The topic of my contribution is a little outside the topic of this conference; it is genetic eng-ineering and abortion. I will try to explain some new developments and how they are a threat to human life and humanity in society, and in medicine. I will not talk about abortion itself or about the problems involved. What I do want to say about abortion is that the legalization of abortion opened the door to a whole array of other manipulations concerning all of human life right from its beginning that we are facing now and which are continuing.

I will not deal in detail on all of the medical developments with respect to the beginning of life because each of these topics could take pages of discussion.

· Artificial insemination with donor sperm

· In vitro fertilization and embryo transfer and some other variations of this technique (GIFT (an Artificial procreation technique, ICSI)

· Egg cell, sperm, and embryo donation

· Surrogacy (commercial or altruistic hiring the womb of another woman)

· Embryo experimentation

· Prenatal diagnosis / selective abortion

· Pre-implantation diagnosis (PID) and selective embryo transfer

· Germ-line gene therapy (somatic cell gene therapy) to try to heal diseases or disorders that have a genetic background

· Cloning

· Transplantation of tissue from aborted fetuses. That this is the result of abortion, is very clear. More than ten years of research have given very poor results, but nevertheless, people want to go on and have these experimentations.

This just gives a small idea of all the problems that have to do with the beginning of life. Many of them have to do with abortion and could only be developed because of the acceptance of the legalized killing of the human embryo.

I will now continue, more specifically, with the genetic field. More and more genetic diseases are being identified and mutations are being located in the genome--the chromosomes of the human being. This makes it possible to diagnose genetic diseases even before birth. The Human Genome Project is a worldwide project of trying to sequence all the genetic information in the human genome in the chromosomes. They think that project will be finished in 2004. They will have to sequence three billion base pairs as the building blocks of DNA.

I attended a conference just a few days ago on the genome project and was told there that by now, two genes are identified and located daily. This can be compared to ten years ago when only one gene per year could be located and identified. From a technical and scientific point of view, it is fascinating. But there is another side to it, and that is the way we are going to use it.

Prenatal Diagnosis

With amniocentesis, a bit of the amniotic fluid is taken. It contains cells from the unborn child which can be further investigated. By this method, it is possible to make a chromosome picture to see if all the chromosomes are present and if they are all in the correct situation and correct shape. So it is also possible to detect any chromosomal disorder. The most frequent disorder detected is that there is one chromosome too many. Especially chromosomes 13, 18 and 21, which are the ones that can have three copies instead of two. At this point the fetus is viable, can live, but especially those having numbers 18 and 13 will mostly die soon after birth. And of course, the trisomy of 21 which leads to Down Syndrome,;yet persons with this syndrome normally can live very well.

In most cases of this type, the mother chooses to undergo an abortion when the disorder is detected. Not in all cases I must say. It depends also on the counseling and in certain centers in the Netherlands, especially the Catholic centers and the Catholic University, there is a lower rate of abortion after detecting an chromosomal disorder than in some of the other centers. Though it is still high and it is too high, there is apparently an influence by personal counseling. While the counselors are saying they are non-directive in counseling and they try to be so, we all know that is theoretical. There is really no neutrality in these things when we are speaking about saving human life.

More and more disorders can be detected which is also true for prenatal diagnoses. So it will become possible to screen babies before they are born with genetic disorders with any deviation from what is considered normal. This often results in abortion. This is, I think, a most serious danger in recent developments.

Pre-Implantation Diagnosis (PID)

It is very interesting to understand the following. Pro-life people were always saying it is not only wrong to kill the unborn baby but that it is also a burden on the woman to have the abortion. This was often made very relative with sayings like, “Of course it is serious, but having the child is very serious as well”. But now some researchers want a new technique. They want to apply the pre-implantation diagnosis. For this, they use as an argument the psychological burden on the woman for having an abortion.

