Comprehensive coverage

The genetic revolution

Seven years after the "Human Genome" project was launched, it turns out that the technology is almost complete and from now on, new discoveries will quickly appear, such as the adventure garden, which was recently revealed. Prof. Doron Lantz, head of the Israeli Center for Genome Research, is trying to reassure those who are worried

Noam Berkowitz, Haaretz, 9.1.98

Many years have passed since theoretical science managed to amaze the world with a sensational discovery. But all these years were just a time-out before the new scientific revolution that was coming: "The Human Genome Project". Seven years ago, the American government announced this project, a global research operation with an investment of three billion dollars in 15 years. Since then news trickles from time to time about a new garden that has been discovered. One of the latest discoveries: the adventure garden. This is a huge project that combines thousands of researchers in many countries in the world, including Israel. Because of its dimensions, some tend to liken it to the American space project or the Manhattan Project that produced the nuclear bomb. A publication on behalf of the Weizmann Institute needed the phrase "brave new world" to describe the reality after the operation.
Prof. Doron Lantz, 49, from the Department of Molecular Genetics at the Weizmann Institute, head of the Israeli Center for Genome Research, is well familiar with Aldous Huxley's book describing a programmed and gloomy future world whose inhabitants are genetically modified. According to Lantz, the genome project heralds a world completely different from Huxley's. Lantz is well aware of the concerns, the talk about the inherent dangers in controlling the mechanisms of life. He himself is not afraid at all.

In his eyes, all this talk is the result of ignorance and prejudice. What is the "human genome"? This is all the genetic information contained in the DNA molecules found in every cell of the body. The exact number of genes is not yet known, it is estimated to be at least 80 thousand. Prof. Lantz wants to emphasize that whatever the number of genes - they are all found in every person. You and I have exactly the same eighty or one hundred thousand genes. The difference between you and me in everything we differ in - the shape of the nose, the color of the eyes, intelligence, mental tendencies, tendencies to like certain foods or certain smells - is due to the fact that we have different versions of a certain number of genes

like a guided missile

In the future, each person's personal genome map will be a primary diagnostic tool in any medical treatment, and also a necessary tool for family planning or, in contrast, planning a professional career and an educational path. The first, most obvious benefit is in the field of medicine. Economists predict that the post-genomic drug market will reach, by 2010, a turnover of 45 billion dollars per year. "Every disease, whether genetic or 'normal', such as cancer or hypertension - ultimately results from a certain defect in the genes," said Doron Lantz.
"In about 5000 cases, the problem can be focused on a single protein. Diseases such as cystic fibrosis, color blindness, hemophilia, Tay-Sachs, muscular dystrophy, all result from a very specific defect in a single gene and are called monogenic diseases. The project has already identified the genes of several hundred of them, and when completed will identify them all. In each of the cases, a very wide opening was opened for the development of new drugs, in the biomedical and biotechnological industry.

How will these drugs fundamentally differ from the old drugs?

So far, drugs have been developed mainly by trial and error. They produced thousands of substances and tested their effects and in the end found that one of them showed a certain medical activity, but they could not determine in advance what it would be. With the new method, you find the gene, find out what is defective and design a drug that will act like a guided missile that will bind to the defective site in the protein and change its structure a little in a way that corrects the defect. This is called 'computer aided drug design' and as more genes are discovered, a huge gate to this field opens. One can understand how rare it is that such a process happens by chance, and that an old generation drug would bind with perfect precision, without side effects.

Why are there no such drugs on the market yet?

In many cases, a single-gene disease appears in many different mutations. For example, cystic fibrosis, which is the most common genetic disease in humans, is caused by a defect in the protein found on the cell membrane. The result is breathing problems, fluid secretions in the lung lining and more. All this results from a change of one letter in the DNA, but there are more than a hundred different versions of mistakes in the population. It is possible that a different drug is needed for each case, and the pharmaceutical companies are currently checking what can be done.

