Joe Alcock MD

With that caveat in mind, my view is that evolution can inform most human illnesses, either in terms of phylogenetics, constraints, host-pathogen arms races, or evolutionary concepts of aging. Be sure to refresh your memory on all of these by reading this post again:

Read  http://evolutionmedicine.wordpress.com/categories-of-evolutionary-medicine-hypotheses/  before your presentation.

JA

So, after you have digested your turkey and pie, and spent time with your families, it will be time to focus on your final presentations.

By the way, here is the lecture handout from this week: milk

Be sure to click on the links above that describe the grading rubric and give another example of a final project presentation.

Here is what I will be looking for: Try to spend at least 50%, preferably more, of your time talking about ultimate causation, evolutionary considerations, or natural selection. In past years students have started their presentations with a lot of detail about proximate causes and leave their discussion of an evolutionary hypothesis until the last slide or two. That is not good. While I am listening to your presentation, I am waiting for the evolutionary hypothesis and evidence that you understand how to consider diseases in terms of evolution and natural selection  (otherwise I would not be teaching this course!). So make sure that evolution appears in your presentation before the halfway point in your presentation.

Read the section on evolutionary categories of disease (link above). One part of your grade is correctly identifying the category of evolutionary hypothesis, e.g. genetic conflict in pregnancy, evolution of virulence, host-pathogen arms race, balancing selection, gene-environment mismatch, etc.) If you can identify one or more concept from class, you will be rewarded! I am happy to answer questions by email this weekend.

It is good to include at least one alternative hypothesis. However, you do not need to include 3 alternatives as I did during my fatty acid presentation. We will want to hear about alternative evolutionary hypotheses, but sometimes there might not be such an alternative. In that case the alternative, or null hypothesis, might be a non-evolutionary hypothesis. I will write more about this in a future post this weekend.

Finally, practice your presentation, preferably with a timer. You all did well during your Journal Club presentations, but I understand the temptation to talk longer than you anticipated when you are excited about a topic. We will be under a pretty strict time constraint. I want you to aim for 12 – 15 minutes per presentation.

Good luck,

Joe

Next, read about the concept of lactase persistence and the concept of race in medicine:Unkindest cup

Finally, read this brief piece on human milk carbohydrates: First human prebiotics

This week’s writing assignment will be brief:

It has been suggested that 20% of the carbohydrate content in breast milk is indigestible by the infant! It might seem paradoxical and wasteful that the mother converts easily digested fuel (glucose) into indigestible milk oligosaccharides. Why doesn’t natural selection decrease or eliminate the production of oligosaccharides in human breast milk?

No more than 1/2 page please.

Long chain saturated fatty acids, because of their structure and high melting points, tend to stiffen the phospholipid bilayer when they are taken up into the cell membranes of bacteria (at least for some organisms). This makes membranes stiffer, and makes some bacteria more resistant to many stresses (such as high temperature during fever and exposure to gastric acid). Polyunsaturated fatty acids have a low melting point because their nonlinear conformation prevents close stacking, thus reducing the weak intermolecular bonds between hydrogen atoms. As the number of double bonds increases, so does the fluidity. This explains why PUFA like vegetable oils are liquid at room temperature while saturated fats like butter are solid. The same effect increases the fluidity of cell membranes and can decrease resistance to stress. PUFA can kill bacteria by themselves, with increasing antimicrobial effects with an increasing number of double bonds, as seen in the following figure adapted from Knapp and Melly ( J Infect Dis 154:1 84-93):

In this figure the number of carbon atoms is 20, and the number of double bonds follows the “:”. Saturated fatty acid fails to inhibit Staph aureus, while killing increases with each additional double bond.

It turns out that this pattern, increased antibacterial effects of unsaturated fat compared to saturated fat, holds for a variety of gut pathogens. This bioactivity of fatty acids may explain why the human immune system treats saturated fat and polyunsaturated fat differently.

Here is the powerpoint from today:

Dietary Inflammation

Next week we are going to talk more about the Paleolithic diet and the evolution of lactase persistence.

