Truly preventive medicine

Although pre-implantation genetic diagnosis added to health basket , most couples with genetic defects still have to gamble on passing them on.

3r (photo credit: Courtesy)
(photo credit: Courtesy)
You probably know about IVF, but have you heard of PGD? If the abbreviation is unfamiliar, you're not alone, as even many physicians have not heard of it. Yet pre-implantation genetic diagnosis, used in conjunction with in-vitro fertilization, is making it possible for couples who carry or even suffer from serious genetic defects to have completely normal, non-carrier babies. Some Jewish "traditions" you wouldn't want to pass on: One in five Ashkenazi Jews is a carrier of a genetic condition. PGD, developed in stages in various parts of the world, is now offered at Tel Aviv Sourasky Medical Center, Jerusalem's Shaare Zedek Medical Center, Sheba at Tel Hashomer, Rambam Medical Center in Haifa, Hadassah University Medical Center in Jerusalem's Ein Kerem and Kaplan Medical Center in Rehovot. The very expensive double procedure has been subsidized for health fund members with supplementary insurance, and is performed for a high fee in most of these Israeli hospitals. But only at Shaare Zedek has it been offered for free from the beginning, in March 2004. Now the government has added PGD to the basket of health services paid for by the members' health funds and subsidized by the Treasury. But this coverage is limited; it gives each couple a maximum of two healthy children David Fuld, a non-practicing Orthodox rabbi, a mohel and a New York real estate mogul who with his wife Anita established and funded Shaare Zedek's PGD unit, will continue to offer unlimited PGDs for qualified Israeli couples. The 62-year-old Fuld, who has performed about 13,000 circumcisions as a mitzva, first became interested in the subject as a result of being an unpaid circumcisor. He has even circumcised many of the babies born healthy thanks to the unit. As a successful businessman, he says he "wanted to open this PGD lab to give back some of what I have received." The beauty of PGD is that it does not involve abortion, says Fuld in a recent interview with The Jerusalem Post, but merely the selection of healthy eggs for fertilization or of healthy, non-carrier embryos for implantation. As Shaare Zedek is a Jewishly observant hospital, the avoidance of abortion is a real plus. It is used even to identify embryos with genetic deafness or with neurofibromatosis, which can result in minor cosmetic symptoms or very serious ones. Among the 45 genetic disorders for which the PGD lab has tested embryos (or polar bodies attached to newly removed or fertilized eggs) - are fragile X, monotonic dystrophy, cystic fibrosis, Tay Sachs, Bloom, Gaucher, thalassemia, Duchenne muscular dystrophy, familial dysautonomia, Niemann-Pick disease (type A), Fanconi, Canavan, retinoblastoma, Marfan, CIPA and other syndromes. THE SHAARE ZEDEK lab, one of the few in the world willing to work on any disease, was also a pioneer in testing for genetic markers and not only mutations. The lab has also done sex selection of embryos for a couple who received approval from the Health Ministry committee that discusses such applications; this particular couple also needed PGD for preventing the implantation of an embryo with a disease. The waiting time for PGD for a previously tested disease treatment is about a month, the time it takes a woman to start a new cycle for IVF. If the disease is one the lab has never done before, treatment can take three months, because an entirely new system has to be set up. The benefactor has visited the top genetics departments in the world, including those at Harvard and Baylor, and says Shaare Zedek's "is second to none. The staff are especially skilled, devoted and caring. Shaare Zedek was the only place with a high level of genetics, medicine, fertility, ethics and halacha. There is no combination like this in the US," Fuld says enthusiastically: "This just the beginning. Our goal is to create a genetic center for world Jewry; we want to do anything we can to reduce the suffering of the Jewish People." The lab could easily attract medical tourists, as PGD+IVF abroad costs up to three times the fees charged foreigners coming to Shaare Zedek. Having invested $2 million in the hospital's PGD unit so far and coming to Jerusalem monthly, Fuld says "it is the most successful thing I have done in my life." The result of his initiative are 62 healthy children so far - including a set of triplets and 10 sets of twins - born at Shaare Zedek, along with 20 women pregnant with 27 fetuses. The oldest child, born to a woman with myotonic dystrophy (which entails muscular degeneration, cardiac defects and impaired vision) whose risk of having a baby with the disease