A "Safer" Cigarette? Prove It, Say Critics

A controversial marketing campaign touting a cigarette-like product as less likely than conventional cigarettes to cause cancer and other smoking-related illnesses is drawing fire from public health officials, scientists, and antismoking advocates. The new marketing effort comes only 4 weeks after the US Supreme Court ruled that the Food and Drug Administration (FDA) lacks the authority to regulate tobacco products.

At R. J. Reynolds Tobacco Holdings (RJR) Inc's annual shareholders meeting, CEO Andrew J. Schindler announced that RJR was marketing a cigarette called Eclipse with the claim that the product may present smokers with "less risk of cancer and certain other diseases, such as chronic bronchitis and possibly emphysema."As part of the new marketing campaign, RJR is using newspaper and magazine advertising along with direct marketing, aimed primarily at consumers in the Dallas–Fort Worth area. Until now, the product has been available only in test markets in Chattanooga, Tenn; Lincoln, Neb; and parts of Atlanta.

Eclipse is also being sold on the Internet. While the site is intended to be age-restricted (to people 21 and older), critics worry that the anonymity of such transactions will allow minors to purchase the product.

"We've just completed a nationwide survey of young people that showed that the vast majority of kids believe it's easy to get tobacco products off the Internet," said Matthew Myers, president of the Campaign for Tobacco-Free Kids. "The only way to ensure that you're not selling to kids is through face-to-face transactions."

Unlike conventional cigarettes, almost all of the tobacco in Eclipse is heated rather than burned. The smoker lights a heat source at the cigarette's tip, a carbon rod containing a powder derived from tobacco. This carbon rod is insulated by two mats of glass fibers that sandwich a layer of tobacco-containing paper, which provides tobacco flavor during the first puffs. The heat passes from the carbon rod through a layer of tobacco and glycerin, creating an aerosol containing nicotine and other substances, which the smoker inhales.

Although cigarette companies have marketed "light" and "low-tar" brands for decades, with the implication that such brands present less of a health risk than traditional cigarettes, RJR is making much more explicit claims for Eclipse. Advertisements say that compared with other cigarettes, "Eclipse may present less risk of cancer" and "produces less inflammation in the respiratory system, which suggests a lower risk of chronic bronchitis, and possibly even emphysema."

However, critics in the health community charge that such claims should be independently verified before consumers or physicians assume the product poses less risk than conventional cigarettes.

"It is not at all clear that a sufficient science base exists to support a bold claim that this tobacco product may reduce the risk of cancer," said Health and Human Services Secretary Donna Shalala in a statement. "Nor is it clear what advice doctors should give their smoking patients who wonder if they should switch to a product like Eclipse."

The announcement of RJR's health claims for Eclipse prompted Shalala and leaders of health advocacy groups to once again urge Congress to pass legislation giving the FDA the power to regulate cigarettes and other tobacco products.

"We think the health claims are outrageous and premature," said John Seffrin, PhD, of the American Cancer Society. "We believe that the product cannot be properly evaluated until there is a full empowerment of the Food and Drug Administration to oversee the industry in general and their health claims in particular."

In fact, some critics contend that products such as Eclipse should be regarded not as a cigarette but as a nicotine-delivery device (such as the nicotine patch) that is not exempt from FDA scrutiny.

"Nicotine patches and gum had to undergo rigorous review and approval by the FDA prior to their introduction into commerce," said John R. Garrison, CEO of the American Lung Association. Eclipse should not be excluded from regulatory oversight simply because it looks like a cigarette and is manufactured by a tobacco company, he said.

RJR said its own studies showed that the smoke from Eclipse contains lower levels of many of the carcinogens present in the smoke produced by conventional cigarettes, that Eclipse produced fewer skin tumors in mice, and that smokers switching to the product had a reduced exposure to DNA-damaging chemicals, less bronchial inflammation, and less inflammation in the lower lungs.

Schindler said the company presented its research findings to a scientific advisory panel and that the panel concluded that Eclipse posed less risk for smoking-associated cancer and for inflammatory-based diseases of the respiratory system than conventional cigarettes.

However, critics charge that the company's claims of health benefits should be viewed in the context of a long history of deceiving the public about the health effects of its products.

"Forty years ago, the tobacco companies implied that low-tar cigarettes were safer, and millions of Americans switched rather than quit," noted Myers. Yet studies suggest that the industry's "light" cigarettes are no safer than other brands.

"R. J. Reynolds picked the scientists and picked the tests [for Eclipse], but without an independent government agency such as the Food and Drug Administration to determine what tests are necessary and to test the product, there's no scientifically valid reason to accept R. J. Reynolds' claim that this product is safer," said Myers.

Schindler conceded that RJR's scientific advisory panel described the company's research as inconclusive with respect to Eclipse's cardiovascular effects. Even if Eclipse does lower the carcinogenic risks associated with smoking conventional cigarettes, critics point out it is unlikely to reduce cardiovascular risks.

