Diseases, molecular

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

The Nobel Prize chemist Linus Pauling related the mechanism of sickle cell anemia to a genetic defect in hemoglobin synthesis and thus defined the first molecular disease. Pauling s groundbreaking paper in 1949 was boldly titled Sickle Cell Anemia A Molecular Disease. Many claim that this discovery laid the foundation for molecular biology. What is the chemistry that is at the heart of this pioneering work ... 

Question 7.11 Why Is Sickle Cell Anemia a Molecular Disease ... 

Pauling L., Itano H. Sickle cell anemia, a molecular disease. Science 110 (1949), 543-548. 

Feldman, S. and Tauber, A. I. (1997), Sickle cell anemia Redefining the first molecular disease Bulletin of the History of Medicine, 71, 623-650. 

Pauling L, Singer SJ, Wells JC. Sickle cell anemia a molecular disease. 

The Editors have striven, as in previous years, to include in the present volume reviews on greatly diversified subjects, all of timely importance. The article on mellituria in Volume 4 has been supplemented by a survey of galactosemia, and we expect to follow in future volumes with reviews of other inborn errors of metabolism or, in modern parlance, of molecular diseases. Likewise, the article on peptiduria supplements that on aminoaciduria in Volume 2 and that on microbiological assay of vitamins extends previous summaries on the nucleogenic vitamins. The haptoglobins lie on the borderline of hematology. 

Diseases of people come in many flavors. There are infectious diseases (measles, mumps, influenza, AIDS,...), nutritional deficiency diseases (scurvy, beriberi, kwashiorkor,...), degenerative diseases (Alzheimer s disease, osteoporosis,...), cancer (of the lung, breast, prostate, liver,...), and single-gene inherited diseases or molecular diseases. In the last category, an important and instructive example is provided by sickle cell anemia. Let s consider this disease and begin to develop a sense of how we can understand it on the basis of what we now know about proteins. 

Sickle-Cell Anemia Is a Molecular Disease of Hemoglobin... 

One insight into molecular disease was the recognition that mutations that cause many diseases, e.g.,... 

Pauling, L., H. A. Itano, S. J. Singer, and I. C. Wells, Sicklecell anemia a molecular disease. Science 110 543-548, 1949. A classic paper. 

Also in 1949, Pauling, Itano, Singer, and Wells published a now-famous article in the journal Science Sickle Cell Anemia A Molecular Disease. Itano, working in Pauling s laboratory,... 

Pauling called it history s first molecular disease —caused an international sensation. Itano and Singer s follow-up work demonstrated a pattern of genetic inheritance for the disease and added to its importance as one of the cornerstone discoveries in modern medicine. 

And the world listened. Now in his mid-50s, Pauling was the world s foremost chemist. His ideas about the chemical bond had revolutionized the field his chemistry textbooks were among the most popular and influential ever written his ideas about protein structure and molecular disease had made history. He had been awarded honorary doctorates by the world s greatest universities and had won almost every significant honor available to chemists. 

Senior Fellow, Molecular Disease Branch National Institutes of Health (NIH)... 

Rosse, W.F. Paroxysmal nocturnal haemoglobinuria as a molecular disease. Medicine 1997 76 63—93... 

Zech, L.A. Laboratory of Mathematical Biology, National Cancer Institute, and Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (40, 25, 149, 281)... 

During recent years several diseases have been shown to be molecular diseases. They involve the manufacture by the patient of molecules that are abnormal that is, that have a structure different from the molecules manufactured by other people. 

---