Also posted here on LessWrong.
Tl;dr: Far-ultraviolet light has potential as a human-safe germicide, but its safety is not established. In particular, evidence that it is not carcinogenic exists for only one of two mechanisms for ultraviolet carcinogenicity. In addition, use of far-ultraviolet light in public spaces to prevent the spread of SARS-COV-2 or other pathogens leads to a host of other concerns that need to be addressed.
In 2017, Nature published a paper that investigated the possibility of using far-UVC light to combat a future influenza pandemic. The paper went mostly unnoticed by non-academics, as is the norm for technical journals, but now with the novel coronavirus and the first pandemic of its kind in 100 years, the public at large is paying attention to ideas from the frontiers and fringes of biology and medicine. Last month, far-UVC’s safe germicidal potential was the subject of a post by Roko Mijic and Alexey Turchin on LessWrong. They call the use of far UVC in public spaces “one of the most promising and neglected ideas for combating the spread of covid-19,” and lament “Why hasn’t this already been considered by relevant authorities? Far-UVC appears in a literature review by WHO, but it is not currently being acted upon as the amount of evidence in favor of safety and efficacy is small.”
I’ve spent the last few weeks educating myself on the literature surrounding far-UVC’s safety, and I’ve come to a clear conclusion. Is the use of far-UVC to combat pandemics in general a good idea? Yes. Should research on it be expanded? Yes. But using far-UVC in public spaces to combat COVID-19 would be way way way premature.
First, a couple of disclaimers:
Disclaimer 1: I am not a biologist or a doctor. I don’t have anything near a professional’s expertise on human biological questions. There may be inaccuracies or misunderstandings throughout this post, although of course I’ve done my best.
Disclaimer 2: My method for research tends to be browsing Wikipedia to find general information, and using Wikipedia’s citations and external links to find more rigorous discussion of specific information. I try to be wary of Wikipedia’s shortcomings—I read talk pages and check citations—but even so, bias and inaccuracy on Wikipedia will inevitably seep into my perspective. I’ll leave it up to the reader to decide exactly how this research method affects my credibility.
Basic Biophysical Argument for Safety and Efficacy
Ultraviolet (UV) light is electromagnetic radiation that is shorter wavelength (higher energy) than visible light and longer wavelength than X-rays. The UV light that can be found on Earth is broken into three subcategories: UVA, closest to visible, (315-380 nm), UVB (315–280 nm), and UVC (280-200 nm). Although the sun emits light in all three UV categories, as well as visible and infrared (IR), not all the light reaches us on the surface. UVC is absorbed by the ozone layer, and the only UVC light we experience comes from artificial sources.
UVC light has been used as a germicide since the mid-20th century, but not in public spaces. Nucleic acids (DNA and RNA) strongly absorb UVC light, which means that when UVC light enters a cell, photons will hit genetic material, damaging or destroying it. This makes UVC light a strong germicide, but it also means that it is highly carcinogenic, cataractogenic, and toxic to human cells. Accordingly, its use as a germicide is relegated solely to environments like water sanitation systems where humans won’t be exposed.
However, there is still hope that UVC could be used safely in human environments in the future. There is some evidence that a certain band of UVC light, “far-UVC” (200-220 nm) is safe for humans while remaining toxic to pathogens.
The basic biophysical argument for why far-UVC might be safe hinges on the fact that mammals are much bigger than bacteria and viruses. This band of UVC light is absorbed by proteins, as shown in the following figure from one of the first papers to formulate the idea.
Figure: “Mean wavelength-dependent UV absorbance coefficients, averaged over published measurements for eight common proteins”
In essence, protein can block far-UVC light so that it does not reach DNA. Mammalian cells tend to be 10-25 μm in diameter, while bacteria tend to be 1 μm and viruses even smaller. Because of this size difference, far-UVC light has to pass through more protein before it gets to a mammalian nucleus, and accordly it should be much weaker by the time it hits mammalian DNA. In addition, on most parts of the body, we are protected by an outer keratin-rich (keratin is a protein) layer 10-40 μm thick called the stratum corneum. Cells in the stratum corneum are somewhere philosophically between dead and alive—they maintain homeostasis and complex intercellular environments, but they lack DNA, so they are safe from cancer. Because it passes first through the protein-rich stratum corneum, far-UVC light should be greatly attenuated before it even reaches the cell membranes of vulnerable cells.
Of course, if we’re going to be using far-UVC light around humans, we need more than just a biophysical argument. We also need empirical evidence. So what does the empirical evidence suggest about safety? The Nature article cites three studies that experimented with far-UVC light on human cells, on lab grown human skin, and on live mice. These studies show promise for far-UVC as a safe germicide, but they’re far from fully establishing safety.
