From September 19th to 20th this year, the U.S. Food and Drug Administration held a meeting to discuss whether to approve the world's first human clinical trial of "artificial womb" technology, triggering heated discussions around the world. What exactly is an artificial womb? What is its relationship with fertility? How far away is it from actually being put into use? ...
▲Image source: HashemAl-Ghaili
Ichijo once launched a questionnaire on artificial uterus in 2021.
And contacted Shanghai obstetrician and gynecologist Liu Jiangqin,
and the world’s largest artificial womb laboratory——
The artificial womb team at Eindhoven University of Technology in the Netherlands
Founder GuidOei,
Conducted a complete popularization of artificial uterus.
▲Viewers who participated in a survey generally have a positive attitude towards artificial wombs
Liu Jiangqin said that artificial womb actually has two concepts:
One is Ectogensis, where "the machine completely replaces the mother body".
That is, machines replace women’s reproduction,
Currently not operational;
The second is Ectogestation in which "the machine part replaces the function of the mother body".
It is technically feasible in multiple laboratories around the world.
▲Artificial uterus model at Eindhoven University of Technology in the Netherlands Picture source: TUeCursor
GuidOei said,
Their artificial uterus model has achieved certain breakthroughs.
In the future, this technology is expected to
Improve the survival rate and quality of life of premature infants,
and help women who are having trouble conceiving.
Editor: Chen Weiqin
Editor: Chen Ziwen
▲Conceptual diagram of the “artificial womb factory” conceived by Yemeni molecular biologist Hashem Al-Ghaili
In 2021, a survey was launched on "What do you think of artificial wombs" and received more than 14,000 messages with different reactions: "The last tool to save fertility rate", "Only by experiencing the pain of childbirth can we truly understand maternal love", "Is this technology like cloning, destroying the laws of nature?"...
Despite this, 80% of those who participated in the survey supported it, and 30-year-old Xiao A was one of them. In order to give birth to a healthy child, she gave up her job at the Shanghai Taxation Bureau with an annual salary of 300,000 yuan.
When she was pregnant for the first time, the pressure in the office was very low every day because she was competing for a promotion. Her baby passed away in a sudden miscarriage. "The doctor said it was a natural miscarriage and the embryo could not survive in the belly."
After that, Little A decisively gave up the promotion and salary increase, quit her job to adjust her physical condition, and finally welcomed her second baby in the third year. However, she also discovered her husband's cheating. "While I was going through the divorce process, I looked back on the past five years. I focused all my attention on preparing for pregnancy and protecting the baby. Due to physiological reasons, the child seemed to be my sole responsibility."
"Why should I care about artificial wombs? Because I want a world where men and women are truly equal in their investment in children."
▲Stills from "The Matrix"
The artificial womb that Little A longs for "starts from the fertilized egg, the embryo grows outside the mother's uterus, and the machine completely replaces the mother's body" is academically called Ectogenesis, and it still only exists in science fiction novels and movies.
In 1923, physiologist Haldane, J.B.S. first proposed the concept of "artificial uterus". He conducted a comprehensive discussion on "Ectogenesis" at the University of Cambridge and believed that in the 21st century, humans will no longer follow primitive instincts to have children, and 70% of babies will come from "Ectogenesis."
Intellectual Dora Russell agreed with Haldane and believed that women would be liberated from the need to have children, no longer play mothers, no longer grovel, no longer bound to housework, and no longer excluded from public affairs.
▲In January 2021, the First Affiliated Hospital of Zhengzhou University successfully implemented my country’s first “artificial uterus” in vitro culture of fetal sheep. Image source: Zhengzhou University official WeChat
Today, nearly 100 years later, an artificial womb called Ectogestation has the function of "a certain stage of the fetus grows outside the mother's womb, and the machine replaces part of the mother's body."
This type of artificial uterus model research, which is known as "as difficult as landing on the moon", is being carried out in various laboratories around the world: Eindhoven University of Technology in the Netherlands, Children's Hospital of Philadelphia in the United States, and the First Affiliated Hospital of Zhengzhou University in China, etc.
▲The EXTEND device has been successfully tested on animals: In 2017, a team from the Children's Hospital of Philadelphia in the United States put a fetal sheep equivalent to 23-24 weeks in humans into a "biological bag", and the lamb was successfully born after a 4-week "pregnancy period"
What is the medical concept of artificial uterus? Simply put, it is a machine that continues to nurture premature babies on behalf of the mother.
