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Artificial Wombs Delivering on Fertile Promises by Colleen Carlston

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Artificial Wombs Delivering on Fertile Promises by Colleen Carlston Focus: Brave New World Artificial Wombs Delivering on Fertile Promises By Colleen Carlston ust over 30 years ago on July 25, J1978 the first test-tube baby, Louise Joy Brown, was born in England(1). She was heralded as Super Babe by the papers but since that time repro- ductive science has improved to the point where in-vitro fertilization (IVF) is a routine procedure in fertility clinics around the world. At this point some 4 million babies have been conceived using IVF(2). This has en- abled numerous couples that otherwise might have remained childless to conceive. Sperm and egg donors and surrogate mothers have further ex- panded the possibilities for those wanting a family. However, for many the price of hiring a surrogate remains prohibitively high and increasingly couples have been out-sourcing their childbearing to women living in developing countries(3). Yet this carries its own risks when it comes to ensuring proper pre- natal care conditions and what can be done when a surrogate changes her mind about keeping the baby. Experiments involving nuclear trans- fer into an egg may soon mean that even a 75-year-old man could create an embryo using a donor egg and swapping the nucleus for his own(4). Alan Trounson, the director of the California Institute for Regenerative Medicine in San Francisco, believes, “it will be possible that we’ll be able to extend the fertile period for women by credit: 20th U.S. edition of Anatomy Gray’s of the Human public domain. Body, fall 2008 • Harvard Science Review 35 ArtificialWombs.indd 35 2/9/2009 10:58:03 PM Focus: Brave New World producing germ cells from iPS [induced Pluripotent Stem-cell] technology, or by a variant of nuclear transfer, so somatic cells [which make up most of the body’s cells] become germ cells and are refreshed genetically”(1). The limit- ing step will therefore probably not be her preliminary results in 2001 she was how to make the embryo, but what to bombarded with calls from infertile This picture shows a premature goat fe- do with it when a suitable uterus is not women begging to be test subjects(5). tus kept alive in an artifcial placenta. easily available. She was so affected by this that she Professor Hung-Ching Liu at Cornell halted her research into artificial wombs After 10 days she moved some of the University’s Center for Reproductive for a year while she contemplated the embryos back into natural wombs. Medicine has been growing endometrial trajectory her research would take. She After 17 days she removed all embryos tissue (the uterus lining) since 2001 ultimately decided to continue because and found that those left in vitro died and firmly believes it is possible for of the hope that she can help women before reaching full term (21 days); fetuses to be grown outside a woman’s with damaged uteruses to conceive(5). however, the embryos that had been uterus(5). In 2003 a mouse embryo implanted back into mice seemed small grew to almost full term (it was moving How to Build an Artificial but otherwise normal(7). The endome- and breathing) in an endometrial tissue Womb trium produced to help support embryo “bubble” but died just a few days later. In creating an artificial womb, Dr. growth and so was key to having the In a similar line of research, Professor Liu appropriated techniques devel- mice continue to develop outside the Yoshinori Kuwabara at Juntendo Uni- oped for making artificial skin used in womb. Dr. Liu has also grown human versity in Tokyo worked with incubating grafts(5). Collagen and chondroitin, embryos to 10 days in artificial wombs goat fetuses in plastic tanks containing both biodegradable, formed a matrix but no further because current federal an amniotic fluid-like liquid and using for the harvested endometrial cells to regulation in the United States prevents a pump connected to the umbilical grow upon. This matrix conformed to growing human embryos beyond two cord (6). the organism’s natural uterine shape, weeks in a lab(4). So why has relatively little attention so the human artificial uterus was Ideally, embryos could implant in the been paid to research that could lead to bowl-shaped while the mouse’s was a artificial womb and at some point this a major change in reproductive capac- doughnut-shaped section to mimic its whole structure could be implanted ity? In fact, much work goes unpub- tubular uterus. Over time the matrix back into the woman. Since it would lished because of the uproar it might itself decayed leaving only the endome- have been grown using the woman’s create among activists, politicians, and trial tissue whose growth was fueled by own cells there would be no fear of religious figures for its social implica- hormones