Watching a performance of Henrik Ibsen’s play Ghosts as an undergraduate, I was appalled by the dawning realization that young Oswald had congenital syphilis as collateral damage from his father’s wanton lifestyle. Afterwards, as a zoology student steeped in evolutionary biology, I pondered the origins and spread of human venereal diseases. How, I wondered, could natural selection possibly favour an exclusively sexual route for disease transmission in a genuinely monogamous primate?
Human venereal diseases
The World Health Organization estimates that around the world over a million people are infected every day with a sexually transmitted disease. 50,000 of those cases are in the USA alone. Prominent examples are bacterial infections such as syphilis, gonorrhea and chlamydia and viral diseases including genital herpes, human papillomavirus and the human immunodeficiency virus (responsible for AIDS). Particularly intriguing is syphilis, a much-documented disease caused by the spiral-shaped bacterium Treponema pallidum passing through breaches in skin or membranes during sexual intimacy. Once in the bloodstream, the bacterium latches onto cells and eventually causes extensive damage. Untreated syphilis has 4 distinct stages: primary (mostly with a single painless skin ulceration), secondary (typically with unsightly diffuse skin eruptions), latent (largely symptom-free), and tertiary (with notable damage to body parts such as skull, heart and brain, one sequel being dementia). Congenital syphilis occurs when the bacterium passes from placenta to fetus during late pregnancy.
The first written accounts of a syphilis epidemic followed an invasion by French troops in Naples (Italy) in 1494/1495, spawning “French pox” as one of its many names. Its origin was attributed to sailors returning from the New World with Columbus. As Robert Knell explains in a 2004 paper, syphilis was “an acute and extremely unpleasant disease” on first appearance in Europe. But virulence declined rapidly and 500 years later it had become a milder, chronic disease. Symptoms were probably very severe initially because syphilis — presumably with a newly acquired sexual mode of transmission — entered a European host population lacking natural defences. But natural selection favouring reduced virulence of the bacterium brought about the subsequent rapid decrease in severity. It is counterproductive for a parasite to trigger early death or debilitate and disfigure its host, deterring sexual partners. Syphilis is still quite pernicious, but its pathological symptoms are much milder than they were.
Controversy long surrounded the origin of syphilis as a venereal disease, but resolution is now at hand. The topic is complicated because Treponema pallidum includes four known subspecies that are virtually indistinguishable in physical appearance and serology. Yet only the subspecies causing syphilis, T. p. pallidum, is transmitted sexually. The others are all transmitted through simple skin-to-skin or oral contact, usually during childhood, and cause diseases with distinctive symptoms: yaws (T. p. pertenue), pinta (T. p. carateum), and bejel (T. p. endemicum). In 2008, a wide-ranging genetic study of all subspecies by Kristin Harper and colleagues revealed that sexually transmitted syphilis strains originated most recently and are closest relatives of New World strains causing yaws. But Old World yaws-causing strains occupy the base of the evolutionary tree, suggesting that they arose first. Harper and colleagues therefore proposed a 3-stage model for the distribution and evolution of different forms of Treponema pallidum: (1) An original non-venereal form in the Old World spread first to the Middle East and Eastern Europe (giving rise to bejel), and subsequently to the Americas (yielding New World yaws). (2) European explorers carried a strain from the Americas back to the Old World, giving rise to syphilis. (3) Syphilis strains spread from Europe around the globe.
Sexually transmitted diseases in nonhuman primates
Ideally, comparison with other primates should yield valuable clues to the evolution of human venereal diseases, but scanty knowledge is a handicap. Nevertheless, valuable insights eventually emerged from an ingenious indirect approach. In a milestone 2000 paper, Charlie Nunn and colleagues presented results of comparisons using counts of white blood cells (leucocytes) to indicate disease risk. Leucocytes provide one of the first lines of defence against infections. The researchers compiled leucocyte counts for a representative sample of 41 primate species and tested 3 alternative hypotheses for higher disease risk: (1) larger groups or greater population density, (2) greater exposure to pathogens on the ground because of faecal contamination, and (3) more promiscuous mating.
The primary finding was that leucocyte counts were significantly greater in species where females have more mating partners. By contrast, leucocyte counts showed no significant relationship with the other factors tested. Analyses were repeated using a combined index of female mating promiscuity derived from relative testis size and duration of female mating activity per cycle. This index was also significantly correlated with leucocyte counts. In 2002, Nunn further consolidated these findings in a follow-up paper presenting results for an increased sample of 100 primate species.
