Doing it like bunnies!

The Guardian reports, with some titillation, about a study published recently in the International Journal of Impotence Research on the effects exposure to mobile phones has on the sexual behavior of male rabbits (the surprisingly tame photo here is from the same Guardian story).

A group of researchers studied the effects of electromagnetic exposure to the genitals of 6 rabbits for 8 hours a day for 12 weeks, using as controls 6 rabbits exposed to phones that were turned off, and 6 rabbits with no exposure to phones. They tested them by introducing "teaser" females (it's not clear if they were trained or not) into the cages of the males, and measuring receptive behavior, ejaculation frequency, and hormone levels. Did the bunnies get a buzz on their phones?

The complete paper is available only to those with subscriptions, but from the abstract we learn the following:

Abstract

Mounts without ejaculation were the main mounts in the phone group and its duration and frequency increased significantly compared with the controls, whereas the reverse was observed in its mounts with ejaculation. Ejaculation frequency dropped significantly, biting/grasping against teasers increased notably and mounting latency in accumulated means from the first to the fourth teasers were noted in the phone group. The hormonal assays did not show any significant differences between the study groups. Therefore, the pulsed radiofrequency emitted by a conventional MP, which was kept on a standby position, could affect the sexual behavior in the rabbit.

Obviously, this study is meant to address the question of whether long term exposure to electromagnetic waves is harmful to mobile phone users, not just what it does to a rabbit's sex life (especially given how infrequently rabbits carry cell phones for 8 hours a day, on or off). A number of studies have shown little or no effect on risk of brain cancer (maybe), which we blogged about here, but because phones are hung from a belt, or kept in pockets probably for more time than they are held up to the ear, the question of other than brain effects is an obvious one. Of course, there's probably less distance between the phone and a rabbit's genitals than a human's, but even so, the results of this study are suggestive in more ways than one.

A common slur against mankind is that men haven't the metabolic energy to serve their two main organs, their brain and their nethers. So this study may show that either way, a phone call is a bad thing.

R r r i n n g g! Who's Calling?

The study that we've all been waiting for for 10 years to tell us whether cell phones cause brain tumors is.....inconclusive! As reported in the International Journal of Epidemiology, the World Health Organization's International Agency for Research on Cancer (IARC) conducted a large case-control study of 13,000 people in 13 countries, with interviews of 2700 users with a type of brain tumor called glioma, another 2400 with meningioma, and 7500 controls with no cancer. They chose people most likely to have been the heaviest cell phone users in the last 5-10 years, people in urban areas and aged 30-59. Controls were matched on age (within 5 years), sex and region of residence within each country. (Phone image from freefoto.com.)

Subjects were asked to recall details about their cell phone usage over 10 years -- average call duration, use of hands-free devices and so on -- and the questionnaire also asked for information about socio-demographic variables (though they ultimately used educational level as a surrogate for socioeconomic status), occupational exposure to electromagnetic fields and ionizing radiation, medical history, medical exposure to x-rays or MRI, and smoking. Information about the location of the tumor was also asked.

The majority of subjects in this study were not heavy users of cell phones. Among meningioma cases, the prevalence of regular cell phone usage was 52% during a single year, and 56% among controls, and among meningioma controls, lifetime usage was about 75 hours, or about 2 hours a month.

The odds of having meningioma or glioma with regular cell phone use compared with controls (those without cancer) was 0.79 (95% confidence interval: 0.68-0.91) for meningioma cases and 0.81 (CI: 0.70-0.94) for glioma, in the entire study population. The odds ratio (OR) varies somewhat by hours of usage, but is always below or around 1 (an odds ratio of 1 means that the test variable, in this case cell phone use, was not found to effect risk of disease), which, if taken literally, suggests that risk of brain tumor was reduced with cell phone usage, though the researchers believe that some systematic bias rather than an actual protective effect of cell phones is more likely to explain this result. Age and sex seemed to make no difference to the results. An important point is that these OR values are specific to this particular sample, and are only as good as the sample itself was 'representative' (and of what).

The authors calculated hundreds of odds ratios, broken down by age, sex, location of tumor, SES, hours of phone usage, and so on, and some were greater than 1. They found, for example, that the OR for glioma for those with the greatest call time (over 1640 hours cumulative use) was greater than 1. That some ORs were greater than 1, even if there was no actual effect, is not surprising, since with a 95% confidence level 5% of the results are expected to be positive by chance alone, so whether or not they have found any real association is still open to question. But, the fact that this is just the association that was being tested in this study would mean that more weight should be given to this finding, though the OR didn't gradually increase with use, which argues against it being a conclusive result. 

