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11/29/2022

Sunday Spotlight: A Brief History of Harvey Cushing and his Contributions to Medicine

 
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​Author: Evan G. Gross, BS

Affiliation: University of Alabama at Birmingham School of Medicine

​Summary
Harvey William Cushing (1869–1939) is widely considered the “father of American neurosurgery” for his numerous innovations and discoveries that helped establish neurosurgery as a distinct surgical field. Cushing performed over 2000 operations on brain tumors over the course of his time at Harvard and Johns Hopkins. At the turn of the 20th century, prior to Cushing’s rise as a neurosurgeon, the mortality rate for intracranial operations stood at 30–50%. By the end of Cushing’s career in the 1930s, records of his surgeries reflected a mortality rate of only 8% (Black, 1999). He was a gifted artist and prolific writer of over 300 publications covering a range of topics from pituitary adenomas and acoustic neuromas to hemostatic innovations and cerebrospinal fluid circulation. He described distinct neurological phenomena for which he is eponymously credited, including Cushing’s disease, Cushing’s reflex, Cushing’s ulcer, and others. Finally, he was a stern and dedicated teacher to an entire generation of 20th century neurosurgeons (Figure 1).
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Figure 1. Harvey Cushing making a postoperative sketch dated 1928. Photo courtesy of the Cushing/Whitney Medical Library, Yale School of Medicine.

​

​Cushing’s Early Life (1869–1891)

Cushing was born in Cleveland, Ohio on April 8, 1869, the youngest of ten children. His great-grandfather, grandfather, father, and older brother were all physicians. Cushing attended Yale from 1887–1891, where he received his Bachelor of Arts degree. During his first 2 years at Yale, Cushing studied Latin, Greek, history, and literature. Physiological chemist and Yale professor Russell Chittenden introduced Cushing to physiology which solidified his pursuit of a career in medicine (Fulton, 1946).
 
Medical Training (1891–1900)
Cushing attended Harvard Medical School from 1891–1895. Like many medical students of the time, Cushing helped administer ether anesthesia to numerous surgical patients. In January of 1893, during Cushing’s second year of medical school, one of Cushing’s patients undergoing operation for a strangulated hernia rapidly declined. In his diary, Cushing noted “a sudden great gush of fluid from the patient’s mouth,” and the patient died shortly thereafter (Fulton, 1946). Although the cause of death was uncertain, this experience pushed Cushing to the brink of quitting medicine. In a letter to his father, Cushing wrote “I supposed I had killed the patient. The operation was completed in spite of the episode, as a demonstration to the class. I slunk out of the hospital, walked the streets of North Boston the rest of the afternoon, and in the evening went to the surgeon’s house to ask if there was any possible way I could atone for the calamity to the man’s family before I left the Medical School and went into some other business” (Fulton, 1946). After encouragement from the attending surgeon, Cushing and fellow medical student Ernest Codman began the first anesthetic recording of each patient’s respirations, pulse, and temperature throughout the surgical procedure (Shephard, 1965) (Figure 2).
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Figure 2. Anesthetic record by Harvey Cushing dated July 16, 1895. Photo courtesy of the Treadwell Library, Massachusetts General Hospital.



​Upon completion of medical school in 1895, Cushing began his 1-year internship with the surgical service at Massachusetts General Hospital (MGH). During December of 1895, German physicist Wilhelm Roentgen published his seminal paper on his discovery of x-rays (Tubiana, 1996). Although the Crooke tube Roentgen used for generating x-rays would not be introduced to MGH until May of 1896, Cushing immediately recognized the significance of Roentgen’s discovery. In February of 1896, Cushing wrote to his mother that “Everyone is very excited over the new photographic discovery. Professor Roentgen may have discovered something with his cathode rays that will revolutionize medical diagnosis. We won’t be able to have secrets anymore.” (Fulton, 1946). By May of 1896, Cushing had helped establish the use of Crooke tubes for generating x-ray images in MGH’s out-patient service. Cushing personally made radiation-sensitive emulsion film, captured patient radiographs, and developed the film (Doyle, 2017). Cushing’s first report on the use of x-rays came in 1897, describing 2 patients each with a gunshot wound to the spine and a bullet localized using x-rays. Upon completion of his internship in 1896, Cushing moved to Johns Hopkins Hospital where he began training under William Halsted, often hailed the “father of American surgery,” and William Osler, often hailed the “father of American internal medicine” (Gunderman, 2010). Over his years at Johns Hopkins, Cushing adopted Halsted’s surgical techniques of gentle tissue handling and meticulous hemostasis. This afforded Cushing superb operative results, low mortality rates, and low infection rates compared to peers across the rest of America and Europe (Jay, 2001).
 
