Shares

Before I start into the meat of this post, I feel the need to emphasize, as strongly as I can, four things:

I do not receive any funding from the telecommunications industry in general, or wireless phone companies in particular. None at all. In other words, I’m not in the pocket of “big mobile” any more than I am in the pocket of big pharma. I don’t own any stock in telecommunications companies, other than as parts of mutual funds in which my retirement funds are invested that purchase shares in many, many different companies, some of which may or may not be telecommunications companies. (I should probably go and look at the list.) None of my friends or family work for cell phone companies. I don’t have a dog in this hunt. I really don’t.

I say this because these are the most common accusations I hear whenever I venture into this particular topic area, and I thought I’d just clear that up right away in order (hopefully) to preempt any similar comments after this post. Indeed, one of the favorite retorts to anyone who criticizes fearmongering about cell phones is to try to insinuate that that person is only doing so because he or she is in the pocket of industry, and I’ve been at the receiving end of such claims. Unfortunately, I’m sure someone will probably show his or her lack of reading comprehension and post one of those very criticisms of me. It’s almost inevitable. Even though posting such disclaimers never works against the “pharma shill” gambit when I write about vaccines or dubious cancer cures, nonetheless hope springs eternal.

Now that that obligatory unpleasantness is out of the way, let me move on to say that I’m very puzzled about something that happened last week.

I know that being puzzled isn’t particularly unusual for me. Indeed, I’m frequently puzzled about a great many things. I can’t figure out how, for example, anyone with the slightest bit of reason or critical thinking ability can believe that homeopathy is anything other than water treated with, in essence, magical spells accompanied by shaking or do anything other than laugh when informed what homeopathy really is and how it supposedly “works.” I can’t figure out how anyone can look at the mass of interlocking evidence from multiple different scientific specialties supporting evolution and reject still reject one of the most powerful scientific theories ever to spring from the human mind, deciding instead that creationism or its bastard offspring, “intelligent design” creationism is anything more than pure religion or rank religion-inspired pseudoscience. I can’t figure out why American Idol or Survivor is so amazingly popular.

And I can’t figure out why on earth the University of Pittsburgh Cancer Center released this warning about cell phones last week:

PITTSBURGH July 24, 2008, 07:13 am ET · The head of a prominent cancer research institute issued an unprecedented warning to his faculty and staff Wednesday: Limit cell phone use because of the possible risk of cancer. The warning from Dr. Ronald B. Herberman, director of the University of Pittsburgh Cancer Institute, is contrary to numerous studies that don’t find a link between cancer and cell phone use, and a public lack of worry by the U.S. Food and Drug Administration. Herberman is basing his alarm on early unpublished data. He says it takes too long to get answers from science and he believes people should take action now — especially when it comes to children. “Really at the heart of my concern is that we shouldn’t wait for a definitive study to come out, but err on the side of being safe rather than sorry later,” Herberman said.

Dr. Herberman is a highly respected cancer center director whom I’ve in general thought well of, and the University of Pittsburgh Cancer Institute is a highly respected cancer center. I know a few people there, and in the past I’ve worked closely with two surgeons who trained there. One in particular remains my collaborator, even though I’ve moved on from the institution where we were once partners.

That’s why I can’t help but wonder just what on earth Dr. Herberman was smoking when he decided to issue this warning, given my general respect for the University of Pittsburgh to the point where I once even tried to land a faculty position there. His announcement strikes me as being rash in the extreme, especially given that its text even admits outright that the published data at present do not appear to support a link between cell phone use and brain tumors. Consequently, I conclude that this is alarmism that, I suspect, even a prominent blogger known to be somewhat receptive to the claim that cell phones cause brain tumors (Revere) would have a hard time supporting, because it goes far beyond the published evidence and is based on “early unpublished data.” Scaring the nation based on “early unpublished data” that can’t be examined by the entire medical and scientific community is generally not a good idea. That’s why I’ve been asking over the last few days: Why on earth did Dr. Herberman do it?



