For life on this planet, iron is not optional. It is essential. When our iron levels are low, we can get sick, and when they get really really low, we can even die. But you know what they say, too much of a good thing can be a bad thing. In the case of iron, the genetic condition hemochromatosis is often to blame for iron overload, but why is too much iron a bad thing? In this episode, we explore that question and many others, starting with why iron is a biological non-negotiable and how a lack of iron regulation in hemochromatosis can lead to severe tissue damage. Then we’re going Deep Time™ to suss out the origins of our dependence on iron, a journey that eventually leads us to the Neolithic Revolution and the 20th century realization that a certain ancient medical practice is not as obsolete as previously thought. Tune in to catch us ironing out the details of this incredibly common genetic disorder.
| History | Biology |
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| Butler, Thomas. “Plague gives surprises in the first decade of the 21st century in the United States and worldwide.” The American journal of tropical medicine and hygiene 89.4 (2013): 788. | Kane, S.F., Roberts, C. and Paulus, R., 2021. Hereditary hemochromatosis: rapid evidence review. American family physician, 104(2), pp.263-270. |
| Crosby, William H. “A history of phlebotomy therapy for hemochromatosis.” The American journal of the medical sciences 301.1 (1991): 28-31. | Pietrangelo, A., 2010. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology, 139(2), pp.393-408. |
| Datz, Christian, et al. “Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women: a protective role against iron deficiency?.” Clinical chemistry 44.12 (1998): 2429-2432. | Adams, P.C., 2015. Epidemiology and diagnostic testing for hemochromatosis and iron overload. International journal of laboratory hematology, 37, pp.25-30. |
| Denic, Srdjan, and Mukesh M. Agarwal. “Nutritional iron deficiency: an evolutionary perspective.” Nutrition 23.7-8 (2007): 603-614. | Iron: Fact Sheet for Health Professionals. NIH, June 15,2023. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/ |
| Distante, S., et al. “The origin and spread of the HFE-C282Y haemochromatosis mutation.” Human genetics 115 (2004): 269-279. | Hurrell, R. and Egli, I., 2010. Iron bioavailability and dietary reference values. The American journal of clinical nutrition, 91(5), pp.1461S-1467S. |
| Heath, Kathleen M., et al. “The evolutionary adaptation of the C 282 Y mutation to culture and climate during the European Neolithic.” American Journal of Physical Anthropology 160.1 (2016): 86-101. | Piskin, E., Cianciosi, D., Gulec, S., Tomas, M. and Capanoglu, E., 2022. Iron absorption: factors, limitations, and improvement methods. ACS omega, 7(24), pp.20441-20456. |
| Hodgskiss, Malcolm SW, et al. “A productivity collapse to end Earth’s Great Oxidation.” Proceedings of the National Academy of Sciences 116.35 (2019): 17207-17212. | |
| Hollerer, Ina, André Bachmann, and Martina U. Muckenthaler. “Pathophysiological consequences and benefits of HFE mutations: 20 years of research.” haematologica 102.5 (2017): 809. | |
| Khan, Fida A., Melanie A. Fisher, and Rashida A. Khakoo. “Association of hemochromatosis with infectious diseases: expanding spectrum.” International Journal of Infectious Diseases 11.6 (2007): 482-487. | |
| McCullough, John M., Kathleen M. Heath, and Alexis M. Smith. “Hemochromatosis: Niche construction and the genetic domino effect in the European Neolithic.” Human Biology 87.1 (2015): 39-58. | |
| Moalem, Sharon, et al. “Epidemic pathogenic selection: an explanation for hereditary hemochromatosis?.” Medical hypotheses 59.3 (2002): 325-329. | |
| Olejarz, Jason, et al. “The Great Oxygenation Event as a consequence of ecological dynamics modulated by planetary change.” Nature communications 12.1 (2021): 3985. | |
| Parapia, Liakat Ali. “History of bloodletting by phlebotomy.” British journal of haematology 143.4 (2008): 490-495. | |
| Quenee, Lauriane E., et al. “Hereditary hemochromatosis restores the virulence of plague vaccine strains.” The Journal of infectious diseases 206.7 (2012): 1050-1058. | |
| Symonette, Caitlin J., and Paul C. Adams. “Do all hemochromatosis patients have the same origin? A pilot study of mitochondrial DNA and Y‐DNA.” Canadian Journal of Gastroenterology and Hepatology 25.6 (2011): 324-326. | |
| Wade, Jon, et al. “Temporal variation of planetary iron as a driver of evolution.” Proceedings of the National Academy of Sciences 118.51 (2021): e2109865118. |
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