Although nicotine is not considered a carcinogen, it increases heart rate and blood pressure and constricts blood vessels. Carbon monoxide also creates cardiovascular stress by impairing the transport of oxygen in the blood and may be linked with the development of coronary heart disease. Plasma nicotine levels in test subjects who used Eclipse were reportedly comparable to those achieved when the subjects smoked their regular brands, and carbon monoxide levels were at least as high, if not higher.

"By its own admission, RJR says that the new Eclipse brand cigarette does nothing to protect smokers from cardiovascular disease caused by smoking," said M. Cass Wheeler, CEO of the American Heart Association. "Each year, 400,000 people die from tobacco use, and fully 50% of them die from heart disease and stroke."

Also missing from the company's advertisements are concerns raised by John L. Pauly, PhD, and colleagues at Roswell Park Cancer Institute, in Buffalo, NY. Pauly and colleagues reported in a 1998 study that most of the filters of Eclipse cigarettes they examined were contaminated by glass fibers and particles, presumably broken off from the mats of insulating glass fibers during the manufacturing process.

Scientists for RJR say the glass fibers pose no risk to consumers. Yet there are plausible reasons why such fibers may pose a health risk, said Pauly.

He and his colleagues demonstrated in experiments using smoking machines that some fibers would probably be dislodged from the cigarette and ingested or inhaled into the lungs. There's also evidence from animal studies that if glass fibers of a size comparable to those contaminating the Eclipse filters are inhaled into the lungs, they can remain there for prolonged periods. Moreover, a team of researchers from Duke University Medical Center concluded in a 1994 review of the available information from animal and epidemiologic studies that glass fibers may be at least as potent a carcinogen as asbestos fibers.

Documents from RJR show that the company was aware that glass fibers are released from the filter during smoking and that epidemiology studies of fiberglass workers found fibers in the lungs of a substantial proportion of the workers, said Pauly. "Thus RJR knew glass fibers could be inhaled and could remain in the human lung for a prolonged time," he noted.

That's information the company isn't sharing with consumers, added Pauly. "RJR has withheld information about the use of glass fibers in cigarettes in promotional videos, newspaper ads, instruction leaflets, and at many scientific meetings," he said.

Whether glass fibers and particles actually do pose a health risk for Eclipse users, RJR's dismissiveness concerning the issue underscores that consumers cannot rely on the company to conduct all the tests necessary to evaluate its relative safety, says Myers.

"In essence, R. J. Reynolds is saying ‘trust me,'" said Myers. "It makes one feel like Charlie Brown, every fall, when Lucy pulls the football away when he's about to kick it. At some point, the American public has to learn."

Boston—Evolving from dream to reality in only a few years, tissue engineering is beginning to provide clinical options in urology. This is quite an accomplishment, said Anthony Atala, MD, of Harvard Medical School, given that 10 years ago keeping urothelial cells alive in the laboratory for more than a few weeks was difficult.

Atala, who spoke at the American Society of Andrology meeting last month, has contributed much to the success of the field. It was at Harvard under his direction that the first urologic application of cell-based tissue engineering—the injection of autologous cells for the correction of vesicoureteral reflux in children—took place.

In this treatment, investigators inject a bulking agent under the ureteral orifice that changes the angle of the ureter and narrows the lumen, thereby preventing retrograde urine flow into the kidney, Atala explained. The injected material, which consists of chondrocytes grown from a biopsy of the patient's ear and a hydrogel called alginate, eventually forms a permanent cartilaginous structure that holds the ureter in place.

The new procedure can be performed in a 15-minute outpatient operation, a notable improvement over the standard surgical treatment, which requires a 4-day hospital stay. With phase 1 trials having shown the safety of the new procedure, phase 2 and 3 trials are under way, and results should be available in about a year, Atala said.

The same procedure has been applied to the correction of urinary incontinence in adults, with the chondrocyte/hydrogel mixture injected into the bladder neck. Phase 1 trials have been completed for this application. Atala said he and colleagues are also investigating this method to inject smooth muscle cells mixed with hydrogels for use in plastic and reconstructive surgery.

A number of additional applications of tissue engineering technology are currently under study, said Atala. For example, his group has used tissue regeneration for urethral reconstruction. "One of the first applications we tried," he said, "was for hypospadias, in which the urethra is not developed all the way to the tip of the penis." In many pediatric patients with this condition, he explained, there is a lack of native urologic tissue for surgery. Grafts from nonurologic tissues can be used, but doing so may increase hospitalization time and morbidity. Atala's group uses a collagen scaffold seeded with the patient's own urothelial cells for urethral repair. More than 60 patients have had this surgery, he said, and at 3-year follow-up, there has been no incidence of stricture formation in any patient.

