In 2000, Steve booked an appointment with Dr Simon Mallal, a clinical immunologist. Steve was diagnosed with HIV, and Dr Mallal was an expert in HIV clinical care and research.

Dr Mallal recommended his treatment include one of the leading drugs for inhibiting HIV, Abacavir, but warned him that about 1 in 20 patients who take the drug will experience a life-threatening reaction within the first few weeks.  Steve famously asked, “Well, you are a clever bloke, Simon. Can’t you come up with a test to tell if I would be one of the unlucky ones?”. 

Little did Steve know that his question would result in the first personalised genetic medicine test to be introduced into primary care globally and a translational roadmap for other tests to follow.   

Humble beginnings 

Dr Mallal established the first local area network (LAN) in WA to connect Royal Perth Hospital and Sir Charles Gairdner Hospital. Through this system, he created the WA HIV Cohort Study to support clinical management and population-level research.  

A key focus of this early research was to understand the ways HIV became rapidly resistant to drugs and to trial different combinations to improve patient survival.   

Early triple therapy cocktails achieved this but caused stigmatising side effects such as loss of fat on the face and elsewhere.  WA studies showed this could be prevented by avoiding two drugs that damaged the mitochondria and killed fat cells.  

Another fortuitous question that arose in the clinic while seeing another patient, Stephen, resulted in a momentous discovery and chain of events.  HIV was routinely sequenced to identify the emergence of drug resistance.  

Dr Mallal noticed that all patients with a particular genetic type, HLA-B51, would have a mutation at one specific position in the virus.  

Stephen was an exception because he had been treated immediately after exposure before his immune response could cause the mutation.  

This set in train a study published in Science that showed all the positions mutated by all the HLA types could be identified if enough patients were studied.   

Microsoft researchers read this study and asked Dr Mallal to present this work in a small conference room at their headquarters in Seattle.  He titled his talk ‘Using the most powerful tools to address the most important problems of our time.’ Unexpectedly, Bill Gates later watched a video of the talk on their servers, which resulted in a $12.6M Gates Foundation Grant and collaborative machine-learning studies with Microsoft on how viruses and man have co-evolved.   

In 2000, Emeritus Professor Steven Schwartz AM (then Vice Chancellor of Murdoch University), invited Dr Mallal to establish the Centre for Clinical Immunology and Biomedical Statistics (CCIBS).  

Based out of a demountable in a car park at Royal Perth Hospital, the team worked tirelessly to understand the relationships between the immune system, genetics, drug sensitivities and more.  

A few years later, alongside Murdoch University Professor Ian James, Dr Mallal established iiid. 

After proposing to build a research precinct for the Institute, the Commonwealth provided $21.5m in capital and Dr Mallal worked with the University on fundraising from generous WA donors and the Lotteries Commission toward the Institute’s $64M cost. 

In 2009, the 5,500m2, four level research building, with laboratories, chemical and cell culture rooms, consulting suites and a PC3 lab, was completed. 

The people, equipment and organisational structures were moved from Royal Perth Hospital to the building on Murdoch University’s campus.  

Dr Mallal said colleagues described the building as “akin to an alien spacecraft arriving on campus”.  

Throughout the formative years of the institute, Dr Mallal and the iiid research team made more groundbreaking discoveries and advancements.    

In 2005, Dr Mallal was awarded the WA Premier’s Prize for Achievement in Science and in 2017 Vanderbilt University awarded him the William J. Darby Award for Translational Research that Changed the Practice of Medicine with Dr Elizabeth Phillips. 

This work led to significant advancements in international HIV treatment guidelines and understanding of drug toxicity.       

During this time, Dr Mallal also worked as a consultant clinical immunologist at Royal Perth Hospital, where he managed the care of HIV patients. 

A breakthrough 30 years in the making  

In 2023, Dr Mallal was part of an international team that discovered another critical genetic variant after nearly 30 years of HIV research. 

The study sought to understand the genetics of people living with HIV who are of African ancestries – due to this population being disproportionately affected by the disease. 

Researchers assessed the genetics of close to 4,000 people living with HIV who are of African ancestries around the world and found genetic variants that impact a human gene called CHD1L, which restricts HIV replication. 

This means the virus is unable to replicate as quickly in people who carry specific genetic variants compared to others who do not. 

Dr Mallal was the only Australian contributing author to the Nature study, led by scientists from the Public Health Agency of Canada’s National Microbiology Laboratory, École Polytechnique Fédérale de Lausanne in Switzerland and Imperial College London. 

 “These findings may explain why certain people in these populations have a lower viral load, which slows down the virus from replicating and transmitting,” Dr Mallal said 

Although Australia has recorded a steady decline in rates of HIV over the past decade, this research will be significant on a global scale, assisting the UNAIDS goal of ending AIDS as a global health threat by 2030. 

This discovery was crucial for helping scientists target their medical intervention efforts for HIV and paving a path to new prevention and treatment strategies.  

Dr Mallal’s research continues to drive innovation at Murdoch University and Vanderbilt University, where he is a Professor of Medicine, Pathology, Microbiology, Immunology and Biomedical Informatics and holds the Major E.B. Stahlman Chair in Infectious Diseases and Inflammation.