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Cancer was seen as a disease of excess (too much smoking, ORGAN RESISTANCE radiation, pollution etc.); the generation of an evil, foreign life- A common observation, even in the most advanced of malig- form which battles and invariably destroys its host. Excess must _ nancies, is that some organs and tissues appear resistant to cancer be cut down, taken away, burned or poisoned. This logic, com- spread and invasion. The small intestine not only resists spread bined with the frustration and hatred generated by this invulnera- but also very rarely develops primary cancer. Perhaps there is ble nemesis, had locked us into the mindset that dominates current specific immunologic capacity in the small intestine that prevents therapies—therapies that have failed us for so long, yet which we _ cancer from developing and protects it from tumour spread. refuse to abandon. A quick search of anatomy and immunology books revealed that the small intestine is blessed with its own immune protection STANDARD CONCEPTS OF CANCER in the form of lymphoid aggregates called "Peyer's patches". I would like to outline the concepts that have dominated cancer = Much of the function of this line of defence is restricted to the research and therapies over the past few decades. Understanding small intestine and does not circulate. This could account for the failure is a useful tool in attaining success. cancer resistance being local. By definition, cancer is a rogue cell which multiplies without Studies of lower animals, particularly birds, indicated that their respect for normal systems of cellular control and develops into a = main immune-processing organ was not the thymus but was locat- mass that invades and destroys normal tissue and structures. It is ed in their embryonic and foetal intestine. Could this part of a powerful, mindless beast that spreads, grows more rapidly than human immunology have been delegated an unfairly low status? normal tissue and ultimately leads to the death of the host. In the animals, their capacity to transfer immune resistance to the Cancer growth rate may be slowed or accelerated by a variety entire body is optimal early in life. What if human correlation of infections. Even in its natural history, cancer growth is not exists whereby there is transfer of resistant factors between constant, for during the life of the patient the disease often grows Peyer's patches (and immune responses localised to the small in spurts. It is not uncommon for some cancer metastases to intestine in later life) and the rest of the body early in life? shrink, while most increase in size. In view of the logic supporting Cancer, the "mindless beast", starts thymic supplementation and the hope in a localised area, invades circulato- . that restoration of an atrophied organ ry and lymphatic systems, then A quick search of anatomy and would destroy disease, there was spreads throughout the body. Certai i another interesti bservati ith cancers exhibit specific patterns of | Immunology books revealed that f veision io Peers patches. Intestinal spread, long held by conventional the small intestine is blessed with lymphoid aggregates atrophied with teachings to be dictated by the pat- its own immune protection in the age. We had been so obsessed with tern of circulatory distribution of the thymus that perhaps we had over- micro-tumour emboli. This belief form of lymphoid aggregates looked the real saviour. furthers the concept that cancer is a " U " rampaging monster, cast by chance to called Peyer s patches . THOUGHT TO ACTION spread its deadly seeds. Passively carried by blood and lymph to their spent a good deal of time at the Peter new targets, cancer cells are undiffer- McCallum Cancer Institute in entiated, non-specific parcels of destruction that care not where Melbourne where my father was receiving treatment. He had they lodge and are not part of the decision-making process in their —_ introduced me to several oncologists and I approached them with Thad yet to start medical school but travels to new organs. my ideas. The general response was condescending but usually polite. Dr Ian Cooper, chief haematologist, was not only support- SEARCHING FOR MISSING DEFENCES ive but also advised me to formulate my ideas as an experimental A few observations regarding cancer in its population and age protocol and present it to Dr Jose of the Immunology Department. distribution are cited repeatedly in immunotherapy literature. The reply to my preliminary correspondence was surprisingly Essentially, increased cancer incidence occurs with immunodefi- encouraging: I was invited to address the weekly group meeting ciency; and age, particularly past puberty, also appears to be a of the immunology research team. I prepared theory, protocol and promoting factor. an experimental design. Tf one considers only these observations, one can conclude that The presentation was informal and pleasant. Researchers from after puberty there is a loss of some vital immune-protective around the world had submitted protocols for review by this unit. agent. If only we could identify it and replenish it, perhaps we Immunostimulants, interferon, interleukin, lymphocyte harvest could then triumph over this living nightmare. pre-chemotherapy: the suggestions were complicated but the The most likely candidate for our source of white blood cells in themes familiar. I had heard or read about all these concepts shining armour seemed to be the thymus gland, a master immune- before; worse yet, the experiments had been done and repeated cell generator which atrophies by early teenage years. Its degen- years previously. I felt encouraged; my protocol was the only eration seemed to correlate with increased appearance of cancer. original idea being presented on that day. Surely a new concept Therapies have proliferated over the years where part or all of | would be more appealing to a research unit on the cutting edge of the thymus, its products and hormones were used to treat cancer _ technology than simple repetition of prior failures? patients. Results were marginal to non-existent, yet, of all the To demonstrate that Peyer's patches could be stimulated to pro- borderline alternative therapies, thymus supplementation persists duce anti-cancer activity, I proposed that lymphocytes isolated most stubbornly. Propelled by a romantic notion, hope does not from these aggregates be tested against those taken from the fade—even when it is a false hope. spleen and other sources for efficacy against cancer. For obvious This restricted logic may have been sound. Perhaps we had fix- reasons I chose multiple myeloma as the cancer system to attack. ated on the wrong atrophied organ. An important design feature was the testing of ordinary extracts to Cancer was seen as a disease of excess (too much smoking, radiation, pollution etc.); the generation of an evil, foreign life- form which battles and invariably destroys its host. Excess must be cut down, taken away, burned or poisoned. This logic, com- bined with the frustration and hatred generated by this invulnera- ble nemesis, had locked us into the mindset that dominates current therapies—therapies that have failed us for so long, yet which we refuse to abandon. SEARCHING FOR MISSING DEFENCES A few observations regarding cancer in its population and age distribution are cited repeatedly in immunotherapy literature. Essentially, increased cancer incidence occurs with immunodefi- ciency; and age, particularly past puberty, also appears to be a promoting factor. If one considers only these observations, one can conclude that after puberty there is a loss of some vital immune-protective agent. If only we could identify it and replenish it, perhaps we could then triumph over this living nightmare. The most likely candidate for our source of white blood cells in shining armour seemed to be the thymus gland, a master immune- cell generator which atrophies by early teenage years. Its degen- eration seemed to correlate with increased appearance of cancer. Therapies have proliferated over the years where part or all of the thymus, its products and hormones were used to treat cancer patients. Results were marginal to non-existent, yet, of all the borderline alternative therapies, thymus supplementation persists most stubbornly. Propelled by a romantic notion, hope does not fade—even when it is a false hope. This restricted logic may have been sound. Perhaps we had fix- ated on the wrong atrophied organ. NEXUS 31 DECEMBER 1997 - JANUARY 1998