Prof. Michel Rebel, Weizmann Institute, member of the UNESCO International Committee on Ethics in Biological Research
Prof. Michel Rebel
The discussion of the possible medical consequences of the genetic replication method is fundamentally different from the discussion of the applications in animals. The purpose of developing the method of genetic reproduction of animals is to enable the breeding of herds of animals with an economically important genetic trait, such as the production of protein of medicinal value found in milk. The genetic identity between the animals may allow homogeneous production from each individual in the replicated herd.
As doctors, we face far more weighty ethical questions. For the purpose of the discussion, we will focus on two main questions: Is there a medical benefit to humans in this scientific development? Is it morally correct to apply the method to humans?
The progress in scientific research, such as in the field of deciphering and mapping the human genome and in the field of in vitro fertilization methods, provides so many opportunities for medicine that these possibilities must be discussed seriously, despite the moral challenges they pose. This is also true regarding the medical consequences of the genetic replication method.
One of the basic assumptions in the establishment of committees to discuss ethical questions in the field of biological research is that the role of these committees is to define the limits of what is possible, what is allowed, and not to prohibit new techniques in advance and in a sweeping manner.
The ban violates the human right to enjoy the progress of science. The ban also does not provide effective protection against those with the malicious intention of evading the ban and committing crimes under a veil of secrecy. Thus, in fact, the ban does not bring the desired result, and it is better to choose - instead - a way of close supervision that will allow the use of science in a way that will truly contribute to what can be called "correcting the world", which is ultimately the main role and ambition of man.
This discussion will try to define the place of the replication method in the field of medicine and consider its value and usefulness for solving the individual's medical problems. It is clear that today, the replication method is not technically sufficiently established for it to be possible to seriously discuss its application in the field of human fertility. But for the sake of the ethical discussion, let's assume that such an application of the method is already possible and medically safe.
1. Genetic replication as part of in vitro fertilization methods The genetic replication method can be described as another one of the methods for artificial in vitro fertilization, which we have become accustomed to in medical practice in the last twenty years and which have mostly won ethical solutions. It should be noted that the State of Israel is a world leader in this field and has the largest number of IVF clinics per capita that apply various techniques that allow many infertile couples to give birth.
The usual method for in vitro fertilization is, of course, by a meeting between egg and sperm, which is carried out in a dish in the clinic's laboratory. Fertilization can be with the partner's egg taken after hormonal treatment and with the husband's sperm, which makes it possible to overcome different types of infertility in the woman.
In case there are no eggs, an egg donation from another woman is needed. In the case of male infertility, fertilization is done with a sperm donation, usually from a sperm bank.
The ethical questions in these fertilization techniques seem relatively easy today, but they exist. First, we must not forget the opposition to the first attempts that existed (and still exists in certain circles such as the Catholic Church) because creating a child in a test tube is against human dignity. In addition, difficult ethical questions arise when infertility requires the use of a sperm or egg donation from a non-partner, which is usually an anonymous donation. There are religions where this is not moral, and halachic questions also arise in Judaism (for example, fear that descendants of the same donor will marry each other). Not knowing part of the genetic inheritance can also make it difficult for a medical diagnosis that the child born from an anonymous donation may need.
In order to minimize the need for sperm donation, a second method of fertilization was implemented, which was the injection into the egg, through a fine glass needle, of individual spermatozoa taken from the testicles of the infertile partner. With this method called ICSI (Intra Cytoplasmic Sperm Injection) it is possible to achieve fertilization of the egg with immature sperm cells. But the principle is preserved that at the time of fertilization, 23 chromosomes of a man meet with 23 chromosomes of a woman.
Also in the replication method, needles are inserted into the egg in order to a) pump out the DNA. the nuclear (chromatin) of the egg, b) insert a complete cell with 64 chromosomes, under the outer envelope (zona pellucida) of the egg. Activation of an electric field causes fusion between the cytoplasm of the egg and the cell, and causes the beginning of embryonic development. For many years, the scientists dealing with animal reproduction thought that fertilization could only be achieved with a cell from an embryo in the first stages of its development. In 1997, it was proved for the first time that a cell from an adult animal could be used, and as a result the discussion about possible applications of the replication method in humans intensified.
