The Trouble with Testosterone
Page 15
And unlike the potato chip chemical, thiarubrine occurs in Aspilia in high concentrations. It’s not widespread in nature, however. It is known to be present in several members of the sunflower family, such as Ambrosia, but its special properties weren’t discovered until 1984, when it was found in the plant Chaenactis douglasii, used by native Canadians to treat skin sores.
Thiarubrine is an exceptionally potent drug. It kills a wide range of fungi, bacteria and nematodes at low concentrations as well as or better than commercial preparations do. Thiarubrine is antiviral, has been found to reduce some solid tumors and has inspired three patent applications for its medicinal potential. That’s more than one can say for the average potato chip chemical.
Even if Aspilia leaves are used medicinally, however, experiments so far have failed to determine their chemical value. In fact, the botanist Neil Towers of the University of British Columbia and his colleagues, despite repeated effort, have failed to find thiarubrine in the leaves, though the chemical is always present in the root of Aspilia. There is a growing body of evidence that Aspilia might actually be swallowed for its physical properties. Two of us, Huffman and Richard Wrangham, report in a forthcoming article that all the African apes swallow leaves and that all the leaves swallowed have one unifying feature: rougher (“hairier”) surfaces than typically occurs on leaves in ape habitats. Perhaps there is some unknown benefit to swallowing a rough leaf; or perhaps there are desirable chemicals in the trichomes, as there are in some plant families such as the Asteraceae, to which Aspilia belongs. The search for answers goes on.
Of course, as Mr. Sapolsky notes, the critical evidence of self-medication will be consumption of medicinal plants by sick animals that subsequently get well. For chimpanzees, the evidence is anecdotal but striking. Huffman has twice observed patently sick chimpanzees in the Mahale Mountains National Park, in Tanzania, selecting a common plant item that is used hardly ever (possibly never) by healthy chimpanzees—the pith of Vernonia amygdalina, another medicinal plant used by people in many parts of Africa. In each case, the chimpanzees meticulously removed the leaves and outer bark from several young shoots and chewed on the exposed pith, sucking out the bitter juice. The animal’s rate of recovery was comparable to that of local people, the Tongewe, who use the plant as a treatment for similar symptoms. The chemistry of V. amygdalina is well known. There are two major classes of bioactive compounds, sesquiterpene lactones and steroid glucosides. As with thiarubrine, those compounds have demonstrated exceptional antiparasitic activity. And yes, Mr. Sapolsky, those drugs are rare in the chimpanzee environment. Chewing the Vernonia pith may well become the first proven case of chemical self-medication in nonhuman primates.
Far less is known about any direct effects of plants on primate fertility, but the possibilities are compelling. Take the exploitation of Enterolibium contortisiliqiuim fruits by muriquis, the largest and one of the rarest of South American monkeys. What drew the attention of another of us, Karen B. Strier, to Enterolibium, compared with other fruits in the muriquis’ diet, was the special journeys they made to the edge of their forest to reach the Enterolibium fruits. Muriquis consume the fruits only at the onset of the mating season. Interestingly, the fruits contain high levels of stigmasterol, a substance with well-documented effects on fertility in sheep and humans. The effects of stigmasterol on muriqui reproduction are not yet known, but these observations now make them a topic of considerable interest.
Since the first publications of Aspilia’s properties a range of observations has shown that elephants, bears, coatis, and capuchins all use natural chemicals as something other than food. We can take such anecdotes and build them into evidence. In an era of shrinking biological resources, we don’t think it’s such a good idea to rely only on studies of rats. Let’s keep an open mind about ways of exploring the natural world. Who knows, out of little Aspilia leaves big zoopharmacognosies might yet grow.
Richard Wrangham
Harvard University
Cambridge, Mass.
