Under the Microscope:Cancer is a common and greatly feared disease. One in three of us get cancer over the course of a lifetime. The disease has stoutly resisted the efforts of science to find cures. In 1970, US president Richard Nixon announced a War on Cancer amid great optimism that the disease would be controlled within 10 years, writes Prof William Reville.
Unfortunately cancer is still with us and, with the exception of a few types, little progress has been made in uncovering cures. One possible reason is that the conventional model of how cancer is triggered and develops is flawed. A new theory may be much closer to the bullseye, as explained by Peter Duesberg in the May 2007 edition of Scientific American.
Yes, this is the same Peter Duesberg who claims that HIV does not cause Aids, a claim firmly rejected by mainstream science. However, Duesberg is a brilliant scientist with a solid track record - in 1970 he isolated the first cancer gene from Rous sarcoma virus. His hypothesis about cancer is controversial but is taken seriously by mainstream science.
The basic unit of biological organisation is the cell. Its biochemistry is controlled by genes. Genes are made of DNA and they control the cell by specifying the proteins that are made. Proteins carry out most of the work in the cell and, in particular, proteins known as enzymes, the catalysts that allow biochemistry to proceed quickly enough and controlled enough to sustain life. DNA is an information rich molecule and this information codes for proteins. The length of DNA sufficient to specify one protein is called a gene. DNA, like all large molecules in the cell, is constantly undergoing damage caused by the environment. Because DNA is crucial, there are mechanisms in the cell to repair damaged DNA. But mistakes can occur during repair and, consequently, information not intended to be there can enter the DNA. This misinformation is called a mutation. A mutation will result in an altered protein being made.
The human cell contains about 40,000 genes and these are grouped into 23 different structural groups called chromosomes. The cell contains two copies of each chromosome (one donated by the mother, the other by the father). This is called the diploid state. Cells regularly divide in two to form daughter cells. The chromosomes are duplicated in this process and the copies are separated from each other on a structure called the spindle, each daughter receiving a copy.
The process of cell division is carefully controlled under normal circumstances. In cancer the controls that regulate cell division go awry and the cells proliferate out of control and also develop the ability to migrate (metastasis) from their organ of origin to another locus in the body, where they continue to grow in an uncontrolled manner. The conventional thinking as to why this happens is that mutations in genes (proto-oncogenes) that control cell division change them into genes (oncogenes) that allow cell division to proceed unchecked.
But, Duesberg draws our attention to another fact: "In every known instance of cancer, individual genes may contain mutations, but entire chromosomes are also severely scrambled, duplicated, broken, structurally rearranged or missing entirely." Duesberg's hypothesis, supported by growing evidence, is that this chromosomal "chaos" is not, as the prevailing model holds, a side effect of malignancy, but "the direct cause and driving force of cancer".
In the normal cell the chromosomes are carefully maintained and cells with altered or abnormal numbers of chromosomes are rarely viable. Down's Syndrome is a rare exception, but illustrates the effects that result from the presence in the cell of just one extra copy of the small chromosome, number 21.
Normal cells are diploid, but cells in solid cancerous tumours are always aneuploid, meaning they have gained or lost chromosomes or segments of chromosomes. The total DNA of a cancer cell can rise to over twice or fall to less than half the DNA of a normal diploid cell. Since DNA codes for proteins, cancer cells will therefore produce a spectrum of proteins grossly distorted in individual amounts compared to the normal cell. This would disrupt the sensitive controls necessary to maintain the normal biochemical economy of the cell. The spindle that segregates chromosomes during cell division is complex and delicate and would suffer distortions in cancer cells. Once aneuploidy begins therefore "additional derangement of the chromosomes is likely".
Duesberg lists six characteristics of cancer that, he claims, cannot be explained by the conventional mutation theory, but can be explained by aneuploidy. For example, many agents (carcinogens) are known to cause cancer - cigarette smoke, asbestos, dioxin, and so on. Many of the most potent carcinogens induce no mutations in cells, but all cause "higher than usual rates of breakage and disruption" of chromosomes. This strongly suggests carcinogens act as "aneuploidigens" rather than as mutagens.
Risk of cancer grows with age. Duesberg argues that if the mutation hypothesis were correct, cancer rates would be much higher in infants because they could inherit mutations that would increase risk and need only accumulate perhaps one more mutation after birth that would, in concert with the inherited mutations, trigger the initiation of cancer. But cancer in children is relatively rare with the significant exception of children with congenital aneuploidy, eg Down's Syndrome.
If the current mutation hypothesis is wrong, we cannot expect that interventions designed to treat or prevent cancer that arise out of this hypothesis will be very successful. The new hypothesis deserves to be rigorously tested.
• William Reville is Associate Professor of Biochemistry and Public Awareness of Science Officer at UCC - understandingscience.ucc.ie