Researcher Highlights
Snakes alive

Clinical researcher Dr Geoff Isbister courts controversy as he challenges time-honoured beliefs about the treatments given to envenomed patients.

Dr Geoff Isbister doesn't take himself too seriously. The good-humoured researcher admits he originally chose a career in medicine because he thought it could fund his musical interests. Laughing about a 'joke' piece he published in The Lancet, Geoff also recounts a time when he became the terror of Australia Post after receiving hundreds of dead spiders in the mail.

Such easy conversation and quick wit belie the fact this ambitious academic is deadly serious about studying deadly poisons.

"I'm an investigator and a busy clinician," he says.

"My mission is simple – I want to better understand the pathophysiology of envenomation in patients."

"I also want to generate evidence regarding the efficacy of both conventional and new treatments."

Despite the controversy surrounding his work, the National Health and Medical Research Council Senior Research Fellow has affected major changes in the way spider and snakebites are managed in Australia. Using science as a weapon, Geoff is cutting a swathe through long held beliefs, myths and unquestioned conventions, leaving disbelief, derision and ultimately, more efficient practice, in his wake.

The spark that drives

Having always possessed a veracious appetite for knowledge, Geoff initially combined a degree in science and medicine so he could better understand the chemical and biological machinations behind clinical practice. Coming to the end of his undergraduate study, the unconventional researcher worked with a local GP in country NSW, where snakebites and their treatment immediately captured his interest.

"I found them fascinating," he recalls.

After completing a stint as an emergency physician in Darwin and Sydney, Geoff returned to Newcastle in 2000 to work in toxicology.

"The thing about medical specialties is that you deal with one part of the body and nothing else," he explains.

"But drugs, bites and stings affect every part of the body, and that's what I was interested in."

"Newcastle has the best known toxicology unit in the world."

The Great Australian bite

With the urban setting of Sydney's Royal Prince Alfred Hospital seriously limiting his opportunities to investigate snakebites, Geoff turned to documenting spider bites for his doctoral thesis. Recruiting 750 participants, this was his first multicentre study of toxinology treatments.

"I debunked the myth that whitetail spider bites cause ulceration and necrosis," Geoff divulges.

"My work also informed the development of definitive and simplified treatment protocol for all Australian spider bites in clinical practice."

Intrigued by the information gleaned during his spider bite research, Geoff took to reviewing the clinical delivery of redback spider anti-venom. Initially undertaking a study comparing intramuscular to intravenous delivery of existing antivenom to redback bite victims, he was surprised to discover no difference in recovery time or self-reported pain between delivery options. A placebo randomised control study followed, which replicated the findings.

"The evidence was quite startling," he says.

"It was published in the Redback Spider Antivenom Evaluation (RAVE II) Study and has changed clinical practice related to the administration of redback antivenom."

Shedding old skin

Geoff is a main driver behind the Australian Snakebite Project (ASP), a multicentre project collecting data on presumed and definite snakebite victims in more than 150 hospitals across the country. Like the spider study before it, collating a mass of clinical information on snakebite cases has created a complete picture of the symptoms of envenomation. It's also provided evidence to change practice around the administration of escalating dosages of antivenom.

"We showed continual delivery of antivenom over the course of snakebite treatments is redundant," he claims.

Working with his colleagues from the Clinical Toxicology Research Group at the Mater, Geoff is undertaking studies of snake envenomation in Sri Lanka. There, it is possible to recruit thousands of cases per year.

He's also working with a PhD student to convert what is currently an expensive, lab-based process into an affordable bedside diagnostic kit that identifies enzymes found in snake venom.

"The most common bedside test is a clotting test," Geoff explains.

"That's fine if the snake causes clotting problems, but there's no way to know if the patient is going to develop paralysis, say from a krait bite."

"The only way you know they've got neurotoxicity is when they've got it, and then it's too late."

"So rather than giving antivenom to everyone who comes in, this method allows us to test for this enzyme in the patient's blood and give the antivenom within an hour or two to prevent paralysis occurring."

Keeping them safe

As well as being a prolific researcher, Geoff is also a working clinician, overseeing the treatment of 800 - 1000 patients with two other clinical toxicologists, who are admitted to the Mater for pharmaceutical overdose treatment each year.

Geoff is also one of a handful of toxicologists working for the NSW Poisons Centre. When rostered on, he can field up to 10 calls a night from physicians needing advice for the treatment of patients in other hospitals.

"My research into pharmaceutical overdose is less about treatment and more about risk assessment and understanding how drug overdoses affect the body," Geoff notes.

"The team at the Mater has changed clinical practice through the creation of the QT nomogram, which is a way to assess risks related to abnormal electrical changes in the heart caused by dosages of particular drugs."

A greater understanding of risks related to the QT interval (interval seen in an electrocardiogram test of the heart function) has similarly informed a study into the sedation of violent or aggressive patients presenting at the Mater's Emergency Department. Initially run at the Mater, the DORM study has since been extended to one thousand patients across six emergency hospitals.

"The protocols and treatments identified in the trial have been adopted by hospitals nationwide," Geoff advises.

"These decrease the risk of violence to staff and other patients."

Snakes in the grass

Geoff isn't concerned about his detractors. He blames misunderstandings and blind belief in untested anecdotal evidence for the negative sentiment created by his findings on the effectiveness of antivenom.

"Most people would strongly believe that antivenom is a magic bullet," he says.

"Even when there are no trials or evidence to support it, they believe it works."

The risk of severe allergic reaction, and exorbitant costs are two factors Geoff cites as motivators for further assessment of the effectiveness of antivenoms.

"There is no question about whether antivenoms are efficacious," he declares.

"But we need to understand, on an antivenom by antivenom basis, a creature by creature basis, if they actually change the course of the envenomation, how much we need to administer, and when."

Laughing as he sums up his life's work, the head of the University of Newcastle's Clinical Toxicology Research Group notes the hypotheses he develops at the beginning of studies are most often proven wrong – even though he is staunchly defensive of his previous research.

"The moment I am not able to accept that I'm wrong is the moment I will pack up and stop doing research," he promises.

"There's been very few studies where I have gotten the results I want and that's what makes it interesting."

"I also like that my work is controversial, because that's what makes it fun."