Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-25T02:48:31.687Z Has data issue: false hasContentIssue false
  • English
  • Français

Systematics of the Age-Dependence of Some Neurological Disorders

Published online by Cambridge University Press:  01 August 2014

P.R.J. Burch
P.R.J. Burch*
Affiliation:
Department of Medical Physics, University of Leeds, Great Britain
*
Department of Medical Physics, University of Leeds, The General Infirmary, Leeds LS1 3EX, Great Britain

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The age-dependence of malignant diseases has received various interpretations, whereas that of nonmalignant diseases has been relatively neglected. Nevertheless, the age-distributions of diseases in both categories conform to the same stochastic laws.

Many, and perhaps all, natural disorders with a reproducible age-pattern can be described in terms of a simple model: The disease process is initiated in a genetically-predisposed person through the random occurrence of a small number (r) of somatic gene mutations in each of a small number (n) of growth-control stem cells. Each specifically-mutant stem cell propagates a “forbidden clone” of descendant cells. These cells, or their humoral products, attack those target cells that carry complementary recognition macromolecules. The resulting disturbance to target cells leads to the symptoms and signs of autoaggressive disease. In the classical infectious diseases, an extrinsic factor — the invading microorganism — is essential to the release of forbidden clones from restraints imposed by the host's endogenous defence mechanism.

This general thesis is illustrated with reference to the age-distributions of. Wilson's disease; idiopathic facial (Bell's) palsy, recovery and denervation groups; poliomyelitis; Parkinson's disease; schizophrenia; and multiple sclerosis. Clinically-distinctive forms of a given disease, such as Huntington's chorea or Bell's palsy, often have a distinctive age-pattern.

In addition to differences in n and/or r, it can be inferred that each such clinically-distinctive form of a disease is characterized by a distinctive predisposing genotype. The age-dependence of each stage of a progressive disease has a special interest.

Thus, the onset of “definite and probable” cases of Parkinson's disease (Mayo Clinic data) requires two forbidden clones, each of which is initiated in a predisposed person by five specific somatic mutations. Late deaths from Parkinson's disease (as recorded by the Registrar General of England and Wales) require a third such forbidden clone.

Progression in this neurological disorder, as in certain malignant diseases, corresponds to an increase in the number of pathogenic forbidden clones. The internal mathematical and biological consistency of this type of quantitative evidence powerfully corroborates the forbidden clone theory of age-dependent autoaggressive disease.

Type
4. Chronogenetics
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 23 , supplement S1 , January 1974 , pp. 157 - 172
Copyright
Copyright © The International Society for Twin Studies 1974

