Speaker script, episode 5: Rebellion of the Cells
Revolution 1848. A time of political change in Germany, a time of new scientific
discoveries: just like every other living creature, the human being is an organism
made up of cells, strictly organized in a state. This is how the famous cell
pathologist Rudolf Virchow saw it. Illness, in contrast, means chaos. Renegade
cells refuse to serve the general good of the body.
But some things remained puzzling. What causes the cells to rebel, and what is
cancer? It was not until the turn of the century that the many clues were put
together to reconstruct the process which results in cancer. The surgeon Karl
Heinrich Bauer sets down the knowledge of his time on paper as if it were an
accusation. His thesis: cancer forms because of changes in the genetic material
of cells. The genetic program of a cell is always reproduced when a cell divides,
similar to a melody. Errors in the copying, mutations, can cause cells to go out of
control. The uncovering of carcinogenic factors was to become Karl Heinrich
Bauer's life's work. The founding of the German Cancer Research Centre in
Heidelberg was a result of his initiative.
This feared disease still holds onto many secrets. But scientists are now on the
track of the anti-social behaviour of the cancer cells: cancer cells refuse to accept
the programmed cell death which limits the lifetime of normal cells. Every cell in a
human being's body has its special tasks. However, the job may be terminated at
any time. Signals tell the cell when it is time to retire and to trigger the suicide
program. The cell dies, and its remains are cleaned up without leaving behind any
residue.
Tumour tissue in an intestine, extreme enlargement. Cancer has spread without
restraint and deactivated the programmed cell death. Cancer can attack any
organ. Radiation, chemotherapy and surgery aim at eliminating completely
malignant cancer cells. The removal of a brain tumour shows how difficult that
can be. It is surrounded by healthy tissue on all sides. Even the greatest care and
the highest standard of technical perfection cannot guarantee that every tumour
cell will be removed, ensuring that new growth of the cancer is prevented in the
long term. A tumour does not form from all cancer cells. But there is a certain
amount of risk.
Prof. Meuer: „We assume that cancer cells form daily due to numerous external
and internal influences on our bodies. There are estimates from people, who are
willing to make such estimates, we can naturally only guess, that such an event
occurs eight to ten times a day and that one of the mechanisms which prevent the
spontaneous change in a cell in the direction of a cancer cell from actually
becoming a cancerous illness is the defence by the immune system."
Animated
film
(length:
1:30 min)
We are not helplessly at the mercy of malignant changes in our bodies. Cancer
cells, which of course develop from normal cells, carry structures on their
surfaces which give them away. Phagocytes, representatives of the non-specific
defences, can apparently recognize some properties. They destroy any cancer
cells bearing these properties. The precise recognition mechanisms have not yet
been clarified.
Natural killer cells. They are also counted among the non-specific defences.
Equipped with a substantially more precise sense of touch, they are some of the
most important front-line fighters against cancer. They destroy cells which have
changed pathologically, while sparing healthy tissue.
A trip through the oesophagus in the direction of the stomach. In some cases, an
infection triggers stomach tumours. If the bacteria are discovered early enough,
they can be treated with antibiotics. In this case, a malignant tumour has already
formed in the stomach. Although the tumour is clearly different from its
surroundings, the immune defence was unable to stop its growth.
Prof. Meuer: „There is a definite connection between immune weakness and the
development of cancer. We know this from patients whose immune system
functions have been repressed by medication, e.g., following transplants, in order
to prevent rejection processes. In these cases, the risk of developing cancer rises
by a factor of twenty to one hundred, depending on how the immuno-suppressive
treatment is carried out. Another example is the AIDS disease in which a virus the HI virus - destroys precisely those cells which are responsible for the defence
against cancer. An AIDS patient also has a substantially greater risk of developing
cancer than a healthy person."
A natural killer cell attacks the large blood cancer cell. If the immune defence is
defeated, leukaemia must be treated using other means.
Leukaemia is one of the most common forms of cancer in children. Thanks to
modern chemotherapies which kill the malignant cells, the chances of being cured
are good. Leukaemia can be detected in the blood picture. A strikingly large
number of white blood cells from which the immune cells also form are not
mature. They display a uniform shape. In comparison, a normal blood picture with
mature cells in a large variety of shapes.
A bone marrow donation can compensate for the lack of mature blood cells in
leukaemia patients. Healthy bone marrow contains the important stem cells which
produce blood. The diversity of blood cells which maintain life develop from these
stem cells after the transplant.
No hair. A consequence of chemotherapy and radiation, which destroys more
than only the sick blood cells. Isolated from surroundings, no noteworthy
defences: waiting for the life-saving bone marrow transplant. A functioning
immune system arises again from donor cells after weeks.
One and a half years later. The treatment was successful. The immune cells from
another person have accepted their host and have not triggered any notable
rejection.