The question of whether cell phones cause or contribute to the development of brain tumors is not as easy a question to answer as one might think. Indeed, I suspect that the very difficulty of answering the question is what contributes to the amount of woo that has come to surround the whole issue of cell phones, complete with useless “cell phone shields” and various other devices that will supposedly obviate any risks, whether real or not. First, there is the issue of biological plausibility. Radiowave energy at the power level used by most cell phones, is not ionizing. It’s not even close, being several orders of magnitude too weak to break chemical bonds. Our understanding of cancer is that, in general, ionizing radiation is what is required for radiation to cause or contribute to cancer. That does not mean that there might not be a potential, as yet undiscovered, mechanism by which non-ionizing radiation might cause cancer, but simple physics and chemistry make the hypothesis that cell phone radiation causes or contributes to brain tumors not particularly plausible on the basis of currently understood biology. Too, we can actually test radiofrequency radiation in the same power range used in cell phones on cells in cell culture in order to determine whether exposure to such radiation can cause changes associated with malignant transformation. There is one confounding effect that has to be controlled for in such experiments (but is not always), namely that radiofrequency radiation interacts with water in order to heat it. Still, there are no compelling studies showing any specific effect of radiofrequency radiation on cells to induce changes associated with malignant transformation, at least none that I’m aware of. Animal studies are prone to the same sorts of problems as cell culture studies, but even so there is no good quality animal data that I’m aware of implicating cell phone radiation in the formation of cancer. On a basic science basis, at present there doesn’t appear to be strong evidence (or much of any evidence at all) supporting plausible mechanism by which cell phone radiofrequency radiation might cause cancer or an actual effect in which they do.

Another form of evidence that might be suggestive that cell phones are causing cancer would be in the form of pure incidence data. Cell phones were first introduced into the U.S. in the 1980s, but their use didn’t become widespread until the late 1990s, mainly because before that they were too expensive, bulky, and generally unreliable. I got my first cell phone in 1997, and the thing was a brick, with high per-minute charges and really high charges for roaming or long distance. In fact, it wasn’t long before I wondered why I bought the damned thing and signed up for a three year–yes, three year–contract, given how little I ended up using it. In any case, we might expect that, if cell phones were causing brain tumors, there might be a generalized spike in the number of cases of brain tumors recently. There hasn’t been any such dramatic increase over the thirty year period from 1975-2005.

Of course, we may not have been using cell phones widely for long enough to see the increase, given that the lag time from an exposure to the development of cancer is often two decades. That brings us to epidemiological studies. For us to consider any epidemiological to be support for the hypothesis that cell phones cause brain cancer, there must be a few key results. First, there must be an increased incidence of brain cancer in cell phone users. It’s even more convincing if there is some sort of dose-response phenomenon. In other words, there should be an increasing risk of cancer that is strongly correlated with increasing cell phone use. Other results that also support the hypothesis would be tumors correlated with proximity. In other words, do people who primarily use their left hand to hold their phones to their ears tend to get tumors primarily on the left and people who primarily hold their phones with their right hand tend to get tumors primarily on the right? Finally, there should be a plausible lag time between exposure and tumor development consistent with known lag times for cancer, say 10-20 years, and some specificity. In other words, does exposure to cell phone radiation correlate with certain types of tumors and not others? There are other aspects of the results of a study that can more strongly support the hypothesis that cell phones cause brain cancer, but these are the main ones.

In general, however, getting “clean” data from an epidemiologic study of cell phone use that can support a strong enough correlation to suggest causation is very difficult indeed. In order to correlate cell phone use with an increased incidence of brain tumors, it’s necessary somehow to be able to reliably quantify cell phone usage. This presents a big problem. It’s generally not possible to continuously observe people with their cell phones for years on end and obtain objective measurements, and certainly it’s not impossible to do so for people who have brain cancer now and whose exposure ten or twenty years ago is the possible contributory factor that we are interested in studying. Another way to try to come by this information is to ask people how much they use their cell phones. However, memories are unreliable, and such methods are very prone to recall bias in the form of people with brain tumors being more likely to remember their cell phone use as having been “heavy.” That’s not even counting trying to control of the number of potentially confounding factors, such as heavy cell phone use being associated with certain jobs or professions or, especially for 10-20 years ago when cell phones were far less common, with higher socioeconomic status, or even region of the country, given the uneven penetration of cell phone technology out from the urban areas that were covered first–especially 10-20 years ago. Then there’s the shift in technology from analog to digital cell phone technology that occurred in the early 2000s, which changed the power and frequencies used.

