One potential solution to the depth problem was to increase the energy of the x-rays used in therapy (i.e., shorten their wavelengths; see chapter 2) so that they would be more penetrating, and some investigators were pursuing that approach. This strategy, however, was largely dependent upon technological progress by physicists and engineers in producing the next generation of x-ray machines, and that progress would occur slowly. Current cancer patients would require an alternative, shorter-term strategy, not dependent on future advances in physics. The best alternative turned out to be the employment of radioactive sources, typically radium or radon, to irradiate tumors. The gamma rays from these radioactive sources had higher energies and were thus more penetrating than Crookes tube x-rays, thereby allowing treatment of even the deepest tumors.
Another advantage of radioactive sources was that they were quite small. They could, therefore, be used either externally, by holding the source over the area of the body containing the tumor, or internally, by placing it directly within or on the surface of the tumor.
One of the first recorded suggestions to use radium sources internally came from an unlikely person: Alexander Graham Bell (1847–1923), the inventor of the telephone. In a 1903 letter to a physician in New York City, Bell proposed his idea:
I understand … that [x-rays], and the rays emitted by radium, have been found to have a marked curative effect upon external cancers, but the effects upon deep-seated cancers have not thus far proved satisfactory. It has occurred to me that one reason for the unsatisfactory nature of these latter experiments arises from the fact that the rays have been applied externally, thus having to pass through healthy tissues of various depths in order to reach the cancerous matter. The Crookes tube, from which the [x-rays] are emitted is, of course, too bulky to be admitted into the mass of a cancer, but there is no reason why a tiny fragment of radium sealed upon a fine glass ampule should not be inserted into the very heart of the cancer, thus acting directly upon the diseased material. Would it not be worthwhile making experiments along these lines?12
Bell was indeed on to something. Why not bring the radiation source directly to the tumor? (This therapeutic strategy is now called brachytherapy—from the Greek word brachys, meaning “short distance”—and is in widespread use in radiation therapy to this day.13) But this idea of Bell’s wasn’t the brainstorm that it might seem. Others had thought of it, but there was a huge obstacle that Bell failed to appreciate. Purified radium, one of the rarest materials on Earth, was extremely expensive even when obtainable. It simply wasn’t an option to routinely treat patients with radium unless there was a ready, and affordable, supply. In 1904, the dean of New York Medical College (another homeopathic medical school) lamented:
Further progress in the use of radium for curing disease will be practically impossible. … When Prof. Curie and other eminent European scientists are totally unable to procure desirable specimens of the substance, there is small chance of anyone else doing so. The Austrian government has positively refused to allow any more of it to leave that country for the present,14 and there is as yet no other known source of what may be called a working supply of the element.15
With time, several hospitals in Europe were able to secure small amounts of radium and use it with some success in cancer treatment, but no hospitals in America had any therapeutic quantities. This was still the situation in 1908—the fateful year that Eleanor Flannery Murphy was diagnosed with uterine cancer.
Eleanor Flannery Murphy (1856–1910) was the beloved sister of prominent Pittsburgh industrialists James J. Flannery (1855–1920) and Joseph M. Flannery (1867–1920). The Flannery brothers were among the wealthiest men in the United States. Starting out in a highly successful undertaking business, they later wanted to diversify their holdings into other business ventures. So they used some of their fortune to buy the patent rights for a flexible stay bolt that was used in the manufacture of railroad locomotives at a time when the railroad industry was in its prime.16 At some point their bolt manufacturing business was in search of better metal alloys, and they soon identified vanadium alloy steel as superior to all others. But vanadium was in short supply. This led them into the vanadium mining business. Soon they were supplying vanadium for the steel industry. Vanadium alloy steel was soon in high demand for a variety of industrial applications, not just bolts. (It was used in the lock gates of the Panama Canal, and in Ford automobile parts.) By 1908, it seemed that the Flannery brothers had the Midas touch. They were millionaires three times over, thanks to successive fortunes made in undertaking, bolt manufacturing, and vanadium mining.
When doctors told them their sister’s condition was terminal, the brothers did not take the news with resignation. The only glimmer of hope offered by physicians was treatment with radiation from radium. Since purified radium for medical treatment was unavailable in the United States, Joseph Flannery immediately set sail for Europe to find some, buy it, and bring it back home for his sister’s treatment. He spent months combing Europe, desperately trying to purchase radium from anyone, at any price, to save his sister; but he found little, and no one who had any was willing to sell. Disheartened, he returned home to be with his sister at her death.
After Eleanor died in 1910, Joseph vowed he would cure cancer by commercially producing radium for radiation therapy. He and his brother incorporated the Standard Chemical Company of Pittsburgh for the sole purpose of commercial radium production for medical use. Radium had recently been discovered in the carnotite ore of the Paradox Valley in Colorado and Utah.17 The plan was to purchase this ore and extract the radium.
