by Steve Connor
01 July 2014
over the creation of a virus
that could render
the human immune system
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 neutralizing
antibodies, effectively making the human population defenseless
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
analyze 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 defense 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.
Yoshihiro Kawaoka's study
has yet to be
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
"He took the 2009 pandemic flu virus
and selected out strains that were not neutralized 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 defenseless if it ever escaped from his laboratory,"
"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 criticized 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
"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.
during the 2009
outbreak, in Mexico City (Getty)
"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 Tom 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 defenses," 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
"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.
questions and answers
Why is this experiment different from what
has been done before?
This is the first time that someone has taken a strain of
influenza virus, called H1N1, known to have caused a global
epidemic, in other words a "pandemic", and deliberately mutated
it many times over.
It can then evade the neutralizing
antibodies of the human immune system, which have protected much
of the human population since the virus first emerged in 2009.
What has been done previously in
Professor Yoshihiro Kawaoka of the University of
Wisconsin-Madison attempted to increase the transmissibility of
the H5N1 bird flu strain by genetic manipulation and repeated
infection in laboratory ferrets, an animal model of human
H5N1 is highly lethal when it
infects people, but in the wild it is very difficult to transmit
from one person to another and is usually caught by direct
contact with infected poultry.
flu virus from 2009
Professor Kawaoka's most recent published research was on
reconstructing the 1918 flu virus, the genetic structure which
was known from samples retrieved from the frozen corpses of its
victims buried in the Arctic, from wild strains of bird flu
isolated from ducks.
He managed to do this, but the study
was widely criticized as "stupid" and "irresponsible".
Why does he want to do this work?
The aim is to understand what is known as "gain of function".
What does it take, genetically, for
a virus to become more infectious or more lethal? If we could
understand this process then we would be in a better position to
develop drugs, vaccines and other measures to protect ourselves
from a sudden emergence of a new and deadly flu strain, or so
Professor Kawaoka has argued.
Does he have the support of other
There is a big split within the scientific community over this
kind of work.
Some flu specialists support it,
provided it is done under strictly regulated and controlled
conditions. Others, mostly experts in infectious diseases
outside the flu community, are passionately opposed to the work,
claiming that the risks of an accidental (or even deliberate)
release that will cause a devastating pandemic are too great to
justify any practical benefits that may come out of the work.
Have there been any accidental
releases from labs in the past?
Some experts cite the unexpected emergence of a new H1N1 strain
of flu in 1977, which spread globally over three decades, as an
early example of a flu virus being accidentally released from a
Genetic evidence points to it having
escaped from a lab in China or the Soviet Union.
There are many examples of other infectious agents escaping from
labs. Smallpox virus escaped from Birmingham Medical School in
1978 and killed a medical photographer, Janet Parker, the last
person to die of smallpox.
Foot and mouth virus escaped in 2007
from a veterinary lab in Surrey and in 2004 the SARS virus
escaped from a high-containment lab in Beijing, infecting nine
people before it was stopped.