From September 19th to 20th, the U.S. Food and Drug Administration held a meeting to discuss whether to approve the world’s first human clinical trial of an “artificial womb”. The protagonist of the discussion at the conference, the EXTEND device, is an artificial uterus that simulates a natural uterus.
The device, which has been under development for years at Children's Hospital of Philadelphia, is filled with electrolyte-containing fluid to simulate the environment of amniotic fluid. Doctors will connect blood vessels in a premature baby's umbilical cord to an oxygenating system so that the baby's heart can pump blood as it would in a natural womb.
Researchers stated,EXTEND is currently the closest solution to human trials, if the trial is successful, the device could potentially buy premature babies time for their organs to mature during the critical weeks between extreme preterm birth and late pregnancy.
▲A line of artificial uterus experts: Fransvande Vosse (top), Kok Jasmijn (bottom left), Guid Oei (bottom right)
The Eindhoven University of Technology in the Netherlands is also one of the largest artificial womb research teams in the world. They received funding of 2.9 million euros (approximately RMB 22.61 million) in 2019, and a professional team of more than 200 people has been conducting clinical research on artificial uteruses for more than 4 years. Their artificial womb participated in Dutch Design Week 2018 and is one of the most advanced models in the industry.
▲A model simulating "fetus in artificial womb"
Their artificial uterus model consists of two parts:
1. The round artificial uterus model connects multiple mature medical technologies (extracorporeal circulation technology to treat the heart, dialysis technology to treat the kidneys, extracorporeal membrane lung technology to treat the lungs, etc.). The artificial amniotic fluid inside the model is rich in protein and electrolytes.
2. An intelligent machine that can monitor all organ data, including the baby's heart rate, oxygen supply, brain and muscle activity, etc. The doctor will judge the baby's health status based on the data.
Guid Oei told us, "This technology will potentially help extremely premature fetuses (under 27 weeks) continue to develop their organs and improve their survival rate and quality of life."
"In the more distant future, we want to help women who have difficulty in having children."
▲The "artificial womb" imagined by many people: couples use machines to raise children at home. Photo source: Usbek&Rica
What is the artificial womb that the public is looking forward to?
Different from the "machine replacing part of the mother's body functions" (Ectogestation) studied by doctors and scientists for premature babies, the public has higher expectations for artificial wombs. In a questionnaire of 200 received, 80% of people chose to support artificial wombs, and the vast majority of them hope to "use machines to completely replace the mother's body to give birth to children" (Ectogensis).
Many people have described what they imagine to be an artificial womb. Those with a more optimistic attitude describe the artificial womb as an artificial incubator that will replace the female uterus to gestate children from the beginning of the fertilized egg.
Xiao Cai, a college student born in the 2000s, even believes that artificial wombs are the future trend and wrote a fantasy timetable:
In 2026, artificial wombs will be put into use, bringing hope to women who cannot become pregnant;
In 2035, more and more women will use artificial wombs to give birth, increasing social competitiveness;
In 2038, artificial wombs to give birth to children became a social pandemic;
In 2041, egg trading is legalized, and the eggs of women with good age, appearance, and knowledge are quite popular;
In 2059, the institution of marriage will come to an end...
Support: Solve the regrets caused by physical defects
In a questionnaire and comments received, most of the reasons supporting "machine completely replacing the mother's body" are quite sad.
Among them, the one with a vote rate of 91.5% (the highest) was "Many people are unable to have a healthy child due to physical reasons." The breakdown includes infertility of couples, childbirth crisis at advanced ages, and incomplete development of baby organs.
According to data released by the Population Association of China and the National Family Planning Commission, 1 in every 6 couples in China is experiencing infertility.
For 36-year-old A Miao, the bowl of children and grandchildren that her mother-in-law puts on the table during festivals is the deepest thorn in her heart, which is scarier than abortion, dilation and curettage, and blocking antibody treatment.
In November 2014, July 2015, June 2016, and February 2017, Amiao experienced 4 silent fetal arrests, and the baby was always aborted spontaneously at around 3 months old. For the next four years, she did not dare to get pregnant again.
As a university teacher, facing her mother-in-law who prays to Buddha, tells fortunes, invites monks and engages in superstitious activities at home every day to "bring for the arrival of a grandchild", she can only drag her husband to travel to major infertility specialists across the country, and it is difficult to find the number one expert.