Last year Atala's laboratory demonstrated that they could engineer a functional bladder in dogs (Nat Biotechnol. 1999;17:149-155). From canine bladder biopsies, researchers obtained urothelial and smooth muscle cells, which they cultured and seeded onto spherical polymer scaffolds. They then transplanted the reconstructed bladder into the dog from which the biopsy was obtained, and Atala said evaluations showed that the neo-organs (as engineered body parts are called by their creators) were normal in terms of histology, elastic properties, and ability to retain urine.

So far, this procedure has not been carried out clinically, but about 2 years ago a patient underwent bladder augmentation using an engineered patch of tissue, said Atala. After a year of observation showed good results, a second patient underwent the procedure. There are now seven patients enrolled in a study.

Atala said he believes in proceeding slowly in bringing this new technology to the clinical setting, explaining, "whenever I've had control of a trial, I've done one patient first, waited a year, and then enrolled other patients."

Other tissue engineered devices that Atala hopes will soon enter clinical trials are autologous penile prostheses. Atala said that silicone prostheses are currently used in cases of traumatic injury or to correct ambiguous genitalia, but because silicone is not a biocompatible material, its use can sometimes be problematic.

By seeding biodegradable polymer rods with chondrocytes harvested from rabbit ears, his group created cartilage rods that were elastic and able to withstand compression in rabbits. Studies showed that the implants were well tolerated for the length of the 6-month study, and the animals were able to copulate, produce sperm, and impregnate their mates.

Encapsulated cells are another promising technology. Researchers in Atala's laboratory have shown that Leydig cells encapsulated in alginate/poly-L-lysine microspheres can secrete testosterone in culture and in rats. Atala said that in vivo, the protected covering allows nutrients to reach the cells and hormones to escape while preventing the relatively large host immune cells from attacking the cells.

These constructs may be useful in treating such conditions as androgen deficiency and prostate cancer. Atala's group is also applying this microencapsulation technique to ovarian cells for the release of progesterone and estrogen.

In spite of its promise, Atala stressed that it is important to recognize that tissue engineering is still a new field that will have its problems just like any other developing technology. Nevertheless, as work continues to yield such exciting results, he said, he is "guardedly excited."

Atlanta—African health ministers have added a new postscript to a familiar message. Their nations need more aid from industrialized nations if devastating health crises are to be resolved, but they want more control in decision making and less bureaucratic red tape in obtaining aid.

More specifically, they want the United States to commit $10 billion during the next 5 years. They also admonished a major donor—the World Bank—for having complicated procedures that may be preventing up to $1.5 billion in aid from reaching Africans with HIV/AIDS, malaria, and other diseases.

During a rare conference that gathered 35 African health ministers on US soil last month, Swaziland's minister pleaded for action to break down bureaucratic obstacles to obtaining international aid. "We have come all this way to find out practical solutions now, not to publish one more document or proposal. This is very complex—we are dying," said Phestile Dlamini, MD.

The conference, aimed specifically at developing new partnerships with industrialized nations to fight HIV/AIDS and malaria, was organized by the Atlanta-based American Medical Team for Africa, a nonprofit group that provides medical supplies and training for poor African nations. Cosponsors included the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), World Bank, and Joint United Nations Programme on HIV/AIDS.

Conference organizers added malaria to their agenda to keep the widespread parasitic infection from being obscured by the international focus on HIV infection. "Africans believe they are totally isolated in their fight against malaria because the world is not as aware of it as AIDS," said Assane Diop, former health minister of Senegal and now an executive director with the Geneva, Switzerland–based International Labor Organization.

Conference speakers recited dire disease statistics: Africa harbors 70%, or 24 million, of the world's estimated 35 million cases of HIV infection and AIDS. Of the world's 400 million malaria cases, 300 million are in Africa. Every year, about 1.5 million Africans die of HIV/AIDS. The same number, mostly women and children, die of malaria. By 2010, said Vivian Lowery-Derryck, of the US Agency for International Development, HIV/AIDS will have slashed the gross domestic products in many African nations by 20%, and malaria will have cut it by 8%.

Despite stepped-up malaria control efforts—clearing thickets to reduce mosquito vectors, spraying houses with insecticides, and increasing the use of insecticide-treated bed nets—malarial infections in Africa are increasing. In 1998, WHO launched the Roll Back Malaria campaign, with the goal of reducing the worldwide malaria burden by half by 2010.

According to WHO, gains in malaria control during the past half century are being eroded for several reasons. Among them are changes in land use that release mosquitoes to find new breeding sites, refugee migration from civil wars, global climate change, and deteriorating health services.

Increased global travel has given rise to "airport malaria" in industrialized nations. The CDC reports that about 1000 cases of malaria are imported to the United States annually through immigration and through US travelers who are infected abroad.

