Not a Single-Species Affair: How Non-Human Life Impacts Human Medicine

Last Updated on March 12, 2019 by

As a first-year medical student, I lived near a veterinary program. The comparison often made—by both med and vet students, as well as community members—was that med students studied humans, whereas vet students studied everything else. Of course, in its practical aim, medicine is exclusively about people. We undergo a serious study of human biology so as to meet the responsibility of caring for other human beings, and the central challenge of medicine is matching that knowledge to the unique experiences of our patients. We should be careful, however, not to underestimate the importance of non-human life for that purpose. As a scientific endeavor, human medicine is predicated on knowledge of many different types of living things, whether we consider the ecology of our bodies or the pharmacology of our cures. Moreover, the humility of its practitioners stems from recognizing the mutual dependence of human life and the rest of the biosphere. In short, medicine is a multi-species affair.
To start, “we” are quantitatively as non-human as we are human. We host bacteria at the same order of magnitude as our own cells [1], and they are not passively along for the ride. These organisms are living, dying, fighting, swapping genes, undertaking complex chemistry and interacting nonstop with their host. We rely on our bacteria to make our vitamins [2], digest nutrients [3], and help our immune system strike the delicate balance between defense against pathogens and autoimmunity [4,5]. Even in places previously considered sterile—free of bacterial communities, perhaps as “purely human” as you could get— improved genomic methods are turning up resident bacteria: the bladder [6], the placenta [7].
Of course, wherever there are cells, there are viruses eager to cohabitate. All humans sustain chronic infections by both DNA and RNA viruses, modulating our immune systems as members of a bona fide virome [8]. Some 8% of our DNA is actually viral DNA we’ve appropriated as our own—such as the genes for the placenta, a variation on a viral syncytium [9,10]. Our bacteria attract their own viruses too. Like wolves in Yellowstone, these viral predators can shape the composition of the bacterial microbiome, and the physiology of its host in the process [11]. Clearly, then, the human as a single species is simple vanity. We are chimeras, and ecosystems.
Accordingly, any student of human health should take interest in the diverse species of the human ecosystem. Our microbiome has become a hot topic lately, with an emerging role in inflammatory bowel disease, obesity, cancer, even in mental health [12,13]. It is becoming obvious that our acquired microbial flora is involved in disease pathology and a target for treatment, from probiotics to fecal transplants [14,15]. And while this acquired “microbial organ” has yet to make it into physiology textbooks—an omission that may one day be as surprising as that of the heart or kidneys—a few non-human species have always demanded a spot in the curriculum. No doctor can graduate without becoming familiar with grape-like clusters of Staphylococcus or the banana-shaped Plasmodium falciparum. They serve as a reminder that, though high up on the food chain, we will never escape the (micro-)predation that defines earthly life.
Now we live in a historically unprecedented moment for the interspecies dramas of infectious disease. Due to advances in hygiene, vaccines, and antibiotics, it is possible for many of us to not have infection as the chief health struggle of daily life and medicine [16]. We no longer face death and deformity with minor wounds or a neighbor’s cough. The US is not routinely devastated by cholera outbreaks, an exotic filovirus, or vaccine-preventable infections (just yet). But we would be delusional to think that, since these are problems only for the past, or distant multitudes elsewhere on this planet, we have entered the “post-infectious” future. Globalization is spreading new pathogens in new ways, as well as resistance to the drugs we have to fight them [17,18]. And we do have persistent infectious diseases in our country, hidden away—say, in the hospital, where rates of healthcare-associated infections are improving but continue to undermine medical progress [19]. Non-human species will always demand the attention, and respect, of medicine and its students.
