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. 1982 Sep-Dec;55(5-6):487–513.

Window panes of eternity. Health, disease, and inherited risk.

C R Scriver
PMCID: PMC2596554  PMID: 6763817

Abstract

Personal health reflects harmony between individual and experience; it is optimal homeostasis. Disease is an outcome of incongruity leading to dishomeostasis. Relative to earlier times, disease in modern society has higher "heritability" (in the broad meaning of the term). Inherited risks are facts compatible with anticipation and prevention of disease. This viewpoint has major implications for medical practice, deployment of health services, themes of research, and education of health care personnel and citizens.

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Selected References

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  1. Batshaw M. L., Roan Y., Jung A. L., Rosenberg L. A., Brusilow S. W. Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency. N Engl J Med. 1980 Feb 28;302(9):482–485. doi: 10.1056/NEJM198002283020902. [DOI] [PubMed] [Google Scholar]
  2. Blass J. P., Gibson G. E. Abnormality of a thiamine-requiring enzyme in patients with Wernicke-Korsakoff syndrome. N Engl J Med. 1977 Dec 22;297(25):1367–1370. doi: 10.1056/NEJM197712222972503. [DOI] [PubMed] [Google Scholar]
  3. Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
  4. Bromley D. A. The other frontiers of science. Science. 1982 Feb 26;215(4536):1035–1044. doi: 10.1126/science.215.4536.1035. [DOI] [PubMed] [Google Scholar]
  5. Brown M. S., Goldstein J. L. Lowering plasma cholesterol by raising LDL receptors. N Engl J Med. 1981 Aug 27;305(9):515–517. doi: 10.1056/NEJM198108273050909. [DOI] [PubMed] [Google Scholar]
  6. Brown M. S., Kovanen P. T., Goldstein J. L. Regulation of plasma cholesterol by lipoprotein receptors. Science. 1981 May 8;212(4495):628–635. doi: 10.1126/science.6261329. [DOI] [PubMed] [Google Scholar]
  7. Centerwall B. S., Criqui M. H. Prevention of the Wernicke-Korsakoff syndrome: a cost-benefit analysis. N Engl J Med. 1978 Aug 10;299(6):285–289. doi: 10.1056/NEJM197808102990605. [DOI] [PubMed] [Google Scholar]
  8. Childs B. Persistent echoes of the nature-nurture argument. Am J Hum Genet. 1977 Jan;29(1):1–13. [PMC free article] [PubMed] [Google Scholar]
  9. Childs B. The William Allan Memorial Award Lecture. A place for genetics in health education, and vice versa. Am J Hum Genet. 1974 Mar;26(2):120–135. [PMC free article] [PubMed] [Google Scholar]
  10. Christomanou H., Martinius J., Jaffé S., Betke K., Förster C. Biochemical, psychometric, and neuropsychological studies in heterozygotes for various lipidoses. Preliminary results. Hum Genet. 1980;55(1):103–110. doi: 10.1007/BF00329134. [DOI] [PubMed] [Google Scholar]
  11. Clow C. L., Scriver C. R. Knowledge about and attitudes toward genetic screening among high-school students: the Tay-Sachs experience. Pediatrics. 1977 Jan;59(1):86–90. [PubMed] [Google Scholar]
  12. Clow C., Scriver C. R., Davies E. Results of mass screening for hyperaminoacidemias in the newborn infant. Am J Dis Child. 1969 Jan;117(1):48–53. doi: 10.1001/archpedi.1969.02100030050005. [DOI] [PubMed] [Google Scholar]
  13. Comar C. L. Risk: a pragmatic de minimis approach. Science. 1979 Jan 26;203(4378):319–319. doi: 10.1126/science.203.4378.319. [DOI] [PubMed] [Google Scholar]
  14. Comroe J. H., Jr, Dripps R. D. Scientific basis for the support of biomedical science. Science. 1976 Apr 9;192(4235):105–111. doi: 10.1126/science.769161. [DOI] [PubMed] [Google Scholar]
  15. Crow J. F., Denniston C. The mutation component of genetic damage. Science. 1981 May 22;212(4497):888–893. doi: 10.1126/science.7233180. [DOI] [PubMed] [Google Scholar]
  16. Eldredge N. Evolution and prediction. Science. 1981 May 15;212(4496):737–737. doi: 10.1126/science.212.4496.737. [DOI] [PubMed] [Google Scholar]
