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Dr. Tha will heal patients

No more surgeons' scalpels and pharmacists' medicines. The body just needs help from the scientists, who will stimulate the tools it uses to repair itself - cells and chemical signals

by Tamara Traubman
Wednesday, April 18, 2001

Dr. Tha will heal patients
No more surgeons' scalpels and pharmacists' medicines. The body just needs help from the scientists, who will stimulate the tools it uses to repair itself - cells and chemical signals

Future generations will surely be shocked when they read in the history books about the methods used in today's medicine, which rely mainly on poisons
and aggressive surgeries. A scientific understanding that is taking shape now may be much more similar to the healing methods of the future.

According to the supporters of the new concept, medicine will not be based on a scalpel and poisons, but on them
Tools the body uses to repair itself - cells and chemical signals. A disease is actually a cell that has been damaged and stopped functioning properly, and all the knowledge needed to repair diseases is found within the cells themselves. What is needed, according to

The concept in question is to mobilize the body's healing power and discover how to learn to heal itself.

"Each one of us thinks he has a cure for cancer," says Eduardo Materni, professor of developmental biology at the Hebrew University. In his examination he discovered that over 50 articles were published in the scientific press dealing with
in new cancer drugs. "And yet", he says, "except for a few specific cases, in terms of healing and in terms of understanding the system - we actually made very little progress.

"We have to abandon the hope of finding a cure in a bottle," continues Prof. Materni. "It is an illusion to think that a single molecule can really cure complex diseases such as cancer, diabetes, heart disease or schizophrenia. It is impossible to put all the vast knowledge that exists in one cell into a bottle or a pill."

The body's 100 trillion cells control themselves by exchanging chemical signals. The cells secrete chemical signals to influence their behavior

of other cells, and they receive signals through receptors embedded on their surface. Such signals tell the cells of an embryo in the womb to start turning into a brain cell or a muscle cell. Therefore, by providing the appropriate signals, it may be possible to regenerate the brain cell pool in the brains of Alzheimer's or Parkinson's patients, create insulin-secreting cells for diabetics or regenerate heart cells in the bodies of people suffering from heart failure.

Medicine began to use the body's self-healing power decades ago. Vaccines, for example, are one of the oldest and most effective tools for this. But the new concept of healing - known as cellular healing - is not just a continuation of this approach. Most supporters of cellular healing aim at a higher goal: not only maintaining the functioning of broken systems in the body at a level that allows the patient to continue living, but their maximum improvement, until they are as good as new.

Current medical treatment, especially that given for the degenerative diseases of old age, usually helps patients to continue living with heart failure or arthritis. But proponents of cellular healing hope that with the help of stem cells and appropriate signals, it will be possible to replace the worn out or damaged tissue with new tissue.

The cells act almost as independent entities that build themselves when given the proper signals. "I doubt if anyone will ever be able to figure out how to produce a cell based on the accumulated anatomical knowledge," says Prof. Metrani, "but on the other hand, there is a much greater chance of discovering which stem cell signals are needed to become a heart cell."

To this end, say some supporters of the method, the accepted way of thinking in chemistry and molecular biology must be changed. The scientific literature is full of reports of researchers who have identified hundreds and thousands of genes involved in the development of diseases or characterized thousands of the molecular signs present in cancer cells. Instead of trying to identify the role of each of the approximately 30 genes in the human genome and how their various combinations determine the cell's fate (their number may be seven digits long) - it is better to identify the chemical signals that the cells exchange among themselves, numbering several hundred.

Embryonic stem cells

The proteins that send signals to the cells play a vital role in directing the development of the body from a fertilized egg cell to a complete body, made up of a multitude of different types of cells. One of the focuses of research in cellular healing is embryonic stem cells. These cells are present in embryos at a very early stage. All the tissues of the body and its organs are formed from them. They can be compared to living clay from which the body is shaped and repairs itself over the years.

Like clay, stem cells have no special properties. But they can change their shape and become blood, skin, bone, brain or any other tissue in the body. They have the amazing ability to renew themselves. Except for cancer cells, all other adult cells in the body do not have this ability. When stem cells divide, they usually produce one adult cell and one stem cell, thus maintaining their number. Mature cells produce cells that are identical to themselves and can divide a limited number of times, if at all.

Today, people in need of organ transplants have to hope that a suitable donor will be found. Even when a donor is found, they must take drugs for the rest of their lives to prevent their immune system from rejecting the foreign transplant. The cloning of Dolly the sheep and other animals raised a new possibility: to produce a personal repository of organs for transplantation. This is still only a possibility and it is not clear if the method will be successful, because no one has yet tried to apply it to humans. The basic idea is to take a cell from a person in need of a transplant, insert its nucleus into an egg whose nucleus has been removed and create an embryo that will be a genetic twin of that person. When the embryo reaches the age of one week (at this age it looks like a microscopic block of cells), embryonic stem cells will be harvested from it. These cells will be able to be sorted into the cells needed by the patient and transplanted without his body rejecting the transplant.

The discovery of the code

But in order to succeed in reproducing in the laboratory the journey that the cell goes through from being an embryonic stem cell to becoming an adult cell, one must first identify the chemical signals that direct this journey. Scientists have already managed to induce mouse embryonic stem cells to become neurons. The first step in human embryonic stem cells was made last April, when Dr. Benjamin Rubinoff from the Institute of Genetic Therapy at Hadassah Hospital in Jerusalem, and his colleagues from Monash University in Australia and the National University of Singapore, turned such cells into nerve cells. Last November, Prof. Nissim Benvanisti from the Hebrew University and his colleagues from Harvard succeeded in causing human embryonic stem cells to differentiate into a variety of types including bone, skin and nerve. Both teams are now focused on finding combinations of factors that will direct cell differentiation in a more efficient way.

