The life,times,and health care of Harry L Hopkins: Presidential advisor and perpetual patient

Abstract

Harry Hopkins was the most important nontitled allied leader in World War II. He was the advisor to President Roosevelt who managed the diplomacy between Roosevelt, Churchill, and Stalin from 1941 to 1946. Throughout these times, Hopkins was ill and required transfusions, admissions to the hospital, and nutritional supplementation to keep him well enough to travel the world and manage the allied war diplomacy. There has been no unifying theory to account for all his symptoms and his reported pathologic and autopsy findings. In this paper, we will review his political and medical history and a differential diagnosis of his illness.

Keywords

Harry Hopkins World War II gastric cancer Winston Churchill

Introduction

Harry Hopkins was the most important nontitled allied leader in World War II. He was the trusted advisor of President Roosevelt who managed the shuttle diplomacy between Roosevelt, Churchill, and Stalin from 1941 to 1946. Throughout these tumultuous times, Hopkins was seriously ill with a mysterious malady that was variously called, gastric cancer, hemochromatosis, post-gastrectomy syndrome, Crohn’s, celiac disease, and cirrhosis. During World War II he required frequent transfusions, admissions to the hospital, and nutritional supplementation to keep him well enough to travel the world and manage the allied war diplomacy. His medical history has been previously reviewed by historians but there has been no unifying theory to account for all his symptoms and his reported pathologic and autopsy findings. In this paper, we will review his political and medical history and carefully examine his clinical course and the evidence that supports a differential diagnosis of his illness.

Early life

Harry S Hopkins was born on 17 August 1890 in Sioux City, Iowa. He had four siblings and was raised in several cities in Iowa, Nebraska, and Illinois before finally settling in Grinnell Iowa. As a youth in Chicago, he was diagnosed with typhoid and gained the reputation as a sickly child.¹ He attended Grinnell College and after graduating in 1912 moved to New York City and took a job as a social worker. He worked for the New York Association for Improving the Condition of the Poor (AICP). While working for the AICP, he organized one of the first public employment programs in the United States, the Bronx Park Employment Program. From 1915 through 1930, Hopkins worked on various public social programs including the New York City Bureau of Child Welfare, American Red Cross, The Bellevue-Yorkville Health Project, and eventually became the director of the New York Tuberculosis Association.

Hopkins and Roosevelt

In 1931 the governor of New York, Franklin D Roosevelt (FDR), created the Temporary Emergency Relief Association with a 20 million dollar budget. Hopkins was named the initial executive director of the agency and became the president of the agency in 1932 after FDR became aware of Hopkins and his extraordinary organizational talents.

In 1933 when FDR started his first term as President of the United States, he brought Hopkins to Washington DC to run the Federal Emergency Relief Administration, the Civil Works Administration, and the Works Progress Administration. Hopkins was a key figure in the creation of the New Deal and again demonstrated his success at managing agencies with budgets of billions of dollars.

First trip to the Mayo Clinic

In December Hopkins was evaluated at the Mayo Clinic for weight loss, nausea, vomiting, and abdominal pain. These symptoms were similar to those that he experienced in 1934 when he struggled with weight loss and was medically treated for peptic ulcer disease. In addition, he had a family history of gastric cancer.^2,3 He was admitted to St Mary’s hospital in Rochester Minnesota on 11 December 1937⁴ for tests where it was determined that his ulcer disease was causing obstruction accounting for his weight loss. The evaluation of peptic ulcer symptoms in the 1930s and 1940s was predominantly by barium upper GI series.⁵ Hopkins was a lifelong smoker and, therefore, was predisposed to recurrent peptic ulcer disease.

Due to his relationship with the President, Hopkins was cared for by some of the most celebrated physicians of the day. George B Eusterman (Figure 1) was his internist when Hopkins was evaluated at the Mayo Clinic in 1937. He had many contributions to the medical literature but was the first to report the use of barium radiology to diagnose gastric cancer.⁶

Figure 1.

George Eusterman, Mayo Clinic, c1960 (compliments of the archives of the Mayo clinic).

In the 1930s, the medical management of peptic ulcer disease was centered on dietary measures. The “Sippy” diet was a cream-based dietary intervention and was considered the standard of care.^7,8 The importance of vagal and hormonal control of acid had not been established and the importance of H pylori infection in upper gut peptic ulceration would have to wait another 50 years.^9–11 The indications for elective surgery were obstruction or chronic ulceration with pain and weight loss. The distinction between peptic ulcer disease and cancer often was sorted out at the time of surgery.

