Athena Aktipis & Carlo Maley – Evolution of Cancer

Cancer is a micro-evolutionary process at the cellular level. Our guest lecturers next week will show you how the application of evolutionary theory to cancer has potential for a future Nobel prize. It will also illustrate why every medical student needs to understand evolution. (You are the lucky ones!) Cancer evolution has many parallels with the evolution of antimicrobial resistance. Many antibiotic resistance concepts apply here too, especially for the evolution of chemotherapy resistant cancer clones.

Athena Aktipis and Carlo Maley are two extremely talented evolutionary medicine researchers who have launched the Center for Evolution and Cancer at UCSF and are currently at the Center for Evolutionary Medicine at Arizona State University.

Aktipis

Athena Aktipis PhD

Athena Aktipis is the Director of Human and Social Evolution and co-founder of the Center for Evolution and Cancer at the University of California, San Francisco, and a Research Scientist in the Psychology Department at Arizona State University.  She is a theoretical evolutionary biologist, cancer biologist and cooperation theorist who now works at the intersection of these fields.  Dr. Aktipis is the author of the forthcoming book from Princeton University Press “Evolution in the flesh: Cancer and the transformation of life.”

maley

Carlo Maley PhD

Carlo C. Maley is the director of the Center for Evolution and Cancer at the University of California, San Francisco. Dr. Maley is interested in the evolution of cancer, both at the level of cells evolving in neoplasms and at the level of the effects of cancer as a selective pressure on multicellular organisms. The Maley laboratory is exploring fundamental concepts in neoplastic progression, the process by which normal tissue becomes cancerous, and the evolution of therapeutic resistance, for purposes of developing better methods for cancer prevention and therapy. Carlo studies the evolution of clones during neoplastic progression of Barrett’s esophagus as well as the selective effects of therapy in acute myeloid leukemia (AML) and esophageal adenocarcinoma. It is also developing the comparative biology of cancer to determine how large, long-lived organisms like whales are able to suppress cancer 1000-fold better than humans.

You can read more about Athena and Carlo here and here.

Required Reading:

1. Life history tradeoffs in cancer

Optional extras:

2. Aktipis Kwan et al Overlooking Evolution: A Systematic Analysis of Cancer Relapse and Therapeutic Resistance Research. PLoS One. 2011;6(11):e26100. Epub 2011 Nov 17.

3. Aktipis, Maley, and Pepper. Dispersal Evolution in Neoplasms: The Role of Disregulated Metabolism in the Evolution of Cell Motility. Cancer Prevention Research, Feb 2012.

4.  Merlo et al. Cancer as an evolutionary process

Assignment for November 4th: There is no writing project this week. But, I do want you to do some online research for this week. Try to find an article about the pros and cons of widespread screening for cancer. Should we be testing everybody for cancer, at younger and younger ages? If it is true that the earliest cancers are treatable, and finding them makes treatment possible, shouldn’t we screen everybody every year for every cancer? Why or why not?

 

Evolution of Artemisinin Resistance – Lecture Today

Roland Cooper PhD will be giving another talk today in the Innovation Discovery and Training Complex (IDTC) at UNM at 1:00pm, entitled, Translational studies in malaria – surveillance for artemisinin resistance in Uganda.

Map is here.

Flyer is here.

International and Global Health Lecture October 29th 1:00pm-2:00pm

Department of Emergency Medicine, University of New Mexico

Location: IDTC Room 1610

Truth in Research

John Ioannidis published a now classic article Why most published research findings are false.

An easily digestible write up of that paper appeared in the journal Atlantic. Lies, damned lies, and medical science.

Both the above are must reads for anyone embarking on a career in medicine or bioscience.

Now, John Ioannidis followed up his previous work with a new article published this week: How to make more published research true.

I highly recommend reading all of these.

One reason why published research is wrong – cognitive bias:

Screen Shot 2014-10-27 at 10.01.38 AM

(For evolutionary medicine students, the links above are optional extras for discussion only)

Roland Cooper – Guest Lecture 10/28/14

Guest Lecturer Roland Cooper PhD

Title: Evolution of artemisinin-resistant malaria

-1

Roland Cooper PhD is an associate professor in the Department of Natural Sciences and Mathematics at Dominican University in San Rafael, California. Dr. Cooper has studied the genetics and biological mechanisms of drug action and resistance evolution in malaria since 1997. He has been part of the NIH team to discover the genetic basis of chloroquine resistance in Plasmodium falciparum malaria Since 2010 Dr. Cooper has been engaged in translational research on malaria in Uganda, where he studies drug resistant malaria in children, as part of a chemoprevention trial administered by UCSF. His work is now focused on artemisinin resistance evolution in Africa.

plasmodium-life-cycle
No writing assignment this week.

Readings:

Klein

Sibley

Artemisinin resistance evolution NEJM

Student assignment: come prepared to talk about a news headline or journal title that has implications for evolution and medicine. Good luck!

Anorexia of Illness

What is anorexia of illness?

During sickness it is very common to lose one’s appetite and reduce energy intake. This anorexia of illness is one of a group of symptoms collectively known as sickness behaviors. Whether anorexia and other sickness behaviors are adaptive is uncertain and the optimal amount of nutrition to provide during illness is an unanswered question in medicine. However, various authors have speculated that anorexia of illness might be beneficial by assisting host defense during infection or by changing energy provisioning for various parts of the body.  If true, it is possible that providing fewer than normal nutrients during illness might speed recovery and improve survival. On the other hand, malnutrition or starvation has been associated with mortality in infection.