Our results include not only a disproportionately high number of ORs less than 1, but also a small number of elevated ORs. This could be taken to indicate an underlying lack of association with mobile phone use, systematic bias from one or more sources, a few random but essentially meaningless increased ORs, or a small effect detectable only in a subset of the data.

This was a $24.4 million study -- a grant almost as big as a Verizon bill -- with 1/4 of the funding coming from cell phone industry sources, because Verizon or Vodafone really, truly want to know the truth (don't they?). They of course welcomed the lack of clear findings -- as though that meant definitely there was no risk. Go on, call someone and tell 'em the good news!

According to one story reporting the study:

The British-based GSM Association, which represents international cell phone firms, said IARC's findings echoed "the large body of existing research and many expert reviews that consistently conclude that there is no established health risk."

In fact, that wasn't the conclusion of the study (rather it was that there may be a link of heavy usage with glioma, but that more research was needed -- a shocking surprise that they would ask for more grant funding).

So, apart from the clear conflict of interest in the industry funding of and reporting on the results of the study, do we actually know more than we did before the $24 million was spent, and if not, why not?

This was a retrospective study, meaning people were asked to recall behavior from years ago, which is unavoidably unreliable, particularly the farther back one goes. The authors of the study themselves discuss a number of other reasons that the study could be faulty, particularly selection bias, or a refusal to participate by some people who were contacted, which may be systematically related somehow to risk, and information bias, or a differential error in the reporting of past phone usage by cases or their proxies (who were interviewed when a subject with a brain tumor was too ill to answer questions or had died) vs controls. Proxies would presumably not know as much about the subject's usage, and it could be that cases were more motivated to remember cell phone use if it could explain their disease.

Prospective studies, which would follow people at some starting point for a certain length of time and measure as many relevant factors as possible would be a more accurate way to look at this question, and in fact a 30 year prospective study is apparently in the works. But cell phone technology is changing all the time so whether results in 30 years will be relevant to then current technology is rather doubtful.

In any case, the results of the studies done to date pretty convincingly show that the risk, if any is very small, and this raises the major problem with prospective studies: they are very costly, their conclusions don't arrive til your grandchildren are nagging for their first cell phones, and unless they're huge they will only find a very few cases. That might mean we should dismiss the risk, and if the risk were just of hang-nails that would be a reasonable conclusion. But the risk is cancer, and as with other studies of cancer risk, notoriously including cancer risks from radiation, nobody thinks we should just zap away and not worry. So what to do?

There's an obvious reasonable and rational solution: simply to accept that there may be a small, but serious risk, just as we know there are risks of driving cars, flying in planes, or getting dental x-rays. And here, a law can easily be passed that would require that headsets be part of any new mobiles. That would actually be good for Vodafone (not necessarily because of civic responsibility but at least because there'd be more gear to sell) and would obviate the problem unambiguously. If there is a radiation risk to whatever's near your pocket where the phone is stored, that would be even more difficult to detect, since the tissue is denser and thicker there than at your ear.

These large studies use as their null hypothesis that cell phones are safe -- they entail no risk. Instead, they should use as the null the current best-estimate of the risk, and try to reject that hypothesis. This is a different kind of statistical approach (related to what is known as Bayesian analysis, in which you take what you think you know, and adjust your new findings accordingly).

Since there is evidential reason to think cell-phones might be dangerous, but the risk (if any) is clearly small, the burden of proof of new studies should be to reject the idea that the phones are dangerous, not that they're safe, and estimate the maximum risk consistent with the data (if the proper null cannot be rejected). Another statistical issue is the probability ('p-value') used in evaluating the evidence. If the nominal 0.05 value is used, that's rather liberal, since it's not likely that much that's convincing can be said, in terms of small risks, at such a level. But since the risk (if any) is quite serious -- brain cancer -- the proper p-values should be very conservative -- bending over backward statistically, to say that one won't dismiss risk unless the evidence is very strong that there isn't any.

Simply requiring head-sets would be a sound, safe, and sane public health policy. Headsets would also save many lives from accidents due to distraction, as in driving. Such a policy, like fluoridating toothpaste, would have benefits but not inconvenience anybody -- well, hardly anybody. It would greatly inconvenience the epidemiological establishment by depriving it of hundreds of millions of dollars of funds, to support their habit for decades, to prove that......cell phone risk is very small, if any.

Hunting of the mobile snark

Lewis Carroll's Hunting of the Snark, is a poem about a motley crew that sets out to pursue a rare prey, the snark, a rare and indeed fanciful beast. Have we come to the right place?

`Just the place for a Snark! I have said it twice:

That alone should encourage the crew.

Just the place for a Snark! I have said it thrice:

What I tell you three times is true.''

