A SPECIAL REPORT
Who Owns Your Genes?

By GINA KOLATA
 

Mr. Fuchs, who is gay, had had unprotected sex over the years with men who carried the virus. It stood to reason that he, too, would be infected.

But, to his astonishment, the test showed no evidence of the virus. "I said, 'This has got to be wrong,' " Mr. Fuchs said. "Then I took the test again and I took it again." The results never varied.

Over the next six years, Mr. Fuchs repeatedly got in touch with AIDS researchers and asked them to study him and figure out why he seemed to be immune to the virus, H.I.V. But, he said, the scientists told him they were not interested.

Finally, in 1994, Mr. Fuchs, still uninfected, tried again at a place he had approached earlier, the Aaron Diamond AIDS Research Center in New York. This time, he said, the researchers agreed to study him. The result was dumbfounding. Try as they might, in laboratory tests, the center's scientists could not get the AIDS virus to enter Mr. Fuchs's cells.

After months of fevered research, the scientists at Aaron Diamond discovered why Mr. Fuchs and another man with a similar experience were immune. The men had inherited a gene that results in a blocked porthole into white blood cells, preventing the virus from slipping in. The investigators went on to isolate the gene, discover how it worked and learn how many other people have it.

On May 2, the research center was awarded a patent for a test to identify people who have the H.I.V.-resistance gene, allowing it to share in any profits from the test.
 

But what about Mr. Fuchs and the other man, Steve Crohn? They say they approached Aaron Diamond scientists and suggested that they be studied. They offered their blood, they participated in the research project, they helped the research center garner publicity for its discovery.

"I just wanted to do something good," Mr. Fuchs said. "But once money came into the picture, why not have it be shared with me?"

These days more and more patients are asking the same question. Laboratories offer tests for more than 700 human genes, with more being discovered almost daily. And, for almost every gene, some medical institution or some company owns a patent on its use.

"The value of patients' tissues has potentially gone up enormously," said Dr. Barry Eisenstein, the vice president for science and technology at the Beth Israel Deaconess Medical Center in Boston. But, Dr. Eisenstein said, patients whose cells provided the genes that have been patented are almost never compensated.

Whether any money has been made from tests based on their genes -- and in the case of the AIDS-resistance gene, none yet has -- some patients have become wary about providing their tissue for genetic research. A few have demanded money up front before providing tissue. Others are writing contracts spelling out what they are entitled to if they help scientists find genes.

Some experts on patent law say that it would be unfortunate if patients start demanding financial rewards for participating in research.

"I hate to create incentives that would lead people to get greedy," said Rebecca Eisenberg, a patent law expert at the University of Michigan. "I am worried that there are just too many mouths at the feeding troughs of pharmaceutical products."

Other experts say the current system of awarding gene patents seems unjust.

Dr. Robert Cook-Deegan, an investigator at the Kennedy Institute of Ethics at Georgetown University, said: "We have a system where the research participants are treated as pure altruists, but everyone else is treated as a pure capitalist. I don't think that's quite fair."

The problem, said Hank Greely, a law professor at Stanford University, is that the rules of the game seem to have changed.

"It used to be that when you were a research subject, you were doing it for free and you assumed that the people on the other side were doing it for free -- at least for academic research," Professor Greely said. "These days, there is very little academic research that doesn't have some commercial interest, and almost always now the researcher has a potential commercial interest. Someone might say, 'Look, I'm willing to do this for the good of humanity if everyone else is, too. But if someone on the other side is going to make billions of dollars, I want some, too.' "

The Families I
Searching for Good From Sorrow

Daniel M. Greenberg, a real estate lawyer in Homewood, Ill., never thought about potential profit when he helped get a gene search going. All he wanted was to help other families avoid what had happened to him and his wife.

The Greenbergs' first child, Jonathan, was born on June 12, 1981, a perfect present for their fourth anniversary. But they soon began to worry. Jonathan did not roll over when he was supposed to. He never sat up. Finally, when Jonathan was a year old, a neurologist discovered that he had Canavan disease, a rare genetic disorder that is invariably fatal and almost exclusively strikes Ashkenazi Jews, those who trace their origins to Eastern and Central Europe. The Greenbergs were told that Jonathan's condition would only get worse and that he would die before he was a teenager.

(He died when he was 11 years old.)

"Obviously, our lives were shattered," Mr. Greenberg said. "It was a tough haul trying to think of your child as a dying child and never being able to do the things that other children can do."

