Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (51 page)

7. F. M. Sones Jr., E. K. Shirey, W. L. Proudfit, and R. N. Westcott, “Cine-coronary arteriography” (abstract),
Circulation
20 (1959): 773.

8. F. M. Sones Jr., “Coronary Angiography,” in
Beiträge zur Geschichte der Kardiologie,
ed. Gerhard Blümchen (Leichlingen: Klink Roderbirken, 1979).

9. J. Willis Hurst, “History of Cardiac Catheterization,” in
Coronary Arteriography and Angioplasty,
ed. Spencer B. King III and John S. Douglas Jr. (New York: McGraw-Hill, 1985), 6.

10. F. M. Sones Jr. and E. K. Shirey, “Cine coronary arteriography,”
Modern Concepts of Cardiovascular Disease
31 (1962): 735–38.

11. Sones was an inveterate smoker who, even during a coronary catheterization on a patient, would use a long sterile forceps placed on a nearby tray in the pit to pick up a cigarette, have a nurse light it for him, and, after taking a few puffs, return the forceps with its tip overhanging the tray to keep everything sterile. He eventually died of lung cancer in 1985 at the age of sixty-six.

12. Donald B. Effler, introduction to
Surgical Treatment of Coronary Arteriosclerosis,
ed. René G. Favaloro (Baltimore: Williams and Wilkins, 1970), xi.

13. René G. Favaloro, “Saphenous vein autograft replacement of severe segmental coronary artery occlusion: Operative technique,”
Ann Thorac Surg
5 (1968): 334–39.

14. René G. Favaloro,
The Challenging Dream of Heart Surgery: From the Pampas to Cleveland
(Boston: Little, Brown, 1994), 98.

15. Quoted in Julius H. Comroe Jr.,
Retrospectroscope: Insights into Medical Discovery
(Menlo Park, Calif.: Von Gehr, 1977), 94–95.

16. J. H. Jacobson II and E. L. Suarez, “Microsurgery in anastomoses of small vessels,”
Surgical Forum
11 (1960): 243–45.

C
HAPTER
24: “Dottering”

1. C. T. Dotter and M. P. Judkins, “Transluminal treatment of arteriosclerotic obstruction: Description of a new technique and a preliminary report of its application,”
Circulation
30 (1964): 654–70.

2. William C. Sheldon and F. Mason Sones Jr., “Stormy Petrel of Cardiology,”
Clinical Cardiology
17 (1994): 405–407.

3. A. Gruentzig, “Transluminal dilatation of coronary-artery stenosis” (letter to editor),
Lancet
1 (1978): 263.

4. A. Gruentzig, A. Sennings, and W. E. Siegenthaler, “Nonoperative dilatation of coronary artery stenosis: Percutaneous transluminal coronary angioplasty,”
N Engl J Med
301 (1979): 61–68.

5. J. Willis Hurst, “Tribute: Andreas Roland Gruentzig (1939–1985)—a private perspective,”
Circulation
73 (1986): 606–10.

6. Further modifications to the procedure involved atherectomy devices, lasers, and ultrasound for the removal, or ablation, of coronary plaque. As an alternative to bypass surgery, stents are being increasingly used to prop open coronary blood vessels to overcome the constrictions that cause heart attacks. Stents are metal mesh cylinders between 8 and 33 millimeters long and weighing around 27 thousandths of a gram. They are now drug-coated to prevent reclogging from scar tissue and generate more than $66 billion a year in sales.

C
HAPTER
25: A Stitch in Time

1. In his early years, Carrel had taken sewing lessons from a local embroiderer in Lyon to improve his surgical dexterity. After moving to the United States, he used his technique of vascular anastomosis to pursue research on organ transplantation, for which he was awarded the Nobel Prize in 1912.

2. S. M. Levin, “Reminiscences and ruminations: Vascular surgery then and now,”
Am J Surg
154 (1987): 158–62.

3. A. B. Voorhees Jr., “The origin of the permeable arterial prosthesis: a personal reminiscence,”
Surgical Rounds
11 (1988): 79–84.

