Soon after my son Benjamin was born, the chief neonatologist had to swear all the physicians and nurses in the intensive care unit to secrecy as they were about to commit a crime. I was forcing them to break the law and risk their professional credentials alongside my own unfathomable risk as we prepared for my son to become the first baby in the world to receive an experimental, illegal treatment that was not yet approved by the FDA. This was the moment that I had dreaded, but it was also the moment that filled me with hope for my son’s life.
When the warm liquid trickled down my legs in the seventh month of my pregnancy, I knew my membranes had ruptured, and my son was going to be born two months too early. This was in 1987, and as a neonatologist myself, I knew too well how sick he could get. Once I got to the hospital I was made to lie on the bed with my head down and feet up to reduce the loss of fluid. “You must stop this delivery. He cannot come out so soon,” I blurted out to my obstetrician. She started an infusion of a drug that slows down the labor but warned me, “You know I have to deliver your baby in 24 hours.” The standard of practice is to deliver the baby soon after the membranes rupture to prevent infection of the baby. Jeff, my physician husband, supported me in my request to delay the birth.
Most premature babies lack surfactant, a substance that keeps our lungs open and functioning properly. The lungs of premature babies without sufficient surfactant collapse, and they struggle to get oxygen into their blood. I feared the worst; my baby in the intensive care unit for weeks — even months — struggling to breathe, and without enough oxygen, he may not survive. Rarely, some premature babies have enough surfactant, but I could not count on it. 25 years earlier, John F. Kennedy’s son, Patrick was born just as premature as Benjamin, and he died from the exact condition that I feared could take my son.
Before moving to UCLA in 1984 I had worked at the University of California, San Francisco, and came to know Dr. Clements, who had discovered surfactant. At that time, he had started testing an artificial surfactant that he had developed in premature rabbits. As Benjamin was likely to be born premature, I wondered if I would be able to ask him for some of this artificial surfactant for Benjamin. But Dr. Clements was in San Francisco and I was in Los Angeles.
Each day I bargained with my obstetrician to continue giving me the drug and stop the labor so my baby could mature inside my uterus for one more day. The drug did not stop the labor pains completely. It did slow the progress of labor, though the labor contractions grew more dysfunctional in nature and the pain more intense. My sensitive emotional husband knew about the dangers of premature birth for our son, but he was more upset and worried about me. It was very hard for him to see me in constant pain. I was desperate to buy more time for my son inside my uterus so his lungs could mature, and I was willing to keep suffering the pain of labor for as long as it would take.
One day, after ten days of labor, my obstetrician marched into my room and said she was going to deliver Benjamin right there and then. She was not going to listen to me anymore. My body had undergone too much stress and Ben needed to come out.
One of my colleagues at UCLA, a researcher, was also studying surfactant at that time and he had started collaborating with a scientist in Japan who had extracted the surfactant from the lungs of cows in slaughterhouses. He was now testing this surfactant in premature lambs, but as a researcher myself, I knew that it often took years before a treatment at the animal testing stage gets approved by the FDA for use in humans.
I called my colleague just before they started to roll me into the delivery room. He was getting ready to leave the country on one of his many speaking engagements. “Is there any way we can use the cow surfactant for my baby, in case he needs it?” I asked. “He is going to be born any minute now. My obstetrician insists on delivering him now and you know he is going to have problems with his lungs.” I knew that this was an outrageous request. Research with surfactant had just begun in animals, and in 1987 the idea of using it in human babies was still somewhere in the distant future.
“Usha,“ he said, “I don’t think so. We haven’t even started clinical trials in babies with any surfactant preparation, leave alone this one! I can’t promise this cow surfactant would be safe to use in your baby. And besides,” he said, “this is all absolutely illegal without FDA approval.” I don’t think that I gave any thought to the ethics of my request, or the fact that I was asking my colleagues to be unethical. I just had images in my mind of the many premature babies that I had taken care of in the NICU: the premature babies that struggled to breathe, the babies that ruptured their lungs from the pressure of the ventilator, the babies that remained attached to ventilators for weeks or months, the babies that only survived with severely damaged lungs, and the babies that died from lack of surfactant. I couldn’t bear to see Ben suffer.
My colleague was a world-renowned neonatologist and researcher who could not afford to jeopardize his career with an illegal act. “But can you tell me if it works in your premature lambs?” I insisted from my hospital bed, minutes before being wheeled into the hospital delivery room. “It does seem to be working” he confessed.
