Pictured:  Mechanism of pumpy doom, or savior to us all?  Neither!

Pictured: Superbug spawner, or savior to us all? Neither!

Recently, I was sitting in a meeting and reached for the dispenser of Purell hand sanitizer sitting on the conference room table. A colleague of mine gave a small, rueful shake of her head to the person on her other side. Apparently I had erred. I asked what was the matter, and got a brief answer to the effect of “because superbugs.” We exchanged nothing more about it; the interaction was over before the alcohol had dried from my hands.

I wouldn’t have thought anything of such an interaction with anyone else, but my colleague is a PhD student in immunology, six years older and more schooled than I, doing her doctoral research in a lab run by a physician-scientist — a specialist in infectious disease, no less. A touch ironic.

And so I noticed a need for some mythbusting: alcohol-based hand sanitizers do not breed resistant bacteria.

Superbugs: whence they come

Antibiotics breed resistant bacteria. I’ll leave the topic of antibiotic stewardship out of this post — suffice to say that antibiotic use and the resultant resistant microbes are a serious problem — but I’ll explain how alcohol-based sanitizers do not breed “superbugs,” either bacteria or viruses. I’ll then touch on the hygiene hypothesis as it pertains to personal hygiene.

First, bacteria. Antibiotics have specific mechanisms of action by which they weaken or kill bacteria. Take penicillin and its derivatives (β-lactam antibiotics) as a classic example: they inhibit the synthesis of the peptidoglycan wall of gram-positive bacteria at the final transpeptidation step. This in turn renders the bacteria fragile and vulnerable to physical and osmotic stress, as well as unable to divide. This inhibition process requires high molecular precision.

This specificity is what characterizes antibiotics’ function. It is also what creates a selection pressure for bacteria to evolve to survive what was previously toxic to them. We tend to think of evolution as a process taking place over millions of years, but it’s faster for microorganisms — a lot faster. The vast numbers of bacteria, their short time of replication, and their capacity for horizontal gene exchange, accelerate their evolution when they are in the presence of an environmental pressure such as an antibiotic.

These factors create the dangerous potential for evolution of bacteria into resistant strains. Over time, and with improper use, antibiotics can breed superbugs.

Why you shouldn’t worry about (alcohol-based) sanitizers breeding resistant bacteria

What, then, separates Purell from penicillin? The answer lies in the mechanism of action of ethanol — a type of alcohol, and the active ingredient in Purell and similar products.

(It is important to note that I have deliberately specified alcohol-based hand sanitizers in this post. They are by far the most common kind of instant sanitizer. Other active ingredients, like triclosan, may promote resistance, because they have different mechanisms of action.)

While antibiotics target very specific cellular processes, ethanol is a nonspecific bactericidal agent. It disrupts several bacterial functions at once, “caus[ing] membrane damage and rapid denaturation of proteins, with subsequent interference with metabolism and cell lysis.”

This is not something that can be evaded as simply as activating a specific gene and secreting β-lactamase to destroy the antibiotic, for example. Tolerance to the action of ethanol would take much longer to evolve, and would be comparable to the organism becoming an extremophile.

Moreover, antibiotics are administered over the course of days or weeks (or even months) and therefore represent a sustained environmental pressure against which bacteria can evolve. By contrast, alcohol in hand sanitizers is present for about twenty seconds and is gone — there’s no continuous stress against which the bacteria are being selected. Further, because of the very brief exposure, there is no opportunity for the bacteria to replicate in the presence of ethanol — and therefore a negligible selection pressure over time.

Alcohol hand sanitizers and viruses

Next, viruses. The ethanol in hand sanitizers is effective against some viruses, for the same main reason: overwhelming force. Ethanol can denature the protein coat of some (not all) viruses, or break down the outer lipid envelope (depending on the type of virus in question).

There’s another reason, quite different from the case of bacteria: viruses are obligate intracellular parasites that need to be inside a cell to replicate. Viruses on the surface of the skin aren’t even replicating, and therefore a denaturant such as alcohol doesn’t constitute a selection pressure. No evolution, no resistant organisms!

And so, just as they don’t breed resistant bacteria, alcohol-based sanitizers don’t breed resistant viruses. (And neither do antibiotics, as those are ineffective against viruses and wouldn’t create any selection pressure either.) Alcohol hand sanitizers are second only to hand washing (which is sometimes absolutely necessary), and nonetheless represent an important and convenient approach to curtailing contagion, especially in hospital environments.

But there’s another reason some people object to hand sanitizers.

The hygiene hypothesis

We can kill bacteria and viruses with sanitizers, and it does not breed resistant strains…but should we? The hygiene hypothesis — the idea that we need microorganisms — is another concern that often comes up along with the worries about superbugs. Basically, the rationale is that nuking microganism populations could have unfortunate unintended consequences for human health, even if it doesn’t breed superbugs (Harriet Hall has discussed the hygiene hypothesis previously, reviewing a book about it in the process).

