[Pharm-policy] Peter Gorner's Canavan gene patent story

[James Love]

Thanks to Professor Jon Merz for providing this pointer to the original
Chicago Tribune article on the Canavan gene patent lawsuit.
Jamie

http://chicagotribune.com/news/metro/chicago/article/0,2669,ART-48233,FF.html


Parents suing over patenting of genetic test

By Peter Gorner
Tribune Staff Writer
November 19, 2000

In the first case of its kind, the families of dead and dying children
cursed by a genetic brain disease are suing the researchers they once
trusted but whom they now view as trying to profit from their children's
illness.

Using blood and tissue from two Chicago-area children and others who
died of Canavan disease—a rare neurological disorder also known as
spongy degeneration of the brain—researchers found the gene responsible
for the illness and in 1997 received a patent on it.

Chicago-area parents Daniel and Debbie Greenberg, and other parents
involved in the research, say the patent and a commercial test with
strictly enforced licensing has impeded further study into the disease.
The tests, given to people thinking about having children but fearful of
passing on the disease, are restricted in a number of ways by the patent
holders, ensuring that more children will be born into a life of pain
and hopelessness, the families contend.

The lawsuit, filed pro-bono by the Chicago-Kent College of Law, marks
the first time tissue donors have taken researchers to court for the
control of a gene. The suit does not directly challenge the patent, but
instead alleges that the researchers secretly obtained it using the
genetic information and financial resources that had been donated for
the public good and began charging royalties and limiting the
availability of testing.

Defendants include the Miami Children's Hospital, where the gene was
discovered and the test developed, and Dr. Reuben Matalon, the lead
researcher.

The lawsuit has attracted little attention thus far, but could help
establish rules of ownership of human genes at what many believe is the
dawn of a biotech revolution.

"It's a unique case," said Laurie Rosenow, an attorney with Chicago-Kent
who helped prepare the complaint filed Oct. 30 in U.S. District Court in
Chicago. "Research participants have charged their rights were violated
because they were misused by researchers for financial gain. It could
shape future genetic collaborations."

The families, along with the New York-based Canavan Foundation and other
plaintiffs, seek to block Miami Children's Hospital's commercial use of
the Canavan gene and recover damages of more than $75,000 derived from
royalties collected for the gene test.

The Canavan Foundation was forced to stop offering free genetic
screening, according to the complaint, after being advised that it would
have to pay royalties and comply with other licensing terms.

But the Canavan case goes beyond the disease. The bigger issue is how
much the public has to say about the profits and other fruits of genetic
research, especially when one considers that hundreds of similar tests
are expected to be the initial payoffs from the $3-billion
taxpayer-funded Human Genome Project. No gene test can be developed
without the help of families battling the disease.

"This case is the ultimate nightmare of how a gene patent can be used
against the very families who made possible the discovery of the gene,"
said Judith Tsipis, a professor of biology at Brandeis University and
vice president with the National Tay-Sachs and Allied Diseases
Association Inc., another of the plaintiffs.

Miami Children's Hospital has declined to discuss the case, citing the
litigation. Matalon—who worked closely with the plaintiffs for years,
found the gene and developed a carrier test—did not reply to requests
for an interview. In past interviews, he has insisted he has no stake in
the outcome of the lawsuit and gets no royalties from the patent.

One of more than 4,000 inborn errors of metabolism, Canavan disease is
very rare, even in the population it most affects. It strikes 1 in 6,400
children born of Jews whose roots lie in Central and Eastern Europe.

There only are about 200 children in the U.S. with the disease. But once
a child inherits two copies of the Canavan gene, all medicine can do is
stand by helplessly as the child's brain slowly and inexorably
deteriorates.

The body cannot produce a housecleaning enzyme called aspartoacylase,
the deficiency of which leads to a buildup of another enzyme that
destroys the brain's white matter, the myelin sheath that protects brain
cells.

Symptoms usually appear between 3 and 6 months of age and the child will
never be able to walk, talk, or eat independently. Canavan wipes out
thinking, feeling, emotions, vision and muscles. As the disease
progresses, it causes seizures, severe feeding problems, retardation and
blindness. Most youngsters die between ages 10 and 15.

Similar to Tay-Sachs disease, the fight against Canavan has been waged
by people of Ashkenazi Jewish descent, a group that includes 90 percent
of the 6 million Jews in the United States.

In this group, about one person in every 40 is a silent carrier of the
disease-causing gene. When two carriers have children, each baby stands
a 25 percent chance of being born with the disorder.