4. A. B. Voorhees Jr., A. Jaretzki, and A. H. Blakemore, “The use of tubes constructed from Vinyon ‘N’ cloth in bridging arterial defects: A preliminary report,”
Ann Surg
135 (1952): 332–36.

5. A. H. Blakemore and A. B. Voorhees, “The use of tubes constructed from Vinyon ‘N’ cloth in bridging arterial defects: Experimental and clinical,”
Ann Surg
140 (1954): 325–34.

6. Steven G. Friedman,
A History of Vascular Surgery
(Mount Kisco, N.Y.: Futura, 1989), 131–39.

7. A. B. Voorhees Jr., “The development of arterial prostheses: A personal view,”
Arch Surg
120 (1985): 289–95.

C
HAPTER
26: The Nobel Committee Says Yes to NO

1. Author interview with Robert Furchgott, May 2, 2002.

2. Strips of intestine and later of aorta were routinely used to measure the effects of various agents on smooth muscle. Once, in using such strips, a laboratory technician's oversight in forgetting to add glucose to the solution led to an understanding of the energy needs for smooth muscle to contract. Furchgott also acknowledged that it was an “accidental discovery” that blood vessels undergo reversible relaxation when exposed to light. He observed this phenomenon of “photo relaxation” by pure chance. Strips of rabbit aorta placed near a window were observed oscillating. Contractions and dilations were apparent as clouds alternately blocked the sun or moved on to allow bright sunlight through the window. When a technician stood near the laboratory bench, casting a shadow on the preparation, Furchgott saw the strips contract. When she stepped to the side, he saw them relax. It was clearly the shadow that was producing the effect. When he closed the shade on the window, the strips of vessel contracted, and when he opened the shade, they relaxed. Overhead fluorescent lights did not have any effect. Author interview with Furchgott, May 2, 2002.

Years later, Furchgott hypothesized that ultraviolet light activates the release of nitric oxide from the vascular smooth muscle cells.

3. R. F. Furchgott, “A research trail over half a century,”
Annu Rev Pharmacol Toxicol
35 (1995): 1–27.

4. R. F. Furchgott, “The discovery of endothelium-dependent relaxation,”
Circulation
87 suppl. V (1993): V3–8.

5. R. F. Furchgott, D. Davidson, and C. I. Lin, “Conditions which determine whether muscarinic agonists contract or relax rabbit aortic rings and strips,”
Blood Vessels
16 (1979): 213–14.

6. R. F. Furchgott and J. V. Zawadzki, “The obligatory role of endothelial cells in the relaxation of arterial smooth muscle to acetylcholine,”
Nature
288 (1980): 373–76.

7. Ironically, Alfred Nobel, who discovered how to safely formulate dynamite from nitroglycerin, was prescribed nitroglycerin for his angina pectoris late in life, but he refused to take it because of the known vascular headaches of his factory workers.

8. In a further acknowledgment of serendipity, Furchgott's conclusion was based on recalling another “accidental finding” fifteen years earlier when a postdoctoral fellow in his laboratory mistakenly acidified a solution of sodium nitrite. Reaching for a bottle of physiological saline from a laboratory shelf, he had instead grabbed a bottle of acidified saline solution. In acidifying the nitrite, NO was released, and transient vessel relaxation resulted. At the time, Furchgott did not realize the significance of this observation. Now he cites it as a “tantalizing near-miss.” Author interview with Robert Furchgott, May 13, 2002.

9. Robert F. Furchgott, “Endothelium-derived relaxing factor: Discovery, early studies, and identification as nitric oxide,” Nobel Lecture, December 8, 1998,
Les Prix Nobel,
226–43.

C
HAPTER
27: “It's Not You, Honey, It's NO”

1. C. E. Brown-Séquard, “Expérience démonstrant la puissance dynamogénique chez l'homme d'un liquide extrait de testicules d'animaux,”
Archives de Physiologie Normale et Pathologique
5 sér 1 (1889): 651–58, 739–46.

2. E. Laqueur, K. David, E. Dingemanse, J. Freud, and S. E. de Jongh, “Über männliches Hormon: Unterschied von Androsteron aus Harn und Testosteron aus Testis,”
Acta Brev Neerland
4 (1935): 5.