Michael Huffman
Kyoto University
Kyoto, Japan
Karen B. Strier
University of Wisconsin
Madison, Wisconsin
Eloy Rodriquez
University of California
Irvine, California
And my reply:
I am pleased with the letter of Richard Wrangham et al., in that a careful reading of their letter and my piece shows substantial agreement. The authors of the letter, who are leaders in zoopharmacognosy, and I concur that the instances they postulate as being animal self-medication have not yet been proved, nor have the explanatory mechanisms underlying any putative cases. I’m sure they also agree with me that the science writers and members of the lay public who jumped to the conclusion that their exciting findings constituted proof need to be gently taught the pieces still to be filled in. That was the aim of my review.
In considering the as yet unproved premise that animal self-medication exists, I made heavy use of the potato chip example. I can assure the authors that I don’t believe potato chips and Aspilia taste the same. The point of that example was that for chimpanzees to prove that humans self-medicate with potato chips, or for humans to prove the same about chimpanzees and Aspilia, the same things must be demonstrated: First, the food must have enough of the putative medicine to be curative under the conditions consumed. As the authors note, that has not yet been shown for chimpanzees and Aspilia. Second, the food must be relatively unique in possessing such a quantity of the compound. The authors note that such is the case for Aspilia and thiarubrine; to my knowledge, this is their first report of that fact. Third, sick animals must go out of their way to consume that food. In their letter, the authors present pleasing but anecdotal reports that chimpanzees have done so. Thus evidence is beginning to accrue in favor of that case of animal self-medication. As I noted in my piece, I’m delighted to see this take place—once it is proved, I’m as taken with a romantic fact as the next person.
The second speculative area regards the mechanisms underlying any animal self-medication. In contrast to the authors’ reading of my piece, I do not think that such mechanisms are “exclusively concerned with learning.” As I stated, “Social learning may go far to explain the phenomenon.” I am quite open to explanations that invoke more physiological mechanisms once anecdotal reports are translated into more experimental evidence.
Finally, as a fellow primatologist and field biologist who understands the difficulty of studying rare and spontaneous events in animals other than the laboratory rat, I am pleased that we all agree in our conclusions. Whether or not zoopharmacognosy provides us with new drugs already used by animals that are trained (or intuitive) pharmacists, there are numerous other animal skills to be learned about along the way that more than justify these studies.
In other words, we were being a bunch of academics having a fine time arguing with each other over something. Since then, progress has been made on a number of fronts in zoopharmacognosy toward meeting some of the criteria discussed. Huffman and colleagues have continued to observe chewing of the bitter pith of Vernonia amygdalina and have recently reported that such chewing by a chimp with flatulence and diarrhea was associated with a drop in the amount of parasites in the animal’s feces over the next day; the active compound in the plant remains unclear. Wrangham has recently shown that the rates of leaf-swallowing increase among chimps during times of tapeworm infestation. Both Wrangham and Huffman have obtained evidence suggesting that it is not so much the chemical properties of some of these leaves but their mechanical properties that might have medicinal effects—specifically, it looks as if intestinal worms get trapped in the rough hairy surface of the intact leaf as it moves through the intestinal tract. And in a recent review speculating on the mechanisms by which putative medicinal plant use may be acquired, Huffman and Wrangham emphasize a route heavily dependent on Rozin’s and Galef’s work—during times of illness, animals become
less averse to novel foods, and social observation and learning play a large role in the propagation of any discoveries about medicinal plants. Obviously, more work is needed on this fascinating subject and, just as obviously, a critical plug must be made at this point—none of this is going to matter much if we keep destroying the rain forests. No one, regardless of their species, can learn much pharmaceutical science without a pharmacy.
