The course of history was altered by the illness and death of Emperor Frederick III of Germany in 1888. Frederick developed a tumor of the vocal cord. German surgeons planned to operate on him, although the state of such surgery was very primitive at the time, with extremely high mortality. A British specialist, Dr. Morell Mackenzie, was called into consultation. He performed several biopsies that were negative for cancer, and surgery was deferred. Bitter disputes erupted between the German and British physicians involved in the case. With progression of the disease, the presence of cancer became evident, and Frederick died. The liberal Frederick was succeeded by his son, Kaiser Wilhelm II, who led Germany into World War I.
There are few instances in history in which the illness of a head of state has had such a profound effect on subsequent world events like that of Emperor Frederick III1* of Germany. He developed a cancer of the larynx and died 99 days after assuming the throne. The liberal Frederick, who dreamed of establishing a representative democratic government in the German empire, was succeeded by his son, the notorious Kaiser Wilhelm II. The strutting, pompous Wilhelm, insanely jealous of his uncle and cousin who ruled England and Russia respectively, ultimately led Germany into World War I, the outcome of which created the casus belli of World War II. The medical aspects of the story, which are strongly entangled with the political, are of interest because they demonstrate the difficulties of effective medical diagnosis and treatment prior to the availability of modern technology and satisfactory understanding of the nature of many diseases, in this case cancer. It is said that “nature abhors a vacuum”, and this tragic international episode demonstrates how the vacuum created by ignorance can be filled with egotism, nationalism, rancor, unwillingness to accept new ideas, and unrealistic appraisal of the success of one’s own results.
Emperor Frederick III of Germany
The end of the Franco-Prussian War in 1871, led to the unification of the German states under the Prussian King Wilhelm I, who was crowned emperor. Crown Prince Frederick, Wilhelm’s son, favored the unification, envisioning a government with an upper house of princes and a representative lower house, elected by the people. The unification, however, was engineered by the Prussian Chancellor, Otto von Bismarck, who succeeded instead in accomplishing the absorption of Germany by autocratic Prussia under Wilhelm I. The conservative Junkers, led by Bismarck, firmly believed that representative democracy would lead inevitably to the downfall of the nation. At the time of unification in 1871, Wilhelm I was 73 years old. Frederick and his supporters felt that they would soon have their chance to democratize the German autocracy. But the old Emperor Wilhelm lived another 17 years, and Frederick languished in ceremonial posts well into his middle age, while Bismarck’s power grew.
Frederick married Victoria, daughter of the British Queen Victoria. Victoria had received a liberal education and shared her husband’s views. The British monarchs, Victoria and Albert, desired to maintain their family’s blood ties to Germany, and Prince Albert further hoped that the marriage would lead to the liberalization and modernization of Prussia. The English Crown Princess was a constant target of German conservative political figures and journalists, a fact that was to exacerbate the rancor when a British specialist, Dr. Morell Mackenzie, was called to consult on Frederick’s case.
While historians disagree as to whether Frederick, had he survived, would have truly created a liberal state or would not have effectively challenged the deep-seated conservatism and militarism of 19th century Germany, there is little question that his death and replacement by his son put an end to any such aspirations, and contributed to the events preceding World War I.
The larynx, or “voice box”, is a cartilaginous organ that constitutes the entrance to the trachea, or “windpipe”. Two movable ligamentous vocal cords open to permit respiration, and close to produce voice, as expired air is forced through them. The larynx is a frequent site of cancer, and laryngeal cancer often originates on the vocal cord. With current technology, most early cancers of the larynx, particularly those of the vocal cords, are highly curable because the presence of even a small nodule in this location immediately produces a hoarse voice, leading to early diagnosis. Advanced laryngeal cancers require extensive partial or total removal of the larynx, or, at the present time, are often treated by combined chemotherapy and radiation therapy with laryngeal preservation. Reasonably satisfactory cure rates are obtained with all but the most advanced laryngeal cancers in modern practice. Total removal of the larynx (total laryngectomy) results in a permanent opening of the end of the windpipe onto the lower neck, and causes complete loss of natural, lung-powered voice. Some patients are able to produce a monotonous voice by expelling swallowed air. Since the time of the first laryngectomy, devices have been designed to produce voice in these patients. Nevertheless, until the late 20th century there was no consistently reliable device available to restore voice after total laryngectomy. Even now, total laryngectomy is a disabling operation.
