Is Lincoln Earliest Recorded Case of Rare Disease?

By David Brown
Washington Post Staff Writer
Monday, November 26, 2007

Abraham Lincoln was the rarest of men, and John G. Sotos believes that extended all the way to his chromosome 10.

A physician, connoisseur of rare ailments and amateur historian, Sotos believes Lincoln had a genetic syndrome called MEN 2B. He thinks the diagnosis not only accounts for Lincoln's great height, which has been the subject of most medical speculation over the years, but also for many of the president's other reported ailments and behaviors.

He also suspects Lincoln was dying of cancer at the time he was assassinated, and was unlikely to have survived a year. He thinks cancer -- an inevitable element of MEN 2B -- killed at least one of Lincoln's four sons, three of whom died before reaching age 20.

Sotos's theory assigns one of medicine's rarest conditions to one of the nation's best-known figures. It is likely to be controversial. But unlike many historical diagnoses, it can be easily proved or rejected with a DNA test for the single mutation in the gene called RET on chromosome 10 that causes MEN 2B.

Samples of the martyred president's DNA presumably exist in bloodstained fabrics scattered around the country and in eight skull fragments from Lincoln's autopsy in the possession of the federal government. Whether anyone will be willing to sacrifice part of a relic to answer this question is another issue.

Sotos, 50, is publishing his idea in a Web-based book, "The Physical Lincoln," which is expected to be available next month. He will present his findings at Johns Hopkins Hospital in Baltimore on Wednesday.

"No physician ever removes doubt from his or her mind. I am prepared to be wrong, but I don't expect to be wrong," he said last week.

Sotos is a cardiologist who heads a medical device company in Palo Alto, Calif. Several years ago, he published research asserting that William Howard Taft had obstructive sleep apnea, which went away when he lost a large amount of weight after leaving the White House.

Sotos is supporting his new hypothesis with a 350-page companion Web volume that assembles virtually every known description of Lincoln's health and physical features, as well as those of his relatives.

MEN 2B is short for "multiple endocrine neoplasia type 2B." It is a subtype of a genetic disease whose sufferers invariably develop cancer in a hormone-producing organ. Some are born with tumors. Nearly every victim gets cancer of the thyroid gland, and about half also get cancer of the adrenal gland. In about half the cases, patients inherit the disease from a parent. (Sotos thinks there is some chance that Lincoln's mother, who died at age 34, may have had it.) In the remainder of cases, the mutation appears spontaneously in the sufferer, who can then pass it on to children.

MEN 2B is the "rarest of the rare hereditary cancer syndromes," said Jeffrey F. Moley, a surgeon and an expert in the disease at Washington University School of Medicine in St. Louis.

Moley's department has 82 patients with MEN 2B in its database. He suspects there are about 500 in all in the United States. If Abraham Lincoln had MEN 2B, he would be the earliest recorded case.

In the patients Moley sees, droopy eyelids with thickened edges and prominent, bumpy upper lips are the most striking features. Most patients also have massively enlarged colons that bulge visibly, gurgle audibly and produce large amounts of gas -- symptoms not generally attributed to Lincoln.

"The facial appearance is not convincing. Overall, I don't think so," Moley said after learning of the theory and consulting a few pictures of Lincoln.

But, he added, there are always exceptions. Some abnormalities are so subtle that not even the patient notices them. "I would not rule it out completely," Moley said.

Others have speculated that Lincoln might have had Marfan syndrome, a genetic condition characterized by long arms, legs and fingers, loose joints, often a breast-bone deformity and a weakness of the aorta, the body's largest artery, which can burst and cause sudden death.

The discovery in 1991 that Marfan syndrome is caused by one of numerous mutations in a gene for fibrillin, a component of elastic tissue, led some people to propose testing Lincoln's DNA for the defect. That was never done, in part because it would have consumed significant amounts of Lincoln's bodily relic.

MEN 2B can also cause a "marfanoid" appearance, and that's what first brought the diagnosis to mind, Sotos said. What clinched it was the 16th president's lips.

One of MEN 2B's many manifestations are neuromas, or lumps of nerve tissue, on the tongue, lips and eyelids. There are no pictures of Lincoln's tongue, but his lips have a bumpy appearance in photographs. The hint of a lump on the right side of his lower lip is even visible in the engraved image on the $5 bill.

