Test-tube babies are not born in test tubes—when does an embryo become a “person”? |

IVF has changed the way we reproduce, but it has also changed our view of ourselves in a way few people realize. It has shown us that humans develop from a single cell, which has made the boundary between cells and humans more complicated.

One view is that the embryo is a group of cells that "exploit" the maternal environment for its own selfish interests. This is particularly evident in the earliest stages of the embryo (such as the blastocyst stage) - the embryo looks more like "human tissue" than a person. When we are able to see and even intervene in the early stages of individual life with the help of in vitro fertilization technology, we find that our usual concept of personality is no longer sufficient to define the status of this living entity.

Therefore, the purpose of the intractable ethical debates surrounding assisted reproductive technology is not only to establish appropriate legislative basis. These ethical debates are also trying to redefine "what is a person": these clusters of cells were once all we had, when did they become us?

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By Philip Ball

Translation | Li Ke, Wang Yating

We have known for at least a few centuries that sexual intercourse is not necessary for reproduction. The first recorded artificial insemination was performed by the Scottish surgeon John Hunter in the 1770s. Hunter allegedly impregnated the man’s wife with sperm from a man. A more detailed account of artificial insemination appeared in 1884, when the American doctor William Pancoast impregnated a woman under general anesthesia (chloroform was used as an anesthetic) using sperm from a donor. (Original note: “Donor” was not a concept of the time. The sperm reportedly came from one of Pancoast’s students, who was considered the most handsome and dashing of his students. The students were sworn to secrecy.) Earlier, Pancoast had examined the sperm of the woman’s husband under a microscope and found that he was infertile. Pancoast apparently thought he was doing a favour. Neither the woman nor her husband knew that Pancost had performed artificial insemination at the time. Pancost later told her husband about the situation, but the wife was kept in the dark. (Original note: The reason for hiding the truth from his wife is unknown. Although the ethical issues of this artificial insemination seem shocking today, this has also prevented people from discussing this incident in depth. Was it because they were afraid that the mother would no longer love her child after knowing the truth? Was it because they were afraid that she would be shocked and ashamed of the operation? Was it because they were afraid that she would condemn Pancost and his students? Is the starting point of this paternalistic chauvinism simple? This incident is undoubtedly a node worth recording in the evolution of public attitudes towards assisted reproductive technology.)

At the time, microscopes were revealing the biology of conception. In 1879, Swiss zoologist Hermann Fol first observed a sperm entering an egg, though the fertilized egg apparently did not form an embryo. But after Carrel and Barros improved tissue culture techniques, creating embryos was one of the first things researchers tried. In 1912, American anatomists John McWhorter and Allen Whipple found that they could keep three-day-old chicken embryos alive in vitro for up to 31 hours. A year later, Belgian embryologist Albert Brachet showed that he could keep rabbit blastocyst-stage embryos alive in a dish.

Using sperm and eggs to create a live embryo outside the body—true IVF—is another matter. In the 1930s, American biologist Gregory Pincus reported using IVF to produce rabbit embryos. In the 1940s, he even claimed to have successfully fertilized human eggs and sperm in vitro, but his work was never confirmed. The first credible report of IVF helping mammals to reproduce came in the 1950s, by Pincus’s collaborator, Chinese-American biologist Chang Ming-jue. He used IVF to produce live rabbits from female rabbits. To prove that the rabbits were indeed the result of IVF, Chang used rabbits of different colors: He combined eggs and sperm from black rabbits and then implanted the embryos into white rabbits. The resulting rabbits were black.

Human fertilization is more difficult. Fertilization is not just throwing an egg and sperm together and letting them do whatever they want. As I mentioned earlier, fertilization is a complex process that also requires the female reproductive organs to participate. For a long time, no one could find a way to achieve in vitro fertilization because we knew very little about the biological process of fertilization.

In the 1930s, American obstetrician and gynecologist John Rock decided to study the fertilized egg in the earliest stages after conception, launching a project that would be jaw-dropping today. Together with his assistants Arthur Hertig and Miriam Menkin, he searched for fertilized eggs in volunteers who were scheduled to undergo hysterectomies. They suggested to the women that they could have sex the night before the surgery. The women agreed to Rock and others' request to collect fertilized eggs, which showed their generosity and willingness to advance human understanding of fertility and fertility disorders. The fact that the study was approved at all shows that people at the time still did not fully understand the need for medical ethics.