Dr. Rubinoff points out that extensive research is needed before the cells can be transplanted into humans. "We may have to take precautions in case the transplanted cells produce cancerous tumors or unwanted tissues. I think we will have to program the cells in such a way that it will be possible to order them to commit suicide if they start to behave in an undesirable way," says Rubinoff. For example, it will be possible to "equip them with suicide software, which will be made of genes responsible for apoptosis (the cell's self-suicide mechanism). These genes will remain inactive until we decide to activate them with a drug or some substance, which will order them to start working, thus destroying the transplanted cells."

Mature stem cells

As soon as the body is formed, the embryonic stem cells disappear, leaving behind a few descendants that will keep the body in good condition for the years of its life. Until recently, it was thought that these offspring, called mature stem cells, could not become all types of cells, but this belief was disproved after such cells were discovered in almost every type of tissue. Clear evidence of this was published six months ago in the scientific journal "Science" In this report, researchers from the Karolinska Institute in Sweden described how they were able to induce mature stem cells from the nervous system to transform into a variety of other mature cells, including blood, heart, liver and skin cells. The meaning of the research is that all the mechanisms that guide the formation of the blood cells, the heart, the liver and all the other cells created in the experiment are found in the set of cells - and the interrelationships between them - of those organs themselves.
"Today it is clear that in the body itself, in every organ, there is a reservoir of stem cells that exists and actually goes with us all our lives, and has the potential to differentiate in the event of damage," says Dr. Eilat Hayut, head of the stem cell project at the Israeli-American biotechnology company QBI. "The problem is Apparently their quantity is not enough. If we could somehow find factors that would both cause them to multiply and cause them to differentiate, I think this would be one of the most advanced healing methods."

QBI carries out several projects aimed at identifying the proteins that control cell proliferation and differentiation into the various cell types. After such proteins are found, the arduous work of characterizing them and studying their function is required. In order to focus in advance only on the proteins of interest, the company developed a method in which DNA segments that neutralize the activity of genes are inserted into the cells. When such a DNA segment inhibits a gene necessary for differentiation processes, the cell with that segment will disappear from the cell culture that has differentiated into a certain cell type (for example, a nerve cell), and the segment itself will also disappear. If the DNA segment inhibits a gene that inhibits differentiation, that cell type will be more strongly represented in the sorted population, and so will the DNA segment. To identify the DNA segments, the company uses a technology called "DNA chips". The chips are glass plates on which the DNA segments are "printed". On each chip, the researchers print many thousands of DNA segments, and at the end of the process, laser detectors read all the information on the chip.

In this way, the researchers receive information not only about differences in the genes expressed in embryonic cells and adult cells, but also information about the role played by the proteins (encoded in the genes) during cell culture and differentiation. According to Dr. Paz Einat, the chief scientist of QBI, the company has already discovered several dozen new proteins using this method, and is now investigating their roles in cell proliferation and differentiation.

The flexibility of mature tissues was demonstrated in an experiment conducted by Dr. Sara Farber and her colleagues from Sheba Hospital. Dr. Farber used the flexibility of the liver cells to cure mice suffering from a disease similar to juvenile diabetes. She inserted the PDX1 gene into the livers of the mice. This gene contains instructions for the production of a protein essential for regulating the insulin gene and it overpowers the expression of many other genes in the pancreas. Its vital role in the development of the pancreas was proven six years ago when researchers created mouse embryos without this gene - they were born without a pancreas.

The signals sent by the PDX1 protein were so strong that a small group of liver cells abandoned their original function and started producing insulin. "It not only stimulated the insulin gene, but also an entire system that processes insulin and regulates its function," says Dr. Farber.

Inserting the insulin gene into the pancreas of a juvenile diabetic is not expected to be beneficial, because the disease destroys not only the cells that produce insulin but also the other pancreatic cells around them, which are necessary for the normal functioning of the pancreas. That is why introducing the insulin gene will not be enough, because the entire supporting environment is damaged.

The advantage of stem cells is that the experiments carried out on them are not accompanied by the ethical problems associated with experiments on embryonic stem cells. The ethical problem arises from the fact that the embryonic cells are extracted from frozen embryos left after IVF treatments. After they were first isolated in 1998, scientists working in government laboratories were prohibited from studying them in some countries. In the United States, for example,
The ban was only lifted in August after prolonged opposition from abortion opponents. In Israel, there are no regulations prohibiting embryonic stem cell research, nor are there any regulations regulating this research (although all these experiments must be approved
in the national Helsinki committee).

How close is the cure? no one knows Reports of experimental results continue to be received all the time, but the results are mixed and it is too early to judge. See for example the attempt to develop cellular therapy for Parkinson's disease.

Earlier this month, Harvard University researchers reported that embryonic stem cells transplanted into the brains of rats and mice grew into the type of brain cells that degenerate in Parkinson's disease and even formed connections with neighboring brain cells. The following day, the New England Journal of Medicine published the findings of a study in which fetal nerve cells, from aborted fetuses, were transplanted into the brains of 20 Parkinson's patients. The results were mixed: in some patients, the treatment resulted in some relief in the severity of the symptoms of the disease, including the involuntary tremors. But in others the symptoms actually worsened. In a commentary article accompanying the study it was stated,
Because a large part of the transplanted cells did not survive in the brain and because the researchers used cultured cells and not fresh cells. The researchers may not have provided the cells in culture with the environment with the appropriate signals for them to continue functioning inside the body as well.

"The impression that is received today is that we can take a cell, whether it is an adult stem cell or an embryonic stem cell, and play with its fate," says Dr. Rubinoff. "The same factors will be used in both cases, because eventually this information will come together and lead to what we call the cellular revolution."

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