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Professor Øyvind S. Bruland
 

Professor Øyvind S. Bruland

 

The Concept of Targeting

From mythology to modern medicine

Øyvind S. Bruland

This essay traces back in time the concept of targeting, the central theme of this symposium. The cradle of Western Medicine is generally attributed to the Eastern Mediterranean region. However, unbeknownst to most people, important concepts and beliefs, with a bearing on medicine, have roots in the Northern regions several thousand years before Hippocrates. University of Tromsø is the northernmost university in the world and University of Oslo is the oldest one in Norway. Their logos both contain symbolic elements which are of relevance to this symposium. I have attempted to explain these by making use of scientific analogies, medical terms and metaphors.

Ultima Thule

Practitioners of medicine, whether trained physicians or shamans, have always played important roles in the society. They are believed to understand the forces of nature, including the processes causing disease. The divine physicians of the ancient Mediterranean, Asclepius and his father Apollo, had their temple-hospitals. In Epidauros, Pergamon and Rome, healing was brought about by diets, herbs, surgery and psychological therapy – in a word all that today goes under the name of “holistic medicine”. Its tradition goes back to ancient Egypt, Meopotamia, and further east to China and continues to be an important aspect of clinical medicine.

In Greek mythology, Apollo was not only the god of medicine, but also god of the arts. He transformed the raw forces of nature into art giving meaning to the lives of humankind. Apollo enforced plague and other diseases, as well as death. However, he was also the divine master of cure and the relief of suffering. This is reflected in his two attributes: The bow signifying distance, death, terror and awe and the lyre reflecting his role in music, dance and poetry.

According to ancient Greek myths, the northernmost part of the earth was supposed to be inhabited by a people called the hyperboreans. They were a happy people dwelling in everlasting bliss and spring beyond the lofty mountains that gave rise to the piercing blast of the northern winds that eventually chilled the people of Hellas, protected against plague and gave health. The hyperboreans lived in a region inaccessible by land or sea, in a care-free country, exempt from disease, from toils and warfare, a secret Elysium, where men lived to become a thousand years old (1). Apollo, seemingly the most Hellenic of all gods, was apparently of foreign origin. In fact, his mother Leto was a hyperborean, born in the land beyond the northern winds as daughter of King Boreas.

On his travels to the land beyond the northern winds, Apollo was seeking his roots. Here Apollo received the pole with the snake entwined – a symbol later to be associated with the art of medicine. Experiences during these journeys gave him insights into the ultimate mysteries of life, and by virtue of this knowledge he became the indisputable governor of the oracle in Delphi. Ever since, the myths say, each year he leaves Delphi for three months to live among the hyperboreans.

A glimpse of Norse mythology
But there is another, more northernly god who has been chosen to symbolise this symposium, namely the Norse thunder-god Thor. He was no holistic healer. What he did was to use his hammer in the gods’ war against the giants – not indiscriminately, but in a targeted approach to combat those who attempted to destroy cosmic and human balance. Thor, God of the Sky, was in constant battle against the evil forces. Aided by two he-goats he was charging across the firmament. Armed with his magic hammer, Mjølner - forged by the dwarfs, lightning and thunder appeared in his wake. Everything Thor aimed at was destroyed by Mjølner – the ultimate targeting weapon that could single out evil from good.

Norse mythology also tells us about Odin, the father of Thor. Odin was the God of Wisdom. To achieve eternal knowledge and penetrating understanding he sacrificed one of his eyes to be guarded by Mime in the deepest of all wells. Like Apollo, Odin had black ravens to guide and assist him. They kept him informed about everything happening in the world (2). The two birds represented mind and spirit – our intellect and soul. If we are to discover the truth, we all need two kinds of wisdom – in modern parlance our dominant/ rational brain hemisphere and the associative other one. In fact, we all exist at the crossing between Hugin (forwards & future) and Munin (backwards & past). The time is now!
Disease has always been a companion of man. Once upon a time the main battle was the one against the evil forces and the Trolls. One of the battles we are facing today is the “War against Cancer”. As in times of old these battles are formidable. Our enemies are constantly changing, as they constitute part of ourselves - created by forces within, hewn from the same material. Often the threads are so densely entwined that good and evil are inseparable.