The basic idea is thus: Humans have coevolved with commensal organisms and pathogens probably since our distant ancestors became multicellular. Today, our bodies are a habitat for a multitude of microbes and viruses, the majority of which inhabit the gut, making up a community known as the microbiome. It turns out that these microbes number as many as 100 trillion, and the sum of their genes outnumber human genes by a ratio of more than ten to one. Thus, for as long as humans and our predecessors have been eating, we have shared the food we eat with the bacteria in our guts.  Nutrients have Jekyll and Hyde characteristics on the microbiome, and are sometimes helpful and sometimes harmful. Those nutrients that enhance the barrier function of the gut and prevent pathogen colonization and growth have evolved a signaling function that is thrifty, reducing the costs of an immune defense. Nutrients that impair the barrier function of the gut and increase the risk of pathogen colonization and invasion have the opposite effects. In class, we will present evidence that pro-inflammatory and anti-inflammatory signaling by nutrients help compensate for the positive and negative influence that nutrients have on the microbiome.

I will present this hypothesis in the format that I expect you to use for your final presentations, with no more than 15 slides, and taking no more than 20 minutes. However, I will allow more time for discussion afterwards, than you will have for your presentations (professor’s prerogative)!

Eat well, my friends,

JA

P.S. Please read Cani and Delzenne. For your writing assignment, please answer the following question:

Writing assignment: Evidence suggests that a high fat diet changes the composition of the gut microbes. Please explain the effect of eating vegetables and whole grains (high fiber diet) on gut bacteria and the gut’s ability to keep bacteria and their breakdown products where they belong (in the gut).  Explain also why eating a double meat double cheese Lotaburger with fries might be bad for your gut.

1 point extra credit (no more than 1/2 page): In class today, we discussed how maternal delivery of resources to the fetus  (resulting in a big baby or a small baby) can result in developmental programming that can lead to diabetes and obesity down the line. We also mentioned that maternal nutrient transfer to offspring does not end with birth; it continues with breastfeeding. Knowing this, speculate on the effect of breastfeeding on a baby’s likelihood of developing later obesity and diabetes. Defend your answer.

Please remember, the purpose of these writing assignments is to make sure that you read the reading, synthesize the information, and explain the ideas using your own words. I encourage you to read the assignments carefully with plenty of time before class, and thoughtfully craft a brief, logical argument on this topic. A usual these are due in class, on 11/15/11, in hardcopy. Homework turned in after class will receive one point off for lateness, if turned in after 11/15/11 will receive one extra point off per day it is late.

The reading for next week is posted above. Please get started early since it is a book chapter.

Writing assignment (read especially carefully pages 1-4):

Kuzawa points out that humans have the fattest babies of any mammalian species (p. 3-4, look also at Figure 1, p. 15. As he explains, there are several adaptive explanations for why this might be so:

#1. Insulation (p. 3). Human fat might help keep babies warm, since they have immature metabolism and high surface area (and lack of fur)  and thus have have difficulty regulating body temperature.

#2. Surplus energy that can be spent on brain development. This is Kuzawa’s idea, that fat is like a bank account of extra energy that permits human to have large brains that have large energetic demands. As Kuzawa points out, energy use by the brain cannot be turned off, unlike in other tissues like muscle.

For your assignment argue for #1 or #2.

For full credit, the writing assignment will be due in hardcopy in class next tuesday 11/8/11.

For extra credit (1 point), write a paragraph describing the thrifty genotype idea originally described by James Neel, that Kuzawa cites in his introduction. (no more than 1/3 to 1/2 page, maximum. You can look this up).

If you have too much time on your hands, you may watch a video lecture by Chris Kuzawa that he delivered at Yale in 2008. I recommend you watch this. It will really help you with the writing assignment. However, I am going to recap many of his major points in class, so this video is optional. If you want to watch it, you will need Real Player or Media Player to watch the videos. Click here and scroll down on this site and click on Chris Kuzawa’s Talk. As an extra bonus you can also watch David Haig’s excellent lecture on genetic imprinting on Prader Willi syndrome and Angelman syndrome. 

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I promised some additional information on 11/1/11′s topic: genomic imprinting and reproductive conflict.We discussed a variety of esoteric concepts and some phenomena that seem hard to explain via imprinting, e.g. gradual increase in birth weight with birth order, for instance. I should have pointed out that not all these phenomena require an imprinting explanation. Changes in birth weight can occur entirely because of maternal gene expression in the mother, which might serve to increase the delivery of nutrients to the developing fetus differently in different pregnancies. The “maternal provisioning” can occur outside of any effect from the fetus, and thus does not require imprinting to occur.

