Research on prions, the safety of French laboratories questioned
Article by La Croix, published by Pierre Sautreuil on December 6, 2021
A second person who worked in a high security prion laboratory died in November of Creutzfeldt-Jakob disease. Security breaches have resulted in a moratorium on research into these pathogenic proteins for the duration of an inspection mission.
When the first symptoms appeared in March, Alain C. initially believed that his wife Pierrette was very tired. Perhaps it was the move to their home in the suburbs of Toulouse that had exhausted this young retiree from a research laboratory at the Toulouse National Veterinary School (ENVT).
The tests ordered by the family doctor did not indicate anything abnormal. “A depression, maybe. But fatigue is soon compounded by inconsistent behavior. At the beginning of April, Pierrette, 67, sets the table for six people instead of two. A few days later, Alain hears him say that his parents are due for lunch. However, they have been dead for twenty years. Could it be Alzheimer's?
New examinations are carried out. The scanner remains silent, but disturbing spots appear on the MRI. Creutzfeldt-Jakob disease is mentioned. Additional tests at the Purpan Hospital in Toulouse will soon confirm the diagnosis. Alain dares not believe it, but Pierrette knows very well that there is no cure for this degeneration of the nervous system: "You will bring me flowers," she told him. I'm screwed. His condition continued to worsen, until his death on November 4.
Made public in July, Pierrette C.'s disease caused great concern in the research community, and for good reason: she is the second employee of a French laboratory to lose her life after working on prions, proteins. pathogens, some of which cause Creutzfeldt-Jakob disease. A sufficiently serious situation to convince the five research establishments concerned (1) to suspend their work.
Research in this area is indeed likely to advance the understanding of neurodegenerative diseases such as Alzheimer's and Parkinson's, which share common mechanisms with prion diseases. Initially scheduled until the end of October, this moratorium has been extended until the end of the year, while a public inspection mission reassesses the safety of these laboratories. How many more people who have worked with prions are at risk of contracting the disease?
Cuts and stings
Before Pierrette C., Émilie Jaumain, an assistant engineer at the National Research Institute for Agriculture, Food and the Environment (Inrae), who cut herself in 2010 while handling infectious prions, had already lost life in June 2019, at the age of 33. Her family immediately filed a complaint against Inrae. At the same time, his death prompted a first inspection mission to the nine prion laboratories in France.
Published in September 2020, its report concluded that there was satisfactory compliance with safety protocols in these P3-classified laboratories (see below), while noting the disparities from one team to another, and a regulatory framework worthy of being improved. Given the incubation period (sometimes decades) and the incurable nature of prion diseases, the mission recommended setting up monitoring for people exposed during their careers. After an in-depth census, inspectors estimated that five officers had cut or pricked themselves with contaminated tools over the past 20 years.
Except that Pierrette C. was not among these identified accidents. Inrae - the supervisory establishment of the ENVT laboratory - initially indicated that it had no trace of an accident involving it. Information obtained by La Croix shows, however, that Pierrette C. had indeed declared not one, but two work accidents likely to lead to contamination, but which were not followed up, in 2004 and 2005. "We found on the Environmental and Safety register of the ENVT the declaration of two cuts concerning our colleague", recognizes Pierre Sans, director of the ENVT, in an internal email that we were able to consult.
An a posteriori rediscovery that questions the ability of the establishment to set up rigorous monitoring of accidents. And how can we explain the lack of changes in practices after the cuts by Pierrette C.? This question prompted Me Julien Bensimhon, lawyer for the Jaumain family, to ask the Paris prosecutor's office to investigate this second death. In mourning, Pierrette C.'s husband has not yet turned to justice.
Two cases in France, one in Italy
Remains, notes Pierre Sans, to establish the "potential link between these cuts and contamination", by identifying the prion strains that Pierrette C. manipulated. Analyzes indicate that Pierrette C. suffered from the variant of Creutzfeldt-Jakob disease ( vCJD), which is most often caused by eating beef contaminated with bovine spongiform encephalopathy (BSE). The famous "mad cow disease."
Distinct by its symptoms of Creutzfeldt-Jakob disease, this variant is extremely rare: only 28 cases in France since 1996. However, according to the neurologist Jean-Philippe Brandel, head of the National Cell of Creutzfeldt-Jakob diseases, the last three cases of vCJD in the world would be Pierrette C., Émilie Jaumain, and an Italian researcher who died in 2016. Common point: all three worked on prions.
