1205518

research-article2023
EARXXX10.1177/01455613231205518Ear, Nose & Throat JournalPappas and Bikhazi

Historical Perspective—Invitation Only

Ear, Nose & Throat Journal

Babe Ruth’s Anaplastic Epidermoid

1­–5
© The Author(s) 2023
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DOI: 10.1177/01455613231205518
https://doi.org/10.1177/01455613231205518
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Theodore N. Pappas, MD1 and Nadim B. Bikhazi, MD2

Introduction
Babe Ruth may be the most recognizable name in the his-
tory of professional baseball. Several years after his hall of
fame career, he developed an anaplastic epidermoid naso-
pharyngeal carcinoma and died of a widely metastatic dis-
ease. This article will review the details of his medical
history, including the use of an experimental drug which
was used to treat his tumor.

Professional Baseball Career

George Herman Ruth was born on February 6, 1895, in
Baltimore Maryland. At the age of 7 he was sent to the St.
Mary’s Industrial School for Boys, where he spent 12 years
learning a variety of skills, including baseball.1 At the age
of 18 years, he signed a professional baseball contract and
played his first major league game with the Boston Red
Sox in 1914. As a starting pitcher and power hitter he
helped the Red Sox win the World Series in 1915, 1916,
and 1918 (Figure 1). After the 1919 season, Ruth’s con-
tract was sold to the New York Yankees, where he spent
the next 14 years and was a key participant in 4 World
Series titles. His home run totals for his career and for a
single season stood as league records well past his retire-
ment. He was inducted into the inaugural class of the
Major League Baseball Hall of Fame in 1939.2
Ruth enjoyed good health until his 50s, when he had his
right knee operated on for pain due to a cartilage problem
from his playing days. In 1945, he was advised by his phy-
sician to drink less alcohol and reduce his body weight. He
was able to lose from 278 pounds to 238 pounds “without
dieting,” but it is unclear if he lost weight by consuming
less alcohol or if the weight loss was the first sign of his
malignancy that was discovered the following year.3
Figure 1. George Herman Ruth 1919. Photo available at
https://www.loc.gov/pictures/item/2016827093/.
sinus infection by his physician, Philip MacDonald. In
November of 1946 he required admission to the French
Hospital in New York City with worsening left face pain
and swelling.5 Ruth had deteriorated so significantly that
he entered the hospital in a wheelchair.5 Clinically, his
exam was described as “Horner’s Syndrome,” associated
with paralysis of the left palate and left vocal cord.6 His
left eye was swollen, and his left face pain gave him a
continuous headache. Early during this admission, some of
his symptoms were thought to be due to a dental problem,
but extraction of 3 teeth did not relieve any symptoms.5,7
Dr. MacDonald called in a variety of specialists when
Ruth’s symptoms progressed to the point that he could no
longer swallow, his left eye was swollen shut, and he could
1
Department of Surgery, Duke University, Durham, NC, USA
2
Department of Otolaryngology, Ogden Clinic, South Ogden, UT, USA

Medical History Received: September 5, 2023; revised: September 12, 2023; accepted:
September 15, 2023
Sinus Infection Corresponding Author:
Theodore N. Pappas, MD, Department of Surgery, Duke University
In September of 1946, Ruth complained of head-and-neck School of Medicine, Box 3479, Duke University Medical Center,
symptoms that started with hoarseness of his voice.4 This Durham, NC 27710, USA.
progressed to pain over his left eye, which was treated as a Email: theodore.pappas@duke.edu

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2 Ear, Nose & Throat Journal 00(0)