In 1944, Locke and Menkin claimed to have achieved the first in vitro fertilization in humans using eggs collected during hysterectomy. Locke and his colleagues were able to observe the fertilized eggs begin to divide, but that was all: they did not grow true embryos in a petri dish. In later research, Locke made groundbreaking contributions to the development of oral contraceptives.

In the early days of IVF, there was a certain wildness and risk-taking in the academic world, and research to test hypotheses often relied on boldness, eloquence, and a certain amount of hubris. In the 1960s, while working at the National Institute for Medical Research in north London, physiologist Robert Edwards did his best to obtain eggs from surgeons and gynecologists who shared his goals. The eggs were obtained during ovarian surgery, but without the consent of the egg "donors". Such freedom was the norm at the time. Although Edwards was motivated by relieving the suffering of infertility, in this picture of male doctors creating "new life" with the help of unsuspecting women, we can't help but see that cultural attitudes about assisted reproduction have not changed much since Pancoast's time. As the anthropologist Lynn Morgan has pointed out, one of the characteristics of the history of embryology is that the women who provided embryos or eggs are anonymous: they are often treated as a source of unidentified biological material to be manipulated in research. Some feminists are wary or even averse to reproductive technologies, perhaps because of a legitimate concern that these technologies are reverting to old ways of controlling and dominating women.

However, Edwards did not value fame and honor. On the contrary, his efforts were attacked and ridiculed by his peers. Edwards' doctoral student Martin Johnson summarized the working atmosphere of the team at that time:

To be honest, when we were doing our PhDs and even as postdocs in his lab, we were extremely unsure about the ethics of his research and didn't want to get too involved. Part of that was because as graduate students and early postdocs, we were quite disturbed by the depth of hostility to the work from outsiders - when Nobel laureates, Royal Society fellows, and rising stars of the discipline... denounced Bob and said he shouldn't be doing this research...you can't help but wonder, what on earth are we doing in our lab?

Despite skepticism and opposition from his peers, who considered the work unethical—for example, prominent biologists such as James Watson and Max Perutz later warned that IVF might produce babies with severe birth defects (note: when you realize that IVF has not produced animal pups with severe birth defects in animal experiments, the fact becomes even clearer: these fears have no scientific basis)—and the refusal of the British Medical Research Council to fund his research, Edwards, in 1969, in collaboration with his student Barry Bavister and gynecologist Patrick Steptoe, published a paper in Nature detailing the process of human sperm entering an egg in vitro. “Human fertilized eggs may be used to treat certain infertility conditions,” they wrote. The following year, Edwards, Steptoe, and their clinical assistant, Jean Purdy, published photos of human fertilized embryos at the 16-cell stage. By 1971, they were able to culture human embryos in vitro to the blastocyst stage.

Steptoe was familiar with the surgical techniques of reimplanting embryos into the uterus, and the researchers knew that there would be no shortage of volunteers, even if the procedure was highly uncertain and even dangerous.

The moment of fertilization? The sperm is about to enter the egg. Image source: Science Photo Library

But these photos of human embryos in a dish have a deeper meaning: For the first time, we can see the beginning of life's journey, which until now has been traced only to a tiny, human-like mass of tissue with a shrimp-like head already formed.

To think about ourselves in terms of development, we first need to be able to witness the process of development. "The embryo we talk about today is a relatively new concept," says Lynn Morgan. "A hundred years ago, most Americans probably couldn't imagine the image of a human embryo." Morgan points out that some cultures do not regard aborted embryos as real people, nor do they believe that they have the same moral status as people. (Original note: In some cultures, even newborn babies are not necessarily considered fully human. This is because infant mortality rates were very high before the 20th century, and this high mortality rate may have created a certain psychological distance between people and newborn babies.) Currently, many "anti-abortion" groups use images obtained through biomedical technology and use these images to prove their point. They use the fetus in the womb to represent the embryo, suggesting that from the moment of conception, the embryo is already a person.

According to science historian Nick Hopwood, the concept of "human development" is actively constructed rather than just a revealed "fact about life." According to him, this construction process began with embryology in the late 19th century. At that time, biologists and physicians believed that the formation of an embryo was an intricate but unremarkable biological process. They also believed that the moral issues raised by embryo formation could be clarified or even resolved through more scientific understanding.

