Teardrop Cells.

September 10, 2006 1:09 PM

Vernon Ingram, who discovered the molecular cause of sickle cell anemia, has died.Dr. Ingram, a professor and active neuroscientist at MIT, demonstrated that conversion of glutamic acid to valine at position 6 of the ß-chain of human hemoglobin [Note: .pdf of original paper] was the sole abnormality in sickle hemoglobin. This seminal observation, which was based on an early version of 2-D protein electrophoresis, demonstrated that a protein abnormality in which a single amino acid is altered can produce a complex clinical disorder. Linus Pauling said, in response to Ingram's discovery, "“It is astounding that the difference in structure is so small – only about a dozen atoms out of 10,000 in the molecule are different. On such small atomies man’s fate depends!” Often called "The Father of Molecular Biology," Ingram's discovery is part of a remarkable, fascinating, and century long scientific endeavour to understand the biology of sickle cell disease.
posted by scblackman (12 comments total)

Two additional notes: First, unbeknownst to me, Ingram died on August 17th. His obituary appeared in the Boston Globe just today because a memorial service in his honor was being held today. Second, "teardrop cells" refer to dacrocytes, mis-shapen red blood cells that look like tears, and are seen in the blood smear of patients with certain blood disorders (e.g., myelofibrosis, pernicious anemia, myeloid metaplasia, thalassemia, and some hemolytic anemias).


posted by scblackman at 1:16 PM on September 10, 2006

I remember taking "Introduction to Genetics" and learning about sickle cell--a single substitution could produce a terrible disease. It impressed upon me how powerful the 'blueprint' was, and how fragile we were, and I eventually changed my major. Thanks for the reminder.
posted by toma at 1:51 PM on September 10, 2006

I just wanted to add that not only was Vernon an amazing scientist, he was also heavily involved in some of MIT's less conventional but well-loved and oft-imitated educational initiatives. For many years he led the Experimental Study Group*, a home at MIT for small-group freshman-level classes taught by outstanding upperclassmen, interesting seminars, and a strong community built around hammocks, Thursday night apple pies, and tesselating lizards.

*the joke being that after 35 years, it's still an experiment.
posted by whatzit at 2:34 PM on September 10, 2006

Nice post.

This is my field (pathology).

Sickle cells = drepanocytes.

*hates reading hemoglobin electrophoresis*
posted by i_am_a_Jedi at 4:51 PM on September 10, 2006

What Linus isn't saying there is that we've gone from a mostly a mostly hydrophobic side chain to something that's actually charged in most environments. Had it been a conservative substitution, like leucine or alanine, it might not make any difference at all.
posted by Kid Charlemagne at 5:03 PM on September 10, 2006

In a story with some interesting parallels to the tale of sickle cell anemia, a recent study discussed in the New Scientist, argues that cystic fibrosis, due to another single gene mutation which is fatal in a double dose, has been selected to its current surprisingly high levels in people of Western European descent because it confers resistance against tuberculosis.
posted by jamjam at 6:03 PM on September 10, 2006

,
posted by yhbc at 6:11 PM on September 10, 2006

Also, on jamjams theme, Sickle cell anemia is prevalent in populations from west africa because it confers resistance to malaria.

Evolution sez: better to live in pain than die of malaria.

A great loss to science BTW.
posted by lalochezia at 8:35 PM on September 10, 2006

Sickle cell anemia is prevalent in populations from west africa because it confers resistance to malaria.

Spherocytosis and elliptocytosis, two more oddly-shaped red blood cell disorders, also provide malaria resistance, but are far less horrible than sickle cell, and rarely fatal. More of a chronic annoyance, really. Why couldn't evolution have chosen one of them to become the prevalent protective mutation in Africa, rather than such an awful one?
posted by Asparagirl at 8:40 PM on September 10, 2006

Outstanding post cblackman.

Evolution sez: better to live in pain than die of malaria.

Why couldn't evolution have chosen one of them to become the prevalent protective mutation in Africa, rather than such an awful one?

Evolution? It seems a bit presumptious to lump every genetic mutation under a theory of reproductive fitness. Many mutations, it seems, tend to lead to extinction, rather than evolution. "Surival of the fittest" is not the same thing as reproductive fitness (i.e., evolution.)
posted by three blind mice at 9:16 PM on September 10, 2006

It's not like the evolution committe gets together and makes informed decisions on these things after checking out all the options. Individuals live long enough to get their genes into the next generation or they don't.
posted by Kid Charlemagne at 12:47 PM on September 11, 2006

TBM and KS: Well, duh. Note use of the word 'sez' rather than 'says'.

There is a high correlation between sickle cell and malaria suvivability. Furthermore, there are a variety of plausible mechanisms postulated which are contingent on having the mutations that cause SCA. Thus, having the mutations that lead to SCA in malarial zones enables you to reproduce more effectively and care for your infants so *they* can reproduce more effectively, and results in a wider spread of SCA-causing mutations in these areas than areas not subject to malaria.

Not QED, but as pretty close for this kind of science.
posted by lalochezia at 1:04 PM on September 11, 2006