"All the world's a stage we pass through." - R. Ayana

Tuesday, 10 March 2015

The Artificial Womb Is Born: Welcome To the World of the MATRIX

The Artificial Womb Is Born:
Welcome To the World of the MATRIX


By Perri Klass

”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 2020, 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.”

scifi artificial womb sculpture3

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.

From The New York Times @ http://www.nytimes.com/1996/09/29/magazine/the-artificial-womb-is-born.html
PLEASE NOTE: This article was written in 1996…

Artificial wombs: The coming era of motherless births




Scientifically, it’s called ectogenesis, a term coined by J.B.S. Haldane in 1924. A hugely influential science popularizer, Haldane did for his generation what Carl Sagan did later in the century. He got people thinking and talking about the implications of science and technology on our civilization, and did not shy away from inventing new words in order to do so. Describing ectogenesis as pregnancy occurring in an artificial environment, from fertilization to birth, Haldane predicted that by 2074 this would account for more than 70 percent of human births.

His prediction may yet be on target.

In discussing the idea in his work Daedalus–a reference to the inventor in Greek mythology who, through his inventions, strived to bring humans to the level of the gods–Haldane was diving into issues of his time, namely eugenics and the first widespread debates over contraception and population control.

Whether Haldane’s view will prove correct about the specific timing of when ectogenesis might become popular, or the numbers of children born that way, it’s certain that he was correct that tAt the same time, he was right that the societal implications are sure to be significant as the age of motherless birth approaches. They will not be the same societal implications that were highlighted in Daedalus, however. 

Technology developing in increments

Where are we on the road to ectogenesis right now? To begin, progress has definitely been rapid over the last 20-30 years. In the mid 1990s, Japanese investigators succeeded in maintaining goat fetuses for weeks in a machine containing artificial amniotic fluid. At the same time, the recent decades have seen rapid advancement in neonatal intensive care that is pushing back the minimum gestational age from which human fetuses can be kept alive. Today, it is possible for a preterm fetus to survive when removed from the mother at a gestational age of slightly less than 22 weeks. That’s only a little more than halfway through the pregnancy (normally 40 weeks). And while rescuing an infant delivered at such an early point requires sophisticated, expensive equipment and care, the capability continues to increase.

A comprehensive review published by the New York Academy of Sciences three years ago highlights a series of achievements by various research groups using ex vivo (out of the body) uterus environments to support mammalian fetuses early in pregnancy. Essentially, two areas of biotechnology are developing rapidly that potentially can enable ectogenesis in humans, and, along the way, what the authors of the Academy review call partial ectogenesis.

Because a fetus develops substantially with respect to external form and internal organs during the second half of pregnancy, our current capability to deliver and maintain preterm infants actually is a kind of partial ectogenesis. Supported by all of the equipment in the neonatal intensive care unit (NICU), a premature infant continues its development as a normal fetus of the same gestational age would do inside the mother’s uterus, but with one important exception. Inside the womb, oxygenated, nourished blood comes in, and blood carrying waste goes out, through the placenta and umbilical cord. Once delivered, however, a preemie must breathe through its lungs, cleanse the blood with its liver and kidneys, and get nutrition through its gastrointestinal tract.

But because these organ systems, especially the lungs, are not really ready to do their job so early, there is a limit to how early a developing fetus can be transferred from womb to NICU. Known as viability, the limit definitely has been pushed back with special treatments given to the mother prior to delivery and, just after birth, directly into the preemie’s lungs, and with intensive support. But the 22 week gestational age may be around the absolute limit for survival for a fetus that will have to depend on lung-breathing, not to mention other organs, rather than its mother’s nourished blood.

