The Evolution and Medicine Review

…bridging the gap.

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Editor’s note on ISEMPH commentaries

On behalf of Randy and myself I just wanted to thank all conference attendees who have sent in commentaries on the many sessions. I think, in all, I received and posted 19 commentaries – a terrific response! Randy and I hoped that we would get good science journalism rather than something that read like the abstract to a scientific paper and you all rose to the brief! Commentaries were breezy, upbeat, full of good humor, occasionally witty, and above all truly informative. It’s been a great exercise in collective reportage.

I’m personally sorry that circumstances made it impossible for me to come to Duke this year but reading and editing these wonderful contributions brought the conference alive for me. I hope to meet you all in the Netherlands at next year’s annual conference, even if (thanks to the British referendum decision to leave the European Community) I now will have to apply for a visa to attend!!

Frontiers of evolutionary medicine

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Nikki Burt fires in this commentary on the “Frontiers of Evolutionary Medicine.” See also, Ashley Snyder’s coverage of the same session.

Stephen Stearns organized one of the last ISEMPH sessions “Frontiers of Evolution,” and, as you would expect, it had a diverse group of contributors representing a range of evolutionary medicine topics, global regions, and career stages.

Cynthia Beall kicked off the session as its first speaker presenting on “Hemoglobin Concentration and Reproductive Success of Tibetan Highlanders.” Beall and colleagues conclude that these distinct phenotypes are linked to better reproductive success but that more work needs to be done to better understand the mechanism for this and the genetics at play in the community.

Following Beall was Michelle Freed from Durham University presenting the work of her fellow Masters students and advisor Gillian Bentley “Is it Time to Re-evaluate the Mismatch Concept?” This speculative paper presented how the mismatch concept is often improperly applied both by practitioners and pseudoscientists. The presentation generated a thoughtful discussion from researchers around the field.

Speaker Emmanuel Milot presented his research groups work on “Eco-evolutionary Dynamics and Natural Selection on Health Related Traits in Human Populations.” The presentation focused on some of the preliminary work being done with the demographic data from their extremely well documented French Canadian Sample. Integration of these greater than 300 year genealogies with genetic data is the next step of the research.

Closing out this final session was Hillard Kaplan presenting for his group on their work “Cancer in an Indigenous Native South American Population: Initial Insights Into the Natural History of Cancer in Traditional Subsistence Populations. This presentation of new data on cancer rates for the Tsimane is the first step in understanding differences in cancer types and rates between individuals living under traditional subsistence patterns and WEIRD populations.

The session was diverse and highlighted just a sliver of the wide variety of research and theory being done in the field of Evolutionary Medicine.

Behavior and vulnerability to disease

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Thanks again to Cynthia Beall for covering this session for the Evmedreview.

 

The session on behavior and vulnerability to disease covered anxiety, post-partum depression, post-traumatic stress disorder, and the ‘fourth trimester’ of pregnancy. The methods ranged from mathematical modeling to prospective cohort studies and intensive interviewing of small samples.

Frazer Meacham presented a model of normal anxiety and anxiety-associated diseases. The elements included good or bad environments modeled as dangerous or not, the frequency of danger and the easy of detecting danger. The model suggested two ways to become anxious: one is to encounter danger as in the case of PTSD, and the other is to encounter cues of danger as in the case of OCD.

Molly Fox presented the results of a prospective study of 300 women post-partum and nine months later. She made the surprising observations that post-partum depression is not recognized by the DMS or by the WHO as a diagnostic category! This was the first symptom-based characterization of PPD.

Levent Sipahi presented interesting data on PTSD and epigenetics. Interestingly, he found that pre-trauma levels of methylation contribute to the severity of symptoms after trauma. He concluded that PTSD is a biologically functional and appropriate response to trauma exposure.

Kristin Tully reported on the fourth trimester of pregnancy using a group of 20 intensively studied women participating in patient centered research. The project idenfitied a need for policies and service to bring together patients, clinicians, researchers and other stakeholders to define patient-centered priorities in the first 12 weeks after birth. Key, interrelated health themes are (1) maternal mood; (2) infant feeding; (3) sleep and fatigue; (4) sexuality, contraception, and birth spacing; (5) substances, medications, and environmental exposures; and (6) physical recovery from childbirth.

Andrea Graham and Soay sheep

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Many thanks to Cynthia Beall for this commentary on Andrea Graham’s Plenary talk “Why do immune systems harm their bearers? The evolutionary biology of friendly fire”. 

Andrea Graham of Princeton University walked us through a tale of two species and two islands during her plenary talk “Why do immune systems harm their bearers? The evolutionary biology of friendly fire”.

The species were Soay sheep on Hirta Island, Scotland and humans on Taiwan. She reported that sheep with more antinuclear antibodies (ANAs, a measure of self-reactivity and thus risk for autoimmune disease) were more likely to survive severe winters and had longer lifetimes. The trade off, however, was lower reproduction for both male and female sheep. Elderly people on Taiwan manifest a fascinatingly similar profile of higher levels of ANA associated with lower risk of death.

