Personal Reflections
Science …..
"The years of anxious searching in the dark, with their intense longing, their intense alternations
of confidence and exhaustion and the final emergence into the light
— only those who have experienced it can understand it."
Albert
Einstein
Science, despite the usual, unemotional and distant description of its findings, is an expression of the deeply rooted human
quest for hidden contexts. Yet, scientific insight can not simply be worked out. Similar to the arts, it constitutes a creative process,
which however is less due to the creativity of single scientists but rather reflects the sometimes intuitive assembly of the puzzle
pieces gathered by generations of scientists and the tentative addition of new pieces. In this sense, science perhaps resembles a
highly complex and deeply fascinating game, which is hard to elude when once begun.
Scientific research, particularly in the natural
sciences, however is highly dependent on institutional framework conditions, most notably the typically time-limited funding of research
projects, and due to this form of funding is also subject to constantly changing trends and fashions. These framework conditions,
of which the outsider usually is largely unaware, not only guide the paths of science but also the fate of scientists, whose existence
is constantly dependent on attracting new research funds by their findings and ideas, an endeavour that, in view of declining research
funds and average funding rates of 20 to 30 %, in long term rather resembles gambling.
In this sense, science, like any other aspect
of life, is an outcome of circumstances, personal encounters and luck. Thus, instead of introducing myself, I would rather like to
tell you my personal, human story of our research project, hoping to give you an understanding of my motivations for the aims of our
association.
The beginning of a passion .....
In 1985, when, as a young biochemist,I first went to the lab of Prof. Dr. Ernst Ferber
at the Max-Planck-Institute for Immunobiology in
While
pursuing my project of enzyme purification, I spent the spare time during my purification runs reading more about the physiological
role of macrophages. And I still remember the day when I first encountered a description of macrophage antitumor activity, mediated
by a factor that selectively destroys all kinds of tumor cells. I was totally intrigued. So I asked my colleague in the lab, Dr. Inge
Flesch for all she knew about this topic. She provided me with more literature and I started to dig deeper and deeper into this field.
At
that time, the TNF story had just reached its climax. TNF had been purified and cloned and was considered the "magic macrophage antitumor
bullet" to revolutionize cancer therapy. While discussing all I had soaked up from the literature with Inge, she just mentioned that
she was not so convinced about TNF being the factor responsible for macrophage tumor killing, as in her own experiments TNF had no
effect on tumor cells killed by macrophages. I was stunned. That meant that there had to be a(n) additional antitumor factor(s) produced
by activated macrophages. And since Inge, during her PhD thesis, had devised a unique protein-free culture system for macrophages,
which allows direct biochemical analysis of proteins secreted by macrophages, for a biochemist it was tempting to take a closer look
at these molecules. Inge agreed and so a "hobby" side project was born.
It took a fairly short time to verify that the culture fluid
of activated macrophages indeed contains a factor that was killing TNF-resistant tumor cells. Soon thereafter, both Inge and I left
the institute for new positions, but decided to keep our hobby project going.
After setting up new laboratories, we continued with
the project and in spring 1988 ended up with a protein fraction from the culture fluid of activated macrophages, corresponding to
a molecular mass of about 170 kDa, which was clearly distinct from TNF and fulfilled all the criteria for a novel macrophage antitumor
factor, i.e. specifically and selectively killing various types of tumor cells, all of which were totally resistant to TNF.
The increasingly
intense preoccupation with the topic however, more and more started to go beyond the scope of a hobby project and thus demanded a
fundamental decision. So I decided, to put all my eggs in one basket, give up my position and devote my work entirely to the further
investigation of the novel antitumor factor, also meaning that further on, I would have to raise the required financial means via
research grants by myself. This would not have been possible, if Prof. Ferber had not allocated the necessary space for my small research
group in his lab and thus had made my return to the Max-Planck-Institute for Immunobiology possible.
So, the hobby project finally
had turned into something serious and a purpose of life. Unfortunately, Inge, due to her duties at the
A
scientific thriller takes its course
At the same time, TNF started to lose its nimbus as a miracle cure for cancer, because of accumulating
discrepancies concerning its antitumor effects, but most importantly because of its life-threatening side effects. So, I was even
more surprised, when Prof. Ferber one day came to me and asked me, whether “my“ novel factor was not TNF, after all. In his hands
he held an “old“ publication from 1975, describing the original discovery of TNF in the serum of LPS-treated mice, resembling by far
more the data for MTC 170 than those for TNF. I was perplexed. I had done every conceivable experiment to exclude that MTC 170 was
identical to TNF. So I began, quite irritated, to dig up the whole original literature about TNF in the library of the Max-Planck-Institute.
