Could artificial wombs be a reality?

The uterus is just another organ that biomedicine will eventually replace, right? Possibly. Medicine does seem to be going in that direction. In recent years, the media have presented stories, including from this writer, that the era of motherless birth beckons, so we should begin pondering the social-political-economic consequences, as we do with all emerging biotechnologies.

Not so fast — some critics say the debate is getting ahead of itself, that there is no need to even discuss artificial wombs yet for several reasons. The main one is that nobody is currently working to develop one, in part because we don’t understand enough about the placenta.

The first point is true; nobody is working on ectogenesis — the term coined by J.B.S. Haldane in 1924, referring to human development outside the mother, through the entire 40-week process, from conception to birth. However, medical science is moving incrementally toward 40-week ectogenesis by gradually pushing back the age that a fetus can be extracted from a womb and survive.

As for the second point, there have been major advances in the realm of artificial placentas; in fact, that developing technology is why new records for fetal prematurity may be just around the corner. Moreover, a true artificial uterus would not need an artificial placenta.

The placenta is part of the conceptus package that develops from a fertilized egg.

The interface between machine and biology would be in the tissues on the maternal side of the placenta, not the fetal side, and there’s a driver for advances in this area short of the goal of motherless birth: The need for alternatives to advanced lung support for keeping extremely premature infants alive.

Survival of preterm infants with current technology

The closest phenomenon to motherless human birth is preterm birth slightly later than halfway through pregnancy. Capability for rescuing pre-term infants has been increasing dramatically since the 1970s.

This has resulted in an increasing number of premature infants surviving when born at gestational ages down to 23 weeks. At that level of prematurity, survival is still only around 20 percent, but it’s increasing in parallel with technology advances.

When it comes to the theoretical minimum survivable gestational age, however, not much has changed for almost 30 years. The record is 21 weeks and five days, set back in 1987, and since then no survival has been reported for anyone born younger than 22 weeks gestation.

The situation can be compared with old age, where today, due to improving medical knowledge, an increasing number of people live into their hundreds, but the longest verified life-span of any human is 122 years, 164 days.

Just as the ability for humans to live beyond their early 120s will depend on the advent of new approaches such as gene therapy and stem cell-based treatments, fetuses will begin surviving extraction from the womb at gestational ages below 22 weeks, only when neonatologists implement strategies completely different from those used today. But very different strategies are around the corner.

The reason why fetuses can’t be kept alive outside the mother at gestational ages below 22 weeks has a lot to do with the lungs. Before premature birth, mothers can be given corticosteroid treatment to advance fetal lung maturation.

Immature lungs do not produce functional surfactant, a substance that lowers the tension in lungs, but surfactant can be administered into the premature newborn’s lungs so they can stretch better, and the newborn can be mechanically ventilated.

These treatments work pretty well for low birth-weight infants born at gestational age of 30 weeks or so, but employing them in infants born at 28, 26, or 24 weeks or lower gets progressively trickier.

At 21 weeks gestation, the lungs simply are too premature to work with, so if a fetus is to remain alive, it must receive oxygen, and dispose of carbon dioxide, through a pathway that bypasses the lungs.

Could Artificial Wombs Be a Reality?OLYMPUS DIGITAL CAMERA

Of course, there is a pathway for exchanging oxygen and carbon dioxide that bypasses the fetal lungs. It’s the umbilical cord and it connects the fetal circulation to the placenta, which connects with the maternal circulation, while the fetus floats in amniotic fluid inside the uterus.

Prior to birth, oxygenated blood from the mother moves through the placenta and umbilical cord and enters the right side of the fetal heart, but most of it does not go to the lungs.

That’s because pressure in the fetal lungs is high, plus there are two connections between the right and left circulation, one inside the heart (called the foramen ovale), the other between the pulmonary artery and aorta (called the ductus arteriosus), This anatomy is very different from the arrangement after birth and it allows the oxygen-rich blood from the mother to move directly to fetal body tissues.

Artificial womb technology and clinical translation: Innovative treatment or medical research?