She recalled the situation of most of the patients she met in the ward: their bodies were consumed in the process of indefinite preparation for pregnancy, all social activities after get off work were cancelled, and the relationship between husband and wife gradually became rigid.
In this survey, about 80% of people said that they or their relatives and friends had had similar experiences. Almost everyone said that doctors could not give an accurate reason. The child's sudden premature birth or fetal arrest was the result of nature's survival of the fittest.
▲In the Korean drama "Postpartum Care Center", as an advanced working woman, she receives childbirth "re-education"
Lingling, a 38-year-old living in Guangzhou, said that including herself, there are many female friends around her who need a "uterus".
Two of them suffered from uterine cancer and had to "cut off their uterus to survive." Unfortunately, her second baby was miscarried at 17 weeks.
"When a couple in a family has a stable relationship and has the financial conditions to have a second child, women often face the hurdle of 'advanced maternal age.'" Lingling explained that many women's bodies can no longer bear pregnancy, but this desire to "have a new life" is more desirable than any wealth or promotion.
She went to a community hospital to open a file before and found that the five mothers who opened the file that day were all over 35 years old.
▲"Postpartum Care Center" talks about the plight of professional women
Support: Liberate the inequality brought about by childbearing to women
Among those who support it, the idea that machine reproduction will "liberate women from the unequal treaties brought about by childbirth" has a vote rate of 69.5% (second). The inequalities mentioned include workplace, family and social pressures.
60% of the people who participated in this questionnaire were women, and most of them mentioned that pregnancy is the biggest inequality between men and women in the workplace. Whether it is looking for a job, getting promoted and raising salary, furthering studies and starting a business, or preparing for pregnancy, ensuring pregnancy, and recovering after childbirth, giving birth makes women passive.
When Yihui was pregnant, she was competing for a promotion spot with several colleagues in the same position in the unit. She often traveled on business and solved a difficult case, but she suddenly had a miscarriage before the news of her promotion came.
After she recovered, she discovered that promotions had been given to people with less ability than her. The leader secretly came to her and said, "Everyone knows that you are thinking about getting pregnant, and they all want you to have a good rest."
Yafan, who was born in the 1990s, admitted that his friends generally have DINK ideas and do not want to have children until they are at least 35 years old.
She feels that compared to those born in the 80s, women born in the 90s will despise the idea of "sacrifice work for family". Especially when she heard her sister who had given birth in the office talk about the painful experience of transverse incision, perineal scission, and orthopedic surgery, she felt that artificial uterus was a reliable solution.
▲"Home on the Slope" tells the story of how women suffer great injustice in the family and society because of childcare.
April, who has lived overseas, said with a smile: "In China, childbirth can easily become a family affair."
Even if many women accept failure calmly, the people around them cannot. "You can't control your husband or mother-in-law."
Incoordination of family relationships may lead to "coldness between husband and wife", "mother-in-law's harsh words" or "parents' disappointment". The number of people who believe that artificial wombs can help alleviate family conflicts is 68% (third).
Linda, a kindergarten teacher, said that because of her own miscarriage, the previously peaceful relationship between mother-in-law and daughter-in-law was torn apart. "My mother-in-law ridiculed me and said that people of the previous generation would not have such things, and it was all due to my squeamishness. But in fact, several colleagues around me have experienced sudden miscarriage, which is very common in our group. But my mother-in-law doesn't think so."
Taozi's mother has been looking forward to a grandson since she got married. She waited for 10 years. Only later did she learn that Taozi had a "missing fallopian tube".
Due to a long period of fruitless pregnancy, the relationship between Amiao and her husband has gradually become tense. "At home, the two of us are often very tired and speechless because of the physical adjustments for in vitro fertilization."
In addition, some netizens mentioned some indirect effects, believing that artificial wombs will have a positive effect on certain groups.
Mina, a post-90s generation, believes that machine surrogacy will greatly reduce black market surrogacy or overseas surrogacy;
Mr. Wang, born in 1985, admitted that he did not want to get married, but he wanted to have a child. Artificial womb could help singles like them;
Ami born in 1995 said that China's post-90s and post-00s generations may have less desire to have children than raising cats. Using machines to give birth to children is obviously a way to solve the "low birth rate" in the future.
▲In "The Matrix", the scene where Neo wakes up from the Matrix is full of the absurdity of technology destroying mankind.