Cushing’s Wanderjahr (1900–1901)
Cushing spent 14 months in Europe from July of 1900 to August of 1901 conducting research with a primary focus on understanding intracranial pressure. Cushing arrived in Liverpool, England in July of 1900. He spent time with surgeon Victor Horsley who performed the first retrogasserian ganglionectomy in 1890 (Wilkins, 1963). However, Cushing was unimpressed with Horsley’s surgical technique, noting that Horsley would “make a great hole in the [patient’s] skull” and often complete his surgeries in “less than an hour” with little concern for hemostasis and “blood everywhere” (Cushing, 1901). In October of 1900, Cushing traveled to Lausanne, Switzerland where he studied under surgeon Cesar Roux. Like his impression of Horsley, Cushing found Roux to lack compassion for his patients in the perioperative period. Patients would endure surgeries while “shivering with cold” and “no anesthetic,” and Roux even refused Cushing’s offer to perform the anesthetic technique he had learned under William Halsted at Johns Hopkins. Despite these disappointments in Lausanne, Cushing helped physiologist Charles Sherrington in mapping the motor and sensory cortices of apes through direct electrical stimulation of different cortical regions. Cushing would continue his research of cortical mapping in America (Figure 3).
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Figure 3. Sketch of the human motor cortex by Harvey Cushing dated 1907. Photo courtesy of Cushing/Whitney Medical Library, Yale School of Medicine.



​The most noteworthy period of Cushing’s Wanderjahr was spent in Bern, Switzerland from November of 1900 to May of 1901, where he spent time with physiologist Hugo Kronecker and surgeon Theodore Kocher. To investigate the response of cerebral vessels to changes in intracranial pressure, Cushing worked with Kronecker to devise a pulley system that applied precise force to the cerebral cortex of living canine subjects. Cushing would perform a craniectomy, apply the pulley system to the canine cerebrum, replace the cranial defect with a glass window, and observe changes to vascular diameter while manipulating intracranial pressure through his pulley system (Fulton, 1946). From these experiments, we arrive at the eponymous Cushing reflex whereby cerebral perfusion pressure drops as intracranial pressure increases, triggering an increase in arterial blood pressure to restore blood flow to the brain. In addition to his experiments with Kronecker, Cushing operated alongside surgeon Theodore Kocher. Cushing noted that Kocher was painstaking in his surgical technique and meticulous about hemostasis, a welcomed departure from Cushing’s experiences in Liverpool and Lausanne (Modlin, 1998). Like William Halsted, Kocher had a profound influence over Cushing’s surgical technique. After his 14-month Wanderjahr, Cushing visited Kocher in Bern, Switzerland many times over the years, and even told Kocher that he would “unhesitatingly and with perfect confidence put [himself] in [Kocher’s] hands” if undergoing surgery (Fulton, 1940).
 
Cushing’s Return to Johns Hopkins (1901–1912)
Cushing returned to Johns Hopkins in August of 1901 where William Halstead agreed to allow Cushing to focus on neurological surgery. At the beginning of the 20th century, it was uncommon for American surgeons to specialize in a particular field, but Halstead made an exception for Cushing. By 1910, Cushing had operated on approximately 180 brain tumors with a mortality rate of only 10–15% compared to the 30–50% mortality rates across the rest of America and Europe (Greenblatt, 2003). Thus, Cushing helped transform intracranial surgery from feasible to clinically effective through his years of specialization at Johns Hopkins. Perhaps Cushing’s largest single work was his contribution to the textbook “Surgery” edited by William Williams Keen, where Cushing prepared a 276-page monograph entitled “Surgery of the Head” which included 154 of Cushing’s detailed operative illustrations (Jay, 2001). In his final years at Hopkins, Cushing focused on disorders of the pituitary gland and operations of the sellar region (Figure 4). In January of 1913, Cushing published a comprehensive monograph entitled “The Pituitary Body and Its Disorders” where he described pituitary basophilic adenomas and hypercortisolism (Cushing, 1913).
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Figure 4. Harvey Cushing alongside a patient with acromegaly. Photo courtesy of the Cushing/Whitney Medical Library, Yale School of Medicine.