Now they acknowledge it, because they say they can develop this new technique that makes it unnecessary to have an abortion. The PID means that from the very early embryo in the dish, in vitro, they can take one or two cells and have a chromosomal diagnosis which will indicate whether the embryo has a genetic disorder or not. If it has one, then this embryo is not transferred into the uterus of the woman and so will never be born. The truth of the matter is, that it is a very early form of prenatal diagnosis, but as there is no ‘pregnancy’ from the side of the woman, technically no abortion will be necessary to prevent the birth of the child with a disorder.

Right now in the Netherlands, there is a proposal being prepared for law that would allow this kind of research and practice. It has taken quite some time and I can remember ten years ago when we were just starting in our institute, that this issue came up and there was a lot of indignation in parliament about “how could people do that with human embryos?” Now it seems to be acceptable. It is interesting that this law only includes the possibilities for research that have to do with genetic disorders and procreation, not with other kinds of research with embryos.

But the law is still in preparation and not yet discussed in parliament and already one of the mayor council boards of the government (de Gezondheidsraad - the Health Council), is advising the Minister to widen the scope of the law and open possibilities for other research. I will come to this later, because this has to do with very new developments in biomedicine.

Methods of Research Before Birth

To summarize, we have the following methods of research:

· Carrier Screening

· IVF. Pre-implantation diagnosis that is straight after conception

· Choreonic villi diagnosis about 8 weeks after conception

· The Triple Test; not a diagnosis but, in fact, a risk screening. From the blood of the pregnant woman the concentration of three different substances are measured and together with the age of the woman, it is possible to calculate the risk that the unborn baby will have for Down Syndrome, or one of the neural-tube defects. If that risk is considered relatively high (over 250), then the pregnant woman is offered a diagnosis, an amniocentesis. In most countries now, pregnant women who are 36 years of age and older can have prenatal diagnosis for chromosomal disorders.

But the majority of children with Down Syndrome, are born from women younger than 36 years old because most children are born from younger women. So it is said, “We can detect a lot more children with Down Syndrome and neural-tube defects if we screen all pregnant women of all ages with the Triple Test and then have the amniocentesis done on those women who have an increased risk.” This would make every pregnancy, first of all, a risk and only in second place, a happy expectation. It would completely change the mentality and the outlook and experience of being pregnant and expecting a child. All pregnancies could become tentative. “Let’s have a try”, and if it’s alright, then the pregnancy is acceptable. Then that child will be accepted as a child able to come into the world.

Fortunately, all this is still heavily debated, and there are a lot of people, including those in medical circles (in the Netherlands at least), that do not want to introduce it at full scale. But of course, others are pressing the industry because a lot of testing means a lot of money to be made.

· Amniocentesis

· At the end, echo or sonography is well known and can be used earlier during the pregnancy with modern techniques.

So, here is a whole battery of screening possibilities. Carrier screening is a problem of its own and I cannot enter into that whether that is desirable or not, depending on many circumstances. Sonography can be very useful and helpful, and is mostly being done for the best interests of the mother and her child. Most of the other techniques are done in order to detect any disorder with the possibility of abortion as a consequence. So, we have entered into a kind of quality screening of the child before birth.

This focus on genetics has several backgrounds. One of them is that other reasons -- determinants as they are called -- for diseases are to a certain extent, under control, like deficiencies (e.g., food deficiencies) and infections. So, the relative contribution of genetic disorders to the whole load of diseases in the population is on the increase.

A second reason is that there is somehow a focus on genes again. We have had that before, at least in the Netherlands, and I think in other Western countries as well. There was a swing toward social circumstances as being the reason for disorders and problems in the 1970’s and the beginning of the 1980’s. Then it was almost considered a crime to talk about the genetic background behavior because it was immediately associated with eugenism and discrimination.