Partial gastrectomy

On 20 December 1937, Hopkins underwent a partial gastrectomy and gastrojejunostomy for an obstructing mass in the distal stomach.¹² His surgeon, Waltman Walters (Figure 2), conducted a high subtotal resection with a “polya” type of reconstruction with an enteroenterostomy below the gastrojejunostomy.^2,13 The final pathology on the gastrectomy specimen confirmed a stage III gastric adenocarcinoma.² Despite the advanced stage of this tumor, his Mayo Clinic physicians stated that the chance of recurrence was only 33%.¹⁴ Walters, who joined the Mayo staff in 1924, was one of the best known gastrointestinal surgeons of his day.¹⁵

Figure 2.

Waltman Walters, Mayo Clinic, c1945 (compliments of the archives of the Mayo Clinic).

Hopkins was eventually discharged from the Mayo Clinic on 15 January 1938¹⁶ and he recuperated at the New Orleans home of John Hertz the founder of Yellow Cab and the Hertz rental car company, originally known as Hertz-U-Drive. A month later, he continued his slow recuperation in Coral Gables at the winter home of Joseph P. Kennedy Sr.¹⁷ During this recovery, Hopkins was invited to Warm Springs by the President to discuss the ailing economy. FDR was in the process of increasing taxes and decreasing spending in an effort to deal with a worsening federal deficit. Hopkins recommended a plan that was exactly opposite to that which was planned by the President. Hopkins suggested that government spending should markedly increase on social programs and for the Federal Reserve to loosen credit, based on Keynesian principals.

By June of 1938, Hopkins was recovering well from his surgery and was reexamined at the Clinic for an outpatient evaluation.¹⁸ By the winter of 1938, Hopkins had sufficiently recovered that FDR appointed him as Secretary of Commerce,¹⁹ but in 1939, his health again took a turn for the worse. It started in March of 1939 with what Hopkins thought was a bad flu.²⁰ These “flu” symptoms would persist, on and off, for the remainder of his life. He became chronically troubled by weakness and weight loss associated with vomiting, cramping abdominal pain, and diarrhea after eating (bloody stool was not reported) reminiscent of malabsorption.² Roosevelt’s physician, Ross McIntire (Figure 3), recommended to Hopkins that he stay on a low fat diet likely recognizing that the malabsorption of fats was a major cause of Hopkins’ diarrhea. Ross McIntire, an ear, nose, and throat surgeon, had been the personal physician to FDR since his first term.²¹

Figure 3.

Ross McIntire MD 1939, White House Physician. From the Harris and Ewing Collection, Library of Congress.

Hopkins was sent back to the Mayo Clinic in late March 1939, was evaluated by barium upper GI series for recurrent cancer and none was found. The negative workup was communicated from Dr Eusterman to Hopkins’ doctors suggesting that he adhere to a “more hygienic mode of living…”.²² This reference and others suggest that Hopkins’ dietary indiscretions were frequent.

With the “good” medical report in hand he then traveled at the end of March 1939 to Warm Springs Georgia to be with the President. While at Warm Springs, Hopkins described himself as having “wobbly legs”. His trouble with leg weakness continued into the summer of 1939 as did his weight loss and clinical syndrome of malabsorption. During that summer he was visited by his son, Robert, who was surprised by how sick his father appeared. Robert Hopkins observed that his father was weak, with leg spasms and spent most of his time in bed in July of 1939.²³ Dr McIntire was overseeing most of his medical care at this time and continued to prescribe a bland diet and injections of liver extract.²⁴ McIntire was still blaming the after effects of the winter flu when Hopkins traveled back to Rochester Minnesota.²⁵

Second admission to the Clinic

He was again admitted to the Mayo Clinic on 22 August 1939,^26,27 and was still in the hospital on 1 September when Hitler invaded Poland. Hopkins continued to deteriorate as the Mayo physicians were divided on how to treat the President’s advisor. In a letter that Hopkins sent to his brother he stated that his serum protein was 1/3 the expected value.²⁸ As Poland rapidly fell to Blitzkrieg, a new Mayo physician was involved in the care of Hopkins. Andrew Rivers was consulted and recommended a combination of blood transfusions, injections of vitamins, iron, and nutritional supplementation. Rivers was a world renowned Mayo physician with a specialty in peptic ulcer disease.²⁹