But the brothers found it hard to recruit financial backers. Carnotite ore contained relatively little radium, and there was no known method to commercially extract it. The brothers were, therefore, forced to invest all of their personal wealth into the project, hoping that success would restore their fortunes, and Joseph devoted his entire attention to that success. He bought mining claims, mining equipment, and a stove factory in Canonsburg, Pennsylvania, 18 miles southwest of Pittsburgh, which he converted into a radium extraction plant.18
By 1913 the company produced its first purified radium, but at tremendous cost. To manufacture one gram (about three aspirin tablets) of purified radium required 500 tons of carnotite ore, 500 tons of chemicals, 10 million liters (about 2.5 million gallons) of water, 1,000 tons of coal, and the labor of 150 men.19
Unfortunately, production costs were so great that Standard Chemical’s radium prices were still too high for most American hospitals to buy any. Sadly, Standard Chemical ended up selling almost its entire radium supply to different European countries, and American hospitals continued to do without.
But one American physician, Dr. Howard Atwood Kelly (1858–1943), a gynecologic cancer surgeon at the Johns Hopkins School of Medicine, was able to obtain some of Standard Chemical’s radium with the help of James S. Douglas (1837–1918).20 A medical philanthropist, Douglas bought some and donated it to Johns Hopkins for medical research. Douglas’s motivation was similar to the Flannery brothers’. He had also suffered a personal loss—a daughter to breast cancer—and was also on a mission to cure cancer with radium. Kelly used that radium with some success to treat gynecologic cancers, and he wanted more, a lot more, for his private gynecology clinic. But he wanted it at substantially reduced prices. Working with Douglas, who was also a mining engineer, Kelly lobbied the federal government to nationalize domestic sources of carnotite ore to keep it out of the hands of private entrepreneurs, who could manipulate prices. But the US Congress refused to go along.
After being rebuffed by Congress, Kelly and Douglas decided to purify their own radium. They created the not-for-profit National Radium Institute, which soon cut a deal with the US Bureau of Mines. The institute would buy the carnotite ore and the bureau would provide the technical expertise to extract the radium.21 Whatever technology the bureau developed for radium extraction would be freely disseminated to others. Since no secrets would be kept, the
free availability of the information about radium extraction technology would presumably encourage others to enter the market, thus further increasing the radium supply and driving down the cost. Moreover, the institute agreed to transfer its entire radium-processing facilities over to the government once Kelly and Douglas had satisfied their own radium needs.
FIGURE 6.1. AUTORADIOGRAPH OF RADIUM-CONTAINING ORE. Howard Atwood Kelly used Becquerel’s photographic film procedure (termed autoradiography) to detect and measure the presence of radium in raw ore. By comparing the ability of ores from different locations to expose photographic film over a fixed time period, he could judge the relative radium contents of different deposits. This 50-hour exposure of film to carnotite ore from the Paradox Valley of Colorado includes a clearly silhouetted image of an overlying key. The metal key blocks the ore’s emitted radiation and serves as an internal negative control for the exposure. (Source: Photograph provided courtesy of the Alan Mason Chesney Medical Archives, The Johns Hopkins Medical Institutions)
Employing the bureau to develop the extraction technique proved to be a shrewd move. Its scientists developed a methodology that turned out to be much more efficient than Standard Chemical’s. This allowed the National Radium Institute to produce a gram of radium from 200 tons of ore, as opposed to the 500 tons required for Standard Chemical’s procedure.22 By 1916, the institute had produced several grams of radium at a cost of only $40,000 ($869,000 in 2015 US dollars) per gram; less than one-third of radium’s price on the world market. Once Kelly and Douglas had all the radium they needed (8.5 grams; about the mass of two US Jefferson nickels) they dissolved the institute and handed the facilities over to the US Bureau of Mines as promised. The joint venture between the federal government and the private sector had been an unqualified success, and others jumped into the business on the coat tails of the National Radium Institute and Standard Chemical. Soon, newer and more efficient extraction and purifications methods were developed. Prices then dropped further, to the point that it even became feasible to use small quantities of radium in consumer merchandise, such as in paint for watch dials. The ready availability of purified radium soon created a whole new consumer products industry based on radioactivity.23 From 1913 to 1922 the United States dominated the radium market, producing 80% of the world’s supply.
But the heyday of radium production in the United States started to wane in 1920. For one thing, both Flannery brothers died that year from the Spanish flu. But more importantly, higher-grade radium ore was discovered in the Belgian Congo, and the inferior carnotite ore from Paradox Valley simply couldn’t compete. Finally, in 1922, Standard Chemical signed a contract with the Belgian producer, Radium Belge, in which the former agreed to stop all its radium mining activities in exchange for being sole distributor of Radium Belge’s radium in the Western Hemisphere.24
Back in Baltimore, Kelly’s radiation therapy practice was growing in leaps and bounds. His private clinic, at 1418 Eutaw Place, expanded to include the neighboring dwellings (1412–1420) and became known as the Kelly Hospital.25 It had both diagnostic and therapeutic radiology equipment for diagnosis and treatment with x-rays, and a stockpile of five grams of radium—the largest stash of purified radium in the world.26 His hospital was the largest radiation therapy operation in the nation at the time, and performed virtually all of the radiation therapy in the state of Maryland.27
In 1916, Kelly presented his hospital’s data on radium treatment of 347 women with cancer of the uterus or vagina to the American Gynecological Society.28 Kelly described the impressive results: “The most remarkable fact about the radium treatment … was that it often cleared up cases which had [spread all the way] to the pelvic wall … great massive cancers choking the pelvis … Over 20% of this remarkable group had been apparently cured.” These findings by the most respected gynecological surgeon of the age made brachytherapy an overnight sensation and the treatment of choice for most gynecological cancers.
