Transplanting the Human Face

Face transplant pioneer Maria Siemionow

Should composite tissue grafts, such as face transplants be performed in children?

Greg Borschel, recently recruited to the Hospital for Sick Children (1) reviewed the world experience with this dramatic and complex intervention.

Thirteen face transplants have been performed for problems such as facial burns, dog bite, bear attack, neurofibromatosis and gun shot wounds. He drew attention to the challenges: as a small donor pool, worse immunological challenges when skin is transplanted, and the surgical, psychological, rehabilitation, patient selection and ethical issues.

Jennifer Flynn, philosopher in residence at HSC and a recent fellow at the Joint Centre for Bioethics carefully laid out the ethical issues:

1. The risk benefit ratio is a challenge because of medical uncertainty, the finite life of the graft, and the probability that children may need a second graft as their body matures;
2. Informed consent is complexified in the paediatric population as parents or other substitute decision makers will be held responsible for the outcome as the child matures.

Consent of the donors also raises questions about potential morally dubious motivation. Parents of a deceased child might "want to look at my child's face in the future". Personal identity is closely linked to the face, and social adjustment, especially in the teen years, will be predictably difficult.

Candidate selection must include careful evaluation of the psychological health of the child following facial trauma. She recommended that the surgical question be referred to the Research Ethics Board in view of the novelty and ethical complexity of the procedure. Finally, the question arises of how badly off the patient will be without a transplant, compared to the potential problems and the prospect of a lifetime on imunosuppression.

Greg Borshel

Maria Siemionow who performed the first successful face transplant in the United States was then introduced by Ron Zucker. Maria used the Mona Lisa to deconstruct the importance of the subunits of the face, the texture, function, the identity, the role of beauty, the range of expression and the impact of the face on social life.

The first challenge that her team faced was the technical challenge, performing face and scalp transplants in Lewis rats. These operations took approximately six and one half hours. She learned that transplanting bone as part of the composite graft brings in progenitor cells which help survival of the graft as the animal becomes a chimera. She added eye, ear and dental components to the graft over a period of ten years and 1000 grafts. The next phase was cadaver studies. She learned that 1192 square centimeters or 52x29 centimeters of skin is needed to cover the human face. She and her colleagues performed cadaver grafts six years before her first human transplant.

The second challenge is the identity issue, much beloved by the media. She worked with different models of a boy and a man's facial bony structure and showed how different the appearance of the same face becomes based on the infrastructure. She and her colleagues studied identity from various aspects. We are identified by our voice, our walk and other characteristics in addition to the face, though the face is the most prominent manifestation of identity.

Before carrying out the first human face transplant, she had done one thousand animal transplants, 40 cadaver studies and had 65 publications in top journals, including bioethics journals. She wanted to be sure that when she ventured into the experimental phase in human patients that she "would not be perceived as a Doctor Frankenstein." Based on her research alone, she was twice voted by the Membership of the American Association of Plastic Surgeons the winner of its highest honour - The James Barrett Brown Award in 2004 and again in 2007. The first human face transplant was not performed until 2008.

Gaining approval from the Institutional Review Board/ Research Ethics Board was another challenge. The Cleveland Clinic board comprised 40 members including scientists, clinicians, lawyers and lay members. She met with them weekly over a period of one year to secure approval.

The next problem was gaining approval from organ procurement organizations such as the Center for Organ Recovery & Education (CORE), The Gift of Life Program in Michigan and LifeBanc in Cleveland. This required travel to the offices of these organizations and presentations to convince their members took 4 years.

Patient selection was the next challenge. The importance of this question is dramatically illustrated by the Chinese patient who had suffered a bear attack. After he was transplanted, he moved too far away from the transplant centre to be rescued. When he deliberately stopped his imunosuppression and switched to herbal medicine, he lost the graft and eventually died. There have been two deaths among the thirteen patients who have received face transplants.

Maria's patient was a formerly beautiful woman who suffered a gun shot wound to the face inflicted by her husband. She had been healthy and stable with a tracheostomy and feeding tube through 23 operations. The cosmetic result of these interventions was unsatisfactory. Other examples of the selection problems included a burn patient who had no available back-up sites for skin grafts if the transplant was rejected, and a cancer patient whose cancer free status would remain questionable, particularly on immunosuppression.

Complex theoretical issues of justification were explored. Should older patents be excluded? In the hand transplant experience of 50 patients, they proved to be poor adapters. The cortical reorganization required was far more successful in younger patients. Should blindness be a contraindication? Patients who are blind cannot see signs of rejection in the mirror. They need constant supervision by another to be sure their medications are correctly administered, and they cannot exercise their face while looking in the mirror, as required for rehabilitation.

The fifth challenge is the team - an enormous interactive group of psychologists, microsurgeons, ethicists, anesthiologists and others. A total of 30 staff were required for the 22 hour transplant operation. The cost of the procedure, approximately $500,000, was somewhat lower than the total cost of the 23 reconstructive procedures that preceded it. Following transplantation, Maria's patient underwent a period of rejection which responded to increased immunosuppresion. She now has normal two- point discrimination and thermal sensation at 22 months. She can eat, smile and phonate. The challenges from the media were substantial. Social reintegration of the patient into family and work is also a challenge. There have been only two women among the eleven facial transplantations. The social expectation of facial beauty in women is a biasing factor.

Christopher Forrest

Her work was published last year in The Lancet (2). Overall this 20 year tour de force of scientific and clinical perseverance and humility was a thrilling experience to learn about. It was heard by a packed auditorium and given thunderous applause. She closed simply by saying "you need a face to face the world".

In answer to a question from Christopher Forrest, Maria told us that she is working in the laboratory to develop an antibody which selectively blocks alpha-beta T cells and spares gamma- delta T cells, which are tolerogenic. This approach is now being tested in kidney transplant patients. She is also fusing cells ex-vivo to make chimeric cells for induction of tolerance in rats, and is attempting to develop chimeric cells from human cord blood.

M.M.

1. See also The Surgical Spotlight, Spring, 2010

2. Maria Siemionow, Frank Papay, Daniel Alam, Steven Bernard, Risal Djohan, Chad Gordon, Mark Hendrickson, Robert Lohman, Bijan Eghtesad, Kathy Coffman, Eric Kodish, Carmen Paradis, Robin Avery, John Fung. Neartotal human face transplantation for a severely disfigured patient in the USA. The Lancet, 2009, 374, 9685: 203 - 209