Then the Greenbergs' second child, Amy, turned out to have the disease, too. Desolate, Mr. Greenberg eventually decided that maybe something good could come out of his tragedy if he could help scientists find the gene that, when mutated, leads to Canavan disease.

In 1987, he found a researcher who was eager to do the work, Dr. Reuben Matalon at the University of Illinois Hospital in Chicago. Mr. Greenberg said he organized tens of thousands of dollars in donations and grants for the project, including several thousand dollars of his own money, and helped Dr. Matalon obtain needed blood, urine and skin biopsy samples from children with Canavan disease and their parents.

Dr. Matalon began making progress. Then he was recruited by Miami Children's Hospital, which wanted him to establish a center for research on genetic diseases, with a multimillion-dollar annual budget. At the University of Illinois Hospital, Dr. Matalon said, his research budget, excluding donations, had been no more than $10,000 a year.

It was in Miami, with substantial financing from Children's Hospital, that Dr. Matalon, in 1993, finally isolated the Canavan disease gene.
 

"My contract said every invention I make would be theirs, and that's it," Dr. Matalon said. "I am not in the inventing business. I am a research person. If they make money on me, I don't care."

The patent for the gene was issued to the Miami Children's Hospital Research Institute on Oct. 21, 1997.

In the meantime, Dr. Matalon had moved on to the University of Texas Medical Branch at Galveston. The Miami Children's Hospital Research Institute, an affiliate of the hospital, retains control of the commercial uses of the Canavan disease gene.

Marc Golden of Golden Group Intellectual Capital was brought in to help the hospital decide how best to use the patent. At first, he said, the hospital considered donating the gene patent to the public and forgoing royalties on any test. It eventually chose not to, he said, because it feared that there were so few people who needed the test that laboratories would not bother to publicize it.
 

After months of deliberations and negotiations with academic and commercial laboratories, Mr. Golden said, the hospital decided to charge a royalty fee of $12.50 per test. The money, he said, would partly offset the hospital's costs in paying for Dr. Matalon's research, and the amount would not be overly burdensome to people paying for the test. The hospital hopes to use some of the royalty money to publicize the test, he added.

But the families who got the research going are not assuaged. They want the gene test in the public domain, available to laboratories free of charge and free of the encumbrance of licensing agreements.

"We gave our samples to be used for the public good," said Judith Tsipis, a parent of a boy with Canavan disease and the director of the genetic counseling program at Brandeis University. "They were not given to Miami Children's. Had they told us they wanted to patent it, we probably would have found another researcher who had the same goals as we did. Finding the gene is not an impossible task."

Mr. Greenberg shares her sentiments. "I am disappointed and disheartened and disgusted," he said.
 
 

The Families II
Aiding Research, With a Wider View

Like Daniel Greenberg, Sharon Terry of Sharon, Mass., found herself with two children with a rare genetic disease that she had never known existed. And like Mr. Greenberg, Ms. Terry realized that the only way anyone would look for the gene that made her two children ill would be if she provided money, body tissue and medical histories from families whose members harbored the gene.

But Ms. Terry did one thing that had never occurred to Mr. Greenberg. She and her husband, Patrick, made researchers sign a contract giving the families rights to share in the profits from any gene patent that might arise.

Ms. Terry's son and daughter have pseudoxanthoma elasticum, which causes mineralization of elastic tissue.

The most serious consequence is blindness, which occurs when the membrane behind the retina calcifies and develops cracks. Blood vessels leak through the cracks, destroying vision.

"There were people dabbling in the disease, but their major frustration was that they had just four or five families," Ms. Terry said. She saw an opportunity. Establishing a foundation, PX International, Ms. Terry and her husband, a manager of a construction company, found 2,000 people with the disease, set up a repository to store tissue samples, and began raising money for research. It took them just four years.

"We said, 'We can get you as many sibling pairs and as many patients as you want,' " Ms. Terry said she told researchers. The group had no trouble finding scientists who were eager to work with them.

"They are so delighted that we will do all the grunt work," she said.

The researchers happily signed her group's agreement, Ms. Terry said. They readily agreed to its clause saying that the foundation had to be named in any patent applications arising from the work, that any profits or revenue from the discoveries be shared with the foundation and that any genetic test must be made readily available to the foundation, she said.

Now, Ms. Terry said, the gene has been found.

She worked closely with the Genetic Alliance, an advocacy group in Washington for people with genetic diseases, in formulating the contract.