That was a bit exaggerated then, but now it has completely swung to the other side. There is a renewed focus on genes as an explanation for disease and disorders, but also as a cause for certain behaviors. You all have heard about the ‘gene for homosexuality’ for example, and ‘genes for alcoholism, suicide and delinquency’ -- even for being lazy! I found a very interesting expression by Benson in Time Magazine, dated June 24, 1996, regarding this type of geneticism: “Our genetic blueprint has made believing in an Infinite Absolute part of our nature”. So the fact that some people believe in an infinite absolute, in other words believe in God, is genetic in nature. They say it is in the genes that some people tend to believe. That is simply incredible!

But let us not forget that this type of thinking is directing research programs and health care programs, and is also somehow, shaping our view of the human being. It was interesting to notice that the researchers who are working with the Human Genome Project are now leaving simple genetic determinism because they are getting so much data and are becoming more and more aware of the enormous complications. It also becomes more plausible to speak of some particular gene accounting for whichever behavior is chosen. But the popularization of current genetic thinking and clinical genetics is still quite deterministic.

Medicine in the Next Century

This topic I would like to develop a bit further. Before birth it is possible to have a screening, to have a diagnosis of quality, but it is also possible later on during the lifetime to have genetic diagnoses. And this may well change our methods of health care and the mentality toward health care as a whole.

At the moment in the Netherlands, we have on average about 60 years of healthy life. Thereafter come the first symptoms of disease when we may go to a doctor and he produces a diagnosis. He gives first one treatment and if necessary other treatments. If a treatment does not work, for instance with cancer, we will be treated otherwise to postpone death. Yet after some time, if the situation becomes life-threatening, we may try a life-saving intervention which may or may not succeed. If not, we die. So at the moment, present health care is directed toward treating and caring for people with health problems to overcome the illness in order to get them well.

However, new developments and possibilities for detecting risks and possible risk factors, are going on. They identify genes and human genetic predispositions that would indicate what our risks are and what genetic possibilities we have of protection against disease, or facilitating disease. So, imagine what could be the emphasis of health care in 2000 or 2005, just after the DNA sequencing has been finished?

Even at an early age, right after or maybe before birth using pre-implantation diagnoses, all kinds of diagnoses will be possible to detect whether there is a risk developing for a certain disease. The next step is to try to control these risk factors or determinants for diseases. All this is done in an attempt to improve life-expectancy. This would imply that health care could become management of health, not care for the ill, but determining help for the healthy to manage their health.

In this respect, it is possible that every disease would then be, in a sense, a failure of health management. Maybe I am exaggerating and emphasizing a certain point that may never become true in this way, but this sort of development could lead to a kind of criminalization of disease. I put that very strongly and I realize that, but it is to make the point clear.

In essence, it could become your fault, if you have not taken ‘proper’ measures either before birth or after, or have not taken tests to control your health situation. It then becomes your own fault if you fall ill. I don’t say that this will happen in the next ten years, but I do think that this could be one consequence of risk factor thinking and knowledge of genetic factors that do influence, to a certain extent, the health condition. I think it is very important to continue to emphasize that health care should always be in the primary place, a care of people with health problems.

Of course, I am not against prevention nor living wisely and practicing good health methods. But a sociologist at a genetics conference two weeks ago who was doing research on how people deal with these issues, said: “People are talking now of cancer genes, a breast cancer gene for women especially, or a gene for cancer of the colon, as cause for cancer. But only five percent of breast cancer is genetic. Just imagine how much cancer is caused by smoking, which is of a completely different origin (behavior). But we don’t talk about that aspect any longer. We now talk about ‘the cancer gene’.”

It is interesting that one of his statements dealt with how we focus on technical, genetic causes by which we think we can control disease without giving a thought to having to change our lifestyle (quit smoking); without having to make personal decisions about our own health.

Somatic Cell Gene Therapy

An example of genetic manipulation in a direct sense, is Somatic Cell Gene Therapy. For instance, in Sickle-Cell Anemia, one form of a blood disease, the cells would be taken out of the patient and treated in vitro with the correct gene. Then the correct gene would be introduced into the stem cells of the blood cells in the patient’s bone marrow. These modified cells would then be transferred back into the same patient in the hope that now they could produce healthy cells that are able to produce healthy blood. That would be one treatment for this blood disease.

