Illustration. Adi Emanuel

We May Soon Gestate Babies in Fluid-filled Bags – and It Will Save Lives

As genome engineering technology leaps forward, the day is approaching when pregnancy itself can be managed outside the body

In “Brave New World,” Aldous Huxley writes about labs in which the traits of future infants are selected. Fetuses destined to become simple workers undergo manipulation to lower their IQs. Others are calibrated to develop frigophobia – an unnatural fear of cold – so that they can work at the equator. In some, the sense of balance is tampered with, enabling them to work more readily in outer space. The basic attributes of each individual are corrected and modified according to a predetermined future.

A fantasy some of us harbor is to engineer our own genius babies – with light or dark hair, of basketball-player height – to suit our personal taste. In short, designer babies. But at least some of what was once science fiction is today an integral part of artificial insemination.

Some inherited diseases are caused by a disorder in a single gene. Various syndromes are related to the sex of the embryo. Once an initial cell cluster forms, the genes of the embryo can be examined to ascertain its sex, and whether it is carrying a hereditary disease. Thus, only embryos not carrying the flawed gene will be returned to the uterus.

For ethical reasons, most countries in the developed world prohibit additional manipulations. The only modification parents are permitted to make is to reject an embryo in accordance with certain conditions. In China, though, at least one scientist thought the situation was too restricted.

In November 2018, a Chinese biophysicist named He Jiankui announced that he had succeeded in altering the genetic structure of twins with the use of CRISPR technology, which allows change at the level of gene. Jiankui’s goal was to render the embryos resistant to the AIDS virus by modifying a particular gene. According to him, the children had been born the preceding month.

Jiankui did not publish an article about the case in any peer-reviewed scientific journal, and his methods were not examined by an external team of scientists. Jiankui forged the documents of the committee that “approved” the research, and it’s not even known whether the parents who took part in the project gave their agreement. Moreover, no external verification exists that the effort achieved its goal – in other words, that the embryos were genetically modified in the lab and that the modifications were expressed in the newborns.

The most important aspect of this research, however, lies in the discussion it stirred about the possibility of genetic editing of embryos. Existing technology allows gene editing to be carried out by the splicing out of undesirable elements and their replacement with others. In contrast to the process of in vitro fertilization and the subsequent transfer of the resultant healthy embryo into the uterus, gene editing works by modifying the existing genome.

The biological dilemma is relatively straightforward. The human genetic system is complicated and complex; modification in one place could cause unexpected change. Accordingly, it’s necessary to wait with experiments involving humans until we’re certain that a particular modification is genuinely site-specific. We’re short of information that would enable precise genetic manipulation, and it may take decades before we’ll be capable of repairing embryonic flaws with certainty. Here, too, as is often the case, technology advances faster than ethical discourse.

The ethical issue, however, is far more complicated. Should the modification of the genetics of embryos be allowed? There’s a difference between not using an embryo with a known fatal condition and repairing a genetic flaw.

The World Health Organization has established a panel of experts tasked with setting international criteria for what may and not be done to human embryos. In the meantime, genetic manipulation is prohibited in most of the world, and special authorization is required to perform embryonic genetic modifications.

Even as the various committees meet and discuss the issues, however, a Russian biologist named Denis Rebrikov has announced that he is planning to carry out additional CRISPR experiments on human embryos. He intends to modify the same gene that He Jiankui did, but in a different way, in the hope of achieving better and more precise results.

Risk-free pregnancy?

In the 1999 film “The Matrix,” the protagonist discovers that he and other humans are hooked up to a sophisticated computer program that simulates a human environment. The machines running the world use human bodies to produce energy, and people are no longer “born,” but are, rather, bred in vast fields so they can be used in powering the computers. They still think they’re experiencing life, however, because they are connected, through the brain, to machines, and spend their whole life in a liquid-filled bag.

Is this a utopia or a dystopia?

