“Implications of Anthropogeny for Medicine & Health,” a public CARTA symposium

Cardiologist Barbara Natterson-Horowitz entered an operating room where her patient was already on the table. She’d had many patients in the past through the University of California at Los Angeles Medical Center, which trained her well for that moment. The foot sticking out from under the surgical towels, however, didn’t belong to a human. It belonged to a lion. How did being a human cardiologist prepare Barbara to work on lions? Humans and lions can’t be that similar, especially through the eyes of a doctor… right? Last Friday, Barbara kicked off the symposium “Implications of Anthropogeny for Medicine and Health” by highlighting the similarities of her patients across species. It was the first of many research talks that questioned the differences between humans and other animals and between populations of humans, as well as the similarities we have from shared origins. The University of California at San Diego (UCSD) and the Salk Institute’s Center for Academic Research and Training in Anthropogeny (CARTA) joined forces with the Arizona State University (ASU) Center for Evolution and Medicine to sponsor the symposium, which was free and open to the public. During talks that were peppered with descriptions of edible liquid gold, killer sugars, battles within wombs, and studies within tombs, visitors learned about the traits and diseases that make us human (and animal) products of our world.

Anthropogeny, or the study of human origins, is a vast discipline, but this joint seminar focused on how what we know (and, perhaps more frequently, how what we don’t know) about our origins affect medicine and health. Barbara Natterson-Horowitz, Professor of Medicine in Cardiology at the David Geffen School of Medicine at the University of California at Los Angeles, started off the research talks by making us leave our ideas of humans as exceptional and unique at the door. Many of the diseases that humans face occur in other vertebrate species. Polar bears, beluga whales, and big cats get breast cancer; various bird species get atherosclerosis; and a variety of species show signs of compulsive behaviors. Overall, the starting message for the symposium was clear: Bad human habits increase our risk of certain diseases, but the vulnerability to these diseases is ancient.

Building on this wide base of shared disease vulnerability, Distinguished Professor of Medicine and Cellular & Molecular Medicine at UCSD, physician, and co-director of CARTA Ajit Varki then focused in on ways in which humans are unique in our vulnerability to disease. Humans and chimpanzees are nearly 99% similar at the level of protein production, yet humans deal with issues that, as far as we know, no other animals face, including malignant malaria and typhoid fever. Additionally, even some of the most common afflictions we share—heart attacks and heart failure—seem to be caused by different pathological mechanisms in humans versus in other great apes. Focusing on the underlying similarities and differences that make us vulnerable may help us identify what genes and molecules underlie the manifestation of these diseases.

From these two starting comparative views of disease, speakers throughout the symposium then introduced us to a variety of subjects including trade-offs associated with health and with reproduction, environmental mismatch, and special examples of strong natural selection in adapting to our varied environments. All talks communicated the importance of the environment as a context that shapes how our bodies function.

Randolph Nesse, Foundation Professor and Founding Director of the Center for Evolution and Medicine at ASU, moved from a phylogenetic view of disease toward a genetic one, asking why natural selection hasn’t eliminated genes that cause disease and promoted genes that make life easier. Why, for example, must women give birth through the birth canal, rather than through a belly zipper? Throughout his talk, Randy explained that animal fitness is a balancing act that can have many negative trade-offs. Natural selection works toward improving reproductive fitness rather than health, which can cause developments that help the young and harm the old, that benefit one sex at the expense of the other, or that use specific molecules or anatomy that become ingrained and can be nearly impossible to change. If we continue studying our origins and human and animal evolution, we may be able to learn the underlying explanations for our genetic variations that cause problems for human health. In particular, Randy suggested that, rather than continuing to focus research on genetic differences that cause disease, it may be more informative to identify and study the genes that we all share that make us vulnerable to disease.

