Journal Club September 23

Each group will present their assigned article on 9/23/14

The name of the game of these presentations is to present the major ideas of the article and to provide a critique. Each student will need to make part of the presentation individually.

Each group must decide whether they think the article is a good one or not. There is at least one questionable article in the bunch.

Each group will have 20 minutes to make their presentation. Each group will need to meet or Skype to discuss how you are going to divide up each topic for presentation next Tuesday.

Grading will be based on how well the student is able to explain the following:

1) What is the condition or disease described in the paper?

2) What is the proximate explanation for the disease (no more than a sentence or two).

3) What are the evolutionary hypotheses to explain the condition? If there are multiple hypotheses, each student should present an individual idea. The evolutionary reasoning should be carefully explained so that the audience can understand the concept.

4) Does the paper present any data? Are the ideas supported by evidence?

5) Does the logic of the paper make sense? Is it a flawed paper that whose conclusions are questionable?

6) Which hypothesis makes most sense to you? Would you recommend the paper for the next year’s class?

Additional points towards the grade will be given for presentation style. This includes good eye contact and understandable speech.

Group 1:

Greaves Human Skin Pigmentation

Group 2:

Rhys-Evans Aquatic Ape

Group 3:

Yolken Psychosis and infectious agents

Group 4:

Lindqvist Factor V Leiden and Evolution

Personalized Genomics

What does personalized medicine mean in the era of inexpensive gene sequencing? What can we make of our own personal genetic variation? We will explore these ideas in next Tuesday’s class, with Katina Krasnec’s guest lecture.

Here is the essay question for next week:

Do you think personalized medicine and genome sequencing is the way of the future? What are the risks and benefits of having this genetic information? How should patients and medical professionals use personal genomic data in light of privacy concerns and potential treatments?

1) Galvani and Novembre. The evolutionary history of the CCR5 Δ32 HIV-resistance mutation. Microbes and Infection (2005) vol. 7 (2) pp. 302-309 Microbes and Infection 2005 Galvani

2) Vargas et al. Pros and cons of a missing chemokine receptor—Comments on “Is the European spatial distribution of the HIV-1-resistant CCR5-Δ32 allele formed by a breakdown of the pathocenosis due to the historical Roman expansion?” by Eric Faure and Manuela Royer-Carenzi (2008). INFECTION, GENETICS AND EVOLUTION (2009) vol. 9 (4) pp. 387-389 INFECTION GENETICS AND EVOLUTION 2009 Vargas

3) Glass. CCR5 deficiency increases risk of symptomatic West Nile virus infection. Journal of Experimental Medicine (2006) vol. 203 (1) pp. 35-40 Journal of Experimental Medicine 2006 Glass

4) Caulfield et al. Reflections on the Cost of “Low-Cost” Whole Genome Sequencing: Framing the Health Policy Debate. Plos Biol (2013) vol. 11 (11) pp. e1001699  Plos Biol 2013 Caulfield
5) The man who had AIDS and now does not

6) Atlantic article

7) Big data DNA

Optional extra:8) Optional Reading Allers et al. Evidence for the cure of HIV infection by CCR5 32/ 32 stem cell transplantation. Blood (2011) vol. 117 (10) pp. 2791-2799 Blood 2011 Allers

and 9) NYT

When to treat…when to leave alone

In this weeks class, we introduced the idea of normal in medicine. What is normal? Can the concept of adaptation help guide what to do with an “abnormal finding”? We confront these questions all the time in the hospital. Now it is your turn to weigh in.

Lets start with a patient case: He is 48 years old, with a history of alcohol abuse, and a fever for 2 days. He has been coughing with grey sputum and bloody streaks for the last 24 hours. Increasingly short of breath, he calls 911 and is brought to the emergency department.

His chest x-ray looks like this:

Left lower lobe pneumonia

His temperature is 40°C.  Anything above 38°C (100.4 °F) is considered a fever.

Blood cultures are drawn and antibiotics given. He is transferred to the ICU because his oxygen levels and blood pressure continue to drop. In the ICU, his doctor diagnoses him with septic shock. She also orders a dose of acetaminophen (also known as tylenol or paracetamol) to reduce the fever. Medications like tylenol that reduce fever are known as antipyretics, and are commonly prescribed for febrile patients in and out of the hospital.

Was the tylenol a good move or a bad one?

Evidence from animal studies support the view that fever is beneficial (read the abstracts in the links in this section). Matthew Kluger back in the early 1970s showed that a behavioral fever was critical in keeping lizards alive after experimental infection with gram-negative bacteria. Kluger subsequently showed that fever improves bacterial killing by immune cells.

One relevant fact, arguing for the evolution  of fever, is the fact that it exists in a wide variety of organisms, as reviewed here. Even some invertebrate organisms exhibit a behavioral fever, including grasshoppers, honeybees and snails.  Animal studies suggest that antipyretic use (aspirin) increases mortality from Streptococcus pneumoniae infection With these lines of evidence, you would think that we should certainly not treat fever with tylenol. But we still do, all the time. The human data is not as clear as the animal studies. Some evidence suggests that treating fever is not harmful for our patients.