In the beginning of the 1980’s, very hopeful publications about the possibility of gene therapy were published. But fifteen years later and after a lot of research, no patient had been cured of any genetic disease by gene therapy. I am not saying that people should not continue. I don’t think it is ethically problematic in itself and I don’t object to it ethically. But I do think that again the concept for, at least, the treatment of genetic disease is still starting from too much genetic determinism.

Too often, we are given the idea of manipulating genes as a kind of ‘Legos’ (children’s toy building blocks) as if genes were building blocks and one could be taken out and replaced by another. Such replacement is only done in one organ, but genetic disorders are in all the cells and are systemic. I mention this as a development. People now think that the new understanding of genetic disorders and genetic codes will probably be easier to treat pharmaceutically than with gene therapy. That could be so, I don’t know.

Germ-Line Gene Therapy

In mice, during the development of the embryo from the inner cell mass of the blastocyst (that will grow out to the individual) researchers have taken out cells and developed these in so-called Embryonic Stem Cells. If you take these Embryonic Stem Cells you can modify and manipulate them in vitro; for instance, add a gene or any kind of DNA and then put them back or inject them into another blastocyst. Then this embryo will consist of two types of cells: the cells of the original but also the genetically modified stem cells that have been injected and will develop into certain tissues of that mouse. In this way, it is in principle possible if the cells that are injected develop into the sexual organs (what is still a matter of chance) that produce the gametes, to have a Germ-Line Gene Therapy. By this means, the germ-line of the individual is changed.

What people now want to do in the Netherlands is not this. The scientists who made the recent proposal for embryo research want to exclude this, but the next generation of researchers may not. They have now proposed to develop Embryonic Stem Cells from human embryos.

Why? These Embryonic Stem Cells that develop from the inner cell mass are Pluri-Potent, they cannot develop into a new embryo altogether, but in principle they can develop into any tissue of an embryo. Scientists now want to take these Embryo Stem Cells to make a kind of bank -- a continuous tissue culture of these Embryonic Stem Cells. This is very interesting from a purely scientific point of view, because with these cells you can study the differentiation process and the embryonic development of the human being.

By the way, you could do it to a large extent with animal embryos. They think that they could use such a bank of Embryo Stem Cells and then have these develop by tissue culture into specific tissues, which could replace organs and could be transplanted into people who have deficiencies of certain organs. So we wouldn’t need so many organs.

This procedure would not be legal if the law for embryo experimentation that is being discussed right now in parliament, would be accepted. But even before it is discussed, researchers already claim that it should be broadened in its scope. That also scientific investigations and research should be possible with human embryos, the so-called IVF-surplus embryos, in order to develop these tissue cultures of Embryonic Stem Cells.

Cloning

Let us develop this point further. Cloning has been tried with husbandry animals like mice. With mice, it was possible to develop Embryonic Stem Cells, however, it appeared to be very difficult with cows and sheep. That is why the people in Scotland did the cloning. If people try to make Embryonic Stem Cells from human embryos and if it would not be possible, then it could be a temptation to do human cloning.

Those who are proposing to do culture Embryonic Stem Cells, I am sure, do not want to do any genetic modification in the germ. But after one more generation, there may be future researchers who will say, “It would be very interesting to have the genetic modification, the introduction of the correct gene, and the disease treated if everything goes well.”

Conclusion

So we see there is a lot of development and discussion and I think that we will still have a number of debates in the Netherlands, and probably in other countries as well, about this proposal of embryo experimentation. Because it would be clearly a straight forward instrumentality of human life, it should be opposed. This step would probably provoke further steps of genetic manipulation of human beings. Then we really don’t know what we are doing and we should never attempt it.

Dr.ir. H. Jochemsen

Director - Prof.dr. G.A. Lindeboom Instituut voor Medische Ethiek

This article is an edited version of the spoken text at the conference; it still bears the marks of a lecture.