The film maintains that such a future would be blacker than black, and that the purpose of humans is to thrive far from the control of machines, free to do whatever they please, and of course to continue to multiply by means of pregnancy and birth. But imagine a situation in which embryos are bred in bags of liquids that nurture them as they develop and can be “harvested” when they are ready. Perhaps “The Matrix” presents a sort of utopia?

Pregnancy is an extreme physiological condition, which has the potential to endanger the life of the mother and the fetus. According to WHO data, 830 women die around the world every day from pregnancy and childbirth complications – leading to a total of more than 300,000 deaths, for example, in 2015. And 99 percent of those deaths occur in developing countries, about half of them in sub-Saharan Africa and a third in South Asia. The risk of mortality from complications of pregnancy and delivery is particularly high among girls under 15.

By comparison, in the United States, about 700 women a year die as a result of pregnancy and labor complications, and more than 50,000 women develop various complications during pregnancy and childbirth. What is truly worrisome in this context is that while there is a downward trend in the world, in the United States there was a significant increase in maternal mortality during the past decade.

The main causes of death in pregnancy are bleeding, contamination and preeclampsia. In developed countries, such as those in Europe, efficient, safe treatment exists for these disorders. The primary contributing factors to pregnancy and childbirth complications are poverty, lack of access to health services, and a dearth of information about safe and healthy pregnancy and delivery. Even if the number of cases in developed countries is far lower, the reasons remain identical.

In all countries, premature delivery – namely, before the 37th week – is a leading cause of child mortality. The earlier a child is born, the less mature his organs will be, something that can lead to systemic failure, infection and death. About a million infants die worldwide every year due to complications arising from premature birth. Around 60 percent of the preemies are born in countries of Africa and East Asia. The causes of premature birth vary, and include multiple pregnancies, infections and a range of chronic diseases.

In developed countries, there are options for assisting women in labor, treatments for preventing premature birth and, of course, access to proper health services. In addition, once they are born, preemies can get far better treatment in developed countries, thus significantly lowering the mortality rate associated with premature birth.

External mothers

The uterus is far more than a bag filled with fluids. It’s a combination fetal sleeping bag, restaurant, toilet and oxygen mask. Its mission is to safeguard the developing embryo from slightly after fertilization until the fetus is delivered. “Safeguard” in all senses: to enable the passage to the fetus of nutritional substances and oxygen, and the evacuation of waste via the placenta, which is connected to the uterus by the umbilical cord, and also to protect the fetus physically in various situations. Because the placenta filters the substances that reach the fetus, only a small number of diseases the mother might contract are transmitted to the embryo. Oxygen passes through the blood directly into the fetal body by means of special blood vessels in the umbilical cord.

Medicine today is able to preserve the infant’s body temperature, protect it from the environment and supply it with nutrients, but it doesn’t know how to introduce oxygen directly into its blood. The only “artificial uterus” that exists today is the incubator. Its disadvantage is that it’s capable of helping only infants born from the sixth month on. In other words, an incubator is not capable of assisting an infant born earlier than that, still less could it be the venue for a full pregnancy.

The ideas presented below for technology that could potentially enable out-of-body pregnancies are still in stages of experimentation in animals, and not yet close to being tried in human beings.

• Idea No. 1: Biological bag

The first stage in the development of an artificial uterus is to try to advance the period during which the fetus can be born and survive. That is, to develop a sophisticated incubator. That’s exactly what the “biological bag” (biobag) looks like. Durable and sterile, it’s made of transparent polyethylene, making it possible to monitor the fetus and to maintain uterine-like pressure and form. It’s filled with artificial amniotic fluid, the fetus is placed in it and connected to an exchange system through the blood vessels in its umbilical cord (just like in the womb: oxygen and nutrients pass from mother to fetus; carbon dioxide and waste pass from fetus to mother). The bag is closed – and we have an incubator potentially capable of keeping preemies alive already from the fifth month of pregnancy.

