The lure of non-traditional remedies for all sorts of ailments has been with us for centuries ranging from herbs, to fruits, to plants, to salts of several heavy metals. As described in the previous Chapter, NCI tested tens of thousands of compounds, including plants, marine invertebrates, and algae, in a vast and expensive but low yield effort to uncover anti-cancer agents. Yet, a number of clinically useful agents emerged from the search, including Irinotecan (Camptosar®), extracted from the Camptotheca Acuminata, a fern-like deciduous tree; Paclitaxel (Taxol®), extracted from the Pacific Yew tree; Etoposide (VePesid®), extracted from Podophyllum Peltatum, a North American herb; and Vincristine (Vincasar PFS®), extracted from the periwinkle plant. Such a powerful endorsement of the medicinal properties of plants is often used to justify the promotion of many empirically unproven “natural” means to treat ailments ranging from backaches to cancer. On the other hand, despite recent progress understanding the nature and causes of cancer, its standard treatment remains inefficacious at best and harmful at worst, and the lives of patients with disseminated cancer continue to be wretched and short. In such an environment, the stage was set for the proliferation of new alternate cancer treatment approaches, often promoted by self-serving healthcare providers or charlatans making farfetched claims. For historical perspective, I will cite only some of the most outlandish cancer remedies of the eighteenth, nineteenth, and twentieth centuries that captured the public imagination, including the “Storck” and “lagartija” cures, the “cura famis” and “treatment by cold”, and the Gerson diet, respectively.

In the eighteenth century, Anton Storck (1731–1803), a Viennese physician and Rector of the University of Vienna, claimed that a concoction of his based on hemlock (the highly toxic plant that caused Socrates death) was highly effective against breast and uterine cancers when administered in sufficiently high doses to cause faintness (his version of today’s toxicity-limiting approach to chemotherapy dosing), though he had few followers and the method was abandoned. A colorful example of the extraordinary gullibility of physicians and of the public followed publication of a 14-page booklet, in 1783, by José Felipe Flores (1751–1824), a physician and professor at the Real University of Guatemala, praising the curative properties of a Central American lagartija (lizard) [489]. This particular lizard could cure many illnesses, including venereal diseases, leprosy, and cancer. The lizards had to be beheaded, skinned, disemboweled, and swallowed whole “while the flesh is still warm” [490]. One lizard per day was generally sufficient, but the dose could be increased to three lizards daily, which, according to Mexican Indian tradition, was always effective. To make the remedy more palatable and patients more compliant, animals could be sliced into small pieces and made into wafers or pellets “slightly smaller than a bullet”[491]. The exotic nature of this treatment, its peculiar formulation and dosing schedule, and the fact that it was shrouded in the mystique of an old American Indian remedy contributed to its immediate success and enthusiastic acceptance throughout Europe, where Flores’ booklet was translated into French, German, English, and Italian. The lagartija cure was the subject of innumerable testimonials, several books and reports, and of at least one doctoral thesis before it finally vanished into oblivion half a century later.

In the nineteenth century, two of the most interesting cancer cures were the cura famis and treatment by cold. These are of interest to us because, although they rallied few patrons at the time, they resurfaced mutated in the late twentieth century, inspired by advances in molecular biology and biotechnology. The cura famis, or cure by starvation, consisted of starving the cancer through a water diet that could last up to 40 or 50 days. However, patient non-compliance and its ineffectiveness led to a more radical variant: the severing of the cancer’s blood supply. The idea is attributed to William Harvey, who observed that ligation of afferent testicular arteries, to deprive the testis of nutrients, resulted in testicular atrophy and necrosis [492]. However, testicular cancer was the only natural target for such an approach given its anatomy that facilitated access to feeding vessels, and the procedure never caught on, despite its well-founded if simplistic rationale. One and a half centuries later, a variant of cura famis reappeared under the name of angiogenesis inhibition, or the starving of tumors using biological agents that inhibit new vessel formation necessary for cancer growth [493]. The treatment by cold, proposed by British surgeon John Hughes Bennett (1821–1875) consisted of applying cold, which he described as “one of the most powerful means we have to slow the progress of cancer” [494]. Bennett’s method entailed applying a mixture of two parts of chopped ice and one part of sea salt to the tumor for 15–20 min each week [495]. Although this treatment had no effect on cancer progression, it seemed to alleviate pain. Bennett is better known for his emphasis on the use of the microscope in medical pathology, and is credited for first describing leukemia, though the credit should rightfully go to French physician Alfred Donné (1801–1878), inventor of the photoelectron microscope, also known as photoemission electron microscopy. Ironically, Bennett questioned the validity of Pasteur’s pivotal experiments refuting spontaneous generation. It is worth mentioning that, although Bennett’s treatment by cold method never achieved any degree of success, the concept resurfaced at the end of the twentieth century in the form of heat and hypoxia used as an adjunct to chemotherapy in futile attempts to enhance the susceptibility of cancer cells to the cytotoxicity of cancer drugs [496]. Heat or cold have been delivered during surgery (“thermo- or cryosurgery”), under magnetic resonance imaging guidance, to treat drug-resistant cancers, especially in anatomically inaccessible sites such as liver metastases, with limited success [497, 498]. The recycling of old ideas about cancer treatment is a reminder of the biblical admonition,

The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun [499].

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