Hopkins failed to improve and in fact was told that he had less than 4 weeks to live. He was discharged in the middle of September when he returned to Washington DC where FDR insisted that Dr McIntire consult with the former Surgeon General, Rear Admiral Edward R Stitt MD, in an effort to save Hopkins from his continued downhill course.^30,31 Dr Stitt had an international reputation in the field of tropical medicine. He was admitted to the Naval Hospital in Washington DC where he was again put on a special diet. He slowly recovered and was discharged but largely house bound from October 1939 through March of 1940.³²

Taking up residence at the White House

By late spring of 1940, Hopkins was ready to resign his position as Secretary of Commerce due to his poor health, but he had recovered sufficiently to return to his most important position as presidential advisor. On 10 May, Roosevelt invited Hopkins to stay at the White House as the 1940 election approached and the war in Europe expanded. For the next 3.5 years, Hopkins stayed in the Lincoln suite and worked daily with the President, with a card table serving as a desk.

The President prevailed in his third-term election bid against his Republican opponent, Wendell Willkie. Unfortunately the problems in Europe worsened as Hitler’s “Blitz” of British cities caused massive devastation. Winston Churchill, the Prime Minister of the United Kingdom, attempted to lift the spirits of the British citizens by his public words while he privately was petitioning FDR to support the allied war cause. By late December, it was apparent that England required material support to withstand Hitler’s constant bombing and inevitable plan for a cross channel invasion. FDR gave his “arsenal of democracy” speech on 29 December and Lend-Lease was born. FDR sent Hopkins to England in January of 1941 to talk to Churchill and work out the details of the Lend-Lease program. The press often criticized the FDR/Hopkins relationship since Hopkins did not have an official title in the government for many of his functions. In fact, the press assumed that Hopkins would become ambassador to England when this trip was announced but FDR admitted that Hopkins was not strong enough to carry out the functions of an ambassador.³³ Upon his arrival in England, Hopkins was ill but he rallied quickly and met with Churchill as planned. Due to his obvious illness Churchill described Hopkins as…“a soul that flamed out of a frail and failing body. He was a crumbling lighthouse from which there shone the beams that led great fleets to harbor”.^34,35

Lend lease

Upon returning to the United States, Hopkins was put in charge of the 7 billion dollar Lend Lease budget, the initial allocation approved by Congress in mid-1940. Lend Lease program, formally titled An Act to Further Promote the Defense of the United States, was designed to lend the WWII allies 50 billion dollars of war matériel on the theory that they would repay in kind after the war. Although there was a presumed administrative structure described in the allocation bill, FDR and Hopkins initially bypassed those provisions and for the first several months Hopkins controlled the spending from his card table in the Lincoln bedroom. During this time Hopkins continued to struggle with weight loss and weakness and was regularly getting transfusions in the White House.³⁶

By July of 1941, with the Lend Lease program in full swing, Hitler opened an eastern front with Russia and Hopkins was again sent to London to confer with Churchill. FDR had decided that Hopkins needed to extend the provisions of Lend Lease to Moscow to make certain that the Eastern Front would not collapse under the weight of the German Wehrmacht. Despite the fact that Churchill was not happy about supporting Stalin, Hopkins flew to Russia in late July to meet with “Uncle Joe” (FDR’s favorite nick-name for Stalin). The trip to Moscow was very difficult on Hopkins. He had stopped over in London where he was already ill but then flew in the gun turret of a PBY (Consolidated Aircraft Corporation patrol bomber) around the north coast of Norway and down into besieged Moscow. Hopkins was ill throughout the trip but he rallied as he prepared for the meetings with the Russian leadership.³⁷

Hopkins met with Stalin and discussed what provisions Russia needed to continue the fight on the Eastern Front. Hopkins immediately flew back towards England on 1 August but unfortunately lost his bag with all his medications. He became very ill on the trip back and was taken directly to HMS Prince of Wales Battleship in the North Atlantic and received medical care that included a transfusion. Churchill was also on the Prince of Wales and together they crossed the Atlantic to meet with FDR at Placentia Bay Canada where the Atlantic Charter was signed on 14 August 1941.³⁸

During the first week of November of 1941, Hopkins was at Hyde Park with the President, working on production problems that were hampering the operational side of Lend Lease. His legs became so weak that he could not walk and he was admitted to the Naval Hospital in Washington DC on 5 November.³⁹ While in the hospital, he received blood transfusion, nutritional supplements but little rest. He continued to help administer the now 12 billion dollar Lend Lease program during his one-month stay in the hospital. He felt renewed on 3 December when he was released from the hospital just 4 days prior to the Japanese attack on Pearl Harbor.