A 2004 paper by Matt Anderson and colleagues provided independent backing for Nunn’s findings using a different dataset for leucocyte counts in 38 nonhuman primate species. Analysis confirmed that higher counts are significantly correlated with the degree of multiple mating. Using relative testis size as an indicator of mating promiscuity provided additional corroboration. However, the authors rightly cautioned that their results do not establish a causal relationship between leucocyte counts and mating promiscuity. Further research is needed.
It is actually somewhat surprising that leucocyte counts are linked to sexual transmission of diseases rather than social group size, population density or terrestrial activity. But perhaps this is because sexually transmitted diseases can penetrate the body deeply and generally persist, thanks to adaptations to counter the host’s immune system. It makes sense for promiscuously mating primate species to have more circulating white blood cells that might block an initial sexually transmitted infection.
Implications for humans
Surprisingly, implications for humans from the association between white blood cell (WBC) counts and mating promiscuity in other primates have been largely ignored. This sentence in the 2000 paper by Nunn and colleagues passed largely unheralded: “In humans, WBC counts are more consistent with monogamy than promiscuity." Cluster analysis revealed that humans align most closely with harem-living gorillas and monogamous white-handed gibbons. As both have low levels of sperm competition, this provides additional evidence against the claim that humans are biologically adapted for marked sperm competition. (See my previous posts Sperm Wars: Dispatch From a Conscientious Objector and Kamikaze Sperms or Flawed Products? posted on August 7 and October 16, 2013.) Instead, considerable evidence points to fundamental human adaptation for a single-male mating system with little sperm competition.
A 2010 paper on immunity genes by Gabriela Wlasiuk and Michael Nachman neatly yielded independent corroboration of the results originally reported by Nunn and colleagues. Across a spectrum of higher primate species (monkeys, apes and humans), Wlasiuk and Nachman examined patterns of evolution for 15 immune defense genes in relation to promiscuity and various other factors that might influence disease risk. They estimated rates of evolution along different branches in the primate tree. For 10 genes producing proteins that interact closely with pathogens significantly higher rates were found along branches leading to more promiscuous species. This provides valuable additional support for the notion that sexual promiscuity plays an important rôle in the evolution of the immune system. Promiscuously mating species have not only more circulating leucocytes but also more finely tuned defensive proteins.
Interestingly, the human lineage generally showed relatively low rates of evolution in comparison with other primates, resembling primates with single-male mating systems rather than those that mate promiscuously. Once again, there is no evidence for human biological adaption for sperm competition. Ironically, then, humans are not biologically adapted for promiscuous mating, as is reflected by relatively low levels of circulating white blood cells and slowly evolving defensive proteins, yet suffer from many sexually transmitted diseases. Departure from our ancestral mating patterns has a heavy price.
Anderson, M.J., Hessel, J.K. & Dixson, A.F. (2004) Primate mating systems and the evolution of immune response. Journal of Reproductive Immunology 61:31-38.
Boyd, R.H. (1955) Origin of gonorrhoea and non-specific urethritis. British Journal of Venereal Diseases 31:246-248.
Harper, K.N., Ocampo, P.S., Steiner, B.M., George, R.W., Silverman, M.S, Bolotin, S., Pillay, A., Saunders, N.J. & Armelagos, G.J. (2008) On the origin of the treponematoses: A phylogenetic approach. PLoS Neglected Tropical Diseases 2(1):e148:1-13.
Harper, K.N., Zuckerman, M.K., Harper, M.L., Kingston, J.D. & Armelagos, G.J. (2011) The origin and antiquity of syphilis revisited: An appraisal of Old World pre-Columbian evidence for treponemal infection. Yearbook of Physical Anthropology 54:99-133.
Knell, R.J. (2004) Syphilis in Renaissance Europe: rapid evolution of an introduced sexually transmitted disease? Proceedings of the Royal Society of London B (Supplement) 271:S174-S176.
Mitjà, O., Šmajs, D. & Bassat, Q. (2013) Advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta. PLoS Neglected Tropical Diseases 7(10): e2283:1-9
Nunn, C.L. (2002) A comparative study of leukocyte counts and disease risk in primates. Evolution 56:177-190.
Nunn, C.L., Gittleman, J.L. & Antonovics, J. (2000) Promiscuity and the primate immune system. Science 290:1168-1170.
Rothschild, B.M. & Rothschild, C. (1995) Treponemal disease revisited: Skeletal discriminators for yaws, vejel, and venereal syphilis. Clinical Infectious Diseases 20:1402-1408.
Wlasiuk, G. & Nachman, M.W. (2010) Promiscuity and the rate of molecular evolution at primate immunity genes. Evolution 64:2204-2220.