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stone conductor paper; Scissors Victory Stone; Bone marrow cell transplantation defeats cancer and AIDS

A bone marrow transplant that includes stem cells of the blood system in a patient suffering from both blood cancer and the HIV virus, succeeded, thanks to the resourcefulness of a researcher in Germany, to eliminate both diseases. Although this is not a suitable process for most AIDS patients, the researchers hope to gain new insights into the fight against HIV.

Bone marrow stem cells. Photo: Northwestern University
Bone marrow stem cells. Photo: Northwestern University

One morning, three years ago, Mr. X woke up with a coppery taste in his mouth. A quick check in front of the mirror revealed that his gums were bleeding badly. His doctors took blood samples and came to an unconventional, but very unequivocal diagnosis: Mr. X is unlucky at all. By the age of 40, he was infected with the HIV virus that causes AIDS, developed cancer in the bone marrow, reached a terminal condition and lives in Germany.

The positive side was that until the cancer started, the doctors were able to stop the spread of the virus in the body of X (whose real name is under medical confidentiality). In its early stages, the HIV virus usually works quietly underground: over a period of weeks to years, it spreads to all the white blood cells in the body. These cells protect us from infections, and as the virus kills more and more of them, the immune system weakens.

Those of us who did a degree in biology probably remember one of the first and simplest experiments in the laboratory, during which a petri dish is left open in room air for a short time. The plate contains a substrate rich in nutrients, which bacteria and fungi are able to utilize for their needs. It is enough to leave the plate open for several hours so that at least some bacterial and fungal spores fall into it and grow quickly. Within two weeks, the plate will look like a wild forest in miniature - mushroom circles and bacterial colonies will cover the substrate all over the plate.

Our body is like that plate: not only is it rich in nutrients, but we also breathe millions of bacteria and fungi into our lungs every day. The main reason why these tiny invaders cannot grow inside us lies in the active white blood cells, which constantly fight infections. Once the HIV virus kills a large part of the white blood cells, we are left naked from the protection provided by the immune system. The bacteria, fungi and viruses multiply without restraint, secrete toxins and steal the necessary nutrients for the body's cells. Under these conditions, it is clear why AIDS patients die soon after their immune system collapses.

Mr. X's only consolation was the fact that he lives in the Western world, where there are drugs against the virus. The drugs inhibit the spread of the virus from one white blood cell to another, thereby slowing down the rate of white blood cell death and the breakdown of the immune system. Currently, the drug cocktail is able to delay the breakdown for more than thirty years.

If there are drugs for HIV, why hasn't the virus gone from the world yet? The main problem is that the drugs have to be taken daily, and they are expensive. really expensive In order to gain twenty more years of life, the patients have to take the cocktail every day. The cost of this dubious pleasure, continued every day for twenty years, is estimated at $450,000 per patient. Patients who have comprehensive health insurance can afford such payments, but in developing countries like Africa there are almost no health funds that can offer the drugs to the public.

The second problem with the drugs is that they only inhibit the spread of the virus inside the body. They don't kill him. If the carrier has unprotected sex, he may still transmit the virus to his son or partner. This was Mr. X's life before he got cancer. He woke up every morning, took a pill, two or three, and went on with life as usual, while the drugs stop the spread of the virus.

It can be said that Mr. X's luck improved unexpectedly, when bone marrow cancer was discovered in his body. The bone marrow describes an area that exists in the center of the long bones, and it can be compared to the factory that produces the white blood cells. Because the cells are constantly dying in their fight against infections, the bone marrow makes new white blood cells as needed. Cancer in the bone marrow results in non-stop production of white blood cells, disrupting the ability of the bone marrow to also produce red blood cells and platelets. Without platelets, the blood cannot clot, which is why bone marrow cancer patients are especially vulnerable to bleeding.

We would think that a massive production of white blood cells would improve the condition of the immune system, but the opposite is true. Every complex machine contains a large number of parts: screws, gears, levers, pumps and more, all of which function with each other. Similarly, the immune system also consists of a large number of different white blood cells, each of which has a specific role. The cancer causes only one white blood cell to make many copies of itself, thereby disrupting the delicate balance and the whole machine - the immune system - collapses.

X's doctor, Dr. Gro Hutter, decided that only extremely drastic treatment had a chance of stopping the cancer. Hutter wanted to use a combination of radiation and extremely aggressive chemotherapy to kill all cancer cells in the body. In such medical treatment, the phrase "the operation was successful, the patient died" is often true, because it also results in the death of most of the patient's bone marrow cells. For this reason, new bone marrow cells obtained from donors must be transplanted immediately after radiation. The new cells are supposed to take the place of the dead bone marrow cells, and produce new white blood cells.