What are the options for preventive treatment?

This is, for example, gene healing, which is based on supplying a normal gene to the body, instead of the defective gene. Let's take muscular dystrophy as an example, which is a disease studied at the Weizmann Institute. It is known that a protein in which a problem causes the disease is found in the walls of the muscle cells. When this protein is damaged, the muscle cells do not connect properly and atrophy results. There are today the first attempts to make the muscles absorb the normal gene and then they will start translating it into a normal protein

Is it possible to push a normal gene into each of the millions of cells in the muscle?
It is possible to prevent it from entering brain cells as well, for example in many cases one thinks about the transport of genes using viruses. All known viruses, from rhinitis to AIDS, their whole world is sticking to target cells and injecting their DNA into the cell to force it to produce more viruses. They have an ability to recognize and some of them stick specifically to certain cells and not others.
In gene therapy, the ability of the virus to harm is sterilized, and the normal gene is planted in its DNA.

It sounds a bit awkward…

There are also other methods. Basically, you can inject DNA in a special capsule and direct it to the desired cells

Have there been any successes?

Process control measures are being developed today. I'm not saying it will happen tomorrow, but it is developing and I believe that by the end of the project, good control measures will be developed

Is the child spoiled? made new

But there is a much simpler way of preventive treatment", Lentz continues, in the spirit of the famous joke 'Is the child spoiled? It's alright. We will become new'. That is: to make a perfect person, genetic therapy is not necessary, but a prenatal diagnosis. Remember, each chromosome appears in two copies, and most genetic diseases only appear when both copies are damaged. Conclusion: Most genetically damaged children are born with a statistic of one in four - the chance of receiving a defective gene from both the father and the mother. "There will be kits that will allow testing of all 5000 genetic diseases and all their variants, and spouses will be able to find out which genetic diseases they may pass on to their children.
These kits, called 'DNA chips', are under really rapid development. This is one of the fronts of the research, among other things also here at the Weizmann Institute

What will couples do if they find out that they are going to bequeath a genetic disease to their children?

Genetic tests are already used today, in connection with those diseases that have already been discovered. In the ultra-Orthodox religious sector, couples are sometimes advised to find another match, without explaining exactly why. Of course, such an approach is not suitable for the general public. 99 percent of people won't be willing to leave their sweetheart just because he has a defective gene. That's why amniotic fluid tests are done today

And in the future?

When there are kits that test all genetic diseases, things will go like this, in my estimation: couples who are in a risk group will be tested immediately in the first weeks of pregnancy, when the fetus is tiny and miscarriage does not cause problems. If it turns out that the fetus carries both defective genes, an abortion will be performed. These will be the routine measures, because gene therapy will be very expensive and obviously will not always work. As you guessed, it will be very complicated to insert normal DNA into all the cells. Some will be absorbed and some will not, and then the healing will not be perfect.

Why not try IVF in such a case?

it's a problem. There are 5000 genetic diseases and lots of people will need this service. In my opinion, abortion is the most logical way, especially in a population that is ready to have an abortion and especially in a very early stage of pregnancy. It is much simpler to let nature take its course.

Will the genetic revolution provide long-awaited cures for diseases such as cancer, Alzheimer's and allergies?

This question takes us to the field of polygenic diseases. If you check in hospitals, you will find that the typical inpatients are people with multigenic diseases. The classic genetic diseases result from a defect in a single gene, they are relatively easy to identify, it is easy to isolate the gene and it is easy to develop a cure strategy. In multigenic diseases, which I call combinatorial diseases, it proceeds like in Toto form. You get a disease if you caught a combination of numbers. Let's say there are 15 different genes and each has 3 different natural forms. No single defect causes disease, but if you are lucky enough to catch 12-13 you have a disease, 14-15 a serious disease. The genome project will make it possible to discover all the genes and also all the forms of each gene. When we know all this we will be able to find out what is the combination of genes that causes Alzheimer's, mental illness, blood pressure, cancer, heart disease and alcoholism.

