Modesty is a Risk Factor for HIV.

Never suppose conspiracy where complexity will suffice.

Meta: One of my heroes, Cory Doctorow, made a tweet thread out of last year’s piece, A Monopoly on Poop, and it looks like I’m getting a lot of new subscribers from that. To all new readers: welcome! This post is a bit of a wild one, so please have a look at the ones mentioned in the welcome email if you’d like a better idea of what this blog is usually about, or check my most recent if you’d like to see me abuse science to conjure a fire-breathing dragon.

If any of my readers aren’t familiar with Cory Doctorow: he's like Leonardo DiCaprio for people who care earnestly and deeply about net neutrality, labor laws, and using technology to make the future more equitable rather than less. Check him out.

Long before we had “lab leak” theories of COVID-19, there was another virus, with origins that were equally fertile ground for conspiracy theorists’ speculations. Russian intelligence circulated the notion that it had been whipped up in a lab at Fort Detrick at the behest of the CIA, to rid the nation of drug addicts and gays. Anti-colonialist ideologues pointed to the nebulous and ever-nefarious white devil, or to the World Health Organization’s mass vaccination campaigns. Religious evangelists assured their congregations that it was the divine wrath of God punishing the sinners, like they always find a way to do.

The boring reality is that—like SARS CoV-2—the human immunodeficiency virus is a zoonosis, a lucky virus that made the jump from one animal host to another and, due to a variety of factors, was wildly successful in its new home.

But characterizing it as a single “lucky leap” glosses over some important facts about the history of the disease, and the way epidemics really happen. The story of HIV’s ascendancy into a global epidemic isn’t nearly so simple as the narrative around COVID.

How Did Humans Get a Chimp STD, Anyway?

It’s impossible ever to know the full story of the initial transmission, where a strain of Simian Immunodeficiency Virus (SIV) made the leap to humans and became HIV, but we can make some inferences. Key among them: we know it wasn’t a single event. It’s happened at least five times, and almost certainly many more, because there are at least that many genetically unique strains of HIV floating around.

SIV is incredibly widespread among other primates, with versions of the virus found not only in chimpanzees, gorillas, and monkeys, but even distant cousins like the lemurs of Madagascar, which last had contact with apes of the African mainland fourteen million years ago. This suggests that, not only has the virus been around that long, it was probably present in whatever common ancestor those animals had—meaning that as lineages of that ancient proto-ape diverged into the primate species of today, the virus came along, evolving and changing with them.

Often, as many as 90% of a given species in the wild will have SIV—although in most, it causes no discernible illness. The best explanation for this is that each species of primate has its own unique strain of the virus, and fourteen million years is a long enough time to figure out how to keep one pathogen in check. Critically, while there are documented instances of wild chimps etc. dying from AIDS-like illnesses, most of these appear to be the result of them succumbing to a strain of SIV that originated in a different kind of primate.

So: chimp-SIV doesn’t give chimps AIDS, but macaque-SIV does…if it gets into a chimp. This is important, because apes often eat other species of ape in the wild, and this is likely the main vector for interspecies transmission. After all, humans killing a chimpanzee for its meat—and in the process, getting blood in a wound sustained in the struggle—is the leading theory to explain how HIV first made its way into people.¹

Coupled with the apparently ancient nature of the virus, this suggests something kind of crazy: that SIV is so ubiquitous among primates because it offers a genuine fitness advantage—a defense against being eaten by other primates.

The Treaty

This is not the kind of fitness that’s visible at the scale of everyday events. Seen close-up, SIV looks like a pure detriment for the host, because even if the animal’s body can keep its SIV in check 99.9% of the time, the virus could always mutate to escape the immune system. That it is detrimental to its host in some way is supported the absence of a “native” SIV strain in humans: for the past million years at least, we’ve been at the top of the food chain among primates, which means there’s no fitness advantage to having monkeys that eat you get sick. Lacking a beneficial counterweight, the virus was selected out.