A student raised the question of imprinting as an all or nothing phenomenon, for example the IGFR pattern of inheritance that Haig discussed in his admittedly long paper. It turns out that partial expression of genes can also occur. This was recently shown in mice.

However, classic imprinting is usually thought of as a process that either turns on gene expression or completely silences it.

That process is thought to occur in the gene duplication/deletion events that can lead to human developmental disorders:

These disorders include Beckwith-Wiedeman syndrome (caused by either duplication of paternal IGF2 or inactive maternal CDKN1C), Prader Willi syndrome (caused by deletion of paternal 11p15.5 portion of chromosome 15 or duplication of maternal chromosome 15), among others.

The example that I tried to explain in class is that of Prader Willi syndrome. The chromosome that is involved in this syndrome is pictured here:

The genetic region at 15q11-q13 are usually expressed only when inherited from the father. Prader Willi syndrome occurs when that region is deleted in paternally derived genes, or when the maternally derived gene is doubly expressed, which happens when the baby inherits a two copies of chromosome 15 from the mother. In both cases, paternal imprinting is lost. Because of this maternal influence in prenatal fetal development and postnatal behavior is unopposed. This unmasking of maternally influence/imprinting makes these babies undemanding of maternal resources, they grow slowly in utero, they have a poor suck mechanism at birth, and they are remarkably un-picky when it comes to eating food (and non-food items) so that early weaning is the default condition. You can read more about this, and its opposite, Angelman’s Syndrome in this paper by David Haig.

Please read the following carefully before class!
1) Haig D. Genetic Conflicts in Pregnancy. Quarterly Review of biology. Volume 68(4). Dec 1993, 495-532:

Genetic conflicts in human pregnancy

2) Ness and Grainger  Male remale reproductive proteins and reproductive outcomes.

Writing assignment:

Why do genes from mothers and genes from fathers have different effects when expressed in the placenta or fetus?

You will all be given a break for this week. There is no writing assignment for next week.

Instead I want each of you to do some online searches on topics that you might want to do for your final project. Be prepared to come to class and discuss some of the things that you found. Read the section above on literature searches in evolutionary medicine. You can also, of course, use other search engines, like google or bing to look up some interesting information. We can discuss other strategies of gathering information during class next week.

Readings for next week (important to be prepared for discussion):

Easy required readings:

1. pork problem and 2.antibiotic resistance

3. antibiotics in agriculture

Optional reading on Banning antibiotics for animals in Denmark:

Lecture topic:

The topic of October 25 th is antibiotic resistance. We will explore how pathogens evolve resistance to antimicrobial agents and how medical professionals and researchers can develop strategies to reduce the evolution of resistance.

There are several strategies for reducing bacterial evolution of resistance.

1) Limiting use of antibiotics to proven bacterial infections and making sure that patients take their full course. This is what the CDC recommends. Some doctors are valiantly trying to make this a reality. Will they be successful?

2) Designing new antibiotics as the old ones become obsolete. Pharmacologists are screening thousands of plant and insect and other organisms for antimicrobial activity. There can be great financial reward in inventing a new antibiotic. Therefore the free market and the impressive capabilities of modern biotechnology should meet the needs of people into perpetuity. (Right?)

3) Cycling antibiotics. If you have 4 classes of antibiotics, you would use only one class for a certain period of time, then switch to the next, and so on over a predetermined period of time. The idea would be that just when bacteria might start to develop resistance, you switch to another. By the time you return to any given antibiotic in a cycle, hopefully the bacterial population would be sensitive to it. The rationale for persistence of sensitivity is that in between the times that antibiotic #1 is used, the bacterial population would have been selected for resistance to different antibiotics (#2, 3, 4)and they would lose resistance to the antibiotic #1. Seems logical doesn’t it?

4) Holding some antibiotics in reserve. Because much of the time resistance is incomplete, sometimes doctors can get some benefit from increasing dosages or increasing the schedule of older drugs. Then when necessary we pull the bigger guns off the shelf.

It turns out that some of these have been tested. Some work better than others.
See you next tuesday,

JA