Since the news of Pierrette C.'s illness, at least one other person with an accident has come forward. This is a retired technician from the same research unit as Émilie Jaumain, who, in 2005, also cut her left thumb with "a prickly tool that was used to manipulate the brains of mice infected with prions. human, ”reports the CGT in a press release. The union deplores that Inrae has never contacted her again to inquire about her state of health.
What do researchers and agents currently working on prions think? Hard to say. Research on these pathogenic proteins is a tight-knit microcosm of only a hundred people in France. Several trade unionists have expressed their difficulties in collecting testimonies internally. If a school director contacted recognizes "questions" among the staff, two researchers contacted by La Croix, who prefer to remain anonymous, confirm that these deaths have heightened some concern among several of their colleagues who, like them, are studying or have studied prions.
"It is of course difficult to avoid any contaminating gesture, we remain human, anyone can make mistakes," admits one of them. "In the lab as elsewhere, zero risk does not exist, and accidents are not always declared. So these contaminating gestures are necessarily underestimated. »Does he have fears for his health himself? “Yes and no… When I decided to work on prions, I knew there was a risk involved. I also know that when I take my car, I might not reach my destination. This is my philosophy of life. But when asked if he's ever cut or pricked himself, his answer only comes after a moment, evasive: "I'd rather not flaunt that.”
Discovered only forty years ago, prions are still in the dark. Thus the risk of contagion by aerosol, highlighted in 2011 by a scientific article edited by Professor Adriano Aguzzi. An argument for the proponents of stricter regulations, which is not without causing some controversy. If he finds this study "solid and interesting", Doctor Jean-Philippe Brandel points out that there is only one article on this subject, and that its conditions are not those of a laboratory. A quarrel that illustrates the need for further research into the routes of contamination, as noted in the 2020 inspection report.
Precariousness
In addition to researchers, there are also technicians in the laboratory, who do not necessarily have the same self-sacrifice, nor the same theoretical and practical training. This was the case for Pierrette C. and Émilie Jaumain. "Émilie was very young, she was on a fixed-term contract, she had no experience, and we put her directly in a P3 prions lab," says Armel Houel, her husband, himself a former agent at Inrae. “A technician follows the orders his managers give him. He had been instructed to collect organs from mice infected with human prion with sharp steel tweezers from a cold block. Her hands were numb. She did not have cut resistant gloves.”
According to the lawyer for the Jaumain family, only one other technician was present in the laboratory when Émilie pricked herself with these tweezers, none of them was trained in what to do in the event of a accident, and the laboratory did not contain the necessary equipment to disinfect his wound. The issue of training is all the more important as the use of short contracts is becoming more frequent in research. "Today, the labs run with precarious people, we change them all the time, we don't keep people trained," laments a trade unionist. I've seen labs where one incumbent supervises eight precarious, that multiplies the risk of accidents."
Several laboratories have stepped up their safety once the disease became known to Emilie Jaumain. A source at INRAE lists the changes that occurred in the months that followed: replacement of metal tweezers with plastic tweezers, purchase of cut-resistant gloves, review of decontamination protocols, adoption of a what to do in the event of an accident, installing a bleach container provided for this purpose, etc. Without abandoning other questionable practices, such as letting doctoral students work alone, without supervision, on weekends, in a P3 laboratory.
A "best practice guide" aimed at harmonizing safety standards is to be presented on Tuesday, December 7, to the Health, Safety and Working Conditions Committee (CHSCT) at the Ministry of Higher Education and Research. A first step before the publication of the public inspection report, and perhaps a lifting of the moratorium. Not sure as far as this is enough to rebuild confidence. Joined by La Croix, the secretary of the CHSCT, Lorena Klein, has already indicated that she will ask for her extension.
High security research laboratories
P1 and P2, "class 1 pathogen" and "class 2 pathogen" laboratories
The laboratories are classified according to the degrees of dangerousness of the pathogens, from 1 to 4. Group 1 studies those which are "not liable to cause disease in humans" and the 2 those moderately dangerous for which "there is a prophylaxis or effective treatment.”
The P3. These units work on pathogens which can "cause serious disease in humans" and "present a risk of spread in the community", but for which there is generally a prophylaxis (preventive health measures considered effective) or a recognized treatment. Besides the prion, this includes research on tuberculosis, HIV, H1N1 (swine flu), Sars-CoV-2, etc.
The P4. There are around sixty of them in the world (three in France, two of which are military). These labs study pathogens that cause "serious disease in humans", are "at high risk of spreading into the community" and go untreated. Ebola-type hemorrhagic fevers, smallpox and Nipah-type infections are studied.
