Saturday, November 16, 2013
The Artificial Womb Is Born
It may be born but it remains still born and is essentially experimental today. Yet it is the future. The problems with human childbirth are both real and physically costly and avoidance is to be desired. This does not mean avoidance of the hormonal changes or the bonding aspects but avoidance of the excessive physical changes forced on the mother.
I do expect that inside perhaps even two decades that women will be able to opt for artificial child bearing. It will also quickly become the norm.
This also means that a wide range of natural and unnatural errors can be voided in the course of business. The bioethicists will go crazy.
The Artificial Womb Is Born
''One by one the eggs were transferred from their test-tubes to the larger containers; deftly the peritoneal lining was slit, the morula dropped into place, the saline solution poured . . . and already the bottle had passed on through an opening in the wall, slowly on into the Social Predestination Room.'' Aldous Huxley, ''Brave New World''
The artificial womb exists. In Tokyo, researchers have developed a technique called EUFI -- extrauterine fetal incubation. They have taken goat fetuses, threaded catheters through the large vessels in the umbilical cord and supplied the fetuses with oxygenated blood while suspending them in incubators that contain artificial amniotic fluid heated to body temperature.
Yoshinori Kuwabara, chairman of the Department of Obstetrics and Gynecology at Juntendo University in Tokyo, has been working on artificial placentas for a decade. His interest grew out of his clinical experience with premature infants, and as he writes in a recent abstract, ''It goes without saying that the ideal situation for the immature fetus is growth within the normal environment of the maternal organism.''
Kuwabara and his associates have kept the goat fetuses in this environment for as long as three weeks. But the doctor's team ran into problems with circulatory failure, along with many other technical difficulties. Pressed to speculate on the future, Kuwabara cautiously predicts that ''it should be possible to extend the length'' and, ultimately, ''this can be applied to human beings.''
For a moment, as you contemplate those fetal goats, it may seem a short hop to the Central Hatchery of Aldous Huxley's imagination. In fact, in recent decades, as medicine has focused on the beginning and end stages of pregnancy, the essential time inside the woman's body has been reduced. We are, however, still a long way from connecting those two points, from creating a completely artificial gestation. But we are at a moment when the fetus, during its obligatory time in the womb, is no longer inaccessible, no longer locked away from medical interventions.
The future of human reproductive medicine lies along the speeding trajectories of several different technologies. There is neonatology, accomplishing its miracles at the too-abrupt end of gestation. There is fetal surgery, intervening dramatically during pregnancy to avert the anomalies that kill and cripple newborns. There is the technology of assisted reproduction, the in-vitro fertilization and gamete retrieval-and-transfer fireworks of the last 20 years. And then, inevitably, there is genetics. All these technologies are essentially new, and with them come ethical questions so potent that the very inventors of these miracles seem half-afraid of where we may be heading.
Between Womb and Air
Modern neonatology is a relatively short story: a few decades of phenomenal advances and doctors who resuscitate infants born 16 or 17 weeks early, babies weighing less than a pound. These very low-birthweight babies have a survival rate of about 10 percent. Experienced neonatologists are extremely hesitant about pushing the boundaries back any further; much research is aimed now at reducing the severe morbidity of these extreme preemies who do survive.
''Liquid preserves the lung structure and function,'' says Thomas Shaffer, professor of physiology and pediatrics at the School of Medicine at Temple University. He has been working on liquid ventilation for almost 30 years. Back in the late 1960's, he looked for a way to use liquid ventilation to prevent decompression sickness in deep-sea divers. His technology was featured in the book ''The Abyss,'' and for the movie of that name, Hollywood built models of the devices Shaffer had envisioned. As a postdoctoral student in physiology, he began working with premature infants. Throughout gestation, the lungs are filled with the appropriately named fetal lung fluid. Perhaps, he thought, ventilating these babies with a liquid that held a lot of oxygen would offer a gentler, safer way to take these immature lungs over the threshold toward the necessary goal of breathing air. Barotrauma, which is damage done to the lungs by the forced air banging out of the ventilator, would thus be reduced or eliminated.