Up close, it doesn’t even seem to be a particularly good deterrent against predation. Your average lemur would probably prefer—I don’t know, a shell? Some other defense mechanism that lets it survive, rather than killing its predator months or even years later? Hell, they’d probably settle for being poisonous, or having a weird vestigial bone that serves no purpose other than getting lodged in predators’ throats once in a while. At least that would work on things besides other apes, and the predator would be likely to die before it has a chance to eat the rest of your family.

But Darwin doesn’t do requests, and he’s usually got bigger plans than a little lemur could even imagine. After all, if you zoom out on the lemur with the “choking bone”, the selection pressure it applies on its predators would only serve to make them smarter, or more dextrous in the long run. From this perspective, SIV is one of the only evolutionary defense mechanisms that’s actually worked against that apex of apex predators, Homo sapiens: people have undoubtedly gotten a lot more leery about eating “bushmeat” than they used to be before HIV/AIDS.

The further you zoom out, the fitter this system of biological retribution becomes. A poisonous creature might kill its predator immediately, but interspecies SIV—being transmissible and having a long latency time before it gets lethal—offers a chance to get their whole family, or even relations beyond that. This creates an evolutionary dynamic where any primate snacking on other primates stands a nonzero chance of getting the entire local population of its species killed.

From Hell’s heart I stab at thee…and thy wife…and thy wife’s boyfriend…and their kids…

This is what I meant earlier, when I said that HIV has made the jump to humans five times, “and almost certainly more”: People have been eating chimps and other apes since…well…since whenever we started looking different enough from them that it didn’t feel like cannibalism. Probably even before. How many times, before we became a globe-spanning society, did this defense system work perfectly? How many remote tribes of humans were wiped out entirely, taking with them their customs and practices, their recipes for ape tartare?²

There’s no way to know.

In a very strange way, SIV is a peace broker. It’s a living truce—or at least a deterrence treaty—flowing in the bloodstream of half the humanoid species on the planet. The evolutionary pressures it has exerted mean that primates alive today are the products of fourteen million years of natural selection favoring a tendency, upon seeing a smaller primate in the forest, to think “Meh” and opt to try and find something else for lunch instead.

Here, zooming out even further, we see another level of fitness emerge: Not for the individual, or even the species, but the entire order becomes fitter from the existence of the simian immunodeficiency virus. Every ape can thrive when they don’t have to worry as much about other apes as predators. A relic of their shared heritage, it’s a weakness to each of them. But in that weakness against each other, there’s unity. That’s strength for the whole branch of the tree.

Monkey See, Monkey Do

Zoonosis-as-a-defense could strengthen any branch of the tree of life in this way,³ but it’s worth thinking about the fact that this particular one emerged in ours. Primates are a social and relatively intelligent bunch of animals. Probably our greatest advantage is that we learn from others of our own kind by watching. It’s memes, (in the classic Richard Dawkins sense of the word) rather than genes, that provide the greatest leaps in fitness in the shortest amount of time.

Consider the aye-aye, which has spent the past few million years growing a very long middle finger which lets it fish grubs out of holes in tree stumps. All it takes is one monkey figuring out how to use a stick for the same purpose, then showing its friends, to begin putting the local aye-ayes out of business.

So it's interesting to me that, among pre-human primates, SIV creates an evolutionary pressure that incentivizes the development and understanding of a pretty complex rule; a taboo.

Thou shalt not eat other primates.
Also, thou shalt not have sex with them, thou freaks.⁴

The basic “taboos” that apply to nearly all life, such as thou shalt not eat things that have been dead a while don’t need to be learned. They’re built-in based on things like smell. But deterring predation among primates is something that requires the animals involved to do some complex classification. “My kind / not my kind” is easy enough, but now we need an intermediate category: my kind-ish. Not similar enough to be a potential mate or rival, but not different enough to eat.