They also deserve serious appreciation. Plants, fungi, and other bacteria synthesize many of the bioactive compounds used to treat illness—classics like penicillin (Penicillium chyrosgenum, fungus), aspirin (Salix alba, white willow), and morphine (Papaver somniferum, poppy) [20]. Some drugs, like metformin (Galega officinalis, goat’s rue) or the statins (Aspergillus terreus, fungus), are such staples of modern medicine that it’s hard to imagine their having anything earthy in their origin. Others, when seen in the context of natural history, are total inspirations for the scientific imagination. The hypertension drug enalapril comes from the venom of a Brazilian pit viper (Bothrops jararaca) [21]—and wouldn’t it make sense for a venom-fanged snake to send its prey into hypotensive submission in order to devour it? Bacteria synthesize two-thirds of FDA-approved antibiotics [22]—and with 3.5 billion years of evolutionary time to elaborate a competitive chemical armory, aimed at the same species we humans seek to control, is there any truer example of “the enemy of our enemy is our friend”?
Of course, it would be a bit too simple to conclude that “Mother Nature knows best”. The rising rates of ER admissions related to use of herbal supplements, thought intrinsically “good” or “safe” by patients, are enough to put that to rest [23]. Still, it is worth recognizing that among all possible combinations of atoms on earth, evolution has already produced a broad set of chemical structures in nature pre-selected for activity within biological systems—in other words, our past and future drugs. Were it not for these compounds, and the extensive biodiversity from which they come, the “medicine” of medicine would be sorely lacking.
There are myriad other examples of how human health is not a single-species affair. A therapy dog can help ameliorate the cruel psychic pains of trauma and depression [24]. A walk through the woods, which in Japanese is given the perfectly poetic term “forest bathing” (shinrin-yoku), can reduce the hormonal and autonomic measures of stress [25]. Even if we don’t stare our dinner in the eye before eating it, we can appreciate that our diet, and the health that hangs in the balance, is a question of non-human organisms—whether a plate of Salmo salar (salmon) and Spinacia oleracea (spinach) or, perhaps less directly, a bag of alliaceous Funyuns. The biodiversity of medicine is uncovered at every level.
In the end, this perspective on medicine is not just good science and good fun, although the two often coincide. For doctors and patients alike, there is an important lesson about our place as human beings. As Einstein stated, “Nature is a magnificent structure that we can comprehend only very imperfectly, and that must fill a thinking person with a feeling of humility [26].” This humility is what we all must feel, gazing openly on the biodiversity implied in our most basic bodily existence. And whether reflecting on our own health, or that of a patient we serve, we can all bear remembering that we are but humble humans involved in a much greater, wonderfully complex web of biodiversity.
Sources:
1 Sender, R., Fuchs, S., & Milo, R. (2016). Revised Estimates for the Number of Human and Bacterial Cells in the Body. PLOS Biology, 14(8), e1002533. doi:10.1371/journal.pbio.1002533
2 Rieder, R., Wisniewski, P., Alderman, B., & Campbell, S. (2017). Microbes and Mental Health: A Review. Brain, Behavior, and Immunity. doi:10.1016/j.bbi.2017.01.016
3 Hilt, E., McKinley, K., Pearce, M., Rosenfeld, A., Zilliox, M., Mueller, E., … Schreckenberger, P. (2014). Urine Is Not Sterile: Use of Enhanced Urine Culture Techniques To Detect Resident Bacterial Flora in the Adult Female Bladder. Journal of Clinical Microbiology, 52(3), 871–876. doi:10.1128/jcm.02876-13.
4 Pelzer, E., Gomez-Arango, L., Barrett, H., & Nitert, M. (2016). Maternal health and the placental microbiome. Placenta. doi:10.1016/j.placenta.2016.12.003
5 Hollister, E., Gao, C., & Versalovic, J. (2014). Compositional and Functional Features of the Gastrointestinal Microbiome and Their Effects on Human Health. Gastroenterology, 146(6), 1449–1458. doi:10.1053/j.gastro.2014.01.052
6 LeBlanc, J., Milani, C., Giori, G., Sesma, F., Sinderen, D., & Ventura, M. (2013). Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Current Opinion in Biotechnology, 24(2), 160–168. doi:10.1016/j.copbio.2012.08.005
7 Thaiss, C., Zmora, N., Levy, M., & Elinav, E. (2016). The microbiome and innate immunity. Nature, 535(7610), 65–74. doi:10.1038/nature18847
8 Bach, J.-F. (2002). The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases. The New England Journal of Medicine,347(12), 911–920. doi:10.1056/NEJMra020100.