barely speak.5,8 When physical exam and X-rays suggested

a neck mass, the team of physicians offered operation.8
Ruth underwent a 2-hour operation on January 6, 1947,
which included biopsy of a left neck mass plus ligation of
several branches of the left external carotid artery.6,9 Ruth
was not told the results of the biopsy, but his wife was
informed that the biopsy confirmed cancer.10
Ruth recovered slowly as he did not walk until January
29 and lost an additional 40 pounds due to his inability to
eat.11 He underwent postoperative radiation therapy to the
left side of his head and neck to control his symptoms.11
News reports from early February described Ruth’s condi-
tion as “fair” and did not mention cancer or sinusitis as a
diagonosis.12,13 Ruth spent his 52nd birthday in the hospi-
tal but was discharged on February 15, looking frail and
weighing only 189 pounds.14,15
Ruth had some symptom relief over the next few
Figure 2. George Herman Ruth, June 13, 1948, Yankee
months. His eating and face swelling improved, and he Stadium, Yankees retire Ruth’s number “3.” Available at https://
was well enough on April 27, 1947, to attend “Babe Ruth commons.wikimedia.org/wiki/File:Babe_Ruth_Bows_Out.jpg.
Day” at Yankee Stadium.16 By June, his symptoms had
recurred, and he was evaluated by physicians at Mount
Sinai Hospital in New York where he was offered an Florida vacation, still feeling well, as he planned a trip to
experimental treatment directed toward his head-and-neck Los Angeles in April of 1948 for the grand opening of the
tumor.17,18 movie “The Babe Ruth Story.” 25,26

