Peter Duesberg

Peter Duesberg

Title
Professor of Biochemistry and Molecular Biology
Department
Dept of Mathematics
Phone
(510) 642-6549
Fax
(510) 643-6455
Research Expertise and Interest
carcinogenesis, aneuploidy, genetic structure of retroviruses, virology, HIV-AIDS
Research Description

Research on new theory that cancers are species of their own.

Over a hundred years of research have shown that all cancers are autonomous, have individual karyotypes and arise only years to decades after initiation by carcinogens.  But despite enormous efforts since, explanations for these long-established characteristics are still debated.

The currently prevailing mutation theory holds that carcinogenesis is slow, because it is caused by rare, stepwise accumulations of 3–8 gene mutations, termed oncogenes.  The mutation theory considers the individual karyotypes of cancers as “consequences” of carcinogenesis.  But the mutation theory has still not identified a set of mutations that is sufficient to convert a normal tissue-specific cell to an abnormal autonomous cancer cell. 

Since the mutation theory continues to elude formal proof, we have recently advanced and tested an alternative cancer theory. This theory holds that carcinogenesis is a form of speciation 1,2.  Four analogies between cancers and conventional species support this theory:  1) Cancers are autonomous growths, 2) have individual clonal karyotypes, 3) arise from precursors only after exceedingly long latencies of years to decades from carcinogens, which may be analogous to the long latencies from one conventional species to another and 4) are immortal.

Mechanism of carcinogenesis.  According to the speciation theory carcinogens initiate cancer by aneuploidization, which automatically unbalances thousands of genes and thus auto-catalyzes chain reactions of further aneuploidizations. Over time, these aneuploidizations have two endpoints, either non-viable karyotypes or very rarely karyotypes of new autonomous cancer species.  The low probability that random aneuploidizations generate a new autonomous cancer species (or other species) explains why cancers have individual karyotypes, why cancers are clonal and why cancers follow initiating carcinogens only after long latencies 2.  

Clonal heterogeneity.  According to the speciation theory the karyotypes of cancers arise from rare rearrangements of normal karyotypes.  By corrupting the normal balance of numerous normal genes, aneuploidy renders numerous cellular functions error-prone - above all mitosis - and thus destabilizes the karyotype.  But despite this inherent instability the karyotypes of cancers are steadily stabilized by clonal selections for autonomy – and are thus ‘heterogeneous’ within clonal margins.   The resulting heterogeneity would be proportional to the degree of aneuploidy.  This dynamic equilibrium between aneuploidy-catalyzed variation and concurrent selection for autonomy resolves the previously unexplained paradox of the “immortality” of cancers despite “genetic heterogeneity”.  

Clinical implications.  The karyotypic-phenotypic flexibility of cancers is the nemesis of cancer chemotherapy, as resistant subspecies steadily evolve at high rates.  But the speciation theory offers preneoplastic aneuploidy as a realistic basis of cancer prevention, e.g. Pap smears, and predicts that the degrees of neoplastic aneuploidy are a testable basis for cancer therapy and prognoses.

References:

1          Duesberg, P., Mandrioli, D., McCormack, A. & Nicholson, J. M. Is carcinogenesis a form of speciation? Cell Cycle10, 2100-2114, doi:16352 [pii](2011).

2          Hirpara, A., Bloomfield, M. & Duesberg, P. Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long Latencies of Cancers. Genes (Basel)9, doi:10.3390/genes9080402 (2018).

In the News

July 26, 2011

Are cancers newly evolved species?

Molecular biologist Peter Duesberg’s theory that cancer results from chromosome disruption rather than a few gene mutations has led him to propose that cancers are actually evolving into autonomous species, akin to parasites.