Both studies highlight the crucial role of longitudinal studies for addressing major questions in evolutionary medicine. The Soay sheep study is 30 years old and the SEBAS study in Taiwan is 27 years old.
The apparent answer to the underlying question – is vulnerability to immune-mediated disease the price of a potent immune system – is yes. Self-reactivity aids somatic maintenance as well as parasite resistance.

Frontiers in evolutionary medicine

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Ashley Snyder presents this commentary on the session “Frontiers in evolutionary medicine.”

 

Evolutionary medicine considers so many different fields of study. The presentations in “Frontiers of evolutionary medicine” represented work on the past, in the present, and for the future as they explored concepts relevant to the study of evolutionary medicine.

“Hemoglobin concentration and reproductive success of Tibetan highlanders” hypothesized the adaptive significance of Tibetan highlanders’ response to high-altitude hypoxia as it was found that the Tibetans have lower hemoglobin concentration. From interviewing Tibetan women who were in their post-reproductive years, they found that Tibetan women who had lower concentrations of hemoglobin had a greater likelihood of live birth and, thus, better reproductive success. Their refined hypothesis considers viability selection for this interesting trait. (Thank you to Cynthia Beall who stepped in to present!)

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Evolution of pathogens

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This commentary on the evolution of pathogens session just in from Elizabeth (Betsy) Uhl.

 

This interesting and important gem of a session started with a presentation by Joseph Graves about how E. coli bacteria like their bling – or rather how they do not like it, as his study found that it was harder for them to develop resistance to triangular versus spherical silver nanoparticles. The second study, presented by Katia Koelle, stressed the importance of acknowledging the ‘rubbish around the ruby’ as she modeled how antigenic variants together with deleterious mutations shape influenza’s hemagglutinin phylogeny. Models were also used to define criteria as to when aggressive versus containment therapy should be used to treat infections in a study presented by Elsa Hansen, and to indicate how cure and superinfection of cells facilitate rapid drug resistance in HCV infection in Ruian Ke’s study. Alison Feder studied how multiple haplotypes of drug resistant RT-SHIV emerged in different body compartments and found evidence that indicated selection and migration of the resistant viruses occurred on the same time scale. The session concluded with a study modeling whether specific immunity structures Plasmodium falciparum strains based upon the blood antigen PfEMP1, which was presented by Qixin He. Overall the session emphasized the power of modeling to characterize the evolution of a variety of pathogens.

Plenary talk by Joshua Schiffman

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Charlie Nunn weighing in here with a commentary on Joshua Schiffman’s plenary talk.

Those of us at the ISEMPH meeting in Durham experienced a fantastic and inspiring plenary talk by Joshua Schiffman, of the Huntsman Cancer Institute and the Intermountain Children’s Hospital in Utah. His talk highlighted the value of comparative research, the effectiveness of case studies, and the ways that biomemetics is relevant to questions in evolutionary medicine.

Josh started with a case study of a young girl, Danielle, with cancer. She was found to have Li-Fraumeni Syndrome, which confers an overall lifetime risk of cancer of about 80-90% (substantially higher than the 50% risk that most of us experience). Often these cancers involve early onset of bone and soft tissue cancers, such as sarcoma. This effect arises from loss of one of the alleles in the P53 gene, which plays a role in controlling cancer. As Josh put it, P53 is like a “superhero” of the genome. One-half of all human tumors are known to lack a functional copy of P53.

Josh then expanded the perspective to consider the emerging importance of comparison in oncology. He reminded us of the famous quote by Rudolf Virchow, “Between animal and human medicine there is no dividing line, nor should there be.” He went on to describe research led by Matthew Breen (NC State University) on naturally occurring cancers in dogs, and how Matthew has used the inbred genetic background of dogs to investigate the genetic drivers of cancer. Findings of identical genetic associations in dogs and people suggest targets for understanding and controlling cancer with new therapies.

Josh then segued to the important example of Peto’s paradox, namely that species of different body size exhibit similar rates of cancer. This finding is paradoxical because one would expect a positive association, with larger bodied animals expected to exhibit a higher rate of cancer, given that more cell divisions would have occurred. For example, one would predict that elephants have much higher rates of cancer than mice. Why, instead, are rates relatively constant across species, irrespective of body size?

With this excellent background, Josh shared his compelling results that copy number of P53 is one of the factors that helps reduce cancer risk in elephants. In particular, he and his colleagues found that elephants have about 20 copies of this “superhero” gene, as compared to just one for humans, and they produce more protein from these extra copies. In experiments involving exposure of cells to radiation, they further showed that elephant cells die at a higher rate (apoptosis) than human cells. The death rate in elephants was about five times higher than in those with Li-Fraumeni syndrome.

