Boston Doctors May Have Cure For Hemophilia

With the help of a beagle named Ellie, Harvard doctors have completed research that could lead to a final cure for hemophilia.

Dr. John C. Norman '50, associate in Surgery, is the head of a project at Boston City Hospital that for the first time has succeeded in curing a dog of hemophilia.

Norman and his associates--among whom is Dr. Victor C. Covelli, Research Fellow in Surgery--earlier discovered the crucial role of the spleen in producing Factor VIII, a substance whose presence in the body prevents hemophilia.

Hereditary Disease

Known as "the disease of kings," hemophilia is a hereditary disease, almost always limited to males, in which blood takes a very long time to coagulate. Normal blood takes five to fifteen minutes to form a clot, but the blood of hemophiliacs may take many hours to do so.

Hemophiliacs are subject to severe and often fatal hemorrhages. Internal bleeding, especially around the joints, has many debilitating effects.

The disease takes the form of a deficiency in antihemophilic globulin--Factor VIII. In normal humans the Factor VIII level in the blood stream ranges from 50 to 200 per cent. Hemophiliacs generally have a Factor VIII level of less than 25 per cent.

A Healthy Spleen

What Norman found is that Factor VIII is produced by the spleen. In the past the treatment for hemophilia has been the injection of Factor VIII into the hemophiliac. Te new method is to replace the defective spleen of the hemophiliac with a healthy one.

The new method has many advantages over the old one. Most important, the hemophiliac tends to produce antibodies which counteract the vital Factor VIII when it is injected. With the new techniques of organ transplant that have recently been developed, it is possible to establish a permanent source of Factor VIII inside the hemophiliac--by inserting an entirely new spleen.

Norman's research has so far been limited to beagles which have been specially bred to produce a strain composed largely of hemophiliac dogs. (The canine disease does not differ significantly from the human form of it.)

The spleen transplant of the dog Ellie is the first totally successful one done by Norman's project. In the past, problems have arisen because the hemophiliac dog rejected the new spleen. Rejection occurs when an animal refuses to accept living tissue from another body. In Ellie's case, doctors avoided the threat of rejection with a combination of immunosuppressors: cortisone, actinomycin C, imuran, and antilymphocyte serum.

The experimental success with Ellie is a prelude to a trial with a human hemophiliac. In most cases the plan is for a normal mother to donate her spleen--which is not usually a vital organ--to her hemophiliac son. The close genetic relationship between mother and son would minimize the difficulty of the transplant.

The risk of the spleen transplant operation is minimal--the same risk that there is in a regular spleen removal, from zero to one per cent.

The hemophilia research has been carried out in the Sears Surgical Research Laboratories in the Cardiovascular Division, of which Norman is director. The project is financed mainly by a grant from the National Institutes of Health.