Pteroyltriglutamic Acid (Teropterin) Treatment Relapse

Dr. MacDonald informed Ruth that a treatment was avail-
able in the form of a “shot” that might help his symptoms.
He was told that “this type of treatment had rarely been
used on a human being before.”17 In his autobiography
entitled, The Babe Ruth Story, Ruth said the matter was. . .
“left up to me. It wasn’t an easy decision. I realized that if
anything was learned about that type of treatment whether
good or bad, it would be of use in the future to the medical
profession and maybe to a lot of people with my same
trouble. So I took the shot.”17
Teropterin, an experimental anticancer drug by Lederle
Laboratories, was a folic acid analog similar to methotrex-
ate, which entered common use in the 1970s.19,20 Ruth was
started on Teropterin (5 mg daily) in June of 1947, during
a brief admission to Mount Sinai Hospital.21 Within
6 weeks of discharge, Ruth had already demonstrated
remarkable improvement.22 His exam on August 14
showed. . .“the mass in the neck had disappeared com-
pletely. His pain has practically gone. He eats solid food
without any difficulty in swallowing. The tenderness to
palpation is gone. The voice has improved a great deal.
The soft palate on the left side now moves as well as the
right side. The left vocal cord is still immobile. He has
gained twelve pounds in weight.”23 In February, Ruth cel-
ebrated his 53rd birthday in relatively good health. He
regained up to 212 pounds, and traveled to Florida where
he vacationed in Miami Beach.24 He returned from his
The New York Yankees retired Ruth’s number “3” jersey
on June 13, 1948, at Yankee Stadium, and Ruth attended
the ceremony (Figure 2). By the end of the month, Ruth’s
symptoms had recurred and he was admitted to Memorial
Hospital in New York City (later known as Memorial
Slone Kettering Cancer Center).27 On admission to
Memorial Hospital, he was found to have a bulging mass
in the left posterior and lateral walls of the nasopharynx,
partial paralysis of the soft palate, and a left shoulder
drop.6 He was treated with additional radiation therapy to
his left neck for his worsening pain and tube feeding for
persistent weight loss 6 On July 20, Ruth had gold seeds
implanted around a lymph node in the left neck, which
resulted in some minor improvement of his pain.6,28 He
developed hiccups near the end of July and a chest X-ray
in August showed new metastatic disease in the right
chest.6 Ruth’s condition worsened as he developed fever,
peripheral edema, and evidence of hypoxia likely from
pneumonia. He died on August 16th, 1948, at 8:01pm.6
The Autopsy
Pathologist Dr. Paul Wozencraft conducted the autopsy on
Ruth an hour after his death. The final pathology of Ruth’s
tumor was confirmed to be an anaplastic epidermoid carci-
noma of the nasopharynx. The tumor had spread regionally
to the skull base, encasing cranial nerves 9, 10,11, and 12.
Pappas and Bikhazi
He also had widespread metastatic disease in the liver,
lung, bone marrow, and adrenals.6
Discussion
Treatment of a Rare Tumor
Anaplastic epidermoid carcinoma of the nasopharynx was
a rare tumor in the 1940s, but at the time of Ruth’s death
most head-and-neck surgeons were familiar with the diag-
nosis and management of the disease. Up to 50% of
patients had cranial nerve symptoms and nearly 70% pre-
sented with palpable lymph nodes in the neck, similar to
Ruth’s clinical course. In the 1940s half of all patients pre-
sented with metastatic disease.29,30
Treatment of nasopharyngeal carcinoma was rarely sur-
gical but the operation on Ruth at the French hospital,
early in 1947, was conducted to secure a histologic diag-
nosis. In addition, several branches of the external carotid
were ligated during the operation. For head-and-neck
tumors of this sort, surgeons in this era, often ligated the
blood supply to control bleeding in the operative field or
reduce symptoms or tumor growth.31 Ruth was treated
with 3 separate episodes of radiation treatment in an effort
to manage his severe symptoms. The first episode of field
radiation occurred at the French Hospital in early 1947
which gave him some temporary relief of symptoms. Ruth
was treated again with external beam radiation in June of
1948, during his final admission to Memorial Hospital.
The symptomatic relief from this second round of radia-
tion was very short in duration. In July of 1948, the physi-
cians at the Memorial Hospital implanted gold seeds
around an enlarged lymph node of his left neck.
Radiation was originally the only effective treatment
that was described for nasopharyngeal tumors. The first
large experience using radiation to treat pharyngeal tumors
was reported from Memorial Hospital in 1917.32 Treatment
of the primary lesion often included combined external
beam radiation plus intracavitary treatment with radium or
radon.33
Today, the treatment cornerstone for nasopharyngeal
carcinoma is concurrent radiation and Cisplatin-based che-
motherapy.34 Both Epstein–Barr virus and Human papil-
lomavirus are thought to be etiologic agents for many
nasopharyngeal carcinomas.35 As with other tumors, the
use of immunotherapy in the treatment of nasopharyngeal
cancer is an area of active investigation.36