This is a hard thing to communicate without language, and it isn’t something you’d expect the average animal to be able to figure out for itself in one lifetime…but nevertheless, for millions of years, we’ve been subject to this selection pressure favoring the capacity to abstract, categorize, and recognize patterns; to notice that a brother or a cousin got sick and died a little while after he ate that mangabey, and that maybe eating anything that looks too much like you is a bad idea.

So it’s interesting that the branch of the tree of life which has been subject to this weird kind of pressure is the one that eventually bore, as fruits, human beings—with the capacity for things like morals, laws, and superstitions. To what extent did this disease, and the constraints it imposed, help shape us as a species?

THIS 💩 IS 🍌

Okay, enough background. I’ve spent so long here exploring the ancient, intimate nature of our relationship with this virus because an understanding of this relationship is necessary, in order to believe what I’m about to tell you next, which is that there are a surprising number of natural HIV inhibitors, some of which appear to be effective at the concentrations you find in nature.

One such inhibitor is found in another species that has an ancient and intimate relationship with primates: the banana plant.

The inhibitor is a special type of sugar-binding protein called a lectin,⁵ and this particular one—called BanLec—is found in the fruit of ripe bananas. It sticks to the sugars on the surface of the human immunodeficiency virus, and inhibits its ability to get into cells.

I’m always wary when I hear about a natural product with an effect profile that seems too good to be true. Usually, if you read the fine print in a study that says something like “blueberries cure cancer”, it turns out you’d need to eat three times your weight in blueberry concentrate to reach the doses they used in their experiments. But that’s not the case here: BanLec’s IC50—or the concentration necessary to reduce a sample of the virus’ infectivity by 50%—is in the nanomolar range—similar to some of the best modern antivirals. Some napkin math with the figures from this paper reporting yields from a BanLec purification protocol shows that your average grocery store banana should have enough in it to bring a liter of liquid up to that concentration.

Now, this is…bananas. While it makes total sense that the fruit would want primates (its main seed dispersal vector) to be healthy, a protein like BanLec shouldn’t be able to make it into the bloodstream intact. Molecules that big don’t get absorbed without specialized transport mechanisms, and I don’t believe in coincidences at nanomolar affinity, so this suggests it must have some mechanism of action in the GI tract.

So what’s going on here? One possibility becomes apparent when you think about which primates the banana wants to encourage fitness in, i.e. those that will propagate its seeds most effectively. Consider the chili pepper: most fruits “want” to be eaten—so why is this one full of pain? The answer is that, unlike the seeds of a watermelon or apple, the seeds of a pepper are easily destroyed in mammals’ digestive tracts, so we’re a dead-end for the plant. Birds’ digestive tracts, on the other hand, pass pepper seeds through unharmed—and they don’t have the same “spicy” receptors we do.⁶ ⁷

Likewise, a monkey that’s too small to comfortably swallow and poop out the seeds of a banana is going to eat around them—which isn’t really fulfilling its end of the bargain, in exchange for the tasty part of the fruit. Because we’re so used to seedless cultivars, harvested while still green and then artificially ripened after shipment, a lot of people have probably never even thought about a banana seed, much less seen one—but they’re big enough that they might give a small monkey like a vervet a hard time.

They’re itty bitty! [Image Credit: Wikimedia User Charles J. Sharp (CC BY-SA 4.0)]

As a consequence, the banana plant has an incentive not only to attract and reward larger primates, but also to give them the ability to eat the small ones without suffering the consequences. Say a bonobo has been keeping his eye on a particular banana plant, as its fruits ripen. One day, checking in on it, he finds an interloping vervet there, stuffing its little face, and spitting out the seeds. The banana plant likely isn’t happy about this; those seeds will take root in the shade of the mother plant, and end up competing for nutrients, water, and sunlight. Maybe BanLec’s job is to allow the chimp to gobble up the vervet, wash it down with a few bananas for desert, and rest easy—before excreting the banana plant’s seeds into an extra nutritious pile of dung, one GI transit time later.

If SIV represents a truce among the primates, maybe BanLec embodies a later alliance—one that let the great apes break the original truce.

