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[SANET-MG] No control over GM microbes
Germs gone wild
By alex roslin
Publish Date: 21-Jul-2005 straight.com
http://www.straight.com/section.cfm?id=172
It is the end of June, and Catherine Anderson is excited about summer
camp. She won’t be playing in the pool or catching butterflies. She is
going to Geneskool. Anderson is the organizer of the two-week camp that
kicked off for the first time at the University of British Columbia this
July. Twenty students entering Grades 10 and 11 got a chance to sequence
DNA and do a family gene pedigree. And, oh, yes, they will create a new
life form: genetically modified Escherichia coli bacteria, better known
as E. coli.
“It’s really easy,” says Anderson, a UBC instructor in dentistry and
medicine and a consultant at Genome British Columbia, a
provincial-federal agency that gets corporate funding to promote
biotechnology.
“We’re using a kit that has E. coli. You put in a plasmid with an
antibiotic-resistant gene and a green fluorescent protein from a
jellyfish. The next day, the kids get to see their kit grow green. Plus,
the E. coli will have antibiotic resistance.”
Anderson quickly adds, “It’s not scary antibiotic resistance. These
bacteria are very safe.”
Geneskool, sponsored by UBC and Genome B.C., is just one of dozens of
places—mostly high schools and colleges—where Canadian teenagers are
being encouraged to try their hand at genetic engineering. “It’s the
perfect marriage between recreation and science,” Anderson says on the
phone from the UBC lab hosting the camp.
It all leaves Joe Cummins stunned. He thinks letting teens create
drug-resistant bacteria is one of the craziest things he has heard.
Cummins is one of Canada’s most prominent geneticists. “I think it’s
spectacularly stupid,” he says over the phone from his home in London,
Ontario. “Any way you cut it, these high-school kids will get it [E.
coli] on them. That’s inescapable among these young kids.”
Cummins, 72, a professor emeritus at the University of Western Ontario,
is a walking library of genetics knowledge. Retired for nine years, he
still works at a dizzying pace, dashing off new papers and scouring
obscure patent applications and the latest genetics research.
On hearing about Geneskool, Cummins immediately thinks of a landmark
Dutch study from 1991. It surprised scientists by discovering that their
lab coats were routinely contaminated by genetically modified bacteria,
which often also penetrated to clothes underneath. “The kids could carry
this into the environment on their hands and clothes, and it [the
antibiotic-resistant trait] can persist in their bodies for years,” he says.
That’s troublesome, according to Cummins, because the students are
giving the E. coli resistance to the antibiotic ampicillin, which is
commonly used to treat bacterial infections and as a last-resort drug
against bacterial meningitis and the deadly strain of E. coli that
killed seven people and made 2,000 sick in Walkerton, Ontario.
The E. coli used at Geneskool is a different, harmless strain. But
Cummins says the risk is that it could pass on its ampicillin resistance
to any of the billions of other bacteria that live in a person’s body or
into the environment if it hitches a ride out of the lab on a student.
At the company that makes the genetic engineering kit, Bio-Rad Canada,
life-science manager Tab Meyers says 70 to 100 of the kits have been
sold across the country in the past four years, each good for a class of
32 students or more. He won’t name any of the schools that bought kits
because he doesn’t want to “give them bad press”. But he says the
drug-resistant E. coli is perfectly safe “unless kids ingest it. It’s
not a biohazard per se. It’s a relatively low dose. The only way they
could come into contact with it is by the hands if they are not wearing
gloves,” he says on the phone from his Toronto office.
One of the guest speakers at Geneskool is Julian Davies, a prominent UBC
professor of microbiology and immunology. Davies also defends the E.
coli experiment. He says there is only a “very small” chance that the
ampicillin resistance would spread to an organism in a student’s body.
“I don’t think people understand risk-benefit ratios. The benefits are
high because you are giving these students knowledge. The risks are
extraordinarily small,” Davies says on the phone from his office. “I’m
probably full of ampicillin-resistant bugs. I never drink any [bacteria]
cultures, but I’ve spilled it on my hand.”
That doesn’t reassure Cummins. “There’s just no way young kids should be
exposed to that resistance marker [gene],” he says. He says high-school
biotech experiments are an all-too-common example of the lax attitudes
of scientists and public officials toward the horde of genetically
modified bacteria and viruses being engineered in labs around the world.