FURTHER READING
For general overviews of zoopharmacognosy, see E. Rodriquez and R. Wrangham, “Zoopharmacognosy: The Use of Medicinal Plants by Animals,” in K. Downum, J. Tomeo, and H. Stafford, eds., Recent Advances in Phytochemistry (New York: Plenum Press, 1993), 27, 89; M. Huffman and R. Wrangham, “Diversity of Medicinal Plant Use by Chimpanzees in the Wild,” in R. Wrangham, W. McGrew, F. de Wall, and P. Heltne, eds., Chimpanzee Cultures (Cambridge, Mass.: Harvard University Press, 1994), 129; K. Strier, “Menu for a Monkey,” Natural History, February (1993):42; and A. Gibbons, “Plants of the Apes,” Science 225 (1992): 921. These contain references to the more technical reports. Huffman’s recent report of a drop of parasite load after feeding on Vernonia amygdalina can be found in M. Huffman, S. Gotoh, D. Izutsu, K. Koshimuizu, and M. Kalunde, “Further Observations on the Use of the Medicinal Plant Vernonia amygdalina (Del) by a Wild Chimpanzee, Its Possible Effect on Parasite Load, and Its Phytochemistry,” African Study Monographs 14 (1993): 227. Wrangham’s recent report concerning the correlation of leaf-swallowing with tapeworm infestation is found in R. Wrangham, “Relationship of Chimpanzee Leaf Swallowing to a Tapeworm Infection,” American Journal of Primatology 37 (1996): 297. [The recent studies suggesting it is the mechanical, rather than chemical, nature of the leaves that is medicinal can be found in: E. Messner and R. Wrangham, “In vitro testing of the biological activity of Rubia cordifolia leaves on primate Strongyloides species,” Primates 37 (1996): 105—and in M. Huffman, J. Page, H. Ohigashi, and S. Gotoh, “Leaf-swallowing by chimpanzees for the control of strongyle nematode infections: Behavioral, chemical, and parasitological evidence.” Congress of the International Primatological Society, Abstract 566.]
References for additional work cited in this piece: T. Scott and G. Mark, “Feeding and Taste,” Progress in Neurobiology 27 (1986): 293. P. Rozin, “Acquisition of Stable Food Preferences,” Nutrition Reviews 48 (1990): 106; also see P. Rozin and T. Vollmecke, “Food Likes and Dislikes,” Annual Review of Nutrition 6 (1986): 433. Rozin’s reviews also discuss the classic cafeteria experiments by Curt Richter. The sauce béarnaise syndrome is discussed in M. Seligman, Biological Boundaries of Learning (New York: Appleton-Century-Crofts, 1972), 8. See also: B. Galef and M. Beck, “Aversive and Attractive Marking of Toxic and Safe Foods by Norway Rats,” Behavioral and Neural Biology 43 (1984): 298; and B. Galef, “Direct and Indirect Behavioral Pathways to the Social Transmission of Food Avoidance,” Annals of the New York Academy of Sciences 443 (1985): 203.
The Dangers of Fallen Soufflés in the Developing World
Michael Poulton, All States Are Full of Noise, 1995; courtesy the artist
Then there was the summer that I took Joseph Odhiombo’s11 blood pressure once a week and, as a result, ate like a hog.
I was spending that summer, as I had for years, living in a tent in the far corner of a game park in Kenya, conducting stress physiology research. Each week, I’d drive thirty miles to the park headquarters to get some gasoline, pick up my mail, have a soda at the tourist lodge. Joseph had recently returned to the lodge as its manager. We had met years before, when I was starting my work and he had an entry-level position in the lodge. Someone in the multinational hotel chain had spotted his competence and discipline, and Joseph had rocketed up the corporate ladder, being transferred here and there among their establishments, learning the ropes. And now he had returned triumphantly to his original lodge, the flagship of the hotel chain, its manager at the inordinately young age of forty.
We were delighted to encounter each other again. His success showed; in the previous decade, Joseph had grown plump, more than plump, a rotund man in that African status symbol, a tailored leisure suit. And he had a problem that he confessed to me on our first meeting—he was suffering from severe high blood pressure. His doctor in Nairobi was worried, as he hadn’t quite come up with a drug yet that was working. Joseph was openly anxious as to whether his life was in danger. It somehow came out that I had a blood pressure gauge, and soon I had volunteered to take his pressure each week. And so evolved our ritual.