9 Zou, S., Caler, L., Colombini-Hatch, S., Glynn, S., & Srinivas, P. (2016). Research on the human virome: where are we and what is next.Microbiome, 4(1), 32. doi:10.1186/s40168-016-0177-y
10 Norman, J. M., Handley, S. A., Baldridge, M. T., Droit, L., Liu, C. Y., Keller, B. C., … Virgin, H. W. (2015). Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease. Cell, 160(3), 447–460. doi:10.1016/j.cell.2015.01.002.
11 Stoye, J. (2012). Studies of endogenous retroviruses reveal a continuing evolutionary saga. Nature Reviews Microbiology, 10(6), 395–406. doi:10.1038/nrmicro2783.
12 Haig, D. (2012). Retroviruses and the Placenta. Current Biology, 22(15), R609–R613. doi:10.1016/j.cub.2012.06.002.
13 Cho, I., & Blaser, M. (2012.) The human microbiome: at the interface of health and disease. Nature Reviews Genetics 13. doi:10.1038/nrg3182
14 Kelly, C. (2013). Fecal Microbiota Transplantation — An Old Therapy Comes of Age. The New England Journal of Medicine, 368(5), 474–475. doi:10.1056/NEJMe1214816
15 Gerritsen, J., Smidt, H., Rijkers, G., & Vos, W. (2011). Intestinal microbiota in human health and disease: the impact of probiotics. Genes & Nutrition, 6(3), 209–240. doi:10.1007/s12263-011-0229-7
16 Hansen, V., Oren, E., Dennis, L., & Brown, H. (2016.) Infectious Disease Mortality Trends in the United States, 1980-2014. JAMA, 316(20), 2149–2151. doi:10.1001/jama.2016.12423
17 Saker, L., Lee, K., Cannito, B., Gilmore, A., Campbell-Lendrum, D. (2004.) Globalization and Infectious diseases: A review of the linkages. World Health Organization. http://www.who.int/tdr/publications/documents/seb_topic3.pdf
18 World Health Organization. (2014.) Antimicrobial Resistance: Global Report on Surveillance. WHO Press. http://www.who.int/drugresistance/documents/surveillancereport/en/
19 CDC. (2016.) National and state healthcare associated infections: progress report. Center for Disease Control and Prevention. https://www.cdc.gov/HAI/pdfs/progress-report/hai-progress-report.pdf.
20 Dias, D., Urban, S., & Roessner, U. (2012). A Historical Overview of Natural Products in Drug Discovery. Metabolites, 2(2), 303–336. doi:10.3390/metabo2020303.
21 Cushman DW, Pluscec J, Williams NJ, Weaver ER, Sabo EF, Kocy O, Cheung HS, Ondetti MA. (1973.) Inhibition of angiotensin-converting enzyme by analogs of peptides from Bothrops jararaca venom. Experientia, 15;29(8):1032–1035.
22 Cragg, G., & Newman, D. (2013). Natural products: A continuing source of novel drug leads. Biochimica et Biophysica Acta (BBA) – General Subjects, 1830(6), 3670–3695. doi:10.1016/j.bbagen.2013.02.008
23 Geller, A., Shehab, N., Weidle, N., Lovegrove, M., Wolpert, B., Timbo, B., … Budnitz, D. (2015). Emergency Department Visits for Adverse Events Related to Dietary Supplements. The New England Journal of Medicine, 373(16), 1531–1540. doi:10.1056/NEJMsa1504267.
24 O’Haire, M., Guérin, N., & Kirkham, A. (2015). Animal-Assisted Intervention for trauma: a systematic literature review. Frontiers in Psychology, 6. doi:10.3389/fpsyg.2015.01121.
25 Park, B., Tsunetsugu, Y., Kasetani, T., Kagawa, T., & Miyazaki, Y. (2010). The physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field experiments in 24 forests across Japan. Environmental Health and Preventive Medicine, 15(1), 18–26. doi:10.1007/s12199- 009-0086-9.
26 H. Dukas and B. Hoffman, Albert Einstein-The Human Side, Princeton Univ. Press, Princeton, NJ, 1979, p. 132.