Christmas Disease

Christmas Disease was first described in an issue of the British Medical Journal on Dec 27, 1952. Successful gene therapy for Christmas Disease was reported fifty-five years later on Dec 6, 2017 in the New England Journal of Medicine. It all started with Stephan Christmas, who was diagnosed in 1949, at the age of two, with a bleeding disorder—of some kind.

Classic hemophilia is hemophilia A. It is due to, (generally speaking), a deficiency of clotting Factor VIII and inherited as an X-linked recessive bleeding disorder, with males (with rare exceptions) being affected. A streak ran through the royal families of Europe and Russia. 

A Bleeder

When Stephen Christmas was two years old he was taken to the Hospital for Sick Children in Toronto, where his bleeding history led to a  diagnosis of hemophilia. This diagnosis would certainly explain a pattern of recurrent and unexplained episodes of bleeding. And at that time, Hemophilia was a well known, if rare, condition. As noted on the site for the National Hemophilia Foundation:

“In 1803, John Conrad Otto, a Philadelphia physician, was the first to publish an article recognizing that a hemorrhagic bleeding disorder primarily affected men, and ran in certain families. He traced the disease back to a female ancestor living in Plymouth, New Hampshire, in 1720. Otto called the males ‘bleeders.’”

There being no known treatment, his parents could only exercise caution and prayer to ward off potentially fatal episodes of bleeding. When Stephen was five, his family returned to London, England to visit relatives.

Stephen Christmas. From  Six Characters...

Stephen Christmas. From Six Characters...

He was admitted to a hospital in London, which had a ready resource that Toronto did not. Nearby, in Oxford was the lab of the pioneering team of coagulation researchers—Rosemary Biggs and R. G. MacFarlane, of the thriving Oxford Haemophilia Centre.  

The Oxford Duo

They found no deficiency of Factor VIII, the essential feature of hemophilia. What they did discover was a deficiency in what is now called Factor IX. A new terminology was needed: Hemophilia A  for Factor VIII deficiency and Hemophilia B for Factor IX deficiency, known to this day as Christmas Disease. In each there is a lack of an enzyme that participates in a cascade  of molecular triggers that results in a clot of fibrin. The defective Factor IX activity is due to a single mutation in the gene whereby cysteine is replaced with serine.

Rosemary Biggs

Rosemary Biggs

RG MacFarlane

RG MacFarlane

Stephan Christmas became a medical photographer and worked for a time at the hospital in Toronto where he was first seen. The only treatments in his era where transfusion of blood and plasma, and this before the availability of screening for AIDS, He contracted AIDS from such transfusions and died of related complications in 1993, at age 46.

Ghost of Christmas Future

Fast forward to 2017 and Hemophilia B gene therapy. A team centered at Children’s Hospital of Philadelphia used viral vector to instill Factor IX gene activity in ten patients with Christmas Disease. 

“Transgene-derived factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use.

Factor IX Defect Hemophilia B

Factor IX Defect
Hemophilia B

Deviant Art Posture by Cilein.

Deviant Art Posture by Cilein.

Merry Christmas, indeed. The online article includes a video summary. This work was preceded by similar work done at facilities in London and elsewhere.

She persisted...

We close with a curios note on the Toronto Canada—London UK nexus. Rosemary Biggs wanted to be a doctor, but her parents were against it. So she got a botany degree from the University of London in 1934, and later a PhD in Mycology—from the University of Toronto. Not to be thwarted, see went back to London and got an MBBS degree, (the equivalent of an MD degree in the US) from the London School of Medicine for Women.  She ended up in the lab of RG MacFarlane and became the first author of the textbook of coagulation and hemostasis that reigned for decades. 

London School of Medicine for Women

London School of Medicine for Women

For a thorough discussion of Hemophilia B see the page on the National Organization for Rare Disorders, (NORD).

For a fascinating discussion of the origin of eponymously named clotting factors see Six Characters in Search of An Author: The History of the Nomenclature of Coagulation Factors.

Leave a comment, emai us at, or check out history of medicine books on our Amazon affliate link.