Exclusive: Controversial US scientist creates deadly new flu strain for pandemic research
A
controversial scientist who carried out provocative research on making
influenza viruses more infectious has completed his most dangerous
experiment to date by deliberately creating a pandemic strain of flu
that can evade the human immune system.
Yoshihiro Kawaoka of the University of Wisconsin-Madison has genetically manipulated the 2009 strain of pandemic flu in order for it to "escape" the control of the immune system's neutralising antibodies, effectively making the human population defenceless against its reemergence.
Most of the world today has developed some level of immunity to the 2009 pandemic flu virus, which means that it can now be treated as less dangerous "seasonal flu". However, The Independent understands that Professor Kawaoka intentionally set out to see if it was possible to convert it to a pre-pandemic state in order to analyse the genetic changes involved.
The study is not published, however some scientists who are aware of it are horrified that Dr Kawaoka was allowed to deliberately remove the only defence against a strain of flu virus that has already demonstrated its ability to create a deadly pandemic that killed as many as 500,000 people in the first year of its emergence.
Professor Kawaoka has so far kept details of the research out of the public domain but admitted today that the work is complete and ready for submission to a scientific journal. The experiment was designed to monitor the changes to the 2009 H1N1 strain of virus that would enable it to escape immune protection in order to improve the design of vaccines, he said.
"Through selection of immune escape viruses in the laboratory under appropriate containment conditions, we were able to identify the key regions [that] would enable 2009 H1N1 viruses to escape immunity," Professor Kawaoka said in an email.
"Viruses in clinical isolates have been identified that have these same changes in the [viral protein]. This shows that escape viruses emerge in nature and laboratory studies like ours have relevance to what occurs in nature," he said.
Prior to his statement to The Independent, Professor Kawaoka's only known public mention of the study was at a closed scientific meeting earlier this year. He declined to release any printed details of his talk or his lecture slides.
Some members of the audience, however, were shocked and astonished at his latest and most audacious work on flu viruses, which follow on from his attempts to re-create the 1918 flu virus and an earlier project to increase the transmissibility of a highly lethal strain of bird flu.
"He took the 2009 pandemic flu virus and selected out strains that were not neutralised by human antibodies. He repeated this several times until he got a real humdinger of a virus," said one scientist who was present at Professor Kawaoka's talk.
"He left no doubt in my mind that he had achieved it. He used a flu virus that is known to infect humans and then manipulated it in such a way that it would effectively leave the global population defenceless if it ever escaped from his laboratory," he said.
"He's basically got a known pandemic strain that is now resistant to vaccination. Everything he did before was dangerous but this is even madder. This is the virus," he added.
The work was carried out at Wisconsin University's $12m (£7.5m) Institute for Influenza Virus Research in Madison which was built specifically to house Professor Kawaoka's laboratory, which has a level-3-agriculture category of biosafety: one below the top safety level for the most dangerous pathogens, such as Ebola virus.
However, this study was done at the lower level-2 biosafety. The university has said repeatedly that there is little or no risk of an accidental escape from the lab, although a similar US Government lab at the Centers for Disease Control and Prevention in Atlanta with a higher level-3 biosafety rating was recently criticised over the accidental exposure of at least 75 lab workers to possible anthrax infection.
Professor Kawaoka's work had been cleared by Wisconsin's Institutional Biosafety Committee, but some members of the committee were not informed about details of the antibody study on pandemic H1N1, which began in 2009, and have voiced concerns about the direction, oversight and safety of his overall research on flu viruses.
"I have met Professor Kawaoka in committee and have heard his research presentations and honestly it was not re-assuring," said Professor Tom Jeffries, a dissenting member of the 17-person biosafety committee who said he was not made aware of Kawaoka's work on pandemic H1N1, and has reservations about his other work on flu viruses.
"What was present in the research protocols was a very brief outline or abstract of what he was actually doing...there were elements to it that bothered me," Professor Jeffries said.
"I'm a distinct minority on this committee in raising objections. I'm very uneasy when the work involves increasing transmissibility of what we know already to be very virulent strains," he said.
Asked what he thought about the unpublished study involving the creation of a pandemic strain of flu deliberately designed to escape the control of the human immune system, Professor Jeffries said: "That would be a problem."
Rebecca Moritz, who is responsible for overseeing Wisconsin's work on "select agents" such as influenza virus, said that Professor Kawaoka's work on 2009 H1N1 is looking at the changes to the virus that are needed for existing vaccines to become ineffective.
"With that being said, this work is not to create a new strain of influenza with pandemic potential, but [to] model the immune-pressure the virus is currently facing in our bodies to escape our defences," Ms Moritz said.
