Use Tools For What They’re For

*Maybe there isn’t and can’t be a simple heuristic you can teach everyone in school or via a PR campaign which will lead to them having making good health decisions in an adversarial information environment, without having any negative effects anywhere else. But you also don’t want people to make bad health decisions. So what do you do? *- Scott Alexander, Ivermectin: Much More Than You Wanted To Know The favorite catchphrase of critics of using ivermectin against COVID-19 isn’t "follow the science" or "believe the experts." They say "IVERMECTIN IS A HORSE DEWORMER!" And in response, ivermectin supporters say things like: MAGAA Puppy is factually correct in the two "Me:" statements.

• From the FDA’s article Why You Should Not Use Ivermectin to Treat or Prevent COVID-19, "The FDA has not authorized or approved ivermectin for use in preventing or treating COVID-19 in humans or animals. Ivermectin is approved for human use to treat infections caused by some parasitic worms and head lice and skin conditions like rosacea."

• And here’s an example of one of the in vitro studies MAGAA Puppy might have been referring to. I don’t know if there are numerous studies, but let’s take his word for it for now. MAGAA Puppy’s critics aren’t disputing these facts. As we know, the reason they emphasize the "horse" in "horse dewormer" is that some people may have been taking horse-size doses of ivermectin and dying from it. I am suspicious. The FDA only claims to have "received multiple reports of patients who have required medical attention, including hospitalization, after self-medicating with ivermectin intended for livestock." I see no mention of death on the FDA’s web page. But if we’re tentatively accepting MAGAA Puppy’s claims about "numerous studies," let’s also tentatively accept critics’ concerns that consumption of veterinary doses of ivermectin is a serious public health concern right now. Critics of ivermectin as a COVID-19 drug are saying that "large doses are unsafe, and small doses are probably not effective." Supporters are saying that "small doses are safe and FDA-approved for human use, and some studies suggest they may be effective." I firmly side with the critics. But why? MAGAA Puppy has probably read more studies than I have on ivermectin as a COVID-19 treatment. It wouldn’t be a high bar to clear. I also think that the "it’s a HORSE dewormer" line is missing the point and is a terrible example of public messaging. I suspect that critics misunderstand why ivermectin supporters are interested in the drug as a COVID-19 treatment, and are choosing a poor line of argument that is failing to persuade or spread necessary and true information about why we should be critical of ivermectin for COVID. My hope is not only to correct this line of thinking, but to show how a simple heuristic could have lead to better outcomes in not only this case, but in several other epistemic debacles of the COVID-19 pandemic. Drugs are a tool. Some tools can be effective at tasks they were never designed for. The other day, I used a the sheet of glass from a picture frame as a straight edge while cutting a mat board for the photograph I was framing. My mom puts salt on the slugs in her garden to kill them, even though salt wasn’t designed by anyone, for anything. But most of the tools we use every day were designed by a human to accomplish a specific task, and they are overwhelmingly most useful for that particular job. A hammer can be used for a few things besides hammering in a pinch, but not too many. Mostly, a hammer is for hammering. Cups are mostly for drinking out of, and for things very similar to their original purpose of holding small quantities of liquid. Occasionally, a tool can be used for a side purpose, one for which it was not originally intended. Hammers can be for bell-ringing and battle and carnival games. In all cases, this is because the shape or mechanism of the tool happens to fit the target, such as a boxing ring bell or the skulls of one’s foes. Drugs can also be reused for a side purpose. This is called "off-label prescribing," and one in five prescriptions in America is off-label. If we could list out all the many, many activities that people do around the world, for how many of those activities would a hammer be a useful tool? For a vanishingly small fraction. I can’t use a hammer to plant roses, blow my nose, get to work, or pay my taxes, at least without a whole lot of creativity! I forgot to mention that hammers also make excellent wall-hangers.The reason we can often find side purposes for tools is because people understand the tool’s shape and mechanical properties, the activities they do on a daily basis, and can find a few additional cases where the tool would be helpful. That same intuition applies to drugs. We generally discover drugs in one of two ways. One is to identify a molecular target and try to design a tool that would affect the target in a desirable way. This is like choosing a location on a river, and trying to design a bridge to get across it. The other way is to screen many compounds for their medical usefulness, and see what effects they have. That’s a bit like planting a packet of unlabeled, mixed seeds from all around the world and seeing what grows. If you try to repurpose a bridge design for another river, you’ll have to consider your crossing site very carefully, or else the bridge probably will not accomplish what you need it to. Likewise, if you hope that a particular seed in your packet of mystery seeds will turn out to be a daikon radish, you’re likely to be disappointed. Ivermectin, and really any drug not deliberately designed either to bolster the human immune system or to fight viruses (and more specifically COVID-19), is deeply unlikely to be directly effective against COVID-19 for the same reason your mystery seed is unlikely to be a daikon radish. In general, it’s wise to use tools for what they’re made for, unless you have a clear, compelling idea of how the shape of that tool will be useful for the physical demands of some other task. Even then, tread carefully, and only proceed if you have an opportunity to gather compelling evidence. When I used the glass sheet as a straight-edge, the ragged edge scraped ink off of the photo and permanently damaged it. I think that critics should stop emphasizing the "horse" in "horse dewormer," and start emphasizing dewormer. Ivermectin doesn’t bolster the human immune system to help it fight against helminths. Nor does it reduce the harmful side-effects of an immune response. Ivermectin is a worm poison.

