Ectogenesis, the development of a baby outside of the mother's body, is a concept that dates back to 1923. That year, British biochemist-geneticist J.B.S. Haldane gave a lecture to the "Heretics Society" of the University of Cambridge in which he predicted the invention of an artificial womb by 1960, leading to 70 percent of newborns being born that way by the 2070s. In reality, that's about when an artificial womb could be clinically operational, but trends in science and medicine suggest that such technology would come in increments, each fraught with ethical and social challenges.
An extra-uterine support device could be ready for clinical trials in humans in the next two to four years, with hopes that it could improve survival of very premature infants.
Currently, one major step is in the works, a system called an extra-uterine support device (EUSD) –or sometimes Ex-Vivo uterine Environment (EVE)– which researchers at the Children's Hospital of Philadelphia have been using to support fetal lambs outside the mother. It also has been called an artificial placenta, because it supplies nutrient- and oxygen-rich blood to the developing lambs via the umbilical vein and receives blood full of waste products through the umbilical arteries. It does not do everything that a natural placenta does, yet it does do some things that a placenta doesn't do. It breathes for the fetus like the mother's lungs, and encloses the fetus in sterile fluid, just like the amniotic sac. It represents a solution to one set of technical challenges in the path to an artificial womb, namely how to keep oxygen flowing into a fetus and carbon dioxide flowing out when the fetal lungs are not ready to function.
Capable of supporting fetal lambs physiologically equivalent to a human fetus at 23 weeks' gestation or earlier, the EUSD could be ready for clinical trials in humans in the next two to four years, with hopes that it could improve survival of very premature infants. Existing medical technology can keep human infants alive when born in this 23-week range, or even slightly less —the record is just below 22 weeks. But survival is low, because most of the treatment is directed at the lungs, the last major body system to mature to a functional status. This leads to complications not only in babies born before 24 weeks' gestation, but also in a fairly large number of births up to 28 weeks' gestation.
So, the EUSD is basically an advanced neonatal life support machine that beckons to square off the survival curve for infants born up to the 28th week. That is no doubt a good thing, but given the political prominence of reproductive issues, might any societal obstacles be looming?
"While some may argue that the EUSD system will shift the definition of viability to a point prior to the maturation of the fetus' lungs, ethical and legal frameworks must still recognize the mother's privacy rights as paramount."
Health care attorney and clinical ethicist David N. Hoffman points out that even though the EUSD may shift the concept of fetal viability away from the maturity of developing lungs, it would not change the current relationship of the fetus to the mother during pregnancy.
"Our social and legal frameworks, including Roe v. Wade, invite the view of the embryo-fetus as resembling a parasite. Not in a negative sense, but functionally, since it obtains its life support from the mother, while she does not need the fetus for her own physical health," notes Hoffman, who holds faculty appointments at Columbia University, and at the Benjamin N. Cardozo School of Law and the Albert Einstein College of Medicine, of Yeshiva University. "In contrast, our ethical conception of the relationship is grounded in the nurturing responsibility of parenthood. We prioritize the welfare of both mother and fetus ethically, but we lean toward the side of the mother's legal rights, regarding her health throughout pregnancy, and her right to control her womb for most of pregnancy. While some may argue that the EUSD system will shift the definition of viability to a point prior to the maturation of the fetus' lungs, ethical and legal frameworks must still recognize the mother's privacy rights as paramount, on the basis of traditional notions of personhood and parenthood."
Outside of legal frameworks, religion, of course, is a major factor in how society reacts to new reproductive technologies, and an artificial womb would trigger a spectrum of responses.
"Significant numbers of conservative Christians may oppose an artificial womb in fear that it might harm the central role of marriage in Christianity."
Speaking from the perspective of Lutheran scholarship, Dr. Daniel Deen, Assistant Professor of Philosophy at Concordia University in Irvine, Calif., does not foresee any objections to the EUSD, either theologically, or generally from Lutherans (who tend to be conservative on reproductive issues), since the EUSD is basically an improvement on current management of prematurity. But things would change with the advent of a full-blown artificial womb.