"The work is designed to identify potential circulating strains to guide the process of selecting strains used for the next vaccine...The committee found the biosafety containment procedures to be appropriate for conducting this research. I have no concerns about the biosafety of these experiments," she said.
Professor Kawaoka said that he has presented preliminary findings of his H1N1 study to the WHO, which were "well received".
"We are confident our study will contribute to the field, particularly given the number of mutant viruses we generated and the sophisticated analysis applied," he said.
"There are risks in all research. However, there are ways to mitigate the risks. As for all the research on influenza viruses in my laboratory, this work is performed by experienced researchers under appropriate containment and with full review and prior approval by the [biosafety committee]," he added.
Yoshihiro Kawaoka of the University of Wisconsin-Madison has genetically manipulated the 2009 strain of pandemic flu in order for it to "escape" the control of the immune system's neutralising antibodies, effectively making the human population defenceless against its reemergence.
Most of the world today has developed some level of immunity to the 2009 pandemic flu virus, which means that it can now be treated as less dangerous "seasonal flu". However, The Independent understands that Professor Kawaoka intentionally set out to see if it was possible to convert it to a pre-pandemic state in order to analyse the genetic changes involved.
The study is not published, however some scientists who are aware of it are horrified that Dr Kawaoka was allowed to deliberately remove the only defence against a strain of flu virus that has already demonstrated its ability to create a deadly pandemic that killed as many as 500,000 people in the first year of its emergence.
Professor Kawaoka has so far kept details of the research out of the public domain but admitted today that the work is complete and ready for submission to a scientific journal. The experiment was designed to monitor the changes to the 2009 H1N1 strain of virus that would enable it to escape immune protection in order to improve the design of vaccines, he said.
"Through selection of immune escape viruses in the laboratory under appropriate containment conditions, we were able to identify the key regions [that] would enable 2009 H1N1 viruses to escape immunity," Professor Kawaoka said in an email.
"Viruses in clinical isolates have been identified that have these same changes in the [viral protein]. This shows that escape viruses emerge in nature and laboratory studies like ours have relevance to what occurs in nature," he said.
Prior to his statement to The Independent, Professor Kawaoka's only known public mention of the study was at a closed scientific meeting earlier this year. He declined to release any printed details of his talk or his lecture slides.
Some members of the audience, however, were shocked and astonished at his latest and most audacious work on flu viruses, which follow on from his attempts to re-create the 1918 flu virus and an earlier project to increase the transmissibility of a highly lethal strain of bird flu.
"He took the 2009 pandemic flu virus and selected out strains that were not neutralised by human antibodies. He repeated this several times until he got a real humdinger of a virus," said one scientist who was present at Professor Kawaoka's talk.
"He left no doubt in my mind that he had achieved it. He used a flu virus that is known to infect humans and then manipulated it in such a way that it would effectively leave the global population defenceless if it ever escaped from his laboratory," he said.
"He's basically got a known pandemic strain that is now resistant to vaccination. Everything he did before was dangerous but this is even madder. This is the virus," he added.
The work was carried out at Wisconsin University's $12m (£7.5m) Institute for Influenza Virus Research in Madison which was built specifically to house Professor Kawaoka's laboratory, which has a level-3-agriculture category of biosafety: one below the top safety level for the most dangerous pathogens, such as Ebola virus.
However, this study was done at the lower level-2 biosafety. The university has said repeatedly that there is little or no risk of an accidental escape from the lab, although a similar US Government lab at the Centers for Disease Control and Prevention in Atlanta with a higher level-3 biosafety rating was recently criticised over the accidental exposure of at least 75 lab workers to possible anthrax infection.
Professor Kawaoka's work had been cleared by Wisconsin's Institutional Biosafety Committee, but some members of the committee were not informed about details of the antibody study on pandemic H1N1, which began in 2009, and have voiced concerns about the direction, oversight and safety of his overall research on flu viruses.
"I have met Professor Kawaoka in committee and have heard his research presentations and honestly it was not re-assuring," said Professor Tom Jeffries, a dissenting member of the 17-person biosafety committee who said he was not made aware of Kawaoka's work on pandemic H1N1, and has reservations about his other work on flu viruses.
"What was present in the research protocols was a very brief outline or abstract of what he was actually doing...there were elements to it that bothered me," Professor Jeffries said.
"I'm a distinct minority on this committee in raising objections. I'm very uneasy when the work involves increasing transmissibility of what we know already to be very virulent strains," he said.
Asked what he thought about the unpublished study involving the creation of a pandemic strain of flu deliberately designed to escape the control of the human immune system, Professor Jeffries said: "That would be a problem."
Rebecca Moritz, who is responsible for overseeing Wisconsin's work on "select agents" such as influenza virus, said that Professor Kawaoka's work on 2009 H1N1 is looking at the changes to the virus that are needed for existing vaccines to become ineffective.
