Did Lincoln have cancer? Credit: Library of Congress

Scientists have long speculated about the health of the sixteenth American president Abraham Lincoln, whose long, lanky features were reminiscent of the genetic disorder Marfan syndrome, and whose melancholy hinted of depression. Now, John Sotos of Palo Alto, a cardiologist, rare-disease hobbyist (and consultant for the television series House M.D.), has thrown his hat in the ring with a new book1 and a new diagnosis: a rare, cancer-causing genetic disorder called MEN2B.

Q. So why did this diagnosis take so long to bring to light?

The theory that Lincoln had Marfan syndrome was proposed in 1962. It became a white-hot debate for a few years and then it sort of cooled off. It heated up a little bit again when the Marfan gene was discovered in the early 1990s2. But what I learned is that all that heat and light was generated on really an amazingly thin examination of the Lincoln historical record.

Q. How did you arrive at this diagnosis?

I didn?t really do anything specific about Lincoln until the summer of 2006. Then two things happened. First, a friend of mine told me that a new Marfan-like syndrome had been discovered called Loeys-Dietz syndrome3. And Loeys-Dietz had this unusual finding of a bifid uvula [a cleft in the soft palate at the back of the mouth].

That was fine. But about six months later I was reading this random book that had been on my bookshelf for years about the civil war and it mentioned that Lincoln?s fourth son, Tad, had a cleft palate. Cleft palate and bifid uvula are really the same thing. They are just different points on the spectrum of a possible single disorder. So, I did a few weeks of research, and became more and more convinced that Lincoln had Loeys-Dietz syndrome, and then I talked to [Johns Hopkins geneticist Hal] Dietz about it, and became less convinced. So, at this point I thought well, I?m not going to worry about this anymore, I?ve wasted enough time on it. What I?ll do is collect the notes that I have in a little self-published book so that the next guy who tries this won?t have to repeat all the work I did.

We don?t know anything about Lincoln?s flatulence, but we do know he was constipated.

So, I just worked on that sort of accumulation of facts for the book, and then one night a light bulb sort of went on. I was reading a different article entirely and it made me think of medullary thyroid carcinoma which is associated with marfanoid habidis [overgrowth of bones resulting in long limbs] in a syndrome known as MEN2B. And I thought, well, maybe I?ll just check out MEN2B in Lincoln and see if that?s a match.

Q. How rare is MEN2B?

There have been no numbers that I?ve seen on what the exact prevalence is, but it?s probably about one in a million. I?ve never seen a patient with this disease and most physicians have never seen a patient with this disease.

Q. What symptoms does it cause?

Overgrowth of bones. And then there?s overgrowth of neurally derived cells. The benign overgrowth produces neuromas, which are little balls of proliferated nerves that accumulate in mucosal tissues sort of like knots in wood. It turns out that Lincoln had a characteristic sign of this. He had a big lower lip that was asymmetric and bumpy. One of the lumps on Lincoln?s lips is on the five dollar bill.

The other place you get neuronal proliferation is in the gut. So people become constipated. They also become flatulent. We don?t know anything about Lincoln?s flatulence, but we do know he was constipated, and a couple of his law partners would apparently talk about this.

Q. It also causes malignant growth. Does that cause a serious type of cancer?

The two characteristic cancers of MEN2B are medullary thyroid carcinoma and pheochromocytoma. So, what I think was going on was that Lincoln had medullary thyroid carcinoma for a number of years. Lincoln was 56 when he was shot, which is pretty old for someone with this disease, and that?s the greatest challenge for the diagnosis. There are cases in the literature of people with metastatic medullary thyroid carcinoma where people live for 15, 20, 25 years without treatment. It?s an unusual beast in that regard.

Q. This didn?t turn up in autopsy (though it was pretty clear that it was a bullet that killed him). What?s the evidence that he had cancer?

Visitors to the White House frequently spoke of how thin he looked. Then in his last three months his health turned for the worse. He was almost continuously ill in one way or another and my suspicion ? and I won?t go so far as to say my diagnosis ? but it is suspicious that he had three symptoms of pheochromocytoma during this time: headache, orthostatic syncope [he would faint when standing up] and cold, clammy hands and feet, which he complained to a friend about. In fact, this friend saw Lincoln put his feet so close to the fire that they steamed.

Q. Could this diagnosis be checked, theoretically?

Yes. 95% of the people who have MEN2B have the same single codon variant and this is something that is routinely tested for today.

Q. Will it be checked?

Access to Lincoln's body is impossible. After a grave-robbing attempt years after his death, his son reburied Lincoln in an 8 cubic foot block of concrete encased in iron bars. So nobody is getting to him except with a bomb.

There are all kinds of biological materials floating around though that would have his DNA in it. Those with the best claim to be authentic are a few fragments of his skull that were left over in the autopsy instruments and are now owned by the Department of Defense. There are also a lot of blood stained artifacts around? There?s really no shortage of Lincoln DNA that?s above ground. The trick is getting people to release samples.

Q. Your book, The Physical Lincoln, is self-published. Why?

I sent an article manuscript to some medical journals to publish. It entered into peer review at one medical journal and it was rejected because I didn?t have room enough in the paper to make a case that Lincoln was marfanoid; that is somewhat in dispute in the literature.

And to make the case for MEN2B it was just impossible for me just to condense it down. I realized that to convince people of all the evidence for this theory it would take more space than a journal would permit me to have.

Q. Do you have any interests in trying to diagnose other public figures?

That?s a landmine. I do, but I don?t think I want to talk about it. He?s in office and he?s very powerful? You can go to my website and see what I?m thinking there.