​Cushing’s Time at Harvard University’s Peter Bent Brigham Hospital (1912–1933)

In 1912, Cushing accepted the position of surgeon-in-chief at Peter Bent Brigham Hospital in Boston. During this time, Cushing authored over 200 publications across the gamut of neurosurgical diseases and techniques. Cushing would serve in World War I as head of U.S. Base Hospital no. 5 in Passendale, France from May of 1917 to February of 1919 where he and fellow Harvard physicians and nurses treated countless casualties of war (Fulton, 1946). After the war, Cushing continued at Peter Bent Brigham Hospital. Cushing performed and wrote about gasserian ganglionectomy for treating trigeminal neuralgia and transsphenoidal resection of pituitary tumors. He described stomach ulcers as a frequent consequence of intracranial tumors which are eponymously called Cushing ulcers. In 1925, Cushing published his Pullitzer prize-winning biography of his mentor Sir William Osler who had died in 1919 (Cushing, 1925). He worked with American neurosurgeon and neuropathologist Percival Bailey to develop a classification system for gliomas based on tumor histogenetics (Bailey & Cushing, 1927). Cushing was an innovator in electrosurgery and hemostasis. He invented the first clips for cranial vasculature to minimize blood loss and found that skeletal muscle fragments promote coagulation, a mechanism that the medical community is still investigating today (Morla, 2022).

References: 
  1. Black PM. Harvey Cushing at the Peter Bent Brigham Hospital. Neurosurgery. 1999;45(5):990-1001. doi:10.1097/00006123-199911000-00007
  2. Fulton JF. Harvey Cushing: a Bibliography. Springfield, Illinois: Charles C Thomas, 1946.
  3. Shephard DA. Harvey Cushing and anaesthesia. Can Anaesth Soc J. 1965;12(5):431-442. doi:10.1007/BF03004404
  4. Tubiana M. Wilhelm Conrad Röntgen and the discovery of X-rays. Bull Acad Natl Med. 1996;180(1):97-108.
  5. Doyle NM, Doyle JF, Walter EJ. The life and work of Harvey Cushing 1869-1939: A pioneer of neurosurgery. J Intensive Care Soc. 2017;18(2):157-158. doi:10.1177/1751143716673076
  6. Gunderman RB, Seymour ZA. Harvey W. Cushing. AJR Am J Roentgenol. 2010;194(2):296-298. doi:10.2214/AJR.09.3356
  7. Jay V. The Legacy of Harvey Cushing. Arch Pathol Lab Med. 2001;125(12):1539-1541
  8. Wilkins RH. Neurosurgical Classic number 13. J Neurosurg. 1963;20:1009-1022. doi:10.3171/jns.1963.20.11.1009
  9. Cushing H. Notes Made During a Sojourn of Fourteen Months in Some Parts of the Old World, 1900 June to 1901 August. Manuscripts and Archives, Yale University Library. New Haven, CT: Yale University; 1900–1901.
  10. Modlin IM. Surgical triumvirate of Theodor Kocher, Harvey Cushing, and William Halsted. World J Surg. 1998;22(1):103-113. doi:10.1007/s002689900357
  11. Fulton JF. Arnold Klebs and Harvey Cushing at the 1st International Neurological Congress at Berne in 1931. Bull Hist Med. 1940;8:332–354.
  12. Greenblatt SH. Harvey Cushing's paradigmatic contribution to neurosurgery and the evolution of his thoughts about specialization. Bull Hist Med. 2003;77(4):789-822. doi:10.1353/bhm.2003.0168
  13. Cushing H. The Pituitary Body and Its Disorders. Annals of Surgery. 1913;57(1):137-142
  14. Bailey P, Cushing H. A classification of the tumours of the glioma group on a histogenetic basis, with a correlated study of prognosis. British Journal of Surgery. 1927;14(55):554-555. doi.org/10.1002/bjs.1800145540
  15. Cushing H. The Life of Sir William Osler, 2 vols. Oxford Clarendon press. 1925.
  16. Morla S, Deguchi H, Zilberman-Rudenko J, et al. Skeletal muscle myosin promotes coagulation by binding factor XI via its A3 domain and enhancing thrombin-induced factor XI activation. J Biol Chem. 2022;298(2):101567. doi:10.1016/j.jbc.2022.101567

​Conflicts of Interest: The authors report no conflicts of interest concerning the material or methods used to develop this manuscript.

Acknowledgements: No acknowledgements.

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