Volume 34, Issue 4Could Artificial Wombs Be a Reality? First published: 29 November 2019 https://doi.org/10.1111/bioe.12701

In 2017 and 2019, two research teams claimed ‘proof of principle’ for artificial womb technology (AWT). AWT has long been a subject of speculation in bioethical literature, with broad consensus that it is a welcome development. Despite this, little attention is afforded to more immediate ethical problems in the development of AWT, particularly as an alternative to neonatal intensive care. To start this conversation, I consider whether experimental AWT is innovative treatment or medical research. The research–treatment distinction, pervasive in regulation worldwide, is intended to isolate research activities and subject them to a greater degree of oversight. I argue that there is a tendency in the literature to conceptualize AWT for partial ectogenesis as innovative treatment. However, there are sufficiently serious ethical concerns with experimental AWT that mean that it must not be first used on humans on the basis that it is a ‘beneficial treatment’. First, I outline the prospects for translation of AWT animal studies into treatment for human preterms. Second, I challenge the conceptualizations of experimental AWT as innovative treatment. It must be considered medical research to reflect the investigatory nature of the process and guarantee sufficient protections for subjects. Identifying that AWT is research is crucial in formulating further ethico‐legal questions regarding the experimental use of AWT. Third, I demonstrate that clinical trials will be a necessary part of the clinical translation of AWT because of requirements laid out by regulators. I consider the justification for clinical trials and highlight some of the crucial ethical questions about the conditions under which they should proceed.

Two research teams, in the U.S. and Australia, claim to have established proof of principle for artificial womb technology (AWT).1 Both teams have designed ‘artificial womb devices’ that they claim will revolutionize the treatment of preterm neonates.

The devices, the EVE2 platform and the biobag, are intended to facilitate the process of gestation ex utero (ectogenesis), enabling preterms to continue to develop. When artificial wombs (AWs) are used to continue gestation ex utero this is described as partial ectogenesis.

3 Partial ectogenesis could significantly reduce mortality and morbidity rates amongst preterms. Both teams explicitly anticipate the clinical application of their device as a treatment for preterms in the near future.

See also:  Omitting “that”

Little attention has been afforded, however, to how experimental AWs might be ethically justified as an alternative to existing treatment.

Following recent animal studies of the biobag (2017) and EVE platform (2019), there has been renewed interest in the socio‐ethical implications of AWs.4 This debate treats the development and human use of AWs as a foregone conclusion.

The focus on future implications neglects more immediate ethical problems concerning the translation of AWT from concept and animal studies into treatment. Arguments are frequently made that ectogenesis is a moral imperative5 and a welcome development.6 Claims that AWT should be actively sought imply that risks in research are justified to achieve this end.

Often scholars ignore the fact that research on humans, both pregnant people and preterms, would be necessary, or they downplay the risks involved. Work exploring the ethics of experimental AWT focuses on full ectogenesis (rather than partial ectogenesis)7 or pre‐dates the recent scientific studies8 and is therefore more abstract. This paper addresses this gap in the literature.

How and when might it be ethical to use experimental AWT on humans? These questions are increasingly important as researchers consider translating their devices into treatment for preterms.

In this paper I address these questions by considering whether AWT is an innovative treatment or medical research. A distinction between innovative treatment and research is pervasive in bioethical literature,9 and is at the foundation of regulation in many jurisdictions.

10 The basis of this distinction is that research subjects need more protection than patients receiving medical treatment. Research is directed towards the production of generalizable knowledge in the interests of future patients/medical science.11 Innovative treatment, however, aims to treat the patient in their best interests.

The subject of medical research is more vulnerable than a patient receiving medical treatment because there is not the same guarantee that the investigator is acting in their interests.

12 Consequently, research is subject to a higher level of ethical oversight13 than the normal ethical constraints of medical practice (treatment in the patient’s best interests)14 to protect the research subject.

Because of the ethical tensions innate in the innovative treatment–research distinction, categorizing activities is essential wherever possible. Berkman et al. advocate that this is the easiest way to ensure that activities are afforded the appropriate ethical oversight and that investigators/clinicians are aware of their responsibilities to subjects/patients.15

It is often assumed that AWs are an extension of (but an improvement on) current methods in neonatal intensive care (NIC).16 The assumption implies that partial ectogenesis should be conceptualized as innovative medical treatment.