It is important to emphasize that just as in the first two methods of in vitro fertilization, in the replication method the embryo develops in the laboratory plate only for a period of a few days during which the cells of the embryo divide in preparation for the creation of the blastocyst, and then it is implanted into the uterus of the mother who will give birth to it at the end of the pregnancy.
There is no "industrial process" in the replication method as is sometimes presented. Every baby that is born using the cloning method, will be born to the mother exactly as is done today with the accepted methods of in vitro fertilization. The pregnancy can take place in the uterus of the woman from whom the egg was taken, and the cell used for fertilization can also be from her or her partner. There is no need for a surrogate (unless the woman cannot carry the fetus). According to most opinions in Halacha, the birth mother is a legal mother.
As mentioned, in the current state of the research, it is not possible to include the replication method among the other alternatives to artificial insemination because the success rate in animals is so low and there is no proof that the method will work at all to fertilize a human egg that will develop into a normal embryo. This requires research. But it must be remembered that the ICSI method was also considered impossible for a long time, and that with all methods of in vitro fertilization, the percentage of success in rooting the embryo in the uterus under conditions that will lead to a successful pregnancy is about 20%. But if science develops, there will most likely be a significant improvement in the results. If we assume that the replication method will be an alternative to in vitro fertilization in the future, the first moral question is what medical benefit to the individual will we derive from this revolutionary method.
2. Possible medical benefit from the replication method
A. Infertility treatment: In a couple where the husband's infertility causes a complete absence of sperm cells, the woman's egg can be fertilized with a normal somatic cell from the husband's body. The child will then be a genetic twin of the husband, and the genetic paternity will not be that of a man foreign to the marriage as in the case of sperm donation. If the fertilized cell originates from the woman, the baby will be her genetic twin. If the woman does not have eggs, a donor egg can be taken, but since the nuclear DNA is removed from the egg, the child will be genetically attributed to the husband or wife from whom the fertilized cell came. Even in the event that the husband and wife are both barren, they can be guaranteed children genetically attributed to them.
B. Treatment of a hereditary disease: in a couple where both are carriers of a mutation that causes a severe genetic defect in a homozygous state, it is possible to give birth to a child who will be a genetic twin of the husband or wife and, like them, will be a heterozygous carrier and not sick. In addition, the method will also prevent the transmission of a dominant mutation. If only one of the partners is a carrier of the mutation, the egg can be fertilized from a cell of the non-carrier parent. That way the offspring will no longer carry the mutation.
These are two possible medical indications that can be a balm for the individual in need. Of course, there are other medical applications that are difficult to specify today.
3. Ethical aspects:
One can first ask if there is justification for the couple to want a child genetically attributed to them. Maybe it's better to adopt a child. The answer is that science gives a new option here, which expands the number of options between which the couple can freely choose. If after a consultation that will show them all the options, they will choose the replication method, why prevent it from them? The desire to give birth in his image and likeness is important to many couples and may not be important to others.
Another difficulty is that the child will be a genetic twin, like a brother or sister of the cell donor, and will resemble him more than enough. In nature, genetic twins are born with a frequency of 1:270 births. Many works have been done in order to establish the degree of identity between genetic twins. When the twins grow up in different family environments, a match of only 50% was found in personality traits and intellectual traits (such as IQ). The genetic identity does not dictate the behavior, because the environment, education has an effect that weighs no less than that of the genetic load. In addition, in the case of duplication, the "twin" will be born from another womb, to another woman when it is known that the diet and lifestyle during pregnancy affect the development of the fetus. The cloned child will be less similar than a genetic twin, what is more, will be born a generation after his twin. The age difference will greatly diminish the similarity. From work on animals, it is already clear that there is no absolute identity between cloned animals, perhaps because of the action of the mitochondrial DNA of the egg, or the effect of the location in the womb or the mother's diet. Therefore, the method of genetic replication will not produce identical copies of humans, because there is no genetic script.