“Date that will live in infamy”

On 7 December, while reports from Hawaii were relayed to the President describing the devastating Japanese attack, preparations were made for FDR to ask Congress for a declaration of war. Hopkins had a role in crafting the “date that will live in infamy” speech including the next to the last lines “With confidence in our armed forces—and with the unbounding determination of our people—we will gain the inevitable triumph–so help us God”. From that point forward, until the President’s death, Hopkins went from the manager of Lend Lease to the President’s strategic war advisor.⁴⁰

Hopkins’ weakness and difficulty walking flared again and required admission on 16 January 1942. During a 2-week stay at the Naval Hospital, he was again transfused and also received intramuscular injections of liver extract for presumed B12 deficiency.⁴¹ Hopkins was discharged from the hospital on a special diet and a long list of medications (Table 1). Unfortunately the diet and medications were not enough to keep him out of the hospital, being admitted again for 5 days at the end of March.⁴²

Table 1.

Special diet and medications prescribed by the Naval Hospital to Harry Hopkins in February of 1942 (Sherwood, p. 494).

Appella powder as necessary (an apple-based nutritional supplement) (http://archpedi.jamanetwork.com/article.aspx?articleid=1178345)

Liver extract 5cc IM injections every other day for 2 weeks, Lederle Company (to treat B12 deficiency) (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933806/pdf/bullnyacadmed00550-0003.pdf)

Calcium gluconate (for calcium deficiency)

Haliver oil with vitamin D at breakfast, Abbott Company (excellent source of vitamin D) (http://onlinelibrary.wiley.com/doi/10.1002/jps.3080211217/pdf)

Dry diet, liquids only between meals (post gastrectomy diet)

Amino acid powder, Mead Johnson Company (protein source in patients with maldigestion)

Hepavex Compound before each meal, Lilly Company (compound containing carnitine and other nutritional supplements) (http://www.invesa.eu/en/INT/view-product/hepavex-200/p57)

Alutropin prior to each meal, Campbell Products Company (an aluminum hydroxide antacid) (https://casetext.com/case/campbell-products-v-john-wyeth-bro)

V-cap with each meal, Abbott Company

By April, Hopkins was well enough to accompany General George Marshall to London to discuss how the United States should enter the European War Theater. This time the delegation flew on a Pan American Clipper and Hopkins was accompanied by Commander J. B. Fulton, a navy doctor assigned by Ross McIntire to look after Hopkins. These negotiations often required conversation on Churchill^’s terms which included all night sessions where the conversation was lubricated with brandy. FDR was aware that this pace and lifestyle would often wear down Hopkins, so he instructed Marshall to “put Hopkins to bed under 24-hour guard of the Army…” Fortunately Hopkins got his rest because by the time he returned to New York City on 19 April he was looking well.⁴³ Despite the fact that Hopkins was accompanied by a physician, Dr Fulton admitted that Hopkins did not always adhere to his medical regimen.⁴⁴

Through the late spring and early summer of 1942, Hopkins’ health held, and he actively participated in the debate of a potential allied invasion of western France versus North Africa. One of the lead British participants, Allan Brooke, commented on the extraordinary impact that Hopkins had on the decision-making, especially when his “miserable health is taken into account”.⁴⁵

Hopkins (and Marshall) made a second trip to London on 16 July 1942 but returned to Washington in time for his planned 30 July wedding to Louise Macy. The wedding occurred in the Oval study on the second floor of the White House and Roosevelt served as best man.⁴⁶ Despite his hectic schedule Hopkins remained well through the end of 1942 and into January of 1943 when he accompanied the President to Casablanca for their famous allied meeting. While FDR and Churchill were making plans for the war after North Africa, Stalin’s Red Army had finally won a victory in an Eastern Front battle, as they captured 90,000 German soldiers and held Stalingrad.

