Home Faculty and Research Faculty by Name Peter Duesberg

Peter Duesberg

Professor of Biochemistry and Molecular Biology

Lab Homepage: http://mcb.berkeley.edu/labs/duesberg/

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Research Interests

Research in Carcinogenesis: Aneuploidy, an abnormal balance of chromosomes is (i) ubiquitous in cancer, is (ii) proportional to the degree of malignancy of cancer, and (iii) inevitably generates abnormal phenotypes, because it alters the dosages and expression of thousands of normal genes. Take Down syndrome, a trisomy of chromosome 21, as an example. In view of this we have recently proposed that aneuploidy is sufficient to cause cancer. Our hypothesis proposes that cancer-specific chromosome combinations, or aneusomies, cause cancer-specific phenotypes. According to this hypothesis carcinogens initiate carcinogenesis with a random aneuploidy. Aneuploidy then renders chromosome segregation and maintenance error-prone because it unbalances teams of spindle proteins, repair enzymes, and even centrosome numbers. The resulting chain reaction of chromosome reassortments then generates cancer-specific aneuploidy and further random aneuploidy autocatalytically.

The aneuploidy-cancer hypothesis predicts all peculiar aspects of carcinogenesis, particularly those that have remained paradoxical according to the competing gene-mutation hypothesis: For example,
1) The ubiquity of aneuploidy in cancer. In contrast, the mutation hypothesis predicts diploid cancers.
2) Carcinogens function as aneuploidogens. This was confirmed with non-mutagenic and mutagenic carcinogens. For example, 100% of Chinese hamster cells transformed in vitro by the non-mutagenic polycyclic aromatic hydrocarbons (PAHs) were aneuploid. But non-mutagenic carcinogens are a paradox of the mutation hypothesis.
3) Aneuploidy prior to carcinogenesis. This has been confirmed by us and others.
4) The slow kinetics of carcinogenesis, from experimental or accidental carcinogen to cancer. This is explained by the low probability of evolving cancer-specific aneuploidies by random chromosome assortments - a process analogous to phylogenesis. By contrast, the mutation hypothesis predicts carcinogenesis without lag, because mutation is instantaneous.
5) The genetic instability and the corresponding heterogeneous phenotypes of cancer. These are based on the inherent instability of the aneuploid karyotype. But, stable phenotypes are predicted by the mutation hypothesis because gene mutations are stable.
6) The ability of cancer cells to become resistant against a selected, chemotherapeutic drug, and simultaneously against many unselected drugs. This is also explained by aneuploidy-catalyzed reassortments of chromosomes, encoding selected and un-selected resistances in the same chromosomes. This hypothesis also explains the failure of diploid cells of cancer patients to become drug-resistant.
7) The low risk of transformation of human cells by carcinogens, compared to rodent cells, is thought to reflect the high resistance of human cells to aneuploidization. This is currently tested experimentally.

The aneuploidy-cancer hypothesis predicts improvements in cancer prevention by eliminating aneuploidogens from food and drugs, and in therapy by early detection of preneoplastic cells, eg. Pap smears, based on the presence of aneuploidy.

Research in Virology: A thorough audit of the HIV-AIDS hypothesis leads to the conclusion that the various AIDS epidemics of the US, Europe and Africa have chemical bases, namely toxic, recreational drugs, DNA-chain terminators prescribed as anti-HIV drugs and malnutrition.

Selected Publications

Chromosomal Chaos and Cancer. [P. Duesberg (2007) Scientific American 296, May 52-59]

Cancer drug resistance: The central role of the karyotype. [P. Duesberg, R. Li, R. Sachs, A. Fabarius, M.Upender & R. Hehlmann (2007) Drug Resistance Updates 10: 51-58]

The chromosomal basis of cancer. [P. Duesberg, R. Li, A. Fabarius & R. Hehlmann (2005) Cell Oncol 27 (5-6) 293-318]

Does aneuploidy or mutation start cancer? [P. Duesberg (2005) Science 307 (5706):41-2]

Chromosomal alterations cause the high rates and wide ranges of drug resistance in cancer cells. [R. Li, R. Hehlmann, R. Sachs, P. Duesberg (2005) Cancer Genet Cytogenet 163 (1) 44-56]

Aneuploidy, the primary cause of the multilateral genomic instability of neoplastic and preneoplastic cells. [P. Duesberg, A. Fabarius, R. Hehlmann (2004) IUBMB Life 56 (2) 65-81]

Aneuploidy approaching a perfect score in predicting and preventing cancer: highlights from a conference held in Oakland in January 2004. [P. Duesberg, R. Li, D. Rasnick (2004) Cell Cycle 3 (6) 823-8]

The chemical bases of the various AIDS epidemics: recreational drugs, anti-viral chemotherapy and malnutrition. [P. Duesberg, C. Koehnlein, & D. Rasnick (2003) J Biosci 28 (4) 383-412]

Multistep carcinogenesis, a chain reaction of aneuploidizations. [P. Duesberg, & R. Li (2003) Cell Cycle 2, 202-210]

Instability of chromosome structure increases exponentially with degrees of aneuploidy. [A. Fabarius, R. Hehlmann, & P. Duesberg (2003) Cancer Genet Cytogenet 143, 59-72]

Last Updated 2007-09-20