No One Told Ruth He Had Cancer
It has been alleged that Ruth never knew he had cancer,24
which is supported by the fact that his autobiography did
not mention cancer as a possible diagnosis explaining his
debilitating illness.37 Ruth’s wife stated that he was not
3
told he had cancer, but she presumed that he knew. When
he was asked how he felt, Ruth was quoted as saying “. . ..
Lousy. And they think they are kidding me. But they aren’t.
I know what I got.”38 Ruth’s knowledge that he was being
treated with an experimental drug, and his rational for tak-
ing it (“. . .it would be of use in the future. . . to a lot of
people with my same trouble. . .”) suggests that he knew
the diagnosis.17 Additionally, when Ruth was admitted to
the Memorial Hospital in New York City, he was quoted as
saying, “Doc, this is Memorial. Memorial is a cancer hos-
pital. . .”39 Based on this evidence; it is likely that Ruth
presumed he had cancer without being told by his doctors.
Before it was common to tell patients their diagnosis, stud-
ies demonstrated that most patients knew they had cancer
without being told by their physician.40
Withholding a cancer diagnosis from patients was com-
monplace in the previous century. The origin of this “ethi-
cal” policy is unclear but likely was seen as humane in an
era when effective treatments for cancer were limited.41
By the 1940s and 1950s families were often informed of a
cancer diagnosis but the patient was rarely told despite the
use of surgical or radiation therapies.42,43 In 1953 a survey
of providers stated that the wide majority of providers did
not inform cancer patients of their true diagnosis.44 By the
1960s, medical ethics began to shift to greater honesty
toward patients and their medical conditions.45,46 Today
clinicians almost never withhold a cancer diagnosis from
patients, even children.47,48
How did the Press Handle the News of Babe
Ruth’s Illness?
The press appeared to be in on the secret of Ruth’s diagno-
sis before his death, but they withheld that information
from the public until after Ruth died. The news reports
which appear on August 12, just 4 days before his death,
stated that Ruth was suffering from a “throat ailment.”49
On August 17, the day after Ruth died, the headline on the
front page of the New York Times stated that Ruth “fought
losing battle against cancer for 2 years.”50 A case report of
a “famous figure” who received Teropterin was reported
on by the Wall Street Journal in September of 1947. The
newspaper article celebrated that a 52-year-old patient
with head-and-neck cancer had been treated in June of
1947 with intramuscular Teropterin and had a dramatic
response to the drug. The case study did not name Ruth but
was authored by one of Ruth’s doctors and was reported at
a national cancer meeting in the summer of 1947.21,51
Experimental Therapy Without Consent
While experimental cancer therapy was uncommon in the
early to mid-20th century, the standards for conducting
4 Ear, Nose & Throat Journal 00(0)
clinical research were introduced with the Nuremberg
Code in 1947.52 In addition, the rules for obtaining consent
for experimental therapy were not formally established
until the 1960s with the introduction of the Helsinki
accord.53 Prior to Helsinki, consent was an informal pro-
cess, documentation was not required, and physicians
were given latitude in making risk versus benefit decisions
for the patients.54 Although this seems odd today, it was
certainly a common practice in the previous era. Based on
the description in his book The Babe Ruth Story, Ruth
must have given, at least, verbal consent to receive the
experimental drug, Teropterin. His statement that they
“. . .left it up to me. It was not an easy decision,”. . . sug-
gests that knew that the drug had not been adequately
tested in humans but was willing to take the risk associated
with this experimental treatment.17
Conclusion
George Herman Ruth died in 1948 of complication of an
anaplastic epidermoid carcinoma of the nasopharynx. His
tumor presented in 1946 with severe pain of the left head
and neck, dysphagia, and significant hoarseness. Consistent
with ethical norms of the day, Ruth was not informed by
his physicians that he had cancer. During his first admis-
sion to the hospital, Ruth underwent an operation in an
effort to diagnose and palliate his symptoms. Ruth did not
improve with surgery but did have some improvement
with field radiation to the left head and neck. When his
symptoms worsened again, he was offered an experimen-
tal medication Teropterin, a folic acid analog, which had
only been used in animals before Ruth agreed to the injec-
tions. His clinical response to Teropterin was dramatic but
lasted less than a year. His symptoms recurred in the sum-
mer of 1948 prompting an admission for supportive care at
the Memorial Hospital in New York City where he died on
August 16, 1948.
Acknowledgments
None.
Data Availability Statement
None (this historical review does not contain data).
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
Ethical Statement
None required.
Grant Number
None.
Informed Consent
None required for this historical review.
Trial Registration
None.
ORCID iD
