The Ethics of Genetic Screening
A Jewish perspective on issues related to screening for Tay-Sachs disease.
Tay-Sachs disease is a particularly tragic, inherited illness. A baby is born healthy, with no indications of an abnormality. Sadly, at approximately six months of age, the formerly cheerful baby gradually loses its previously gained milestones and undergoes physical and mental deterioration. The baby loses muscle tone and stops smiling, crawling, and turning over, losing its ability to grasp or reach out. Eventually, the child becomes blind, paralyzed, and unaware of the surrounding world. Death almost always occurs by age five.
The underlying defect in Tay-Sachs disease is a lack of an enzyme called hexosaminidase A, an enzyme that is necessary for breaking down specific fatty substances (ganglioside GM2) in brain and nerve cells. These fatty substances build up and gradually destroy brain and nerve cells, until the entire central nervous system stops working. While there are rare cases of later onset Tay-Sachs disease1 (which may be less severe), the infantile type of Tay-Sachs is by far the most common.
Is there a Torah obligation to seek genetic screening for Tay-Sachs? If genetic screening is permitted or required, when should people be tested? To whom shall we reveal the results? Should we inform employers, insurers, and relatives? What are the ramifications of testing positive for an abnormal gene? Are there different ramifications of testing positive before versus after marriage?
In this article, we will use the gene for Tay-Sachs, found in high prevalence in the Ashkenazi Jewish population, as a representative example of the issues arising when testing for a recessively inherited disease.
A LESSON IN GENETICS
A gene vs. a disease
In order to understand the Jewish approach to genetic screening, background information is required. We must first make a clear distinction between a gene and a disease. One may carry a gene for a disease without manifesting any ill effects. One's genotype, or genetic makeup, is merely a description of a person's genes. If one expresses the trait coded for by the lethal gene, we say that his phenotype, or physical nature, is positive for the disease.
Modes of inheritance
Diseases may be inherited in several ways, the two simplest mechanisms being autosomal recessive and autosomal dominant. The cells of human beings carry two copies of the gene for each trait, however the copies may not be identical. One requires two genes for a recessive trait to be manifested, while one requires only one gene for a dominant trait to be manifested. For instance, one may carry a single gene for blue eyes and another for brown eyes, yet one's eye color will be brown, since brown eye color is a dominant trait. One would require two blue eye genes to actually have blue eyes.
Why do kids get Tay-Sachs and adults get breast cancer?
Offspring could develop the disease only if both parents are carriers and both passed it on to their child -- a one in four chance per pregnancy.
Recessively inherited diseases, such as Tay-Sachs, tend to affect children.2 In such a recessively inherited disease, those with two defective genes would die as children, while people carrying one copy of the gene would be phenotypically normal, but risk passing the gene on to their offspring. Practically speaking, this means that for any lethal genetic disease that manifests exclusively before reproductive age, there must be many unaffected adults carrying the gene for the deadly disease in question. The only way (barring mutation) that the offspring of a carrier could develop the disease would be if their spouse also carried the defective gene and both passed it on to their child, a one in four chance per pregnancy.
This is both a blessing and a curse. Since carriers are healthy, there is no simple way to remove the gene from the gene pool. 3 We would have to bar all carriers from having children, a prospect which is both unethical and cruel. On the other hand, we could easily prevent the birth of babies with recessively inherited diseases (such as Tay-Sachs and cystic fibrosis) by preventing carriers from marrying.4
For any dominantly inherited trait or disease, only one copy of the gene for that trait is required, such as in the case of brown eyes mentioned above. Any child who inherits even one copy of the defective gene for a disease such as Huntington Disease (a lethal neurological disease) will almost certainly develop the disease, although the age of onset may be between two years and over 80 years. All lethal dominantly inherited diseases must have adult onsets or there would be no one to pass on the disease to the next generation. These diseases would also be virtually impossible to eradicate, since mutations are fairly common and we would have to forbid people who are currently healthy (but are likely to develop the disease) or already manifesting the disease, to marry. Some forms of breast and ovarian cancer demonstrate dominant inheritance.
Why screening for recessively inherited diseases is less traumatic
The Jewish community has had a lot of experience dealing with screening for recessively inherited diseases through Tay-Sachs testing programs for over 30 years. Because one is only testing for a gene, but not for a disease itself, there is a definite psychological benefit. There is no direct threat to the health of the person being tested. The carrier remains healthy following the discovery of the carrier state -- only potential offspring are affected. Additionally, knowledge of the carrier state empowers one to act to prevent the birth of children with a tragic disease. Therefore, the person being tested can retain their self-image of normal health.
The traditional Jewish community has been very receptive to Tay-Sachs testing. Jews have used the knowledge gained from testing to significantly decrease the incidence of Tay-Sachs births, with segments of the Orthodox community virtually eradicating Tay-Sachs births by an ingenious method of preventing carriers from marrying (which I will describe later in this article). Widespread testing has also been strongly encouraged by all segments of the Jewish community. Nevertheless, many issues arise even in testing for a recessively transmitted disease.
