Fortunately for Spencer, chocolate candy bars melt at temperatures just below human body temperature, and he noticed that the candy bar had melted well before any of his tissues were burned by the microwave heat. As it turned out, the inventor of the microwave oven died of natural causes at the age of 76, apparently never suffering any burns or other known health ailments from his years of work with microwaves.
While all these developments were taking place with consumer products in occupational settings, the medical community was simultaneously developing radiation technology for its own purposes. And there was great excitement. At the same time that occupational exposures were revealing the cancer risks associated with high doses of ionizing radiation, physicians were showing, ironically, that high doses of ionizing radiation, when focused on tumors, could actually cure cancer. Curing cancer is something that had never been achieved before without radical and disfiguring surgery. This was the first inkling of the highly mercurial nature of radiation, and it would complicate people’s views about radiation and health forevermore.
CHAPTER 6
THE HIPPOCRATIC PARADOX: RADIATION CURES CANCER
Physician, heal thyself.
—Luke 4:23
FOOLS RUSH IN
No one was better witness to the schizophrenic nature of radiation than Chicago physician Emil Herman Grubbe (1875–1960). He was the first to recognize that radiation might cure cancer, as well as cause it. But he learned this the hard way.
Grubbe came to the world of radiation the way many had—through the electric light bulb. At the tender age of seven, he was taken to McVicker’s Theatre in Chicago to see a public demonstration of Edison’s newly invented light bulb.1 As fate would have it, by the age of 20, he was actually employed in the business of making light bulbs in partnership with an itinerant German glass blower, Albert Schmidt.
Grubbe had entered the light bulb business because of his earlier entrepreneurial interests in platinum mining. Platinum had not yet made its debut in the jewelry business, but it was used in the electronics industry, primarily for carrying electrical circuits through the walls of glass containers. Since this was precisely the circuitry requirement of a light bulb, the major market for platinum was in electric light bulb manufacturing. Seeking to expand the Chicago market for platinum, Grubbe decided to establish his own electric light bulb company.2
It wasn’t long before Grubbe started thinking of new products that his light bulb company could manufacture, and he began, under Schmidt’s urging, to subscribe to the journal Annalen der Physiks und Chemie (Annals of Physics and Chemistry) to mine for ideas. It was in one of the issues of this journal that he learned of Crookes tubes, and thought they might be a potential new product for his company. He allegedly even corresponded with William Crookes about the design, and soon Grubbe and Schmidt were making Crookes tubes.
In preparation for entering the commercial market, Grubbe and Schmidt produced a number of prototype Crookes tubes. Their approach was to empirically test different types of electrode shapes to see which gave the best performance in a trial and error process similar to what Edison had done to identify the best light bulb filament. In doing this work, Grubbe’s hands became itchy, swollen, and blistered. It was about this same time (January 6 to January 19, 1896) that Grubbe first learned of Roentgen’s discovery that x-rays were emitted from Crookes tubes, and he suspected these to be the cause of his hand problems.
Now it just so happened that Grubbe was a very busy guy. Not only was he running his own light bulb business, he was also studying part time to be a physician at the Hahnemann College of Medicine. When he attended school with his hands bandaged, his professors inquired about his health troubles. He told them about his work with the Crookes tubes and how he assumed that x-rays were to blame. One of the professors, Dr. John Ellis Gilman (1841–1916), remarked that if x-rays were so damaging to normal tissue, they might be effective in destroying diseased tissues such as cancerous tumors. With that remark, the field of radiation oncology was born.3 The date was January 27, 1896—just one month after Roentgen’s publication of the discovery of x-rays (December 28, 1895).
As remarkable as it may seem, Grubbe started treating patients just two days later! Dr. Reuben Ludlam (1831–1899), another one of Grubbe’s professors, referred one of his difficult breast cancer cases to his student.4 Mrs. Rose Lee had advanced breast cancer that had returned after two surgeries. Desperate, she arrived at Grubbe’s light bulb factory at 10:00 a.m. on January 29 for treatment with x-rays. Grubbe administered to her the first of what would ultimately become a total of 18 x-ray treatments. The treatments did reduce her pain. Nevertheless, she died a month later.
Other late-stage patients came and were treated, and though most died shortly afterward, Grubbe was not deterred. He knew that doctors were sending him only their worst cases; those who had advanced disease and were very close to death. He hoped that by demonstrating some improvement even in these patients doctors would start sending him patients with earlier-stage disease—ones in which a significant therapeutic benefit was more likely to occur. Grubbe later recalled: “I continued to make use of x-rays for treatment purposes for several years. Most of the … patients referred to me were moribund and … many died … soon after I began to make x-ray applications. [Later], patients exhibiting more favorable … conditions arrived for treatment [and in some cases, the results] were so striking as to create quite a sensation.”5
To put this in perspective, in 1896 there were virtually no effective medical treatments for most diseases, let alone cancer. Furthermore, there was no mechanistic understanding of disease beyond germ theory, and even for the diseases caused by germs, there were still no antibiotics to treat them.