Safety Concerns for Individuals
What happens to a person who has been repeatedly irradiated by far-UVC light? What are the health risks? What do we know? What don’t we know?
UV light is famously carcinogenic, so cancer is a central concern when it comes to assessing far-UVC’s safety. Accordingly, the three safety papers mainly seek to assess cancer risk. Of course, cancer can be slow to develop, so it isn’t possible to irradiate test subjects and count cancer cases within a reasonable timeframe. Instead, cancer must be indirectly assessed.
Cancer is caused by genetic mutations—we’re as certain about that as we are about anything in human biology—so by measuring DNA damage you can get some sort of measure of carcinogenicity.
So that’s what the authors did. They measured DNA damage under 207 nm light in lab grown human skin in vitro, under 207 nm light in mice in vivo, and expanded their results to 222 nm light on both human skin and mice. Their results were certainly promising, but the work is far from sufficient for fully demonstrating cancer safety.
There are two separate mechanisms for DNA damage from UV light, and the safety studies really only address one of the two mechanisms. We’ll discuss them separately:
Direct DNA damage
Direct DNA damage occurs when photons are absorbed by DNA. The excited DNA breaks the bonds between the nucleotide bases, and the bonds can reform with adjacent bases instead of opposite bases, disrupting the double helix structure in a type of lesion called a pyrimidine dimer.
UVB and UVC light can both interact directly with DNA in this way. This is the mechanism for UVC’s germicidal action, but at lower intensities, instead of lethal DNA destruction, lesions can turn into mutations. The body reacts to this kind of damage by killing and shedding damaged skin cells in the form of sunburn.
I feel pretty confident that this kind of damage does not happen in mammalian skin from far-UVC light. First, the basic biophysical argument is strong. Few photons should reach the nucleus (and number of photons should basically determine number of lesions). The light needs to pass through the keratin-rich (and therefore far-UVC absorbing) stratum corneum before even reaching the relevant parts of the epidermis.
The empirical evidence is also compelling. Experimentally, in vitro, as expected, irradiating lab-grown human skin with standard germicidal UVC light caused a huge number of pyrimidine dimers—standard germicidal UVC light is highly carcinogenic. Irradiating the human skin model with far-UVC, however, caused no statistically significant increase in these types of DNA lesions:
Figure: Induced yield of two types of pyrimidine dimers, from fluences of standard germicidal UVC and from far-UVC light.
Additionally, in live mice, there was no evidence of sunburn in mice exposed to far-UVC—suggesting that direct DNA damage must be minimal. The skin of unirradiated mice and the skin of mice irradiated with far-UVC looked the same, while in mice irradiated with standard germicidal UVC, the skin was visibly altered and had a thickened epidermis.
Figure: A.) Representative cross-sectional images of mouse skin. B.) Average epidermal thickness for non-irradiated mice, mice under standard germicidal UVC, and mice under 207 nm UVC.
Indirect DNA damage
Indirect DNA damage occurs when photons are absorbed by other molecules in the cell, and these molecules react to form free radicals and other reactive species, which in turn react with (other molecules which react with other molecules … which react with) DNA, causing mutations via an oxidative stress mechanism. UVA, UVB, and UVC light can all cause indirect DNA damage. This kind of damage causes skin cancer, but importantly it does not activate the same defenses as direct DNA damage—no sunburn.
The biophysical reasoning that suggests that far-UVC doesn’t cause direct DNA damage doesn’t apply neatly for indirect damage: Far-UVC is quickly attenuated in the outer layer of the skin, but how far can reactive chemical species formed near the surface propagate? Could they make their way down to vulnerable cells in the epidermis? As far as I can tell, the answer to this question is unknown. Indirect DNA damage is only relatively recently understood, completely unrecognized in 1980 and remaining somewhat controversial up through the early 2000’s—it wasn’t until 2009 that the WHO recognized tanning beds as a definite cancer risk—so there’s still a lot of uncertainty. What is known is that in general, chemicals can diffuse through the skin, and some of the chemical species we’re worried about are stable in the body. More research is needed to rule out this possibility.
In addition, the empirical evidence for far-UVC’s safety from direct DNA damage does not apply to indirect DNA damage. The mouse’s lack of sunburn in the in vivo study is meaningless as indirect DNA damage does not cause sunburn. The lesions they look for, pyrimidine dimers, are specific to direct interactions between photons and DNA. Indirect DNA damage causes different lesions.
Cancer Safety Conclusion
Although the results are promising, cancer safety has not been fully established. Direct DNA damage is minimal, but indirect DNA damage is a huge open question.
