AT THE age of 4, Doreen Flynn’s first daughter, Jordan, was diagnosed with Fanconi anaemia, a rare genetic blood disorder that leaves people underweight and with a 700-fold greater chance of developing cancer. It is unlikely that Jordan will live past her early twenties.
Flynn and her husband wanted to have more children, partly because a bone-marrow transplant from a healthy sibling would be Jordan’s best shot at survival. They decided to undergo pre-implantation genetic diagnosis, an IVF technique designed to ensure only healthy embryos are implanted. A Detroit-based lab, Genesis Genetics Institute, isolated two apparently disease-free embryos that would be bone-marrow matches for Jordan and implanted them at a hospital in Atlanta in early 2003. Julia and Jorjia were born 34 weeks later. Both have Fanconi anaemia.
Fortunately, reports of such errors connected to clinical genetic testing are extremely rare. Mark Hughes, the founder and chief clinician at Genesis, says that since the earliest days of his company 17 years ago, there have been only nine such instances out of several thousand tests conducted. “There is going to be an error rate in any diagnostics, and it’s especially tricky in this instance,” he says, because genetic testing relies upon identifying a very short DNA sequence among the large volume of DNA that comprises the human genome.
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Human error may also play a part. In the Flynns’ case, a genetic test on Julia’s bone marrow suggests a match with one of the eggs diagnosed as diseased, which may have resulted from a simple mix-up of samples, although no firm conclusion has been reached. But no one can say which samples got mixed up and when and where the error could have occurred. Flynn did not follow up the implantation with the recommended amniocentesis that could have detected the disease before birth.
However, last week another case highlighted the potential costs of a lab or hospital getting a genetic test wrong. In what many are calling a “wrongful birth lawsuit”, the Ohio Supreme Court upheld the right of Helen and Richard Schirmer to sue their healthcare provider, the Children’s Hospital Medical Center in Cincinnati, for returning the wrong results of a fetal genetic test to diagnose trisomy 22, a genetic defect that causes severe mental and physical retardation. Their son, Matthew, was born with the condition in 1997.
Surprisingly, there is no American organisation that tracks errors of this kind. In fact, while lab workers must possess basic ualifications and follow standard laboratory procedures, the actual practice of genetic testing to diagnose disease is less regulated than most blood tests, for which laboratories must undergo regular proficiency testing to assess their accuracy.
The problem is not confined to the US. A 2003 study by the European Commission’s Joint Research Centre reports that more than half the genetics labs surveyed throughout Europe did not undergo any regular form of inspection.
Meanwhile, the diversity and popularity of genetic testing is skyrocketing. A recent survey by the OECD group of industrialised countries showed that the number of genetic tests carried out in these countries increased from 875,000 in 2000 to 1.4 million in 2002. There are now more than 900 distinct genetic tests in the US, compared with about 300 in 2002 – and that doesn’t include the burgeoning number of “non-medical” home-testing kits sold to families over the internet (see “Gender tests for sale on the web”).
“The number of genetic tests carried out in OECD countries increased from 875,000 to 1.4 million in just two years”
This expansion is being driven both by a rapid growth in the number of genes discovered and advances in the technologies available to detect them. Some genetic responsibility advocacy groups now wonder how widespread a tale like the Schirmers’ could become.
“We don’t have lists and lists of errors to point to right now,” says Gail Javitt, a policy analyst for the Genetics and Public Policy Center (GPPC) at Johns Hopkins University in Baltimore. “But if this type of testing continues to expand without proper safeguards, we’re going to experience more than just a minimal number of errors.” She thinks that while the majority of labs maintain high standards, any lack of regulation “creates an environment in which poor performers can continue in the marketplace and bad actors go undetected and uncensored”. Doctors and patients need a way of distinguishing between high and low quality laboratories, she says.
The largest area of growth is in “homebrew” tests for rare genetic diseases. These are tests developed by individual laboratories that are used by a relatively small number of people each year.
The procedure for each test can vary widely between labs. One problem regulators face is in establishing which parts of the process are common enough to be scrutinised. Organisations such as the GPPC are also calling for more training for doctors who interpret and act upon test results.
In 2000, the US Centers for Medicare and Medicaid Services launched a notice of intent to create rules ensuring the quality of genetic testing, but difficulties in regulating the system have led to long delays. The OECD is attempting to develop similar guidelines for its member countries, which include the US, UK and much of Europe.
“Doctors and their patients need a way of distinguishing between high and low quality laboratories”
In the meantime, Jordan Flynn is now 6 years old, and in the past few months her bone marrow has begun to deteriorate. “I make it through the day by not thinking about it,” says Doreen Flynn. “But we’re coming to the point when we’re going to have to explain things. We’ll have to tell her about her two sisters. I don’t even know where we’ll begin.”
Gender tests for sale on the web
With her husband stationed in Afghanistan, Erin Rivera of Tampa, Florida, thought it would be a nice surprise to send him the message that they were going to have a little boy.
Erin had bought the Baby Gender Mentor DNA test kit over the internet from Acu-Gen Biolab in Lowell, Massachussetts. It claims to be able to determine the sex of a child with 99.9 per cent accuracy 15 weeks before it can be determined via an ultrasound scan, using a simple blood sample collected by the mother.
One month after the test confirmed that Erin was pregnant with a boy, the head of the clinic, C.N. Wang, telephoned her to say that the test had also revealed that the child could be suffering from some form of trisomy, a genetic defect that causes problems with mental and physical development.
The test was wrong: last Thursday, Rivera gave birth to a healthy baby boy. “This ruined my pregnancy,” she says. “It put me through nine months of hell for nothing.”
She is joining a class action suit against Acu-Gen Biolab that was filed last month, along with as many as 90 other women. Most claim that the test got the sex of the baby wrong. Several others insist that Acu-Gen incorrectly informed them that their child had a genetic defect. Wang declined to comment when contacted by żěè¶ĚĘÓƵ.
There is no law regulating the hundreds of home genetic tests on the web, most of which come from the US. These range from paternity tests to suggested herbal remedies for different “DNA types”. “How would we regulate them? That’s a good question,” says Steve Gutman, director of in vitro diagnostics at the Food and Drug Administration.