3. L. L. Stanley, “An analysis of one thousand testicular substance implantations,”
Endocrinology
6 (1922): 787–94.

4. V. Pruitt, “John R. Brinkley, Kansas physician, and the goat gland rejuvenation fad,”
Pharos,
Summer 2002, 33–39.

5. NIH Consensus Conference Development Panel on Impotence, “Impotence,”
JAMA
270 (1993): 83–90.

6. H. A. Feldman, I. Goldstein, D. G. Hatzichristou, et al., “Impotence and its medical and psychological correlates: Results of the Massachusetts Male Aging Study,”
Journal of Urology
151 (1994): 54–61.

7. B. Handy, “The Viagra Craze,”
Time,
May 4, 1998, 50–57.

8. “A Stampede Is On for Impotence Pill,”
Wall Street Journal,
April 20, 1998.

9. Pfizer chose the name Viagra, perhaps because its marketing executives thought it evoked potency by suggesting “Niagara” and “vigor.” Levitra's name came from the word “elevate.” Furthermore, the prefix
le
implies masculinity—at least to the French—and
vitra
suggests the word “vitality.” Donald G. McNeil Jr., “The Science of Naming Drugs (Sorry, ‘Z’ Is Already Taken),”
New York Times,
December 28, 2003.

C
HAPTER
28: What's Your Number?

1. N. Anichkov and S. Chalatov, “Über experimentelle Cholesterinsteatose: Ihre Bedeutung für die Entstehung einiger pathologischer Prozessen,”
Centralblatt für Allgemeine Pathologie und Pathologische Anatomie
1 (1913): 1.

2. J. W. Gofman, F. Lindgren, H. Elliott, et al., “The Role of Lipids and Lipoproteins in Arteriosclerosis,”
Science
111 (1950): 166–71.

3. L. I. Dublin and M. Spiegelman, “Factors in the higher mortality of our older age groups,”
Am J Public Health
42 (1952), 422–29.

4. Goldstein had attended medical school there, and his brilliance was recognized by the chairman of the department of internal medicine, who offered him the opportunity to return to establish the division of medical genetics after he completed his fellowship training elsewhere. Six years after graduation, he returned to his alma mater as an assistant professor to work with Michael Brown, whom he had encouraged to join the faculty a year earlier.

5. M. S. Brown and J. L. Goldstein, “Familial hypercholesterolemia: Biochemical, genetic, and pathophysiological considerations,”
Adv Intern Med
20 (1975): 78–96.

6. The idea of cell receptors was known, but it had never been studied in relationship to fat and cholesterol in the blood.

7. M. S. Brown and J. L. Goldstein, “Binding and degradation of low density lipoproteins by cultured human fibroblasts: Comparison of cells from normal subjects and from a patient with homozygous familial hypercholesterolemia,”
J Biol Chem
249 (1974): 5153–62.

8. Y. Watanabe, “Serial inbreeding of rabbits with hereditary hyper-lipidemia (WHHL-rabbit): Incidence and development of atherosclerosis and xanthoma,”
Atherosclerosis
36 (1980): 261–68.

9. Lipid Research Clinics Program.
JAMA
251 (1984): 351–64, 365–74.

10. Bob Banta, “Nobel Pair Trace Solution of Cholesterol Puzzle,”
Austin American-Statesman,
October 27, 1985.

11. In yet another example of unintended discovery, lovastatin (marketed as Mevacor by Merck) was uncovered in a search of fungal metabolites for a possible new sulfa drug. A. W. Alberts, “Discovery, biochemistry and biology of lovastatin,”
Am J Cardiol
62, no. 15 (1988): 10J–15J.

12. The units are expressed in milligrams per deciliter.

C
HAPTER
29: Thinning the Blood

1. J. McLean, “The thromboplastic action of cephalin,”
Am J Physiol
41 (1916): 250–57.

2. W. H. Howell and E. Holt, “Two new factors in blood coagulation—heparin and pro-antithrombin,”
Am J Physiol
47 (1918): 328–41.