By Alice Dembner

Dr. David Trentham is the chairman of the Department of Rheumatology at Harvard. He has used the antibiotic Minocin for successfully for many with rheumatoid arthritis and scleroderma. He decided to study the drug in those ages 6 to 14 and asked drug maker Wyeth for a donation of ,000 worth of the antibiotic. Wyeth, which made billion last year in total sales of drugs and other products, had acquired a small company that supported Trentham's previous studies of minocycline in animals and in adults. But this time, the answer was an unequivocal no.

''While scientifically interesting, the concept and design is not consistent with our current business objectives,'' wrote a company official in a letter that Trentham said stunned him.

While company officials later said patient safety was the reason for the denial - the antibiotic can cause some side effects, such as discoloration of the teeth - Trentham believes the letter gave far more insight into the company's reasoning.

Trentham's translation of the letter: If minocyline worked, it might compete with a blockbuster drug called Enbrel that Wyeth now markets for both adult and juvenile rheumatoid arthritis. Enbrel costs ,300 per month for adults and has life-threatening side effects, while Wyeth's brand of minocycline, called Minocin, costs only 0 for an adult monthly dose, Trentham said. And unlike Enbrel, minocycline is no longer under patent, so many companies could benefit from the drug's success.

As rheumatologist Trentham put it, ''It's a commercial decision, and it's unfortunate for the patients.''

Trentham said it was the first time in his career that a drug company had turned down his request for support of a study. But other researchers said denials are becoming more common as the drug market becomes ever more competitive.

''It happens all the time,'' said Dr. Raymond Woosley, a prominent drug researcher who is vice president of health sciences at the University of Arizona. ''They don't want you to study their drug because of what you might find or how your finding might affect another drug they're marketing. They want to control the data on their drug.''

While companies have no legal obligation to support research by doctors who don't work for them, many scientists believe they have a moral responsibility to society.

''When a company refuses to allow someone to do legitimate research on their drugs, we all lose out,'' said Sheldon Krimsky, a Tufts University professor who has studied relationships between academic researchers and drug companies. ''Their interest is in their market share, not in public well-being.''

A spokeswoman for Wyeth, however, said economics played no role in the company's decision. ''The decision was made primarily on safety,'' said Natalie de Vane. ''The company felt there were newer medications that could be studied that didn't have the side effects that this particular drug has. Minocin is contraindicated in young children and there were very young children in this proposal.''

While minocycline carries an FDA warning against use in children under 8 because of possible permanent discoloration of teeth, Trentham said that is a far cry from the warning on Enbrel, of serious and sometimes fatal infection or sepsis. Nonetheless, Enbrel was approved by the FDA in 1999 for use in juvenile rheumatoid arthritis for those patients who fail other treatments.

Despite the rejection by Wyeth, Trentham is forging ahead. He secured a ,000 grant from a small private foundation, the Road Back Foundation, to fund lab fees for the six-month study and will buy Minocin from Wyeth, and then charge study participants or their insurers for the drug. But he said he worries that that will make it much harder to recruit participants and will delay the study, now scheduled to begin this summer. He plans to recruit patients across the country who are not currently taking Enbrel or another treatment, methotrexate.

''It's terribly important to get to the bottom of whether Minocin works in children with juvenile rheumatoid arthritis because of the benign nature of Minocin,'' said Trentham, who is known as an antibiotic enthusiast.

Juvenile rheumatoid arthritis affects up to 50,000 children in the United States, causing painful swelling, stiffness and deformity of joints and sometimes stunting growth. While some children outgrow it, others fight the disease their whole lives. Doctors believe it is caused by a malfunction of the immune system and typically treat children with anti-inflammatory drugs starting with ibuprofen and moving to more potent drugs.

If minocycline works consistently in children, Trentham said, it would also be a safer alternative to two other common treatments for JRA - steroids and methotrexate. Steroids can stunt a child's growth, and methotrexate, often used to treat cancer, can be toxic to the liver and it can harm the immune system when given in higher doses than usually given in children.

Some pediatric rheumatologists said, however, that methotrexate is not as risky and minocycline is not as safe for children as Trentham suggests. A cousin of tetracycline, it commonly is used to treat severe acne. But it can discolor teeth and skin, irritate the stomach, and, in rare instances, it can cause liver or kidney damage and has been associated with lupus.

''We're able to control a large number of our patients with currently available drugs,'' said Edward Giannini of Cincinnati Children's Hospital, a senior scientist with an international consortium that studies pediatric rheumatology treatments and helped test Enbrel and methotrexate. ''I don't see much of a need to look at this drug, because we feel it's only partly effective in adults. But there's no harm in studying it.''

Concern about side effects of methotrexate led Melanie Masala to bring her daughter, Gloria, to Boston for treatment with minocycline. ''I was wondering which was worse, the disease or the cure,'' she said.

With minocycline, Marsala said, Gloria's transformation was ''incredible.'' As Gloria said: ''Before, not many people liked to play with me because I couldn't do the things they wanted to do. Now, I ride my bike, I rollerskate, I can jump, I can even climb a little.'' And Trentham said she is growing again, catching up to her classmates, without any medication side effects.

Scientists do not understand why minocycline appears to help some arthritis patients. A national study of 219 adults with rheumatoid arthritis, supported by the National Institutes of Health and published in 1995, found, however, that minocycline significantly reduced joint swelling and tenderness in more than half of patients, although a dummy pill caused similar improvement in about 40 percent. Lederle Laboratories, which then made Minocin, provided the drug and placebo free for the study. Wyeth subsequently bought Lederle and helped market Enbrel, which chalked up 0 million in sales last year.

Trentham, who was one of several investigators for the NIH study, chose to use Minocin for his new study for consistency, rather than other generic versions of the antibiotic made by other drug companies.

Getting free drugs for research is ''especially a problem when the company has a competing drug,'' said Woosley, a professor of pharmacology and medicine. He and colleagues were thwarted a few years ago, he said, when they wanted to study the side effects of an older synthetic estrogen replacement. The company, which he declined to name, refused because officials were worried the study would focus attention on the side effects of a new drug they were developing.

''From a business point of view, it makes sense. Why should they get involved in anything that might harm them?'' said a Boston-area researcher, who requested anonymity because he feared alienating companies from which he regularly seeks support. ''But the research community is trying to find out the truth, about mechanisms and side effects of drugs and how they are best used clinically. And the drug companies' posture impedes that. It's gotten worse year by year and the last two years have been impossible.''