Faculty Research Page

Peter H. Duesberg

Peter Duesberg

Professor of Biochemistry, Biophysics and Structural Biology

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

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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, clonal karyotypes.  (2) Oncogenes are not sufficient to transform normal cells to cancer cells.  (3) Carcinogens induce cancers only after exceedingly long latencies of many months to decades.  (4) Cancers are karyotypically flexible, whereas conventional mutations are stable.  (5) All cancers are immortal, despite karyotypic flexibility.

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

This speciation theory of carcinogenesis would explain, why cancers have individual karyotypes.  It would also explain, why oncogenes are not sufficient to cause cancer.  Further it would explain the notorious long latencies from carcinogens to cancer by the very low probalbility of forming a new autonomous karyotype by random karyotypic rearrangements of a precursor - much like in conventional speciation.  

But would this theory also explain, why cancers are genomically flexible, and why cancers are immortal?

Currently we are testing the speciation theory of cancer as an explanation for the unique characteristics of cancer, autonomy, individuality, long latency, clonality and the unique karyotypic flexibilty, as follows:

Speciation theory of cancer.  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 mitosis genes that segregate, synthesize and repair chromosomes.  Thus aneuploidy catalyzes chain reactions of random karyotypic variations automatically.

These chain reactions have two stable endpoints (see graphic): 

1) Cell death from lethal karyotypes, and

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

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 karyotypic subspecies, eg. metastasis and drug-resistance.

The steady generation of Immortalizing variants by karyotypic flexibility would also explain, how cancers become avoid Muller's ratchet, ie. the fatal consequences of accumulating lethal mutations.  As a result of thier inherent variability cancers are immortal.

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:  Several past reviews of the virus-AIDS hypothesis led to the conclusion that the various AIDS epidemics of the US, Europe and Africa have chemical bases, namely toxic recreational drugs, inevitably toxic DNA-chain terminators prescribed as anti-viral drugs and malnutrition.  A recent paper in the Ital J Anat Embryol confirms and extends this view (Duesberg et al., 2011).  A precursor of this paper was censored in 2009, a few months after its publication in Medical Hypotheses (Enserink M. (2010) Science vol. 237, p1316).

Current Projects

Our theory makes several predictions that we are now testing experimentally:

(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 with 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

Bloomfield M and Duesberg P (2016) "Inherent variablility of cancer-specific aneuploidy generates metastases" Molecular Cytogenetics, 9:90.

Bloomfield M and Duesberg P (2015) "Karyotype alteration generates the neoplastic phenotypes of SV40-infected human and rodent cells" Molecular Cytogenetics, 8:79.

Erickson N and Duesberg P (2015) "What if HPV does NOT cause cervical cancer?” SaneVax newsletter, January 21, 2015.

Duesberg P (2014) "Does aneuploidy destabilize karyotypes automatically?" Proc Natl Acad Sci U S A, Epub 2014 Feb 25.

Bloomfield M, McCormack A, Mandrioli D, Fiala C, Aldaz CM and Duesberg P (2014) "Karyotypic evolutions of cancer species in rats during the long latent periods after injection of nitrosourea.” Molecular Cytogenetics 7:71.

McCormack A, Fan JL, Duesberg M, Bloomfield M, Fiala C, Duesberg P. (2013) "Individual karyotypes at the origins of cervical carcinomas."  Molecular Cytogenetics 6:44.

Duesberg P, McCormack A. (2013) "Immortality of cancers: a consequence of inherent karyotypic variations and selections for autonomy." Cell Cycle 12: 783-802.

Duesberg P, Iacobuzio-Donahue C, Brosnan JA, McCormack A, Mandrioli D, Chen L. (2012) "Origin of metastases: Subspecies of cancers generated by intrinsic karyotypic variations." Cell Cycle 11:1151-66.

Duesberg P, Mandrioli D, McCormack A, Nicholson JM. (2011) "Is carcinogenesis a form of speciation?"  Cell Cycle 10:2100-14.

Duesberg PH, Mandrioli D, McCormack A, Nicholson JM, Rasnick D, Fiala C, Koehnlein C, Bauer HH, Ruggiero M. (2011) "AIDS since 1984: no evidence for a new, viral epidemic -- not even in Africa."  Italian Journal of Anatomy and Embryology 116:73-92.

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.

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 2017-01-18