Dinosaurs and Ancient Civilizations: Reflections on the Treatment of Cancer

Abstract

Research efforts in the area of palaeopathology have been seen as an avenue to improve our understanding of the pathogenesis of cancer. Answers to questions of whether dinosaurs had cancer, or if cancer plagued ancient civilizations, have captured the imagination as well as the popular media. Evidence for dinosaurian cancer may indicate that cancer may have been with us from the dawn of time. Ancient recorded history suggests that past civilizations attempted to fight cancer with a variety of interventions. When contemplating the issuewhy a generalized cure for cancer has not been found, it might prove useful to reflect on the relatively limited timethat this issue has been an agenda item of governmental attention as well as continued introduction of an every evolving myriad of manmade carcinogens relative to the total time cancer has been present on planet Earth. This article reflects on the history of cancer and the progress made following the initiation of the “era of cancer chemotherapy.”

Perspective

Evidence from Dinosaurs (250 to 65 Million Years Ago)

Unraveling the history of cancer may provide insights and improve our understanding of the etiology, pathogenesis, and intervention of this disease. While it had been thought that there was generally ample evidence that cancer was a normal population phenomenon in dinosaurs, doubts still lingered as conclusive evidence was lacking. Earth history is divided into aeons, eras, and periods. Dinosaurs and other prehistoric reptiles roamed the Earth during the Mesozoic era for about 185 million years, which lasted from 250 to 65 million years ago. This era contained three periods called the Triassic, Jurassic, and Cretaceous.

Recently, metastatic cancer and osteomas (in mosasaurs) were reported (Rothschild BM, Witzke BJ, and Hershkovitz I [1999]. Metastatic cancer in the Jurassic. Lancet 354 (9176), 398.). Even more recently, researchers undertook an epidemiological investigation of tumors in dinosaurs (Rothschild BM, Tanke DH, Helbling M 2nd, and Martin LD [2003]. Epidemiologic study of tumors in dinosaurs. Naturwissenschaften 90 (11), 495–500). These investigators used computed tomography for fluoroscopically screeningmore than 10,000 specimens of dinosaur vertebrae for evidence of tumors. Of the specimens examined, investigators reported tumors in bones of Cretaceous hadrosaurs (duck-billed dinosaurs). In this species, maximum cancer susceptibility was approximately 3% of bones examined, which showed lumps by imaging identified as various types of tumors including hemangiomas, metastatic cancer, desmoplastic fibroma, and osteoblastoma. The familial pattern found seemed to reflect a genetic propensity or, alternatively, the result of environmental mutagens because these dinosaurs likely ate foliage of conifers rich in carcinogenic tannins, phenols, and resins.

Taking into account the limitations of the diagnostic tools used to study remains, there is an agreement that cancer in dinosaurs is relatively scarce. Age at death, diet, and environmental factors may have a significant influence on the incidence of these cancers.

Evidence from Ancient Civilizations (Egyptian, Greek, and Roman)

A recent overview of the literature investigating the presence of cancer in ancient civilizations has been published (David AR and Zimmerman MR [2010]. Cancer: an old disease, a new disease or something in between? Nat Rev Cancer 10, 728–733). Evidence of cancer in humans has been uncovered in the earliest medical records found left by the ancient Egyptians (3000–800 bc). Evidence consists of hieroglyphic inscriptions along with papyri writings noting both benign and malignant tumors. Egyptian culture allowed for working with human bodies as evidenced by the mummification of the dead. The first histological confirmation of cancer in an Egyptian mummy revealed that cancer was indeed present in ancient times (Zimmerman MR [1977]. An experimental study of mummification pertinent to the antiquity of cancer. Cancer 40, 1358–1362). In this report, Zimmerman diagnosed the presence of rectal cancer in an unnamed mummy who had lived in the Dakhleh Oasis during the Ptolemaic period (ce 200–400). The fact that palaeopathology has shown that cancer is present in ancient remains of Egyptians necessitated the need for the ancients to counter attack this disease. Deciphered papyri from around 1500 bc contain descriptions of cancer along with surgical intervention and treatments. Evidence for the use of surgical removal of superficial tumors has been found during this time. Deep-seated tumors were treated using different prescriptions including ears of pigs and other parts of animals and fish in such dispensions as poultices, ointments, and enemas. Thus, ancient Egyptian physicians treated patients for several forms of cancer, and their documents have provided both evidence of the disease along with the treatments administered at the time. Egyptians were considered the “fathers of pharmacology” as some treatments used were believed to be “magical” but were, in fact, true therapeutic remedies.

