A case of almost eugenics
Since marrying, the S's have been trying to bring children into the world, but their desire has been overshadowed by the knowledge that their future offspring may suffer from a congenital syndrome characterized by severe degeneration of the muscles, impaired vision and limited cardiac function.
The 34-year-old wife is well aware of the perils of myotonic dystrophy: She and three of her siblings were born with the disease. One died at an early age. She also knows that every pregnancy poses a 50 percent risk that the genetic defect will be passed on to her offspring.
"The severity of this disease differs," explains Professor Ehud Margaliot, director of the In Vitro Fertility (IVF) department at Shaare Zedek Medical Center in Jerusalem. "Sometimes, the children are very ill and sometimes the symptoms appear only in adulthood. But there is no way to predict this at the outset."
The S's refused to undergo genetic testing during their first pregnancy, and Mrs. S gave birth to a healthy child. But deciding "not to gamble" with their second pregnancy, they chose a form of genetic testing new to Israel and performed at Shaare Zedek during the previous year. The technique is a unique version of pre-implantation genetic diagnosis (PGD) that has been used around the world for more than decade.
The method of genetic screening of ova at Shaare Zedek makes it possible to prevent the formation of fetuses stricken with genetic disease. The method requires the use of IVF in couples who do not necessarily have fertility problems. The technique examines the genetic structure of the fertilized ovum before it is implanted in the womb. If evidence of congenital disease is identified in the genetic material of the ovum, the ovum is not implanted to produce a pregnancy. Thus, seven months ago, Mrs. S gave birth to a son who is not afflicted with myotonic dystrophy.
Implementation of this type of PGD at Shaare Zedek was made possible by a donation by American millionaire Rabbi David Fuld, who wished to prevent the birth of children with congenital defects in Jewish families.
Fuld has donated about $700,000 to the project, one of the largest single donations to the field of genetic medicine in the local health care system. The donation was earmarked for the purchase of equipment and the training of medical staff in the implementation of this method in Cyprus.
The system of genetic testing at Shaare Zedek is conducted in collaboration with the Genetic Medicine Unit and the IVF Unit in the hospital. According to Professor Efrat Levi-Lahad, head of the Genetic Medicine Unit and one of Israel's leading medical geneticists, 24 couples have been treated in the project to date. A total of 37 IVF treatment cycles have been conducted in conjunction with the project. The only infant born in the context of this project is the son of the couple who feared myotonic dystrophy.
According to project leader Dr. Gheona Altarescu, of the Genetic Medicine Unit, six additional women are in advanced stages of pregnancy following genetic testing of this type. The success rate of achieved pregnancies at Shaare Zedek is similar to that of similar projects in Europe - about 19 percent.
The genetic testing method at Shaare Zedek is a unique form of PGD that has been used to screen unfertilized and fertilized ova in the world for more than a decade, and in genetic institutions in six public medical centers in Israel in recent years - Ichilov in Tel Aviv, Sheba at Tel Hashomer, Haddasah Ein Kerem in Jerusalem, Kaplan in Rehovot, and Rambam in Haifa. According to Levi-Lahad, the method implemented at Shaare Zedek, "decreases the rate of false diagnoses," in comparison with more conventional methods. But opinions in the medical community differ regarding the efficacy of this method.
According to Levi-Lahad, statistics provided by the developer of this method reveal that the range of errors in diagnosis using this system is minimal - less than 1 percent. On the other hand, statistics provided by medical centers in Europe suggest that conventional PGD methods in Israel have a rate of diagnostic error as high as 9 percent. "I don't believe that there is such a thing as zero errors," says Levi-Lahad. "We tell parents that the chance of an error is about 3 percent."
The problematic nature of informing parents of the level of accuracy in genetic testing is apparent in statements made to Haaretz by a senior member of the Genetic Institute at Ichilov Hospital. According to him, before performing genetic testing, the staff tends to tell parents that the diagnostic accuracy is "close to 100 percent."
As to the donation by Rabbi Fuld, Professor Margaliot says, "He donated the money so that people would not terminate pregnancies. He is a rabbi and a mohel, and, in his opinion, termination of pregnancy is a terrible thing from a religious point of view."
Levi-Lahad and Margaliot add that Rabbi Fuld first requested that the project be earmarked only for Jews, but that they refused. "We explained to him that such a thing was not possible - that this is not the way things work in the hospital," they said. In practice, all the couples treated so far with this method have been Jewish. Three Arab couples received initial genetic counseling, but the genetic defect that produced disease in the case of one couple was not identified and the remaining two couples decided not to employ the method.
In conventional PGD, the ovum is fertilized by sperm and after the embryo has divided into 8-10 cells, a few days later, one of the cells is removed and its genetic material is examined. Embryos that do not carry the genetic defect are subsequently implanted into the uterus.
In the method performed at Shaare Zedek, material in the unfertilized ova is examined instead of a cell from a fertilized ovum. In addition, the testing process is more rigorous. After the ovum is fertilized by the husband's sperm, the genetic material is re-examined, at the stage employed in more conventional screening methods; but according to Levi-Lahad, Shaare Zedek also employs a different method at this stage of embryonic development. While conventional screening methods remove a cell from the embryo by means of a laser, Shaare Zedek uses mechanical methods to remove the cell. According to her, this technique may significantly increase the successful implantation of the embryo in the uterus.
According to Levi-Lahad and Margaliot, the entire process, and particularly the rigorous testing of genetic material, reduces diagnostic error.
