When the world's first face transplant was performed in France in 2005, it pushed medical boundaries and made headlines. Yet the procedure's future was very much in doubt.
The surgeons, operating on a 38-year-old Frenchwoman whose face had been mauled by her pet Labrador, had to surmount the opposition of prestigious medical societies, which declared the procedure unethical and immoral. Critics, including surgeons who had lost out in competing to do the first face transplant, said the pioneering team did not follow ethical and legal guidelines.
But the first comprehensive review of every face transplant reported since then -- 28 in seven nations, counting the French case but not two done in Turkey since the review was completed -- has removed many of those early doubts. The report, published online Sunday by The Lancet, says the procedure is generally safe and feasible, and should be offered to more patients.
The endorsement is cautious: The researchers note that the operation is still experimental, risky and expensive (at least $300,000), and patients must be carefully chosen. After the transplant, recipients face continual risks of infection and reactions to toxic anti-rejection drugs.
But the paper adds that for many people --victims of genetic disorders, gunshots, animal bites, burns and other accidents -- transplants can ease or erase the grotesque deformities that leave them subject to taunts, discrimination, isolation and serious depression. Conventional reconstruction techniques are often inadequate, and can produce terrible scars and deformities at the sites in the patient's body from which tissue is removed and transferred to the facial area.
By contrast, face transplants have transformed the lives of nearly all surviving recipients. They have regained their ability to eat, drink, speak more intelligibly, smell, smile and blink; many have emerged from ostracism and depression. Four recipients are back to work or school. (Three patients have died.)
The idea of one individual wearing another's face initially frightened some critics. But contrary to such fears, no recipient physically resembles the stranger who gave it.
The new face "is a pretty unique blend of the recipient and the donor, and it is not as if you would recognize the donor walking down the street," the review's senior author, Eduardo D. Rodriguez of NYU Langone Medical Center, said in an interview. He holds degrees in medicine and dentistry, and led the team that performed a full facial transplant in 2012, when he was at the University of Maryland.
Dr. Rodriguez said he and his co-authors spent nearly a year reviewing medical journals and news accounts and interviewing other surgeons who performed the 28 transplants.
Skeptics doubted that recipients would ever regain normal facial sensations -- feeling a kiss or a fresh breeze, smelling freshly mowed grass. But some did, as soon as three months after the transplant.
Some critics said nerve repair would take too long to achieve functional gains, for instance in eating and swallowing. While restoration of motor function was slower, some patients could bring their new lips together by six months and close their mouths by eight months. By three months, some could swallow and produce intelligible speech. Smiling began later, after about two years, and continued to improve after eight years.
Not surprisingly, the overriding reason for success was a rigorous pre-transplant effort to identify candidates who would be motivated to stick to an anti-rejection regimen and had a strong social support system. Deciding who is a face transplant candidate can be more grueling than the surgery, which can take longer than a day. Surgeons can spend years training for the procedure, then months more seeking a donor with a compatible complexion, bone structure and other important characteristics.
Dr. Rodriguez said he undertook the review to help improve future case outcomes and determine how many face transplants needed to be done to convince health insurers to pay for them, as they do for kidney, liver, heart and other organ transplants.
Early successes have led to new ethical questions. How long should a severely disfigured individual wait after receiving other therapy before getting a face transplant? What should be the youngest eligible age? (Recipients have ranged from 19 to 60.)
Government agencies have contributed to pressure for expansion. "With some victims from fire, police and military armed services, it can be argued that we have a moral imperative to restore them to safety," Dr. Rodriguez said.
But the costs of surgery and anti-rejection therapy require lifelong financial support. Many recipients need post-transplant surgical revision for such problems as bone and dental realignment, which increases infection risk and poor wound healing.
Different transplant centers use different techniques, and the Lancet review calls for a central registry to which surgeons can report standard data at specified intervals to help determine long-term successes and failures. There is little such follow-up information now beyond a year after surgery, partly because many transplants have been done since January 2012. A registry might also help show whether differences in technique accounted for differences in outcomes.
Of the three recipients who died, one disliked the side effects of immunosuppressant drugs and resorted to other remedies that led to multiple rejection episodes and death. A second, who had simultaneous transplants of both hands, developed an infected graft at 12 days and died two months after the combined surgery. The third death resulted from a recurrence of cancer in an HIV-positive patient who had undergone cancer surgery before the face transplant.
The deaths underscore the need for better measures to eliminate candidates with underlying medical conditions and those judged to be potentially noncompliant, Dr. Rodriguez said.