“This is typical of much of Canadian biotechnology,” he says. “They tend
to be wildly careless.”
So far in the debate about genetic engineering, tiny germs have mostly
escaped attention. The focus has been on things like GM-food labels and
the ethics of designer babies or cloned pets. Yet the single most
genetically transformed organism isn’t canola, sheep, or the
glow-in-the-dark pet GloFish. It is the wee little E. coli bacterium,
which lives by the billions in every person’s gut. The E. coli is the
love machine of the living world. It multiplies so fast that a single
organism’s offspring could weigh as much as the Earth in two days if
they didn’t run out of food or space. Drug-making companies harness the
awesome sexual power of the E. coli and other microbes as their main
workhorses on which to experiment with new drugs. New species of E. coli
are created every day after being chopped up and reshuffled with genes
from people, pigs, jellyfish, and viruses like HIV. The E. coli is so
prolific at passing on its genes, in fact, that it can do so even after
it is dead.
That’s what keeps Cummins up at night. How are labs making sure that
engineered microbes don’t escape into the environment and pass on their
traits in an uncontrollable way? The question may seem like a
no-brainer, but Canada and the United States have virtually no special
legal or regulatory requirements for the safety of labs that work with
GM bacteria and viruses. The main confinement and disposal rules are
voluntary guidelines. The hundreds of Canadian and U.S. labs that make
GM microbes are on the honour system. Regulators in both countries don’t
even know how many such labs exist or what they are creating. And
neither country requires labs to report any but the most serious GM lab
accidents.
In the foothills of the Rockies, in Denver, Colorado, Suzanne Wuerthele
shares Cummins’s worries. She is not just another run-of-the-mill
biotech skeptic. Wuerthele has been a risk- assessment expert at the
U.S. Environmental Protection Agency for 20 years and is its regional
toxicologist for six western states.
“There has been a lot of hype about GM plants and salmon, but
microorganisms have much more potential to do things we would not be
happy with and to do it without us even knowing about it,” she says.
Wuerthele had a front-row seat for one near-catastrophe: the case of the
rogue Klebsiella planticola. It all started just over the Rockies from
Wuerthele’s office, in Oregon’s lush Willamette Valley. There, in Oregon
State University’s botany department, professor Elaine Ingham stepped
into her lab one day in 1992, not imagining that she would stumble on a
potential biotech Chernobyl.
Her grad student was in a panic. The Mason jars in which they were
growing wheat were filled with brown mush. Ingham had gotten an EPA
grant to test a genetically engineered strain of Klebsiella, a common
soil bacterium. A European company was planning to commercially market
the modified bacterium, K. planticola, which was being touted as a
miracle product for farmers—engineered to decompose plant stubble and
debris left over on fields after harvest time. The process would create
valuable byproducts: fertilizer sludge and alcohol.
But when Ingham, a soil microbiologist, saw her jars, the flaw in this
intrepid plan became clear. All 15 wheat plants growing in soil with the
engineered K. planticola were dead, while the plants growing with
natural K. planticola were just fine. Ingham repeated the experiment
four times in different soils, with the same results: the GM Klebsiella
killed the plants. If the nasty bacteria got out in the wild, she
surmised, it would probably spread uncontrollably, wiping out crops,
forests, and ecosystems in its path and unleashing an environmental
disaster.
“That would have been the end of terrestrial plants,” she says in a
phone interview from Corvallis, Oregon, where she now runs an
organic-consulting business. “It would have dispersed any time a bird
moved it to another field.”
Alarmed, Ingham contacted the EPA. She was told the agency had already
determined the product was safe and was close to approving it for
experimental field trials in the open air. “You’ve got to stop that,”
Ingham replied.
The EPA shelved the monster germ. And then the episode was promptly
forgotten. The reaction to Ingham’s finding was also curious. Scientific
journals refused to publish the results; it took seven years to find one
that would. In the meantime, Ingham and her grad student came under
attack from biotech supporters and both ended up quitting the
university. Today, many scientists have never heard of the near miss.
Wuerthele still finds the episode troubling and says it illustrates the
government’s sometimes hands-off approach to overseeing genetic
engineering. “We don’t really know what would have happened,” she says.
“This microorganism interfered with plant growth. It could have caused
serious agronomic problems and it could have spread, but we don’t know
how far.”
