Department of Molecular & Cell Biology

Home Faculty and Research Faculty by Name Peter Duesberg

Peter Duesberg

Professor of Biochemistry, Biophysics and Structural Biology

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Research Interests

Research in carcinogenesis

Cancer is currently attributed to the mutation of specific genes, which are called oncogenes. 

This theory does, however, not explain why:  (1) All cancers have individual, abnormal (aneuploid) karyotypes.  (2) Oncogenes are not sufficient to transform normal cells to cancer cells.  (3) Mutations induce cancers only after exceedingly long latencies of many months to decades.  (4) Cancers are genomically unstable, whereas conventional mutations are stable.  (5) All cancers are immortal, despite genomic instability.

In view of the ubiquity of 'abnormal' karyotypes in cancers it is tempting to think that this abnormality could be normal.  In that case carcinogenesis would be a form of speciation.

This phylogenetic cancer theory would explain, why cancers have individual karyotypes.  It would also explain, why oncogenes are not sufficient to cause cancer, and why it would take a long time to convert a normal cell to a cancer cell,

But would it also explain, why cancers are genomically unstable, and why cancers are immortal?

Currently we are testing the following phylogenetic cancer theory as an explanation of the many characteristics of cancer.

Phylogenetic cancer theory.  Carcinogens, like mutagenic X-rays and non-mutagenic aromatic hydrocarbons, initiate carcinogenesis by inducing random aneuploidy (the loss or gain of chromosomes or segments of chromosomes).

Aneuploidy destabilizes the karyotype by unbalancing 1000s of collaborating genes – particularly the balance-sensitive genes that segregate, synthesize and repair chromosomes. 

Thus aneuploidy catalyzes automatically chain reactions of random karyotypic evolutions, which have two stable endpoints (see graphic): 

1) Cell death from lethal karyotypes, and

2) Rare genesis of new, autonomous species with individual karyotypes – alias cancer cells.

Phylogenetic cancer theory

Owing to the inherent instability of aneuploidy cancer karyotypes are flexible within clonal margins.  These margins reflect a dynamic equilibrium between destabilization by aneuploidy and selection for autonomy. There is no autonomy outside these margins (see graphic).

As a result cancers are clonally heterogeneous.  This heterogeneity and the underlying flexibility explain how cancers progress from bad to worse by evolving ever-new phenotypes such as metastasis and drug-resistance.

Flexibility in the face of adverse genetic (Muller's ratchet) and environmental conditions would also explain immortality.

 Benefits of the speciation theory.  The theory that carcinogenesis is a form of speciation predicts improvements in cancer prevention based on elimination of aneuploidogens from food and drugs, and on early detection of preneoplastic and neoplastic aneuploidy for the prevention and treatments of cancer.

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. For Africa, please see my paper in Medical Hypotheses (Duesberg et al., 2009).

Current Projects

Our theory makes several predictions that we plan to test:

(1) Since genesis never repeats itself, our theory predicts that different cancers induced by the same carcinogen have individual karyotypes and phenotypes: 'One cancer – one karyotype'.

(2) The theory predicts that new variants of a given cancer, eg. drug-resistance, or metastasis, correlate with karyotypic variation, rather than mutation.

(3) The genomic instability of cancers is generated by aneuploidy. If correct the instability is (a) proportional to the degree of aneuploidy and (b) typically affects both the numbers and structures of chromosomes simultaneously, because aneuploidy simultaneously unbalances 1000s of genes.

Selected Publications

Klein, A., N. Li, et al. (2010). "Transgenic oncogenes induce oncogene-independent cancers with individual karyotypes and phenotypes." Cancer Genet Cytogenetics 200(2): 79-99.

Nicholson, J. M. and P. Duesberg (2009). "On the karyotypic origin and evolution of cancer cells." Cancer Genet Cytogenet 194(2): 96-110.

Li, L., A. A. McCormack, et al. (2009). "Cancer-causing karyotypes: chromosomal equilibria between destabilizing aneuploidy and stabilizing selection for oncogenic function." Cancer Genet Cytogenetics 188(1): 1-25.

Duesberg, P. H., J. M. Nicholson, et al. (2009). "HIV-AIDS hypothesis out of touch with South African AIDS - A new perspective." Med Hypotheses online, June 2009.

Fabarius, A., R. Li, et al. (2008). "Specific clones of spontaneously evolving karyotypes generate individuality of cancers." Cancer Genet Cytogenetics 180(2): 89-99.

Duesberg, P., R. Li, et al. (2007). "Cancer drug resistance: The central role of the karyotype." Drug Resist Updat 10(1-2): 51-8.

Duesberg, P. (2007). "Chromosomal chaos and cancer." Sci Am 296(5): 52-9.

Duesberg, P., R. Li, et al. (2006). "Aneuploidy and cancer: from correlation to causation." Contrib Microbiol 13: 16-44.

Duesberg, P. (2005). "Does aneuploidy or mutation start cancer?" Science 307(5706): 41-42.

Duesberg, P., R. Li, et al. (2005). "The chromosomal basis of cancer." Cell Oncol 27(5-6): 293-318.

Li, R., R. Hehlmann, et al. (2005). "Chromosomal alterations cause the high rates and wide ranges of drug resistance in cancer cells." Cancer Genetics Cytogenetics 163(1): 44-56.

Duesberg, P., A. Fabarius, et al. (2004). "Aneuploidy, the primary cause of the multilateral genomic instability of neoplastic and preneoplastic cells." IUBMB Life 56(2): 65-81.

Last Updated 2011-02-17