Still, the capability to push back the limit is around the corner. One of the two developing key technologies is the artificial amniotic fluid filled environment that has continued to develop with laboratory animal models since the work with goats in the 1990s. The other area is embryo transfer. Not only can a developing mammal be transferred from the uterus of its own mother to that of a surrogate, but gradually investigators are reproducing the endometrium–the cell layer of the uterus that contains and nourishes the pregnancy–as a cell culture, or an in vitro model. The convergence of these technologies will make it possible to transfer a developing human into a system that includes the placenta and umbilical cord and supplies all consumables (oxygen and food), and removes all waste, directly through the blood.

Thus, survival and continuing development would not depend on the lungs and other organs being ready yet to do their job. Applying such a system to fetus delivered in the middle of pregnancy would constitute real partial ectogenesis. Furthermore, since bypassing the developing, not fully functional organs, stands to improve survival substantially, and might even decrease the costs of extreme premature birth, the movement of the technology from research to clinic is inevitable.

Once that happens, there will be no obstacle against pushing the limit further, toward full ectogenesis. But there will be no obstacle to pushing the limit akin to how lung viability has placed an obstacle to conventional pre-term care. At some point, an in vitro fertilized egg could be planted directly into the artificial womb, with no need for a natural uterus even for the early stages.

Societal implications

An artificial womb may sound futuristic, and in Haldane’s time this may have supported a perception that realizing the technology would go together with controlling the birth rate and eugenics controlling which humans come to life, and thus which genetic traits get passed down to future populations. But today, we could do these things without ectogenesis. We have plenty of contraceptive methods and can sterilize people, or make them more fertile, while pregnancies can be induced with implanted embryos made with in vitro fertilization.

If anyone is working on a eugenics program at present, they can use surrogate mothers and don’t really require an artificial uterus–unless, we imagine a society that routinely, forcefully sterilizes all females, so that whoever has the artificial uterus has a monopoly on reproduction, ectogenesis does not relate particularly to those 1920s issues. Instead, the artificial uterus would simply move the pregnancy outside of the woman’s body. When considering societal consequences, that’s the main factor that we need to keep in mind, and doing so we see that it does relate to many currently controversial issues.

Considering abortion, for instance, while the proposition that a fetus, even an embryo, is a person with a “right to life” is a religious belief that cannot be imposed on everyone else, the main argument for the right to choose is a woman’s right to control her body. If a developing embryo or fetus is not viable and the mother wants it out of her uterus, that’s her right.

But what happens once we have the technology to remove it from her without killing it and let the pregnancy continue in an artificial womb? Already, with NICU technology pushing back the survival limit, the timing of viability affecting the legality of abortion, has been challenged by abortion foes. The prospect of ectogenesis stands to turn the viability issue on its face, and it will be interesting to see where that leads.

While social conservatives might be receptive about what an artificial uterus might do to the abortion paradigm, make no mistake they’d probably not be happy that the technology also stands to make it much easier for male gay couples to have babies. All they’d need is an egg donor; no more need for a surrogate mother to take the embryo into her uterus and carry it for 40 weeks. That’s easier for any gay couple in terms of practicality, waiting periods, and money. The same thing goes for a transgender person wishing to have a child.

Finally, because of the sheer numbers, the artificial uterus could have major implications for heterosexual women with fully functional uteri. Many who want children of their own might prefer to forego pregnancy yet would hesitate to hire a human surrogate. Not only is it expensive, but the surrogate could grow fond of the fetus she’s carrying, so why bother taking the risk?

On the other hand, the mind set could be quite different if the surrogate were a high tech jar. It’s your baby with no worries about competing mothers. I’m not suggesting that all potential mothers would opt for this, but Haldane’s guess might not be so unrealistic in that it might end up being a substantial fraction of the population.

David Warmflash is an astrobiologist, physician and science writer. Follow @CosmicEvolution to read what he is saying on Twitter.

From Genetic Literacy Project @ http://geneticliteracyproject.org/2015/01/04/artificial-wombs-the-coming-era-of-motherless-births/

For more information about artificial wombs see http://nexusilluminati.blogspot.com/search/label/artificial%20wombs
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