Theodore N. Pappas https://orcid.org/0000-0001-9110-4849
References
1. Wagenheim K. Babe Ruth: His Life and Legend. Praeger
Publishers; 1974.
2. Schumach M. Babe ruth, baseball’s great star and idol of
children, had a career both dramatic and bizarre. New York
Times, August 17, 1948.
3. Babe Ruth celebrates 52nd birthday. Los Angeles Times,
February 7, 1946.
4. Ruth B, Considine B. The Babe Ruth Story. Pocket Books;
1948:212.
5. Ruth B, Considine B. The Babe Ruth Story. Pocket Books;
1948:213.
6. Wozencraft P. The autopsy of george herman ruth. The
Memorial Hospital, August 16, 1948:28A.
7. Babe ruth is improving: his sinus infection reported respond-
ing to treatment. New York Times, November 28, 1946:50.
8. Ruth B, Considine B. The babe ruth story. Pocket Books;
1948:214.
9. Neck surgery on babe ruth ‘satisfactory’: hospital silent on
aliment. Chicago Tribune, January 7, 1947:23.
10. Ruth C, Slocum B. The babe and I. Prentice-Hall Publishing;
1959:196.
11. Ruth B, Considine B. The babe ruth story. Pocket Books;
1948:215.
12. Babe ruth ‘not so good.’ The Washington Post, January 29,
1947:11.
13. Babe ruth ‘fair’. The Washington Post, February 3, 1947:8.
14. Crowd cheers as babe ruth goes home. The Atlanta
Constitution, February 16, 1947:13C.
15. Ruth B, Considine B. The babe ruth story. Pocket Books;
1948:216.
16. Ruth B, Considine B. The babe ruth story. Pocket Books;
1948:218.
17. Ruth B, Considine B. The babe ruth story. Pocket Books;
1948:224-225.
18. Babe ruth back in hospital. New York Times, June 25,
1947:27.
19. Farber S, Cutler EC, Hawkins JW, et al. The action of ptero-
ylglutamic conjugates on man. Science. 1947;106:619-621.
Pappas and Bikhazi
20. Frei E III, Jaffe N, Tattersall MH, Pitman S, Parker L. New
approaches to cancer chemotherapy with methotrexate. New
Engl J Med. 1975;292:846-851.
21. Cure for cancer? New synthetic drugs appear to halt the
growth of malignant tumors. The Wall Street Journal,
September 11, 1947:2.
22. Babe ruth’s condition reported very good. Chicago Tribune,
June 28, 1947:20.
23. Laurence WL. Ruth never knew of cancer malady. New York
Times, August 17, 1948:15.
24. Ruth celebrated his 53rd birthday. Los Angeles Times,
February 7, 1948:11.
25. Werden LA. Sun-tanned babe ruth, back from vacation in
Florida, says he feels ‘better than ever.’ New York Times,
March 28, 1948:1.
26. Ruth B, Considine B. The babe ruth story. Pocket Books;
1948:205.
27. Babe ruth ‘doing well.’ New York Times, June 29, 1948:30.
28. Babe ruth improving: home run king responding to radiation
treatment. New York Times, July 3, 1948:10.
29. Fox CC. Carcinoma of the nasopharynx. Arch Otolaryngol
1948;48:390-401.
30. Graham VP, Meyer RR. Experiences with nasopharyngeal
carcinoma. Radiology 1948;50:83-91.
31. Blair VP. Ligation and temporary constriction of the arteries.
In: Surgery and Diseases of the Mouth and Jaws. CV Mosby
Company; 1912:542.
32. Janeway HH. Radium therapy in cancer at the memorial
hospital in New York. PB Hoeber Publishing; 1917.
33. Martin HE, Blady JV. Cancer of the nasopharynx. Arch
Otolarngol. 1940;32:692-727
34. Lee AWM, Lin JC, Ng WT. Current management of naso-
pharyngeal cancer. Semin Radiat Oncol. 2012;22:233-244.
35. Chua M, Wee J, Hui EP, et al. Nasopharyngeal carcinoma.
Lancet 2016;387:1012-1024.
36. Wong K, Hui EP, Lo K-W, et al. Nasopharyngeal carcinoma:
an evolving paradigm. Nat Rev Clin Oncol. 2021;18:679-695.
37. Ruth B, Considine B. The babe ruth story. Pocket Books Inc;
1948.
5
38. Ruth C, Slocum B. The babe and I. Prentice-Hall Publishing;
1959:197.
39. Ruth C, Slocum B. The babe and I. Prentice-Hall Publishing;
1959:207
40. Hanganu E, Popa G. Cancer and truth. J Med Ethics.
1977;3:74-75.
41. Davis L. Medical ethics and the art and practice of medicine.
NEJM. 1937;217:206-212.
42. Lynch JJ. What must the cancer patient be told? Linacre Q.
1955;22:127-130.
43. Cheever D. Medical ethics. NEJM. 1941;224:837-844.
44. Fitts WT, Ravdin IS. What philadelphia physicians tell
patients about cancer. JAMA. 1953;153:901-904.
45. LaForet EG. The “Hopeless” case. Arch Int Med.
1963;112:314-326.
46. Rhoads PS. Medical ethics and morals in a new age. JAMA.
1968;205:517-522.
47. Jenkins V, Fallowfield L, Saul J. Information needs of
patients with cancer: results from a large study in UK cancer
centers. Brit J Cancer. 2001;84:48-51.
48. Stein A, Dalton L, Rapa E, et al. Communication with chil-
dren and adolescents about the diagnosis of their own life-
threatening condition. Lancet. 2019;393:1150-1163.
49. Spiegel I. Babe ruth is critically Ill. New York Times, August
12, 1948:1.
50. Schumach M. Famous diamond star fought losing battle
against cancer for 2 years. New York Times, August 17,
1948:1.
51. Hutchings BL. The synthesis of pteroyl-alpha-glutamylglu-
tamic acid and pteroyl-mu-glutamyl-mu-glutamylglutamic
acid. In: Program of the 4th International Cancer Research
Congress, September 2-7, 1947; St Louis, MO.
52. Shuster E. Fifty years later: the significance of the Nuremberg
code. NEJM. 1997;337:1436-1440
53. Ndebele P. The declaration of helsinki, 50 years later. JAMA.
2013;310:2145-2146.
54. Langer E. Human experimentation: cancer studies at Sloan-
Kettering stir public debate on medical ethics. Science.
1964;143:551-553.