And can we cure these diseases?

First of all we can lower the level of risk. A major part of any treatment is diagnosis. For example, a certain tendency to mental illness is sometimes strengthened by improper treatment. Today, dozens of different diseases are probably classified as 'schizophrenia'. If we knew all the nuances, we would know how to give a much more effective preventive treatment. Besides reducing the risk, we will be able to develop much more sophisticated drugs that will treat the various combinations.

Fast, cheap, accurate

What else will the genomic revolution be useful for, except in the field of medicine?

Farming will be much more accurate. It will be easier to identify plant diseases and create improved plants. This is a technique that has existed for a long time, in plants and animals. Until today they did it by trial and error, by hybrids. At the end of the project or even before it will be possible to do this specifically, to penetrate the exact place where you want to improve. For example, a peach is sweeter but also more durable, not durable and tasteless like it is today.

Some consumers shy away from genetically modified products as a result of superstitions. A peach that has undergone genetic engineering is no different from a peach that has undergone ten generations of hybridization. It's just faster, cheaper and more accurate. True, in many European countries, genetically modified plants are opposed, and this, in my opinion, is a great degree of ignorance. I hope that intelligent people will not be swayed by these objections.

Why not produce improved humans?

In humans this will not be done. It was decided not to move forward in this direction, at least for now. We will not open new humans. This is a social decision, similar to limiting the license to carry a weapon or limiting the speed of travel on the roads. The whole world has decided to avoid changing the genome at the sperm or egg level, avoiding thinking about how to create a taller, blue-eyed, stronger and smarter person.

What will parents do to a fetus with a 50% chance of getting cancer?

This is a moral, ethical question, and I have no special status to answer it. I can tell you how I personally approach the problem. When there is a chance of having breast cancer, it is recommended that a woman be examined more often, in order to advance detection and facilitate treatment, if required. A person who knows he has a tendency to skin cancer will spend much less time in the sun. A person who has a congenital predisposition to lung cancer will feel much more determined to quit smoking or not to start at all. We will have a whole collection of guiding aids that will tell us what to do and how to behave in order to reduce the chance of an outbreak of disease.

A machine can choose

Does the genetic revolution hold that the influence of the environment on a person's development and health is negligible?

Not necessarily, clarifies Prof. Lantz. "Even the most rigid genetic diseases can have an impact on the environment. In polygenic diseases the environment has much more influence. A different combination of genes can be expressed in a different way, according to the environmental conditions

Today there is a widespread opinion that diseases such as cancer, blood pressure and ulcers are mainly caused by environmental conditions, because of a certain lifestyle. No one denies that there is an increased chance of the diseases you mentioned when leading a certain lifestyle. The right thing is to find out all the other parameters to incorporate them into the lifestyle. It may turn out that an ulcer is caused by irritation and nerves, but only in 15% of the cases, and then we can solve the problem with appropriate drugs in most cases. We would still advise people to get angry less, but by just telling them not to get angry, you solve almost nothing, or worse: you make people who had fun getting angry, lead a crowded lifestyle until the end of their lives without any need.

Will we discover that there is a group of genes that dictates the state of mind, behavior or character?

for sure. Recently, a gene was discovered that is known as the "Gen for Adventurers", but even before the genome project we knew that certain mental traits such as intelligence, haste, courage, lack of caring, have a hereditary element. Before we didn't do anything with it and I predict that in the future we won't actually do anything special with the new genes that will be discovered in this area.

The project will finally reveal what is the hereditary part of the character, compared to the free part, which is shaped by the environment?

