A TALE OF TWO TECHNOLOGIES

Far-UVC light disinfection and mRNA vaccines are both potent life saving technologies. In the fight against Covid-19, one was thrust into the limelight, while the other languished in the shadows

Emerging new technologies can offer exciting new opportunities, yet also present us with a dilemma; how do we balance the promised benefits against the potential risks? A caution led approach may eliminate risk in the short term, but endanger human well-being in the long term, through delays and barriers to adoption. On the other hand, rushing to embrace innovative technologies may lead to unintended adverse consequences.

Often described as the ‘precautionary’ and the ‘innovation’ principles, these differing approaches are tricky to reconcile, with no definitive “correct” point of balance. Numerous factors can shift the balance one way or another. The EU is renowned for a cautious approach, whereas the US promotes innovation through light touch regulation. China has it own distinctive approach, reflecting their political and cultural make-up.

The purpose for which the novel technology is designed can also shift the balance. Regulation of medical biotechnology generally favours the innovation principle, whereas regulation of biotechnology for agriculture, public health and environmental protection more often applies the precautionary principle. For the latter, endless new studies are required to ‘prove’ absence of any potential harm, rather than demonstrate clear benefits. Public perception - scepticism or enthusiasm - can also tip this balance, as can the social context; the application of new innovations in times of crisis are more likely to be supported than in situations that lack such a sense of urgency.

In response to the ongoing COVID-19 pandemic, two very different technologies emerged, each with huge potential to protect human health - mRNA vaccines and Far-UVC light. mRNA vaccines were adopted with great eagerness, with regulators applying the innovation principle, thus saving millions of lives. The “willingness to take acceptable risk based on the value of the opportunity” was crucial. In contrast, the bar was set considerably higher for Far-UVC, with ongoing precautionary evaluation hindering progress and widespread adoption. The back stories to these two novel technologies could not be more different.

mRNA biotechnology

The origin of mRNA biotechnology lies in life’s magical biochemistry and a molecule found in all living cells – natural ‘messenger’ RNA, or mRNA. These ubiquitous molecules act like instruction leaflets, carrying vital information for building and assembling the thousands of molecules necessary for life to function - hormones like insulin, digestive enzymes such as pepsin, and antibodies, vital components of the immune system.

For decades, the concept of synthetic mRNA had teased scientists with the promise of revolutionising medicine, from treating cancer to developing vaccines. In principle, any disease fighting molecule could be built within living human cells, once those cells had received the necessary mRNA instructions. Living cells could then become the factories, bypassing many of the costly and time consuming synthetic fabrication steps required to make pharmaceuticals.

Unfortunately, for a long time the intrinsically unstable and potentially toxic nature of synthetic mRNA, combined with the potential for serious adverse immune responses, kept mRNA technology firmly off-limits. These obstacles did not deter Dr Katalina Kariko, whose perseverance and key insights enabled synthetic mRNA to be tamed yet remain robust enough to be considered sufficiently safe and effective for use in human medicine. For her ground breaking work Katalina was awarded the Nobel prize.

Applying this technology to vaccines seemed an attractive opportunity. All that is required is to deliver into our cells pathogen specific mRNA instructions for building tiny but crucial parts of those pathogens, called antigens (In the case of SARS-CoV-2, the mRNA vaccine instructions are translated into the spike protein). These artificially induced invaders then stimulate our immune systems to produce antibodies, amongst other immune molecules, thus preparing a defence from future attacks.

