Can far-UVC light be safely used as germicide? (help understanding a paper)

Question

I've been trying to familiarize myself with the literature on far UVC light as a germicide. My question mostly pertains to figure 4 of this paper. The paper investigates the efficacy of 207 nm light for killing MRSA without damaging human cells. Figure 4 shows that you can get 4 logs of cell kill for MRSA with relatively little damage to human cells. The authors treat this as a very promising result. This is where I'm confused: Yes 207 nm light kills MRSA selectively, but it still kills a lot of human cells: to get 4 logs of MRSA cell kill, you need a fluence that kills 80% of human cells. Killing 99.99% of bacterial cells while also killing 80% of human cells seems obviously not good enough. But the authors don't touch on this point: They just point out that it kills 5000x more MRSA cells than human, and interpret the result as promising. What am I missing here?

Answer 1

This is a great biological question! It asks a lot about how empirical science is done in the field of modern biology! I'm glad we encourage such questions from curious people who want to learn more.

There is another paper here that discusses using a similar frequency range of UVC radiation (207-222 nm) as a biocide:

The biophysical reason is that, due to its strong absorbance in biological materials, far-UVC light does not have sufficient range to penetrate through even the outer layer (stratum corneum) on the surface of human skin, nor the outer tear layer on the outer surface of the eye, neither of which contain living cells; however, because bacteria and viruses are typically of micron or smaller dimensions, far-UVC light can still efficiently traverse and inactivate them.

Safety perhaps derives from the relatively exponential damage that far-UVC light can do to bacteria and viruses, while the layers and types of human cells that would get exposed are surface cells and mostly already dead or expendable. A 20% constant survival rate of vulnerable cells may be an acceptable trade-off, as those cells which are vulnerable would not typically be exposed (short of a wound or other exposed tissue, maybe), while the figure you cite suggests that you can raise the intensity of UV light linearly and kill exponentially more MRSA (or other disease-causing bacteria).

Answer 2

First of all a disclaimer, I am not an expert in this subject, but I have read these studies and came to this understanding. There might be a chance I get a lot of stuff wrong.

From another paper by the same authors, this time regarding 222nm UVC:

We have previously shown that 207-nm light emitted by a filtered krypton-bromine (Kr-Br) excilamp has bactericidal efficacy while being minimally cytotoxic to human cells in a 3D skin tissue model in vitro (7) and in a hairless mouse skin model in vivo (8). Thus, continuous exposure of the wound to far-UVC light during surgery may inactivate the microbes alighting directly onto the surgical wound from the air.

This shows the limited scope of its use presented by the paper as a way to sterilize the air immediately around the surgical site instead of sterilizing the surface of the patient, though it might also mean that further uses are not researched enough.

Also, it is important to analyze how the far-UVC affects human cells. In the 2013 paper you mentioned, Buonanno's team tested 2 methods of irradiating human cells with 207nm far-UVC. The figure you quoted is the dosage response curve of normal human skin fibroblasts, which are located in the dermis of human skin. In the experiment, these cells were cultivated on petri dishes and irradiated directly with UV light. This is not what you would normally expect when a person is exposed to UV, as the epidermis covers these cells and shields them from far-UVC radiation.

Normal human diploid skin fibroblasts (AG1522) were obtained from the American Type Culture Collection (Manassas, VA, USA) ... Briefly, cells were trypsinized within 5–10 min of exposure, suspended in growth medium, counted, diluted and seeded in 100-mm dishes with numbers resulting in ∼100 clonogenic cells per dish.

This brings us to the other method of measuring the effect of irradiance on human cells, which is the use of a 3-D human skin model, aka lab-grown human skin. The skin sample was then irradiated, after which they measured the amount of by-products caused by UV degradation present inside the nuclei of the epidermis. The results show almost undetectable levels of UV damage by-products, even at 150 mJ/cm^2, the dose which resulted in a 4.7-log reduction of MRSA and a 0.9-log reduction of dermal cells. These results are consistent with the cited literature that far-UVC will not penetrate the epidermis far enough to reach the cell nuclei of the first layer of skin.

In terms of the safety of 207-nm UV light, the lack of induction of typical UV-associated pre-mutagenic DNA lesions in the epidermis of a 3-D skin model is again consistent with biophysical expectations based on the limited penetration of 207-nm UV light, and consistent with earlier studies using 193-nm laser light [23].

So there you go, it turns out the far-UVC might kill 88% of non-skin human cells on the first layer, but the same dose will kill 99.998% of MRSA bacteria. The same team behind this paper has since went on to test 222nm UVC, live mice, as well as against H1N1 aerosol, and the studies show even more promise in this regard in requiring far lower irradiances to achieve a 4-log reduction in those microbes.