We now know that this is not the case. In fact, the opposite is true. It is hard to understand what IVF reveals about the development of an individual. What kind of imagination does it take to connect a crying baby to a small mass of cells that, after all, look like a bunch of soap bubbles?

We tried to use a word to link a common device in chemistry laboratories - the stage for in vitro fertilization - with the sacred fruit of pregnancy. The word is "test tube baby".

Test tubes have never been used in IVF; their role is purely symbolic. The term “test tube baby” first appeared in the early 20th century, when the public’s understanding of biology was still rudimentary. To them, creating life through chemical means sounded entirely possible, even imminent. In those days, what we today call IVF—the union of sperm and egg outside the body, and perhaps the continued growth of the fertilized egg outside the body—was a feat that seemed not too far from God’s creation of life.

Children placed in glass containers have long been part of the human imagination of life and death. For centuries, the bodies of stillborn babies, miscarriages, and deformed infants have been preserved in jars. As Susan Merrill Squires documents, the idea of ​​a creature not only stored in a bottle after death but actually created in an artificial environment made of glass dates back to at least the Middle Ages and the Renaissance. Alchemists and mystics of the time claimed to be able to create little people in the laboratory and even provided recipes for their creation. In Faust, Goethe described how such creatures were created and clarified the moral basis on which they should be evaluated.

In vitro cell culture changed this narrative and gave us the test-tube baby. In his 1924 book Daedalus, or Science and the Future, JBS Haldane described the prospect of ectogenesis, or pregnancy outside the body. This inspired his friend Aldous Huxley to write a famous satirical novel nearly a decade later, Brave New World. In Brave New World, babies grown in vitro are chemically manipulated to create a system of social classes based on intelligence.

Haldane believed that this (hypothetical) technology could bring benefits to humanity. It could support the emancipation of women - which Haldane welcomed in principle - and the social engineering of eugenics to keep the human race alive. Haldane and Julian Huxley worried that as opportunities for women increased, more educated and intelligent women would be less willing to have children because they would find that life was not just about domestic drudgery. But due to a lack of opportunities, the "lower classes" would continue to reproduce, and (Haldane worried) the human gene pool would become weaker with each passing year. As the narrator of Daedalus, or Science and the Future explains from the perspective of the 21st century:

If it were not for ectomorphism, human civilization would undoubtedly collapse in the foreseeable future, because the inferior members of the population would have greater fertility. (Original note: Unfortunately, Haldane preferred to use "fertility" to refer to the actual number of offspring, rather than the potential ability to produce offspring. This ambiguous usage is still prevalent and no less misleading.)

The possibility of artificially creating humans in a controlled laboratory environment using in vitro fertilization raised concerns about population control and the decline of civilization in the period between the two world wars.

Haldane never expected that everyone would accept his vision of the future. “From the rubbing of wood to the soaring sky, there is no great invention that has not been regarded as an insult to some deity,” he wrote, “but if all physical and chemical inventions are blasphemous, then every biological invention is even more perverted and depraved.” Haldane was well aware that some people would view in vitro fertilization and related techniques of manipulating conception in the laboratory as “unseemly and unnatural,” and they were. In 1938, Nora Burke published an overreactionary article in Tidbits inspired by Schengweiss’s tissue culture work (see page 215). In it, she referred to “chemical babies” and asked, “What on earth are these creatures?” The title of the article—“Would You Love a Chemical Baby?”—provoked the reaction of rejection the author hoped for.

But it seems that it was none other than Thomas Schengweiss himself who coined the term "test-tube baby." In his 1926 lecture on tissue culture, Schengweiss said: "It is clear that the idea of ​​'test-tube baby' is not a fantasy." "Test-tube baby" is a more resonant term than Haldane's "in vitro development", which sounds more like a scientific term. Anyone can grasp the meaning of the word "test-tube baby" and feel a mixture of emotions: surprise, excitement, and possibly fear. It is a symbol of modernity itself: a symbol of humanity in an era of scientific control over life.

A common picture of "test tube baby": when implanted in the uterus, the embryo is still in the pre-blastocyst stage, but the image of a baby is often used to represent these embryos. Image source: Shutterstock

In short, "test tube baby" is the right term for the time being. That a person can be the product of a miraculous technology is almost an inevitable result of industrial mass production. After all, industrial mass production seems to produce everything in people's lives on an assembly line, a standardized, tested and commercialized process.