Source: https://www.researchgate.net/publication/356474248_Messenger_RNA_mRNA_Vaccine_Large_Scale_Manufacturing

Despite the fact that this technology unlocked an entirely new way of making vaccines that was rapid and relatively straightforward, no mRNA vaccine had ever been licensed until the impending crisis of a pandemic came knocking on our doors. The unfolding, awful human toll pushed authorities to accelerate COVID-19 vaccine development. This involved “an unprecedented flow of cash” along with flexible decision making, leading to “some of the fastest vaccine development and testing in modern history”. Emergency authorisations were issued even before completion of phase 4 clinical trials, a stage ideally required to monitor real world effectiveness, safety concerns and resolve outstanding questions. In the words of Dr Thana Cristina de Campos-Rudinsky, from the Princeton Institute for International and Regional Studies -

“These unknowns include…..whether or not the vaccine prevents viral transmission, how the vaccine affects different groups, as well as the vaccine’s long-term safety profile...The UK’s and many other countries’ decision in approving a COVID-9 vaccine without complete certainty illustrates the complexities of public health decisions…..Health policies always involve some level of risks, many layers of complexity and difficult trade-offs among competing policy goals, relative utilities, objective values and principled reasons.”

These judgements were reasonable, given the circumstances. Had we waited until we had full certainty on all these questions, many millions more people would not be alive today. The urgency of the situation required us to apply the innovation principle, focusing more on the potential benefits rather than the unintended risks. But did we apply the same level of urgency to another powerful tool for combating disease, Far-UVC technology?

Far-UVC technology

Unlike the biological origins of mRNA vaccines, the genesis of far-UVC emerged from a physical phenomenon - light waves, or more precisely, electromagnetic radiation. Just as ocean waves vary considerably when measuring from crest to crest, light waves also assume different wavelengths as they travel through space. Measured in nanometers - that’s a billionth of a meter - light waves range from the longer wavelengths of radio waves to the billionth of times shorter gamma rays. This continuum of wavelengths is described by the electromagnetic spectrum.

source https://www.canada.ca/en/health-canada/services/sun-safety/what-is-ultraviolet-radiation.htm

Sandwiched between visible light waves and X-rays are the Ultra Violet (UV) light waves, which are classified into three bands – UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm). Most of us are familiar with the longer UVA and UVB wavelengths in sunlight that provide us with vitamin D and make us feel good, but too much exposure can lead to skin cancer and cataracts, hence the need for sunscreens and protective clothing.

The shorter UVC wavelengths are highly efficient and potent light disinfectants. Effective against all known microbial pathogens - whether on surfaces or airborne - UVC 254 nm light disinfection is an established 80 yr old technology that has been widely used in water disinfection, food decontamination and the control of TB in hospitals and homeless shelters. In fact for decades it has been known that established UVC is “effective in reducing disease transmission, even for highly contagious airborne diseases such as measles, influenza and the common cold”. However, in western societies, with the arrival of vaccines and antibiotics, the control of infectious diseases using UVC light largely fell out of fashion. [For those interested, an excellent in depth article on the history of UVC light disinfection and the key pioneers of this technology can be found in: Ultraviolet light and indoor air disinfection to fight pandemics: A technology long overdue. ]

Established UVC technology can potentially cause skin and eye irritation, “although the long-term health risks are considered to be negligible compared with common solar UV exposures”. Nevertheless, to completely avoid any adverse effects, conventional UVC has been limited to upper room applications only, when used in occupied settings. Encouragingly, more recent research has found that by shifting to slightly shorter UVC wavelengths, notably 222 -230 nm, informally known as Far-UVC, not only is the effectiveness against pathogens maintained, but numerous published peer reviewed studies show no measurable negative impacts to skin and eyes under direct exposure, despite including much larger doses that would be allowed in real world settings.

Unlike conventional 254 nm UVC, the shorter wavelengths of Far-UVC cannot penetrate further than the outermost layers of human skin (which is composed of dead epithelium cells), nor cause any detectable eye irritation, making it suitable for all occupied spaces. In fact, Far-UVC expert Dr Ewan Eadie, Head of Scientific Services for Photobiology and Optical Radiation at Ninewells Hospital in Dundee states that “Far-UV exposure of 30,000 hours or 3.5 years is equivalent to 10 minutes in the sun.” So long as the source of Far-UVC is from filtered lamps that screen out any other potentially hazardous wavelengths, it is completely safe.