On December 31, 1873, Theodore Billroth performed the first successful total laryngectomy. Prior to that time, surgeons succeeded in performing the operation of “laryngofissure” by opening the larynx in the midline, like a book, and removing small tumors or other lesions directly. Nevertheless, even though these remarkable surgical feats had been accomplished by a few surgeons in the largest hospitals in Europe and the United States, it was not until the second decade of the 20th century that these operations could be performed with acceptable mortality, and with a consistent cure of the cancer. Most patients died of infection postoperatively, and failure to understand the nature of cancer and the limitations of the various procedures usually led to ineffective tumor removal.
To cure a disease, it is necessary to diagnose it and appreciate its nature. The larynx is situated deeply within the throat, and is not visible through the open mouth. The electric light was not invented until 1879, and was not adapted for use in medical instruments until considerably later. Cocaine was introduced as a topical (surface) anesthetic in 1884--thus permitting relatively comfortable examination and manipulation of the throat in the awake patient. The only practical means of visualizing the laryngeal interior, including the vocal cords, was with a dental mirror placed against the patient’s palate (“indirect laryngoscopy”)--providing a reflected view of the larynx in the mirror. In the gas-lit era of the 19th century, illumination was provided by reflected sunlight, mineral oil lamps, and similar sources. Biopsies were performed usually with a curved biting forceps that was guided by the mirror image onto the site to be sampled. Considerable skill was required to visualize the vocal cords, and to obtain an adequate and accurately placed biopsy specimen--in poor light, with an often coughing and gagging patient.
Various diseases produce tumor-like masses or ulcers. These include tuberculosis, tertiary (third stage) syphilis, both prevalent in the 19th century, as well as cancer. It is impossible to tell them apart by simply looking at the lesions. In 1858, Rudolph Virchow1 published his monumental work on the microscopic diagnosis of diseased tissue. For the first time, by microscopic examination of very thin slices of tissue, physicians were able to make definitive diagnoses of disease processes by recognizing the cellular changes characteristic of each. Microscopic examination of tissue obtained at autopsy examination provided the essential knowledge to accurately characterize disease. In the living patient, the procedure of biopsy--that is, microscopic examination of a small specimen obtained from a tumor mass or other abnormal area, permitted accurate diagnosis of malignancy. In current medical practice, no definitive treatment, surgical or other, of any cancer would be undertaken without biopsy proof of malignancy and classification of its type. In the late 19th century, this paradigm was the frontier of medical science.
Morell Mackenzie was the most highly respected British pioneer in laryngolgy of his time. In addition to numerous other publications, his two volumes on Diseases of the Throat and Nose2 were universally recognized and became the standard textbook of laryngology, not only covering the whole field as it existed at the time, but also anticipating many advances that owed their inspiration to the author. Mackenzie devoted himself intensively to the development of laryngoscopy and devised numerous instruments for removing polyps and other lesions from the larynx. He strongly advocated submission of pathologic material removed from the larynx for microscopic examination, thus helping put laryngology on a sound scientific basis.
In 1863, Mackenzie leased a house on Kings Street, London, which he turned into a dispensary to treat diseases of the throat. This dispensary grew, became famous, and eventually was moved to larger quarters, becoming the Hospital for Diseases of the Throat. It was the first specialized facility for the diagnosis and treatment of laryngeal diseases. The large volume of clinical material concentrated there enabled Mackenzie to develop enormous experience and make great strides in the development of laryngology.
The story of Mackenzie and the Crown Prince, later Emperor, Frederick has been told in considerable detail by Scott Stevenson3, and has been reported in the more recent medical literature.4
Sir Morell MacKenzie
In January, 1887, the 55-year-old Frederick, then Crown Prince, became hoarse. Examination by Professor Gerhardt of the University of Berlin revealed a pale red nodule on the left vocal cord. Gerhardt attempted to remove the lesion with a forceps, but succeeded in obtaining only a fragment of material. He then attempted destruction of the lesion by galvanocautery. After 13 such treatments, the nodule persisted and cancer was suspected.