and growth factors. organ rejection(8). Liu then tried im- tions. Or worse, the premature hope In the mouse model, Dr. Liu placed planting mice artificial wombs carrying it might instill in would-be parents. embryos on this artificial uterus and embryos into adult mice; however, they credit: Knight, Jonathan. “An out of body experience“ NATURE|VOL 419 | 12 SEPTEMBER 2002 Jonathan. “An out of body experience“ NATURE|VOL credit: Knight, When Professor Liu first announced watched them implant and develop. failed to survive, most likely because the 36 Harvard Science Review • fall 2008 ArtificialWombs.indd 36 2/9/2009 10:58:03 PM Focus: Brave New World A futuristic vision of a world with artifi cial wombs. blood vessels that normally connect the by swallowing too much mother and the fetus formed improp- amniotic fl uid fetuses could erly(5). To address this, Liu’s colleague suffer severe fl uid retention. studied murine AGPAT, which is a gene As a preventative measure that stimulates blood-vessel formation the fetuses were fed seda- within the uterus. Women in whom tives to slow down activity this gene is missing or mutated tend and swallowing. However, a to miscarry. This gene could also have month-old child birthed us- implications for cancer treatment, since ing these techniques suffered tumors likewise rely on blood vessel after-effects of the sedatives Louise Joy Brown was fi rst introduced networks to receive nutrients and expel and could neither stand nor breathe to the world as Superbabe. waste. on its own (6).This was unfortunate While Dr. Liu has been working to considering one aim of this research company Anecova tries to circumvent help those who have trouble conceiv- was to redress hypoplasia, a form of this shortcoming. They created a 5mm ing, Dr. Kuwabara has been work- underdevelopment of the lungs, one of long and less than 1 mm wide perfo- ing from the other the major causes of death in pre- rated silicon capsule that can carry lab- end of gestation: to “Fertility is mature infants unable to breath, created embryos and be placed inside a woman’s uterus(10). This provides a help women who just half the which kills around 100 babies each year in Japan alone(6). Dr. more natural environment for the 2 to suffer miscarriages equation. or very premature Kuwabara eventually gave up 5 days fertility clinics grow embryos births(8). In 2000, Providing for this line of inquiry, but similar before selecting the healthiest for im- he fabricated an the children experiments are now being em- plantation into the womb. Currently acrylic box contain- already present ployed in Australia in an attempt these early embryos are incubated in a ing a mixture of and preventing to restore declining nurse shark growth medium that must be changed every few hours. Critics say this new sodium and potas- unwanted populations(9). sium chloride, glu- It is also important to deter- treatment is unlikely to succeed since pregnancies credit: “Life after Superbabe.” Nature 454, (2008): 253. cose and proteins mine how liquid media should eggs naturally develop in the fallopian kept at 39.5 degrees should also be be adjusted during the course tubes rather than the uterus. However, Celsius to mimic priorities.” of pregnancy. Even incremental if this device can create a higher success the amniotic sac. changes in hormone or protein rate, it means that fewer eggs will have Into this box he placed 4-month old levels can have major effects on the to be harvested from women. Most IVF goat fetuses removed by Caesarean offspring. During gestation, the embryo treatments now require women to take section and connected their umbilical implants and a placenta and amniotic hormones kick egg production into cords to an artifi cial placenta(5). While sac form between the embryo and the overdrive, which can sometimes lead most children died some survived for womb. Hormones, nutrition, blood, to dangerous side-effects. three weeks, reaching full term for a oxygen, and waste pass through the goat but all were deformed or had lung placenta as needed. Think of it as a Women and the Artifi cial Womb problems. Since the 42-liter container high-end aquarium, but a even more In Aldous Huxley’s futuristic Brave was larger than a normal womb the complicated. Even IVF treatments have New World published in 1932, babies fetuses could have been overly active diffi culty creating as good an environ- grew in tubes. In 1970 Shalumith Fire- and taken in too much oxygen, which ment for early embryonic development, stone wrote in The Dialectic of Sex: is toxic at high concentrations. Also, and a new invention by the Swiss The Case for Feminist Revolution that fall 2008 • Harvard Science Review 37 ArtificialWombs.indd 37 2/9/2009 10:58:04 PM Focus: Brave New World artificial wombs should be developed to free women from “the tyranny of their sexual-reproductive roles”(5).
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