Allied victories at Kursk, North Africa, Sicily, and Southern Italy, carried the US and a moderately healthy Hopkins until the end of the summer of 1943. Unfortunately by the end of August after returning from the Allied conference in Quebec, Hopkins was back in the hospital, this time at the new Naval Hospital at Bethesda, Maryland. He again received blood transfusions and vitamins to treat his exhaustion, diarrhea, weight loss, and weakness. The recommended 3 months of rest offered by his doctors turned into 2 weeks.⁴⁷ Hopkins left the hospital on 11 September to return to the White House as planning for “Overlord” (Allied cross channel invasion of France) was beginning.

By November the President and Hopkins were traveling again, this time aboard the Battleship Iowa headed towards Tehran and a meeting with Stalin and Churchill. When Hopkins met with one of his sons on 20 November in Carthage on his way to the “Big 3” conference, he was described as “exhausted and not at all well.”⁴⁸ His health held and the conference went well as the three leaders planned what would turn out to be the latter stages of the war.

Second laparotomy at the Mayo Clinic

At the start of 1944, Hopkins and his new wife had moved out of the White House but he quickly found himself back in the hospital. He was admitted to the Bethesda Naval Hospital on 4 January, again with the “flu”. His weight was 126 lbs and he was again treated with transfusions, vitamins, and a protein-enriched diet. This time he did not improve. He left the hospital but was getting outpatient injections twice each day. He was recommended to return to the Mayo Clinic for a laparotomy with the hope of finding a cause of his persistent weight loss, diarrhea, and weakness. As Hopkins continued to struggle with his chronic illness he was given the news that his youngest son, Stephen, was killed in action in the Pacific Theater. Hopkins was forced to cope with this personal loss while anticipating the next step in management of his illness, a major operation.⁴⁹

On 29 March he underwent his second laparotomy where, much to everyone’s surprise, his gastric cancer had not recurred. His gastrojejunostomy was revised and he recovered enough to be discharged on 7 May to recuperate at the White Sulfur Springs West Virginia, where he could get medical care at the Army’s Ashford General Hospital while occasionally staying at the Greenbrier Hotel.⁵⁰ He did not return to his home in DC until 4 July, well after the successful D-Day invasion, still not fully recovered from his surgery.⁵¹ By this time he had been ill and outside the day to day war management for many months and his relationship with FDR had cooled slightly. In September of 1944 the Allied leaders were meeting again in Quebec and Hopkins was not invited despite the fact that he had improved enough to travel.⁵²

After the Presidential election in November of 1944 (FDR’s fourth), Hopkins found himself in better health and the President’s key advisor again. Plans were put into place for a meeting of the allied leaders in Yalta in the Crimea. There were some in the government who thought that Hopkins would not survive the trip because the recovery from his last operation had been incomplete.⁵³ Hopkins himself wrote a note to his own daughter, Diana, which included his will and instruction that Mrs Roosevelt would help her if anything happened to him. The trip to Yalta was complicated because there were stops in London, Paris, Rome, Naples, and Malta. Unfortunately, Hopkins became ill during the flight to Malta. Once in Malta, he became weak, with severe abdominal pain and diarrhea. As Roosevelt arrived on 2 February 1945, Hopkins had rallied and was able to greet the President on the battleship Quincy in the Grand Harbor at Valetta Malta. Of the American delegation, the President looked even worse than Hopkins. The upcoming meeting with Stalin and Churchill would be the President’s last.⁵⁴

On 3 February 1945 all parties flew to Crimea where Hopkins was described with pale yellowish skin “stretched tight over the bones of his weary face”⁵⁵ (Figure 4). Hopkins went directly to bed when he arrived, suffering from severe diarrhea. He was instructed by doctors to eat only cereal but Hopkins, famous for dietary indiscretion, continued to eat caviar, cabbage, which only worsened his abdominal pain. He camped out in his room which was fortunately close to the bathroom where he spent most of the conference and would only emerge to attend the afternoon plenary sessions. On 11 February, Hopkins did not participate in the final Yalta photo shoot because he was back in bed trying to recover sufficiently for the long trip home. As the presidential party aboard the battleship Quincy sailed the Mediterranean anticipating the 9-day trip home, Hopkins became so sick that he insisted on putting ashore at Algiers. He had lost 18 lbs on the trip and he felt he would not survive the trip home on the battleship. He had been getting plasma transfusions and liver extract and he was worried that this continued therapy on the ship home would not sustain him.⁵⁶

Figure 4.

Harry Hopkins in Crimea 1945.