Gerhardt summoned Ernst von Bergmann, Professor of Surgery at the University of Berlin, for a consultation. von Bergmann recommended immediate surgery. He apparently planned a laryngofissure but intended to proceed with a laryngectomy if required. There seems little question that von Bergmann minimized the risk and extent of the procedure that was contemplated. This was not justified based on his or other contemporary results of laryngofissure or laryngectomy for treatment of cancer. Further consultation was advised and the patient was seen by Professor Tobold, a senior Berlin laryngologist, who examined the Prince and agreed with immediate surgical exploration.
At this point, Morell Mackenzie was called from London to give his opinion. There has been doubt and endless controversy as to whether the request for Mackenzie’s presence was initiated by Frederick’s German physicians or through the influence of Frederick’s wife and the British royal family. Publicity shyness was not one of Mackenzie’s shortcomings. He was friend and physician to a glittering array of theatrical and operatic celebrities of the day, and enjoyed being interviewed and seeing his name in print, a tendency that was to exacerbate his later difficulties. Mackenzie was pleased and flattered to be summoned by a personal envoy of Queen Victoria to minister to the Crown Prince of Germany.
Ernst von Bergmann
When he examined the Prince, Mackenzie noted a pea-sized nodule on the posterior (back) part of the left vocal cord, partly beneath the cord. There was slight limitation of motion of the vocal cord and slight congestion (redness and swelling) of the surface. Mackenzie recommended a biopsy that he attempted with unfamiliar German forceps. He succeeded in removing only a small portion of the nodule, which was sent to the famous pathologist Virchow. Virchow could find no evidence of cancer in the small specimen and requested a second piece of the lesion. A second biopsy attempted a few days later was unsuccessful, partly due to inflammation of the recently biopsied left vocal cord. In an action that was to set the stage for further animosity, Gerhardt examined Frederick immediately after the biopsy and accused Mackenzie of injuring the uninvolved right vocal cord with his forceps (which was highly unlikely as Mackenzie was renowned for his dexterity).
About two and a half weeks later, Mackenzie successfully removed about half of the tumor, and again Virchow could find no evidence of cancer. Surgery was deferred indefinitely, and Mackenzie undertook responsibility for Frederick’s further treatment. He eventually removed the remainder of the lesion from the left vocal cord, and once more the specimen (examined by Virchow) was negative for cancer. After cauterization of a small recurrence on August 7th, the left vocal cord healed completely and the growth never recurred, although there was transient swelling of the tissue.
The Prince decided to winter in the mild climate of San Remo, in Italy. On November 5th, immediately after his arrival there, Mackenzie’s assistant, Mark Hovell, noted swelling of the larynx. When Mackenzie examined the Prince, he now suspected cancer. Almost immediately, recriminations began from all quarters. Mackenzie had detractors and supporters. The arguments were heightened by the intense personal hatreds that many of the great European teachers of the same subject held for each other, as well as animosity between the British and German physicians. The most destructive aspect of the controversy was the daily appearance of the criticisms and the most intimate details of Frederick’s health in the public press. These reports were published with complete disregard for the feelings of the individuals involved as “Royalties” were news, and their most intimate affairs were of public interest. Newspaper reporters descended on San Remo, badgering Mackenzie and others, while publishing daily reports. Treatment with potassium iodide was suggested to rule out syphilis, causing great personal embarrassment to Frederick when the suspicion of syphilis was reported in the newspapers.
The consultants, including Mackenzie, finally agreed that the Prince had cancer and recommended a laryngectomy. The Prince, however, refused to undergo a laryngectomy but agreed to have a tracheostomy (insertion of a tube directly into the trachea to relieve airway obstruction) if it became necessary. Frederick’s motives for declining laryngectomy were quite reasonable. Even if it were successful, the functional disability engendered by the operation would render him unsuitable to function as a ruler. He also felt that he had a better chance of surviving to become emperor by not undergoing surgery. Although he had publicly accepted news of his fate with great dignity and calmness, privately Frederick grieved over his illness. Naturally, the confidential physician’s report of Frederick’s cancer was leaked to the press.