An Odyssey
The fight against cancer has indeed been a difficult journey. The finding of the perfect drug and the search for a universal cure (Panace) by making use of the arcane – a forgotten wisdom and the art of medicine, has always been a dream of mankind.

The body of knowledge about cancer is steadily growing, but what we still don’t know is an almost overwhelming challenge. The journey has been an exciting adventure, ample with challenges and disappointments, but also with some spectacular rewards. The path to the present stage has been a “navigation between Scylla and Charybdis” – a balancing act between the therapeutic effects and the unwanted adverse complications. Despite all therapeutic improvements we are today still only curing just above half of our patients. We are still under way – the odyssey must continue.

Odyssevs spent twenty years away from home – ten years fighting before Troy and then ten years striving to reach his home. The passage between Scylla and Charybdis was not his only challenge. There were temptations and tribulations en masse. He was tossed around at sea by the roaring winds. He was caught by the Cyclops ogre, exposed to the song of the Sirens, and he watched the languishing lotus eaters.

Odyssevs too visited the northernmost part of the world, where there is no darkness at night. He even went down to Hades and the realm of death. He paid a price. But the journey was worth it in a double sense: For the adventure of it all – and of course for the success that he achieved, coming home and reinstating himself as a king. He reached his target.

Targeting – a central concept in cancer therapy, is usually credited to the father of chemotherapy, Paul Ehrlich. At the turn of the last century, he proposed antibodies as “magic bullets”, envisaging the use of polyclonal antisera to deliver toxic agents directly to bacteria and other target cells (3). In his own words: “What makes serum therapy so extraordinarily active is the fact that the protecting substances of the body are products of the organism themself, and that they act purely parasitotropically and not organotropically. Here we may speak of magic bullets… In these cases chemical substances must come to aid the treatment. Instead of serum therapy, chemotherapy must be used”. Today thanks to the hybridoma technology, monoclonal antibodies are indispensable tools in our diagnostic and therapeutic armamentarium (4).

An adult human consists of about 30 x 1012 cells, and the genes, now defined in numbers, constitute a blueprint for all life processes. Both environmental factors and our genetic make-up predispose an individual to cancer. We are currently drowned in chaos of fragmented knowledge and information about the processes involved in the malignant transformation. Carcinogenesis is probably best understood in an evolutionary perspective (5), but are we willing to accept and take the con-sequences/implement the dogmas involved in Darwinian medicine? (6)

In my world, music may serve as a metaphor for the complexity of neoplasia. Is cancer the “rhapsodic music of life”? There are few notes in the vocabulary of music and a relatively limited number of instruments. However, an infinite number of combining them exists; in rhythms, harmonies, intonation, keys, and overtones.

Man will never solve the ultimate mysteries of life, because in the end we are part of the problem we are trying to solve
(Max Planck)

Hubris and Nemesis
Our ancestors were vulnerable and at the mercy of their destiny. They were overwhelmed by the forces of nature, and defenceless with regards to life, illness, accidents and death. Also modern man, crawling the long and tortuous road from cradle to grave, often faces the same fundamental realities. The solutions are too often veiled in mist. In a mythological perspective disease is to leave logos and enter chaos, and etymologically, medicine means mystery.

During the 20th century science and technology dramatically changed the basis for human existence on earth. Nuclear technology renders it possible to virtually destroy the biological basis for human life. Biotechnology, still at its infancy, opens vast possibilities for use in medicine, but also has its dangers that may challenge our existence. It is currently difficult to predict the impact of well-intended use and, at the same time grasp the unforeseen dangers of misuse. The promises must be considered against the potential dangers.