Final visit to the Mayo Clinic

Hopkins was back in DC on 24 February, but immediately returned to the Mayo Clinic on 26 February.⁵⁷ For the first time the Mayo physicians decided he had celiac sprue. They again treated him with transfusions and careful dietary management. Hopkins could not gain weight but did start to feel better. He was still in the hospital at the Mayo Clinic on 11 April when FDR died of a stroke in Warm Springs Georgia. Hopkins left the Clinic on the 13^th to return to Washington DC for the President’s funeral. Hopkins was brought to the White House to brief President Truman where Hopkins was described as looking “like death, his skin a cold white with no flesh underneath it”.^58,59

After the funeral, Truman wanted Hopkins to go to Moscow to arrange a final meeting with Churchill and Stalin to discuss Stalin’s possible breach of the Yalta conference agreement. This time he traveled with his wife, who was determined to make Hopkins adhere to his transfusions, injection schedule, and his dietary restrictions. He arrived at the Kremlin on 26 May 1945, 4 days before Hitler would commit suicide. Although his health continued to fail, he completed his meetings with Stalin and prepared the way for the final meeting of Truman, Churchill, and Stalin at Potsdam.⁶⁰

In July of 1945, Hopkins resigned his government service with a letter to Truman.⁶¹ During his last trip to Washington DC, Truman awarded Hopkins the Distinguished Service Award on 4 September 1945.⁶²

By October he had worsening nausea, vomiting, and diarrhea while he was still getting transfusions at the townhome in Manhattan that Hopkins and his wife were renting. He was admitted to Memorial Hospital in New York City on 9 November where he was jaundiced with ascites and evidence of liver failure. He died at the age of 55 on 29 January 1946.⁶³

Cause of death

It is clear that Hopkins died of the complications of cirrhosis. The signs of jaundice, ascites, and ultimately gastrointestinal bleeding suggest that the terminal cause of death was unmistakable. This is reinforced by the finding of nodular cirrhosis at the time of autopsy. The cause of his liver disease is less clear. There are times that Hopkins’ drinking habits might have been described as excessive, but the multiple transfusions (at least 35 blood transfusions and numerous transfusions of pooled plasma) that he received in the last 5 years of his life were a likely source of viral hepatitis and therefore a cause of cirrhosis.²

Hopkins had a curative resection of Stage III gastric cancer in 1937. This histology was reviewed by Halsted and appears to be accurate.² The cure of his cancer was documented by his second operation at the Mayo Clinic in 1944 and the lack of tumor seen on autopsy. Despite his curative resection, he developed a debilitating disease that started after his 1937 gastrectomy and continued until his death in 1946. This debilitating disease presented with a syndrome that included weight loss, abdominal pain, diarrhea, malabsorption, visual disturbance, leg weakness, and gait instability. The differential diagnosis for this syndrome includes B12 deficiency, malabsorbtive enteropathy, post-gastrectomy syndrome, Crohn’s disease, enteropathy-associated T cell lymphoma, and Whipple’s disease.

B12 Deficiency

In the differential diagnosis, vitamin B12 deficiency appears to account for most of the symptoms. The most in-depth analysis of the subject of Hopkins’ diseases was provided by Halsted in his 1975 manuscript.² He suggests that much of the presenting syndrome was simply malnutrition related to an enteropathy and that a presumed B12 deficiency would have been a secondary condition due to malabsorption. Hopkins often had hemoglobin measured at 10 g/100 mL or less and on his blood smear his red cells were routinely called macrocytic consistent with megaloblastic anemia, a classic finding in patients with B12 deficiency.² Although he did not manifest any psychiatric symptoms that occur with B12 deficiency, he did have some of the neurologic signs including difficulty with balance and progressive weakness.^2,23 The visual disturbances that Hopkins experienced have been poorly characterized, simply being referred to as poor vision and impaired dark adaption. This nonspecific finding could be present with B12 deficiency or celiac disease.²

The medical evidence supports the possibility that B12 deficiency was the primary illness that disabled Hopkins from 1937 until his death. Pernicious anemia is very unlikely given the fact that he had a gastric analysis during his 1937 admission to the Mayo Clinic.² Achlorhydria associated with pernicious anemia was very easy to identify in 1937 and was probably ruled-out early in his time at the Mayo Clinic.⁶⁴