Non-cancer cell damage
Another potential point for concern is non-cancer cell death. The in vitro study found that significant fluences of 207 nm light kill 80% of exposed human fibroplasts (dermis cells):
Is this concerning? Maybe not. Except on mucous membranes and open wounds, exposed cells will be dead-ish (part of the stratum corneum) to begin with. Still, more investigation is needed: Is it okay to repeatedly destroy the surface layer of cells on our eyes? It may not be a problem, but I’d want at least a couple expert opinions if not a safety study before exposing my eyes to something like that.
And the fibroplast cell death also raises the question: What is killing the cells? The authors kind of gloss over this point—they cite another paper and say it’s probably mostly cell membrane damage. Before far-UVC is widely implemented, we need to be more confident that it is in fact cell membrane damage and not something more nefarious.
Limited Scope of Safety Studies
It’s also important to note the reason why the safety studies were conducted: The authors envisioned using far-UVC to fight antibiotic-resistant bacterial infections during surgery. They thus assumed a surgical environment, which means that applicability to public spaces is limited:
The mouth is covered by a face mask in surgery. Safety has not been established for the parts of the inside of the mouth that don’t have the stratum corneum. If we’re all wearing face masks, then this isn’t a problem, but if we’re imagining far-UVC light can let things go back to “normal,” then we need to think about the safety of our mouths. The insides of our mouths of course won’t be as exposed as our skin (the exact level of exposure depends on the positioning of the germicidal lamp, the reflectivity of surfaces, and the tics and facial posture of the person in question), but they will be exposed enough that we should know more about far-UVC’s cancer risk on mucous membranes.
And what about exposed wounds? Once again, safety has not been established for cells not covered by the stratum corneum. In the surgical environment, the nurses and doctors will not have exposed wounds. The patient’s decreased risk of surgical site infection is likely worth the unknown risks of far-UVC light on exposed flesh. But what if I’m walking around in public spaces with a skinned knee?
Finally, the safety studies focus entirely on mammals. In the surgical environment, humans are the only relevant entities that need to be protected. Many public spaces are open to pets, livestock, and urban wildlife. Even if you only recognize the value of animals’ lives with respect to what they can do for humans, many people keep reptiles or birds that they love, many people eat birds and fish and insects, and we rely on various organisms from across the animal kingdom for ecosystem stability. We should probably try to avoid causing a skin cancer epidemic in non-mammalian clades.
Even if far-UVC is completely safe for humans and other macroscopic organisms, the potential for widespread use of far-UVC leads to a number of other concerns that need to be addressed before such a solution is implemented.
In general, germicides should be used conservatively because of the potential for acquired resistance. Medicine is an evolutionary race to nowhere, with pathogens evolving to survive whatever we use to fight them. UVC light is no exception. As discussed in a literature review, one research group managed to teach E. coli to better survive UVC irradiation.
In the case of the lab-created E. coli acquired resistance, the degree of resistance was fairly weak. Lethal doses of light were still very possible. It’s not currently known whether or not full resistance by microorganisms is possible or likely. More experimentation will offer future scientists a clearer picture.
In the meantime, we should reserve UVC light for cases with high potential benefit and lower potential for acquired resistance. Ubiquitous use of far-UVC light in public spaces has the potential to teach resistance to all future pathogens, so that when the next epidemic or pandemic comes along, we’ll be completely neutered.
Is a More Sterile World a Healthier World?
UVC light kills more than just pathogens. It kills all microorganisms indiscriminately. We don’t know what would happen if we killed all bacteria in our public spaces. It could lead to problems. Bacteria play an important role in a lot of ecological processes like the decomposition of organic waste. And if it turns out that it is a bad idea to destroy all microorganisms in our public spaces, it’s not necessarily something we can come back from. An established colony of beneficial or harmless bacteria can protect against the growth of harmful bacteria. If you kill your gut bacteria with antibiotics you risk getting a harmful new microbiome. Could the same be true at a grocery store?
The Law of Unintended Consequences
Even if we can establish safety for the concerns I’ve raised above, we can never be sure that we’ve thought of everything that can go wrong. In environmentalism we recognize the “Law of Unintended Consequences:” We are very very far from understanding the world perfectly, so big technological shifts will always have unforeseen effects.
Of course, the law of unintended consequences is not a reason to hold back on change entirely. We can never know the consequences of our actions fully, so if we always avoided acting on uncertainty, we would never do anything at all. But it is possible to mitigate the potential adverse effects. In general, it is better to roll out something like this in a smaller environment where it has high potential to help (like in surgical rooms). Safety results can be assessed in those small environments before we expose the public at large.
The Stickiness of Social Change
Everything I’ve said so far is a concern, but desperate times call for desperate measures. Could the use of far-UVC be worth it, if limited to the worst of the COVID pandemic? This is the wrong question. We need to ask: If we start using far-UVC in public spaces during the pandemic, realistically, will we stop using it when the pandemic is over? Things like this tend to have staying power.
