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The New York Times
August 29, 2006 Tuesday
HEADLINE: Saving Lives With Tailor-Made Medication
BYLINE: By CLAUDIA DREIFUS
DATELINE: MEMPHIS
BODY:
In Mary V. Relling's office in St. Jude Children's Research Hospital sits a
small ceramic statue of St. Jude Thaddeus, the patron saint of impossible
causes.
Dr. Relling, the head of the department of pharmaceutical sciences at St.
Jude, has a fondness for impossible causes.
Her own is pharmacogenetics, a clinical discipline in which doctors use
high-tech genetic testing to custom-make drugs to patients' individual needs.
Though pharmacogenetics is controversial and not yet widely done, Dr.
Relling, 46, travels the country advocating its use. At St. Jude, patients with
leukemia are now routinely given genetic tests to determine their individual
response to a medication. ''We've seen it save lives here,'' she said. ''That's
made me a believer.''
When hundreds of patients are given a drug, she continued, ''some will get
no benefit, others will have terrible side effects, and still others will get
benefits with tolerable side effects.''
Gene variants may be the cause.
Q. How is this tailoring of drugs different from the way they're currently
ordered?
A. Till now, there's been a one-size-fits-all approach. In most cases, an
average dose of a medication is ordered, and then, if the patient suffers side
effects, the dosage is adjusted. With gene testing, we can customize the
prescription.
Here at St. Jude, we've been gene-testing every child who comes to us with
leukemia. I study acute lymphoblastic leukemia -- A.L.L., the most common
childhood cancer. When a youngster comes in with A.L.L., we get a sample of
their DNA. We put it on a special computer chip that scans a half-million
different places on the genome. Mostly, we're looking for unusual variations of
the genes and misspellings of the genetic code.
We have a database from earlier patients that helps us predict a patient's
risk of relapse and which misspellings are likely to result in drug
sensitivities.
Q. Are there other diseases where the process might be useful?
A. The same medicine we use to treat leukemia is also prescribed for Crohn's
disease and ulcerative colitis. So that same genetic test could be employed to
reduce side effects with those conditions.
At the moment, there seems to be a lot of promise for pharmacogenetics in
the treatment of arthritis, heart disease, colon cancer and even psychiatric
diseases like depression and schizophrenia.
Q. One can almost hear economists everywhere groaning, ''Oh, no! Not another
test to add to health care costs!''
A. The basic research behind pharmacogenetics -- figuring out which genes are
important with the various drugs and diseases -- is costly. But on the clinical
level, you can save money. With leukemia, we've seen that testing costs are
minor compared to the savings gained by avoiding drug reactions, blood
transfusions and additional hospitalizations.
Q. How widespread is genetic testing for prescriptions?
A. It's very rarely used. Most probably, you can find it at some academic
centers in big cities. And, of course, for many medications, the research isn't
in yet about which genes are important and why. But even where tests have
been
approved, insurers don't cover all the costs, and that's hindered this from
growing.
Most prescribers don't understand genetics very well. The fruits of the
Human Genome Project have only been out for about five years, and a lot of
doctors and pharmacists did their training before that.
I've heard people say that medicine won't change until there are major
lawsuits against prescribers who fail to use tests to individualize therapy.
Q. How have the drug companies responded to the promise of
pharmacogenetics?
A. Unfortunately, they are not set up for it. The big pharmaceutical companies
have a different business model. They make their money from blockbuster drugs
that reach millions of people with standardized doses. They don't want their
markets to fragment, which is the obvious effect of pharmacogenetics.
Genomic testing is going to mean that we define smaller and smaller markets
for every drug. Instead of one medication for high blood pressure, a
manufacturer will have to produce dozens of variants and combinations.
It's already difficult to get drugs that benefit smaller numbers of
patients. ''Orphan'' drugs are often not manufactured because they help only a
small group.
In pediatric cancer, we see what happens to orphan drugs because children's
cancers are rare and, thus, orphan diseases. Of the nine drugs we regularly use
for leukemia, seven have been unavailable for varying periods of time during the
last decade.
Q. What can you do in that situation?
A. We're trying to start making it here at St. Jude. We're not a drug
manufacturer, and it isn't easy for us to do. We're also working with
pharmaceutical companies to see if we can't help them make it available. But we
can't depend on market forces for our supply.
We've seen that the pharmaceutical companies, if they are interested in
cancer drugs at all, are mostly concerned with adult cancers -- the larger
market.
Q. How did you become a pharmacist?
A. I attended the University of Arizona in the late 1970's, as a French major.
In my freshman year, I took the required chemistry course with a brilliant
teacher, William Lippincott. He made chemistry come alive. Becoming a
pharmacist
seemed like a practical route to a chemistry career, with good job possibilities
after graduation.
Even today, it's a great profession for a young person to consider. There
is a tremendous demand.