  17. Eriksson C. J. Elevated blood acetaldehyde levels in alcoholics and their relatives: a reevaluation. Science. 1980 Mar 21;207(4437):1383–1384. doi: 10.1126/science.7355298. [DOI] [PubMed] [Google Scholar]
  18. Estes J. W. The practice of medicine in 18th-century Massachusetts: a bicentennial perspective. N Engl J Med. 1981 Oct 29;305(18):1040–1047. doi: 10.1056/NEJM198110293051802. [DOI] [PubMed] [Google Scholar]
  19. Finch C. A., Huebers H. Perspectives in iron metabolism. N Engl J Med. 1982 Jun 24;306(25):1520–1528. doi: 10.1056/NEJM198206243062504. [DOI] [PubMed] [Google Scholar]
  20. Francke U., Holmes L. B., Atkins L., Riccardi V. M. Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13. Cytogenet Cell Genet. 1979;24(3):185–192. doi: 10.1159/000131375. [DOI] [PubMed] [Google Scholar]
  21. Freeman J. M., Finkelstein J. D., Mudd S. H. Folate-responsive homocystinuria and "schizophrenia". A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med. 1975 Mar 6;292(10):491–496. doi: 10.1056/NEJM197503062921001. [DOI] [PubMed] [Google Scholar]
  22. Fries J. F. Aging, natural death, and the compression of morbidity. N Engl J Med. 1980 Jul 17;303(3):130–135. doi: 10.1056/NEJM198007173030304. [DOI] [PubMed] [Google Scholar]
  23. Garraway W. M., Whisnant J. P., Furlan A. J., Phillips L. H., 2nd, Kurland L. T., O'Fallon W. M. The declining incidence of stroke. N Engl J Med. 1979 Mar 1;300(9):449–452. doi: 10.1056/NEJM197903013000901. [DOI] [PubMed] [Google Scholar]
  24. Gerald P. S. X-linked mental retardation and the fragile-X syndrome. Pediatrics. 1981 Oct;68(4):594–595. [PubMed] [Google Scholar]
  25. Gilbert W. DNA sequencing and gene structure. Science. 1981 Dec 18;214(4527):1305–1312. doi: 10.1126/science.7313687. [DOI] [PubMed] [Google Scholar]
  26. Goldstein J. L., Anderson R. G., Brown M. S. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature. 1979 Jun 21;279(5715):679–685. doi: 10.1038/279679a0. [DOI] [PubMed] [Google Scholar]
  27. Goldstein J. L., Brown M. S. The LDL receptor locus and the genetics of familial hypercholesterolemia. Annu Rev Genet. 1979;13:259–289. doi: 10.1146/annurev.ge.13.120179.001355. [DOI] [PubMed] [Google Scholar]
  28. Goldstein J. L., Hazzard W. R., Schrott H. G., Bierman E. L., Motulsky A. G. Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest. 1973 Jul;52(7):1533–1543. doi: 10.1172/JCI107331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Gordon J. W., Ruddle F. H. Integration and stable germ line transmission of genes injected into mouse pronuclei. Science. 1981 Dec 11;214(4526):1244–1246. doi: 10.1126/science.6272397. [DOI] [PubMed] [Google Scholar]
  30. Gori G. B., Richter B. J. Macroeconomics of disease prevention in the United States. Science. 1978 Jun 9;200(4346):1124–1130. doi: 10.1126/science.653358. [DOI] [PubMed] [Google Scholar]
  31. Hall J. G., Powers E. K., Mcllvaine R. T., Ean V. H. The frequency and financial burden of genetic disease in a pediatric hospital. Am J Med Genet. 1978;1(4):417–436. doi: 10.1002/ajmg.1320010405. [DOI] [PubMed] [Google Scholar]
  32. Harris H. Enzyme variants in human populations. Johns Hopkins Med J. 1976 Jun;138(6):245–252. [PubMed] [Google Scholar]
  33. Johnson R. C., Cole R. E., Ahern F. M. Genetic interpretation of racial/ethnic differences in lactose absorption and tolerance: a review. Hum Biol. 1981 Feb;53(1):1–13. [PubMed] [Google Scholar]
  34. Kan Y. W., Dozy A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5631–5635. doi: 10.1073/pnas.75.11.5631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kan Y. W., Lee K. Y., Furbetta M., Angius A., Cao A. Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia. N Engl J Med. 1980 Jan 24;302(4):185–188. doi: 10.1056/NEJM198001243020401. [DOI] [PubMed] [Google Scholar]
  36. Kidd K. K. Genetic linkage and hemosiderosis. N Engl J Med. 1979 Jul 26;301(4):209–210. doi: 10.1056/NEJM197907263010409. [DOI] [PubMed] [Google Scholar]