In humans, the influence of the environment, personal attitude and education are so great that a cloned child will probably grow up in a fairly normal way. He will perceive the cell donor as a father because of his paternal behavior, and if the mother donated the cell, the very act of giving birth will make her the mother of everything. So it does not seem that the relationship of a twin brother will negate the feeling of fatherhood or motherhood. Some say that the method endangers the family structure. It can be argued against that the method increases the desire to give birth in cases where another birth is not possible. Our company willingly accepts families of various types today, single parents for example. It is difficult to see why procreation by the replication method that would help a couple to give birth without the donation of a foreign reproductive cell, would cause damage to the image of the family.
A serious objection to the replication method is that there is no sexual combination of genetic cargo here. This claim would be justified if it was about making the method of reproduction the only method of procreation. But if it is about medical use in individual cases, it is difficult to see the moral flaw. Some argue that gene mixing is as important to evolution as nature proves. But in fact we know that in the last million years the human species of Homo sapiens has undergone very few genetic changes. The development of the human race is mainly by the transfer of cultural baggage from generation to generation and the constant acquisition of intellectual knowledge.
Making the mixing of genes a moral value seems excessive. It is true that a minority of gene mixing, such as in marriages between relatives, or incest, carries within it a genetic danger of breeding defects. But this does not concern the replication method, in which a genome that has already "worked well" in a person living before us will be transferred to a new embryo. It is unlikely that a person suffering from a severe genetic defect would want to pass it on to their offspring through replication.
In addition, if mixing genes was a supreme moral value, it would be difficult to understand why in most cultures - including and perhaps especially in Judaism - people marry within a limited cultural community. Anthropologists prove that this was already done in the primitive village. The very existence of genetic diseases that are more common in certain communities, such as Tay-Sachs in Ashkenazim or a mutation in the BRCA1 gene in them and in some other Jewish communities, shows that there is no complete genetic mixing. It is true that this does not justify complete preservation of the gardens. The claim that everyone is allowed to be different is true and that this difference is based on the many genetic differences between people. But again the mere existence of genetic twins does not negate this principle. Humans sometimes look like someone else's double even though they are not twins, and having genetic twins does not detract from the general difference between humans. Even the medical use of replication in some cases does not endanger the difference between people, but it is clear that wholesale use of the method for non-medical reasons must be prevented.
Precisely because the replication allows a solution for couples who wish to give birth without an external and anonymous donation of reproductive cells, the method seems halachically appropriate to many rabbis. It will allow the fulfillment of the mitzva of Pro and Rebu and does not violate a serious law in Judaism that permits other interventions in the fetus, such as crossing it for the purpose of pre-pregnancy diagnosis of a genetic disease in order to prevent mental danger to the mother who will carry the fetus in her womb after implantation. In this, Judaism differs from Christianity, which sanctifies the fetus as a person for everything from the moment of fertilization and consequently prohibits in vitro fertilization. It is also interesting that birth without sex was mentioned as a possibility, especially if for a medical purpose, by one of the greatest interpreters of the Talmud from the XNUMXth century, the Mairi (Sanhedrin sez:).
4. Permissible limits
In addition to the medical indications mentioned above, other uses have been proposed for replication that arouse fear of surfing beyond the permissible limits or that have no medical justification.
A. Organ transplant applications
Lack of organs and tissues for transplantation is one of the biggest problems in medicine today. It has been suggested that tissues from cloned embryos can be grown in the laboratory that will be genetically and immunologically compatible with the patient from whom the cell will be taken for fertilization. For now, it is not possible to grow organs such as heart or kidneys in the laboratory, but it is possible to grow pancreatic cells for transplantation in a diabetic patient or genetically engineered nerve cells for transplantation in Parkinson's patients. The ethical question is whether it is permissible to produce embryos for these purposes. In the Jewish view that does not see the sanctity of a person in a fetus before the fortieth day, there is perhaps a possibility to take advantage of this method. On the other hand, it seems immoral to start a pregnancy and grow a fetus until it has kidneys or bone marrow for transplantation. But Rabbi Tendler, an American Jewish Ithakan, does not completely rule this out on the condition that the pregnancy is not for the purpose of harvesting an implant but for the purpose of giving birth to a child who, by the way, will become an implant donor. Of course, there is no permission here to take a vital organ, because it is nothing but murder. But the principle that as long as the child is "an end and not a means" this is not forbidden, is an important ethical principle.