Far UVC is particularly effective for pathogen reduction, as it is able to quickly treat large volumes of air, and thus achieves far higher equivalent air changes per hour than is practically feasible with ventilation or filtration alone. Studies have shown well over 90% pathogen deactivation within minutes. This rapid rate of removal is vitally important for highly infectious diseases such as COVID-19. With Far UVC we can forget ‘equivalent air changes per hour’ – we are talking about air changes per minute.

The potential for UVC light and specifically Far-UVC in disease control is huge. Edward Nardell, Harvard Medical School Professor of Global Health and Social Medicine, one of the key pioneers of UVC light disinfectant, with decades of experience researching airborne infection prevention, describes Far-UVC as an “untapped potential to mitigate airborne infections”, stating -

“It is not an exaggeration to claim that the most effective, evidence‐based, cost‐effective, safe and available engineering intervention to disinfect air is being largely ignored during a lethal viral pandemic spread predominantly by the airborne route.”

Despite all of this evidence and experience, governments and public health bodies have been strangely reluctant to adopt and promote this promising technology. Unlike mRNA vaccines, where rapid deployment under the innovation principle was seen as essential, Far-UVC lags behind, beset with obstacles, with requests for more data and a focus on arbitrarily looking for potential harms, rather than accepting the clear benefits. This has led to a seemingly endless barrage of sometimes spurious questions over safety and efficacy, which has had the effect of slowing public acceptance and official adoption of a lifesaving technology.

What about ozone & VOCs?

Ozone is a well known air pollutant. Indoor background ozone levels in the absence of Far-UVC typically range from 4-6 ppb (parts per billion). The current FDA guidelines stipulate that indoor concentrations from medical devices should not exceed 50 ppb. Two “real-world” studies (one in a hotel room and the other in an office), showed an increase of approximately 5 ppb with Far-UVC lamps switched on. Both studies employed higher Far-UVC doses than the recommended limit and the rooms were comparatively well sealed, suggesting that additional Far-UVC ozone generation is unlikely to be a significant issue. This has been further corroborated by Dr Ewan Eadie (Head of Scientific Services for Photobiology and Optical Radiation at Ninewells Hospital, Dundee), who showed that Far-UVC lamps running at 10% of maximum output did not generate additional ozone, yet were still extremely effective at inactivating pathogens. Another study in an animal care facility, conducted by Dr David Brenner (Professor of Radiation Biophysics, Columbia University), found no enhanced Far-UVC ozone generation.

Some studies conducted in sealed laboratory aerosol chambers have found that Far-UVC can lead to elevated ozone levels, and unfortunately these data have been reported out of context, leading to unwarranted concerns. We don’t live in sealed aerosol chambers, and the basic ventilation rates and natural ozone decay in real world settings effectively eliminates this as a problem.

Ozone can also react with ‘Volatile Organic Compounds’ (VOCs) in indoor air, to create secondary pollutants harmful to human health. One ubiquitous VOC found in cleaning and personal hygiene products is limonene, which is particularly reactive with ozone. This has been raised as a potential concern for Far-UVC, but without adequate ventilation is already a potential indoor air quality issue, irrespective of Far-UVC use. In reality, the previous studies showing little or no Far-UVC ozone effect in real world scenarios also did not demonstrate Far-UVC enhancement of secondary pollutants. If limonene were to be an issue for air quality, the answer is better control of ventilation and a more frugal use of scented products and cleaning materials.

What about the skin microbiome?

Bizarrely, concerns have been raised about Far-UVC disrupting the skin’s natural microbiome. Handwashing, alcohol sanitizers, bathing and showering are all known to disrupt the natural balance of the skin microbiome, but notably, this was not an issue raised by public health agencies regarding the constant exhortations to sanitize our hands. In any event, these surface effects are known to be transient, whether Far-UVC or washing induced.