"More and more of our organizations are interested in this, and they become savvy very fast," said Mary Davidson, the alliance's executive director. The groups are familiar with the Canavan disease story and they have taken careful note, Ms. Davidson said.

But there can be a danger in demanding too much too soon. "People may find that if they overreach in these contracts, the thing that they felt so valuable is something no one is interested in pursuing," said Robert P. Merges, a law professor specializing in patent law at the University of California at Berkeley.

That happened to a Boston family whose members had long life spans, which made them of great interest to Dr. Thomas Perls, a gerontologist at the Beth Israel Deaconess Medical Center in Boston. The family told Dr. Perls that he could use their tissue to search for a longevity gene, but only if the medical center paid a huge sum of money.

Dr. Perls refused.

Dr. Eisenstein, of Beth Israel Deaconess, said the medical center was uncomfortable with paying one family when others were donating their tissue. But, he said, there are no rules in this new arena, and the hospital might well have reached a different decision if a group of long-lived families had formed an organization like PX International.

"The bottom line is that none of us are smart enough to know where to begin," Dr. Eisenstein said. "There is no easy answer. We're in the midst of a national debate."
 
 

The Future
Searching for Fair Treatment of All

Mr. Crohn and Mr. Fuchs, the men who are resistant to the AIDS virus, would like to press their claims. "Somebody, somewhere, has to decide who owns our genetic material," Mr. Crohn said.

But, the men said, it is beyond their means to take on this legal battle.

They take comfort in the fact that two of the scientists they dealt with at Aaron Diamond, both of whom have since moved to other institutions, said they personally would be pleased if the two men could receive some compensation, assuming the patent ever makes money.

But David Jackson, a lawyer in Hackensack, N.J., whose firm filed for the patent on behalf of the Aaron Diamond AIDS Research Center, said the question of whether to compensate Mr. Crohn and Mr. Fuchs never came up as part of the process of obtaining the patent.

And experts in patent law say that in the few cases like this that have gone to court, the outcomes favored the patent holders and not the individuals who asked for a share of patents.

The most famous legal case over ownership of tissue involved John Moore, a man with a rare form of leukemia who argued that researchers in California took his cells, realized the cells made a valuable biological substance and patented cell cultures derived from his body. Mr. Moore sued, asserting that the cells were his property and demanding their return. But in 1990 the California Supreme Court ruled that he and other patients did not have property rights over their tissue.

Then there was the case of Marlo Brown of Petaluma, Calif.

In the early 1980's, Ms. Brown noticed that several cats in an animal shelter that she ran were ill with a disease that looked to her like AIDS. She took the cats and detailed notes to an animal virologist at the University of California at Davis and suggested that they had a feline version of AIDS and that he use their tissue to find the virus.

He did, and ended up discovering not only a feline AIDS virus but also a test for it and a vaccine to protect cats. The University of California obtained patents on the test and the vaccine. But Ms. Brown asked what about her? Was she not an inventor too? A Federal District Court said in the mid-1990's that she was not, ruling that her contribution did not entitle her to share in the patent.

Professor Eisenberg, the patent expert from the University of Michigan, said the courts say that patents for molecules like genes should go to the person who envisions what they look like and identifies a practical use for them. "You can't envision a molecule by saying, 'Here's a disease, here's some tissue, go for it,' " she said.

"The fact is that we rely on the private sector to develop diagnostic and therapeutic products, and the private sector is profit driven," Professor Eisenberg said.

"People may contribute their tissue in the expectation that nobody is going to make a profit on it, but that's a little naïve. There's no free lunch here."

The reason for patents is to provide incentives for inventors, Professor Eisenberg said.

"When people see these innovations creating millionaires and billionaires overnight," she said, "they may think, 'Why not me?' "

But, she said, the truth is somewhat different. "Most patents have no value," Professor Eisenberg said. Developing gene products, she said, "is a very risky invention -- you have an occasional big winner that justifies all the dry holes."

But, said Professor Merges, the patent expert at the University of California at Berkeley, scientists should not be surprised when patients feel cheated.

"It would be hypocritical for a researcher to say, 'I'm outraged that patients are interested in the commercialization of their tissue' while at the same time the researcher has his name on 15 patents," Professor Merges said. "There's a sort of mercantilization going on in medicine."

The risk, said Professor Greely of Stanford, is that patients will refuse to participate in genetic research, fearing that they will be exploited.

"You don't want research subjects to feel cheated and embittered and betrayed," he said. "In the long run, for research with human subjects to survive, those human subjects have to feel that they've been treated fairly."