Opposition: Challenging social structures and natural laws
In a survey conducted by Ichijo, 20% of people clearly expressed their opposition to artificial wombs (Ectogensis).
Many of the mothers mentioned their own experiences during childbirth. Xinyi, who was born in the 1980s, said that after a full 20 hours of labor, the moment she saw the baby crying in front of her, she suddenly felt so great.
"Maternal love is greater because of childbirth." She believes, "If everyone chooses to avoid the pain of childbirth and cannot experience the vibration of life, then the phenomenon of abandoning children may become more and more serious."
▲Men generally have more concerns about artificial uterus than women
Compared to women, some men who participated in the survey viewed artificial uteruses from a higher and further perspective. One part of it proposed that "artificial wombs, like cloning, destroy the natural laws of human beings."
Mr. Li, an engineer born in the 1980s, pointed out, "The use of machines to replace women in childbearing is actually depriving women of their fertility since ancient times, and the value of some women will also be reduced, so this is a provocation to the social structure."
Mr. Ma from Guangdong further refined the possible social impact of artificial wombs:
Any further development of life sciences must go through detailed calculations, because this is an irreversible process, which is why the government has explicitly banned "reproductive cloning" and "gene-edited babies."
A handful of netizens also mentioned: "The development of artificial uterus is expensive, and in a short period of time, 99% of the population cannot afford the expensive treatment. This is an obvious imbalance between supply and demand. Why not spend such high funds on more meaningful things?"
▲The artificial uterus Ectogenesis in the public imagination. Picture source: Hashem Al-Ghaili
▲The artificial uterus Ectogestation that scientists are studying
Even if there is no research in the direction of "machine completely replacing the mother's body", major artificial womb research institutes around the world are still facing a lot of doubts: Isn't artificial womb the next step in cloning? Doesn't this violate the laws of nature?
Oei from the Dutch team responded: Their machine will only serve extremely premature babies in the future. Because of ethics, religion, government, beliefs, etc., they don't want their models to serve women who don't want to have children.
Considering the difficulty of research and development of artificial uterus, most experts believe that the technology of "artificial uterus partially replaces the mother's body to conceive a child" will mature in 10 years, while the research time required to "completely replace the mother's body" is about 50 years, and the process will be controversial and may not necessarily receive support from society and the government. "Using machines to give birth to children" is an appeal that will not be realized within 3 to 5 years.
▲The experiment by the Children's Hospital of Philadelphia team in the United States showed the changes in fetal sheep on the 4th and 28th days after entering the "biobag". The fetal sheep continued to develop during the process.
"Artificial uterus (Ectogestation) is a well-known 'moon landing' project in the medical community." Liu Jiangqin, a Shanghai obstetrician and gynecologist, explained that in the medical community, projects to extend human lifespan are regarded as research on the "maximum boundary" of life; and how small a fetus can come into this world and survive is regarded as research on the "minimum boundary" of life.
"According to current technology, the smallest viable baby in the world is 21 weeks plus 4 days, and the smallest baby in China is 22 weeks plus 6 days. So can the development of artificial wombs open up smaller boundaries to 20 weeks or even 18 weeks?"
Dr. Liu Jiangqin recalled the story of “extracorporeal circulation technology” (heart-related), one of the origins of artificial wombs. In the United States in the 1960s and 1970s, many parents took hospitals that "abandoned treating premature babies" to court, which promoted the development of medical technology.
A baby named Dolly was found to have trisomy 21, left ventricle, and multiple chromosomal abnormalities at birth. The doctors at the time believed that the child could not be saved, so they gave up treatment. This was considered "natural" by the medical community at the time. The parents believed that the child could survive, and out of grief, they sued the hospital to court. During the course of the lawsuit, the child died.
"In order to give these children the right to survive, society has promoted the development of extracorporeal circulation technology." Dr. Liu explained.
"So today, when we discuss artificial wombs, we won't just analyze its difficulty and cost, we will also consider the hope of survival it represents."
Life that was originally unable to survive due to objective reasons has the right to live because of the advancement of science and technology.
▲Professor Guid Oei is explaining the principle of artificial uterus to parents. Image source: TUeCursor
The clinical application of artificial uterus (Ectogestation) still requires long-term research and experiments, but this does not affect the unlimited enthusiasm of scientists around the world for it.
During the interview, both Chinese and foreign doctors mentioned the same concept: Perhaps artificial wombs can only be used to treat premature babies in the near future, and their scope of application is very narrow, but its future has unlimited possibilities.