Is there a moral obligation to screen and if so, when?
While the Torah obligates us to guard our health,5 it does not necessarily follow that testing ourselves for recessive genetic traits (that do not directly affect our health) is included in the mitzvah. Nevertheless, Rabbi Moshe Feinstein favored Tay-Sachs testing and considered the possibility that testing might be a moral obligation.6 He states that while one may usually ignore a small risk that society finds acceptable (See: Taking a Risk),7 not being tested for Tay-Sachs is like closing one's eyes to an obvious danger. He also points out the severe emotional repercussions of not testing if a Tay-Sachs child is born.
Yet, Rabbi Feinstein feared that testing teenagers could hurt the self-image of those testing positive and lead to discrimination against them when seeking a spouse. He recognized that despite assurances from the medical community that carrying the Tay-Sachs trait presents no health issues for the individual or his offspring (so long as both spouses are not carriers), many people will shun marrying into a family with a genetic defect. Therefore, Rabbi Feinstein insisted on safeguards to protect confidentiality, advising testing of youngsters on an individual basis (and not mass screening), and only when he/she is prepared to start dating.
Rabbi Feinstein's approach is the approach of Dor Yeshorim, an organization that functions in the traditional Jewish community where formal introductions precede first dates. Dor Yeshorim carries the conclusions of Rabbi Feinstein to their logical conclusion. Being a carrier for Tay-Sachs does not impact on the health of the individual being tested and only affects potential offspring. Therefore, so long as marriage between carriers is prevented, there is no reason for anyone to be informed of the test results, including the prospective spouse and even the person himself!
Dor Yeshorim tests people for a variety of recessively inherited diseases,8 most notably Tay-Sachs, only informing matchmakers whether a prospective match presents a problem of genetic incompatibility.9 Neither of the young people is told of their carrier status, but any potentially disastrous matches are averted. This anonymity is crucial in preventing Tay-Sachs status from causing emotional pain before marriage. It avoids initial emotional attachment between carriers by preventing their meeting, and prevents catastrophe after marriage (if two carriers marry). Dor Yeshorim has prevented many genetically incompatible matches before the couples ever met!10
On the other hand, Rabbi J. David Bleich,11 law professor at Yeshiva University, feels that testing should be done on a mass scale when children are young. He argues that appropriate education of the Jewish community could lead to the removal of the stigma attached to having a bad gene. He feels that proper instruction is the cure for the ignorance that leads to discrimination towards people carrying recessive genes such as Tay-Sachs and while he appreciates the goals of Dor Yesharim, he objects that:
. . .in refusing to divulge the results of genetic tests to either the young men and women affected or to their parents, a negative stereotype is dramatically reinforced. The hocus-pocus of assigning numbers and later announcing that the prospective marriage of the bearers of matched numbers will either be propitious or will not be propitious imbues the process with a Byzantine-like quality.
Testing after marriage
Obviously, testing for lethal recessive traits (such as Tay-Sachs) before marriage allows the greatest latitude in decision-making. One may choose to go the Dor Yeshorim route or to discuss one's carrier state with any potential mate. In any case, the full range of options remains open.
The options for two Tay-Sachs carriers who are already married are much more limited because of the Torah12 command to be fruitful and multiply. Since the Torah commands us to attempt to have children, Jewish law does not permit deliberately sterile marriage.13 While adoption is certainly meritorious, it still does not fulfill the Biblical obligation of procreation.
Artificial insemination by a non-carrier donor raises issues of adultery, paternity, and inheritance, while it does not fulfill the mitzvah of procreation. From the woman's side, egg donation and surrogacy raise similar questions, but additionally, raises the problems of establishing maternity. Is the genetic mother or the birth mother considered the baby's true mother? Naturally, the question of surrogacy also leads to concerns regarding the ethics of buying and selling eggs and use of a woman as an incubator for hire.
Is amniocentesis and abortion of affected fetuses a viable option? From a Jewish perspective, abortion is generally reserved only for cases involving danger to the mother (See: Abortion in Jewish Law). While this surely includes the mother's emotional health, such as severe post-partum depression and suicidal ideations, it usually does not include the health of the fetus.14 In fact, Rabbi Moshe Feinstein forbids amniocentesis for the purpose of fetal diagnosis of Tay-Sachs, ruling that the mere performing of the procedure transgresses the Biblical commandment of not placing a stumbling block before the blind.15 He argues that by offering the test, the physician is party to likely decision to abort if the fetus is positive for Tay-Sachs disease.
A viable option for married couples
The most promising option for such couples is pre-implantation genetic diagnosis. The parents agree to conceive their offspring via in vitro fertilization. The three day pre-embryo, made up of approximately eight cells, has one cell removed to be tested for a specific genetic defect before implantation. Only a zygote that is not homozygous (having two defective genes) for Tay-Sachs would be implanted. Rabbi Yosef Shalom Eliyashuv, possibly the most influential posek [authority in Jewish law] in Israel today, has permitted pre-implantation diagnosis and implantation of healthy zygotes to prevent cases of Fragile-X and even in a case of a woman with neurofibromatosis who only had skin lesions.16 Pre-implantation genetic diagnosis, which is already accepted by some rabbinic authorities, is likely to be acceptable to most Jewish legal experts when used to prevent serious diseases in offspring.