On top of this, the physicians of the day had divided into two warring camps, the allopaths and the homeopaths, each with diametrically opposed philosophies about how disease should be treated. Of the two battling groups, the homeopaths seemed to be winning the war.
The allopaths used noxious drugs, such as arsenic and mercury, and other aggressive treatments, such as bloodletting, to drive out disease. Patients often became sicker and died because of the treatment. The basic underlying treatment philosophy was “what doesn’t kill them, makes them stronger.” Many did not get stronger. They simply died.
Homeopaths on the other hand were disciples of Christian Friedrich Samuel Hahnemann (1755–1843), a German physician. At one point Hahnemann was experimenting on himself to determine what effect, if any, overdoses of cinchona bark would have on a patient. The bark of the cinchona tree (actually a large shrub native to the tropical Andes) was first used in herbal medication for fever by Quechua tribes of South America. It eventually became widely used in Western medicine as the only effective remedy for malaria.6 Hahnemann slowly increased his dose of the bark and found that he experienced symptoms that he thought mimicked the symptoms of a malarial patient. From this anecdotal experience, he made a universal conclusion about how medications worked to control disease, and invented a new branch of medicine grounded largely on two principles. The primary principle was that agents that cause specific symptoms in healthy people could be used as treatments for the same symptoms in ill patients. This contrarian approach was highly counterintuitive and, in fact, is complete nonsense. Regardless, homeopathic patients often improved, while allopathic patients typically deteriorated.
The comparative success of homeopathy is likely explained not by its first principle, but by its second: the therapeutic benefit of any agent is enhanced through dilution. Thus, many homeopaths diluted their chemical remedies to such an extent that there were only trace quantities of the agent in the doses they delivered to patients. So technically speaking, they were not treating with anything at all. Their better results over the allopaths are, therefore, best explained by the fact that while the allopaths were poisoning their sick patients, the homeopaths were just letting nature take its course, and their patients were getting better on their own.
In light of the overall ineffectiveness of most therapeutics of the time, whether allopathic or homeopathic, the ability of x-rays to combat the most formidable disease—cancer—was nothing short of miraculous. No wonder Grubbe said his x-ray treatments created “quite a sensation.”
Although the therapeutic effectiveness of radiation in treating cancer soon became widely accepted, the underlying biological mechanism remained a complete mystery. Some proposed that the radiation transformed the cancer cells back into normal cells. Others held that cancerous tumors resulted from bacterial or parasitic infections, and that the radiation killed the parasite or bacteria. But Grubbe had his own hypothesis.
Grubbe believed that x-ray exposures caused high levels of irritation to the tumor, which, in turn, resulted in an increase in its blood volume. The increased blood then brought large number of leukocytes (white blood cells) that then choked circulation through the tumor. Deprived of circulatory nutrition, the tumor starved to death. Remarkably, this explanation, based on an irritation hypothesis, is reminiscent of the mechanism for cancer causation proposed by Virchow. You may recall Virchow’s hypothesis was that tissues suffering prolonged irritation were at risk of becoming cancerous. Thus, according to Grubbe, irritation was supposedly the underlying mechanism for both the cause and cure of cancer. Although this was a unifying mechanistic hypothesis, it still didn’t adequately explain how radiation could produce two opposite biological effects. That explanation would be a long time coming.
With a lack of any validated biological mechanism, x-ray treatment of cancer needed to advance empirically, with trial and error refinements to doses, numbers of treatments, and intervals between treatments. These treatment parameters needed to be determined by each physician, based on his own experience with patients when using his particular equipment, because, as Grubbe had warned, Crookes tube x-ray outputs were not standardized. There could be very different x-ray doses between Crookes tubes even at the same voltage and current settings. Grubbe advised his fellow practitioners that they must proceed with caution when treating patients because treatment results could vary tremendously, and perhaps catastrophically, between Crookes tubes. Not only that, different tissues seemed to have very different sensitivities to radiation, although why that should be was not yet clear.
Grubbe downplayed the significance of the radiation burns that patients sustained on their skin as a result of x-ray treatment, saying that these effects were always reversible with time (just as the Curies had believed for both skin ulcers and anemia) and, in any event, severe skin burns could be effectively treated with petroleum jelly. Nevertheless, he recommended the use of a mask made of lead foil, with an opening just over the tumor, to minimize the dose to surrounding normal tissues. Yet, he made no recommendations to the physicians about protecting themselves during patient irradiation, and presumably he took none himself.
Why Grubbe decided to deliver his radiation doses to tumors a little at a time is unclear. For his very first patient he spread the dose out over 18 separate treatments spaced days apart. It may be that he was worried about overdosing the patient. By delivering the dose a little at a time (i.e., fractionating the dose), while closely monitoring the patient’s response, he lessened the chance of a catastrophic overdose. But even after he had empirically determined appropriate dose levels for treatment, he still used highly fractionated doses. Possibly, he simply wanted to increase profits by charging patients by the treatment. (Grubbe was highly mercenary.) Still, it is equally likely he believed that by diluting the radiation doses he was increasing their potency for cure, since this was one of the tenets of his homeopathic training. In any event, his decision to fractionate the doses no doubt contributed immensely to his treatment successes, but it had nothing to do with homeopathy philosophy.