Again the controversy raged. Mackenzie was blamed for the delay in treatment. Virchow felt that Mackenzie was trying to blame him for the missed diagnosis. Mackenzie denied any intention of doing so and tried to defend himself by noting that it was rare for cancer to remain undiagnosed after three separate negative biopsies (which was, and still is, a correct observation). There were further recriminations in the newspapers and from political quarters against the Crown Princess who shared the blame with Mackenzie for preventing the original surgery. On February 9, 1888, because of increasing obstruction of the airway by laryngeal swelling, a tracheostomy was performed by Friedrich von Bramann, an associate of von Bergmann.
Mackenzie remained at San Remo to attend the Prince and returned with him to Berlin on March 9th, 1888, when Wilhelm I died and Frederick became Emperor. While in San Remo, a sputum specimen had been examined by Heinrich von Waldeyer, the great German anatomist, and was considered compatible with cancer. This still inconclusive report was nevertheless the most objective documentation of cancer ever obtained during Frederick’s life.
The reign of Emperor Frederick III lasted 99 days until his death from pneumonia on June 15th, 1888.2* Mackenzie remained constantly in attendance during that time. An autopsy carried out by Professors Virchow and von Waldeyer revealed that the interior of Frederick’s larynx had been replaced by a large ulceration containing a nodule of what apparently was cancer, according to the description from a microscopic examination. A large malignant lymph node, not detected during life, also was present on the left side of the neck.
The ugly mixture of medicine and politics produced repercussions in both areas. Following Frederick’s death Mackenzie returned to London, a tired and defeated man. The £12,000 that he had been paid for 13 months of attendance to the Emperor did not begin to compensate him for the financial difficulties created by prolonged absence from his practice. He had lost many of his patients to several of the young laryngologists he had trained.
Calumny abounded in the medical world. The German physicians, who wanted to fix the blame squarely on Mackenzie, published a vitriolic account of Frederick’s case entitled Die Krankheit Kaiser Frederick des Dritten.5 This report minimized the danger of laryngofissure and emphasized von Bergmann’s reported seven successful cases (none of which were for cancer). Gerhardt’s accusation that Mackenzie injured the vocal cords was reiterated, and the entire publication proceeded on the same rancorous note.
Angered by this attack, Mackenzie published The Fatal Illness of Frederick the Noble6 in his own defense. Although his desire to attack his detractors was understandable, the book was injudicious to say the least. Mackenzie was advised to withhold publication but he could not resist, and the book was sold widely in England. Among its various arguments was intense criticism of Gerhardt for his cauterization of the original lesion and of von Bergmann for causing an abscess by creating a “false passage” during a tracheostomy tube change. Both Die Krankheit Kaiser Frederick des Dritten and The Fatal Illness of Frederick the Noble were full of meaningless, petty criticisms that did nothing to enhance the stature of their authors. Although Frederick the Noble may have helped Mackenzie express his anger, it was looked on with considerable disfavor by the British medical establishment. He was criticized by the Royal College of Surgeons and the British Medical Association, and found it necessary to resign from the Royal College of Physicians. He retained some enthusiastic supporters, however, and before his death, Mackenzie founded the British Rhino-Laryngologic Association. He died of pneumonia on February 3rd, 1892, at the age of 54.
During his brief reign as Emperor, although unable to speak because of the tracheostomy, Frederick did his best to fulfill his obligations and plans. An edict that he wrote before he ascended to the throne that would limit the powers of the chancellor and monarch under the Constitution was never put into effect, although he did force the Minister of the Interior to resign when evidence indicated that the Minister had interfered in the Reichstag elections. He moved to improve relations with England, Norway, and Sweden. Wilhelm II, on assuming the throne, immediately abandoned all of his father’s policies and ideas, and eventually led Germany into World War I.