At this point, a particularly capricious thought occurred to Hutter's mind, that if he had come up with it during his medical studies, he certainly would not have received the diploma. Hutter knew that although the HIV virus needs to attach to the cell membrane in order to penetrate it, it is not able to easily get close to the cell membranes. Like mountain climbers, the virus needs grip points on the surface of the cell, to which it can attach itself and with which it will pull itself closer to the cell membrane. Such grip points are found, of course, only on the surface of the white blood cells that are vulnerable to the virus, and exist in the form of two proteins: CD4 and CCR5.

In his searches in the literature, Hutter discovered that some European residents have automatic protection against the virus. Studies conducted on these people, some of whom had unprotected homosexual intercourse with hundreds of partners, showed that they were not affected by the virus. These are actually human mutants. Although they are not able to shoot laser beams from their eyes, or fly in the air, their mutation will be much more useful than all of these, if the HIV virus becomes common in the population.

In that single percentage of the European population, the CCR5 protein, which serves as a grip for the virus, is not present on the surface of the white blood cells. Those lucky enough to have the same mutation are immune to most variants of the HIV virus. Even if the virus penetrates his body, it is not able to effectively infect the white blood cells, and therefore it is also unable to reproduce.

"If we transplant bone marrow cells with the HIV-immune mutation," Hutter said to himself, "the bone marrow will surely produce white blood cells with the same mutation, which will be immune to the virus!"

When the time came for the bone marrow transplant, the doctor tested bone marrow samples from eighty possible donors, hoping that one of them would have the desired mutation. In the 61st sample he found what he was looking for: cells lacking the CCR5 protein. These were the same cells he implanted in Mr. X, and now he can only cross his fingers and hope that X does not die from the transplant itself, which kills up to 30 percent of patients.

This was the point where X's bad luck gave a sharp break and did a complete U-turn.

Today, two years after the transplant, there is no trace of the cancer cells in Mr. X's body. The aggressive radiation and chemotherapy managed to kill all the cancer cells. The transplant also went well: the new bone marrow cells were absorbed by the body and began to produce new, healthy white blood cells.

And what about the virus? Immediately after the transplant, Mr. X stopped taking the drugs that suppress the virus, due to the fear that they would also damage the sensitive bone marrow cells. To this day, the virus has yet to break out again in X's body.

After the transplant, the virus suddenly found itself in a very different living environment than it was used to. If in the past he could attack and infect many white blood cells, now all white blood cells are sealed to him, because they all lack the CCR5 protein. He had effectively lost his hold on them, and could not penetrate them. Today, two years after the transplant, it is still not possible to detect the virus in samples taken from the blood and other tissues.

Is it possible to adopt the bone marrow transplant as a way to treat AIDS? Although the treatment is possible in principle, it is not a practical solution. Such a transplant is an expensive medical procedure with a large number of possible complications. Even if the transplant is successful, the patient will have to take drugs that suppress the immune system for the rest of his life, so that the body does not reject the transplanted cells.

Another way of applying the lessons is in genetic engineering of the bone marrow cells of HIV patients. Already today, viruses are used to insert new genes into cells, or to paralyze and cut existing genes. In 2000, an experiment was conducted during which viruses were used that 'injected' a new gene into the bone marrow cells of ten bubble children. These children lacked a certain gene, without which the bone marrow cells cannot produce white blood cells. The gene injected into the cells completed the deficiency, and the bone marrow cells were restored and managed to create an effective and healthy immune system. It is possible that in a similar way it is possible to use viruses that can reach the bone marrow cells and disable the gene necessary for the production of CCR5.

possible? Probably yes, and even in the near future, but one must be careful of the possible and problematic consequences of the technique. Of the ten bubble children who participated in the experiment, four developed bone marrow cancer in the years after the experiment. The cancer appeared because the new gene was inserted near an existing gene, disrupting its way of working. Since that experiment, the scientific community has decided that it is necessary to reach a more complete understanding of the viral infection process, before using it for genetic engineering in humans.

Where does X's story end? As of today, the virus has not yet been found again in his body tissues, despite repeated routine tests. At the same time, most experts do not believe that the renewed immune system was able to eliminate the virus from the body. Cases are known in the professional literature where the HIV virus managed to find a hiding place within an unknown population of cells within the body, and in this way managed to survive even without staying inside the white blood cells. The consensus is that the virus is still hiding in X's body, but is unable to cause a total infection of the mutant white blood cells. Although the virus's sting has been neutralized, the danger remains, because under certain conditions the HIV virus can undergo a mutation that allows it to infect even cells without CCR5. In this case, the mutant cells will be exposed to infection by the virus, and the disease will break out again.