Ivermectin and its related drugs act by interfering with the nerve and muscle functions of helminths and insects. The drug binds to glutamate-gated chloride channels common to invertebrate nerve and muscle cells. The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, paralyzing and killing the invertebrate. Ivermectin is safe for mammals (at the normal therapeutic doses used to cure parasite infections) because mammalian glutamate-gated chloride channels only occur in the brain and spinal cord: the causative avermectins usually do not cross the blood–brain barrier, and are unlikely to bind to other mammalian ligand-gated channels. So ivermectin is effective against worms because it binds and opens chloride channels in nerves and muscle cells. It’s safe for humans because it doesn’t have anatomical access to any of our own cells that have these channels. This mechanism of action will be completely ineffective against viruses, because viruses don’t have cells at all. They’re closer to the size of a single receptor than to the size of a cell, and they’re not even really alive. When critics emphasize the "horse" in "horse dewormer," they may be taken as implying three things, whether they mean to or not:

• People shouldn’t take horse-size doses of ivermectin because it’s unsafe for humans at such high dosages.

• People shouldn’t take ivermectin because it’s for animals, not humans.

• Ivermectin is ineffective against COVID-19 because its mechanism of action is particular to horse physiology, perhaps because ivermectin works by stimulating the horse’s immune system or something. Only the first of these implications is correct. My guess is that many ivermectin supporters would like to take human-size doses, if they were conveniently available. But to get an ivermectin prescription, you have to go through a doctor, and they already know what kind of response they’ll get if they ask their doctor for an ivermectin prescription for COVID-19. So they get it from the farm store. Ivermectin opponents don’t want to have to become biomedical experts to carry the day in this debate. Ivermectin supporters probably don’t want to have to do that either. Nobody in this debate wants to catch COVID-19. Both sides think they are following the science, using their common sense, and doing their due diligence. My guess is that much of this confusion could have been avoided if both sides stuck to a heuristic of using tools for what they’re for. Focus on the tool and what it was originally designed to do. Then consider the new task for which you’re considering repurposing it. Why do you think the physical shape of the tool will fit that purpose? Or what is similar about the physical dynamics of the original and new task, so that you expect the old tool will fit the new task? Only once you’ve answered these questions does it help very much to gather evidence. Imagine that you’d found 100 scientific studies showing that shovels are great for brushing your teeth. Would you believe them? No, of course now. You can visually imagine what it would be like to brush your teeth with a shovel, and conclude that it will not work. And besides, digging holes is nothing like brushing your teeth. All those scientists are being dummies. With ivermectin, or any other drug, you lack the ability to visualize how the drug will physically affect the new biological system you’re using it against. So all you’re left with is considering the task at hand. Of course, COVID-19 and intestinal worms are both diseases, but just about anyone is aware that not every drug is good against every disease. Ivermectin is a dewormer. It is not an antiviral, and never was designed for that. Nor is it for bolstering your immune system or use as an anti-inflammatory. So you can pretty much write off ivermectin as a COVID-19 drug in the absence of flagship-quality evidence in favor of it. If the FDA approves ivermectin for COVID-19, and scientists come to consensus on the mechanism by which it is effective for that purpose, I’ll change my mind. I don’t need to know what that mechanism is, or evaluate the evidence myself. I think this heuristic works for other pandemic debates as well.

