An early warning system: preparing for the next pandemic

The COVID-19 pandemic has starkly exposed the significant shortcomings in the world’s capabilities to rapidly detect and respond to emerging infectious diseases before they can escalate and reap havoc.

Originating from a novel coronavirus that first appeared in Wuhan, China, in December 2019, the disease spread rapidly around the world. By the time the World Health Organization (WHO) declared it a pandemic, COVID-19 had already reached numerous countries, with about 130,000 confirmed cases and nearly 5,000 deaths. [1] Beyond the devastating loss of lives, the pandemic disrupted economies and pushed many public health systems to the brink of collapse. As of July 2023, the global tally stood at over 768 million confirmed cases and more than 6.9 million deaths. [2]

However, COVID-19 is not an isolated event but part of a recurring pattern of pandemics throughout history. Over the centuries, infectious diseases such as cholera, plague, and influenza have previously ravaged human civilizations. And the rise in urbanization, globalization, and ecological factors - such as climate change, deforestation, and increased contact between humans and animals - has further increased the likelihood of future outbreaks, epidemics, and pandemics. Biohacking and bioterrorism scenarios are further increasing the threat.

Nowadays, an emerging infectious disease can spread rapidly across the globe, facilitated by international air travel - underscoring the urgency to establish a global pathogen surveillance and monitoring system. Such a system would enable the early detection of infectious agents with pandemic potential, allowing for the prompt implementation of effective measures to impede the further spread of infection.

But creating a robust early alert system for pandemics presents a multitude of challenges. It is precisely due to these complexities that we selected this work with the potential to help establish a global pandemic early warning system, for our 2023 Future Insight Prize.

Since its establishment in 2019, we’ve been honoring exceptional scientists with the Future Insight Prize, recognizing groundbreaking work with the potential to solve some of the world’s most pressing challenges in health, nutrition, and energy. Alongside this prestigious annual prize, we provide a of up to €1 million to support the advancement of cutting-edge technologies that have the potential to transform visionary concepts into tangible realities.

Pandemic preparedness was announced as the first focus area for the prize during the Curious2018 Future Insight Conference. In July 2019, we awarded the prize to visionary researchers developing “pandemic protectors” –  to safeguard humanity against future global diseases. Later that same year, the devastating COVID-19 pandemic started. In 2023, we now return again to the area of pandemic preparedness, after allocating the 2020 prize to multidrug resistance, in 2021 to technologies to secure the nutrition of a growing world population – and in 2022, to reducing CO2 in the air.

This year’s recipient of the €500,000 Future Insight Prize is Khalid Salaita, Professor of Chemistry at Emory University in Atlanta, Georgia (USA). His groundbreaking work is centered around the creation of a fully automated electronic sensor for the surveillance and tracing of airborne viruses in real-time, which could play a crucial role in the ongoing battle against infectious diseases.

“The dream product, which would resemble something like a smoke detector but would detect pathogens, could be used in locations such as airports, schools, or any crowded areas. Ideally, anyone who was in that area at the time of detection would be promptly notified that they’ve been potentially exposed to a pathogen,” envisions Salaita. “Crucially, it would also generate real-time maps of where new airborne viruses are emerging and where they’re being detected – providing a window of opportunity for swift action to stop them from spreading.”

Salaita’s envisioned solution offers a major advantage as such as system could be integrated with minimal disruption or interference to people’s lives. This is in contrast to more invasive techniques, such as nasal or throat swab testing, which were widely used to monitor for infections during the COVID-19 pandemic.

His ambition is to develop an innovative solution that could address current gaps in testing both for the presence of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, as well as future respiratory viruses with pandemic potential that are spread through the air.

Salaita didn’t set out to develop a viral-detecting sensor, but the story began through an unexpected discovery that came from his curiosity-driven research into nanomotors. His innovative technology revolves around these incredibly minuscule man-made devices capable of converting energy into mechanical motion.

According to Salaita, the fundamental principles governing nanomotors are distinct from those governing macroscopic machines, with the key difference being their size, which ranges from 1 to 100 nanometers. To contextualize this scale, a strand of human hair measures approximately 80,000 to 100,000 nanometers in width – and a single gold atom has a diameter of roughly one-third of a nanometer. [3] Additionally, a strand of human DNA – the genetic blueprint within cells – is 2.5 nanometers in diameter. At this nanometer scale, water “feels” as thick as honey, and Brownian motion forces are so violent so to prevent gliding of a moving object. Under these conditions, the design rules for making motors need to be reimagined.

Like many other researchers in this field, Salaita draws inspiration from nature – seeking to emulate the activity of motor proteins found in cells, such as myosin in our muscle cells. These nanoscale biological motors exhibit exceptional efficiency at converting chemical energy derived from the breakdown of a fuel called adenosine triphosphate (ATP), into mechanical energy that they use to move along tracks within the cell.