The knowledge X imparted to medical science is priceless, and may help develop treatments for other AIDS patients. He himself continues to live his life without taking the anti-HIV drugs, but always aware of the presence of the foreign invader in his body. He is unable to forget that the virions are waiting for the moment of fitness - for that one mutation that will allow them to gain the upper hand in the fight against the immune system. But what can be done? As Louis Aragon said, "Life is full of thorns, but it's life after all." All that is left is to hope that X will continue to live a long life, and the legacy of the care he demonstrated on his body will help in its various derivatives in many others.

18 תגובות

  1. someone something:
    The answer you gave was already given before.

  2. The topic is important and fascinating and the article - as usual - is fluid and pleasant to read.
    In the latest issue of Scientific American in Hebrew there is a series of exhaustive articles on all the knowledge that exists on the subject, but it seems to me that Roy mentioned all the important things that appear there.
    The main story about the man who recovered from the disease does not appear there - probably because these are articles that were translated (with a delay) from the English edition in which the story had not yet been published.
    This story appeared about a month ago in Haaretz newspaper (but in a much less in-depth form than it appeared here).

  3. I agree the whole thing is vague, but that's the information I have. I tend to believe that these are not white blood cells that survived the radiations, because there is evidence that even people who lost all their white blood cells to the virus, continued to be carriers of the virus.

    Apparently these are target cells that are still unknown to science. And again, the matter is indeed ambiguous, but this is the current knowledge.

  4. What are those "undetected cells"?

    White blood cells that survived the radiation with the virus in them?
    If so, then the chance of re-infection (by mutation) is limited in time (until the infected cells die from the virus).

    Or what are these target cells unknown to science?
    The matter is very vague

  5. Thanks for the compliments. I'm glad you enjoyed the article.

    cool responder,

    The answer to the first question is that X's immune system has not yet collapsed. The anti-HIV drugs inhibited the spread of the virus in the body and thus did not allow it to kill the white blood cells.

    Since radiation and chemotherapy destroy the bone marrow recipient's immune system, there is no need to suppress their immune system. Surprisingly, it turns out that precisely the transplanted bone marrow may attack the new body, because the cells it produces do not necessarily recognize some of the new tissues, to which they are exposed for the first time. This is why, even in a bone marrow transplant, drugs that suppress the immune system must be taken.

    straw man,

    The virions (the units of the virus) are probably in cells that have not yet been located. Those cells may continue to produce new virions and release them into the body. If mutations occur in the virion production process, they may pass them on.

  6. "Waiting for the hour of fitness - for that one mutation that will allow them to win the upper hand in the fight against the immune system"

    Wait, to mutate they have to replicate. But they said they are unable to attack Mr. X so how can they mutate inside his body?

  7. Great write up! I especially liked "Mr. X has no luck at all […] has reached a terminal condition and lives in Germany."

    Lami Bachar: As far as I understand, at the beginning of the spread of AIDS, in the 70s and 80s, most of the infected were homosexuals. I assume that it is about that time, and the aforementioned people had unprotected sex because the existence of the virus was not yet known to the public.

  8. Not a new idea, I saw a movie over 5 years ago where (Hallmark) where
    There was a pair of identical twins, one of whom contracted AIDS and the other gave him a bone marrow donation, of course they did not consider the idea of ​​immunity from the disease then...

  9. The Safe Migdal company with its sticky advertisement on the left is also a type of persistent and disturbing virus.
    I was convinced for sure in other companies!!!

  10. I agree with Yoav, absolutely great writing. A revolutionary evolution can be seen from Roy's first articles to the present day. You become the undisputed ruler of popular science writing and you do it in a welcoming and equal way for everyone.

    The material itself is very interesting and of course we would love to hear about new developments in this regard. Of course, to stand still you have to run as fast as possible - meaning, it is very doubtful whether removing the virus's receptor will really bring about the end of the war against it.

    And on a slightly critical note:
    "Studies conducted on these people, some of whom had unprotected homosexual intercourse with hundreds of partners, showed that they are not affected by the virus"
    It should be mentioned that today the trend is reversed and in contrast to what was common in the early 90s, today it is known that the majority of those infected with the virus are actually from the heterosexual population.

    Greetings friends,
    Ami Bachar

  11. One thing I did not understand, how is it possible that the body of a person whose immune system has collapsed would reject the transplantation of bone marrow cells?
    And even after that, the immune system is created in the new brain cells, so why would it reject them?

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