What about cost?

The widespread deployment of Far-UVC will undoubtedly be cost effective. The costs to society of the failure to control the transmission of SAR-CoV-2 are unfathomable. Welfare benefits, strained healthcare systems, high costs of treatments and lost productivity are escalating as a result of this one virus alone. In 2023, the German economy was estimated to have lost 0.8% of GDP due to workplace absences from Covid-19, and McKinseys have calculated that the days lost to ‘mild’ Covid infections will reduce US workforce availability by up to 2.5%. Investment in Far-UVC will carry a price tag, but as Dr Ewan Eadie remarks -

“The cost of Far-UVC is unlikely to be borne directly by the individual, and in any case is in flux due to market competition and manufacturing advancements. Products tend to be more expensive during the ‘innovators’ and ‘early adopters’ phase of the adoption curve , which is arguably where Far-UVC stands at the time of writing. Following successful early adoption of and confidence in the technology it is projected that the cost of Far-UVC installations would decrease.”

The financial benefits of Far-UVC would also be greatly enhanced as unlike disease specific vaccines, it is effective against multiple pathogens.

Will the public accept Far-UVC?

In contrast to mRNA vaccines, where the messaging was very clear on the benefits and safety of a ground breaking technology, a lack of public awareness of Far-UVC as a safe and effective tool for killing airborne viruses and bacteria has hindered progress. However, Dr Ewan Eadie has demonstrated that that when the basic concepts of Far-UVC are clearly communicated, public opinion improves. To accelerate progress he strongly recommends clear public health messaging and states

“Such channels utilised for current health protection measures could be leveraged to provide informative and reputable information on Far-UVC, as presently there is a lack of such information. A centralised, freely accessible resource would be key in appropriately conveying information on Far-UVC to the wider public.”

Diverging approaches

Trapped within the precautionary principle, Far-UVC has struggled to make significant headway. Despite a proven track record and an excellent safety profile, it’s use to date has been limited. While the UK Ministry of Defence is understood to have installed Far-UVC units and the technology has been regularly seen in the White House, there is an eery silence around Far-UVC within wider public health circles.

In contrast, under the innovation approach, mRNA vaccines were placed firmly in the limelight, with rapid deployment, even before all the questions concerning safety aspects and efficacy could be fully resolved. The outstanding questions of durability, side effects and transmission prevention have now been answered. Current research aims to address these shortcomings, with fine tuning of the mRNA vaccines to reduce reactogenicity and ongoing research to develop better, more durable COVID-19 vaccines. As with all emerging technologies, post deployment monitoring, research and refinement are crucial. For Far-UVC however, it appears that every last detail and scrap of uncertainty needs to be addressed before we consider it as a viable technology.

In Conclusion

It is a sobering thought that had we waited for phase 4 trials to be completed for the mRNA vaccines, millions more people would have died from Covid-19. A focus on the potential benefits through the adoption of the innovation principle was essential. It is an equally sobering thought that had society similarly fast tracked Far-UVC technology, with it’s own ‘Operation Warp Speed’ of huge investment, rapid research and full government support and promotion, countless more lives would have been saved, and millions spared the ravages of Long Covid. And if we had applied Far-UVC alongside the mRNA vaccines, we might now genuinely be here in 2024 contemplating the effective elimination of Covid-19.

This is not even about going back to pre-pandemic 2019. We now have better tools and greater knowledge to engender a twenty first century revolution in public health, and a huge leap forward to a future where infectious diseases are no longer viewed as an inevitable fact of life we must endure.

The tale of Far-UVC is one full of regrets, but it is not too late. In this Tale of Two Technologies, were we to fully embrace Far-UVC as a vital tool for combating disease, to paraphrase the great storyteller Charles Dickens, ‘it will be a far, far better thing we do, than we have ever done; it will be a far, far better future we go to than we have ever known’.