There are observers that such an approach can lead to the creation of a defective child, for example without a head (as a result of some intentional genetic change in the embryo) in order to take organs from it. There is a difficult challenge to traditional ethics here, because in most religions, such a defect has fallen that does not have a "human figure" and also lacks human rights. But there is an abysmal difference between something that happens in nature, and an act directed even for a medical purpose.
In error, there are also those who confuse replication with voluntarily causing genetic defects in order to produce second-class humans. It is important to emphasize that this is not a serious claim (to say the least). On the contrary, the replication is the preservation of the genetic load of the donor of the fertilizing cell, and the method of replication has no help or means to cause intentional defects (or "improvements") in the embryo. One of the challenges of ethics is to describe
Any technology precisely and not to mix things up and go into science fiction of the type of Aldous Huxley books.
One of the inventors of in vitro fertilization, Prof. Edwards from Britain, already brought up the possibility twenty years ago of freezing about half of the embryo's cells after fertilization in a dish and thus preserving a kind of "twin" for the embryo to be born. The intention was that if later the need arose for "spare parts" for a person who was born, it would be possible to "use" the frozen half of the embryo. Then there was no need to wait for the emergence of the replication method to come across immoral ideas.
Nevertheless, crossing an embryo into two is done for the purpose of pre-pregnancy diagnosis, and has also been applied in the Netherlands for reproduction. The justification for this action was that it would allow a woman to go through the difficult hormonal treatment for in vitro fertilization only once, and she would be able to give birth to several children in the space of many years. Perhaps there is no moral flaw here, if we consider the fact that embryos and eggs are frozen to preserve them until the woman wants another pregnancy.
B. Reproduction for procreation for non-medical reasons and the illusion of genetic identity
One of the causes of moral excitement around the method of reproduction is the possibility for a woman to give birth without the intervention of a man at all. Some may see this as a threat to the value of the male in human society, although a survey would surely reveal that most women love men not only for the purposes of reproduction. But the question remains, is using reproduction in order to allow a lesbian couple to give birth without needing a male, ethical? Replication also opens for the first time to gay men the possibility of having a child genetically attributed to them, albeit with the help of a surrogate woman. Here the ethical principle of medical prescribing can help draw a line between what is allowed and what is forbidden. It can be argued that a homosexual couple knows in advance that we cannot naturally give birth, therefore there is no pathological condition here that the doctor cures. However, it must be remembered that the methods accepted today for artificial insemination are heavily used by homosexual couples, mainly in the UK.
Because of the illusion that genetic duplication results in the birth of a person identical to the cell donor, much has been written about the possibility for an adult to copy himself into a young person, as a kind of drug of youth, or for bereaved parents to recreate the child who was killed or died. Beyond the fact that there is no ethical medical indication here, the public must be educated in the terrible illusion that genetic identity is a general identity. Test proofs have already been presented above
Genetic twins showing that the mental difference between them reaches 50% compared to 75% difference in non-genetic twins. There is no genetic script in a person, and the environment, education and personal history make each person special and one of a kind.
Giving birth to a child who may have a physical resemblance but a different character and emotions than expected, can be a cruel illusion. In an era of great advances in the field of human genetics, and as the day approaches when everyone will know their individual genetic makeup as a result of the Human Genome Project, it is of the utmost importance to let the public know that there is no absolute genetic prescription.