Some of the diseases and other problems we encounter in human health are due to trade-offs in our physiology. Ruslan Medzhitov, a Professor at Yale University School of Medicine, discussed a very clear trade-off within our immune system—inflammation. An inflammatory response is a beneficial response of the body to pathogens, but the response itself can also harm our bodies in many ways. It turns out that how an organism responds to infection depends on the type of infecting pathogen—different pathogens cause different types of inflammatory response. Using data from experiments on mice, Ruslan’s research group showed how the common sugar glucose affects an infection and resulting inflammation differently depending on whether the infection is viral or bacterial. Mice seem to handle viral infections better when given glucose (“feed a cold”), while they handle bacterial infections poorly when given glucose (“starve a fever”), potentially causing inflammatory damage to brain tissue. If humans respond similarly, our sickness defenses and behaviors are likely dependent on the environmental context, including what type of pathogen is causing infection.

Reproduction is another physiological trade-off that leads to conflicts not only between appropriate uses of energy, but between the genetic goals of successive siblings, as well as between the genetic goals of each parent of an offspring. David Haig, the George Putnam Professor of Organismic and Evolutionary Biology at Harvard University, explained that humans are unique in that they will provide intensive care to multiple children at the same time. This leads to sibling competition that may go so far as microchimerism, in which a child deposits cells into its mother during pregnancy that may have some effect on the investment later children receive. Additionally, because the mother’s family is not the same as the father’s family, a tug-of-war in gene expression happens between the paternal and maternal genes within a developing offspring. A father’s genes will pull for more reproductive investment than the mother’s genome should give. The asymmetry of desired parental investment can lead to visible trade-offs for a mother’s reproductive health, through the lens of her offspring’s growth rate, behavior, and other traits.

But for those of you who dislike this competitive, conflict-filled view of reproduction, do not fear… as we learn more about reproduction and the conflicts that occur within, we are also learning about amazing ways in which a mother and her child communicate with each other to aid in the proper nutrition of a growing baby. Katie Hinde, Associate Professor in the School of Human Evolution and Social Change and the Center for Evolution and Medicine at ASU, delved into the science of breast milk, a product that integrates nutrients, immune molecules, and hormones in a combination that can change across hours, days, and developmental stages within a mother, as well as between individuals, populations, and species. The act of nursing may enable an infant to send signals to the mother, helping shape the recipe of breast milk it receives. These precise provisions have been described as “liquid gold,” but the formula substitutes that are provided in health care lack this precise, changing recipe. As Katie outlined this fantastic integration of environmental signals into parental care, she also highlighted the vast room for improvement of infant care if we focus more research on the liquid gold of breast milk.

As we work to improve nutrition of our infants, there is a lot we can do to improve adult human nutrition as well. With obesity, heart disease, and diabetes epidemics developing across the globe in recent decades, many have argued that in some societies, our bodies are struggling with overabundant food and low physical output—conditions we’ve never before experienced regularly. If a trait that is helpful in one environment ends up being harmful in another, we call this an environmental mismatch. One example of environmental mismatch becomes clear when comparing Western populations to the hunter-gatherer Tsimane (pronounced tchi-mah-neigh) people of Bolivia. In our modern society, we have moved away from a subsistence lifestyle and have created a relatively sterile environment, where rates of parasite infection are low and energy is easy to find and store. Having lost our close parasite friends, and having removed energetic challenges to physiology, many health problems appear in far greater numbers than ever recorded. Atherosclerosis, for example, is an ancient disease, as we have learned from the calcified arterial beds of mummies (yep, you read that correctly… mummies). However, in our society, we experience much higher rates of atherosclerosis than subsistence populations. Michael Gurven, Professor of Anthropology at UC Santa Barbara, discussed how the Tsimane experience much lower rates of atherosclerosis than Westernized populations. In fact, Tsimane people generally have arteries that appear to be 20 to 25 years younger than expected based on their age. However, the “normal” arterial age is based off of Western populations, even though the conditions experienced by these populations are very new in the human evolution timeline. Thus, as we try to improve human health and nutrition, we should keep hunger-gatherer populations and our previous environmental conditions in mind as we try to define medically what is normal and as we try to address modern health epidemics.