It is natural to come to believe what you hear asserted many times (to wit: the nonsense the right wing loonies have said about the health-care plan, or ... what Fox 'News' says is news). Even in science, it is easy to show how such things happen to those of us who are supposed to be, and fancy ourselves to be, very critical 'evidence based' judges of the world.

Sometimes this fits our predispositions but often the story is more complex. Often we are chasing after truths about rare causal phenomena, where adequate data are tough or impossible to collect and it is sometimes not even clear what we need to collect.

Do mammograms cause more cancer than they detect, or treatment for tumors that would have regressed on their own? What about dental x-rays or occupational exposures such as, for example, work in a molecular genetics lab that uses radioisotopes for labeling reactions?

Or, to take the story on the CNN website on Tuesday that triggered this post, does mobile-phone usage cause brain cancer? The concern has been around since some early studies about a decade ago, but most subsequent studies have not confirmed the effect. The idea is that a cell phone emits weak electromagnetic radiation that, when held close to the head can cause DNA damage that leads to cancer. Yet, the energy level would seem to be too small to do that, based on what's known about DNA. And some studies (including the one reported this week) claim the additional persuasive kind of evidence that the side of the head the user prefers to listen with is the side that preferentially develops a tumor.

The CNN story reports that a decade-long World Health Organization study of cellphone risk is due out by the end of the year, and that it will claim "significantly increased risk" of some brain tumors. A meta-analysis of 23 different studies, that is, one that unified the separate studies into a single overall analysis, published in The Journal of Clinical Oncology in December, 2008, found a slightly increased risk as well, in the eight studies the authors deemed likely to be the most accurate (that is, they were double-blind, and not funded by mobile phone companies; this is actually true--the studies funded by phone companies in fact found that mobile phone use was slightly protective!).

But even people who defend the idea that cellphones are risky don't deny that there are problems with each of these studies. They are all retrospective, for one thing, which increases the possibility of faulty memory of phone usage, or the amount of head-side preference, and many were too short-term--e.g., six months--to adequately measure risk, since brain tumors generally develop over years, not months. So, even the data from the best of these studies is not conclusive, partly because of the way these studies were designed and partly because if there is a risk from cellphone use, it's small and going to be very difficult to tease out, even with the best of studies.

Other studies of the risks of low-dose radiation have been notoriously plagued by similar issues--yet are important for setting exposure limits to radiation workers, medical patients, etc.

But, if cellphone risk is real, this is a genetic story in that the tumors would be due to some exposed cell by bad luck acquiring the wrong set of mutations that led it to stop obeying 'don't grow' signals. But the changes are inherited from the first brain cell to its descendants in the brain, but not transmitted in the germ line. Of course, and here would be yet another challenge to detect, some individuals might be susceptible because their brain cells have inherited some set of mutations that already lead them part-way down the path to cancer. (These aspects of change and inheritance are major subjects in our book.)

However, the reason the evidence for mobile-phone effects seems implausible to some may (again, if the effects are real) be because the assumption that the cause is DNA damage. Suppose it is some other induced change in cell behavior. Then perhaps the arguments about energy levels are wrong. One might guess what the other types of change might be.....but we are not the ones to do such guessing since that would be far out of what we know anything about.

Still, questions such as these show the elusive nature of making sense of data when the snarks we're trying to catch are elusive.

If the exposure is, from our normal point of view, very very small and hard to estimate, and the outcome very rare, how can we tell? Even a single cancer can be a tragedy for that individual. But do we outlaw mobiles for that?

Like the assertion in the poem, we see the same claim made repeatedly in the media, reporting this study or that. We also see the same denial of the assertion made repeatedly in the media and in some other study. Is repetition a good basis for holding either opinion about such causal claims?

Clearly repetition without evidence is not in itself any kind of criterion. Anyone can say anything (as the group leader did in regard to the snark). For well-known statistical reasons, even a large study can fail to detect a small effect, with there being no design problems or fault on the part of the scientist. Flip a coin twice: though the true probability of a Heads is 1/2, many times you'll get two heads or two tails.

Many important problems in biology are like this and because of the seriousness of the outcome, radiation exposures are among them. But we're besieged with claims about this or that risk factor, where the risks are thought to be substantially more than with cellphones, and yet we can't seem to get a definitive answer even then.

Evolution works slowly, or so it seems. So slowly that mutation is very rare, selective differences very small, and life's conditions highly irregular. As with other small causal factors and rare or very slow effects, it is difficult to know what evidence counts the most. It presents a sobering challenge to science. And lots of room for strong, if often emotional rather than factually solid debate.

After all, it turned out that the snark was a boojum, you see!

-Ken and Anne