Couples who wish to make use of this method of genetic testing must undergo IVF, thereby increasing the suffering of the women and reducing their chance of becoming pregnant - the chance of achieving a pregnancy in IVF is no more than 25 percent. According to Margaliot, the removal of any embryonic cell for the purpose of genetic testing decreases the chance of implantation of the embryo in the uterus by 10 percent.
Another inherent problem in this technology is the cost. The cost of genetic testing of ova at Shaare Zedek is more than NIS 5,000 per treatment cycle and does not include the additional cost of IVF. Every treatment cycle, therefore, costs between NIS 10,000-30,000 in total, and the first treatment cycle is usually unsuccessful. Typically, a woman must undergo a few treatment cycles before pregnancy is achieved.
Health maintenance organizations (HMOs) in Israel did not cover the costs of this type of testing in the past, and the Maccabi HMO only recently decided to partially cover the cost for clients who subscribe to their premium service package. Until now, Fuld's donation paid for the lion's share of the cost of examinations and treatments engendered by the project.
Fuld also contributes to the advancement of the Shaare Zedek project by maintaining relations with the method's developer, Dr. Yuri Verlinsky, an American physician who directs the Reproductive Genetics Institute, a private clinic in Chicago.
Verlinsky was the subject of controversy in the past. Many physicians viewed the advances that he made in the technology of fertility with suspicion, and publicity surrounding the purchase of ova by his clinic did little to enhance his reputation. However, he is now a sought-after lecturer at medical conferences and a very popular subject of interviews in the press. There is a branch of Verlinsky's clinic in Cyprus, where Shaare Zedek physicians trained in the new genetic testing method thanks to Fuld's intervention.
The implementation of the Shaare Zedek genetic testing method to identify genetic defects also permits the choice of the sex of implanted embryos. Gender is identified in the fertilized ovum, and implantation in the uterus of one sex or another may be requested by the couple. While the Health Ministry has published protocol pertaining to the choice of fetal sex and outlined instances in which this is permissible, the protocol does not include criteria pertaining to the choice of sex in the context of testing for disease.
In addition to questions pertaining to the extent of the benefit of this method for many couples, the performance and use of this form of genetic testing raises many ethical questions regarding its societal implications. In some European nations, like the United Kingdom, clear limits have been imposed on genetic testing of this sort. In other countries, like Germany, Austria, and Italy, the method is absolutely forbidden. According to some senior physicians, the use of the method in Israel is licentious and every doctor and hospital is free to act according to whim.
In addition, Israel lacks a definitive list of diseases and defects that justify the approval of termination of pregnancy by medical authorities. It is accepted practice here to approve the termination of a pregnancy in which a genetic defect or disease has been identified, while some countries in Europe forbid abortion in similar cases.
For two years, Shaare Zedek has been using the method of genetic testing of ova to prevent the birth of infants who suffer from more than 20 genetic defects. But are these defects sufficiently severe to justify the birth of children?
In some countries, these conditions are not considered sufficient reason to prevent birth, and some of these defects are not regarded as "diseases." Although PGD is used to prevent serious conditions such as Fragile X Syndrome, a genetic condition that results in mental impairment, and cystic fibrosis, a disease that may cause life-threatening lung infection in its most severe form, this genetic testing method is also used to prevent the birth of children who are deaf or hearing impaired, children with dwarfism, children with a disease that causes birthmarks and benign tumors of the skin and other parts of the body, and children who will be infertile in adulthood.
So who decides which genetic conditions justify the use of PGD and which do not?
At Shaare Zedek, this decision is made by an internal ethics committee. Members of the committee include Professor Avraham Steinberg, a pediatric neurologist and expert in medical ethics and Jewish law, hospital Rabbi Moshe Peleg, and Professors Levi-Lahad and Margaliot. In other hospitals that perform genetic testing, a permanent committee of this type does not even exist.
The Health Ministry now plans to make an effort to regulate this matter in joint meetings of its own Supreme Helsinki Committee on Genetic Research in Humans and the Ministry of Science appointed National Council of Bioethics. The committee is chaired by Professor Bolislav Goldman, a former senior official at Sheba Medical Center who, in addition to being the personal physician of Prime Minister Ariel Sharon, leads the ministry's Health Services Basket Committee, and Professor Michel Revel, of the Weizmann Institute, who heads the National Council of Bioethics, which includes many key players from various government bodies that examine bioethical issues in Israel.
The committee now meeting to discuss the regulation of PGD was also responsible for recommendations approved by the Health Ministry in May and pertaining to the choice of fetal sex. These limitations were published in a document distributed by the Health Ministry to all medical institutions in Israel that drew severe criticism of the ministry's conduct in the approval of the choice of fetal sex for personal and societal reasons. Retired judge Shlomo Shoham, Ombudsman for Future Generations in the Knesset, said that the Health Ministry should have promoted comprehensive public debate of the question before coming to a decision. Indeed, government health authorities in some Western European nations do not permit the choice of gender for non-medical reasons.
Critics of PGD claim that the technology grants physicians excessive moral and societal power to decide what is a "worthy life" and what is a "life that is so miserable that it justifies the prevention of its creation at the point of conception." For example, is it just to prevent the birth of deaf children by this method? Is it just to prevent the birth of children who are infertile? And is it just to prevent the birth of children whose congenital disease will appear only at an advanced age?
According to these critics, PGD could become a platform for an attempt to genetically improve the human race not only by preventing disease but by genetic manipulation to increase the prevalence of prefered genetic traits. In addition, they claim that interferring with the formation of life at such an early stage could have severe biological implications for the human race that are difficult to predict. The biological effects in children who were created from ova that were genetically tested may only be witnessed many years from now.