Wuerthele found herself at the centre of yet another GM flap in the
mid-1990s. Becker Underwood, an Iowa-based agrifood giant, wanted the
EPA’s approval for a genetically modified strain of a soil bacterium
called Rhizobium meliloti. An EPA colleague asked Wuerthele to look at
the agency’s risk assessment. The product was to be the first GM microbe
okayed for commercial sale in North America. Rhizobium is a naturally
occurring soil bacterium that lives on the roots of legumes; it had been
engineered to allow farmers to increase alfalfa yields.
The problem for Wuerthele was that the bacteria were also engineered to
contain marker genes that conferred resistance to two antibiotics used
against tuberculosis, tularemia, and the plague. (Scientists often
insert drug-resistant marker genes into GM microbes and crops so they
can later tell if a particular organism is genetically modified or not.)
The drug resistance could pass on to other organisms in the environment,
Wuerthele thought. Would it spawn a superbug, an antibiotic-resistant
pathogen dangerous to humans?
Wuerthele was flabbergasted when she saw the risk assessment. “It was a
joke, three or four pages, and it didn’t ask any questions,” she says.
“I got kind of wound up, asking a lot of questions about this.”
Wuerthele discovered that 2,000 species of legumes growing in North
America also have Rhizobium on their roots. No one had studied how the
product might affect them. Would they become invasive superweeds? To
make matters worse, it wasn’t even clear that the bacteria really helped
alfalfa grow better.
In Washington, EPA officials, under enormous pressure to okay biotech
products, dithered for years about what to do. Finally, the product was
referred to an outside advisory panel. Only one of the six scientists on
the panel gave it the thumbs up. When it became clear the EPA would move
to approve the bacteria anyway, one member, Conrad Istock, resigned in
protest. “It’s just good practice not to leave antibiotic resistance in
organisms that you are going to release,” Istock, now a visiting fellow
at Cornell University, says in a phone interview from his home in
Ithaca, New York. “According to risk-benefit analysis, if it has no
benefit why take the risk?”
The EPA approved the Rhizobium for sale in 1997. The agency never
followed up to study the impact of the antibiotic-resistant bacteria,
Wuerthele says, or even to see if it actually helped farmers grow more
alfalfa.
In Canada, Joe Cummins was one of the few scientists in the world to
take an interest in the Klebsiella and Rhizobium cases. He had been
warning about biotechnology for years, but this was worse than anything
he had imagined. “Potentially, it was a doomsday scenario,” he says of
the K. planticola close call. “The regulators in the U.S. and Canada are
very harebrained and not attuned to the consequences of their actions.”
The lack of government oversight, Cummins says, has allowed GM
drug-resistant microbes to escape from labs for many years. And that, he
believes, may be a big reason for the rise of drug-resistant diseases
around the world in the past 30 years.
It is a controversial claim that runs counter to orthodox scientific
opinion, which holds that the main culprit is the overuse of antibiotics
in hospitals and cattle feed. But Cummins says antibiotics have been
widespread since the Second World War, while supergerms started
appearing in huge numbers only in the 1970s—coinciding with the rise of
genetic engineering. Cummins detailed his alternative theory in a 1998
study he coauthored in the journal Microbial Ecology in Health and
Disease. The stakes, the study said, are very grave: the World Health
Organization had predicted that drug-resistant bugs would cause a global
disease pandemic.
“Biotechnology has effectively opened up highways for horizontal gene
transfer and recombination, where previously, there was only restricted
access through narrow, tortuous footpaths,” the study said. “These gene
transfer highways connect species in every Domain and Kingdom with the
microbial populations via the universal mixing vessel, E. coli.”
Cummins’s study said government regulations on GM bugs were “grossly
inadequate”. As an example, it mentioned Novo Nordisk, a Danish biotech
giant that has admitted to routinely discharging genetically modified
microbes into the water and air along with other effluent. (On its Web
site, the company says it discharged 10,000 GM microbes per millilitre
of waste water and 100,000 GM microbes per cubic metre of air emissions.
It says the discharges were safe and okayed by Danish authorities, but
it also reports several accidents that released GM microbes into the
sewer system.) The study concluded by calling for an independent public
inquiry into how biotechnology has contributed to supergerms.