Stevenson,7 upon analyzing the details of the case, concluded that Frederick died of cancer of the larynx, but the course of the disease was far from typical. Most likely, the cancer intervened upon syphilis in this case; von Waldeyer’s examination during life was the best evidence for the cancer, but was not conclusive. The postmortem examination was more conclusive for the ultimate diagnosis of cancer. The autopsy finding of replacement of most of the larynx with a large necrotic3* ulceration was consistent with the diagnosis of syphilis, as was the temporarily favorable response to treatment.
The unfortunate result of this case was that laryngeal biopsy was discredited for decades. In modern times, a more adequate biopsy specimen would be obtained using current technology, and the diagnosis of syphilis (extremely rare after penicillin) would have been made by blood testing.
In sum, Mackenzie was both right and wrong, but probably helped Frederick preserve what life remained for him. By his insistence on confirmation of the diagnosis by biopsy, Mackenzie was well ahead of his time. His reluctance to proceed with surgery was completely reasonable, particularly in view of the results of such surgery in the late 19th century. Interpretation of the biopsy specimens was confounded by the co-existing syphilis. Nevertheless, the preponderance of evidence indicates that Frederick actually did have cancer. Even in current practice, there are uncommon situations when surgery may proceed in the absence of pathologic confirmation, particularly when biopsy diagnosis is obscured by intercurrent disease or previous treatment. Of course, the expected results of such surgery are infinitely better now than they were at Mackenzie’s time. The poor results of both laryngofissure and total laryngectomy prior to 1900 have been discussed. The point is actually moot as Frederick would have refused total laryngectomy, as he did when it was offered. Laryngofissure without laryngectomy, in all likelihood, would not have cured him, even if it had been done earlier in 1887.
Had Mackenzie not interfered with the originally proposed surgery, the outcome probably would have been worse. Perhaps the most dramatic scenario of what might have transpired was described by Carl Ludwig Schleich, as quoted by Stevenson.8 Schleich had gone to watch his old friend and colleague, von Bergmann, operate on the afternoon of the very day Die Krankheit Kaiser Frederick des Dritten was published. Before commencing the operation, von Bergmann addressed his audience of students, explaining that the patient had exactly the same condition as Kaiser Frederick. The diagnosis of cancer had been confirmed by biopsy and von Bergmann announced that he would demonstrate how he would have saved the Kaiser’s life had he been allowed to operate. As the operation proceeded, however, von Bergmann discovered that the disease was not confined to “one small area behind the vocal cord”—rather, it was a more extensive lesion, invading the “region above the larynx”. After an interval of one and a half hours, von Bergmann announced “Gentlemen, we have been mistaken. This is not carcinoma at all - it is diffuse tuberculosis of the larynx. I am discontinuing the operation.” The patient died within the next two hours. As Schleich speculated, had a similar event occurred in the case of Frederick, the progress of surgery would have been injured for a generation.
1* The names of several of the Germans in this story, such as Emperor Frederick III, Rudolph Virchow, and Theodore Billroth, have been anglicized, as they are well known in English language literature by these names. “Kaiser Bill” has always been known as Wilhelm II, and the other Germans are referred to by their German names.
Emperor Frederick III of Germany
Sir Morell MacKenzie
Ernst von Bergmann
2* The year 1888 is known as the “Year of the Three Emperors” (Wilhelm I, Frederick III, and Wilhelm II).
3* Dead tissue
This story is adapted from Silver, CE. Surgery for Cancer of the Larynx and Related Structures, New York, Churchill Livingstone, 1981. © Carl E. Silver
Carl is Professor Emeritus of Surgery at the Albert Einstein College of Medicine in New York. He was Chief of the Division of Head and Neck Surgery at Montefiore Medical Center from 1974 until his retirement in December 2005. In addition to a surgical practice devoted entirely to the treatment of patients with tumors of the head and neck, Dr. Silver published numerous scientific papers, monographs, book chapters, and several movies and videotapes. He is best known as author or co-author of five books on head and neck cancer. After retirement, Dr. Silver moved to Scottsdale, Arizona, and has continued to produce scientific papers for publication, as well as a forthcoming book. Dr. Silver and his wife Gail have been married for 49 years. They have four children and six grandchildren.