This probably isn’t BanLec’s only purpose, of course. It likely also helps primates maintain control over their “native” strain of the virus, or even keep another species’ strain at bay if they get infected: acute-phase HIV spends a lot of time hanging out in the GI tract, where the antiviral protein might actually do some good, even if it’s not absorbed.

Obviously, this is not to suggest that people go off their HIV meds in favor of bananas. That research has actually been done, horrifyingly enough, and it didn’t go well: Back in 2007, the president of The Gambia rose to international infamy for claiming to be able to cure AIDS, and requiring his “patients” to go off their actual meds while under treatment. His substitute regimen included a secret potion made of various jungle herbs, and—wouldn’t you know it—a hearty helping of bananas.

Curiously enough, this was three years before the first scientific reports of BanLec’s HIV-inhibiting properties came out, which makes me think there’s a degree of legitimacy to the then-president’s claim that his controversial cure was based on traditional medicinal knowledge. If knowledge of a natural treatment for HIV/AIDS were to come from anywhere, the oral traditions of the riverland jungles on the continent where our species first evolved is exactly where you’d expect to find it. Pity it didn’t work very well; apparently a lot of people died as a result.

Enough Monkey Business

One other thing to know about lectins is that they’re very resistant to digestion—which means that BanLec would likely be just as effective by the time it reached the colon as when it started out. This raises another interesting possibility: that BanLec might be acting as a kind of PrEP—reducing transmission of the virus within a species. While it’s hard to know what percentage of wild primates owe their SIV+ status to receptive anal sex, the behavior is common enough among many species that it’s probably a transmission vector of some importance.

In humans though, we don’t have to guess—in 2018, 65% of all new HIV cases in the US were attributable to “male-male sexual contact”, according to the CDC.

Now, I expect the average reader would balk at the idea that a banana-rich diet might reduce the risk of getting HIV. I did, at first—partly because the sex education curriculum where I grew up was very focused on encouraging abstinence, and using fear as the primary means to achieve that. Whether it was pregnancy, herpes, or HIV, the key takeaway we got was: it could happen your first time.

But looking at the actual numbers, I was surprised to learn just how low-virulence HIV really is: bottoming for someone who is HIV+, you’ve got a roughly 1 in 74 shot of contracting the disease. That’s an average from a meta-analysis, but the variance across studies is pretty wild, too; one estimated a risk of roughly 1 in 29, while another pegged it at less than 1 in 200.

But probabilities are just statements about our uncertainty; at the end of the day, whether it happens or not comes down to concrete things like the infected person’s viral load, whether their partner has skin tears or lesions, and a million other things. With numbers in the neighborhood of 1% to start with, it suddenly doesn’t sound so crazy that something like a dietary factor could influence your risk.

The Importance of Being Dirty

There’s another natural molecule that has activity against HIV, and which seems likely to have a big impact on transmission risk. Unlike BanLec, this one is endogenous to the human body. It’s a chemical called bilirubin.

You might have heard of it from its use in blood tests for liver function. It forms as a breakdown product of heme (the red pigment in your blood cells), and gets excreted into the GI tract by the liver. If your liver isn’t working so well, bilirubin starts to build up in your bloodstream instead, and—because it’s bright yellow-orange—you start to look a little like a character from the Simpsons.

Once your liver squirts bilirubin out into the GI tract, though, it gets transformed by gut bacteria into other “bile pigments”—and it turns out that both bilirubin itself and these transformation products are effective inhibitors of the molecular machinery that makes HIV run. Here, the necessary molar concentrations are about a thousand times higher than for BanLec—but the molecule is hundreds of times smaller, and hundreds of times more abundant. Not only are these compounds abundant enough in stool to reach the concentrations that inhibit HIV activity; they’re abundant enough to be seen with the naked eye. One of these bile pigments, stercobilin, is the reason why poop is brown.