The answer is yes. It is clear today that although a great deal of what exists in the body exists in the genes, and there are also many elements that are determined by the environment. For example height. It is quite clear that there is a gene that determines height, but nutrition has an effect. I will risk the following statement: today we create an approximate but defined line of demarcation between genetic influence and environmental influence, and it is very possible that more and more plots that were previously thought to belong to the environment will move to the area determined by the genes. You mentioned sexual orientation. It was once thought that it was only environmental, today they have not yet discovered a gene for homosexuality but only an indication that such a gene exists. As the genome project progresses, perhaps more will be revealed, and perhaps we will know that there are more genetic sides to the phenomenon. I don't see a fundamental difference in the way in which the human body will be perceived in our eyes at the end of the process. The human body was and will continue to be a wonderful machine. Other machines that are in different environmental conditions also differ from each other.

If it is proven in the end that man is after all just a machine, people might change their perception of themselves, or worse than that - their perception of others?

The human body is a machine, but that is no reason to underestimate it. There is no place to lighten the value of life or detract from the sanctity of life.

It is hard to assume that if a group of genes determining the structure of personality is discovered, it will not have a profound effect on our perception of personality?

Such a group will emerge, but it will be very complex and its expression will be very multifaceted. For example intelligence. To know if it is inherited or not, the genome project is not needed. You take identical twins, give them IQ tests and find that between pairs of identical twins there is a much greater correlation than between non-identical twins, or siblings or just people. This means absolutely clearly that there is a genetic element to intelligence. With the completion of the genome project, when we can easily and quickly test the genomes of large populations, we may discover, surprisingly, that there is a correlation between some genes and between different versions of intelligence. Then we will ask what they do in the brain and we will discover strange things, for example that one of them is responsible for a certain protein, which glues brain cells to each other, and one is responsible for the fact that brain cells in the fetus divide quickly or slowly, and when we understand more we may discover that the brain cells of an especially intelligent person have a slightly different shape. "We will find out exactly what the molecular basis of intelligence is, but we will find that phenomena like intelligence have a lot of 'noise'. That is, in some cases, intelligent people will be discovered who do not carry the classic genome model of an intelligent person. Then we will explain and say - here is a man who was born with the genetic ability for an IQ of only one hundred, but his parents did not give him rest and kicked him in encyclopedias since he was two years old and his IQ increased.

It seems that the completion of the project will give a decisive blow to the followers of the ancient idea that man is not only a body, but also a soul.

The debate about the essence of man did not start with the genome project and will not end there. True, now there will be much more objective evidence that the scientists are right, claiming that a large part of the so-called 'soul' is the result of genetics. But actually we already know that the brain is a chemical machine, we don't need genetics for that. The debate is between ignorant people, who are not ready to look reality in the face, or mystics who are not ready to accept reality as simple, and people who know reality. Everything we do is ultimately the result of something going on in the brain. There is no doubt at all that it is matter that produces the 'soul', the only question lies in the minds of people who ignore all science.

Is it insulting to know you're just a machine?

I can understand that it used to be considered insulting and irritating, but if you know that this wonderful thing we call the soul, if you will, is actually the result of a very complicated machine with many parts and with tremendous flexibility in the relationships between the parts, then you have to accept the reality. This should not change the relationship between the natural sciences and the humanities.

After the project ends, people will feel that they are actually machines, and it only seems to them sometimes that they have free will and choices?

Any machine exhibits phenomena that can be called 'free will', if it is complicated enough. To me, my Macintosh has a measure of free will, given its behavior. What is actually the alternative to perceiving ourselves as a machine? To say that there is a soul that we don't know what it is, and maybe it is something that comes out of the body, goes up to heaven or goes down to hell, and if you are an Indian is reincarnated later in the body of another animal? The idea that the existence of free will requires such stories about 'soul' is really ridiculous.

The word "nefesh" doesn't even exist in your vocabulary?

she exists I call 'soul' the collection of phenomena derived from the brain of the living body and the entire living body. After we discover all the genes and discover that everything is expected, the permission is still given. Because even if all the parts of the machine are predetermined, as a result of the tremendous wealth of possibilities and the tremendous wealth of the psychological ability to undergo change, and the enormous variety of environmental conditions - the end result is that a person has a degree of free will.

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