This potential for staying power is especially dangerous when paired with the preceding three concerns. The risk of acquired resistance increases with use, and we don’t have laws that prevent misuse—when far-UVC as a safe germicide becomes more accepted, it may, like antibiotics, be adopted by factory farms, increasing even more the probability of new resistant pathogens.
Killing all microbes in public spaces for a longer period of time may have worse consequences than limited use during a pandemic. Scientific understanding of the microbiome is still pretty young, but we do know that these beneficial microbes are exchanged between individuals. Ubiquitous far-UVC light would end microbiome exchange in public settings. As far as I can tell, we have no idea what the consequences of this might be.
We don’t know what the unintended consequences of introducing far-UVC light to public spaces might be, but we do know that the discovery of negative consequences often doesn’t end the use of a new technology. For example, in the 1970’s and ‘80’s, it was assumed that UVA light was safe. UVA does not cause direct DNA damage, and indirect damage was not yet discovered. Accordingly, starting in the late ‘70’s, tanning salons that irradiated users with UVA light (causing a “safe” tan without a sunburn) opened up all across Europe and the US. We now have known for more than 10 years that UVA light causes cancer. And tanning beds are still around! In most of the US, tanning beds are not only completely legal, but also accessible to minors. One study found that hundreds of thousands of skin cancer cases per year are associated with the use of tanning beds (they did not give an estimate of how many of these cases end up being fatal). Incorrectly stating that a technology is safe can lead to huge numbers of preventable deaths, even after the mistake has been corrected.
Human Rights and Consent
I don’t want to have a lengthy discussion of ethics here. This post is intended to be more an analysis of safety and potential negative consequences. Still I need to at least bring it up:
What about human rights? Is it okay to irradiate people without their consent? How do you obtain meaningful consent for something like this?
Of course, we irradiate people without their consent all the time with radio and wifi and cell phones, but those are lower energy waves far far less likely to be dangerous. Far-UVC, even if it is non-carcinogenic and doesn’t penetrate the stratum corneum, does definitely affect our bodies: It kills our skin microbiome. Just going off of my gut instinct, I’m ethically fine with wifi, while far-UVC,in a hypothetical future where safety is more established, seems much more ethically questionable.
In the US, we put fluoride in our water. If you don’t want to drink fluoride you have to significantly inconvenience yourself to avoid it. Ethically, does our approach to fluoride work for far-UVC? In the US, we don’t vaccinate people without consent, even though the unvaccinated damage herd immunity. We don’t put vaccines in the water. Is far-UVC in public spaces more like fluoride or more like vaccines?
I know I’ve seemed very negative about far-UVC for the past three thousand words, but I actually am very excited about its potential. It is because it is exciting that I think this kind of safety investigation is necessary.
We should not be using far-UVC as a germicide in public spaces any time soon. A better goal might be smaller-scale implementation within medical wards to prevent hospital spread of coronavirus or other contagious illnesses, but we’re still a long way off from even that. There are a lot of hurdles far-UVC still needs to clear before we decide it is safe. It may well clear those hurdles. I hope it does.
Should investigations into far-UVC be continued? Absolutely. Should the investigations be expanded? As someone who is not broadly knowledgeable about the frontiers of medicine, I have no idea whether far-UVC is being neglected relative to other promising technologies at similar stages of development. Still, the coronavirus pandemic has demonstrated the life-saving value of this kind of research. Public funding into this kind of research should be expanded in general, so that by the time the next pandemic hits we can know better what technologies are safe and effective.
Welch, D., Buonanno, M., Grilj, V. et al. Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases. Sci Rep 8, 2752 (2018). https://doi.org/10.1038/s41598-018-21058-w
Roko Mijic, Alexey Turchin. Ubiquitous Far-Ultraviolet Light Could Control the Spread of Covid-19 and Other Pandemics. LessWrong. March 2020.
Buonanno, M. et al. 207-nm UV light – a promising tool for safe low-cost reduction of surgical site infections. I: in vitro studies. PLoS One 8, e76968 (2013).
Buonanno, M. et al. 207-nm UV Light-A Promising Tool for Safe Low-Cost Reduction of Surgical Site Infections. II: In-Vivo Safety Studies. PLoS One 11, e0138418 (2016).
Buonanno, M. et al. Germicidal Efficacy and Mammalian Skin Safety of 222-nm UV Light.Radiat. Res. 187, 483–491 (2017).
Germicidal UVC Literature Review
Dai T.H., Vrahas M.S., Murray C.K., Hamblin M.R. Ultraviolet C irradiation: an alternative antimicrobial approach to localized infections? Expert Rev. Anti Infect. Ther.2012;10:185–195.