"With that being said, this work is not to create a new strain of influenza with pandemic potential, but [to] model the immune-pressure the virus is currently facing in our bodies to escape our defences," Ms Moritz said.
"The work is designed to identify potential circulating strains to guide the process of selecting strains used for the next vaccine...The committee found the biosafety containment procedures to be appropriate for conducting this research. I have no concerns about the biosafety of these experiments," she said.
Professor Kawaoka said that he has presented preliminary findings of his H1N1 study to the WHO, which were "well received".
"We are confident our study will contribute to the field, particularly given the number of mutant viruses we generated and the sophisticated analysis applied," he said.
"There are risks in all research. However, there are ways to mitigate the risks. As for all the research on influenza viruses in my laboratory, this work is performed by experienced researchers under appropriate containment and with full review and prior approval by the [biosafety committee]," he added.
Contagion film is not far from the truth, warns virus scientist
Dr Ian Lipkin, expert who advised on Soderbergh's movie, says we must be better prepared for outbreak of deadly disease
Email
Marion Cotillard in a
scene from Contagion in which she plays a doctor searching for the
origin of the virus. Photograph: Warner Bros/Sportsphoto Ltd/Allstar
It's a classic Hollywood tale: scientists race against time to
decode a killer virus that is spreading across the world. But the
scientist who advised Oscar-winning director Steven Soderbergh on his new thriller, Contagion, says the events and themes of his latest film carry a very real warning for our times.
Dr Ian Lipkin, professor of epidemiology, neurology and
pathology at New York's Columbia University, was recruited as a senior
technical adviser on Soderbergh's blockbuster. The film, which opened in
cinemas on Friday, charts the emergence of a deadly infectious disease
that ignites a pandemic.
Scientists are first alerted after Beth Emhoff, played by Gwyneth Paltrow, becomes sick after returning from a business trip to Hong Kong and dies two days later. As the virus quickly spreads and the death toll rises, it is down to a team of scientists – including Dr Erin Mears, played by Kate Winslet – to decode the virus so that a vaccine can be produced.
According to Lipkin, the plot is anything but unrealistic. Virus outbreaks are an increasing threat in the 21st century, he says, because of greater international trade and travel, urbanisation, loss of wildlife habitats and inadequate investment in infrastructure for surveillance, vaccine production and distribution.
"Scientists have been accused of overreacting and crying wolf over the threat of virus outbreaks after the influenza pandemic of 2009," Lipkin told the Observer. "Sars [Severe Acute Respiratory Syndrome] didn't progress beyond a few locations, but outbreaks and pandemics will occur and we need to get our heads out of the sand and realise the real risks that we face. More than three-quarters of all emerging infectious diseases originate when microbes jump from wildlife to humans.
"Our vulnerability to such diseases has been heightened by the growth in international travel and the globalisation of food production. In addition, deforestation and urbanisation continue to displace wildlife, increasing the probability that wild creatures will come in contact with domesticated animals and humans."
Lipkin says societies need to be more proactive in combating the dangers. "People need to understand that science is critical to address these kinds of challenges and respond in real time," he said. "We need to be prepared. We need better bio-surveillance, with better detection and better ability to develop vaccines. However, our public health system is underfunded and overwhelmed, and we need more scientists."
Lipkin added: "When I was a kid, the launching of Sputnik made us aware that the United States was falling behind the Soviet Union in the race for space. Now all of us are in a battle that is potentially devastating, only it is not against another country but against microbes."
In Contagion, Soderbergh draws on real-life disease outbreaks, including the 2003 Sars epidemic, which started in Hong Kong and spread to 37 countries, infecting more than 8,400 people and causing 916 deaths.
Lipkin assisted the World Health Organisation and the Chinese ministry of health in managing the Sars outbreak, at some personal peril – he became ill and was quarantined on returning to the US.
"The events portrayed in this film are based largely on real experiences," said Lipkin. "For example, there are scenes in the movie where at the height of the pandemic the streets are deserted, there are food and supply shortages and political instability, and this directly comes out of my vivid memories of what it was like in Beijing during the Sars crisis.
"I was also able to advise actors from personal experience what it feels like to be quarantined – an eerie experience where you are behind glass and cut off from loved ones."
Lipkin is one of the world's foremost microbe hunters and over the past decade has identified more than 400 new viruses. But unlike British cosmologist Dr Martin Rees, who controversially predicted in his book Our Final Hour that civilisation had no more than a 50% chance of surviving until 2100, Lipkin is an optimist.
"Since the Sars outbreak, there has been increased investment to look at wildlife around the world and there is better integration between the different public health agencies both nationally and internationally," Lipkin said. "So there is reason to be optimistic, and I believe we can address the problems.