"Significant numbers of conservative Christians may oppose an artificial womb in fear that it might harm the central role of marriage in Christianity," says Deen, who specializes in the philosophy of science. "They may see the artificial womb as a catalyst for strengthening the mechanistic view of reproduction that dominates the thinking of secular society, and of other religious groups, including more liberal Christians."
Judaism, however, appears to be more receptive, even during the research phases.
"Even if researchers strive for a next-generation EUSD aimed at supporting a fetus several weeks earlier than possible with the current system, it still keeps the fetus inside the mother well beyond the 40-day threshold, so there likely are no concerns in terms of Jewish law," says Kalman Laufer, a rabbinical student and executive director of the Medical Ethics Society at Yeshiva University. Referring to a concept from the Babylonian Talmud that an embryo is "like water" until 40 days into pregnancy, at which time it receives a kind of almost-human status warranting protection, Laufer cautions that he's speaking about artificial wombs developed for the sake of rescuing very premature infants. At the same time though, he expects that artificial womb research will eventually trigger a series of complex, legalistic opinions from Jewish scholars, as biotechnology moves further toward supporting fetal growth entirely outside a woman's body.
"Since [the EUSD] gives some justification to end abortion, by transferring fetuses from mother to machine, conservatives will probably rally around it."
While the technology treads into uncomfortable territory for social conservatives at first glance, it's possible that the prospect of taking the abortion debate in a whole new direction could engender support for the artificial womb. "Since [the EUSD] gives some justification to end abortion, by transferring fetuses from mother to machine, conservatives will probably rally around it," says Zoltan Istvan, a transhumanist politician and journalist who ran for U.S. president in 2016. To some extent, Deen agrees with Istvan, provided we get to a point when the artificial womb is already a reality.
"The world has a way of moving forward despite the fear of its inhabitants," Deen notes. "If the technology gets developed, I could not see any Christians, liberal or conservative, arguing that people seeking abortion ought not opt for a 'transfer' versus an abortive procedure."
So then how realistic is a full-blown artificial womb? The researchers at the Children's Hospital of Philadelphia have noted various technical difficulties that would come up in any attempt to connect a very young fetus to the EUSD and maintain life. One issue is the small umbilical cord blood vessels that must be connected to the EUSD as fetuses of decreasing gestational age are moved outside the mother. Current procedures might be barely adequate for integrating a human fetus into the device in the 18 -21 week range, but going to lower gestational ages would require new technology and different strategies. It also would require numerous other factors to cover for fetal body systems that mature ahead of the lungs and that the current EUSD system is not designed to replace. However, biotechnology and tissue engineering strategies on the horizon could be added to later EUSDs. To address the blood vessel size issue, artificial womb research could benefit by drawing on experts in microfluidics, the field concerned with manipulation of tiny amounts of fluid through very small spaces, and which is ushering in biotech innovations like the "lab on a chip".
"The artificial womb might put fathers on equal footing with mothers, since any embryo could potentially achieve personhood without ever seeing the inside of a woman's uterus."
If the technical challenges to an artificial womb are indeed overcome, reproductive policy debates could be turned on their side.
"Evolution of the EUSD into a full-blown artificial external uterus has ramifications for any reproductive rights issues where policy currently assumes that a mother is needed for a fertilized egg to become a person," says Hoffman, the ethicist and legal scholar. "If we consider debates over whether to keep cryopreserved human embryos in storage, destroy them, or utilize them for embryonic stem cell research or therapies, the artificial womb might put fathers on equal footing with mothers, since any embryo could potentially achieve personhood without ever seeing the inside of a woman's uterus."
