<https://www.sciencemag.org/news/2021/07/france-issues-moratorium-prion-research-after-fatal-brain-disease-strikes-two-lab>
*PARIS—*Five public research institutions in France have imposed a
3-month moratorium on the study of prions—a class of misfolding,
infectious proteins that cause fatal brain diseases—after a retired lab
worker who handled prions in the past was diagnosed with
Creutzfeldt-Jakob disease (CJD), the most common prion disease in
humans. An investigation is underway to find out whether the patient,
who worked at a lab run by the National Research Institute for
Agriculture, Food and Environment (INRAE), contracted the disease on the
job.
If so, it would be the second such case in France in the past few years.
In June 2019, an INRAE lab worker named Émilie Jaumain died at age 33,
10 years after pricking her thumb during an experiment with
prion-infected mice. Her family is now suing INRAE for manslaughter and
endangering life; her illness had already led to tightened safety
measures at French prion labs.
The aim of the moratorium, which affects nine labs, is to “study the
possibility of a link with the [new patient’s] former professional
activity and if necessary to adapt the preventative measures in force in
research laboratories,” according to a joint press release
<https://www.inrae.fr/actualites/suspension-provisoire-travaux-prions-laboratoires-recherche-publics-francais>
issued by the five institutions yesterday.
“This is the right way to go in the circumstances,” says Ronald Melki, a
structural biologist at a prion lab jointly operated by the French
national research agency CNRS and the French Alternative Energies and
Atomic Energy Commission (CEA). “It is always wise to ask questions
about the whole working process when something goes wrong.” “The
occurrence of these harsh diseases in two of our scientific colleagues
clearly affects the whole prion community, which is a small ‘familial’
community of less than 1000 people worldwide,” Emmanuel Comoy, deputy
director of CEA’s Unit of Prion Disorders and Related Infectious Agents,
wrote in an email to Science. Although prion research already has strict
safety protocols, “it necessarily reinforces the awareness of the risk
linked to these infectious agents,” he says.
In Jaumain’s case, there is little doubt she was infected on the job,
according to a paper
<https://www.nejm.org/doi/full/10.1056/NEJMc2000687> published in The
New England Journal of Medicine (NEJM) in 2020. She had variant CJD
(vCJD), a form typically caused by eating beef contaminated with bovine
spongiform encephalopathy (BSE), or mad cow disease. But Europe’s BSE
outbreak ended after 2000 and vCJD virtually disappeared; the chance
that someone of Jaumain’s age in France would contract food-borne vCJD
is “negligible or non-existent,” according to the paper.
A scientist with inside knowledge says the new patient, a woman who
worked at INRAE’s Host-Pathogen Interactions and Immunity group in
Toulouse, is still alive. French authorities were apparently alerted to
her diagnosis late last week. The press release suggests it’s not yet
clear whether the new case is vCJD or “classic” CJD, which is not known
to be caused by prions from animals. Classic CJD strikes an estimated
one person per million. Some 80% of cases are sporadic, meaning they
have no known cause, but others are genetic or contracted from infected
human tissues during transplantations. The two types of CJD can only be
distinguished through a postmortem examination of brain tissue.
Lab infections are known to occur with many pathogens, but exposure to
CJD-causing prions is unusually risky because there are no vaccines or
treatments and the condition is universally fatal. And whereas most
infections reveal themselves within days or weeks, CJD’s average
incubation period is about 10 years.
For Jaumain, who worked at INRAE’s Molecular Virology and Immunology
Unit in Jouy-en-Josas, outside Paris, that long period of uncertainty
began on 31 May 2010, when she stabbed her left thumb with a curved
forceps while cleaning a cryostat—a machine that can cut tissues at very
low temperatures—that she used to slice brain sections from transgenic
mice infected with a sheep-adapted form of BSE. She pierced two layers
of latex gloves and drew blood. “Émilie started worrying about the
accident as soon as it had happened, and mentioned it to every doctor
she saw,” says her widower, Armel Houel.
