COMMENT

Professor Justin Yerbury on animals, humans and the transmission of brain disease

The recent report of the tragic death of a French laboratory technician after a laboratory accident struck a nerve with me. Actually, it struck several. Initially, I could not help but feel drawn to the story because of the parallels to my own story - a fellow scientist contracts the deadly brain disease that she was studying.

The science also caught my attention. The technician was working on Creutzfeldt-Jakob disease which is a fatal brain disorder that can be transmitted. Our own work has shown that proteins that form deposits in the brain in MND can act in a similar manner in the lab.

Taken together with the current pandemic and the mystery of its origin, the story gave me pause to think about my team, our work and more broadly our human species and how the way we interact with animals is increasing the transmission of disease. Please read this opinion piece and consider it food for thought ...

LEADING RESEARCHER: Professor Justin Yerbury received an Order of Australia (AM) for his contribution to MND research and advocacy. Picture: Paul Jones.

LEADING RESEARCHER: Professor Justin Yerbury received an Order of Australia (AM) for his contribution to MND research and advocacy. Picture: Paul Jones.

While the speculation that the coronavirus was made in a laboratory was mere unfounded conspiracy theories, others have pointed out that it is entirely possible that a wild virus could be released into the world through an accidental infection or breach within a laboratory setting.

Researchers in Wuhan who study wild strains of coronavirus have denied claims that a laboratory slip up was the origin of the pandemic that has so far killed more than half a million people. In a cautionary tale, earlier this month a letter to the editor of the New England Journal of Medicine by a group of neurologists and neuroscientists reported that a relatively minor accident has led to the tragic death of a laboratory technician in France.

As tragic as the result of this laboratory accident was, the good news is that there will be no outbreak. The laboratory technician was working on a disease called variant Creutzfeldt-Jakob disease (vCJD), better known as the disease associated with mad cow disease.

Creutzfeld-Jakob disease (CJD) is a very rare neurodegenerative disease that causes a rapidly progressive loss of muscle control and memory, followed invariably by death, usually within a year of diagnosis.

If CJD doesn't sound like your average infectious disease that is because it is far from typical. While most cases of CJD are inherited or spontaneous like other neurodegenerative diseases, such as Alzheimer's disease or motor neurone disease, a small number of CJD cases have been transmitted through invasive procedures such as shared surgical implements, grafts of human brain casing, transplanted human-derived hormone, and even blood transfusion.

As if this transmissible brain disease was not unusual enough, the causative agent is not a living organism, like bacteria or virus, but a single protein, one of the tens of thousands of possible proteins typically made by the human body (and other animals such as cattle, sheep and deer).

This transmissible protein can be folded into two different shapes - an abnormal shape associated with disease and its normal healthy shape. American neurologist and biochemist, Stanley Prusiner, won the Nobel prize for his discovery of this unconventional pathogen. He called the shape-shifting protein a 'prion' and discovered that it reproduced by converting a host's healthy form of prion protein to the abnormal shape.

In the 1980s, there was an outbreak of a prion disease that would come to be known as mad-cow disease (bovine spongiform encephalopathy; BSE) in cattle primarily in the United Kingdom. The outbreak was caused by the practice of using meat and bone meal, from cattle stocks, to supplement calves diet.

Given that the disease seemed to be transmitted through diet, the obvious next question was whether the consumption of BSE-affected beef by the public would result in the transmission of prion disease to humans. The first cases of vCJD, the same version of the illness that the French lab technician acquired, transmitted through contaminated beef were diagnosed in 1995.

The technician was working with mice that had been genetically engineered to carry the human prion protein. A practice common in neurodegeneration research more generally, although the human protein that causes Alzheimer's disease, Parkinson's disease, Huntington's disease and motor neurone disease in mice is different for each disorder.

STARTING OUT: Dr Yerbury working as a medical researcher at UOW in 2010.

STARTING OUT: Dr Yerbury working as a medical researcher at UOW in 2010.

The mice with the human prion protein gene had been infected with sheep prions in a BSE, or mad cow disease form. It might sound like a Frankenstein's monster of an experiment given that is seems to be metaphorically stitched together from four different animals, but since experiments like this can't be performed on humans, scientists need to be creative.

In May 2010, when the French laboratory technician was 24 years of age, too young to had acquired the disease from contaminated beef, she handled frozen sections of brain from the genetically engineered mouse infected with prions.

She accidentally stabbed her thumb with the sharp ends of the curved forceps she used to handle the samples. Bleeding was noted at the puncture site even though she was wearing two pairs of latex gloves. She died nine years later, 19 months after symptom onset. The neuropathological examination confirmed the diagnosis of variant CJD.

This tragedy poses a question about other neurodegenerative disease models and their transmissibility, many of which have now been shown to be transmissible when brain material of diseased mice has been injected into healthy mice.

Current thought though is that prions are particularly unique because they are almost indestructible. It is clear that the more stable an abnormally folded disease-associated protein is, the higher the probability it could be transmitted.

In fact, one of the more stable misshapen proteins called amyloid-beta, which is associated with Alzheimer's was recently found to have transmitted the disease to people through contaminated human brain-derived hormone samples.

While humans continue to use animals for consumption and experimentation, there will be a continued risk of animal to human disease transmission.

It is vital that we have a healthy dose of humility and fear of the biological organisms of Earth and it is clear that occasionally we as a species need to be reminded that as a species we are not at the centre of the web of life but are just one of the plethora of species that share this planet.

A Professorial Fellow in Neurodegenerative Disease at the University of Wollongong and the Illawarra Health and Medical Research Institute, Prof Yerbury is an international leader in Motor Neurone Disease (MND) research.

He continues that research, even while he lives with the disease - leaving him paralysed, unable to speak nor breath independently. He communicates using eye-gazing computer technology.

Once a professional basketballer for the Illawarra Hawks, Prof Yerbury started a science degree at UOW after the death of several family members from MND. He was diagnosed with the disease in 2016.

This story A healthy dose of humility and fear: 'We are not the centre of the earth' first appeared on Illawarra Mercury.