• Clinical masks were designed to prevent the transmission of infections, and are widely used for that purpose by people with skin in the game (doctors and nurses). So you can assume they’ll work against COVID, since they’re being used for the same purpose.

• Vaccines were designed to help your body resist infections. Those that survive clinical trials have strong evidence to support the claim that they do in fact work. Likewise, the new drugs for COVID, Paxlovid and molnupiravir, were designed for that job and have strong evidence behind them.

• Strict, total lockdowns are designed to prevent viral transmission above all else. Moderate lockdowns are designed to balance slowing the spread with many other concerns, such as economics, freedom, and politics. As such, you should be a lot less confident that they work. You don’t have to know exactly how the tool works. I don’t know how my blender works, beyond the fact that it has blades and spins around. Why are the blades at that angle? How does the motor cause them to turn? Why are the walls shaped with that curve? I don’t know, and I don’t care. I just know that the manufacturer designed it to be an effective blender, and tested it out before selling it. So I start by trusting that it will blend, until proven otherwise. Likewise, Pfizer and Merck and all the rest of these big pharmaceutical companies designed their vaccines and drugs to fight COVID-19, and gathered lots of flagship-quality evidence to bolster their claimed success. Nobody with serious standing challenges these claims. So we should start by trusting that their products do, in fact, work. Note that this heuristic also often allows us to come to the right conclusion when the experts are right and when they’re wrong, without putting much thought into it. This heuristic will have some failure modes. It won’t work as well against an (at best) mediocre tool, like aducanumab. This drug was designed for the purpose of treating Alzheimer’s, and it got FDA approved for that purpose. The fact that this was immensely controversial doesn’t helps, by this heuristic. How do we know that the detractors aren’t just the equivalent of anti-vaxxers? It also won’t work well against externalities, as we see with climate change. Gas-powered cars work perfectly well for their advertised purpose of driving, and the CO2 you release from your own personal driving will barely affect you. And it won’t work well when the experts are misguided, make mistakes, or lack integrity. Perhaps their tests are inadequate, or the tool’s real purpose is not what it seems. We deal with this daily, when we consider issues like inadequate testing of the effects of herbicides on wildlife, or the effects of a social media ecosystem that is built primarily to generate advertising revenue rather than to improve social relations. But a rule of thumb isn’t meant to be a conclusive answer. Ideally, we use it with other heuristics, other forms of common sense, to come to a sensible decision. Perhaps "trust your tools, and use them for what they’re for" is a neglected piece of common sense in our era. Many people are surrounded by messages of concern that our tools are making us unhealthy, poisoning the planet, motivating or facilitating murder and suicide, alienating people from one another, causing addictions and unhealthy obsessions, spreading misinformation, and putting the future of humanity at risk. While acknowledging that these problems exist, we don’t have to blame the tools that give rise to them. Instead, we can focus on the tools that solve them. Exercise and a healthy diet promote health. Carbon taxes and solar panels can help solve climate change. Adequate and compassionate policing and mental health services can reduce murder and suicide. Friendship and anti-anxiety medications can reduce alienation. Hobbies and drug treatment programs can help dissolve destructive habits and form better ones. Reading credible sources and consulting with experts helps reduce misinformation, even if it doesn’t remove all the risk of going wrong. And there’s lots of research and action going on into safeguarding the future of humanity. The problem is perhaps not inherent in our tools, but lies in our failure to understand their purpose or make adequate and timely use them.