Caso Clínico

Sickle Cell Anemia
Section 1: The Inquiry Begins
By Debra Stamper Department of Biology, King's College

Objetives:
After completing this section of the case, students will be able to: identify pieces of experimental evidence. determine whether one piece of experimental evidence supports another piece. determine the need for "blind" tests. recognize how the side groups of amino acids caninfluence the overall charge of a protein. recognize the interdependence of the different levels of protein structure recognize the need to address a problem from different angles (or using different techniques)

It was a brisk fall day in Boston--the type of day that Dr. William Castle preferred to start with a cup of coffee while he caught up on his correspondence, which often appeared to be anendless task. As a faculty member of Harvard Medical School, he had always received a fair amount of inquiries, but after he had published his data indicating that pernicious anemia was due to a vitamin B12 deficiency, the amount of mail he received was sometimes overwhelming.

Sitting in his reclining chair he sorted through the large pile that had accumulated. He began to meticulously segregateit into smaller piles he would open in a prescribed order. Usually the delegation of a particular envelope was a relatively easy choice. There were a few that caused him to pause for a moment, such as the one he was currently holding. The return address indicated it was from an Irving Sherman at Johns Hopkins University. Since it was from someone he had never heard of, he was inclined to place itin the pile to be opened later. But on this day he decided to take another sip of coffee and see what Mr. Sherman had to say.

Bioquímica I

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"Well, this may have some merit," Dr. Castle mused to himself. He recognized that these results indicated it was likely that there was a difference in one or more molecules found either in the blood or within the red blood cells. Sincesickle cell anemia was named due to the change in the shape of the red blood cells, the molecule involved was most likely within the red blood cells. Dr. Castle placed the letter in a conspicuous place on his desk so that he would remember to send a reply to the ambitious student.

Bioquímica I

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A few months later, Dr. Castle found himself taking a train to a conference. As usual, hehad brought a manuscript to work on. As he glanced around the car he was surprised to see Linus Pauling sitting a few rows in front of him. Dr. Pauling was a renowned chemist who had been doing some innovative research on elucidating the structure of different proteins. Having met Dr. Pauling at a previous conference, Dr. Castle decided to strike up a conversation. "Well, Linus, this is asurprise." "Hello, Bill. Where are you heading?" "Oh, I've been invited to give the plenary talk at this symposium on the physiology of red blood cells down in Atlanta." "What a coincidence. I'm heading to the same meeting to present some of my recent data on hemoglobin." A surprised look crossed Dr. Castle's face. "I had no idea that hemoglobin had caught your attention." "Yes, I've been working on it forthe last year or so. It appears to have a number of interesting structural properties." Dr. Castle remembered the letter from Irving Sherman. "Linus, have you given any thought to studying hemoglobin from individuals suffering from different forms of anemia?" "I'm not very familiar with anemia. I had thought that anemia was a condition in which the body simply made fewer red blood cells. Is thereany indication that there is a difference in the hemoglobin?" "Until a few months ago I would have told you no, but a young medical student recently mentioned that he has observed that blood from individuals with sickle cell anemia transmits light differently than normal blood. I was thinking that this may be due to some difference in the structure of their hemoglobin." "It definitely seems...