Stem cells can also be obtained from blood donations. They are normally only a
small proportion of the blood. Now that medication can be used to increase
substantially the concentration of stem cells in the blood, this procedure is gaining
in acceptance. The advantage: the donor is spared an operation. The stem cells
can be kept for a long time if deep-frozen. Methods from genetic technology can
be used to multiply and transplant them as needed.
Excerpts from the film, 'The Hunt for CM24'
Researcher: „Already the seventeenth check, still the identical stable results."
Researcher: „Yes, but you know that we have to be doubly careful and triply sure
with a new enzyme, I don't have to tell you that."
Researcher: „The only danger is that there will be no more bone cancer thanks to
CM24."
Researcher:„You know that the entire world is nervous about genetic technology.
What happens if we release something that gets out of control?"
Researcher: „That's ridiculous, we'll just run around in circles until the Americans
and Japanese are ahead of us again."
Scientist Jacob Hofstetter, believes that he has found a weapon against cancer,
code name CM 24. Such alleged miracle drugs are always greedily taken up by
the media. Afflicted people cling to headlines which promise them hope for a cure.
Researcher: „Who the hell are you?"
Cancer patient: „I spoke to you at the concert. Is that it?"
Researcher: „The article is already completely out of date, and journalists, not
even pretty ones…"
Cancer patient: „Please let go of me."
Researcher: „Alright, then I'll have to call security."
Cancer patient: „But you need me, we need each other. And I'm not a journalist.
You're stuck, your work with enzymes is senseless if you can't apply it. I
desperately need it."
Researcher: „Cancer cells generally obey this principle, the chaos principle.
CM24, our killer, also obeys the laws of chaos. It hunts down the cancer cells, and
their end is inevitable."
Cancer patient: „…and all of the cancer cells are dead!"
If only it were so easy! It is not a simple matter to stop the growth of cancer cells.
Scientists all over the world are trying to discover the tricks of the chaotic cells.
Immuno-therapeutic research pursues one goal: the arming of the immune
system in order to improve decisively the recognition of and defence against
cancer cells.
Prof. Meuer: „The actual task of the immune system is to guarantee our physical
individuality. Individuality is recorded in our genes. What we are is set down as a
sequence of molecules in our genes. The immune system recognizes every
change in the genes, whether from inside, that is changes in our own genes, or
foreign genetic material, such as viruses which attack the cells. In all of the cases
in which there is foreign or changed genetic substances in cells, the immune
system can recognize changed cells on the basis of the protein molecules they
produce, which are logically different from the molecules from normal cells, either
because they have been attacked by viruses or mutations have caused internal
changes in the genetic material, precisely by the changes which are also
responsible for the development of cancer."
Animated
film
(length:
0:40 min)
Cancer cells present foreign antigen segments on their surface. These segments
come from the interior of the cell and form as a result of the genetically changed
program. T-killer cells can recognize the deviating structures, but the tumour cells
do not react to the signals. On the contrary, they turn the tables and drive the
defence cell to its death.
A cancer cell, marked in red, makes contact with a healthy cell and triggers its cell
death. This process, also called apoptosis, has already been proven to occur for
several types of cancer. There are other reasons why some cancer cells are
spared by the immune defences.
Prof. Meuer: „Immunological intervention has major consequences for the
enemy, for it usually ends in death. And since the immune system could
theoretically also spring into action against good cells from its own body and could
commit suicide, the decision to attack and kill is controlled very well and very
strictly. That means that many decision levels have to be passed before the red
button is pushed. So the immune system needs a lot of information before it
attacks."
Animated
film
(length:
0:59 min)
The T-killer cells, representatives of the specific immune defence, are masters of
discovery. They recognize suspicious material from the descriptions that are
shown to them. But attack comes only when the express order has been given.
Cancer cells refuse to give the necessary signal and so protect themselves from
destruction. With the help of genetic technology, cancer cells can be
reprogrammed so that they themselves give the deadly signal to attack. This
method, as well as others, is being investigated in Heidelberg. It already works in
a test tube.
In contrast to established methods for treating cancer, most of the immunotherapies are still in the early stages. In some university clinics, including the one
in Homburg in Saarland, physicians are using antibodies as weapons against
cancer.
Thought could not be given to clinical administration until its effectiveness had
been proven in animal experiments. Mouse cells are still required for the
production of the antibodies. It will not be possible to do without animals until a
genetic technology procedure is available. If a mouse is injected with any human
protein, it forms antibodies against it. And they can be used therapeutically in
humans.
The procedure step by step: A mouse is inoculated with the cube-shaped surface
components of cancer cells. The animal develops the appropriate antibodies
against it. A second mouse is inoculated with the ball-shaped projections of
natural killer cells. It forms a specific antibody against it which is shaped
differently.