This was great news! If the cow surfactant worked in premature lambs, an animal that was closer in anatomy and physiology to a premature baby, then it could possibly work in my son. But he was adamant. He could not let us use it.
So, I went into the delivery room and Ben was born. Despite the additional ten days of development I had earned him inside my uterus, his lungs were very immature. He was whisked into the intensive care unit and immediately placed on a ventilator and given 100% pure oxygen. He remained blue and his lungs were struggling to stay open. They were not functioning at all, even with maximum support on the ventilator and the pure oxygen being given to him. The neonatologist brought Benjamin’s X-ray to show me as I lay in the recovery room. His lungs had no air in them. They were solid looking, like the neighboring heart and liver. Jeff and I clasped hands tightly and our hearts sank. What we had feared the most was happening. Our son’s lungs had no surfactant. How was he going to survive?
At my insistence, Jeff called my colleague again and told him how sick Ben was. I knew that he was a kind and thoughtful man. He was also a father, who had adopted a baby from our hospital and provided a home for a child who needed one. Surely he would be compassionate as he must know what I was going through. Faced with the reality of my son struggling to stay alive, he immediately sent the cow surfactant with his assistant before heading for the airport. Recently, when I reminded him about the legal and ethical risks he had taken when agreeing to give Ben the cow surfactant, a surfactant that was not even his to give, he just mused: “I don’t think I worried about the ethics of it. I just worried if it would work as well for Benjamin as it had for the lambs!”
His assistant was by Benjamin’s bedside within an hour of the call. The medical team knew that if he got this treatment, he would be the first baby in the world to get any type of surfactant and they would be part of a ground-breaking experiment, albeit an illegal one. It would have put all the medical staff and the hospital in jeopardy if what they were going to do were to leak. The lead neonatologist came in to see Jeff and I before giving Ben the surfactant. “You are brave,” he said as he left the room.
The atmosphere in the intensive care unit was filled with tension, excitement, and trepidation. Everyone was thrilled to be part of this great experiment. My colleague’s assistant warmed up the cow surfactant by rolling the vial in between her hands. The cream-colored solid substance thawed into a slightly frothy liquid that looked a bit like spit. She explained carefully to everyone assembled around Benjamin just what she would do. First, she would disconnect Benjamin from the ventilator and give him the surfactant through his breathing tube. She warned everybody that the oxygen level in his blood would fall even lower when she did this, but she would quickly reconnect him back to the oxygen. She may have to do this a few times to give him all of the surfactant she had brought.
When the surfactant slid down his breathing tube into his lungs, no one knew what would happen. And then, miraculously, Benjamin’s color began to improve immediately. The doctors had to keep decreasing the oxygen he was getting and also decrease the settings on the ventilator. Jeff described later how his heart was ready to burst when he saw Benjamin’s little fingers and toes turn pinker by the minute. Just twelve hours later, he was detached from the ventilator and placed in an incubator without any oxygen. He was breathing air by himself. Jeff kept coming to see me every few minutes to give me a running commentary on what was going on, so I’ve been able to piece together a vivid picture of what must have happened that day.
On June seventh, 1987, Benjamin got a crude extract of surfactant from a cow’s lungs, un-purified, and untested in babies. It was another two and half years before it was approved for use in October of 1989. From the initial discovery of surfactant in the early 1950s by John Clements, to the association of lack of surfactant with the collapsed lungs in prematurely born babies by Mary Ellen Avery in the late 1950s, followed by many years of experimentation in small and large animals and then many well designed clinical studies in premature babies, to the first approval by the FDA for its use in the care of premature babies, this mission has taken over three decades. Today, all premature babies have access to surfactant and can benefit from it.
As I look back on the events now, I realize just how much all the physicians, nurses, and health care professionals had risked when they agreed to this illegal use of surfactant for Ben. A whistle-blower could have called the red hot-line — which was in every NICU those days — and the credentials of every healthcare professional present could have been jeopardized, as well as that of the hospital. And yet, no one hesitated. Was it their instinctual drive to save a life that took over, or the desperate pleas of a mother that moved their hearts? I will never know. I am just eternally grateful to them. And why was I, the mother, willing to risk using an unauthorized drug on my baby? My being a neonatologist with some knowledge about how surfactant works and my complete faith in my colleague must have been the reason. Ultimately, I think that all involved in the care of Benjamin believed that the scientific evidence that was present at that time — albeit just in animals — and they were willing to take a great leap of faith in the science. And it paid off. It could have backfired with my baby getting sicker, but I don’t think about that ever.•