The danger with such an approach, however, is that it enables experimental AWs to be utilized on an ad hoc basis without objective ethical scrutiny. By failing to recognize the difference between AWT and NIC, we potentially expose pregnant people and preterms to harm.

In this paper, I argue that AWT must be conceptualized as medical research, and be subject to the same strict criteria as all research.

This paper does not examine all the ethical constraints that should regulate experimental AWT, but instead establishes that there are sufficiently serious ethical concerns with experimental AWT that means it must not be first used on humans on the basis that it is a ‘beneficial treatment’.

First, I outline the prospects for experimental AWT with human subjects. Second, I review how AWT has been conceptualized in the bioethical literature, demonstrating why these conceptualizations are problematic.

I argue that experimental AWT must be considered medical research to better reflect the investigatory nature of the process, and to better guarantee protections for the subjects of experimental AWT. I outline that AWT would be required by regulatory authorities to be the subject of extensive clinical trials before such devices are approved for more general use.

Third, I consider whether and how such clinical trials should be conducted by highlighting some of the critical ethical questions that must be addressed in designing such trials.

Artificial womb technology breaks its four minute mile

A major advancement in pioneering technology based around the use of an artificial womb to save extremely premature babies is being hailed as a medical and biotechnological breakthrough.

  • Recently published in the medical publication, the American Journal of Obstetrics & Gynecology, the study presents world-first data demonstrating the ability of an artificial placenta-based life support platform to maintain extremely preterm lamb fetuses (600-700g); equivalent to a human fetus at 24 weeks of gestation.
  • Head of WIRF's Perinatal Research Laboratories and Local Chief Investigator, Associate Professor Matt Kemp, said that whilst previous research had demonstrated the feasibility of extended survival with artificial placenta technology in late preterm fetuses, there was no published evidence that demonstrated the use of the platform to support extremely preterm fetuses — the eventual clinical target of this technology.
  • “For several decades there has been little improvement in outcomes of extremely preterm infants born at the border of viability (21-24 weeks gestation),” Assoc Prof Kemp said.
  • “In the AJOG study, we have proven the use of this technology to support, for the first time, extremely preterm lambs equivalent to 24 weeks of human gestation in a stable, growth-normal state for five days.

“This result underscores the potential clinical application of this technology for extremely preterm infants born at the border of viability. In the world of artificial placenta technology, we have effectively broken the 4 minute mile.”

Assoc Professor Matt Kemp said the latest findings represent a significant milestone in the technology's future implementation into clinical use.

“If we are to improve outcomes for babies born at the border of viability we must recognise that they are not 'small babies'; rather, they are a unique patient demographic that, due to their extremely underdeveloped lungs and limited cardiovascular capacity, require an entirely different treatment approach from older preterm infants.

“The technology was designed to revolutionise the treatment of severely premature newborns. The goal is to offer a bridge between a natural womb and the outside world to give babies born at the earliest gestational ages more time for their fragile lungs to mature.

“With additional refinement, what today might be considered as futuristic technology might soon not be so futuristic and might be standard of care.”

make a difference: sponsored opportunity

Story Source:

Materials provided by Tohoku University. Note: Content may be edited for style and length.

Journal Reference:

  1. Haruo Usuda, Shimpei Watanabe, Masatoshi Saito, Shinichi Sato, Gabrielle C. Musk, Erin Fee, Sean Carter, Yusaku Kumagai, Tsukasa Takahashi, Shinichi Kawamura, Takushi Hanita, Shigeo Kure, Nobuo Yaegashi, John P. Newnham, Matthew W. Kemp. Successful use of an artificial placenta to support extremely preterm ovine fetuses at the border of viability. American Journal of Obstetrics and Gynecology, 2019; DOI: 10.1016/j.ajog.2019.03.001

Artificial womb

Artificial womb

Figure from a 2017 Nature Communications paper describing an extra-uterine life support system, or “biobag”, used to grow lamb fetuses.[1]

An artificial uterus (or artificial womb) is a device that would allow for extracorporeal pregnancy[2] by growing a fetus outside the body of an organism that would normally carry the fetus to term.