Now comes the decisive step: the cells from the two mice which produce the
antibodies are merged with one another. And these new cells produce antibodies
with two different grippers. One fits cancer cells, the other fits natural killer cells.
A therapy using these bi-specific antibodies is not spectacular. Patients are given
infusions with the customized guided weapons. The initial results, for intestinal
cancer for example, are encouraging. However, the long-term effectiveness of the
antibody therapy must first be proven.
Animated
film
(length:
1:39 min)
Cancer cells, scattered from a tumour. Secondary tumours can form at locations
far away from the original spot, even after an operation. These metastases are
feared because every relapse is a deadly threat for cancer patients. With the help
of customized antibodies, physicians hope to prevent the formation of
metastases.
The antibody grabs the cancer cell with one arm and marks it as an enemy object.
A natural killer cell can then dock on the second arm and initiate the destruction.
No matter what surface structures tumour cells may have, only the antibodies
must be able to dock on directly. Even killer cells which would overlook these
cancer cells due to a lack of matching receptors will be deployed. This is the
decisive advantage of bi-specific antibodies.
Prof. Meuer: „Immuno-therapy will probably not be able to replace our
established procedures for the treatment of cancer, so the primary treatment by
the surgeon, for example, the removal of a large malignant tumour, is not the task
of immuno-therapeutic efforts, nor is the desperate situation, that is, the situation
in which everything else has been tried and has failed, the right situation to give
immuno-therapy a chance. For immuno-therapy functions only when there is a
relatively intact immune system present which can still be activated."
Research efforts so far have concentrated on the destruction of minute quantities
of tumour tissue which remain behind following operations. Perhaps more can be
considered in the future.
Prof. Meuer: „As far as the primary treatment is concerned, we should at least
remember that the immune system has at its disposal an enormous potential for
destruction. We see an example of this potential in the rejection reactions during
organ transplants. Within days, ten, fifteen days after an organ transplant, e.g., a
liver, if there is an acute rejection reaction, this enormous organ with one and a
half kilograms of cell mass is destroyed down to the last cell by the immune
system. This shows as a minimum that when the immune system is given the
right information, it can also handle large quantities of tissue."
The sun: engine of life, at the same time a radiating disruptive inferno. Only one
of many environmental factors which have been able to trigger cancer since the
beginning of evolution. Industrialization and rising standards of living subject
people to further cancer risks. Some of them can be easily avoided.
The triathlon competitor Astrid Benöhr. She has been breaking records for years,
but sports mean more to her than just that.
Astrid Benöhr: „From the very beginning, endurance sports - swimming, cycling,
running - were tremendous fun for me, being out in open nature, shutting out the
rest of the world, getting rid of stress, you simply feel better when you get a little
exercise."
Prof. Uhlenbruck: „It has been determined that athletic training in the sense of
an endurance sport leads to an improvement in mental attitude, our sense of wellbeing, the blood circulation through the brain improves, and, what is also very
interesting, our defensive forces, our immune system, improve. We are more
resistant to infections. Today, we can also say that you become more resistant to
the risk of developing cancer, and, what has to do with both of these things, it is
very important for the sport that it is fun and enjoyable and leads to greater
resistance to stress. This means that we can handle stress better, put up with it
more easily and overcome it."
Endurance sports done according to the individual's own ability to perform
improve the body's own defence against cancer. This is the result of a study by
the University of Cologne. Blood samples were taken from a test subject
immediately after standardized training. Back in the lab, natural killer cells and
phagocytes were isolated in the samples. They then had to measure up against
enemy cancer cells in a test tube. The best pictures of the fight, taken with an
electron microscope. Phagocytes have surrounded a cancer cell. It is swallowed
by a phagocyte and digested. This form of defence against cancer works
substantially more effectively in people who regularly do endurance sports.
Yet another research result: the right amount is very important for physical
exercise. People who constantly exceed the limits of their abilities are more likely
to weaken their immune defences. The diagnosis of cancer and the prolonged
treatment leave many patients with the feeling that their bodies have betrayed
them. Doing sports is one way to regain confidence in your own abilities.
Patient: „For one thing, it is fun to exercise, and for another, it is a wonderful
feeling when you realize that you can do things again."
Patient: „I am more even-tempered. I am happier when I come home from doing
sports, it is good for me and my surroundings, for my family as well."
Women who regularly do sports have a substantially reduced risk of breast
cancer. This has been proven in a long-term examination of twelve thousand
Norwegian women. However, the question remains unanswered as to whether
this is a result of a healthier life style or of an improved immune defence from
more exercise.
Laboratory experiments are limited in their ability to simulate what really happens
in a human body. Premature reports of success are of no help to anyone. The
struggle against the rebellion of the cells remains a challenge for science. For the
internal guardians of the body have by no means revealed all of their secrets.