Epistemic status: hand-wavy, but making a serious point

TW: diets.

I recently did some reading about ketogenic diets for cancer, and I’d like to compare and contrast my approach with the explanation on the blog Science-Based Medicine, which consistently presents the “skeptical” perspective on alt-med questions.

David Gorski is a cancer biologist himself, as I am not; his posts are always informative, and I have no quarrel with his facts. I read the studies mentioned in the post, so we’re using pretty much the same set of data points. And I agree with the broad outlines of his claims: ketogenic diets have some promising but by no means conclusive preclinical evidence for brain cancers; they’re definitely not a substitute for chemotherapy in general; and Dr. Seyfried has been overselling his research as a cure for cancer in disreputable alt-med venues.

But I want to pick apart some points of perspective and interpretation.

The first part of the post is all about painting Seyfried as disreputable because of his associations with alt-med institutions. Gorski says of the American College for Advancement in Medicine, “this is not an organization with which a scientist who wishes to be taken seriously by oncologists associates himself.”

Now, I’m not defending the cancer quacks mentioned; these are people who pitch chelation and coffee enemas, things that are pretty clearly scientifically disproven. However, I’m suspicious of the rhetorical trick of guilt by association and argument from consensus. Surely we care about whether Seyfried is correct, not whether he is “taken seriously”, “reputable”, or “legitimate.” These are all social words, not scientific ones, and constitute an emotional appeal to social conformity and authority.

To his credit, Gorski doesn’t stop there; he does make substantive criticisms of Seyfried’s work. But I think it’s worth pointing out when, as happens so often in the biomedical world, a social argument is conflated with a scientific one.

Gorski goes on to criticize Seyfried for “exaggerating how hostile the cancer research community is towards metabolism as an important, possibly critical, driver of cancer” when cancer metabolism is, in fact, an active area of current cancer research. He goes on to say, “Dr. Seyfried, in my readings, appears all too often to speak of “cancer” as if it were a monolithic single disease. As I’ve pointed out many times before, it’s not. Indeed, only approximately 60-90% of cancers demonstrate the Warburg effect.”

None of these facts are wrong, but the interpretation is misleading. Cancer metabolism and metabolic mechanisms for cancer treatments are, in fact, common topics of cancer research; but this ought to be evidence in favor of Seyfried’s hypothesis, that it’s within the range of mainstream science and is supported by many cancer biologists, rather than being pure invention like most alt-med “cancer cures.”

I’d also argue with the statement that “cancer isn’t one disease.” It’s true that not all cancers demonstrate the Warburg effect, but 60-90% is a lot of cancers; a drug that was effective in 60-90% of cancers would be as revolutionary an advance as chemotherapy. An antibiotic that killed 60-90% of bacteria could fairly be said to “kill bacteria.” When most (if not all) cancers have structural features in common, that indicates that talking generally about “cancer” is meaningful, and that it doesn’t make sense to treat every sub-sub-type as though it is a completely different disease. Cancer has both unity and diversity. Saying “cancer isn’t one disease” is a rhetorically loaded move that means “don’t generalize from one type of cancer to another.” But it’s not correct to never generalize; that would utterly paralyze research. How much it’s safe to generalize depends on how common the relevant feature is across cancers; in the case of the Warburg effect, that’s a matter of current debate, but it’s fair to call it pervasive.

I don’t have much criticism of the way Gorski handles the ketogenic diet studies. He’s on the skeptical side, but skepticism is warranted. Mouse studies very frequently don’t generalize to humans; they’re suggestive, but only weak evidence. And while there were two case studies of patients who did notably better than typical glioblastoma patients on ketogenic diets, we don’t have enough patients to be confident that the improvements were a result of the diet.

But then Gorski says, “Clearly, ketogenic diets are not ready for prime time as a treatment for cancer.”

Now, wait a minute. What does that even mean?

As a cancer patient, does it make sense for you to try a ketogenic diet? Well, there’s a plausible mechanism for it to work (particularly in brain cancer), there’s some suggestive evidence in mice and a few humans with brain cancers, and — crucially — it’s just a diet. People go on ketogenic diets all the time, for no other reason than wanting to lose weight. It’s even been shown medically safe (though apparently hard to comply with) in cancer patients. Trying a special diet is pretty low risk, and a reasonable person aware of the evidence might very well choose to try it.

It doesn’t make sense to use a ketogenic diet as a replacement for chemotherapy or radiotherapy in cancers where those treatments work. That would be very unsafe. But for certain advanced brain cancers, chemo barely extends life if at all, and is very unpleasant. If there’s anyone who has a good reason to refuse chemotherapy, it’s someone who’s almost certain to die soon and doesn’t want their last few months to be agonizing.

Is a ketogenic diet for cancer something that every oncologist in the world should be prescribing for his patients? No way. Should it be the “standard of care”? No; there isn’t enough evidence that it helps. But is it worth trying for an individual who wants to? Quite possibly.

The distinction here is about where you put the reader’s locus of identity. Is a reader supposed to imagine herself as a potential cancer patient, considering whether or not to try the diet? Or as a potential administrator, considering whether or not to make the diet a policy for everyone? The rhetorical trick Gorski’s using here is in identifying the reader with a nebulous “we”, as in “should we put cancer patients on ketogenic diets?” You are meant to imagine a consensus, or an authoritative body. The medical profession, the government, something like that. This imagined “we” is the mirror image of the nebulous “they” that conspiracy theorists believe in, the “they” who doesn’t want you to know about cancer cures.

The overall effect of believing in an imagined “we” or an imagined “they” is to make social reality the primary reality. “We” or “they” represents a vague model of “society” — the “respectable” people, the “legitimate” and “reputable” people, the “consensus”. In other words, the tribal elders. If you have a positive association with “the consensus”, as Gorski clearly does, then you want to expel the “disreputable” from the consensus. If you have a negative association with “the consensus”, then you mistrust anything that sounds official and look for fellow mavericks and outsiders. In neither case are you primarily evaluating claims of fact; you are evaluating people.

For instance, the existence of Phase I/II trials of the ketogenic diet on glioblastoma ought to be good news for ketogenic diets. More evidence will soon come in; and the fact that the studies exist at all is further evidence that ketogenic diets are taken seriously by mainstream cancer researchers. However, Gorski treats this as an indictment of Seyfried, because he wanted to do an (uncontrolled) case series of ketogenic diets rather than the more thorough controlled studies. The overall intent of the blog post is to communicate Seyfried is disreputable, cancer is complicated, people who believe in cancer cures are beyond the pale, when one could have used exactly the same facts to make the point ketogenic diets are an exciting possibility for glioblastoma and the preliminary evidence is encouraging.

My own perspective can perhaps be summarized as “a contrarian worldview from mainstream sources.” Looking at ordinary sources like journal articles and historical primary sources, looking at uncontroversial claims of fact, often gives me a view of the world that is quite different from the “we”-based view where “society” is more or less getting things right. My object-level beliefs are rarely that unusual; the connotation of those beliefs is where I differ from most people. I don’t feel myself to be safely nestled in the lamplit circle of “we”; I feel like I’m outside, tumbling in the abyss, with only the frail spark of my mind to illuminate a small patch around me. And I think that, ultimately, the abyss is real, and the lamplit circle is imaginary.