Who should be told?
While in the Dor Yesharim model, an individual does not know whether they carry the gene for Tay-Sachs, most people are tested by labs that do release the results to the person whose blood was tested. Who else should receive this information? This issue is less problematic in a recessively inherited disease than for a dominantly inherited disease. The information that one is a Tay-Sachs or cystic fibrosis carrier should not affect insurance premiums or insurability.
Since siblings share one half of their genes, if someone finds that they are a Tay-Sachs carrier, there is a 50% chance that their sibling is also a carrier. Sharing such information with even more distantly related relatives provides useful information with practical benefits. The knowledge that they may carry the gene may spur them to be tested and to avoid marrying another carrier if they are positive. Short of any irrational stigma attached to possessing the carrier state for a recessive gene, there should be no more reason to avoid sharing the information with others than to hide poor eyesight or any other trait that we generally do not conceal from others. In fact, while poor eyesight actual affects the person, the carrier state has no health repercussions!
Genetic screening for recessive traits is a great boon to the Jewish community (and the rest of the world). Whether done confidentially or publicly, the information gained provides the opportunity to make wise and informed decisions about the future. There are no health ramifications for the person being tested, but by utilizing such means, we can look forward to a future filled with more hope and less disease.
1 These are often referred to as juvenile, chronic and adult-onset forms of hex A deficiency. Affected individuals have low levels of the hex A enzyme that is missing entirely in the classical, infantile form of the disease. This may help explain why symptoms begin later in life and are generally milder than in the classical, infantile Tay-Sachs disease. - http://gunsmoke.ecn.purdue.edu/~kpasquet/project/tays.html (see also http://www.ninds.nih.gov/disorders/taysachs/taysachs.htm)
2 Deadly diseases (such as Tay Sachs) that affect children must necessarily be recessively inherited (unless they are the result of random mutation), since otherwise anyone carrying a single gene for the disease would die before they could have children and the disease would also disappear. Such diseases continue to exist because healthy people carrying a single copy of the defective gene have a one in four risk of passing the disease on to offspring if they marry another carrier.
On the other hand, autosomal dominant diseases (such as some breast cancers) must occur almost exclusively in adults, since the gene for such diseases are carried only in people who will manifest the disease. Were the disease to strike children exclusively, there would be no one of childbearing age to pass on the defective gene or the disease. Exceptions to this rule occur in diseases that have incomplete penetrance, occur due to random mutation, or that are not always fatal.
3 There is very real significance in the variable ways that diseases can be inherited. Unfortunately, there is no ethical way to ever remove a recessive gene such as Tay Sachs or cystic fibrosis from the gene pool. This is because most copies of the defective gene are in normal, healthy people that are only carriers of the gene. For instance it is estimated that one in 30 people of Ashkenazi Jewish descent and one in 30 people of French-Canadian/Cajun descent carries the gene for Tay Sachs. This means that there are hundreds of thousands of carriers, all of whom are healthy people.
4 While limiting choices in marriage partners may appear to be impractical, even if a known Tay Sachs carrier wanted to randomly date within the Ashkenazi Jewish population, he/she would only be precluded from marrying 3% of prospective mates. If the same person would also date non-Ashkenazi Jews, the limitation would be even smaller than one in 30! Most people voluntarily eliminate a much higher percentage of prospective mates based on other less serious criteria such as appearance, height, weight, philosophy, etc. 5 Take heed to yourself and guard your lives carefully (Deut. 4:9) and Guard your lives carefully (Deut. 4:15)
6 Igros Moshe, Even Ha'ezer 4:10
7 Shomer p'saim Hashem Psalms 116:6
8 Dor Yesharim also tests for Canavan, Niemann Pick disease, Gaucher disease, Bloom syndrome, Fanconi anemia, Cystic fibrosis, Familial Dysautonomia, Mucolipidosis IV, and Glycogen Storage Disease type 1a.
9 An individual can also call with their Dor Yesharim number and inquire whether there is any barrier to dating someone else who has been tested by Dor Yesharim if they know the number of the prospective mate.
10 In fact, there has not been a single Tay Sachs baby born in the American or Israeli Haredi communities in several years!
11 Tradition: A Journal of Orthodox Thought, Vol. 34, No. 1: spring 2000
12 Genesis 1:28
13 Tractate Berachos 10A
14 Only one prominent posek allows abortion for Tay Sachs, but his a lone dissenting opinion; see Tzitz Eliezer vol. 9, #51:3; Tzitz Eliezer, vol. 13 #102.
15 Igros Moshe, Choshen Mishpat II; 69:2. There is also a small risk of complications from amniocentesis, including the approximately 1/200 chance of miscarriage.
16 Personal correspondence with Dr. Avraham Steinberg.