Editor's Note: Science Scan is a roundup of recently published biotechnology-relevant research.

Does taking part in a controlled clinical trial of cancer therapy improve one's chances of surviving that disease? What is your opinion?

The widely held belief that people with cancer who take part in clinical trials have better treatment outcomes is disputed by the U.S. authors of a report in The Lancet, dated Jan. 24, 2004. Its title: "Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review." The medical oncologists who tested the supposition are at the Dana-Farber Cancer Institute in Boston.

The group surveyed 26 previously published studies that compared the health outcomes of cancer patients enrolled in clinical trials vs. those not enrolled. Although 14 of their studies suggested a beneficial health outcome for trial participants, most studies did not effectively control for bias. For example, only nine studies required the same entry criteria for participating and non-participating patients. Only three of those found that trial participants had better outcomes than non-participants

"Until more convincing evidence for a trial effect is available," the article's senior author commented, "recruitment messages to patients considering trials should focus on their contribution to advances in treatment. We believe that patients, professionals and third-party players can recognize the crucial function of clinical trials in advancing treatment, and that de-emphasizing direct benefits to patients need not compromise accrual or coverage. We remain optimistic that strong support for trials can flourish on the basis of their unquestioned role in improving options for patients with cancer."

Many oncologists believe that cancer patients who enroll in clinical trials have better outcomes than those who do not enroll. The co-authors "aimed to assess the empirical evidence that such a trial effect exists." After developing a conceptual framework for comparison of trial and non-trial patients, they did a comprehensive literature search to identify studies comparing outcomes between those groups. They identified 26 comparisons from 24 published articles of outcomes among cancer patients enrolled and not enrolled in clinical trials.

Of those, 21 comparisons used retrospective cohort designs; 14 comparisons provided some evidence that patients enrolled in trials have improved outcomes. Only eight comparisons restricted non-trial patients to those meeting trial eligibility criteria. Of those, three reported better outcomes in trial patients than in non-trial patients. The American Federation of Clinical Oncology Societies maintains that treatment in a clinical trial often is a cancer patient's best chance of survival, and that trial access is one of the "basic requirements of quality cancer care." Such claims suggest that trials are viewed not only as a way to improve future treatment, but also as the best therapy for current patients.

One possibility was a comparison with people who were offered trial enrollment but declined. An advantage of that design is that it selects controls from the same pool as trial patients. Its major limitation is that refusal might correlate directly with the outcome in question. For example, patients who enter the trial might be more adherent - more faithfully compliant. "Eligible refuser studies that address these limitations, however, are valuable because they confront directly a crucial question: Should we encourage patients with cancer to accept entry in a clinical trial on the basis of self-interest alone?," the article concludes.

Theory That A Mutated Gene Kept Carriers From Plague Long Ago Proved Wrong

A popular hypothesis holds that the origins of a genetic mutation, widespread among Caucasians of Northern European descent, protects against HIV is plain wrong. The flawed hypothesis suggests that the mutation conferred resistance against plague centuries ago in the Middle Ages, much as it does against human immunodeficiency virus today. The notion was based on the fact that the gene mutation first appeared around the same time that the "Black Death" plague killed one-third of Europe's population in the years 1346-1357. Since HIV was not present in Europe during those years, individuals who acquired the mutation must have been protected against some other disease.

In a brief communication to be published this week in Nature, Scripps research immunology professor Donald Mosier showed the hypothesis to be off base - incorrect. Mosier performed studies that demonstrate that the mutation does not protect against plague infection in mouse models. Thus, it is unlikely to have offered any protection against the plague in humans during the Middle Ages.

The mutation in question is in the C-C chemokine receptor 5 gene, which makes the human receptor protein CCR5. That protein spans the transmembrane of 332 amino acids to gain entry into CD4+ T cells. The mutation was first identified in 1996 in individuals who seemed to be shielded from infection with HIV despite multiple high-risk exposure to the virus. In order to confirm the HIV-plaque concept, an attenuated, non-transmissible form of Yersinia pestis - the bacterial cause of plague - was tested on mice both with and without the CCR5 mutation.

A Different Gene Just Identified Apparently Increases The Risk Of Addiction To Ethanol

Published in the January 2004 issue of Alcoholism: Clinical and Experimental Research, an article is the first to demonstrate an association between a particular gene and ethanol dependence. Its title: "Association of GABRG3 With Alcohol Dependence." The gene is related to a receptor that allows for the movement of gamma-amino-butyric acid (GABA) between nerve cells. GABA is the major inhibitory chemical in the central nervous system. For the study, the investigators, largely at Washington University in St. Louis, analyzed DNA from 262 families - a total of 2,282 members. They tested for association between the GABAA receptor genes clustered on chromosome 15 and alcohol dependence by using a large sample of multiplex alcoholic families.