  37. Ledbetter D. H., Riccardi V. M., Airhart S. D., Strobel R. J., Keenan B. S., Crawford J. D. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med. 1981 Feb 5;304(6):325–329. doi: 10.1056/NEJM198102053040604. [DOI] [PubMed] [Google Scholar]
  38. Lees R. S., Lees A. M. High-density lipoproteins and the risk of atherosclerosis. N Engl J Med. 1982 Jun 24;306(25):1546–1548. doi: 10.1056/NEJM198206243062509. [DOI] [PubMed] [Google Scholar]
  39. Mabuchi H., Haba T., Tatami R., Miyamoto S., Sakai Y., Wakasugi T., Watanabe A., Koizumi J., Takeda R. Effect of an inhibitor of 3-hydroxy-3-methyglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10-levels in patients with familial hypercholesterolemia. N Engl J Med. 1981 Aug 27;305(9):478–482. doi: 10.1056/NEJM198108273050902. [DOI] [PubMed] [Google Scholar]
  40. Martin R. D. Relative brain size and basal metabolic rate in terrestrial vertebrates. Nature. 1981 Sep 3;293(5827):57–60. doi: 10.1038/293057a0. [DOI] [PubMed] [Google Scholar]
  41. McConkey E. H., Taylor B. J., Phan D. Human heterozygosity: a new estimate. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6500–6504. doi: 10.1073/pnas.76.12.6500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. McKusick V. A. The anatomy of the human genome. Am J Med. 1980 Aug;69(2):267–276. doi: 10.1016/0002-9343(80)90388-5. [DOI] [PubMed] [Google Scholar]
  43. Motulsky A. G. Genetics of hemochromatosis. N Engl J Med. 1979 Dec 6;301(23):1291–1291. doi: 10.1056/NEJM197912063012319. [DOI] [PubMed] [Google Scholar]
  44. Murphy E. A. The genetic dynamics of disease. Am J Med Genet. 1981;8(1):35–52. doi: 10.1002/ajmg.1320080106. [DOI] [PubMed] [Google Scholar]
  45. Nelkin D. The science-textbook controversies. Sci Am. 1976 Apr;234(4):33–39. doi: 10.1038/scientificamerican0476-33. [DOI] [PubMed] [Google Scholar]
  46. Newcomer A. D., Hodgson S. F., McGill D. B., Thomas P. J. Lactase deficiency: prevalence in osteoporosis. Ann Intern Med. 1978 Aug;89(2):218–220. doi: 10.7326/0003-4819-89-2-218. [DOI] [PubMed] [Google Scholar]
  47. Pastan I. H., Willingham M. C. Journey to the center of the cell: role of the receptosome. Science. 1981 Oct 30;214(4520):504–509. doi: 10.1126/science.6170111. [DOI] [PubMed] [Google Scholar]
  48. Penchaszadeh V. B. Frequency and characteristics of birth defects admissions to a pediatric hospital in Venezuela. Am J Med Genet. 1979;3(4):359–369. doi: 10.1002/ajmg.1320030407. [DOI] [PubMed] [Google Scholar]
  49. Roberts D. F., Chavez J., Court S. D. The genetic component in child mortality. Arch Dis Child. 1970 Feb;45(239):33–38. doi: 10.1136/adc.45.239.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Robin E. D. Claude Bernard's (extended) milieu interieur revisited: autoregulation of cell and subcell integrity. Clin Sci Mol Med. 1977 May;52(5):443–448. doi: 10.1042/cs0520443. [DOI] [PubMed] [Google Scholar]
  51. Ross R., Glomset J. A. The pathogenesis of atherosclerosis (first of two parts). N Engl J Med. 1976 Aug 12;295(7):369–377. doi: 10.1056/NEJM197608122950707. [DOI] [PubMed] [Google Scholar]
  52. Rutstein D. D., Veech R. L. Genetics and addiction to alcohol. N Engl J Med. 1978 May 18;298(20):1140–1141. doi: 10.1056/NEJM197805182982010. [DOI] [PubMed] [Google Scholar]
  53. Sacher G. A. Evolutionary theory in gerontology. Perspect Biol Med. 1982 Spring;25(3):339–353. doi: 10.1353/pbm.1982.0050. [DOI] [PubMed] [Google Scholar]
  54. Schiffman P. L., Westlake R. E., Santiago T. V., Edelman N. H. Ventilatory control in parents of victims of sudden-infant-death syndrome. N Engl J Med. 1980 Feb 28;302(9):486–491. doi: 10.1056/NEJM198002283020903. [DOI] [PubMed] [Google Scholar]
  55. Schuckit M. A., Rayses V. Ethanol ingestion: differences in blood acetaldehyde concentrations in relatives of alcoholics and controls. Science. 1979 Jan 5;203(4375):54–55. doi: 10.1126/science.758678. [DOI] [PubMed] [Google Scholar]
