From Analogue to AI: A Half-Century of Electron Microscopy Innovation at VIDRL
The Victorian Infectious Diseases Reference Laboratory (VIDRL) is celebrating 50 years of electron microscopy (EM), a milestone that marks half a century of groundbreaking scientific discoveries. This technology has been instrumental in detecting and characterizing novel and emerging pathogens, bolstering Australia's public health preparedness.
Electron microscopes magnify images using electron beams, allowing scientists to visualize viruses, bacteria, and the intricate inner workings of cells with extraordinary detail, far surpassing what standard microscopes can reveal. In medicine, these microscopes provide a powerful tool for understanding how diseases alter the body at its smallest scale.
The Electron Microscopy and Structural Virology (EMSV) Laboratory was established in 1975 at the Fairfield Infectious Diseases Hospital in Melbourne's northern suburbs. It was the first facility to produce in-house diagnostic electron micrographs. Over the past five decades, EM has played a pivotal role in detecting and characterizing infectious agents, particularly during global pandemics such as those associated with HIV (AIDS), SARS-CoV-2 (COVID-19), and MPV (Mpox).
The laboratory became part of VIDRL when the Pathology and Virology services at Fairfield Hospital merged in 1992. It relocated to a purpose-built facility on Wreckyn Street in North Melbourne in 1998, joining the Royal Melbourne Hospital campus network, before moving to its current home at the Doherty Institute when it opened in 2014.
Associate Professor Jason Roberts has led the EMSV laboratory at VIDRL since 2019. In a special report celebrating the 50th anniversary of the laboratory, he describes the evolution of the technology and its enduring contribution to public health in Victoria, Australia, and internationally.
"For five decades, this capability has allowed us to assist in the identification and characterization of pathogens when the cause of disease was unknown. Electron microscopy gives us something few other tools can: an open view of what's really there," said Associate Professor Roberts.
The 1970s were a decade of major virology discoveries, partly driven by advances in EM. In its early years, the laboratory gained international recognition for its work characterizing the strain of Hepatitis A virus that became the basis for Havrix, the first effective hepatitis A vaccine, using its film-based electron microscope.
Throughout the late 1970s and 1980s, EM underpinned major discoveries and outbreak responses, with the ability to directly visualize pathogens proving invaluable when serology or early molecular tests were unavailable or inconclusive.
In the 1980s, the laboratory produced Australia's first ultrastructural images of HIV in culture, supporting early diagnostic confirmation during the emergence of the pandemic. Over the following decades, EM continued to support outbreak investigations, vaccine research, and the study of emerging pathogens.
As public health needs evolved, so did the laboratory. Under the guidance of Dr. John Marshal, who led the laboratory from 1977 until his passing in 2018, the locations changed, from Fairfield Hospital to Wreckyn Street and finally to the Doherty Institute, but the technology also shifted from film-based systems to advanced digital platforms with greater throughput and precision.
Electron microscopy remains a vital part of VIDRL's outbreak response capability. As molecular techniques like PCR became widespread in the late 1990s and early 2000s, EM found a complementary niche: during acute outbreaks involving unknown pathogens, PCR has limitations, as it requires some idea of what to look for; whereas EM, with its 'open view,' could potentially identify and characterize pathogens rapidly after receiving a sample.
In 2020, the EMSV laboratory, in collaboration with the team at the Bio21 Institute's Ian Holmes Imaging Center, captured the first Australian images of SARS-CoV-2, supporting global efforts to understand the virus at the start of the COVID-19 pandemic. Similarly, the laboratory captured the first Australian images of the monkeypox virus in culture, from the first Australian case of pandemic Mpox in 2022.
Innovations such as microwave-assisted sample processing have dramatically reduced turnaround times for sample preparation, while emerging tools like electron tomography and AI-assisted image analysis are expanding the laboratory's analytical power.
"Combined with current advances in genomics and rapidly evolving artificial intelligence tools, electron microscopy stands on the precipice of a revolution in ultrastructural pathology. These advanced approaches allow for rapid confirmation and structural insight, which is critical when dealing with emerging or unexpected threats," said Associate Professor Roberts.
Today, VIDRL's electron microscopy program supports diagnostics, training, and collaborative research. It maintains an archive of over 40,000 images documenting the history of clinical infectious disease in Victoria from a unique perspective.
The Royal Melbourne Hospital's Dr. Katherine Bond, Acting Director at VIDRL, says future priorities include strengthening collaborative networks with national and international partners, developing AI-powered analysis tools for image processing, and continuing to advance rapid detection capabilities for emerging pathogens.
"In the last 50 years, the science has changed dramatically, and electron microscopy has evolved alongside it, supporting major discoveries and public health advances. We are proud to have this cutting-edge capability here at the Doherty Institute," said Dr. Bond.
"Our mission, however, hasn't changed. It's still about protecting public health through precise pathogen detection, responding quickly, and sharing that knowledge."