Cummins’s concerns are dismissed by many scientists. Although some
acknowledge he may be right about GM bugs contributing to antibiotic
resistance, they suggest it is a hypothetical question that isn’t a
priority for action. “I think it is a theoretical possibility and we
need to be vigilant about it, but that’s as far as it goes,” Robert
Burnham, medical director at the British Columbia Centre for Disease
Control, says in a phone interview from his Vancouver office.
At UBC, professor Julian Davies has no doubt that the main culprit in
the rise of virulent new diseases is overuse of antibiotics. “I’m more
worried about natural microbes than genetically modified ones,” he says.
But he agrees that genetic engineering may have been a factor: “You can
never say it hasn’t been.”
But other scientists are concerned. Charles Greer, a scientist at the
National Research Council of Canada, got an Environment Canada grant to
study whether or not GM microorganisms could pass their traits to
natural germs. He thinks releasing microbes with antibiotic resistance
into the environment is a bad idea. “Things like antibiotic-resistance
genes, which can be transferred into other organisms, are clearly the
types of genes you do not want to introduce into the wild,” he says over
the phone from his office in Montreal.
As for GM microbes escaping from labs, Davies says he isn’t too worried.
UBC’s microbiology department, where he works, is allowed to police
itself. He has never seen a provincial or federal inspection of the
department’s labs, he says, and the university doesn’t inspect either.
If anything, Davies believes the system is too cautious. “Most people in
the department are pretty vigilant,” he adds.
Canada’s top cop for GM labs is Paul Payette. He is director of the
Public Health Agency of Canada’s office of laboratory security, where he
oversees 3,000 labs—mostly pharmaceutical and other commercial
facilities—that import all manner of microbes. Four employees are
available to do on-site inspections of all the labs. Payette has no
breakdown of how many of the labs are working with biotech organisms
versus natural ones.
Maureen Best, a senior biosafety consultant at Payette’s office,
confesses that spot checks “do not happen very often” and the safety
office doesn’t keep tabs on lab accidents. “Unfortunately, there is no
national or international reporting mechanism,” she says.
The federal auditor general’s office has expressed concerns about the
lax standards. In a 1998 report, it criticized Canadian biosafety rules
as being weaker than those in the U.S. and called on the lab-security
office to do a review of every lab in the country to verify if the
safety guidelines were being respected. (Payette said he wasn’t sure if
the review was done; later, he wrote in an e-mail that the review had
not been conducted.)
Meanwhile, university lab technicians across the country are full of
horror stories about the facilities where they work: injuries, fires,
explosions, old and faulty equipment, widely varying safety standards.
“There are human errors all the time,” says Hélène Laliberté, a union
official at the University of Montreal who represents 200 lab
technicians, on the phone from her office. “Safety regulations are not a
big priority.”
Maryann DeFrancis, a union health-and-safety rep for technicians at the
University of Toronto, says: “It’s our members’ lives at stake. There
should be a more rigorous approach.” And Kevin Whittaker, a
health-and-safety union rep at McGill University, says from his office:
“Guidelines are fine. The problem is they are not always adhered to.
There is nothing to enforce them. It’s very lax.”
At UBC, lab technicians are not organized into a union. The university
responded to a freedom-of-information request for records on lab-safety
policy, inspections, and accidents by demanding a $2,012 processing fee.
Simon Fraser University responded to a freedom-of-information request
with a letter saying it knows of no accidents at its GM labs in the past
two years. It also sent its latest annual biosafety report, which says
containment equipment in the labs is certified annually. The labs
dispose of microorganisms by heating them at high temperature in a
machine called an autoclave, then tossing them in the garbage or having
them sent to a landfill site. The university has no record of
inspections of the autoclaves, and a table for results of such
inspections is left blank in the report.
At the EPA in Denver, Suzanne Wuerthele says lab safety is a big worry
for her. “There are no [government] inspections to my knowledge of the
facilities that do this, and we don’t even know who they are,” she says
from her office.
Wuerthele is especially concerned about how GM microbes are disposed of
by labs. It is typical, she says, for labs to flush them down the drain
or toss them in the trash after they are autoclaved or sterilized. The
goal is, typically, to kill 99.9999 percent of the microbes, but
Wuerthele says it is normal to have survivors because of the huge
numbers of germs created. “If you make 50 tonnes of something, you may
still wind up with a fairly large number of organisms still alive,” she
says.