5. Positions of bioethical committees on the subject of replication
The danger that the human genome project may lead to a mistaken understanding that man is dictated by the genes he inherited from his parents, is reflected in the work of UNESCO's International Committee on Ethics in Biological Research. In Section B of the Universal Declaration on the Human Genome and Human Rights, adopted by UNESCO in November 1997, it is stated:
"Human dignity commands not to reduce individuals to their genetic traits and to respect the unique and different of them." That is, genetic identity as in the replication method cannot lead to the production of identical people. This is one of the reasons that when, in May 7991, the committee discussed the consequences of cloning Dolly the sheep, it was decided by an overwhelming majority that this method should not be considered specifically and that scientific research should not be prohibited, since the statement also sufficiently emphasizes that the use of genetics must respect human rights and be only for the medical benefit of the individual. But, under political pressure on behalf of several European countries, especially Germany, at the last minute, Article 11 was inserted in the declaration, which says: "Actions that are contrary to human dignity, such as reproduction for the birth of a person, will not be approved." It seems to many representatives that we have made a mistake here because the respect of the human being commands not to be reduced to his genetic traits, but that the human being must be respected through education, raising the standard of living and health and through brotherhood between peoples. The message of a comprehensive and premature ban on a scientific method with considerable medical potential seems negative and causes more harm than good.
Close supervision, as suggested in the statement for other issues in genetics, would certainly be better than a ban in advance and without reservation. One of the human rights is also to benefit from the progress of science, as written in the UN Charter of Human Rights.
A similar negative position was adopted by the European Community in January 1998, which prohibited the reproduction of "a person who is genetically identical to another person", on the grounds that this is contrary to human dignity, and that there is excessive "instrumentation" in the procreation process. In addition to what was said above, it is important to remember here that even IVF was considered at the beginning of the 80s as a way of procreation that is contrary to human dignity and the instrument of procreation that must be an act of love (as was then declared in the Vatican). The experience of the last decade proves that in vitro fertilization has brought many benefits to a person and increased the desire to give birth without harming human dignity.
The Israeli Knesset discussed a bill by MK Hagai Mirom, whose purpose is to ensure that genetic replication for the birth of a person, as well as actions that cause permanent genetic changes in the reproductive cells, will not be carried out for five years. But the law also authorizes the Helsinki Higher Committee for Genetics to monitor developments in science and medicine and to recommend to the Minister of Health the possibilities of allowing types of operations such as these under certain conditions and when the situation warrants it in terms of medical safety and ethics. There is a satisfactory balance here for both law and science, and an educational message for society: scientific progress opens up new possibilities for medicine in the field of genetics and reproduction, but requires in-depth consideration.
It is to be blessed that the State of Israel, which does not have a racist past like the countries of Europe, and sees science and medicine as a way of correcting the world in the spirit of the Jewish tradition in which man shares with the Creator, takes a balanced and educational position. It is also good to treat genetic changes that change heredity in a similar way, in which there is a danger of an illusion of genetic improvement in a person. The public must be educated that there is no ideal genome, and that no person is genetically perfect. There are no good genes and bad genes in humanity. The line must be drawn between genetic therapy of the individual for health reasons and between racial improvement ambitions. Eugenics (improvement) as an aspiration of society is morally forbidden because the main improvement in man is through free education and raising living conditions. Genetics designed to cure an individual's disease is not eugenics.
6. Summary
Three ethical principles in the field of genetics can ensure ethical use of the progress of science.
A. The entire application of genetics will remain in the hands of the doctor in his ethical relationship with the patient, as dictated by the ethical codes of medical behavior. The doctor's intention is to cure the individual.
B. The decision to use genetic manipulation must remain a decision of the individual, with counseling that will allow him to understand the results, but without the dictates of society.
third. Each case must be discussed on its own merits, according to the halachic legal tradition in Judaism, because according to the Rambam, "everyone is an exception." Laws regarding genetics, and especially sweeping prohibitions of scientific areas, do not suit the individual's right to benefit from the progress of science, nor the personal circumstances that vary from person to person.
Every knowledge can be used for good or bad, like the parable of the tree of knowledge, good and bad, but the role of ethics is to bring us to the tree of life, to choose the good for the correction of the world.
* Editor's note: Prof. Rebel is one of the traditionalist scientists who uses this to advance science and not to stop it.