See also:  Making a career of combining art and science | everyday einstein

An artificial uterus, as a replacement organ, would have many applications. It could be used to assist male or female couples in the development of a fetus.

[2] This can potentially be performed as a switch from a natural uterus to an artificial uterus, thereby moving the threshold of fetal viability to a much earlier stage of pregnancy.[2] In this sense, it can be regarded as a neonatal incubator with very extended functions.

It could also be used for the initiation of fetal development.[2] An artificial uterus could also help make fetal surgery procedures at an early stage an option instead of having to postpone them until term of pregnancy.[2]

In 2016 scientists published two studies regarding human embryos developing for thirteen days within an ecto-uterine environment.[3][4] Currently, a 14-day rule prevents human embryos from being kept in artificial wombs longer than 14 days. This rule has been codified into law in twelve countries.[5]

In 2017 fetal researchers at the Children's Hospital of Philadelphia published a study showing they had grown premature lamb fetuses for four weeks in an extra-uterine life support system.[1][6][7]

Components

An artificial uterus, sometimes referred to as an 'exowomb[8]', would have to provide nutrients and oxygen to nurture a fetus, as well as dispose of waste material.

The scope of an artificial uterus (or “artificial uterus system” to emphasize a broader scope) may also include the interface serving the function otherwise provided by the placenta, an amniotic tank functioning as the amniotic sac, as well as an umbilical cord.

Nutrition, oxygen supply and waste disposal

A woman may still supply nutrients and dispose of waste products if the artificial uterus is connected to her.[2] She may also provide immune protection against diseases by passing of IgG antibodies to the embryo or fetus.[2]

Artificial supply and disposal have the potential advantage of allowing the fetus to develop in an environment that is not influenced by the presence of disease, environmental pollutants, alcohol, or drugs which a human may have in the circulatory system.[2] There is no risk of an immune reaction towards the embryo or fetus that could otherwise arise from insufficient gestational immune tolerance.[2] Some individual functions of an artificial supplier and disposer include:

  • Waste disposal may be performed through dialysis.[2]
  • For oxygenation of the embryo or fetus, and removal of carbon dioxide, extracorporeal membrane oxygenation (ECMO) is a functioning technique, having successfully kept goat fetuses alive for up to 237 hours in amniotic tanks.[9] ECMO is currently a technique used in selected neonatal intensive care units to treat term infants with selected medical problems that result in the infant's inability to survive through gas exchange using the lungs.[10] However, the cerebral vasculature and germinal matrix are poorly developed in fetuses, and subsequently, there is an unacceptably high risk for intraventricular hemorrhage (IVH) if administering ECMO at a gestational age less than 32 weeks.[11] Liquid ventilation has been suggested as an alternative method of oxygenation, or at least providing an intermediate stage between the womb and breathing in open air.[2]
  • For artificial nutrition, current techniques are problematic.[2] Total parenteral nutrition, as studied on infants with severe short bowel syndrome, has a 5-year survival of approximately 20%.[2][12]
  • Issues related to hormonal stability also remain to be addressed.[2]

Theoretically, animal suppliers and disposers may be used, but when involving an animal's uterus the technique may rather be in the scope of interspecific pregnancy.[original research?]

Uterine wall

In a normal uterus, the myometrium of the uterine wall functions to expel the fetus at the end of a pregnancy, and the endometrium plays a role in forming the placenta. An artificial uterus may include components of equivalent function. Methods have been considered to connect an artificial placenta and other “inner” components directly to an external circulation.[2]

Interface (artificial placenta)

An interface between the supplier and the embryo or fetus may be entirely artificial, e.g. by using one or more semipermeable membranes such as is used in extracorporeal membrane oxygenation (ECMO).[9]

There is also potential to grow a placenta using human endometrial cells. In 2002, it was announced that tissue samples from cultured endometrial cells removed from a human donor had successfully grown.