Of particular concern to health leaders in Africa is the high rate of resistance to chloroquine, once the first-line treatment for malaria. "Seventy percent of our patients are resistant to chloroquine," Sam Ongeri, PhD, minister of health in Kenya, told the conference. "We are having to change to sulfa drugs to cope with the situation."

HIV has contributed to chloroquine-resistant malaria, said Rick Steketee, MD, MPH, chief of CDC's Malaria Epidemiology Branch. Many Africans infected with HIV presented with fever as their initial symptom and were treated with antimalarial drugs when, in fact, they may not have had malaria, he said. For pregnant women with malaria, Steketee said, sulfadoxine/pyrimethamine given monthly has been shown to reduce the incidence of placental malaria and low-birth-weight infants.

Added to Africa's considerable number of health crises is difficulty in obtaining sources of international aid. Minister Dlamini's passionate appeal for more aid and less bureaucracy was in response to a World Bank official who told the health ministers that up to $1.5 billion in aid is available from the bank "only in conjunction with other partners like WHO, to execute programs that make sense to address these diseases."

Ok Pannenborg, PhD, the bank's lead specialist for health in Africa, said that while bank funds can be transferred directly to African governments, the transfers are made in collaboration with such organizations as WHO and United Nations agencies to provide technical assistance in implementation and to prevent the diversion of funds for military or other nonmedical purposes.

Pannenborg conceded that transfer procedures "are, frankly, terrible." Funds for health and medical aid go through African nations' finance ministries before the health ministers can route them to national and local programs. "You, as ministers of health, know very well that it's very difficult for you to ensure that the monies in your budgets actually end up at the municipal level for outreach workers that treat children and mothers [with] HIV, AIDS, and malaria," he said. "The first step, though, is that it's absolutely necessary to recognize where those monies are most effective."

Yet as the industrialized world begins to take greater notice of HIV's devastating impact on African society, the health ministers continued, complicated oversight procedures to channel aid to their communities can be construed as a no-confidence vote in their governments.

Ernest Mwansa, deputy minister of health of Zambia, said his country has been trying to pursue health reforms that would facilitate direct access to World Bank funds for HIV/AIDS programs. To maintain oversight by WHO or other agencies, he said, "makes the assumption that there is no system of government in our countries. What that means in practice is that we will never rule ourselves very well."

In fact, WHO's Africa regional director, Ebrahim Samba, MD, echoed similar sentiments. For more than 30 years, Samba said, he has been collaborating with US health officials to eradicate or reduce transmission of nefarious diseases in Africa—smallpox, polio, onchocerciasis, and dracunculiasis. Despite such successful collaboration, Samba said, Africans must be allowed a more active role in managing health programs and donor resources.

"The time is gone when you can come, with all the good will in the world, and do it for us. You can't. Let us be partners. You cannot know Africa as we do." Samba rejected the notion that donor funds may be channeled to nonmedical purposes. "We can account for every cent," he said.

Among a list of preliminary recommendations the ministers offered at the conference's conclusion was to urge the United States to allocate $10 billion during the next 5 years to battle HIV/AIDS and malaria in Africa. The ministers asked that Japan and countries of the European Union provide matching funds.

A more equitable, efficient way to access funds for medications may be through the establishment of an international coalition of donors that would create a pool from which African countries could buy drugs based on their ability to pay. The coalition could be coordinated through the US-based Pharmaceutical Research and Manufacturers of America, which represents leading research-based pharmaceutical and biotechnology firms, or through creation of a group similar to it.

Sylvester Flowers, president of San Francisco–based Ramsell Corporation, which manages state pharmacy programs in California, suggested the idea. Pharmaceutical companies have been criticized for antiretroviral drug pricing that makes therapy for most HIV-infected Africans impossible. But Flowers said international donors and African nations must recognize that drug companies have to make profits to continue research and development of new products. In terms of building more partnerships to bring drug treatment to more Africans, he said, "We have to start somewhere."

Other ideas for collaboration discussed during the conference were aimed at using technologies to improve access to medical care in Africa. Eric Bing, MD, MPH, of Charles Drew University School of Medicine, described how the use of telemedicine is being expanded from ophthalmology clinics to HIV/AIDS clinics. "If we can do it in south central Los Angeles, there is no reason it can't be used across states and nations," Bing said.

However, health ministers in the audience called the cost—$20,000 for a central computer unit and $300 to connect each clinic—"bedeviling." Bing noted that WHO has been funding similar projects in rural areas of poor nations. He suggested that additional funding agencies be located and that negotiations for support include ministries of education that also could benefit from telecommunications technology.

Editor's Note: Miscellanea Medica appears in the Medical News & Perspectives section occasionally. Items submitted for consideration should be directed to the attention of Marsha F. Goldsmith, Editor, Medical News & Perspectives.