Study of diverse human populations doesn’t just give us good models to investigate environmental mismatch; such populations also provide us with great examples of natural selection at work. Cynthia Beall, Distinguished Professor of Anthropology at Case Western Reserve University, discussed how human adaptation to high-altitude hypoxia varies in mechanism between different populations. At high altitudes, the air is thinner, meaning there are fewer molecules per volume of air. This causes a problem for organisms at high altitudes that require reliable oxygen delivery to tissues. It’s also a major reason why climbing Mount Everest is such a feat, especially without supplemental oxygen tanks.

Despite these challenges, humans have been living at high altitudes for thousands of years, so how is it that they handle these conditions? And how can others train to endure such conditions? For humans to deal with the low levels of oxygen found at high altitudes, there are a couple short-term physiological solutions. We can either increase our breathing rate to bring more oxygen into our lungs, or we can increase our circulating hemoglobin so our blood can pick up more of the oxygen delivered to our lungs with each breath. Andean highlanders of South America and people living on the Tibetan plateau in Asia differ in their short-term acclimatization and their adaptations to high-altitude life. Tibetans show increased breathing, but their hemoglobin production does not increase to deal with low oxygen levels; the opposite occurs in Andeans. Some of these adaptations to high altitude have occurred at different genetic loci in each of these populations. Cynthia’s talk revealed that, just like there are several routes to summit Everest, often there are multiple ways natural selection can approach the same biological problem.

Variation in physiology was a strong theme throughout the symposium. Lots of this variation is often due simply to differences in environmental influences. For example, our current sleep patterns in the modern world show us how the changed environment of humans may control how much we sleep. Charles Nunn, Professor of Evolutionary Anthropology and Global Health at Duke University, guided us through the science of sleep in primates. Humans sleep less than all other primates, but we have the highest percent of rapid eye movement (REM) sleep. Many hunter-gatherer tribes have short, fragmented sleep that involves napping during the daytime, but in Western populations, we average about 7 hours of sleep during the night. Using studies on the Malagasy and Hadza tribes, Charlie asked why humans are short sleepers, whether we should be wary of midnight insomnia, and if short sleep has negative health effects. In this talk, we were reminded of some of the ideas Randy Nesse had presented—selection acts on reproductive success, not on health. If a shorter duration of sleep gives us more opportunity to strengthen social bonds, to learn from our neighbors, and potentially to reduce risk of being attacked, then it may have been selected for evolutionarily. Thus, a break in sleep here and there may have beneficial origins in our past, even if insomnia hinders your work in today’s world. Whether or not we sleep within homes and whether or not we sleep solidly through the night, Charlie reassured us that we may be getting the best sleep we’ve ever had in our evolutionary history. The development of different patterns of sleep fragmentation between hunter-gatherers and Westerners highlights how much variation exists in health-related behaviors such as sleep.

Overall, this CARTA public symposium explored the complexity of medicine and how our understanding of evolution helps to define and simplify some of that complexity. After an afternoon filled with great presentations, visitors were bid farewell with a musical treat—a wrap-up rap rendition of evolution and medicine by hip-hop guide Baba Brinkman. Baba’s experience performing for conference crowds was apparent, as he got professors and students alike to sing along and show their appreciation with a standing ovation. In one of his final songs, Baba reminded us that for all that we do as humans—whether we write a song, we present research, or a population adapts to a new environment—there are at least three main steps that are shared: performance, feedback, and revision. Hopefully with a better understanding of human origins, medicine will continue to integrate current research for a more revised, deeper understanding of challenges to human and animal health.

 

Visit CARTA for more information on past and future symposia and visit the co-sponsoring Center for Evolution and Medicine for information on available jobs at ASU in evolution and medicine. The symposium was the first public event from the ongoing partnership between UCSD/Salk/CARTA and the Center for Evolution and Medicine. Videos of the talks will be broadcast on UCSD-TV in December 2016. After these presentations are aired, they will be archived on multiple websites, including CARTA, UCSD-TV, iTunes, and YouTube. Visit Baba Brinkman’s website for links to videos and to contact Baba for booking information.