published Thursday, May 3rd, 2012

Cleaveland: How science works

Clif Cleaveland

I know of no better introduction to the process of science than "The Emperor of All Maladies: A Biography of Cancer" by Siddhartha Mukherjee. The author, an oncologist, provides a captivating history of mankind's struggle to understand and to treat malignant diseases. His narrative includes many poignant vignettes of patients across the age spectrum to remind us that disease is finally about individuals and their families.

Science depends upon careful testing and retesting of theories. An apparent breakthrough may collapse with further accumulation of data. Modern science relies upon the collaboration of many investigators around the world.

In the first half of the 20th century, surgery dominated cancer therapy. Scientists possessed little knowledge of the behavior of malignant cells, and chemotherapy did not exist.

Increasingly complex surgical protocols evolved for treating malignancies. The prevailing idea was to separate the patient from the disease. Radical mastectomy, which involved removal of breast and surrounding tissues, including muscles of the chest wall, became the standard treatment for breast cancer. Results were often disappointing, and the surgical procedures were often associated with major complications.

Advocates for simpler therapy -- simple mastectomy or lumpectomy followed by radiation therapy -- gained little headway against traditional surgery. Finally, in 1981 an extensive clinical trial that compared the three treatments was published. This showed no differences in rates of recurrence or death.

Childhood leukemia was an especially perplexing disease. Though uncommon, the disease devastated the health of affected children. There was no solid tumor for surgeons to attempt to remove. Sydney Farber, a one-time pathologist who reinvented himself as a clinician, launched cancer chemotherapy in 1947. Through inspired reasoning, Farber selected a blocking agent for a vitamin for a trial in a desperately ill boy with acute leukemia. The boy had a dramatic, though short-term response.

Research and application of chemotherapy to leukemia and other malignant disease expanded rapidly. Teams of scientists formed at the National Cancer Institute and at university and clinical centers across the country. The goal was to identify a chemical that would kill malignant cells while sparing normal cells. Clinical trials compared single agents to multidrug protocols. Improved outcomes were counterbalanced with side effects, many severe. Some therapies caused other cancers years later. The desire for immediate results in patients outran basic scientific inquiry into biology of cancer cells. Communication between clinicians and laboratory investigators sometimes broke down.

Radiation therapy advanced, especially in the treatment of Hodgkin's disease, a malignancy of lymph nodes. Once again, side effects intruded with acute and delayed injury to healthy tissues.

Screening tests allowed earlier detection of some tumors before they could spread. The Pap smear drastically reduced deaths from cancer of the uterine cervix. Mammograms detected breast cancers at early stages. Tests for blood in stool samples and colonoscopy led to earlier detection of colon malignancies. Today we face questions of when and how often to screen.

On the public health front, the Surgeon General's report in 1964 highlighted the link of cigarette smoking to lung cancer. Ripples from that declaration continue to shake the tobacco industry. Less-publicized studies have implicated a wide array of environmental pollutants, such as dioxin and the pesticide heptachlor.

Political leaders at various times proclaimed "war on cancer" and directed huge sums to accelerate the search for a magical cure. The "wars" produced limited successes.

Slow, methodical research into the genetic makeup of patients and their cancers has opened new possibilities for prevention and treatment. Certain viruses such as hepatitis B can cause cancer. The vaccine for hepatitis B has dramatically reduced the incidence of liver cancer. Other viruses can insinuate themselves into our DNA and lie dormant until a triggering toxin activates them.

Studies of the genetic codes of malignant cells have uncovered genes that switch cell growth on and off. New drugs are being designed to alter this process. As a result, some malignant diseases have become chronic illnesses manageable by daily medications that target chemical reactions within cancer cells.

Eventually a unified approach to cancer will emerge. This will integrate environmental and genetic information in ways that enhance prevention and make diagnosis and treatment more predictable, safer and more effective. Managing costs will be a challenge. Assuring access to care must be a priority to assure that advances in science are open to all.

Email Clif Cleaveland at

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