Progress in Nucleic Acid Research and Molecular Biology
43:135-204, 1992

Latent Viruses and Mutated
Oncogenes: No Evidence
for Pathogenicity


Department of Molecular and Cell Biology
University of California at Berkeley
Berkeley, California 94720

The scientific community has been virtually unanimous in admiring its recent triumphs in biotechnology - above all, the detection and amplification of minute amounts of materials into workable and marketable products. However, in clinical diagnostic applications, the new detection methods have become a mixed blessing, which benefits medical scientists but not necessarily their clients. Since rare signals have become just as detectable as abundant ones, many latent viruses have been detected and have been assumed to be just as pathogenic as active prototypes (1-3). Likewise, cellular mutations have become detectable that do not, or just barely, affect the function and activity of genes. Yet when the affected genes are structurally related to retroviral oncogenes, they are assumed to be just as oncogenic as highly active retroviral oncogenes (1, 4-8). However, the evidence for these hypotheses is only circumstantial-based on structural similarities to classical pathogenic viruses and viral oncogenes. Thus, without direct proof, these hypotheses may open the doors to psychologically harmful prognoses and clinically harmful prevention programs, termed "molecular genetics at the bedside" by Bishop (9)

"Circumstantial evidence is a very tricky thing," answered Holmes, thoughtfully. "It may seem to point very straight to one thing, but if you shift your point of view a little, you may find it pointing in an equally uncompromising manner to something entirely different.... There is nothing more deceptive than an obvious fact...."

- Sir Arthur Conan Doyle, in The Boscombe Valley Mystery, 1928

I. New Technology and Old Theories in the Search for the Causes of Disease

A. A New Generation of Virologists Presents Latent Viruses as Pathogens

B. From Retroviral to Cellular Oncogenes-The Oncogene Hypothesis

C. From Autonomous Pathogens to Multifactorial Causes of Disease

D. The Search for Alternative Hypotheses

II. Inactive Viruses and Diseases Resulting from the Loss of Cells

A. Human Immunodeficiency Virus (HIV) and AIDS

1. The Virus-AIDS Hypothesis

2. The Drug-AIDS Hypothesis

3. The Drug- versus the Virus-AIDS Hypothesis

B. Hepatitis C Virus and Non-A Non-B Hepatitis

C. Measles Virus, HIV, and Subacute Scleroting Panencephalitis

D. Phantom Viruses and Neurological Disease

III. Viruses as Causes of Clonal Cancer

A. Human T-cell Leukemia Virus and Adult T-cell Leukemia

B. Herpes Virus, Papilloma Viruses, and Cervical Cancer

C. Hepatitis B Virus and Liver Carcinoma

D. Epstein-Barr Virus and Burkitt's Lymphoma

IV. Mutated Oncogenes, Anti-oncogenes, and Cancer

A. Mutated Proto-myc Genes and Burkitt's Lymphoma

B. Rearranged Proto-abl Genes and Myelogenous Leukemia

C. Point-mutated Proto-ras Genes and Cancer

1. The Original ras-Cancer Hypothesis Postulates a First order Mechanism of Transformation

2. Ad hoc ras-Cancer Hypotheses Postulating Second- and Higher-order Mechanisms of Transformation

D. int Genes with Integrated Mouse Retroviruses and Mouse Mammary Carcinomas

E. Constitutive Oncogenes, Mutated Anti-oncogenes, and Cancer

V. Conclusions

A. Evidence That Latent Viruses and Mutated Cellular Genes Are Pathogenic Is Circumstantial

B. Helper Genes and Cofactors to Close the Activity, Infectivity, and Specificity Gaps of Hypothetical Pathogens

VI. Alternative Hypotheses

A. Latent Viruses as Harmless Passengers

B. Drugs as Alternatives to Hypothetical Viral Pathogens

C. Mutated Genes and Latent Viruses as Trivial Genetic Scars of Cancer Cells

D. Cancer by Somatic Gene Mutations Unconfirmed

E. Chromosome Abnormalities as Causes of Cancer