was one in two for each pregnancy, is four years old. Shaare Zedek director-general Prof. Jonathan Halevy and medical genetics unit head Prof. Ephrat Levy-Lahad were rather doubtful when Fuld, who had been donating to the hospital since the 1960s, offered to sponsor the PGD center. They were not certain it would be in high demand, and knew it would require a major long-time commitment. Fuld consulted with some of Israel's leading rabbinical arbiters and was given endorsements on condition that PGD would not be used for "trivial reasons." For example, the Shaare Zedek lab is careful to avoid eugenics: Staffers do return embryos that are disease carriers to the womb, so PGD will not artificially eliminate disease for future generations. If the family have a recessive disease and the lab does a polar body biopsy, they select for normal eggs, but the sperm could be carrying a mutation, thus making the embryo a carrier. THE WELL-CONNECTED and persuasive businessman, who has become a self-taught expert in the field, convinced the hospital to set up the special lab and enlist qualified personnel. A handful of Shaare Zedek personnel went to Dr. Yuri Verlinsky's Reproductive Genetics Institute (RGI) lab in Cyprus to become convinced they could set up a PGD lab at Shaare Zedek, and Altarescu and a number of embyologists received advanced trained at the RGI lab in Chicago. A few weeks ago, when Shaare Zedek's administration decided to name its PGD unit for the Fuld family, the real estate magnate and his wife brought more than 34 relatives, including most of their six adult children and 24 grandchildren, to Israel for a festive luncheon at the hospital. As a gift, the Fulds received a photo album of all the healthy babies - without their names to preserve privacy - whose birth had been made possible by the project. The medical professionals who have produced the babies - including PGD lab head Dr. Gheona Altarescu, IVF unit director Prof. Ehud Margalioth, IVF specialist Dr. Talia Eldar-Geva, medical genetics lab director Dr. Pinchas Renbaum and embryologist Dr. Baruch Brooks - along with Halevy and Levy-Lahad were also there to celebrate. Although the error rate in PGD labs around the world has reached as high as 9% and averages around 3%, Shaare Zedek's has fortunately had none, and its pregnancy rate is as high as in the best labs. Instead of using a laser to perform the biopsy, Shaare Zedek utilizes a mechanical method that, Levy-Lahad says, can significantly boost the implantation of healthy embryo in the womb. A special internal committee that includes ethicists meets to discuss each application. Levy-Lahad says she is pleased that PGD has been added to the basket of health services, even though there is a limit of two children. "It is clear why the government put PGD in the basket, as it makes economic sense. Treating a single child with cystic fibrosis is very expensive. PGD is now recognized as an accepted medical procedure. Being subsidized by the state creates a level playing field." Fuld encourages all couples, whether having children or grandchildren, to go for pre- or post-marital screening. "Now they do not have to suffer the tragedy of losing a child, or raising multiply-disabled children," he says. "Now everybody's going to try to do PGD. I don't know if there are enough experts in the field to go around," stresses Fuld. "Adding it to the basket will highlight the superiority of Shaare Zedek, and will make it possible for couples who are carriers or have genetic disorders to produce as many healthy babies as they want rather than gamble with having a sick child or a carrier." Some couples already have one or more genetically diseased or carrier children before they attempt PGD. In about a third of the cases, the polar body attached to the egg is biopsied, says Levy-Lahad. In the remainder, one cell is taken from a few-days-old embryo of fewer than a dozen cells. "We try to biopsy eggs when the disease is not only in the father or carried by him; if it is only in the father, there is no use starting at the egg stage, but this takes twice as much time as taking a cell from an embryo. "What ultimately happens depends on how many eggs there are. If you biopsy only the egg, you don't know for sure if it will develop into an embryo." PGD will not remain static. "A few years from now, she predicted, "there will be a new technique, or PGD will be different and improved. We are already working on DNA chips as a template so we will not have to deal with every case separately. There will be chips with everything on it. The price will go down. This technology will change the landscape. "The innovative technologies and genetic knowledge might enable wider disease screening, and this will bring on new ethical challenges," Levy-Lahad concludes.