“Nature’s motor proteins are still the most efficient we know of today,” says Salaita. “But as chemists, we’re not sophisticated enough to use amino acids to build nanoscale motors yet – however, we do know the rules of assembly of how to efficiently build materials using the building blocks of DNA.”

While the first generation of synthetic DNA motors employed two DNA strands, or "legs”, which “walked” along a track with a mechanical leg-over-leg motion, these structures proved highly unstable and slow-moving – for example, covering just “a single nanometer per minute,” according to Salaita. Although increasing the number of legs enhanced the stability it hindered their coordination, resulting in even slower speeds.

However, in 2015, Salaita’s team made a significant breakthrough by developing the first rolling DNA-based motor. By arranging the legs onto a micron-sized spherical “chassis”, they enabled coordinated motion which significantly improved the motor’s efficiency. Although still far from matching the speed and efficiency of biological motors, the engineered DNA motor could traverse one millimeter in hours, rather than years – a remarkable achievement, considering this was 1,000 times faster than previous iterations. Importantly, the motion of the motor could be imaged using a clip-on microscope lens attached to a smartphone camera – opening up potential real-world applications in disease diagnostics and beyond.

“When we first developed the rolling motor, it was initially out of pure curiosity - to explore whether we could convert chemical energy into mechanical work and make something move,” says Salaita. “But we then started to think about its potential applications.”

This led the team to the idea that the speed or the type of motion displayed by these motors could serve as readouts for sensing, potentially indicating the presence of specific substances in a solution. They then started to explore diagnostic sensing applications, resulting in the award of a patent in 2020 for a simple, low-tech method of performing diagnostic sensing in resource-limited settings or field conditions.

During the initial months of the COVID-19 pandemic, Salaita’s team recognized the potential of adapting their rolling DNA motor – which they dubbed the ‘Rolosense’ – for detecting SARS-CoV-2. This realization led them to kick off a project in 2021 aimed at developing a revolutionary sensing device capable of detecting the virus in the air of indoor spaces.

Their approach involved identifying specific pieces of DNA that could selectively recognize and bind to the spike protein present on the surface of SARS-CoV-2. They attached these DNA strands onto a chassis and then embedded the motors onto the surface of a microchip. The motor operates by rolling across the surface unless it encounters SARS-CoV-2 viral particles that cause it to stall.

“The motor can only generate so much force – and if something is pulling it back, it stops moving,” explains Salaita. “So, if SARS-CoV-2 is present, the motors and the track become mechanically sandwiched by the viral particles, leading to the motor stalling.”

A camera will continuously record the speed of the motors – and if a motor stalls, it would trigger an electronic alarm signal at a central monitoring station. And because the motors can run for up to 24 hours, this allows for fully automatic viral sensing without the need for human intervention.

The researchers have so far demonstrated the ability of the technology to detect SARS-CoV-2, in a variety of different matrices including artificial saliva and human breath condensate. By spiking samples with various concentrations of viral particles, they have determined that even a single viral particle is sufficient to stall the motor, showcasing the sensitivity of their approach. But despite the immense potential of this innovative technology, several challenges remain to develop a prototype sensor for detecting SARS-CoV-2. One significant obstacle is the highly mutable nature of pathogens, especially viruses.

Salaita emphasizes the crucial role of real-time pathogen detection across different global locations as a vital part of the strategy in preparing for future pandemics. "We know that the ability to detect pathogens in real-time and across the world in different locations will be of utmost importance for containing the spread of infectious diseases with pandemic potential," he affirms.

Building on his previous groundbreaking work, he intends to use the funding from the Future Insight Prize to advance toward his long-term objective of creating a sensing device that can effectively detect high levels of any concerning virus in indoor air spaces.

"It’s a real honor to win this award, which will help us to expand the scope of viruses we can detect – and to work towards the integration of both components into a single device," he reflects. He envisions that this progress will establish the foundation for future clinical studies, evaluating the potential of using this novel diagnostic technology in clinical settings or as a home device. Ultimately, the goal is to deploy it in public settings as a monitoring device for the detection of airborne viruses.

Salaita's recognition of the importance of proactive measures and the potential of his innovative technology underscores humanity’s collective responsibility to be better prepared for future pandemics. By leveraging advancements in pathogen detection and surveillance, we can enhance our ability to safeguard public health and minimize the impact of future infectious disease outbreaks.

_{[1] https://www.britannica.com/science/pandemic
[2] https://covid19.who.int/
[3] https://www.nano.gov/nanotech-101/what/nano-size}