What are the possible benefits of illness anorexia?

Exton (1997) postulated that anorexia may be beneficial by limiting the availability to pathogens of essential trace metals, notably iron; and he presented evidence that dietary restriction can enhance certain immune functions.

Straub et al. (2010) proposed an “energy appeal reaction” model that sees the catabolic state of the APR as an attempt to redirect nutrient energy toward meeting the high metabolic costs of fighting infection.

Anorexia also promotes cell apoptosis and might aid in pathogen clearance (LeGrand 2000). Anorexia may also be a gamble on the part of the host that the host can better withstand the nutritional stress better than the invading organism.

Because the host has stored energy reserves, anorexia may disproportionately affect gut pathogens and make infected intestinal epithelial cells more susceptible to apoptosis (LeGrand and Alcock 2012).

Anorexia may occur as a means of preventing pathogenic gut microbes from gaining access to growth limiting nutrients (LeGrand and Alcock 2012).

The idea of permissive underfeeding in critical illness was proposed by Zaloga and Roberts (1994). They hypothesized that maximizing nutrition “may adversely affect the host response to injury, especially when given in excess of energy and protein needs.” Recent evidence suggests that calorie restriction during illness might be protective:

Is there evidence from animal experiments?

Adamo et al. (2007), working on the assumption that anorexia during infection is beneficial, found that force-feeding bacterially infected caterpillars with a high lipid diet increased mortality.

Murray et al. (1978) force-fed Listeria-infected mice back to their preinfection food intake levels and found that these mice with “good/normal nutrition” had lower survival than did the infected sham force-fed mice.

Is there evidence from human trials?

More recently, human trials have shown similar results:

Observational trials:

Patients with higher illness severity were found to have longer stays in the ICU when feeding was initiated early, versus late (Huang et al 2012). Arabi and colleagues showed that achieving target nutrition (e.g. higher calories) is associated with worse outcomes in the ICU (2010) in keeping with previously reported work (Krishnan et al. 2003). This idea remains controversial, and other observational studies have reported better outcomes with higher calorie delivery (Heyland Cahill and Day 2011; Elke et al.  2013).

Randomized controlled trials:

Arabi and colleagues (2011) randomized patients to underfeeding (60%) vs. normal (100%) replacement of calorie needs in critical illness. This group found decreased deaths in the underfeeding group.
Writing Assignment

You are called to do a nutrition consultation for a patient in the ICU. The question is should we feed this patient less calories, more calories, or the same calories as the patient needed before they got sick?

Reading 1: Self-Medication as Adaptive Plasticity: Increased Ingestion of Plant Toxins by Parasitized Caterpillars (for discussion)

Reading 2 Schetz artificial nutrition (for writing assignment)

Reading 3 (mandatory; emailed to you, contact me if you did not receive it)

Optional (but recommended for the writing assignment) reading 4:

Kenra et al Infection and Anorexia

More references:

Krishnan JA, Parce PB, Martinez A, Diette GB, Brower RG. Caloric intake in medical ICU patients: consistency of care with guidelines and relationship to clinical outcomes. Chest 2003, 124: 297-305.

Manipulation

Microbial Manipulation

For an introduction, read this Berkeley Science Review.

And: How Pernicious Parasites Turn Victims into Zombies.

And Carl Zimmer’s article in the New York Times Science section.

The human gut microbiota has been described as a “forgotten organ” that is essential to human health and happiness. Evidence suggests that commensal microbes are protective against allergy, nutrient deficiency, and certain infections. However, not all interactions between vertebrates and their microbes are friendly. Competition for nutrients and other resources can cause conflicts of interest in the metagenome, the combination of human and microbial genes. Metagenomic conflicts of interests might drive some unhealthy eating behaviors, since nutrient energy is shared between the host and microbiota. This hypothesis has implications for food cravings and the obesity epidemic.

1. Required Reading Alcock-aktipis-maley-puppetmaster

2. Optional extra: Lyte 2014 Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior.

Writing assignment (1 page max): Do you think it is likely that our food cravings are driven by the evolutionary interests of our gut microbiota? Why or why not? What are the other explanations for why we crave fatty, sugary, and salty foods? (remember that you do not need to agree with the argument in the paper.)

The Hygiene Hypothesis

The prevalence of allergic diseases has dramatically increased in recent decades, and these diseases currently affect one in five people in the US. Allergic and autoimmune diseases also reduce quality of life and they are expensive, costing approximately $15 billion annually. The massive increase in allergy has occurred along with many social changes, such as altered infant feeding practices, antibiotic use, urban living, and reduced family size. All these lifestyle changes can result in reduced microbial exposure. How important could it be to have a diverse microbiota in early life?  More generally, how does exposure to microorganisms affect chronic inflammation and allergic diseases? Is exposure to a diverse microbial environment a good or bad thing for human? Should physicians treat diseases by manipulating gut bacteria?

Bach 2002

Bach 2002 NEJM 347:12

Writing assignment:

How does exposure to microorganisms affect chronic inflammation and allergic diseases?  Is exposure to a diverse microbial environment a good or bad thing for humans?

Readings:

1)HygieneHypothesis

2) 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis 2010. Rook G. Clinical and Experimental Immunology. 160: 70–79. (optional)

3) Missing Microbes

(If you have time, listen to the interview and read the excerpt in the link above.)

4) Bach Hygiene Hypothesis

Optional extras:

Highly recommended Radiolab program on hygiene and hookworm:

Radiolab hookworm story

Excellent NPR piece on microbiota diversity:

Microbiota