David Bachar

The amniotic fluid is replaced frequently in order to preserve a clean environment for the preemie’s development, the bag itself is placed on a temperature-controlled surface in order to maintain proper body heat, and if an infection is detected, it can be treated with antibiotics. Some medications and other substances can be administered directly via other large blood vessels in the fetal body; this is in fact done with preemies. But the purpose of the bag is to replicate as closely as possible the uterine environment while reducing the need for medical procedures to be carried out on the fetus.

How close are we to using this technology on humans?

Experiments conducted on fetal lambs showed that they developed in the biobag like their fellow animals in the womb. After four weeks in the bag they could be “delivered” and allowed to breathe normally. In human terms, this would be equivalent to delivery in the fifth month – being initially transferred to a biobag and afterward to a regular incubator. Most important, it appears that the brain of the lambs in the biobag developed identically to that of lambs in the womb, with no significant adverse effects. The big advantage of the bag is that it treats the preemie as though it were not yet born, in contrast to a regular incubator, in which the newborn is obligated to breathe on its own and cope with the outside world, to some extent.

• Idea No. 2: Artificial placenta

The placenta is the organ that connects mother and fetus. Oxygen arrives at the placenta by way of the mother’s blood, by means of which it is passed into the fetus’ blood; carbon dioxide takes the opposite route and empties into the mother’s blood for disposal. One of the placenta’s functions is to filter the mother’s blood before it reaches the fetus. When we speak of “substances that infiltrate the placenta,” we are referring to those capable of penetrating the wall of the mother’s blood vessels and passing through to the blood vessels of the fetus, which can cause damage.

The underlying idea of the artificial placenta sounds similar to the biobag, but in this case the preemie is in a regular incubator, though with two significant differences: for one, its lungs remain filled with liquid; and, the blood vessels in the umbilical cord and the cervical vein are connected to a system that enables oxygenation of the blood and removal from it of carbon dioxide. Unlike the biobag, the uterine environment is not fully replicated here, though there is replication of the basic function of the placenta, in order to allow the lungs to develop to a degree that will make it possible to connect the newborn to a ventilator.

How close are we to using this technology on humans?

Experiments have shown that this method is effective and allows the lungs to develop properly. These experiments, too, are currently being carried out on animals to gauge the effectiveness and safety of this technology.

Barbaric present

The science-fiction genre was launched with a story about parenthood being effected without the need for a womb. Victor Frankenstein, conceived in the imagination of Mary Shelley, found a way to connect organs and create new life in his laboratory, without the aid of any reproductive organ.

The idea of containers for breeding babies is scattered here and there in science fiction, but only a few works in the genre examine the effect an artificial womb would have on the life of the mother and the embryo. One of the most fascinating such accounts can be found in “Barrayar,” a 1991 novel by Lois McMaster Bujold. Near the beginning of the book it turns out that the protagonist, a decorated officer, is pregnant. She reflects on the world she came from, in which womb replications are standard practice, and about how she never noticed the difference “between vitro and vivo babies” like her. But at the moment she’s in a backward world, where women are expected to bear the whole pregnancy by themselves, without any choice, unlike civilized worlds where an embryo can be planted in a “replicator,” to wait until its parents obtain a permit to raise it.

Later, it becomes necessary to transfer a fetus from the uterus to an artificial container in order to save its life, and the heroine is delighted to see the civilized replicator, in contrast to the barbaric and primitive style of pregnancy that exists in the world where she is now.

The placenta is transferred to the replicator, and after it’s accepted the connected fetus is moved to it. The umbilical cord is attached to a monitor that injects oxygen into it, and finally the replicator is filled with amniotic fluid and the container is closed, to allow the fetus to go on developing.

In our reality, an artificial womb that will be inexpensive and accessible, and which can be used in developing countries, would be able to save the lives of both the mother and the infant. The more available and the cheaper the technology is, the greater the number of lives that can be saved. In the end, maybe we, too, will look on a world in which women were compelled to carry the fetus by themselves as a barbaric, primitive place.

Dr. Keren Landsman specializes in epidemiology and public health, and is a founder of Mida’at, an organization dedicated to promoting public health in Israel. Special thanks to doctoral student Hadas Sloin, who helped in writing this article.

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