An interesting phenomenon has arisen during the course of multi-year studies related to the rarity of cancer in antiquity. This is of interest especially when considering that hundreds of Egyptian mummies and more than 10,000 dinosaur bones were evaluated. In contrast, the rate of cancer incidence has dramatically increased since the Industrial Revolution. The rarity of cancer in antiquity has been attributed to the lack of pollution and changes in diet and lifestyle, and most recent findings suggest that cancer may be a manmade disease (Nat Rev Cancer 10, 728–733). Thus, while a lack of adequate techniques for disease diagnosis and detection may partially explain the overall lack of cancer found during the millennia, the current cancer trends are now primarily associated with carcinogens in our modern industrialized society (Nat Rev Cancer 10, 728–733). Whether this hypothesis is indeed the case, what is clear from ancient Egyptian and Greek writings along with information accumulated throughout the millennia is that improved understanding of the biological basis for the disease as well as improved cancer treatments is needed.

Overall Cancer Perspective

To put the historical findings into a more modern perspective, in more than 3500 years of attempting to treat cancers effectively, the concept of cancer chemotherapy was initiated only relatively recently in the 1940s with the introduction of nitrogen mustards and folic acid. These initial discoveries using poisonous chemicals for the treatment of tumors were a major medical advance as progress rapidly ensued, leading to improvements in many cancer death rates. Moreover, the potential and realities of targeted anticancer therapies have more recently emerged some 50 to 70 years later. However, much work remains as cancer continues to be a major worldwide health problem, and progress in curing patients with metastatic cancer remains elusive.

In an effort to continue to advance treatments against cancers, Neoplasia continues to serve as a major conduit for the dissemination of relevant and timely information. Neoplasia has published numerous significant articles covering broad areas of research including cell and tumor biology, imaging, genetics, experimental therapeutics, and clinical investigations (Table 1). Neoplasia provides its readership with a broad scope related to many novel and diverse discoveries. The immediate availability of Neoplasia articles to the worldwide clinical cancer research community is a key and unique feature of Neoplasia, and our primary goal is to allow open access of all articles at the time of publication through Pub ed Central. This feature provides authors' research findings to the largest possible readership, thereby ensuring that articles published in Neoplasia will have the opportunity to make a significant impact. Finally, it has been a pleasure to serve the cancer research community as editor this past year, and along with my editorial board, I thank the scientific groups who have published with us and take this as the highest form of honor.

Table 1.

Summary of Published Articles.

Subject	2008	2009	2010
Cancer genetics	[1,3,7,23–26,30,46,54,61,64,65,69,72,76,89,90,102,107,113,117,120,122,125,128,136,140,146]	[154,159,168,171,182,193,218,225,230,250,256,262,265,280–282]	[289,302–304,308,310,315,326,327,336,357,374,381,387]
Cell and tumor biology	[2,9,10,14–19,27,28,32,39,42,47,49,51,53,56,57,59,60,68,73,75,77,78,81,82,84,88,91,96,97,99,101,106,112,114,115,119,121,123,124,126,127,131–134,137–139,143–145,150]	[153,158,161,164,167,170,172,174,177,179–181,183,185,186,188,189,191,192,198,200–202,204,207,209,210,212,213,215,217,220,223,226,229,231-234,236–238,242,244,246,247,249,252,253,260,268,270,271,273,277,279,283,285]	[290,292,293,298–300,306,311–313,316,318,321,322,329,331,332,335,337,339,340,342,344–346,348,351,352,354,355,358,361,363,365–367,369–373,376–378,384,385,388,390,391]
Experimental therapeutics	[4–6,21,22,29,34,35,43,48,50,63,66,70,74,79,80,85,92–95,103,109,110,129,135,148,151]	[155,160,162,166,187,199,206,211,222,224,240,255,261,264,269,284,286]	[287,291,294,295,317,324,333,338,341,350,360,362,379,382,389]
Tumor immunology	[11,33,45,87,98,100,111]	[216,245,248,258,276]	[309,320,323,325,364]
Epidemiology and prevention	[37,41,83,118]	[152,173,178,195,196,208,221,227,228,254,257,266,267,272,274]	[297,386]
Cancer imaging	[20,31,36,40,44,52,71,104,108,149]	[156,157,163,175,176,184,197,205,235,239,241,251,278]	[301,347,356,368]
Clinical investigations	[8,13,55,62,67,105,116]	[190]	[296,305,307,343,349,353,380]
Animal models	[12,38,58,86,130,141,142,147]	[165,169,194,203,214,219,243,259,263,275]	[288,314,319,328,330,334,359,375,383]