The talk ended with a description of Josh’s efforts to turn this exciting comparative finding into a new cancer therapy involving elephant P53 proteins, with exciting results to share. His trials aimed at applying this finding to help cure human cancer are still at an early stage, yet we all left with a strong sense of how a rigorous comparative approach can lead to new cancer therapies. Very exciting!

Paleopathology and Evolutionary Medicine

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Here is Bruce Rothschild’s final report from this year’s ISEMPH conference. Thanks Bruce!

Utilizing historical, skeletal and mummy investigations, evolution of disease through time provides insights into current diseases and new options for their control or eradication. Short term alterations of environment and socio-economic status clearly alter disease prevalence and impact. This is facilitated by persistence of disease macroscopic bone alterations through time and across phylogeny.
Evolutionary development of a form of inflammatory arthritis (spondyloarthropathy) is now tracked back to Australopithicus sediba. Enthesial reaction and subchondral erosions support that perspective.

The evolution of inflammatory arthritis can actually be tracked as a trans-phylogenetic phenomenon as far back as the Permian, 300 million years before present. This approach allowed identification of rheumatoid arthritis as a much more recent phenomenon, curiously in an area not conditioned by tubercular exposure. Variation in microbiome was found not to influence prevalence of the form of arthritis recognized as spondyloarthropathy in non-human primates, but actually altered its skeletal distribution, suggesting a disease-limiting effect of such agents as Bifidobacterium.

The challenge of recognizing treponemal disease on the basis of skeletal alterations was presented, addressing preconceptions and the importance of evidential criteria-based studies.

Evolutionary development of lumbar curves, short transverse and spinal processes, and disk alteratons associated with reorganization of epaxial muscles and increased trunk rotation capability, may be responsible for the 80% lifetime expectance of an episode of low back pain.

Clinical applications of evolutionary medicine principles

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This detailed and interesting review from Mandy Azar needs reading through the MORE link.

 

This thought provoking session on the clinical applications of evolutionary medicine principles began with a case presentation. Dr. Robert Woods presented a case of a woman with a difficult to treat chronic infection of a prosthetic device. Multiple courses of powerful antibiotics and careful deliberation of treatment strategies using evolutionary principles failed to prevent this patient’s demise probably due to inadequate data. Precise analysis later revealed the culprit to be one single organism that probably thrived because of antibiotic resistance and a lack of microbial competition. Dr. Woods astutely demonstrated here, that even with awareness and application of evolutionary principles, there still can be significant challenges in individual clinical cases due to a lack of available evidence-based strategies in evolutionary medicine. He went on to emphasize that as it stands now, there are barriers to translational evolutionary medicine because most evolutionary studies focus on a single evolutionary mechanism in isolation and that often clinical scenarios are more complicated. There is also a dearth of clinical studies looking at evolutionary outcomes. However, he pointed out that such cases serve to illustrate the gaps in our collective knowledge and are useful in teaching and engaging students in evolutionary medicine.

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Our early life microbial metagenome guides developmental phenotypes

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Thanks to Joe Alcock for this fascinating commentary on Marty Blaser’s plenary lecture.

 

Marty Blaser of NYU delivered the second plenary lecture of the conference, entitled “Human Evolution 201: Our early life microbial metagenome guides developmental phenotypes”

Blaser points out that the Yanomami, an Amerindian group of hunter horticulturalists, have the highest microbiota diversity yet discovered on the planet. Most modern industrialized populations have lost 50% of this diversity, suffering increased losses with each of the last few generations in stepwise fashion. Blaser proposes that the ecological destruction of the microbiome is responsible for worldwide epidemics of obesity and autoimmune disease. Birth by cesarean section, formula feeding of babies, and modern diets are all responsible for the disappearing microbiome. But the biggest culprits, says Blaser, are antibiotics.

Millions of antibiotics prescriptions are filled each year in the US. In other countries, such as Peru, antibiotics are available over the counter, along with antacids and batteries. We have long known that antibiotics fatten farm animals from cows to chickens. In the same way, people too are fattened by early antibiotics. Our youngest patients are the group most exposed to antibiotics, which is a problem because it interrupts the normal dialog with microbes that guides developmental decisions. One mechanism involves depletion of gut microbes from antibiotics, leading to a change in Th17 immune cells and antimicrobial peptides in the gut. This causes durable changes in the gut microbiota predisposing to obesity. Transferring these microbes into germ free mice makes recipient mice obese, cementing the link between obesity and antibiotic depleted microbiome.

What can we do about this? Blaser argues that the next steps should focus on arresting or slowing the decline in microbiota diversity. This can be accomplished by choosing antibiotics more carefully. Macrolide antibiotics cause a durable destruction of microbiome diversity, while amoxicillin treated microbiomes bounce back pretty quickly. Childhood antibiotics appear to be particularly destructive and should be avoided when possible.

Better yet, Blaser imagines a day in which doctors restore microbiome species richness. Babies in the future might undergo a microbiome analysis, and then receive lost microbes, which would act like a vaccine to prevent obesity and autoimmune disease.

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