Although all of Kelly’s brachytherapy procedures were commonly referred to simply as radium therapy, in reality much of his radium therapy was actually done with radon that was “milked” from his radium stockpile. Solid radium continually leaches off its progeny, radon, and this radioactive gas was collected using an apparatus given to Kelly by Ernest Rutherford.29 The collected radon was encased in glass ampules that were then placed within brass capsules. It was these brass capsules (sometimes called seeds) of radon, not the parent radium itself, that were typically positioned in and around the tumors.30 When the radon in the ampules had decayed away to the point they were no longer useful for treatment, the ampules were discarded.31
Despite the fact that Kelly was well aware of fractionated radiation therapy, and he readily admitted that smaller quantities of radium introduced over a longer period of time might prove advantageous, he was not a big fan of it. His reasons are not clear. Perhaps he felt he could treat more patients overall if he used a single treatment for each patient, or maybe his surgical training predisposed him to single-intervention procedures. Whatever his reasons, we might expect that his therapeutic results with brachytherapy may have been even more spectacular had he adopted fractionated brachytherapy as the norm, just as Grubbe had for x-rays treatments.
Even though Kelly worked almost exclusively on gynecological cancers, he by no means thought that radiation therapy’s utility was limited to such tumors. He was prescient in his prediction that brachytherapy of prostate cancer might prove to be a particularly promising field. (In 2012, about half of all prostate cancers in the United States were treated with brachytherapy.) He also recommended irradiating neighboring nondiseased lymph nodes when treating Hodgkin’s lymphoma, to quell the spread of the disease. As we’ll see, this recommendation would prove to be visionary.
Notwithstanding the spectacular successes in his professional career, all was not smooth sailing for Kelly. In particular, his use of single high-dose treatments rather than fractionated treatments ended up getting him in some trouble. In late 1913, New Jersey Congressman Robert Gunn Bremner (1874–1914) came to him for treatment of a rapidly growing tumor in his shoulder. Congressman Bremner had been referred to Kelly by fellow New Jerseyan President Woodrow Wilson, who had heard about Kelly’s work with radiation therapy. By the time Bremner ultimately arrived at Kelly’s clinic, however, the tumor had reached a massive size, simultaneously growing in both directions, down the front as well as the back of the shoulder, and nearly meeting under the armpit. On Christmas Day, 1913, Kelly surgically inserted 11 radioactive ampules into the tumor. High doses of cocaine were also administered to reduce the surgical pain, and the ampules were left in place for 12 hours. The New York Times reported on the treatment the next day and noted it was “the largest number of ampules and the most expensive quantity of radium ever used in a single operation.” It touted the treatment as “one of the most important that has been performed in this country and, if successful in producing improvement or cure, will mark a notable [advancement] in the treatment of cancer.”32
But the accolades were premature. The congressman quickly took a turn for the worse, having apparently been overdosed with radiation. When Bremner died in Kelly Hospital a few weeks later, Kelly was accused of being a quack and summoned to appear before the Maryland State Medical Society to explain himself.33 Kelly left for Europe to escape testifying in the kangaroo court, and made the rounds of various European radium experts while he waited for the fury to die down at home. He would later claim that the medical profession “wreaked its vengeance” upon him as “an innovator.”34
Kelly soon resumed practicing radiation therapy at his hospital. But then, in 1919, the Johns Hopkins University instituted a new policy under which all of the medical school’s faculty members were required to be full-time employees of the Johns Hopkins Hospital. Kelly reluctantly resigned his faculty position in favor of maintaining his own private hospital, which he continued to operate for another 20 years.
During all his years of ra
diation therapy, Kelly was never known to have suffered any health consequences from radiation exposure. He was well versed in the fundamental concepts of radiation physics, and he had consulted with many of the early European nuclear physicists, including Rutherford, about how best to handle radioactivity. Kelly always kept his personal radiation doses to a minimum by working quickly, using long forceps to pick up radium sources, and protecting himself behind a lead barrier as much as possible. Today we recognize these safety practices as the fundamental tools of radiation protection practitioners (known as health physicists), who routinely minimize radiation doses to people by means of (1) reducing exposure time to the radiation source, (2) increasing the distance from the source, and (3) shielding the source from the body.
Kelly enjoyed good health and continued working in radiation therapy into his 80s. Then, in 1943, he contracted pneumonia and was hospitalized at Union Memorial Hospital in Baltimore. He died on January 12, at the age of 84. His wife, Laetitia, to whom he had been married for 53 years, and with whom he fathered nine children, was hospitalized at the same time. She died in the next room, six hours later.
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