In November 2017, Jaumain developed a burning pain in her right shoulder
and neck that worsened and spread to the right half of her body over the
following 6 months, according to the NEJM paper. In January 2019, she
became depressed and anxious, suffering memory impairment and
hallucinations. “It was a descent into hell,” Houel says. She was
diagnosed with “probable vCJD” in mid-March of that year and died 3
months later. A postmortem confirmed the diagnosis.
The occurrence of these harsh diseases in two of our scientific
colleagues clearly affects the whole prion community.
Emmanuel Comoy, French Alternative Energies and Atomic Energy
Commission
INRAE only recently admitted the likely link between Jaumain’s illness
and the accident. “We recognize, without ambiguity, the hypothesis of a
correlation between Emilie Jaumain-Houel’s accident … and her infection
with vCJD,” INRAE chair and CEO Philippe Mauguin wrote in a 24 June
letter to an association created by friends and colleagues
<http://www.association-emilys.com/> to publicize Jaumain’s case and
lobby for improvements in lab safety. (Science has obtained a copy of
the letter, which has not been made public.)
Jaumain’s family has filed both criminal charges and an administrative
suit against INRAE, alleging a range of problems at Jaumain’s lab. She
had not been trained in handling dangerous prions or responding to
accidents and did not wear both metal mesh and surgical gloves, as she
was supposed to, says Julien Bensimhon, the family’s lawyer. The thumb
should have been soaked in a bleach solution immediately, which did not
happen, Bensimhon adds.
Independent reports by a company specializing in occupational safety and
by government inspectors have found no safety violations at the lab; one
of them said there was a “strong culture” of risk management. (Bensimhon
calls the reports “biased.”)
The government inspectors’ report concluded that Jaumain’s accident was
not unique, however. There had been at least 17 accidents among the 100
or so scientists and technicians in France working with prions in the
previous decade, five of whom stabbed or cut themselves with
contaminated syringes or blades. Another technician at the same lab had
a fingerprick accident with prions in 2005, but has not developed vCJD
symptoms so far, Bensimhon says. “It is shocking that no precautionary
measures were taken then to ensure such an accident never happened
again,” he says.
In Italy, too, the last person to die of vCJD, in 2016, was a lab worker
with exposure to prion-infected brain tissue, according to last year’s
NEJM paper, although an investigation did not find evidence of a lab
accident. That patient and the lab they worked at have not been identified.
After Jaumain’s diagnosis, “We contacted all the research prion labs in
France to suggest they check their safety procedures and remind staff
about the importance of respecting them,” says Stéphane Haïk, a
neuroscientist at the Paris Brain Institute at Pitié-Salpêtrière
Hospital who helped diagnose Jaumain and is the corresponding author on
the paper. Many labs tightened procedures, according to the government
inspectors’ report, for instance by introducing plastic scissors and
scalpels, which are disposable and less sharp, and bite and
cut-resistant gloves. A team of experts from the five research agencies
is due to submit proposals for a guide to good practice in prion
research to the French government at the end of this year.
The scientific community has long recognized that handling prions is
dangerous and an occupational risk for neuropathologists, says
neuropathologist Adriano Aguzzi of the University of Zurich. Aguzzi
declined to comment on the French CJD cases, but told Science his lab
never handles human or bovine prions for research purposes, only for
diagnostics. “We conduct research only on mouse-adapted sheep prions,
which have never been shown to be infectious to humans,” Aguzzi says. In
a 2011 paper <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020930/>,
his team reported that prions can spread through aerosols, at least in
mice, which “may warrant re-thinking on prion biosafety guidelines in
research and diagnostic laboratories,” they wrote. Aguzzi says he was
“totally shocked” by the finding and introduced safety measures to
prevent aerosol spread at his own lab, but the paper drew little
attention elsewhere.
The moratorium will “obviously” cause delays in research, but given the
very long incubation periods in prion diseases, the impact of a 3-month
hiatus will be limited, Comoy says. His research team at CEA also works
on other neurodegenerative diseases, including Alzheimer’s disease and
Parkinson’s disease, and will shift some of its efforts to those.
Although Jaumain’s diagnosis upset many in the field, it hasn’t led to
an exodus among researchers in France, Haïk says: “I know of only one
person who resigned because they were so worried.”
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