Despite the revolution in biotechnology of the 1990s, the last public
debate about the safety of GM research took place more than 30 years
ago. The setting was the rustic Asilomar Conference Center at the tip of
California’s scenic Monterey Peninsula, where 140 biologists and
regulators gathered in February 1975 amid grazing deer and barking seals
to debate the safety of the fledgling technology of genetic engineering.
Known ever since as “Asilomar”, the conference was provoked by worries
that Frankenstein-type genetic monsters would wreak havoc if they got
into nature. The participants formulated strict guidelines that were
adopted in 1976 by the National Institutes of Health, requiring tight
physical confinement of many biotech experiments and forbidding genetic
research with cancer viruses.
But Asilomar was barely over before the scientific community, eyeing the
lucrative new technology, started lobbying the NIH to loosen its
guidelines, saying they went too far. In the early 1980s, the NIH agreed
to gut its rules, allowing genetic engineering to be done under loose
voluntary safety guidelines and dropping the ban on research on cancer
viruses. Canada adopted similar voluntary guidelines.
Although biotechnology was still in its infancy back then, the rules
remain essentially unchanged today, even though a series of lab
accidents has dramatically highlighted the dangers. Perhaps the worst
case was in 1977, when lab contamination in Russia is believed to have
led to the reemergence of the Spanish influenza virus, which had killed
20 to 50 million people in 1918 and 1919. Two years later, an accidental
release of anthrax at a Soviet military lab in the Ural Mountains killed
64 people. In 2003, SARS escaped top-security labs in Singapore, Taiwan,
and China, prompting a World Health Organization probe that found few
countries have adequate biosafety practices.
And since 9/11, concerns about biosafety have heightened, thanks,
ironically, to $7.5 billion in new U.S. and Canadian funding for
research into defences against biological terrorism. Biowar experts say
even the high-security labs doing much of this research, a lot of it
involving genetic engineering, have sloppy practices, and the chances of
an accident have shot up with all the new research.
“The controls are pretty lax,” says Susan Wright, a leading bioterror
expert at Princeton University who is writing a history of biowar. “The
regulations are not very enforced. I just don’t see them regulating with
any regularity.”
Last October, the Sunshine Project, an Austin, Texas–based biowar
watchdog group, released a troubling survey of 400 GM labs at
universities, private companies, and government institutions that got
U.S. grants for research on bioterror. It found only four percent fully
complied with safety guidelines. “Disregard for federal recommendations
is rampant,” the group reported.
In a follow-up study last February, the Sunshine Project found that only
three percent of scientists studying biowar germs had ever gotten a
grant to work with such bugs before. “Too many scientists with too
little training are handling agents that are too dangerous for their
experience,” the study noted.
In Winnipeg, Canada’s top-security virology lab shows the kind of
problems even the safest facilities can have. Three weeks after it
opened in 1999, the $172-million federal complex, one of only 15
Biosafety Level 4 labs in the world equipped to handle the deadliest
microbes known, accidentally spilled 2,000 litres of unsterilized waste
water into the Winnipeg sewer system. In a bizarre reminder of Soviet
efforts to cover up the Chernobyl disaster, the lab didn’t disclose the
accident publicly for two weeks, prompting angry Winnipeggers to hold a
meeting to demand independent oversight of the sprawling complex, which
is located in a mixed residential-industrial neighbourhood in the city
centre.
The outside oversight never happened, but an audit declared the lab was
safe. “We made the appropriate changes to make sure that could never
happen again,” spokeswoman Kelly Keith says on the phone from the lab.
“We are really one of the top labs in the world—if not the top lab—in
terms of containment.”
But just months later, in January 2000, another spill released 100
litres of lab waste inside the facility. And in 2003, the lab sparked
international concern after word emerged of a possible SARS
contamination accident there. (Keith says that to this day the lab
doesn’t know if it experienced a containment failure at the time or
not.) The lab was again in the news last March when a courier truck
crashed in central Winnipeg on the way to the facility while
transporting anthrax, influenza, and tuberculosis. Several blocks were
cordoned off before authorities announced nothing had spilled.
It all makes Cummins wonder. If a Level 4 lab can have so many
screw-ups, what kind of surprises lurk in less secure places? “We have
grown very careless,” he notes. “It is as if workers and the public are
really insignificant.”
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