As strange as it may seem, this has deadly serious implications for public health. An awful lot of gay men use bowel enemas before sex, to avoid the embarrassment of getting shit on their partner’s dick. In the process, they might be leaving themselves vulnerable to something a lot worse than embarrassment. A 2013 study found some alarmingly strong associations between enema use before “receptive anal sex” and risk of contracting HIV, even when controlling for every possible other variable.

The authors of that paper end their writeup by emphasizing the need for better enemas, under the assumption that it’s things like an improper salt balance in the product, disrupting the physical barriers which would ordinarily prevent HIV from entering the bloodstream. But if bile pigments are a major driver of that effect, it’s the shit itself that’s protective. It would mean you can’t engineer around it unless you also made the enema itself brown. It would mean the most sensible public health policy move is something more like an ad campaign aimed at convincing people to embrace shitdick.

But wouldn’t that just be the way? A tale as old as time, like making cigarette filters out of asbestos. Nature, in her infinite wisdom, equips us with an automatic barrier against this ancient and deadly disease, and then humans go and invent things like modesty and cleanliness, and fuck it all up. After all, what got Adam and Eve kicked out of the garden of Eden? It wasn’t eating the fruit of knowledge—go back and have a look at the text. God didn’t notice when they ate the fruit…or at least, pretended not to. The thing that gets them in trouble is modesty; it’s only when they start trying to cover their junk that God goes ‘ᴡᴀɪᴛ ᴀ ᴍɪɴᴜᴛᴇ, ᴡʜᴏ ᴛᴏʟᴅ ʏᴏᴜ ʏᴏᴜ ᴡᴇʀᴇ ɴᴀᴋᴇᴅ?’ and gives them the boot. Had they but played it cool, dick out, tits out, unbothered—they might still be in the Garden today.

Despite what the televangelists say, HIV isn’t a punishment for sins of the flesh. If anything, it’s a punishment for forgetting where we came from—for breaking the blood truce and eating our chimpanzee cousins, for leaving our old ally the banana behind us, for pretending we’re too good to get a little shit on someone we love.

—🖖🏼💩

1. I tried to have DALL-E make me a photo of a chimp and a human sharing needles for intravenous drug use, but it didn’t really work. Probably for the best.

2. A shame the world will never know the cookbook “How to Eat Macaque”

3. If I had to guess, I’d say this dynamic is probably quite common. After all, viruses have the easiest time making the “jump” between branches of the tree of life when they’re close together: the new host needs to be similar enough to the native host that the infective process can still work, but different enough that its immune system isn’t fine-tuned to deal with the pathogen in the same way as the native host.

4. Two of the three fundamental ‘F’s of life, out right off the bat! An interesting side-effect of the disease’s sex-transmissibility is that—while this strengthens the primate order as a whole, it would also encourage speciation within it, by discouraging “back-crossing” hybridization among species that had recently diverged from one another. There’s a meme about how the existence of the “uncanny valley” phenomenon—the feeling of revulsion aroused by things that look almost human, but not quite—implies that at some time in our history, there was a distinct survival advantage to being creeped out by things that look like a human but aren’t. While this is usually left on a note of woooOOOOOooOOo beware the skinwalkers!, I think it’s far more reasonable to interpret that as evidence of this disease-avoidance process starting to make its way into our hard-wiring, the same way rot-associated chemicals like putrescine trigger an automatic “do not eat” reflex.

5. Not to be confused with lecithins or leptin. As an aside: most lectins are not as friendly as BanLec. See: the ones in red kidney beans that will literally murder you if you try to eat them without cooking ‘em first.

6. The peppers, of course, never counted on something as deranged as a human being—which will deliberately inflict burning pain upon itself just to feel something—coming along. Then again, we also went and invented agriculture, so there are probably more peppers now on Earth than ever before, and maybe it’s a net win for them.

7. If you need further proof that peppers are “for the birds”, think about their shape and color. If you were designing an object to be easy for birds to spot in a forest, wouldn’t you want it to look as much like a beak as possible?