Wednesday, February 20, 2013

Why the hereditary disease hemochromatosis persists

File:Red White Blood cells.jpg

Survival of the Sickest: the Surprising Connections between Disease and Longevity by Dr. Sharon Moalem and Jonathan Price explores the possible evolutionary pressures which have preserved diseases such as hemochromatosis, Type 1 diabetes, high cholesterol levels, and favism. The book gave interesting insights as to why diseases which are deadly today may have been potentiated. While the authors explored several different diseases, this review will focus on the explanations presented for the persistence of hemochromatosis.

Hemochromatosis:
Hemochromatosis, also called iron overload, is a hereditary condition which occurs when the body absorbs too much iron. The result is the accumulation of iron in organs such as the heart, liver, and pancreas, which in turn can lead to complications, including diabetes, liver failure, and heart failure. The symptoms of hemochromatosis can be alleviated through bloodletting, thereby reducing the amount of iron present, or through chelating agents which bind to iron and then may be excreted. If left untreated, hemochromatosis can be deadly.   

Dr. Moalem presents the hypothesis that hemochromatosis, while deadly today, originally protected people from the bubonic plague. Iron is targeted by bacteria, viruses, parasites, and cancer. Disease causing agents require it to persist, and they find it in the human tissue they infect. To combat this, iron is “locked up” when humans become sick in an effort to prevent the disease-causing organism from being able to survive. While people suffering from hemochromatosis have an excess of iron in many tissues, there is less iron than normal present in macrophages, a type of white blood cell. Because the bubonic plague utilized macrophages to spread through the body using the lymphatic system, people who had less iron present in macrophages were less likely to have the plague survive and multiply within the macrophages before it reached the lymph nodes. These people where therefore more likely to survive and pass on the gene for hemochromatosis.

The idea that iron-deficient macrophages are better at combating bacteria has been tested both in vivo and in vitro. In cell culture, iron-deficient macrophages are much more capable of successfully overcoming bacteria. Somali nomads who traditionally have had anemia became more susceptible to infection when given iron supplements. 

During the period of the Black Plague, one of the most famous outbreaks of the bubonic plague, young, healthy men were more likely to die than any other group. At the time, younger men would have been the least likely to have iron-deficiencies, and thus the most vulnerable to the plague. While this is not conclusive evidence as to why hemochromatosis was sustained within the population, it is an interesting hypothesis which is at least partially supported by studies today.

Claire Klimko

Word count: 440 words

Reference:

Moalem, Sharon and Jonathan Prince. Survival of the Sickest: the Surprising Connections between Disease and Longevity. New York: HarperCollins, 2007.

Image from http://en.wikipedia.org/wiki/File:Red_White_Blood_cells.jpg

9 comments:

  1. So individuals with hematochromatosis have excessive iron everywhere in their body expect in the macrophages?

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  2. did the presence of this disease increase after the bubonic plague because people with hematochomatosis were able to survive?

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  3. @Aydan I think the idea is that the iron is sequestered into organs, and the lack of iron in the freely-moving lymphatic system prevents the disease from surviving and spreading.

    @hannahm That is the hypothesis they proposed.

    Since the bubonic plague is no longer widespread, are there still some selective pressures that have been maintaining the disease? Or is hemochromatosis currently in equilibrium?

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  4. This is so cool! Also, interesting that a disease known for causing iron surplus saved people because of a specific type of iron deficiency!

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  5. It would be interesting to see whether descendants of populations heavily affected by the bubonic plague in the past now have higher prevalence of hemochromotosis. That would provide some good supporting data for this hypothesis.

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  6. Does hemchromatosis have the same affect of preventing malaria? Also would having the gene for sickle cell anemia help prevent the bubonic plague as well?

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  7. If the disease has a high enough prevalence today, it would be interesting to examine the environmental factors in the areas where more people with the disease live to see if there is a new reason it persists, or it it is truly an evolutionary artifact as these researchers suggest.

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  8. It'll be interesting to test if people with purely European ethnicity have more iron deficiency than people ethnically from areas that the Bubonic Plague did not affect. Great article, Claire!

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  9. This article reminds me of how those in sub-Saharan Africa with sickle cell anemia are often more resistant to malaria, while those with sickle cell in other areas don't necessarily have that advantage. I'd always wondered if there were other similar situations, where one potentially costly genotype actually helps to protect the individual from another hurtful disease. It's really cool to see that in play here with the bubonic plague and hemochromatosis.

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