[13][14] The tissue sample was then engineered to form the shape of a natural uterus, and human embryos were then implanted into the tissue. The embryos correctly implanted into the artificial uterus' lining and started to grow.

However, the experiments were halted after six days to stay within the permitted legal limits of in vitro fertilisation (IVF) legislation in the United States.[2]

A human placenta may theoretically be transplanted inside an artificial uterus, but the passage of nutrients across this artificial uterus remains an unsolved issue.[2]

Amniotic tank (artificial amniotic sac)

The main function of an amniotic tank would be to fill the function of the amniotic sac in physically protecting the embryo or fetus, optimally allowing it to move freely. It should also be able to maintain an optimal temperature. Lactated Ringer's solution can be used as a substitute for amniotic fluid.[9]

Umbilical cord

Theoretically, in case of premature removal of the fetus from the natural uterus, the natural umbilical cord could be used, kept open either by medical inhibition of physiological occlusion, by anti-coagulation as well as by stenting or creating a bypass for sustaining blood flow between the mother and fetus.[2]

Research and development

Emanuel M. Greenberg

Emanuel M. Greenberg wrote various papers on the topic of the artificial womb and its potential use in the future.[15]

On 22 July 1954 Emanuel M. Greenberg filed a patent on the design for an artificial womb.[16] The patent included two images of the design for an artificial womb.

The design itself included a tank to place the fetus filled with amniotic fluid, a machine connecting to the umbilical cord, blood pumps, an artificial kidney, and a water heater.

He was granted the patent on 15 November 1955.[16]

On 11 May 1960, Greenberg wrote to the editors of the American Journal of Obstetrics and Gynecology.

Greenberg claimed that the journal had published the article “Attempts to Make an 'Artificial Uterus'”, which failed to include any citations on the topic of the artificial uterus.

[15] According to Greenberg, this suggested that the idea of the artificial uterus was a new one although he himself had published several papers on the topic.[15]

Juntendo University in Tokyo

In 1996, Juntendo University in Tokyo developed the extra-uterine fetal incubation (EUFI).[17] The project was led by Yoshinori Kuwabara, who was interested in the development of immature newborns.

The system was developed using fourteen goat fetuses that were then placed into artificial amniotic fluid under the same conditions of a mother goat.[17][18] Kuwabara and his team succeeded in keeping the goat fetuses in the system for three weeks.

[17][18] The system however, ran into several problems and was not ready for human testing.[17] Kuwabara remained hopeful that the system would be improved and would later be used on human fetuses.[17][18]

Children's Hospital of Philadelphia

Artificial wombs may soon become the future — but what are the risks?

The idea of growing babies outside the body has inspired novels and movies for decades.

See also:  "into" versus "in to"

Now, research groups around the world are exploring the possibility of artificial gestation. For instance, one group successfully grew a lamb in an artificial womb for four weeks. Australian researchers have also experimented with artificial gestation for lambs and sharks.

And in recent weeks, researchers in The Netherlands have received €2.9 million to develop a prototype for gestating premature babies.

So it’s important to consider some of the ethical issues this technology might bring.

What is an artificial womb?

Growing a baby outside the womb is known as ectogenesis (or exogenesis). And we’re already using a form of it. When premature infants are transferred to humidicribs to continue their development in a neonatal unit, that’s partial ectogenesis.

When premature infants are transferred to humidicribs to continue their development in a neonatal unit, that’s partial ectogenesis.Shutterstock

But an artificial womb could extend the period a fetus could be gestated outside the body. Eventually, we might be able to do away with human wombs altogether.

This may sound far-fetched, but many scientists working in reproductive biotechnology believe that with the necessary scientific and legal support, full ectogenesis is a real possibility for the future.

What would an artificial womb contain?

An artificial womb would need an outer shell or chamber. That’s somewhere to implant the embryo and protect it as it grows. So far, animal experiments have used acrylic tanks, plastics bags, and uterine tissues removed from an organism and artificially kept alive.

An artificial womb would also need a synthetic replacement for amniotic fluid, a shock absorber in the womb during natural pregnancy.

Finally, there would have to be a way to exchange oxygen and nutrients (so oxygen and nutrients in and carbon dioxide and waste products out). In other words, researchers would have to build an artificial placenta.

