By Lawrence K. Altman, M.D.

New York Times News Service

When the world’s first face transplant was performed in France in 2005, it pushed medical boundaries and made international news. Yet the procedure’s future was 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 countries, 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 by The Lancet on Sunday, 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 that patients must be carefully selected. 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 the 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, Dr. Eduardo 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.

Rodriguez said he and his co-authors spent nearly a year reviewing medical journals and news accounts and interviewing the other surgeons who performed the 28 transplants. Of these, 11 were full facial grafts. Because there is no standard protocol for face transplants, the authors concentrated on analyzing certain immunological, psychological and other functional and behavioral factors for the 18 recipients for whom the information was available.

Some findings were surprising. New faces initially feel numb, as if the recipient had come from a dentist’s office. But the numbness lasts for months.

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 early 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. Although 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 were able to 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 who had a strong social support system. Deciding who is and who is not 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 and then spend months more seeking a donor with a compatible complexion, bone structure and other important characteristics.

Rodriguez said he undertook the review to help improve outcomes in future cases, and to 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 age of eligibility? (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,” 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 the risk of infection and poor wound healing.

Leaders want to avoid the experience in China, where nearly all the initial recipients of hand transplants rejected their donor grafts because government officials stopped payment for anti-rejection drugs and the patients could not afford them.

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.