There are ways to overcome the limitations of retrospective studies. For example, an investigator can try to look at cell phone bills and see the number of minutes used per month, but who keeps their bills from 10 or 20 years ago, which is the time of exposure most relevant to the development of cancer? Alternatively, one can abandon the retrospective study altogether and follow people prospectively and have them report their cell phone usage from their bills every month. However, because brain tumors represent an uncommon form of cancer, thousands upon thousands of subjects would have to be followed this way, and it would take at least a decade or two to start to see any results. Also, it would be very hard to find and enforce a viable control group, given the ubiquity of cell phones.

Despite the difficulties, several epidemiological studies have been done, with largely negative results. Surprisingly, the NPR report actually summarizes them pretty well; so I don’t see a compelling reason to do anything other than quote the article:

The issue that concerns some scientists — though nowhere near a consensus — is electromagnetic radiation, especially its possible effects on children. It is not a major topic in conferences of brain specialists. A 2008 University of Utah analysis looked at nine studies — including some Herberman cites — with thousands of brain tumor patients and concludes “we found no overall increased risk of brain tumors among cellular phone users. The potential elevated risk of brain tumors after long-term cellular phone use awaits confirmation by future studies.” Studies last year in France and Norway concluded the same thing. “If there is a risk from these products — and at this point we do not know that there is — it is probably very small,” the Food and Drug Administration says on an agency Web site.

And:

A French study based on Interphone research and published in 2007 concluded that regular cell phone users had “no significant increased risk” for three major types of nervous system tumors. It did note, however, that there was “the possibility of an increased risk among the heaviest users” for one type of brain tumor, but that needs to be verified in future research. Earlier research also has found no connection.

Our fearless leader Steve Novella also summarized the state of the evidence regarding cell phone use and the risk of cancer and concluded that we can probably rule out a strong correlation between cell phone radiation and cancer, but we do not yet have enough data to rule out a small increased risk of brain tumors due to cell phones, particularly in children. I mostly agree with this characterization of the state of the evidence at present, which is why I find statements like this to be overblown fear-mongering:

A driving force behind the memo was Devra Lee Davis, the director of the university’s center for environmental oncology. “The question is do you want to play Russian roulette with your brain,” she said in an interview from her cell phone while using the hands-free speaker phone as recommended. “I don’t know that cell phones are dangerous. But I don’t know that they are safe.”

I think that a friend of mine, PalMD, got it right when he sarcastically retorted:

Hey, I don’t know for an absolute certainty that my popcorn won’t spontaneously combust, but I’m not yelling fire either.

To which I’d add: Hey, I don’t know with absolute certainty that vaccines don’t cause autism, but I’m not joining the anti-vaccinationists or planning to head off to the second annual “Green Our Vaccines” rally next year as a speaker. (Don’t worry; it’ll never happen unless anti-vaccine activists can provide evidence at least as compelling as the evidence that vaccines are safe.)

The actual warning is even worse, delving into some truly dubious comparisons:

In the early 1980’s, the owners of asbestos mines were reduced to bankruptcy as a result of lawsuits brought by the families of deceased exposed workers. A few years later, a key executive of Johns Manville, the most prominent company, drew lessons from the years of struggle of his industry against medical data and the scientists who were drawing attention to the risks of asbestos. He concluded with regret that greater warnings for the public, the establishment of more effective precautions, and more extensive medical research “could have saved lives, and probably also shareholders, the industry, and the benefits of its product.” [13, 14] We call on the cell phone companies to provide independent access to records of use so that appropriate studies can be carried out.