In contrast, acquired B12 deficiency after subtotal gastrectomy, although rare, had been reported in the 1940s, and may have been due to operative cytoreduction of parietal cells, or chronic gastritis in a small gastric remnant.⁶⁵ Hopkins clearly had worsening megaloblastic anemia after his gastric surgery that partially responded to his transfusions and liver extract injections. The diagnosis of B12 deficiency explains his anemia, leg weakness and the eventual failure of oral nutritional support.⁶⁶

Hopkins’ health changed for the worse after his gastrectomy and never improved. Prior to 1937 his medical illnesses including his peptic ulcer disease and his occasional diarrhea were mild and easily controlled with diet. He had no previous admissions, no visual symptoms, leg weakness, and no anemia. The chronic condition most likely precipitated by subtotal gastrectomy is B12 deficiency.

Celiac disease or gluten sensitive enteropathy

Celiac sprue was the eventual diagnosis that the Mayo doctors settled on in 1945. There were portions of his presentation that mimicked non-tropical sprue, including episodes of diarrhea associated with large ingestions of fat, 6 years prior to his gastrectomy.² The auto-immune nature of this disease and its relationship to dietary gluten was unknown in 1945 so the Mayo doctors could not have known the etiology or how to treat it. Celiac disease was not confirmed on Hopkins’ autopsy but the typical histologic findings of celiac disease (villous blunting, crypt hyperplasia and intraepithelial lymphocytes) were not well understood in 1940s. They may have been recognized as early as 1904, but were not accepted and more widely known before 1954.^67,68 In his 1975 article, Halsted reviewed the Hopkins autopsy slides and commented that the “bowel was not compatible with sprue”. He also noted that the material had been fixed 30 years prior to review, “and autopsy material is not likely to give an accurate picture of intestinal epithelium”.² Autolysis at autopsy is a well-known and common limitation to histologic interpretation of bowel mucosa. In fact, Paulley⁶⁷ notes post mortem changes as one of the road blocks to correctly defining the microscopic pathologic findings in nontropical sprue, thus, the final pathological confirmation of this diagnosis is lacking. No matter what the cause of the enteropathy, Hopkins had evidence of a malabsorbtive syndrome that was not controlled by a low fat diet. Gluten sensitivity is possible but it is not clear why this disease would have worsened after subtotal gastrectomy.^69,70

Post gastrectomy syndromes

Syndromes associated with gastrectomy were common place in the 1930s and 1940s but the most common syndromes were related to vagotomy (there is no evidence that Hopkins had a vagotomy with his gastrectomy for gastric cancer in 1937). The post vagotomy syndromes associated with diarrhea or dumping have been well documented. These syndromes are much less common and much less debilitating with intact vagus nerves despite the extent of the gastric resection. In addition, these syndromes are often reasonably well managed with careful dietary management. The illness that Hopkins sustained in the last 7 years of his life was poorly managed by diet.^71,72

Crohn’s disease

Some of his presenting symptoms may also be the presenting symptoms of Crohn’s disease. Hopkins’ abdominal pain, diarrhea and weight loss could represent small bowel stricturing and fistulae. The main evidence against Crohn’s disease is the fact that regional enteritis was not identified by his Mayo surgeons during his 1937 and 1944 operations. The clinical and pathologic features of Crohn’s disease were well known to the Mayo physicians by the late 1930s. It is extremely doubtful that it was missed at 2 laparotomies, several barium GI series and an autopsy examination.⁷³

Enteropathy-type T Cell Lymphoma (ETL)

High-grade malignant tumors of different cell type can mimic one another on standard histologic evaluation. In current oncologic pathology practice, many high-grade tumors can now be defined using immunohistochemistry. At the time of the original pathological diagnosis of Hopkins’ gastric cancer, and at the time of Halsted’s review of the gastric tumor, immunohistochemistry was not available to help define malignant neoplasms. One possibility to consider given the patient’s clinical course is enteropathic T cell lymphoma, which can involve the stomach and has been reported as a primary tumor in the stomach often associated with celiac disease. The prognosis is somewhat better than that for gastric adenocarcinoma. The Mayo doctors could not have diagnosed ETL since it was not defined in the medical literature until the late 1970s.^74,75

Whipple’s disease

The clinical presentation of diarrhea, weight loss, and abdominal pain, in a male with chronic illness often calls for a differential diagnosis that includes such rare syndromes as Whipple’s disease. The histologic features of Whipple’s disease had been characterized at the time of Hopkins’ death but his autopsy findings do not support this diagnosis.⁷⁶

