(29) "Foot-and-mouth crisis remembered." BBC. 2-17-2011. http://www.bbc.co.uk/news/uk-england-12472230.
(30) "The 2001 Outbreak of Foot and Mouth Disease." National Audit Office. United Kingdom. 6-21-2002. Web accessed 1-31-2014. http://www.nao.org.uk/report/the-2001-outbreak-of-foot-and-mouth-disease/. "Streamlining Farm Oversight." Department for Environment, Food and Rural Affairs. Report by the Comptroller and Auditor General. United Kingdom. 12-12-2012. Web accessed 1-31-2014. http://www.nao.org.uk/wpcontent/uploads/2012/12/1213797es.pdf.
(31) Lab 257: The Disturbing Story of the Government's Secret Plum Island Germ Laboratory. Michael C. Carroll. New York: HarperCollins. 2004. Jacket note.
(32) "McKenna Selected to Head Veterinary Diagnostic Lab." 1-31-2007. Dennis Chaptman. University of Wisconsin-Madison News. Web retrieved 1-1-2014. http://www.news.wisc.edu/13412.
(33) Dunn Residents, Board Oppose Disease Lab. Matthew DeFour. Wisconsin State Journal. 3-8-2007.
(34) Biodefense and Emerging Infectious Diseases. "Are NIAID scientists already studying potential agents of bioterrorism?" The National Institute of Allergy and Infectious Diseases. Last Updated 6-3-2013. Last Reviewed 8-2-2012. Web retrieved 12-31-2013. http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PublicMedia/pages/faqs.aspx#10
(35) "PHRI Receives $2 million Biodefense Grant." The Public Health Research Institute (PHRI) of New Jersey Medical School - Rutgers University. Web retrieved 1-1-14. http://www.phri.or/news/news_inthenews50217.asp.
(36) United States Government Accountability Office Report to Congressional Committees. December 2005. DHS and USDA Are Successfully Coordinating Current Work, but Long-Term Plans Are Being Assessed. GAO-06-132, 12-19-2005. Web retrieved 1-1-14. http://www.gao.gov/new.items/d06132.pdf.
(37) The statement made by RARC Director Eric Sandgren after PETA's epic three-year court battle forced the University to turn over photographs of one of the cats in the Tom Yin lab is similar in its cynical deceit: "It's important to know what the cost is to the animal. It's important to know what the potential benefit is to, in this case it's humans, but a lot of animal research also benefits animals. And then ... you compare those, and decide for yourself whether or not something you think it's ethical, and that's where people have a right to differ." See Chapter 19 "Secrecy."
(38) "Loss of Disease Lab Tied to Opposition: UW-Madison Learns How Its Application for $450 Million Federal Facility Was Rated." Matthew DeFour. Wisconsin State Journal. 7-21-2007. Web retrieved 1-1-2014. http://host.madison.com/news/local/loss-of-disease-lab-tied-to-opposition-uw-madison-learns/article_262313dc-6891-5584-99a4-90ec129a1fa8.html.
(39) Binder, A. R., Scheufele, D. A., Brossard, D. and Gunther, A. C. Interpersonal Amplification of Risk? Citizen Discussions and Their Impact on Perceptions of Risks and Benefits of a Biological Research Facility. Risk Analysis. 2011. 31: 324–334. Web retrieved 1-1-2014. http://onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2010.01516.x/abstract.
(40) "Forget Consensus - More Telling, Less Discussing, Recommends NC State Paper." 11-4-2010. Science 2.0. Web retrieved 1-1-2014. http://www.science20.com/news_article/forget_consensus_more_telling_less_discussing_recommends_nc_state_paper.
(41) High-Containment Biosafety Laboratories: Preliminary Observations on the Oversight of the Proliferation of BSL-3 and BSL-4 Laboratories in the United States. GAO-08-108T, 10-4-2007. Web retrieved 1-31-2014. http://www.gao.gov/assets/120/118000.html.
(42) "Pandemic Avian Flu Genes Made Public." In "The Top 10 Science Stories of 2012." 12-20-2012. Scientific American. Web retrieved 2-2-2014. http://www.scientificamerican.com/article/top-10-science-stories-2012/?page=4.
(43) "An Engineered Doomsday." Sunday Review. New York Times. 1-7-2012. Web Retrieved 1-1-2014. http://www.nytimes.com/2012/01/08/opinion/sunday/an-engineered-doomsday.html?_r=0.