These growths also occur in the intestines and can cause constipation and diarrhea. Lincoln had lifelong constipation, and briefly during his presidency he took mercury-containing pills called "blue mass" to relieve it.

Sotos believes several things point to a diagnosis of cancer. Numerous observers commented that Lincoln became thinner in the White House. Three months before he died in April 1865 at age 56, he fainted while getting up quickly from a chair. He had periodic severe headaches and cold hands and feet. All are symptoms of pheochromocytoma, an adrenaline-producing tumor that is one of the two MEN 2B-associated cancers.

Furthermore, Sotos believes that two of Lincoln's sons, Willie and Tad, also had MEN 2B.

Photographs of them show somewhat irregular lips. Willie died at 11, probably of typhoid fever, and Tad at 18, reportedly of tuberculosis. Sotos believes that Tad had thyroid cancer that had spread to his chest and caused fluid to accumulate outside his lungs, a condition noted by physicians several times.

Lesser arguments for the diagnosis include Lincoln's famously sad face and his predilection for lounging horizontally whenever possible. Sotos believes those were signs of weak muscle tone, sometimes seen in MEN 2B.

A big argument against the theory, however, is Lincoln's age. Some people with MEN 2B die of cancer in childhood. Only recently have many survived into their 40s. Sotos says he has found just two reports of people surviving untreated into their 50s, and admits that Lincoln would have to be a similar rarity.

MEN 2B patients in Japan tend to live longer than those in the United States, even though everyone has the same mutation in the RET gene. Moley, the Washington University expert, speculates that that is because other genes, common among the Japanese but infrequent in Western populations, somehow modify the disease.

Sotos is well aware that a surprisingly large amount of Lincoln biological material exists. In addition to the skull fragments, the National Museum of Health and Medicine in Washington has a lock of hair clipped from around Lincoln's head wound, and the bloodstained cuffs from one of the physicians who performed the autopsy. The autopsy did not include examination of the neck, chest or abdomen, an investigation that might have revealed cancer, if Sotos's hypothesis is correct.

Tim Clarke Jr., spokesman for the museum, said curators in the past decided that "destroying nonrenewable, historically significant material is not in the public's interest," but added that "as technology changes and the social and ethical environment changes, it could be addressed" again.

The National Park Service collection at Ford's Theatre contains a Brooks Brothers overcoat and suit that Lincoln wore the night he was shot; at least two pillows from his deathbed in the Petersen house across the street; and some towel fragments, all with bloodstains, said Bill Line, the Park Service spokesman. He said the service has two "director's orders" that prohibit research that "destroys or consumes" artifacts.

The Chicago History Museum has the bed where Lincoln died, the mattress, a bloodstained bottom sheet, and a bolster. The collection also includes a shawl worn by Mary Todd Lincoln containing bloodstains that are probably from Henry R. Rathbone, an Army major who accompanied the Lincolns to the theater and was stabbed by John Wilkes Booth, Lincoln's assassin.

Russell Lewis, executive vice president and chief historian, said that while the museum has previously rejected the idea of DNA testing of one of those objects, "I think it's definitely possible now that there could be a way to extract something" without destroying the relic.

But that's not the only issue. The museum must first decide the value of the knowledge that might be gained, and the cost it might have for Lincoln's, and possibly others', privacy.

"We are living in a time where people sometimes feel that they have the right to know everything," Lewis said. "As a museum, we have the obligation to consider whether medical information or private information should be revealed."

For his part, Sotos is not going to press for testing. "I think it will happen eventually, and I'm patient enough to wait for that," he said.

One thing is certain. He came by his diagnosis honestly. While in medical school at Johns Hopkins, he wrote "Zebra Cards," a once-popular accessory to an intern's white jacket. It consisted of a deck of cards (later pages of a book) with one side of each card listing a physical finding or symptom, and the flip side all the rare diseases where it was found.

The title refers to the advice to young doctors: "If you hear hoofbeats behind you, don't expect to see zebras." This means: "Resist the temptation to attribute common findings to exotic diseases" or, more roughly translated, "Don't get fancy."

However, a variant of this aphorism is: "When you hear hoofbeats, don't forget about zebras." It is the acknowledgment that rare diseases do exist, and some people do have them. "Zebra Cards" were a way to keep that knowledge at hand.

Sotos thinks he has found a zebra in the American pantheon.

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