In 1966, Dr. Peyton Rous of The Rockefeller Institute for Medical Research received the Nobel Prize in Physiology or Medicine for his discoveries on viral origins of some cancers. In an experiment, he collected cancerous connective tissue from a hen. He then filtered the tissue to remove bacteria as well as cancer cells and administered the purified filtrate to healthy chickens. The chickens that received the filtered substance began to develop cancer. This seemingly simple experiment was key to identifying that this type of cancer in chickens was caused by RSV, the Rous sarcoma virus, named after the scientist that discovered it. Dr. Rous continued to perform many other experiments that verified viruses could cause cancer.
In this Time Machine topic, we travel back in time to 1923 to take a look at another topic published by Dr. Rous in Physiological Reviews on the subject of “red corpuscles”, aka: red blood cells, or erythrocytes (Rous, 1923). In this review paper, Dr. Rous was keenly interested in describing what was known at the time about how and why red blood cells are destroyed in both healthy and diseased states. He wrote, “Somewhere there must exist in the body, if only for a moment, morphological evidence of the disintegration of every red cell.” He described in great detail many of the hypotheses at the time aiming to understand the normal turnover and longevity of red blood cells based on data from multiple species.
The two prevailing hypotheses were that red blood cells were at least in part destroyed by a type of phagocyte, or cells that ingest and break down substances or other cells, as well as by “occupational strain” causing them to break apart due to shear stress as they travel through blood vessels. He wrote, “The view that corpuscles may normally be threshed to pieces in the circulation is not new, nor will it seem strange to anyone who has watched in the living animals, a red cell saddle-bagged at a capillary fork, pulled well-nigh in two, with its bagging portions continually belabored and dragged upon by its passing fellows.” (Rous, 1923)
Dr. Rous detailed how some diseases can destroy or disfigure red blood cells. He noted that transfused red blood cells appear to last about 100 days in humans. Interestingly, Dr. Rous also surmised that differences in the rate of red blood cell destruction between species were inevitable, which research has since confirmed. In fact, the lifespan of a red blood cell is relatively long for humans at about 120 days in comparison to other species. Check out this list from Rodnan et al. (1956):
- Mouse: 22 days
- Chicken: 30 days
- Pigeon: 40 days
- Duck: 42 days
- Marmot: 36 days
- Rabbit: 55 days
- Rat: 58 days
- Pig: 62 days
- Cat: 73 days
- Dog: 100 days
- Humans: 120 days
- Turtle: 500 days (WOW!!!)
A recent review article published in Frontiers in Physiology, revisited the question about how blood cells are destroyed. The authors explained how red blood cells are indeed taken up by macrophages and destroyed after about 120 days in humans. In fact, every second, ~5 million red blood cells are destroyed in a healthy individual! Researchers are still unsure how macrophages can track down old red blood cells and target them for destruction. Several hypotheses have been proposed such as old red blood cells may express different proteins on their surface enabling detection, they may lose their ability to deform and squeeze through small blood vessels, among others. Whatever the signal, as blood is filtered by the spleen it enters a region packed with macrophages, resulting in a high amount of shear stress. Cells that are not able to deform, or are damaged in some way, are detected by these macrophages and destroyed. Although other means of recognizing aged cells likely happen as well (Thiagarajan et al., 2021).
Sources:
P Rous. Destruction of the red blood corpuscles in health and disease. Physiological Reviews. 3(1): 75-105, 1923.
GP Rodnan, FG Ebaugh Jr, MR Spivey Fox, DM Chambers. The life span of the red blood cell and the red blood cell volume in the chicken, pigeon and duck as estimated by the use of Na2Cr51O4: With observations on red cell turnover rate in the mammal, bird and reptile. Blood. 12(4): 355-366, 1957.
P Thiagarajan, CJ Parker, JT Prchal. How do red blood cells die? Frontiers in Physiology. 12: 655393, 2021.
Categories: Aging, Illnesses and Injuries, Time Machine
Tags: American Physiological Society, erythrocye, health, Physiological Reviews, red blood cell
Life Lines by Dr. Dolittle 