There have been questions raised about the hygiene hypothesis concerning hand sanitizers and personal hygiene in general. The hygiene hypothesis has gone through several redefinitions since its 1989 introduction by David Strachan, but can be broadly described as the “potential beneficial role of microbial exposures for the development of asthma, allergies and autoimmune disorders.” The logic is that exposure to antigens (through infection by bacteria, or helminths – parasitic worms) hones the specificity of the immune system, reducing the incidence of autoimmune events.

The hygiene hypothesis is, by definition, not a scientific theory — it is still being evaluated, reformulated, and appended. This summary does a good job of listing some of the gaps and inconsistencies in the hypothesis, some of which include:

  • “…numerous unknown mechanisms and inconclusive findings to date…”
  • “The potential role of viruses has not been explored…”
  • “There is large uncertainty with respect to the potential beneficial effects of probiotics…”
  • “…we still do not know whether prenatal or postnatal exposures matter”; and
  • “…the use of comparative animal models has not sufficiently been explored…”

I don’t mean to cast doubt on the entire idea. The hygiene hypothesis is not pseudoscience. It shows all of the makings of a genuine (if fledgling) scientific idea: plausible mechanisms, explanatory potential, initial validating evidence, reasoned challenges, careful review, and much more to be discovered. What this early-stage status means is that scientific medicine cannot recommend specific actions at this time.

A thorough (if somewhat aged) 2006 review is cautious: “the relationship of the hypothesis to hygiene practice is not proven,” and recommends further study. The authors of this summary succinctly write: “We consider it too early to provide recommendations on an individual level with respect to personal hygiene.” A 2015 paper specific to asthma and allergies concluded: “…neither personal nor home cleanliness was associated with a risk for asthma and allergies. Other microbial components in house dust not affected by personal hygiene are likely to play a role.”

The hygiene hypothesis and hand sanitizers

Concerning the hygiene hypothesis at large, the body of evidence is growing. However, it has not converged on an interpretation — there aren’t enough consistent data to recommend specific interventions. There have been isolated studies, mostly epidemiological or in mouse models, with helminths (parasitic worms) and a few species of bacteria. But there are a prodigious number of “microbial exposures” which might have a potential effect on “allergies and autoimmune disorders,” and the research thus far has explored only a fraction of these.

What we do know doesn’t boil down to advice regarding exposure to pathogens or about personal hygiene. This includes any recommendation for or against using alcohol-based hand sanitizers.

Even if the body of evidence grows large and cohesive and suggestive enough to promote the hygiene hypothesis to a theory, there are still a number of important questions and considerations. For example: is it just antigen exposure that is needed, or is the full-blown infection required to hone the immune system? If it’s the former, then one could reasonably hope for a “vaccine” of sorts that would contain the relevant antigens to coach the immune system (although we well know that many have issues with vaccines). If, however, a true infection is required, it becomes quite a murky question about how prophylactic microbial exposure would be reliably and ethically obtained. In any case, wherever this fledgling area of research leads, it’s sure to be interesting.

Alcohol hand sanitizers have no known downside

Ethanol-based hand sanitizers are a safe and practical approach to personal hand hygiene. While they can’t replace hand washing, use of such products should not be discouraged for fear of breeding microorganisms — because they just don’t.

Fears of unintended health consequences based on the hygiene hypothesis are premature. Although the hygiene hypothesis is a fascinating and potentially promising scientific idea, it is not coherent or complete enough to make specific recommendations about personal hygiene. As such, nothing in the hygiene hypothesis should deter use of ethanol-based sanitizers at this time.

While it is possible that sanitizers have unknown health consequences, it’s a certainty that not using them has consequences.


About the author

Adam Wegman is a junior undergraduate pursuing a BS in biochemistry, after which he plans to matriculate into an MD/PhD program with the goal of becoming a physician-scientist. Though far off, potential medical specialties include pathology, infectious disease, and toxicology; potential research tracks include pathology, host-pathogen interactions, and/or cell physiology. Adam has undertaken a few different research projects so far, including assessing if his college campus had herd immunity against seasonal influenza (it didn’t); testing the ascites of epithelial ovarian cancer patients for bacterial DNA as a potential marker for progression-free and overall survival; and modulating the redox status of Vitis vinifera and Brassica rapa to suppress hypersensitive necrosis.

Adam thinks medicine should be informed by rigorous science, rather than bias-riddled wishful thinking. His interest in pseudoscience had grown piecemeal over the course of several years, mostly through arguments over vaccines, GMOs, naturopathy, reiki, essential oils, and the like.

 

 

Posted by Adam Wegman