  56. Scriver C. R., Clow C. L. Phenylketonuria: epitome of human biochemical genetics (second of two parts). N Engl J Med. 1980 Dec 11;303(24):1394–1400. doi: 10.1056/NEJM198012113032404. [DOI] [PubMed] [Google Scholar]
  57. Scriver C. R., Laberge C., Clow C. L., Fraser F. C. Genetics and Medicine: an evolving relationship. Science. 1978 May 26;200(4344):946–952. doi: 10.1126/science.644337. [DOI] [PubMed] [Google Scholar]
  58. Scriver C. R., Tenenhouse H. S. On the heritability of rickets, a common disease (Mendel, mammals and phosphate). Johns Hopkins Med J. 1981 Nov;149(5):179–187. [PubMed] [Google Scholar]
  59. Shannon D. C., Kelly D. H. SIDS and near-SIDS (second of two parts). N Engl J Med. 1982 Apr 29;306(17):1022–1028. doi: 10.1056/NEJM198204293061704. [DOI] [PubMed] [Google Scholar]
  60. Skinner B. F. Selection by consequences. Science. 1981 Jul 31;213(4507):501–504. doi: 10.1126/science.7244649. [DOI] [PubMed] [Google Scholar]
  61. Sparkes R. S., Sparkes M. C., Wilson M. G., Towner J. W., Benedict W., Murphree A. L., Yunis J. J. Regional assignment of genes for human esterase D and retinoblastoma to chromosome band 13q14. Science. 1980 May 30;208(4447):1042–1044. doi: 10.1126/science.7375916. [DOI] [PubMed] [Google Scholar]
  62. Sutherland G. R. Heritable fragile sites on human chromosomes. VIII. Preliminary population cytogenetic data on the folic-acid-sensitive fragile sites. Am J Hum Genet. 1982 May;34(3):452–458. [PMC free article] [PubMed] [Google Scholar]
  63. Temple G. F., Dozy A. M., Roy K. L., Kan Y. W. Construction of a functional human suppressor tRNA gene: an approach to gene therapy for beta-thalassaemia. Nature. 1982 Apr 8;296(5857):537–540. doi: 10.1038/296537a0. [DOI] [PubMed] [Google Scholar]
  64. Trimble B. K., Doughty J. H. The amount of hereditary disease in human populations. Ann Hum Genet. 1974 Oct;38(2):199–223. doi: 10.1111/j.1469-1809.1974.tb01951.x. [DOI] [PubMed] [Google Scholar]
  65. Trimble B. K., Smith M. E. The incidence of genetic disease and the impact on man of an altered mutation rate. Can J Genet Cytol. 1977 Sep;19(3):375–385. doi: 10.1139/g77-041. [DOI] [PubMed] [Google Scholar]
  66. Turner G., Opitz J. M. X-linked mental retardation. Am J Med Genet. 1980;7(4):407–415. doi: 10.1002/ajmg.1320070403. [DOI] [PubMed] [Google Scholar]
  67. Utermann G., Vogelberg K. H., Steinmetz A., Schoenborn W., Pruin N., Jaeschke M., Hees M., Canzler H. Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III. Clin Genet. 1979 Jan;15(1):37–62. [PubMed] [Google Scholar]
  68. Walker W. J. Changing United States life-style and declining vascular mortality: cause or coincidence? N Engl J Med. 1977 Jul 21;297(3):163–165. doi: 10.1056/NEJM197707212970311. [DOI] [PubMed] [Google Scholar]
  69. Weitkamp L. R., Stancer H. C., Persad E., Flood C., Guttormsen S. Depressive disorders and HLA: a gene on chromosome 6 that can affect behavior. N Engl J Med. 1981 Nov 26;305(22):1301–1306. doi: 10.1056/NEJM198111263052201. [DOI] [PubMed] [Google Scholar]
  70. Williams R. L., Chen P. M. Identifying the sources of the recent decline in perinatal mortality rates in California. N Engl J Med. 1982 Jan 28;306(4):207–214. doi: 10.1056/NEJM198201283060404. [DOI] [PubMed] [Google Scholar]
  71. Worton R. G. Chromosome abnormalities: a major cause of birth defects, stillbirth and spontaneous abortion. Can Med Assoc J. 1977 Oct 22;117(8):849–51. [PMC free article] [PubMed] [Google Scholar]
  72. Wyman A. R., White R. A highly polymorphic locus in human DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6754–6758. doi: 10.1073/pnas.77.11.6754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Wynder E. L. Disease prevention: asking the right questions. Science. 1978 Oct 20;202(4365):265–265. doi: 10.1126/science.694531. [DOI] [PubMed] [Google Scholar]

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