Jewish World Review Feb. 1, 2002 / 19 Shevat, 5762

Antibiotics in livestock feed & human disease

By Robert A. Wascher, M.D., F.A.C.S.

http://www.NewsAndOpinion.com -- THE routine addition of antibiotics to livestock feed has been the subject of debate for years. Opponents of the practice cite the increasing prevalence of human disease-causing bacteria that have become resistant to even the most potent antibiotics. Proponents of the practice cite improvements in the health of livestock and increased meat yield.

However, the lack of research confirming an impact of this practice on human health has rendered the controversy a matter of mostly academic speculation. Until now, that is.

In 1997, the European Union banned a livestock feed additive, the antibiotic avoparcin, due to concerns about the rising incidence of antibiotic-resistant bacteria in the food chain. Avoparcin kills bacteria by impairing cell wall formation, similar to the mechanism of action of the human antibiotic vancomycin, which is used to treat patients with life-threatening bacterial infections (typically involving bloodstream infections with gram-positive bacteria that are already resistant to multiple other antibiotics). Over the past 5 years, several virulent bacterial species have shown ever-increasing resistance to vancomycin, including a particularly nasty bug called enterococcus.

Following the ban on avoparcin in livestock feed, researchers were able to document a reduction in the incidence of vancomycin-resistant enterococcus in the gastrointestinal tracts of food animals. However, the impact of these findings on human disease was unclear. A Belgian study, reported in the journal Science, seems to have the answer.

University of Antwerp researchers cultured enterococci from the gastrointestinal tracts of 353 patients, and then subjected these bacteria to vancomycin exposure. Only 0.6% of the enterococcus cultures were deemed to be resistant to vancomycin, as compared to a documented rate of 5.7% in 1996, when avoparcin was in widespread use in the European livestock industry. The researchers further studied the enterococcus cultures to assess for the presence of a bacterial gene known to specifically confer vancomycin resistance. Their genetic analysis confirmed that the incidence of this resistance gene had fallen, from almost 6% to 0.8%, since the discontinuation of avoparcin in livestock feed.

In the United States, the FDA is currently reviewing the practice of livestock feed supplementation with antibiotics, and is expected to rule on the matter sometime this year. However, the debate has been joined by meat producers and livestock antibiotic manufacturers, most of whom support the routine feeding of antibiotics to livestock.

GENETIC DETECTION OF EARLY COLON CANCER IN THE STOOL

This week's New England Journal of Medicine reports on an interesting colorectal cancer study from Johns Hopkins University. Currently, colorectal cancer is the second most common cause of cancer death in the United States (lung cancer is the first). More than 130,000 Americans will develop colorectal cancer this year, and an estimated 57,000 will die of the disease. When detected at the earliest detectable stage, the disease is often curable with surgery.

However, early colorectal cancer usually causes no symptoms. The single most effective way to detect early colon cancer, at this time, is by screening with colonoscopy. A flexible lighted tube is inserted into the rectum, and a video camera is used to fully examine the interior of the colon. The procedure is somewhat uncomfortable, expensive, and carries a small risk of infection and colon perforation. Other less invasive-and less sensitive-colorectal cancer screening methods include fecal occult blood testing, flexible sigmoidoscopy (in which one-third to one-half of the colon is examined by a flexible scope), the barium enema x-ray test, and, more recently, the experimental "virtual colonoscopy" (utilizing a CT scan x-ray machine). Needless to say, most people are not overly anxious to undertake any of these tests.

The transition from normal colon/rectal cell to colon/rectal cancer cell see ms to follow a fairly predictable path of sequential genetic mutations. Prior to the actual formation of a cancerous tumor, abnormal-but as yet non-cancerous-cells form small benign tumors called adenomas. This early phase in the progression from normal cell to cancer cell generally involves the development of a mutation in a gene called APC. Additional gene mutations can subsequently occur in these "adenomatous cells," leading to the development of colorectal cancer.

The Johns Hopkins researchers developed a highly sensitive genetic test for the APC gene mutation, and then used it to screen the stool of 28 patients with early stage colon cancer, 18 patients with colon adenomas, and 28 patients without evidence of any colorectal abnormalities. Among the 46 patients with adenomas or cancers, 26 (57%) were found to have detectable APC gene mutations in their stool, while none of the 28 patients with normal colons had detectable APC mutations. Although this study missed 43% of the patients with adenomas or cancers, this is a rather impressive degree of sensitivity and accuracy for a screening test that involves testing only the fecal matter for cells sloughed from the lining of the colon and rectum. The fact that it can detect the presence of both cancer tumors and pre-cancerous adenomas is especially compelling.

The field of "molecular diagnostics" has been revolutionized by the recent mapping of the human genome, and promises to offer further stunning breakthroughs in the diagnosis and treatment of a multitude of diseases, including cancer.

GENETIC ANALYSIS OF BREAST CANCERS MAY HELP DECIDE TREATMENT

Briefly, another important study of cancer cell genetics appeared this week, in the journal Nature. The decision to treat breast cancer patients with adjuvant therapy (e.g., chemotherapy, hormonal therapy, radiation therapy, etc.) is often based upon the results of clinical trials that have studied the outcomes of thousands of such patients.

In the case of patients with breast cancer that is still confined to the breast, the decision to offer adjuvant therapy is especially difficult as the benefit of such treatments are thought to be rather modest, overall, in this low-risk patient group. However, even within this low-risk group of patients, 10-30% will go on to develop recurrent breast cancer, and it is these patients who are most likely to significantly benefit from adjuvant treatment.

The authors of this study subjected the breast cancer tumors of patients with early stage cancer to gene array analysis. The technique involves the screening of tumor tissue against thousands of known human genes in an effort to identify those genes that are hyperactive and those that are shutdown in tumor cells.

In 117 young patients with early breast cancer, the authors found a distinctive gene expression pattern that portended of a poor prognosis in these otherwise "low risk" breast cancer patients. Not surprisingly, abnormally hyperactive genes present in the tumors of patients who recurred were those known to regulate the cell division cycle, as well as genes that enable tumor cells to invade surrounding tissues, spread to distant sites, and to recruit new blood vessels for nourishment.

This study suggests that patients with early stage breast cancer could conceivably be screened by gene array analysis to determine those patients most likely to benefit from receiving adjuvant therapy. The ability to make this determination might make it possible for 70-90% of all patients with early stage breast cancer to safely avoid the risks inherent in adjuvant therapy.

This is yet another example of the dramatic recent improvement in our understanding of the genetic underpinnings of normal and cancer cell biology, and the exciting implications of such knowledge with respect to the diagnosis and treatment of cancer and other formidable diseases.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.