It was one that flourished into ornate detail, as befit his role as chief of this pseudovillage. I’d arrive to find the corridor outside his office filled with excited underlings, lodge employees hoping to have their blood pressure read during the interim when I waited for Joseph to receive me. These were typically Masai tribesmen, only a few years out of the bush, who knew and cared nothing about blood pressure or heart disease, but understood that something ceremonial was happening and wanted in on it. I’d take their blood pressure—these lean, hard laborers, the baggage carriers, the gardeners, the workmen who built the place with only hand tools in the equatorial sun. Their pressure would be low, their heart rates an astonishing fifty beats a minute. To each, I’d say the same: “You are going to live to be a very old man.”
Halfway through the hoi polloi, I’d be summoned into the inner waiting room, where the indoor staffers, the guys starting up the management ladder, would be fretting, waiting to roll up the sleeves of their off-the-rack leisure suits for their readings. Their numbers would be up, nothing catastrophic, but definitely on the high side, higher readings than you’d want for someone their age—in other words, usually about the same level as my own blood pressure.
Finally, I’d be summoned into Joseph’s office. He’d greet me warmly, prepare himself under the watchful eye of his two assistant managers, there to learn the proper way to have their blood pressure taken. Silence, anticipation. And always, it would be way too high. “Joseph . . .,” I’d say, in a scolding tone. He’d deflate with worry; it still had not come down. He’d tell me hopefully about the new antihypertensive medication his doctor in Nairobi was hoping to give him; the doctor hadn’t quite gotten permission to import it into the country yet, but he was sure this one was going to help. . . . And I’d begin the next phase of our weekly ritual. “Maybe you should do some exercise, perhaps jog around the lodge a bit,” I’d tentatively venture. He’d giggle happily at the absurdity of this—“But I am the manager; I cannot be seen running around my lodge.” “Well, maybe you should go on a diet, cut back a bit.” “But what will the tourists think of the food here if the manager looks like a starving man?” I’d make a few other hopeless suggestions until Joseph’s anxiety would be subordinated to his hunger. Enough of blood pressure, he’d announce, I must join him for lunch. He would lead me into the corridor to proclaim his blood pressure to the assembled staff, who would gasp with admiration that their leader could achieve such high numbers with his heart. And then, it being impossible to say no to his enthusiastic hospitality, the two of us would descend upon the all-you-could-eat banquet, gorging with abandon.
So went that summer. Years later, as I ponder Joseph’s ill health, it strikes me that this was a man who became sick from being partially Westernized, and in a rather subtle way.
People in the developing world have became sick from being partially Westernized for a long time. Some cases represent the greatest of fears of well-meaning Western aid workers who plunge into some situation hoping to do good and instead make a mess of it. One example that has come back to haunt many a time: look at some nomadic tribe perpetually wandering around a howling wasteland of a desert searching for daily water for their goats and camels, the puddle of stagnant water here or there being all that saves them and their livestock. Obvious solution: haul in some equipment and drill a well for these folks. Expected outcome: no need to wander the desert anymore, plenty of water every day for the animals in this one convenient location. Unexpected additional outcome: the anim
als eat every leaf and tuft of grass within miles, and the high density of animals and their owners now encamped around the well makes communicable diseases leap through herds and through human populations with greater speed and virulence. Result: desertification, pandemics. You don’t want Western centralization of resources until you have Western resistance to diseases of high population densities.
Sometimes people in the developing world became sick from partial Westernization because their bodies work differently from those of Western populations. Think about the world of subsistence farmers eking out a living on their few tropical acres, or the nomadic pastoralists wandering the equatorial grasslands or deserts with their herds. Food and water are often scarce, unpredictable. Salt, essential for life and found in low levels in most foods other than meat, is something to trade riches for, something to go to war over. Bodies make use of these treasures mighty efficiently. Have the first smidgen of sugar and carbohydrates from a meal hit the bloodstream and the pancreas pours out insulin, ensuring that every bit of those precious nutrients is stored by the body. Similarly, the kidneys are brilliant at reabsorbing salt and thus water back into the circulation so that nothing is wasted.