In the fall of 1998, the American College of Obstetricians and
Gynecologists recommended that all Ashkenazi Jewish women undergo DNA
testing for Canavan carrier status, which essentially means doctors who
do not test could be sued for negligence if such a patient has a baby
with the disease.

Within weeks, Miami Children's Hospital launched a campaign to enforce
its patent, at first demanding a $25 fee for every test any lab
performed but later dropping it to $12.50.

The danger to the public of fixed licensing, according to experts, is in
the stacking of royalties charged by all the patent holders of all the
mutations identified in deleterious genes. Individually, they aren't
much; but collectively, they can be onerous.

In addition to the fixed royalty expense, Miami Children's Hospital
restricted the number of laboratories that could do the test and the
number of tests that could be performed each year.

This was done, hospital officials said at the time, because they hoped
to attract one large company to do all the testing because it had an
exclusive license. That way, testing could be widespread as word got
around and the hospital could recoup the millions it spent to discover
the gene.

The move proved to be controversial. The University of Pennsylvania, for
one, called the contract "wretched" and stopped offering the test.
Penn's attitude was not unique: Over the past year, surveys indicate,
one in four laboratories has stopped performing certain genetic tests
because of patent restrictions or excessive costs.

The Canavan gene hunt began in 1981 when Jonathan, the 9-month-old son
of Homewood attorney Daniel Greenberg and his wife, Debbie, was
diagnosed with the disease. At the time, there was no prenatal test for
Canavan and when the couple conceived again, their second child, Amy,
was also afflicted. The Greenbergs have three other children, two of
whom were adopted, and one who was born healthy.

In 1987, the Greenbergs persuaded geneticist Matalon, then working at
the University of Illinois at Chicago, to develop a prenatal test. For
years, the Greenbergs provided Matalon with tissue samples. When
Jonathan and then Amy died, pieces of their brains were provided for
research.

"All the time, we viewed it as a partnership," Greenberg said. "Our
model was the testing program for Tay-Sachs disease. That's what we
hoped would happen again."

Since the 1970s, the test for Tay-Sachs has been widely available and
inexpensive and as a result the disease has largely disappeared from the
Jewish community.

The individual philosophy of researchers also is important in deciding
whether to profit from gene discoveries. When Francis Collins and a
colleague won the worldwide race to identify the gene for cystic
fibrosis and the University of Michigan was granted a patent, it was
decided to prohibit exclusive licensing agreements and charge only a
token $2 a test. Cystic fibrosis is the most common lethal genetic
disease afflicting Caucasians.

When he left Michigan to head the Human Genome Project, Collins clung to
his belief that humanity's genes belong to everybody and should not be
patented.

By comparison, Myriad Genetics and the University of Utah, holders of
the patents for the hereditary breast cancer genes BRCA-1 and BRCA-2,
charge $2,850 for the tests.

"There were basically three ingredients that went into the Canavan
research," said Jon Merz, a bioethicist from Penn who specializes in
legal policies and ethical problems of gene patenting.

"More than 160 families participated in giving DNA samples, urine and
blood samples that led to the discovery of the gene. So a key point was
the direct participation of people most directly influenced by the
disease.

"Another key point was the number of researchers who had the capability
to go ahead and do the research. The Matalon group had no special
skills. In fact, they had applied for funding from the National
Institutes of Health and they didn't get it because they had no track
record in gene research.

"The third ingredient was money. Miami Children's Hospital obviously
threw money at Matalon to do Canavan research. But that's not unique
either. A lot of people will fund research.

"So it turns out the money and research skills were totally replaceable.
The only thing that was absolutely required in order to make the
discovery was the participation of these families."

Moreover, the hospital and Matalon did not get any informed consent from
the families. "They were research subjects," Merz said. "They had a
right to know their rights."

To Merz and other experts, the only comparable case is that of John
Moore, a patient at UCLA whose blood was shown to contain unusual and
valuable viral antibodies. Without Moore knowing, a physician created a
special cell line from Moore's blood, patented it and sold the rights to
a biotech firm.

Moore sued, claiming his tissue was his property, but several courts
rejected his claim because they did not want to slow down the progress
of biotechnology. Giving Moore a property right to his tissue would
"destroy the economic incentive to conduct important medical research,"
they ruled.

"But in this case, the value isn't in the blood itself, but in the
information carried in the blood," Merz said. "These plaintiffs are
saying somebody extracted that value and didn't have their permission to
do it." And even the Moore case recognized that patients must be
informed if the researcher plans to commercialize their tissue.

As Dan Greenberg sees it: "What the hospital has done is a desecration
of the good that has come from our children's short lives. I can't look
at it any other way."