The distance between Haldane's ectopic development and the breeding centers in Aldous Huxley's Brave New World is not that great. But perhaps closer to Schengweis's test-tube baby is the idea of ​​the robot. The idea was first proposed by the Czech writer Karel Capek in his 1921 play "R.U.R." RUR is an abbreviation of the name of a company called Rossum's Universal Robots. Although Capek's robots (the word means "worker" in Czech) may bring to mind humanoid machines made of metal and wires - like the "Terminator" that rips off its artificial skin - the Rossum robots are not like that: they are made of soft flesh.

In the play, Harry Domin, the general manager of RUR, explains that the robots were invented by Russell, who discovered something while experimenting with chemistry in test tubes, trying to create living matter. Russell, a marine biologist, created a new form of "protoplasm" in the test tubes. From a chemical point of view, this protoplasm was much simpler than the protoplasm in cells. "Then he had to get this life out of the test tube," Domin said.

Using this artificial life, RUR created something like dough that could be shaped into organs. “Over there are the vats where they make the liver, the brain, and so on,” Domin said, “and over there is the assembly room where everything is put together.”9 The production process relies on Henry Ford’s automated production model, but the manufacturing technology is clearly based on tissue and organ culture techniques pioneered by people like Carrel and Schengweiss.

The same fears reflected in Capek’s work—fears about the production of homogenized humans on an industrial scale—also drove David H. Keller to write a story titled “A Biological Experiment” in a 1928 issue of Amazing Stories. The story predicted a dystopian future in which sex would be banned and babies would be created in factory vats according to standardized specifications and irradiated and distributed to couples who obtained the necessary government permits. Aldous Huxley’s later novel Brave New World had a similar plot.

Of course, dystopian stories are always more eye-catching than utopian ones. As always, it’s worth noting that these “chemical babies” stories often end with artificial humans conquering humans. R.U.R. established a template for stories where evil robots fight back and conquer humans. This template is still used today, such as the plot of the TV series Westworld and the Skynet system in the movie Terminator. Science fiction is not often about obedient robots. The assumption is self-evident: artificially manufactured people are inherently lacking in morality and therefore cold and ruthless. In Nora Burke’s writing, “chemical babies” are described gratuitously as “sexless, soulless chemical creatures” who may eventually “conquer real humans” and lead to “the end of mankind.” But in Britain in 1938, it’s perhaps not difficult to understand where this fear came from. “How to make a person” has never been a simple scientific question, but a profound and unavoidable sociopolitical question.

The image of the “test-tube baby” was not confined to Amazing Stories magazine, but would have fit right in with the “highbrow” Nature magazine. The origin of the term suggests that it is a mistake to assume (as many scientists do) that science is a matter of hard work and hustling away, when the media and popular culture work together to denigrate science with lurid slogans and images. The truth is that the “professional” and “popular” sides of scientific innovation go hand in hand. Honna Fell’s enthusiasm for promoting and disseminating the work of the Schengweiss laboratory (in large part because of the desire to win support and funding for it) eventually faded after seeing the sensational headlines and science fiction stories about it. When rumors spread in 1935 that the Schengweiss laboratory was planning to create a test-tube baby, Fell was immediately alarmed, insisting that scientists should describe tissue culture only as “a valuable technique, with its own particular advantages and its own limitations.” This did not stop the Daily Express from writing the following year that in Schengweiss’s lab, “living tissues grow and develop outside the body exactly as they would in a whole living animal”. The article quoted a dubious anonymous scientist (“from another laboratory at Cambridge University”) who claimed that the research “has taken the first step towards the society of Aldous Huxley’s Brave New World, by growing babies in test tubes”. As historian Duncan Wilson points out, while Fell herself was happy to spread the work of Schengweiss’s lab, being described as creating soulless chemical babies “was clearly not the publicity she was looking for”.

One might think that the distortion and exaggeration of the facts is due to Fair. But her advice to scientists – that they should talk about their research and try to resonate with their audience – is not wrong. The point is that scientists must recognize that the impact of their descriptions and metaphors is no longer under their control, so they had better be careful about what they say. This conflict is particularly evident in discussions about genetics and genomics today. Scientists are indignant about the public's simplistic understanding of such subjects as genetic determinism, but the public can easily retort with "You said so in the first place."

About the Author

Philip Ball is a science writer, a fellow of the Royal Society of Chemistry, a member of the European Commission's expert group on synthetic biology, and a consulting editor of Nature magazine, where he served as editor for 20 years.