Ivan Illich in his seminal Lancet-paper (7) has critically challenged the role and limitation of modern medicine. He argues that our industrial society may cause inevitable misery by addicting people to its goals. Illich contends that modern medicine not only supports these goals but creates sickness in two ways: Enabling people to exist and function under the conditions of industrial societies and by changing death from being a natural part of life to something attempted to be postponed at all costs. Once death is not longer accepted as an inevitable consequence of life, the person looses his autonomy. Illich argues that the hubris of modern medicine is now making “Everyman” into a potential Prometheus (7). The Medical Associations, the “priesthood of Tantalus”, tantalize mankind with their selling of ambrosia. The independence and control over our existence is surrendered to the medical system. Nemesis is the fate that comes to man for attempting to “be like the gods”.

Today people expect cures for all ills, including cancer, so that they can continue to disregard our warnings of the perils of certain life styles. Emphasising each individual’s responsibility for own health is by many regarded as health fascism. The wishes of man are on a collision course with nature; our own and our surroundings. Our civilisation rapes the earth.

A close relative of biotechnology is information technology. This confronts us with the same problems related to use and misuse, desire and addiction. “Infotainment” and the so-called inspiration technologies are facets that are now leading us out of the real world into “cyber space”. On the temple of Apollo at Delphi Gnothi Seauton is inscribed, i.e. “Know thyself – Remember your limitations”.

Epilogue
The great achievements in technology and medicine in our time are based entirely on discoveries in basic research, which have opened up new, unexpected and unforeseen fields and possibilities. The current trend to concentrate the efforts and resources on applied research and on short-term goals of economic importance, at the expense of basic research, is a matter of serious concern to the scientific community.

Penetrating science needs time, time to reflect on matters, uninterrupted hours for reflection and concentration. Today we possess all kinds of time-saving devices, but less and less time. Probably we are working too much, and thinking too little. Fundamental discoveries often come as unexpected surprises, as gifts to those who explore the unknown. History teaches us that these discoveries can hardly be planned; they come as gifts and surprises to those who tackle crucial questions with an open mind. Serendipity is important in research. It usually hits the observer with a trained and prepared mind, a fact that is not well understood by those responsible for research policy.

Cancer is a matter of growing concern, not only to the medical community and the health authorities, but also to the public, and hence to the politicians. “Tromsø Symposium 2003” has placed targeted cancer therapeutics at centre stage. Attempts are made to present a reminder of what cancer therapy is all about; viz. our efforts to alleviate the suffering and anguish of our cancer patients, and to strengthen their hopes, courage and willpower, and their determination to survive. We have solicited the assistance of the media in advancing the general public’s understanding of the nature of the scientific pursuit, the methods used in cancer research and the considerable difficulties involved in establishing reliable knowledge in biology and clinical medicine. An important task is to explain the long path from unproven hypotheses to proven facts and to explain the essential concept of “evidence based medicine”, a standard that sets academic medicine apart from the many therapies of undocumented value that now are aggressively promoted also in the treatment of cancer.

Progress in science depends upon asking the right questions and to eventually find appropriate answers. Science is pushing the limits of our knowledge and tries to create order out of chaos. How can we win the battle? Knowledge illuminates the pathways to solution. When sunlight hits the Trolls they burst and turn into stone.

References
1. F. Nansen. “In northern mist. Arctic explorations in early times”, W.Heineman (1911)

3. Himmeltweit B (Ed.). The collected papers of Paul Ehrlich. Oxford: Pergamon press (1975)
4. J. Mann. “The elusive magic bullet. The search for the perfect drug”, Oxford University Press, ISBN 0-19-850093-9 (1999)
5. M. Greaves. “ Cancer. The evolutionary legacy”, Oxford University Press, ISBN 0-19-262835-6 (2000)
6. J. Diamond. “Guns, germs and steel. The fates of human societies”. W.W.Norton. ISBN 0-393-31755-2 (1999)
7. I. Illich. “Medical nemesis”. Lancet. May 11th, 30/4: 918–921 (1974)
 
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