References

REFERENCES

Abramson, H., Greenberg, M. 1965. Acute poliomyelitis in infants under one year of age. In Rogers, F.B. (ed.): Studies in Epidemiology: Selected Papers of Morris Greenberg, M.D. [pp. 182–195]. New York: G.D. Putnam's Sons.Google Scholar
Armitage, P., Doll, R. 1954. The age distribution of cancer and a multi-stage theory of carcinogenesis. Br. J. Cancer, 8: 1–12.Google Scholar
Berry, R.J. 1969. Genetical factors in the aetiology of multiple sclerosis. Acta Neurol. Scand., 45: 459–483.CrossRefGoogle ScholarPubMed
Burch, P.R.J. 1963. Mutation, autoimmunity and ageing. Lancet, 2: 299–300.CrossRefGoogle ScholarPubMed
Burch, P.R.J. 1964. Schizophrenia: some new aetiological considerations. Br. J. Psychiatry, 110: 818–824.Google Scholar
Burch, P.R.J. 1965. Natural and radiation carcinogenesis in man. I. Theory of initiation phase. Proc. R. Soc. Lond (Biol.), 162: 223–239.Google Scholar
Burch, P.R.J., Burwell, R.G. 1965. Self and not-self: a clonal induction approach to immunology. Q. Rev. Biol., 40: 252–279.Google Scholar
Burch, P.R.J. 1966. Spontaneous auto-immunity: equations for age-specific prevalence and initiationrates. J. Theor. Biol., 12: 397–409.Google Scholar
Burch, P.R.J. 1968 a. An Inquiry Concerning Growth, Disease and Ageing. Edinburgh: Oliver & Boyd.Google Scholar
Burch, P.R.J. 1968 b. Huntington's chorea. Age at onset in relation to aetiology and pathogenesis. In: Vinken, P.J. and Bruyn, G.W. (eds.): Handbook of Clinical Neurology. [6, pp. 379–398] Amsterdam: North-Holland Publishing Co. Google Scholar
Burch, P.R.J. 1970. New approach to cancer. Nature (Lond.), 225: 512–516.Google Scholar
Burch, P.R.J. 1973. Genetic and pathogenetic implications of the age incidence of Huntington's chorea. In: Barbeau, A., Chase, T.N. and Paulson, G.W. (eds.): Advances in Neurology. [1, pp. 179–190], New York: Raven Press.Google Scholar
Burch, P.R.J., Jackson, D., Fairpo, C.G., Murray, J.J. 1973. Gingival recession (“getting long in the tooth”). Colorectal cancer. Degenerative and malignant changes as errors of growth-control. Mechanisms of Ageing and Development, 2: 251–273.Google Scholar
Burnet, F.M. 1959. The Clonal Selection Theory of Acquired Immunity. London: Cambridge University Press.Google Scholar
Burnet, F.M. 1972. Auto-Immunity and Auto-Immune Disease. Lancaster: Medical and Technical Publishing Co. Ltd. Google Scholar
Burwell, R.G. 1963. The role of lymphoid tissue in morphostasis. Lancet, 2: 69–74.Google Scholar
Cox, D.W., Fraser, F.C., Sass-Kortsak, A. 1972. A genetic study of Wilson's disease: evidence for heterogeneity. Am. J. Hum. Genet., 24: 646–666.Google Scholar
Cumings, J.N. 1959. Heavy Metals and the Brain. Oxford: Blackwell Scientific Publications.Google Scholar
Gedda, L., Brenci, G. 1969. Biology of the gene: the ergon/chronon system. Acta Genet. Med. Gemellol. (Roma), 18: 329–379.CrossRefGoogle ScholarPubMed
Gedda, L., Brenci, G. 1970. The heredity of biological time and population genetics. Diabetes, lupus erythematosus, and peptic ulcer. Acta Genet. Med. Gemellol. (Roma), 19: 493–506.Google Scholar
Jersild, C., Svejgaard, A., Fog, T. 1972. HL-A antigens and multiple sclerosis. Lancet, 1: 1040–1041.Google ScholarPubMed
Johnson, R.T., Richardson, E.P. 1968. The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore), 47: 337–369.CrossRefGoogle ScholarPubMed
Leibowitz, U. 1969. Epidemic incidence of Bell's palsy. Brain, 92: 109–114.Google Scholar
Malzberg, B. 1955. Age and sex in relation to mental diseases. Mental Hygiene, 39: 196–244.Google Scholar
Nobrega, F.T., Glattre, E., Kurland, L.T., Okazaki, H. 1969. Comments on the epidemiology of Parkinsonism including prevalence and incidence statistics for Rochester, Minnesota, 1935-1966. In Barbeau, A. and Brunette, J.R. (eds.): Progress in Neuro-Genetics. [pp. 474–485]. Amsterdam: Excerpta Medica Foundation.Google Scholar
O'Reilly, S. 1967. Problems in Wilson's disease. Neurology (Minneap.), 17: 137–147.Google Scholar
Registrar General 1972. Statistical Review of England and Wales, 1970. Part. I, Tables, Medical. London: H.M.S.O. Google Scholar
Segi, M., Kurihara, M. 1966. Cancer Mortality for Selected Sites in 24 Countries. No. 4 (1962-1963). Tohoku University School of Medicine, Sendai, Japan.Google Scholar
Smithers, D.W. 1962. Cancer: an attack on cytologism. Lancet, 1: 494–499.Google Scholar
Strickland, G.T., Frommer, D., Leu, M.L., Pollard, R., Sherlock, S., Cumings, J.N. 1973. Wilson's disease in the United Kingdom and Taiwan. Q.J. Med., NS 42: 619–638.Google Scholar
Taverner, D. 1965. Private communication to author.Google Scholar
Taverner, D. 1969. The localisation of isolated cranial nerve lesions. In Vinken, P.J. and Bruyn, G.W. (eds.): Handbook of Clinical Neurology. [2, pp. 52–85]. Amsterdam: North-Holland Publishing Co. Google Scholar
Willis, R.A. 1967. Pathology of Tumours. 4th Edition. London: Butter worths.Google Scholar