I don’t know about you, but personally I wouldn’t want investigators combing through my cell phone records without my permission. Of course, it’s hard to see what investigators would do with such data; after all, it wouldn’t be hard to get study participants to agree to give permission to examine their cell phone records, and in that case there would be no need for cell phone companies to provide “independent” access to anything. If investigators are planning on using aggregate ecological data instead of subject-level data, for instance, to try to correlate regions of where cell phone use is heavy with regions where the incidence of brain tumors is higher, then there would be a very high danger of falling prey to the ecological fallacy of epidemiology which is a principle that states that ecological (or group level) analyses are particularly prone to false positive correlations, as happened with this study and this study.

Worse, earlier in the report there was even a comparison with tobacco! Here’s the difference that makes these comparisons specious. Tobacco smoke is a known carcinogen. We have many in vitro and animal studies that allow us to elucidate the mechanisms by which its components can induce lung cancer and other forms of cancer. Similarly, although the mechanism of how asbestos induces cancer is not as clear, we similarly have animal studies that show that asbestos can indeed induce characteristic cancers. In marked contrast, we have no such studies showing biological plausibility for cell phone radiation. That’s why even bringing up the comparison strikes me more as poisoning the well more than anything else. As Steve Novella points out, how do we know that a better comparison isn’t silicone breast implants, which were initially thought to be associated with autoimmune diseases but were later exonerated by the science–but not before Dow Chemicals was bankrupted by lawsuits in the 1990s? We don’t. We need more science. Premature warnings can be almost as bad as warnings that come too late.

Particularly strange is Davis’s statement:

She said 20 different groups have endorsed the advice the Pittsburgh cancer institute gave, and authorities in England, France and India have cautioned children’s use of cell phones.

As PalMD astutely pointed out, these 20 groups did not actually endorse UPCC’s report; rather they endorsed recommendations similar to the recommendations in the report. The recommendations are not too far out there, although they are probably more cautious than current evidence warrants.

I later discovered that Dr. Herberman gave an interview with The Cancer Letter that was published shortly after he issued his warning:

The [Interphone] study was completed and analyzed over two years ago, but “the frustration is, it has not been published yet,” Herberman said. “I’ve talked with several people who are experts, and everyone I’ve talked to who has seen the data say there is clearly at least a two-fold increase in tumors on the side of the head where the cell phone tends to be used.

Even if this characterization of the Interphone study is completely accurate, I still can’t figure out what on earth possessed Dr. Herberman to allow it to be issued now. Even if the unpublished data are as alarming as implied (unlikely, given the number of previous studies that found either no risk or a questionable very slight risk and the low number of brain tumors seen in the U.S. each year to begin with) and the National Research Council in the U.S. is mistaken about its being highly skewed due to selection bias, as a responsible leader in public health and cancer, you don’t pull something like this. It’s irresponsible. A few months to get the data published in a peer-reviewed journal or, if that’s taking too long, presented at a major meeting (where the peer review process is usually less rigorous for abstracts) are not going to make a difference, given the long lag time of cancer. After all, cancer is a disease that develops over years, and even under the worst-case scenario, hypotheses for cell phone use causing cancer postulate years of heavy use as being necessary to result in cancer. Waiting until the data can be published would at least allow scientists and physicians to vet the data and decide if, on balance taking into account its limitations, it warrants such a strong warning. Alternatively, if you really believe you can’t wait a few months because the risk is so compelling, then release the data with the warning, so that scientists can judge whether the warning is warranted.

Of course, that the study authors are having trouble getting their results published makes me wonder whether their findings are as strong as advertised in this warning. No doubt the conspiracy crowd will claim that cell phone companies are somehow “suppressing” the evidence, but nothing’s stopping the authors from publishing their data and conclusions on an open access journal like Public Library of Science Medicine. Doing so would make the data public much faster, and I urge the study authors to consider this option; that is, if getting the data out where it can be evaluated by the cancer community is more important than publishing it in the New England Journal of Medicine.

Fortunately, many Americans seem to have more common sense than our cancer leaders:

“I think if they gave me specific numbers and specific information and it was scary enough, I would be concerned,” Loughran said, planning to call her mother again in a matter of minutes. “Without specific numbers, it’s too vague to get me worked up.”

I couldn’t have said it better myself.

In the meantime while we’re waiting for the data to be published, I hope my boss isn’t one of Dr. Herberman’s golfing buddies.