Today, in Shaffer's somewhat labyrinthine laboratories in Philadelphia, you can come across a ventilator with pressure settings that seem astoundingly low; this machine is set at pressures that could never force air into stiff newborn lungs. And then there is the long bubbling cylinder where a special fluorocarbon liquid can be passed through oxygen, picking up and absorbing quantities of oxygen molecules. This machine fills the lungs with fluid that flows into the tiny passageways and air sacs of a premature human lung.
Shaffer remembers, not long ago, when many people thought the whole idea was crazy, when his was the only team working on filling human lungs with liquid. Now, liquid ventilation is cited by many neonatologists as the next large step in treating premature infants. In 1989, the first human studies were done, offering liquid ventilation to infants who were not thought to have any chance of survival through conventional therapy. The results were promising, and bigger trials are now under way. A pharmaceutical company has developed a fluorocarbon liquid that has the capacity to carry a great deal of dissolved oxygen and carbon dioxide -- every 100 milliliters holds 50 milliliters of oxygen. By putting liquid into the lung, Shaffer and his colleagues argue, the lung sacs can be expanded at a much lower pressure.
''I wouldn't want to push back the gestational age limit,'' Shaffer says. ''I want to eliminate the damage.'' He says he believes that this technology may become the standard. By the year 2000, these techniques may be available in large centers. Pressed to speculate about the more distant future, he imagines a premature baby in a liquid-dwelling and a liquid-breathing intermediate stage between womb and air: Immersed in fluid that would eliminate insensible water loss you would need a sophisticated temperature-control unit, a ventilator to take care of the respiratory exchange part, better thermal control and skin care.
The Fetus as Patient
The notion that you could perform surgery on a fetus was pioneered by Michael Harrison at the University of California in San Francisco. Guided by an improved ultrasound technology, it was he who reported, in 1981, that surgical intervention to relieve a urinary tract obstruction in a fetus was possible.
''I was frustrated taking care of newborns,'' says N. Scott Adzick, who trained with Harrison and is surgeon in chief at the Children's Hospital of Philadelphia.
When children are born with malformations, damage is often done to the organ systems before birth; obstructive valves in the urinary system cause fluid to back up and destroy the kidneys, or an opening in the diaphragm allows loops of intestine to move up into the chest and crowd out the lungs. ''It's like a lot of things in medicine,'' Adzick says, ''if you'd only gotten there earlier on, you could have prevented the damage. I felt it might make sense to treat certain life-threatening malformations before birth.''
Adzick and his team see themselves as having two patients, the mother and the fetus. They are fully aware that once the fetus has attained the status of a patient, all kinds of complex dilemmas result. Their job, says Lori Howell, coordinator of Children's Hospital's Center for Fetal Diagnosis and Treatment, is to help families make choices in difficult situations. Terminate a pregnancy, sometimes very late? Continue a pregnancy, knowing the fetus will almost certainly die? Continue a pregnancy, expecting a baby who will be born needing very major surgery? Or risk fixing the problem in utero and allow time for normal growth and development?
The first fetal surgery at Children's Hospital took place seven months ago. Felicia Rodriguez, from West Palm Beach, Fla., was 22 weeks pregnant. Through ultrasound, her fetus had been diagnosed as having a congenital cystic adenomatoid malformation a mass growing in the chest, which would compress the fetal heart, backing up the circulation, killing the fetus and possibly putting the mother into congestive heart failure.
When the fetal circulation started to back up, Rodriguez flew to Philadelphia. The surgeons made a Caesarean-type incision. They performed a hysterotomy by opening the uterus quickly and bloodlessly, and then opened the amniotic sac and brought out the fetus's arm, exposing the relevant part of the chest. The mass was removed, the fetal chest was closed, the amniotic membranes sealed with absorbable staples and glue, the uterus was closed and the abdomen was sutured. And the pregnancy continued -- with special monitoring and continued use of drugs to prevent premature labor. The uterus, no longer anesthetized, is prone to contractions. Rodriguez gave birth at 35 weeks' gestation, 13 weeks after surgery, only 5 weeks before her due date. During those 13 weeks, the fetal heart pumped normally with no fluid backup, and the fetal lung tissue developed properly. Roberto Rodriguez 3d was born this May, a healthy baby born to a healthy mother.