(44) "Leading Scientists Condemn Decision to Continue Controversial Research Into Deadly H5N1 Bird-Flu Virus." Steve Connor. The Independent. 1-23-13. Web retrieved 1-1-2014. http://www.independent.co.uk/news/science/leading-scientists-condemn-decision-to-continue-controversialresearch-into-deadly-h5n1-birdflu-virus-8463863.html.
(45) "'Untrue Statements' Anger Over Eork to Make H5N1 Bird-Flu Virus MORE Dangerous to Humans." Steve Connor. The Independent. 12-20-13. Web retrieved 1-1-2014. http://www.independent.co.uk/news/science/untruestatements-anger-over-work-to-make-h5n1-birdflu-virus-more-dangerous-to-humans-9018666.html.
(46) "UW Animal Research Achievements." University of Wisconsin-Madison. Web retrieved 1-1-2014. http://animalresearch.wisc.edu/uw-achievements/.
(47) "Flu Shots May Not Protect the Elderly or the Very Young." Melinda Wenner Moyer. 10-18-2012. Scientific American. Web retrieved 1-1-2014.
(48) Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews. 2013. Issue 6. Art. No.: CD001269: "This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding."
(49) UW Associate Dean William Mellon: Bird flu research facilities are secure. Letter to the editor. 4-11-2013. Web retrieved 1-27-2014. http://host.madison.com/news/opinion/mailbag/uw-associate-dean-william-mellon-bird-fluresearch-facilities-are/article_98dc205c-6abc-5d0f-b3e9-f7a9ba68b931.html. Emeritus Professor in the School of Pharmacy, Senior Associate Dean for Academic Affairs, and Associate Dean for Research Policy, William S. Mellon is also the Institutional Officer who signs the Public Health Service Assurance for the university, stipulating that the university and all its employees will adhere carefully to the guidelines for animal care and use set forth in the National Academies of Science's Guide for the Care and Use of Laboratory Animals. (See Chapter 13, Oversight and Regulation.)
(50) "Rick Bogle: Flu Lab Accident Could Leave Millions Dead Within Weeks." The Capital Times. Jul 8, 2014. http://host.madison.com/ct/news/opinion/column/rick-bogle-flu-lab-accident-could-leave-millions-deadwithin/ article_371153c6-2943-5e46-9bae-e6980b751a77.html.
(51) "UW's Tim Yoshino and Susan West: Rick Bogle's Flu Lab Column Irresponsible." The Capital Times. July 11, 2014. http://host.madison.com/ct/news/opinion/mailbag/uw-s-tim-yoshino-and-susan-west-rick-bogle-s/article_84e9f92a-9052-596e-911f-95570f3ee440.html.
(52) "Flu Central. UW Will Be at Center of Research Against Virus." Anita Weller. The Capital Times. Front page, lead story. 3-15-2006. "Flight Lessons." Michael Penn. On Wisconsin. Winter 2006. Cover story. pp 20-27.
(53) "Inside America's Secretive Biolabs." Alison Young and Nick Penzenstadler, USA TODAY. 5-28-2015. http://www.usatoday.com/story/news/2015/05/28/biolabs-pathogens-location-incidents/26587505/.
(54) "NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules." (NIH Guidelines). April 2016. http://osp.od.nih.gov/sites/default/files/NIH_Guidelines.html#_Toc446948390
(55) It is not clear why they censored the names of the virus mutants. They left this information in the report: "The researcher was working in the ABSL-3+ suite performing growth curve analysis of viruses containing mutations in the PB2 protein (part of the viral polymerase complex), in the virus strain background of A/Muscovy Duck/Vietnam/TY93/2007 (H5N1; referred to as ‘TY93’). The viral hemagglutinin (HA) protein of this virus strain possesses a multi-basic cleavage site. Approximately 24 h prior to the incident (on November 8th, 2013), cells in 6-well tissue culture plates were infected at a multiplicity of 0.001 plaque forming units (PFU) per cell (~4 x 105 cells per well). Following the infection, infected cells were covered with approximately 2 ml of media per well, and cultures were incubated."
(56) The accident, the university reported to the NIH, was handled as if it were a "large" spill because their SOPs define a large spill of highly infectious material as 10ml and over.
(57) "Controversial UW-Madison Flu Research Yields New Vaccine Model." David Wahlberg, Wisconsin State Journal. 9-2-2015. http://host.madison.com/wsj/news/local/health_med_fit/controversial-uw-madison-flu-researchyields-new-vaccine-model/article_6538cdc6-54df-59db-ab72-80bd203d9917.html.