Are mice-based e-cigarette studies dangerously misleading?
In laboratories around the world, scientists are exposing mice to e-cigarette vapour to try and learn about the health benefits (or lack thereof) of e-cigarettes. But fundamental differences between the respiratory systems of man and mouse mean that this research has limited effectiveness…
A recent vaping study on mice from UCSD’s School of Medicine and the Veterans Affairs San Diego Healthcare System found, surprisingly, that mice don’t like to vape. The results showed that after being forced to inhale e-cig vapour for one hour a day for four weeks, that the vaping mice showed 10% more inflammation markers (signs of full-body inflammation) than their non-vaping companions.
What does this tell us definitively about the effects of vaping on humans? Absolutely nothing. The conclusion drawn by the lead scientist on the study is this: it “shows that e-cigarette vapour is not benign”. Speaking more accurately, she should have said that “this study shows that e-cigarette vapour is not benign for mice.” Because, as she (probably) knows there are a number of chemicals that are not benign for mice but helpful for humans and vice versa.
Jean-Marc Cavaillon, head of the cytokines and inflammation unit, points to one particular monoclonal antibody which treats lymphoma in mice but would send a human being to intensive care — an anti-inflammatory drug that cures rodents but kills humans. On the other hand, paracetamol and aspirin are both helpful to humans but deadly to mice. Thamaldihide, which eases morning sickness in pregnant women, doesn’t adversely affect mice but causes birth defects in humans. The spate of Thamaldihide-related birth defects in the 50s were a direct result of mice studies that failed to consider how the chemical might react differently in humans.
Mice make poor subjects for e-cigarette studies because of some key differences in their physiology. Here are a million studies that back up that statement:
Two of the most significant differences between mice and humans, from a medical perspective, are 1) the respiratory system and 2) the inflammatory response.
If you’ve been paying attention, you’ll remember that mice’s inflammatory response is exactly what the San Diego scientists pointed to as evidence that e-cigarette vapour is not benign… but time and time again we’ve seen major differences in the way that mice and humans inflammatory responses work. The same holds true for respiratory systems.
Ronald Tompkins, a professor of surgery at Harvard Medical School, found that while humans react to inflammatory stimuli in fairly predictable ways, the inflammatory responses of mice differ wildly. His research caused a furore in the medical community and a massive re-think on the way that scientists use mice models — particularly when studying inflammation. He explained that “we need to recognize that simple [mice] model systems do not reproduce complex human disease”.
Researchers studying acute respiratory distress syndrome have also found that mice models poorly mimic human responses. In 2014, a dozen studies were published in five different journals pointing out the problems with using mice studies in research.
But the scientific community sometimes learns slowly. $200 million was spent developing a drug for tuberculosis that worked wonders in mice, but the drug turned out to be useless when used on humans. Not a total waste of money then — at least we now have a very expensive tuberculosis cure for mice. Dr. Clifton Barry, commenting on the trials, explains that the tuberculosis drug didn’t work as hoped because mice — as you know by this point — have a different inflammatory response and a different respiratory system.
In another example, the antibiotic Linezolid (used to treat respiratory conditions) was studied in mice. In mice, the antibiotic had no effect. But a South Korean scientist said that he was using it in humans and getting fantastic results — results that turned out to be valid. The disease which is treated by Linezolid claims two million lives a year, yet just by looking at mice we would never have learned that Linezolid is an effective cure.
There’s an abundance of evidence that mice make poor e-cigarette study subjects, some of it more obvious than others. For instance, mice can’t cough. This means that when mice inhale e-cigarette vapour, they lack the basic reflex which humans have that prevents them from inhaling too much. If you were immersed in e-cigarette vapour and you couldn’t cough, don’t you think that you might inhale a lot more vapour than is usual?
As pointed out by Sussan of John Hopkins university, in one of our favourite quotes, “you can’t really train mice to vape”.
Mice studies have lead to amazing breakthroughs in fighting polio, yellow fever, and HIV. But it is also time to admit that when it comes to inflammatory responses and respiratory disease, mice are not accurate models.
So why did the San Diego scientists use mice as models?
The above evidence against using mice models (particularly when studying inflammatory responses and respiratory systems) is not some kind of closely-guarded medical secret. In fact, any self-respecting scientist that studies mice could hardly have missed it. Yet the scientists in the San Diego study chose to ignore this body of evidence. Why?
In most cases, scientists use mice as a compromise. We don’t want to risk injuring or killing people with untested substances, so we’ll risk a couple of rodent lives instead. It might seem cruel, but there’s an understandable logic there.
However, the “let’s use mice” logic breaks down when studying e-cigarettes. There are hundreds of thousands of people vaping out there already, so recruiting some subjects wouldn’t be a risk, wouldn’t be too expensive, and it wouldn’t be hard to compare these vapers to smokers. Why study the effects of e-cigarettes on mice when we could be studying the effects of e-cigarettes on humans — which is what we actually want to find out?
Using mice is cheap, but it’s also rife with problems. The mice that are studied on are kept in shoebox size cages and given access to limitless supply of pellets. This means that not only are they the wrong species, but they are also the most obese and lazy examples of their species. We wouldn’t use the most obese, exercise-starved humans as models for our drug trials, so why do we think it’s a good idea to use obese and exercise-starved mice?
It turns out that some scientists do actually use human subjects in their vaping studies.
At roughly the same time that the San Diego scientists released their mice study, Dr. Konstantinos Farsalinos found that smokers who switched to vaping were able to lower their blood pressure from dangerously high to a safer level. This study tracked hundreds of human participants over an entire year and told us something that is actually life saving. His study found that if you are a smoker with high blood pressure that can’t give up on nicotine, you can lower your blood pressure substantially by swapping to e-cigarettes. No mice, no maybes. That’s the kind of knowledge that prevents heart attacks.
Oh, and unlike the San Diego study which is hidden behind a paywall (preventing all but the keenest journalists from doing much other than parroting the press release), Dr. Farsalinos’ research is open access.
Though the studies were released at the same time, and though one looked at humans (you know, the people we are trying to help) and one looked at mice, the mice study is still the one that got all the headlines. Is it just me, or does it look like the media prefers to pick up and run with whichever study paints vaping in the worst light?