The picture that emerged from these studies was obvious. In fact, the original description of TNF was consistent with the findings
on MTC 170 to an astounding extent, whereas the molecule isolated as TNF did not fit this description in numerous aspects. Thus, the
conclusion was close at hand, that MTC 170 activity may have been observed originally, but may have been simply “lost“ during the
isolation of TNF. In response to this hypothesis, Prof. Ferber suggested that I should ask colleagues at the institute, Dr. Chris
Galanos and Dr. Marina Freudenberg about it, since they had been working with TNF for a long time and had witnessed its story right
from the beginning. The conversation with Chris that followed confirmed my assumptions. Chris was not at all surprised about my hypothesis
and said that he and Marina actually had never believed in TNF really being the sought-after antitumor factor, since the best antitumor
effects in the serum of LPS-treated mice can be observed at a time point, when no TNF is detectable in the serum anymore. Thus, we
decided to redo the original experiments on the so-called “tumor necrosis sera“ performed in the seventies, and analyze these sera
both for MTC 170 as well as TNF activity. The result was clear-cut: The sera collected at later time points after LPS injection contained
MTC 170 activity but no detectable TNF. Yet, a single injection of these sera into tumor-bearing mice caused a rapid decay of the
tumors and the complete and permanent cure of the animals, and all that without any obvious side effects.
At this point, by the end
of 1994, Prof. Ferber had retired for health reasons, which gave me the opportunity to take over his lab with my research group. What
followed, in close collaboration with the research group of Chris and Marina, was on one hand the final proof that the cancer-curing
factor was indeed MTC 170, and on the other hand painstaking criminalistic work in order to further elucidate the bewildering connections
between MTC 170 and TNF in cancer defense by macrophages. During these studies, and against all expectations, it also turned out that
the release of MTC 170 in the body after LPS treatment may also occur completely independent of TNF, and hence without side effects,
a situation, generations of scientists may have dreamed of before. By the end of 1997, this exceptionally intense and fruitful phase
finally came to end due to a reorganization of the Max-Planck-Institute, which forced me to clear my lab and thus give up the basis
for my practical research for the moment.
A hard way home
Besides my research activities, in 1994 I had also started to give lectures
on cancer biology and immunology at my home university in
Unfortunately, this way home was accompanied by a number of problems, the most affecting being a severe infection, I had contracted
at a scientific congress just before moving to Salzburg, which in the aftermath substantially compromised my personal working capacity
in long term. In addition to this, all of my biological sample material had been destroyed as a consequence of a short circuit in
a freezer, a worst case scenario for a natural scientist. Nevertheless, I started to build up a new lab to continue work on MTC 170,
especially with respect to the mechanisms of specific cancer cell destruction. On the other hand, I at last started to write down
the data that had been gathered in
Since
publication of results in scientific journals in practice constitutes the only performance record for a scientist, which is crucial
for obtaining funds from public funding agencies, this situation turned out fatal for the further funding of the project, even more
so, since my visiting professorship by then had ended for legal reasons. All efforts to avert this threatening situation failed and
eventually, at the beginning of 2003, besides other severe health problems, led to a chronic fatigue syndrome, forcing me to reduce
my work on MTC 170 to a minimum. It might appear like an “irony of fate”, but just at that point, after four years of futile struggle,
the manuscript of the “revisited“ TNF story was finally accepted for publication in a mid-impact US journal, even without criticism
from the reviewers.
New spring and the return of winter
After a very slow recovery and a slow way back into the lab, in 2006, an invitation
to visit the Oncology Research Institute in
Scientia Pro Sanitas
– Science by people, for people
At this point, deeply frustrated by the notoriously insufficient funding of cancer research by public
funding agencies and the over the years accumulated negative experiences with the pharmaceutical industry and its lack of interest
in biological cancer defense, and at the same time motivated by the in the US well-established practice of funding research by donations,
I started to reflect upon founding a scientific association for further research on MTC 170. And not only because of funding, but
also because it had always been my personal concern, to bring scientific research, which is mainly funded by the public, out of its
institutionalized ivory tower back to the general public, a concern I hope to take account of by this website. Because it is my belief
that science, and in particular biomedical research, first and foremost should serve mankind.
In this sense, it is my sincere hope,
that by this association it will be possible to create a new basis for research on MTC 170 and thus bring 28 years of scientific work
to a conclusion that will benefit diseased people and harness the power of natural cancer defense for mankind, a goal, I feel deeply
obliged to.
The object of passion .....
Acknowledgements
At this point, I would like to express my deep gratitude to
all those people and institutions that have allowed me to initiate and pursue this research project.
At first, I would like to thank
Prof. Dr. Ernst Ferber, who has accompanied this project with great interest and benevolence right from the start. Without his multifaceted
and active support, this project probably never would have prospered. Particularly, I would also like to thank my first “comrade in
arms“, Dr. Inge Flesch, as this project would have never been born without her commitment and cooperativeness. My special gratitude
also goes to Dr. Chris Galanos and Dr. Marina Freudenberg for the years of fruitful collaboration and their multifaceted support of
the project under sometimes difficult circumstances. Last not least, I would like to thank all my coworkers at the Max-Planck-Institute
in
In
I am also deeply obliged
to the institutions that have made this research possible over the years:
The Max-Planck-Institute for Immunobiology in Freiburg and
the
Of course, I would also like to thank my family and all my friends and colleagues,
which have repeatedly supported and encouraged me in difficult situations. In particular, I would like to thank Mag. Peter Hertl,
who has encouraged me with the idea of founding a scientific association with benevolent constructiveness and has provided the last
impulse to its realization. Last, not least, I would like to express my deep gratitude to the people who have launched this association
with me and have themselves actively involved in its goals.
Finally, I would like to wholeheartedly thank Mrs. Hilde Brunner, who providentially
stood at the crossroads at a crucial point of my life, and has guided my steps to
Contact: guenter.schwamberger@sps-research.eu