"Although the development of artificial wombs is no less difficult than the original moon landing and current nuclear fusion, technology will develop in line with our hopes."
▲In the movie "Egg Cabin Generation", couples "share a pregnancy" through a detachable artificial uterus
The U.S. Food and Drug Administration meeting ultimately failed to vote as planned. The agency noted that research on artificial wombs is promising, but unresolved regulatory and ethical issues require further discussion, including:
Is the basis for animal testing sufficient?
Trials need to have adequate sample size, duration, duration of clinical use, risks, historical precedent, safety of exploratory data, device performance, physiological assessment of human factors, clinical pathology and histopathology assessment.
Do current clinical data support risk assessment?
Given the limited animal models and clinical data for artificial womb technology, some clinical studies on the outcomes of premature infants can be incorporated into risk assessment references.
Informed consent and child protection issues
Trials involving premature infants must provide prospects of direct clinical benefit, reasonable risk expectations, and at least one alternative therapy, unless the risk can be proven to be minimal, and the consent of the guardian must be obtained. At the same time, parents may not fully understand the therapy, be in bad mood, and have high psychological pressure. Researchers, surgeons, neonatologists, and bioethicists need to work together to design and implement the study and inform them.
Security monitoring issues
Human trials should pay special attention to adverse events such as perinatal death, critical diseases of premature infants, and death during hospitalization. The agency anticipates that human trials will initially recruit and treat one subject at a time. When adding other subjects subsequently, consideration should be given to including infants with better prognosis (such as survival rate 20-50%), and comparing with conventional treatment to evaluate outcomes such as survival and long-term neurodevelopment.
▲Image source:HashemAl-Ghaili
Q: Under what circumstances will people be the first to use artificial wombs?
A:Dutch experts believe that the fastest clinical trials of artificial wombs will begin after 2024. Parents of premature babies who are born at the edge of viability can voluntarily participate. Experts will judge the baby's physical fitness to determine whether an artificial womb can be used.
Q: How many people are in demand for artificial wombs nationwide?
A:According to the "Global Report on Prematurity" released by the WHO, there are approximately 1.2 to 1.5 million premature babies in China every year, of which 100,000 are born under 26 weeks, making them the early target group for artificial wombs.
Q: How much does an ordinary person expect to spend on using an artificial uterus?
A:At present, the medical cost of a premature baby is about 200,000 yuan per 100 days. Experts predict that the initial cost of an artificial womb will be as high as hundreds of thousands a day, but will fall as the technology matures over time.
Q: How many years will it take for the artificial womb technology to be "nurtured from an embryo" to mature?
A:From now on, clinical trials that are about three years in development will only focus on premature infants. It is expected that the maturity of artificial womb technology that starts from an embryo and does not require a mother at all is expected to take at least 50 years, and there is great controversy as to whether this technology will be completely developed or used.
Q: What is the purpose of developing artificial uterus?
A:The short-term plan is to improve the survival rate and quality of life of premature babies by extending their time in the "uterus".
Guid Oei, an obstetrician and gynecologist from the Dutch team, explained that the lungs of normal premature babies will be exposed to air prematurely, causing organ damage. However, when a premature baby quickly enters the artificial womb from the mother's body, the lungs and respiratory system will continue to sleep. The child will not be "born" from the machine until its organs have developed normally and are complete.
Q: Why is the Chinese team relatively “slow” in developing artificial wombs?
A:Liu Jiangqin, an obstetrician and gynecologist, said that in fact, many hospitals across China have the capabilities and medical equipment to manufacture artificial uteruses. China has not done extensive research, partly because current animal experiments cannot prove that artificial wombs are superior to existing medical treatments. Before artificial uterus can officially enter clinical practice, it requires a complex approval process and phase III clinical studies. Therefore, artificial uterus does not yet have clear advantages at this stage.
References:
1. Liu Jiangqin "What is the Artificial Uterus"
2. Chen Yilin of Zhengzhou University "First time in China!" Mr. Zheng successfully implemented the in vitro culture experiment of artificial uterus fetal sheep! 》
3.Successfuluseofanartificialplacentatosupportextremelypretermovinefetusesattheborderofviability
4.Successful use of anartificial placenta—basedlifesupportsystemtotreatextremelypretermovinefetusescompromisedbyintrauterineinflammation