"We are one world – humans and animals – and we need to take care of one another. We also, for example, need to insist that people move away from technologies that slow down the production of vaccines so that we can develop a vaccine in three months instead of six."
Contagion pays tribute to the scientists and public health officials who dedicate their lives to trying to solve the problem of emerging viruses. Winslet's character is based on Italian scientist Carlo Urbani, who was the first to identify Sars and became infected with the disease while treating patients and died aged 46, leaving his wife and three children.
"The most moving portions of the film were those where I saw people who were very similar to people whom I've known, people who didn't have well-known names, who died in the service of science and public health," said Lipkin. "The film is in some ways a living memorial to them."
- Contagion
- Production year: 2011
- Countries: Rest of the world, USA
- Cert (UK): 12A
- Runtime: 106 mins
- Directors: Steven Soderbergh
- Cast: Bryan Cranston, Gwyneth Paltrow, Jennifer Ehle, John Hawkes, Jude Law, Kate Winslet, Laurence Fishburne, Marion Cotillard, Matt Damon
Scientists are first alerted after Beth Emhoff, played by Gwyneth Paltrow, becomes sick after returning from a business trip to Hong Kong and dies two days later. As the virus quickly spreads and the death toll rises, it is down to a team of scientists – including Dr Erin Mears, played by Kate Winslet – to decode the virus so that a vaccine can be produced.
According to Lipkin, the plot is anything but unrealistic. Virus outbreaks are an increasing threat in the 21st century, he says, because of greater international trade and travel, urbanisation, loss of wildlife habitats and inadequate investment in infrastructure for surveillance, vaccine production and distribution.
"Scientists have been accused of overreacting and crying wolf over the threat of virus outbreaks after the influenza pandemic of 2009," Lipkin told the Observer. "Sars [Severe Acute Respiratory Syndrome] didn't progress beyond a few locations, but outbreaks and pandemics will occur and we need to get our heads out of the sand and realise the real risks that we face. More than three-quarters of all emerging infectious diseases originate when microbes jump from wildlife to humans.
"Our vulnerability to such diseases has been heightened by the growth in international travel and the globalisation of food production. In addition, deforestation and urbanisation continue to displace wildlife, increasing the probability that wild creatures will come in contact with domesticated animals and humans."
Lipkin says societies need to be more proactive in combating the dangers. "People need to understand that science is critical to address these kinds of challenges and respond in real time," he said. "We need to be prepared. We need better bio-surveillance, with better detection and better ability to develop vaccines. However, our public health system is underfunded and overwhelmed, and we need more scientists."
Lipkin added: "When I was a kid, the launching of Sputnik made us aware that the United States was falling behind the Soviet Union in the race for space. Now all of us are in a battle that is potentially devastating, only it is not against another country but against microbes."
In Contagion, Soderbergh draws on real-life disease outbreaks, including the 2003 Sars epidemic, which started in Hong Kong and spread to 37 countries, infecting more than 8,400 people and causing 916 deaths.
Lipkin assisted the World Health Organisation and the Chinese ministry of health in managing the Sars outbreak, at some personal peril – he became ill and was quarantined on returning to the US.
"The events portrayed in this film are based largely on real experiences," said Lipkin. "For example, there are scenes in the movie where at the height of the pandemic the streets are deserted, there are food and supply shortages and political instability, and this directly comes out of my vivid memories of what it was like in Beijing during the Sars crisis.
"I was also able to advise actors from personal experience what it feels like to be quarantined – an eerie experience where you are behind glass and cut off from loved ones."
Lipkin is one of the world's foremost microbe hunters and over the past decade has identified more than 400 new viruses. But unlike British cosmologist Dr Martin Rees, who controversially predicted in his book Our Final Hour that civilisation had no more than a 50% chance of surviving until 2100, Lipkin is an optimist.
"Since the Sars outbreak, there has been increased investment to look at wildlife around the world and there is better integration between the different public health agencies both nationally and internationally," Lipkin said. "So there is reason to be optimistic, and I believe we can address the problems.
"We are one world – humans and animals – and we need to take care of one another. We also, for example, need to insist that people move away from technologies that slow down the production of vaccines so that we can develop a vaccine in three months instead of six."
Contagion pays tribute to the scientists and public health officials who dedicate their lives to trying to solve the problem of emerging viruses. Winslet's character is based on Italian scientist Carlo Urbani, who was the first to identify Sars and became infected with the disease while treating patients and died aged 46, leaving his wife and three children.
"The most moving portions of the film were those where I saw people who were very similar to people whom I've known, people who didn't have well-known names, who died in the service of science and public health," said Lipkin. "The film is in some ways a living memorial to them."
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