This is a new and remarkable technology. Children's Hospital of Philadelphia and the University of California at San Francisco are the only centers that do these operations, and fewer than a hundred have been done. The research fellows, residents working in these labs and training as the next generation of fetal surgeons, convey their enthusiasm for their field and their mentors in everything they say. When you sit with them, it is impossible not to be dazzled by the idea of what they can already do and by what they will be able to do. ''When I dare to dream,'' says Theresa Quinn, a fellow at Children's Hospital, ''I think of intervening before the immune system has time to mature, allowing for advances that could be used in organ transplantation to replacement of genetic deficiencies.''
But What Do We Want?
Eighteen years ago, in-vitro fertilization was tabloid news: test-tube babies! Now IVF is a standard therapy, an insurance wrangle, another medical term instantly understood by most lay people. Enormous advertisements in daily newspapers offer IVF, egg-donation programs, even the newer technique of ICSI intracytoplasmic sperm injection as consumer alternatives. It used to be, for women at least, that genetic and gestational motherhood were one and the same. It is now possible to have your own fertilized egg carried by a surrogate or, much more commonly, to go through a pregnancy carrying an embryo formed from someone else's egg.
Given the strong desire to be pregnant, which drives many women to request donor eggs and go through biological motherhood without a genetic connection to the fetus, is it really very likely that any significant proportion of women would take advantage of an artificial womb? Could we ever reach a point where the desire to carry your own fetus in your own womb will seem a willful rejection of modern health and hygiene, an affected earth-motherism that flies in the face of common sense -- the way I feel about mothers in Cambridge who ostentatiously breast-feed their children until they are 4 years old?
I would argue that God in her wisdom created pregnancy so Moms and babies could develop a relationship before birth, says Alan Fleischman, professor of pediatrics at Albert Einstein College of Medicine in New York, who directed the neonatal program at Montefiore Medical Center for 20 years.
Mary Mahowald, a professor at the MacLean Center for Clinical Medical Ethics at the University of Chicago, and one of her medical students surveyed women about whether they would rather be related to a child gestationally or genetically, if they couldn't choose both. A slight majority opted for the gestational relationship, caring more about carrying the pregnancy, giving birth and nursing than about the genetic tie. ''Pregnancy is important to women,'' Mahowald says. ''Some women might prefer to be done with all this -- we hire our surrogates, we hire our maids, we hire our nannies -- but I think these things are going to have very limited interest.''
Susan Cooper, a psychologist who counsels people going through infertility workups, isn't so sure. Yes, she agrees, many of the patients she sees have ''an intense desire to be pregnant but it's hard to know whether that's a biological urge or a cultural urge.''
And Arthur L. Caplan, director of the Center for Bioethics at the University of Pennsylvania, takes it a step further. Thirty years from now, he speculates, we will have solved the problem of lung development; neonatology will be capable of saving 15- and 16-week-old fetuses. There will be many genetic tests available, easy to do, predicting the risks of acquiring late-onset diseases, but also predicting aptitudes, behavior traits and aspects of personality. There won't be an artificial womb available, but there will be lots of prototypes, and women who can't carry a pregnancy will sign up to use the prototypes in experimental protocols. Caplan also predicts that ''there will be a movement afoot which says all this is unnecessary and unnatural, and that the way to have babies is sex and the random lottery of nature a movement with the appeal of the environmental movement today.'' Sixty years down the line, he adds, the total artificial womb will be here. ''It's technologically inevitable. Demand is hard to predict, but I'll say significant.''
It all used to happen in the dark -- if it happened at all. It occurred well beyond our seeing or our intervening, in the wet, lightless spaces of the female body. So what changes when something as fundamental as human reproduction comes out of the closet, so to speak? Are we, in fact, different if we take hands-on control over this most basic aspect of our biology? Should we change our genetic trajectory and thus our evolutionary path? Eliminate defects or eliminate differences or are they one and the same? Save every fetus, make every baby a wanted baby, help every wanted child to be born healthy -- are these the same? What are our goals as a society, what are our goals as a medical profession, what are our goals as individual parents -- and where do these goals diverge?
''The future is rosy for bioethicists,'' Caplan says.