Carefully read all the links in this section:

1) Young and Saxena’s review in the journal Critical Care on fever and its treatment.

They write:

“Remarkably, at present we do not know what effect treating fever in critically ill patients with infections has on patient-centered outcomes.” In other words, legitimate controversy exists about whether to give a patient tylenol or not.

2) Drewry and Hotchkiss  argue for giving antipyretic treatment for patients with sepsis (blood infection).Point- Should Antipyretic Therapy Be Given Routinely to Febrile Patients in Septic Shock? Yes

3) Moer and Doerschug argue against using antipyretics in sepsis.Counterpoint- Should Antipyretic Therapy Be Given Routinely to Febrile Patients in Septic Shock? No

Optional:  Schortgen et al, about using external cooling blankets for critically ill patients. I recommend reading this if you think we should be treating fever.

Writing assignment – consider the following statement (Young and Saxena 2014):

“arguments based on the evolutionary importance of the febrile response do not necessarily apply to critically ill patients who are, by definition, supported beyond the limits of normal physiological homeostasis. Humans are not adapted to critical illness.

This logic was expressed by Foddy (2012) who wrote: “The argument from evolution assumes some degree of continuity in environmental circumstances, but at present there are strong discontinuities in the structure of our world. Given these changes, it would be foolish to place too much trust in the adaptive quality of traits that evolved across aeons of nomadic hunting and gathering.” One such discontinuity is the availability of ICU care, right?

On the other hand, consider the argument from Fukuyama (2002) who wrote:

“There are good prudential reasons to defer to the natural order of things and not to think that human beings can easily improve on it through causal intervention. This has proven true with regard to the environment: ecosystems are interconnected wholes whose complexity we frequently don’t understand, building a dam or introducing a plant monoculture into an area disrupts unseen relationships and destroys the system’s balance in totally unanticipated ways. So too with human nature … doing nature one better isn’t always that easy, evolution may be a blind process, but it follows a ruthless adaptive logic that makes organisms fit for their environments.”

Depending on your point of view, fever, even if evolved, might or might not be helpful or adaptive for our sickest patients.  The ICU is a novel environment that keeps (some) patients alive who would otherwise die. It is not the environment that humans evolved in (think gene-environment mismatch).  With this in mind, do you think that evolution and adaptation is irrelevant for hospital patients who are closest to death? Defend your answer with your own logic, and with examples from the readings and quotations above. Should we treat patients with fever in the ICU with tylenol (yes or no)?

Strongly recommended – listed to this excellent talk by an expert on fever:

Listen to Paul Young give an evolution-minded lecture on the function of fever and the HEAT trial

Skip the intro by going to minute 3:48.

Additional optional references:

Best and Schwartz. Fever Evolution Medicine and Public Health (2014) 2014 (1): 92. doi: 10.1093/emph/eou014

Fukuyama, F. (2002). Our posthuman future: consequences of the biotechnology revolution. New York: Farrar, Straus and Giroux.

Foddy, B. (2012). The Right and Wrong of Growing Old: Assessing the Argument from Evolution. Philos. Technol. (2012) 25:547–560

Evolution and human genetic variation – adaptation to high altitude

Next week we will cover recent human evolution. Certain populations have adaptations to high altitude hypoxia and to certain foods.

We will discuss the evolutionary biology of high altitude peoples of the Andes, Himalayas, and Ethiopian Plateau. For discussion: How might gene-environment mismatch account for acute mountain sickness in Europeans? How many generations does it take to evolve solutions to the problem of living in a high altitude environment?

We will explore the different routes to physiologic adaptation in Tuesday’s class.

Handout for Tuesday’s lecture:

High Altitude Cultures

Readings for September 2nd:

1. Beall

2. Genes at high altitude

3. Genomic Signatures Reveal High Altitude Adaptation

Optional altitude readings:

http://news.nationalgeographic.com/news/pf/92910801.html

http://www.sciencedaily.com/releases/2010/05/100513143453.htm

http://www.sciencedaily.com/releases/2012/01/120120184530.htm

Also, why do some populations have trouble digesting milk?

Digestive problems with milk are common in some adult populations. However, some people have the ability to consume milk into adulthood, even though adults consumed no milk throughout most of human evolution.

Please read the following about lactose intolerance/lactase persistence:
1) Unkindest cup

2)  Human lactase

Optional extra readings:

3)  Tishkoff

Writing Assignment:

Why do the three major high altitude groups each have different adaptations to altitude?

The evolution of aging

Spawn til you die by Ray Troll

Spawn til you die by Ray Troll

Selection is powerful, but has limits in maintaining function, especially with advancing age. Moreover, tradeoffs involving selection are ubiquitous in biology, and can help explain the evolution of aging.