Animal experiments have used complex catheter and pump systems. But there are plans to use a mini version of extracorporeal membrane oxygenation, a technique that allows blood to be oxygenated outside the body.

  • Once these are in place, artificial gestation could one day become as common as IVF is today, a technique considered revolutionary a few decades ago.
  • And just as in the case of IVF, there are many who are concerned about what this new realm of reproductive medicine might mean for the future of creating a family.
  • So what are some of the ethical considerations?

Artificial wombs could help premature babies

The main discussion about artificial wombs has focused on their potential benefit in increasing the survival rate of extremely premature babies.

Artificial wombs could soon be a reality. What will this mean for women?

We are approaching a biotechnological breakthrough. Ectogenesis, the invention of a complete external womb, could completely change the nature of human reproduction. In April this year, researchers at the Children’s Hospital of Philadelphia announced their development of an artificial womb.

The “biobag” is intended to improve the survival rates of premature babies and is a significant step forward from conventional incubators.

Their results show that lambs (at the equivalent of a premature human foetus of 22-24 weeks) are able to successfully grow in the biobag, with the oldest lamb now more than one year old.

Researchers at Cambridge University, meanwhile, have also kept a human embryo alive outside the body for 13 days using a mix of nutrients that mimic conditions in the womb.

The embryo survived several days longer than previously observed and research only stopped because they were approaching the 14-day legal limit for the length of time an embryo can be kept in a lab.

In other words, our ethics rather than our technology are now the limiting factor.

The key to survival through ectogenesis is reproducing the conditions of the womb. As scientists become better at that, the gap between the longest time embryos can survive and the earliest time a foetus is viable will narrow. When the two timescales meet, we will have the technology for a complete external womb.

It is exactly this kind of scientific discovery that I imagined for my novel, The Growing Season.

In a world that is still similar to present day, the recent invention of an external womb known as the “baby pouch” is changing society.

For some, it has brought equality, freedom and choice, while for others the implications are much more frightening. This world is perhaps only decades away from our own; what will happen when our version of the baby pouch arrives?

The Growing Season by Helen Sedgwick.

There will be amazing medical benefits: it could save the lives of premature babies, help infertile couples, give gay and trans people new fertility options and enable older parents to have children.

It could offer a safer alternative to traditional pregnancy and childbirth and provide a healthier environment for the foetus by eliminating the risks of drugs or alcohol and providing an ideal balance of nutrients, temperature, movement and sound.

But where do we draw the line between ensuring healthy development and only having children deemed to be the “healthiest”? Who decides which type of pregnancy is “best” – women or men? Doctors? Religious leaders? Employers?

There is a danger that whoever pays for the technology behind ectogenesis would have the power to decide how, when and for whose benefit it is used. It could be the state or private insurance companies trying to avoid the unpredictable costs of traditional childbirth.

Or, it could become yet another advantage available only to the privileged, with traditional pregnancies becoming associated with poverty, or with a particular class or race.

Would babies gestated externally have advantages over those born via the human body? Or, if artificial gestation turns out to be cheaper than ordinary pregnancy, could it become an economic necessity forced on some?

But an external womb could also lead to a new equality in parenthood and consequently change the structure of our working and private lives. Given time, it could dismantle the gender hierarchies within our society.

Given more time, it could eliminate the differences between the sexes in our biology.

Once parental roles are equal, there will be no excuse for male-dominated boardrooms or political parties, or much of the other blatant inequality we see today.

Women’s rights are never more emotive than when it comes to a woman’s right to choose. While pregnancy occurs inside a woman’s body, women have some control over it, at least.

But what happens when a foetus can survive entirely outside the body? How will our legislation stand up when viability begins at conception? There are fundamental questions about what rights we give to embryos outside the body (think of the potential for harvesting “spare parts” from unwanted foetuses).

There is also the possibility of pro-life activists welcoming this process as an alternative to abortion – with, in the worst case, women being forced to have their foetuses extracted and gestated outside their bodies.

Be the first to comment

Leave a Reply

Your email address will not be published.


*