Summary explanation of his clinical course

The best explanation for his overall clinical course is that Hopkins had several diseases. Although this violates Occam's razor, there is no single diagnosis that easily explains the complicated syndrome that he endured. Based on the full course of his documented health care, we hypothesize that Harry Hopkins had a curative subtotal gastrectomy for gastric adenocarcinoma but may have developed chronic gastritis or atrophy in his gastric remnant and resultant B12 deficiency. Most of his post gastrectomy syndrome of megaloblastic anemia, muscle weakness, and weight loss can be explained by untreated or partially treated B12 deficiency.

Hopkins had the clinical findings of an enteropathy and this likely explains the “malabsorbtion syndrome” that he manifested. Ultimately in the early 1940s, he developed post-transfusion, viral hepatitis. The ongoing damage to his liver resulted in cirrhosis which was his eventual cause of death.

Conclusion

Harry Hopkins was the key Presidential advisor from the late 1930s until Roosevelt’s death in 1945. During that time he was involved in many of the most important New Deal, Pre-war, and War-time decision and operational strategies that shaped our world for much of the rest of the century. He did so while he suffered from a mysterious illness that stumped his doctors but rarely kept him from his duty-driven tasks.

Footnotes

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.

Author biographies

Theodore N Pappas is the Distinguished Professor of Surgical Innovation in the School of Medicine at Duke University in Durham North Carolina. He is an Ohio native and received his undergraduate degree from John Carroll University in Cleveland Ohio (1977) and his Medical Degree from The Ohio State University in Columbus Ohio (1981). He trained in general surgery at The Brigham and Women's Hospital in Boston Massachusetts from 1981 to 1988 and joined the faculty at Duke University in 1988. He currently serves as the Vice Dean for Medical Affairs in the School of Medicine at Duke.

Sven Swanson, MD is from Iowa and earned a Bachelor of Science in Electrical Engineering from Iowa State University of Science and Technology in 1980. He received his Medical Degree from the University of Iowa in 1984. After completing residency training in Anatomic and Clinical Pathology at the University of Virginia in 1988, and fellowship training in Surgical Pathology at the Hospital of the University of Pennsylvania in 1989, he practiced pathology in Durham, North Carolina at Durham Regional Hospital until early 1998. Since then, he has been practicing pathology at Athens Regional Medical Center in Athens, Georgia.

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Hopkins operated on. New York Times Dec 21^st, 1937, p. 14.

13.

Hopkins’ progress satisfactory after operation at Mayo’s. Chicago Tribune, 22 Dec 1937, p. 5.

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Hopkins Leaves Clinic. The Washington Post, 16 Jan 1938, p. 8.

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Harry Hopkins Regaining Strength in Florida Sun. Chicago Daily Tribune, 17 Feb 1938, p. 16.

18.

Harry L Hopkins to Join James Roosevelt at Mayo’s. Chicago Tribune, 26 June 1938, p. 10.

19.

Olson S. Hopkins Sworn At White House, ‘Very Happy’. The Washington Post, 25 Dec 1938, p. 2.

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Hopkins in Chicago on Way to Mayo Clinic. The Washington Post, 24 Aug 1939, p. 2.

26.

Hopkins goes to clinic. New York Times, 24 Aug 1939, p. 16.

27.

Harry Hopkins to Remain Week Longer in Mayo Clinic. Chicago Daily Tribune, 31 Aug 1939, p. 11.

28.

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30.

Hopkins in Chicago on Way to Capital from Mayo Clinic. Chicago Daily Tribune, 15 Sept 1939, p. 24.

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Kluchhohn FL. Hopkins Rushed to Navy Hospital When President’s Train Arrives. New York Times, 6 Nov 1941, p. 1.

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Hopkins at White Sulphur. New York Times, 16 May 1944, p. 13.

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52.

Hopkins is Back in the White House; Ill Six Months. Chicago Tribune, 7 July 1944, p. 11.

53.

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57.

Hopkins Flown to Mayo Clinic for Checkup. Chicago Tribune, 1 March 1945, p. 1.

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President Sends Hopkins to Stalin. New York Times, 24 May 1945, p. 1.

61.

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Hopkins, 55, Dies in Hospital Here. New York Times, 30 Jan 1946, p. 1.

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