As an example, I am more likely to admit a 70 year old with chest pain than a 20 year old. Understanding age-related risk of death and age-related complications of procedures can be best understood as an outcome of evolution of life history traits.

We are going to cover evolutionary hypotheses of senescence during this week. These hypotheses include antagonistic pleiotropy, declining power of selection, and mutation accumulation.  This link does a nice job of explaining the concepts.

Antagonistic pleiotropy is the concept that a gene for survival or a gene that promotes
reproduction early can be selected for even if it kills you at a later
age. So selection favors juvenile survival at the expense of old age survival. This hypothesis recognizes that most traits have both costs and benefits, and are tradeoffs. The tradeoff in antagonistic pleiotropy is improved health in youth, but disease in old age.

Haldane and Medawar proposed the declining power of selection hypothesis of aging. This proposes that genes for maintenance and repair of the body are selected for more strongly at early ages (pre-reproduction) than after reproductive age. For this: imagine a hypothetical gene that prevents cancer at age 10 and another gene that prevents cancer at age 100. The gene that prevents cancer at age 100 will not have any effect most of the time because most people are dead by age 100 (this remains true even if you take senescence out of the equation – random accidents will claim many lives). The gene that affects 10 year olds is more likely to be expressed and have a benefit simply because most people are alive at age 10. Therefore the old-age gene will be invisible to natural selection, the gene that affects 10 year old will be subject to positive selection.

Medawar extended his idea to include mutation accumulation. This idea posits that the body accumulates deleterious mutations at late ages that, because of the declining power of selection, are not selected against, and thus accumulate. In wild populations, not enough organisms reach advanced age, so these mutations are invisible. If allowed to achieve advanced chronological age, these mutations exert damaging effects, reducing fitness and contributing to senescence.

The disposable soma hypothesis is another idea to explain aging. This hypothesis recognizes that the nonreproductive part of the body (the soma) exists only to support the reproductive part of the body. At any moment in time an adult can devote energy to the maintenance of the body or to reproduction. Put simply, after successful reproduction, the soma is “disposable”, and genes are passed on. This tradeoff is vividly illustrated in adult salmon, which appear to do all their aging at once, immediately after a single reproductive effort. In many animals, bearing offspring shortens lifespan. There is some evidence of this in humans too.

Writing Assignment

Menopause is a strange phenomenon, because it represents premature aging of the female reproductive organs, asynchronous with the rate of decline in function for the rest of the body. It is paradoxical because it would seem that natural selection would favor maximal reproduction throughout the lifespan for humans. Given the fitness benefits of continued reproduction, why does the female reproductive organ age faster than the rest of the body? Humans are nearly unique in having a menopause; apparently killer whales are another example (see below).

Some suggest that menopause evolved because grandmothers are more successful at passing on their genes by investing in grandchildren than in more babies of their own. Others argue that menopause is a consequence of modern medicine prolonging the lifespan of women past 60 when most pre-historic women would be dead. So in the past reproductive aging would have been in sync with aging of the rest of the body. In this view menopause reflects the early mortality in pre-history and is a gene-environment mismatch.

In 3/4 page, explain why women cease to reproduce in middle age? Do you agree with the Grandmother hypothesis?

Readings for next week:

1. Age-old-question Flatt T and Promislow EL. 2007. Science (318) 1255-1256.

2. Why do we age? Kirkwood Austad Nature 2000

3. Evolution of the human menopause Shanley DP and Kirkwood TB. 2001 Bioessays 23. 282-287.

4.  Menopause in killer whales

(Read also the Alcock and Schwartz 2011 and Stearns 2013 papers in the previous post.)

Welcome Evo Med Students

The 2014 UNM Evolutionary Medicine course meets for the first time today in Castetter Hall room 258. (The illustration above shows a timeline of first antibiotic use and date of first recorded antibiotic resistance – from Clatworthy et al. 2007 Nat Chem Biol 3, 541-8). In this class we will discuss antibiotic resistance and a wide variety of other evolutionary topics in medicine.

Readings for this week include:

1. Alcock and Schwartz 2011 A clinical perspective in Evolutionary Medicine: What we

wish we had learned in medical school. Evolution: Education and Outreach, 2011.

2. Stearns . Evolutionary Medicine: Its Scope, Interest, and Potential. Proceedings of the Royal Society B, 2013.

Here are the slides from the first lecture: Introduction to Evolutionary Medicine 2014

 

Microbial Manipulation in the New York Times – Updated.

“Maybe the microbiome is our puppet master”

So writes Carl Zimmer, reporting on a paper that Athena Aktipis and Carlo Maley and I wrote about microbial manipulation of human behavior. Zimmer’s article appears in the New York Times Science section.

Update! Alcock, Maley, and Aktipis was featured on the Evolution and Medicine Review.

Click on the link to read our Bioessays abstract:

Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms

Also: read this excellent recent review on the same topic by Mark Lyte (full text):

Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior.