What do you think?
Triumph of the Heart: The Story of Statins
Over 25 million people in the U.S. alone have benefited from statins--such drugs as Lipitor, Zocor, Crestor, Pravachol, and other cholesterol-lowering medicines--in preventing stroke, heart attack, and other forms of coronary heart disease. But how did these remarkable, life-saving drugs come into being? In Triumph of the Heart , Dr. Jie Jack Li, a medicinal chemist and expert on drug discovery, tells for the first time the fascinating story of statins. Drawn from discussions with many scientists involved in the discovery and development of these drugs, the book illuminates the human side of science by revealing the role played by persistence, luck, and sudden insight that characterize major discoveries. For scientists in the drug industry, health care professionals, students of medicine, and all those intrigued by the basic human drive to explore and discover, Triumph of the Heart offers a compelling view of one of the most important drug discoveries of our time.
- GenresMedicine
224 pages, Hardcover
First published April 2, 2009
About the author
Jie Jack Li
61 books5 followersJie Jack Li earned his PhD in organic chemistry in 1995 at Indiana University. After a stint as a postdoctoral fellow MIT, he worked as a medicinal chemist at Pfizer and Bristol-Myers Squibb from 1997 to 2012.
Ratings & Reviews
Friends & Following
Create a free account to discover what your friends think of this book!
Community Reviews
Displaying 1 - 1 of 1 review
October 18, 2012
Cholesterol
The sources of cholesterol in the body are dietary cholesterol (30%) and cholesterol that the liver synthesizes (70%). The brain contains 23% of the body’s cholesterol. Cholesterol is used not just in cell membranes, but is also a precursor for the synthesis of bile, sex hormones, and the cortisol hormone. Gallstones are 75% cholesterol. The chemical structure (the atoms and bonds) of cholesterol was determined by two German chemists, Heinrich O. Wieland and Adolf Windaus. The three-dimensional structure of cholesterol was determined by British crystallographer Dorothy Crowfoot Hodgkin.
Arterial Plaques
Arterial plaques, which sometimes cause heart attacks and strokes, are made up of cholesterol, immune system cells, and fibrous tissue. In 1913, St. Petersburg scientist Nikolai Nikolajewitsch Anitschkov was the first to connect cholesterol to arterial plaques.
Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL)
The biophysicist John W. Gofman of the University of California at Berkeley used the ultracentrifuge to distinguish LDL from HDL. He discovered that LDL and HDL have different effects on the heart. LDL is a major risk factor for coronary heart disease. LDL carries cholesterol from the liver to the arteries. HDL carries cholesterol from the arteries to the liver.
Framingham Heart Study
The Framingham Heart Study is a long-term cardiovascular study that began in 1948. It identified a number of risk factors for heart disease: cholesterol, smoking, hypertension, diabetes and a sedentary lifestyle.
Seven Countries Study
This was an epidemiological longitudinal that began in 1958 and that demonstrated the effect of cholesterol in the diet on heart attacks and strokes. The Finns in particular had a lot of heart disease because their diet was so rich in fat. Italy had a low rate of heart disease and the Mediterranean diet was promoted as a healthy lifestyle.
Familial Hypercholesterolemia
The receptor for LDL was discovered by Michael S. Brown and Joseph L. Goldstein of the University of Texas Southwestern Medical Center in Dallas. They studied patients with familial hypercholesterolemia. The LDL receptor is a protein that is on the surface of liver cells. After the receptor binds LDL, the cell membrane pinches off and becomes a vesicle inside the liver cell. This removes cholesterol from the blood. The rabbit animal model for the laboratory study of LDL was developed by veterinarian Yoshio Watanabe of Kobe University.
Liver Enzyme Inhibition
Statins work by inhibiting the synthesis of cholesterol in liver cells. The statin molecule blocks one of the steps in the pathway of cholesterol synthesis. This step, this chemical reaction, is catalyzed by an enzyme that removes an oxygen atom from a precursor molecule of cholesterol. The statin molecule blocks this enzyme by binding to the cleft in the enzyme surface that the precursor would like to bind to. The statin molecule is what is called a competitive inhibitor.
Akira Endo: The First Statin
Akira Endo at the Fermentation Research Laboratories at Sankyo Company in Japan developed the first statin, mevastatin, in the 1970s. Endo and his coworkers isolated mevastatin from a fungus called Penicillium citrium. Endo tested the drug on chickens, and it lowered their cholesterol levels in the blood. Akira Yamamoto at Osaka University tested mevastatin on humans and it lowered their cholesterol levels, too. But Sankyo decided not to pursue the drug because it caused tumors in dogs at high doses. But Sankyo did discover a related drug, pravastatin, which was marketed by Bristol-Myers Squibb under the name Pravachol starting in 1991.
Merck: Mevacor and Zocor
Akira Endo and Sankyo shared their work on statins with Merck of Rahway, New Jersey. Merck developed the statin Mevacor (lovastatin). This analog of mevastatin did not cause tumors in dogs. Later, Robert L. Smith of Merck developed another statin that was effective in lowering cholesterol levels: Zocor (simvastatin).
Sandoz: Lescol
In 1984, Faizulla G. Kathawala of the Sandoz Pharmaceutical Corporation of Switzerland invented Lescol (fluvastatin). In 1996 Ciba-Geigy and Sandoz merged to form Novartis.
Parke-Davis: Lipitor
Bruce D. Roth and Roger Newton were the developers of Lipitor (atorvastatin), which was more effective than most statins in lowering blood cholesterol. Parke-Davis merged with Warner-Lambert, and Pfizer marketed the new drug. Warner-Lambert itself was later acquired by Pfizer.
AstraZeneca: Crestor
Crestor (rosuvastatin) was developed by AstraZeneca. It was very effective relative to other statins. In fact, Crestor can even reduce the amount of plaque in the patient’s arteries, not just stabilize it.
Grapefruit Juice
Statins should not be taken with grapefruit juice.
The sources of cholesterol in the body are dietary cholesterol (30%) and cholesterol that the liver synthesizes (70%). The brain contains 23% of the body’s cholesterol. Cholesterol is used not just in cell membranes, but is also a precursor for the synthesis of bile, sex hormones, and the cortisol hormone. Gallstones are 75% cholesterol. The chemical structure (the atoms and bonds) of cholesterol was determined by two German chemists, Heinrich O. Wieland and Adolf Windaus. The three-dimensional structure of cholesterol was determined by British crystallographer Dorothy Crowfoot Hodgkin.
Arterial Plaques
Arterial plaques, which sometimes cause heart attacks and strokes, are made up of cholesterol, immune system cells, and fibrous tissue. In 1913, St. Petersburg scientist Nikolai Nikolajewitsch Anitschkov was the first to connect cholesterol to arterial plaques.
Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL)
The biophysicist John W. Gofman of the University of California at Berkeley used the ultracentrifuge to distinguish LDL from HDL. He discovered that LDL and HDL have different effects on the heart. LDL is a major risk factor for coronary heart disease. LDL carries cholesterol from the liver to the arteries. HDL carries cholesterol from the arteries to the liver.
Framingham Heart Study
The Framingham Heart Study is a long-term cardiovascular study that began in 1948. It identified a number of risk factors for heart disease: cholesterol, smoking, hypertension, diabetes and a sedentary lifestyle.
Seven Countries Study
This was an epidemiological longitudinal that began in 1958 and that demonstrated the effect of cholesterol in the diet on heart attacks and strokes. The Finns in particular had a lot of heart disease because their diet was so rich in fat. Italy had a low rate of heart disease and the Mediterranean diet was promoted as a healthy lifestyle.
Familial Hypercholesterolemia
The receptor for LDL was discovered by Michael S. Brown and Joseph L. Goldstein of the University of Texas Southwestern Medical Center in Dallas. They studied patients with familial hypercholesterolemia. The LDL receptor is a protein that is on the surface of liver cells. After the receptor binds LDL, the cell membrane pinches off and becomes a vesicle inside the liver cell. This removes cholesterol from the blood. The rabbit animal model for the laboratory study of LDL was developed by veterinarian Yoshio Watanabe of Kobe University.
Liver Enzyme Inhibition
Statins work by inhibiting the synthesis of cholesterol in liver cells. The statin molecule blocks one of the steps in the pathway of cholesterol synthesis. This step, this chemical reaction, is catalyzed by an enzyme that removes an oxygen atom from a precursor molecule of cholesterol. The statin molecule blocks this enzyme by binding to the cleft in the enzyme surface that the precursor would like to bind to. The statin molecule is what is called a competitive inhibitor.
Akira Endo: The First Statin
Akira Endo at the Fermentation Research Laboratories at Sankyo Company in Japan developed the first statin, mevastatin, in the 1970s. Endo and his coworkers isolated mevastatin from a fungus called Penicillium citrium. Endo tested the drug on chickens, and it lowered their cholesterol levels in the blood. Akira Yamamoto at Osaka University tested mevastatin on humans and it lowered their cholesterol levels, too. But Sankyo decided not to pursue the drug because it caused tumors in dogs at high doses. But Sankyo did discover a related drug, pravastatin, which was marketed by Bristol-Myers Squibb under the name Pravachol starting in 1991.
Merck: Mevacor and Zocor
Akira Endo and Sankyo shared their work on statins with Merck of Rahway, New Jersey. Merck developed the statin Mevacor (lovastatin). This analog of mevastatin did not cause tumors in dogs. Later, Robert L. Smith of Merck developed another statin that was effective in lowering cholesterol levels: Zocor (simvastatin).
Sandoz: Lescol
In 1984, Faizulla G. Kathawala of the Sandoz Pharmaceutical Corporation of Switzerland invented Lescol (fluvastatin). In 1996 Ciba-Geigy and Sandoz merged to form Novartis.
Parke-Davis: Lipitor
Bruce D. Roth and Roger Newton were the developers of Lipitor (atorvastatin), which was more effective than most statins in lowering blood cholesterol. Parke-Davis merged with Warner-Lambert, and Pfizer marketed the new drug. Warner-Lambert itself was later acquired by Pfizer.
AstraZeneca: Crestor
Crestor (rosuvastatin) was developed by AstraZeneca. It was very effective relative to other statins. In fact, Crestor can even reduce the amount of plaque in the patient’s arteries, not just stabilize it.
Grapefruit Juice
Statins should not be taken with grapefruit juice.
Displaying 1 - 1 of 1 review