We now know that fractionated doses enhance a phenomenon that Grubbe had observed but couldn’t explain; tumors are more sensitive than normal tissues to x-rays. The relatively high tumor sensitivity was critical to successful treatment, but nothing was known about why it occurred. An answer to this question wouldn’t be found for another twenty years. When it finally arrived, it came from an unexpected source: ram testicles.
Scientists in France in the 1920s were searching for a quick and effective alternative to surgical castration (which had high morbidity and mortality rates) for sterilizing rams. They thought that radiation might do the trick, because even as early as 1903 radiation exposure of the genitals was associated with infertility in male radiation workers.7 They found exposure of the ram testicles to x-rays worked. But when the sterilizing dose was delivered all at one time, severe irritation of the scrotal skin occurred. However, if the same dose was delivered a little at a time over several days, sterilization could be still be achieved, yet without the scrotal skin complications.8 But why?
It was later found that rapidly dividing cells, such as the cells that produce sperm (spermatogonium), are relatively sensitive to the killing effects of radiation, and are spared just slightly by the dose being spread out over time. In contrast, slowly dividing cells, such as skin cells (keratinocytes), are less sensitive to the radiation to begin with, and their sensitivity can be even further reduced if the radiation dose is spread out over a protracted period. The net result for testicle irradiation is that fractionating the dose preferentially spares slower growing cells to the detriment of the faster growing ones. Thus, if you fractionate the dose, you can kill off sperm production without critically damaging scrotal skin.
This was also the long-sought explanation for the effectiveness of fractionated dose delivery in tumor radiation therapy. Although men may take issue with the comparison, the situation of testicles surrounded by a scrotum is not unlike the situation of a tumor surrounded by normal tissue. Tumors, like testicles, contain fast-growing cells within, and killing those cells with radiation necessarily involves delivering a dose to the surrounding normal tissue, which can be equated to the scrotum. So by fractionating the dose delivery, tumors can be “sterilized” with radiation while the normal tissue is relatively spared. This is the underlying cellular mechanism that enabled Grubbe to successfully treat tumors with fractionated radiation therapy.9
Grubbe consistently practiced radiation therapy throughout his professional career, while experiencing ups and downs in his health and personal life. A tumultuous marriage to an unfaithful wife ended in divorce in 1911, producing no children, and an engagement to another woman was ended by her shortly before the wedding. He carried on alone, with no family. By 1929 his poor radiation protection practices had finally caught up with him. He had multiple surgeries for a tumor on his upper lip that severely disfigured him. (He had already had his left hand amputated at the wrist earlier that year as the result of a hit-and-run car accident.) Over the following years he had more and more surgeries and amputations over various parts of his body, and he even removed 15 lesions from his own body by himself by means of electrical cauterization. (It is not clear whether he ever treated himself with radiation.) During this time his radiation therapy practice slowly dwindled. It’s likely that his patients had second thoughts about subjecting themselves to radiation therapy treatments when they saw their grossly disfigured doctor. In 1948, he officially retired. By 1951, he was so badly disfigured by his multiple surgeries that his landlord asked him to vacate his apartment because his grotesque appearance was scaring away tenants. He lingered on in agony for nine more years, sometimes contemplating suicide. He finally died in 1960. According to his death certificate, he died from pneumonia while harboring multiple squamous cell carcinomas (skin cancers) with regional metastases.10
&n
bsp; Grubbe’s contribution to radiation therapy went unnoticed for many years, because he failed to publish his original findings. He was also a flamboyant and clownish figure with a grandiose image of himself and a colorful imagination, well known to embellish, exaggerate, and even lie when promoting his own interests. Very few people were, therefore, inclined to take his many stories about his life’s escapades seriously. His claims of priority in radiation therapy, made many years later, understandably met with much skepticism. But at least with regard to the essential facts regarding his initial radiation therapy activities, independent investigation of historical records has confirmed his claims.11 He was indeed the first to treat cancer with x-rays, and he did meet with some remarkable successes. More remarkably, he achieved success despite his adherence to flawed homeopathic concepts. His therapeutic approach was right, but for the wrong reasons. The right reasons wouldn’t become apparent until radiation’s target for cell killing was discovered, and that was still a long way off.
HOLD THE PHONE: BRACHYTHERAPY IS BORN
Grubbe didn’t have a monopoly on cancer radiation therapy for very long. Others independently found the same things that he had, and many physicians demonstrated favorable results with both x-rays and radium exposures. (The first “cure” reported in the scientific literature was for skin cancer in 1899.) But the best results always involved tumors on the body surface. Tumors deep in the body were another matter. For these, penetration of the radiation deep into the tumor tissue was a major problem. X-rays produced by Crookes tubes were not very penetrating because they had relatively low energies. They deposited most of their dose in the overlying surface tissues while the deeper tumors were spared. Even dose fractionation could not overcome this problem.
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