Such a scenario, of course, depends on today's developments not being curtailed or sidetracked by societal objections before full-blown ectogenesis is feasible. But if this does ever become a reality, the history of other biotechnologies suggests that some segment of society will embrace the new innovation and never look back.
A natural material that looks and feels like real leather is taking the fashion world by storm. Scientists view mycelium—the vegetative part of a mushroom-producing fungus—as a planet-friendly alternative to animal hides and plastics.
Products crafted from this vegan leather are emerging, with others poised to hit the market soon. Among them are the Hermès Victoria bag, Lululemon's yoga accessories, Adidas' Stan Smith Mylo sneaker, and a Stella McCartney apparel collection.
The Adidas Stan Smith Mylo shoe, made with an alternative leather grown from mycelium, to be released in 2022.
Hermès has held presales on the new bag, says Philip Ross, co-founder and chief technology officer of MycoWorks, a San Francisco Bay area firm whose materials constituted the design. By year-end, Ross expects several more clients to debut mycelium-based merchandise. With "comparable qualities to luxury leather," mycelium can be molded to engineer "all the different verticals within fashion," he says, particularly footwear and accessories.
More than a half-dozen trailblazers are fine-tuning mycelium to create next-generation leather materials, according to the Material Innovation Initiative, a nonprofit advocating for animal-free materials in the fashion, automotive, and home-goods industries. These high-performance products can supersede items derived from leather, silk, down, fur, wool, and exotic skins, says A. Sydney Gladman, the institute's chief scientific officer.
That's only the beginning of mycelium's untapped prowess. "We expect to see an uptick in commercial leather alternative applications for mycelium-based materials as companies refine their R&D [research and development] and scale up," Gladman says, adding that "technological innovation and untapped natural materials have the potential to transform the materials industry and solve the enormous environmental challenges it faces."
In fewer than 10 days in indoor agricultural farms, "we grow large slabs of mycelium that are many feet wide and long. We are not confined to the shape or geometry of an animal."
Reducing our carbon footprint becomes possible because mycelium can flourish in indoor farms, using agricultural waste as feedstock and emitting inherently low greenhouse gas emissions. Carbon dioxide is the primary greenhouse gas. "We often think that when plant tissues like wood rot, that they go from something to nothing," says Jonathan Schilling, professor of plant and microbial biology at the University of Minnesota and a member of MycoWorks' Scientific Advisory Board.
But that assumption doesn't hold true for all carbon in plant tissues. When the fungi dominating the decomposition of plants fulfill their function, they transform a large portion of carbon into fungal biomass, Schilling says. That, in turn, ends up in the soil, with mycelium forming a network underneath that traps the carbon.
Unlike the large amounts of fossil fuels needed to produce styrofoam, leather and plastic, less fuel-intensive processing is involved in creating similar materials with a fungal organism. While some fungi consist of a single cell, others are multicellular and develop as very fine threadlike structures. A mass of them collectively forms a "mycelium" that can be either loose and low density or tightly packed and high density. "When these fungi grow at extremely high density," Schilling explains, "they can take on the feel of a solid material such as styrofoam, leather or even plastic."
Tunable and supple in the cultivation process, mycelium is also reliably sturdy in composition. "We believe that mycelium has some unique attributes that differentiate it from plastic-based and animal-derived products," says Gavin McIntyre, who co-founded Ecovative Design, an upstate New York-based biomaterials company, in 2007 with the goal of displacing some environmentally burdensome materials and making "a meaningful impact on our planet."
After inventing a type of mushroom-based packaging for all sorts of goods, in 2013 the firm ventured into manufacturing mycelium that can be adapted for textiles, he says, because mushrooms are "nature's recycling system."
The company aims for its material—which is "so tough and tenacious" that it doesn't require any plastic add-on as reinforcement—to be generally accessible from a pricing standpoint and not confined to a luxury space. The cost, McIntyre says, would approach that of bovine leather, not the more upscale varieties of lamb and goat skins.
Already, production has taken off by leaps and bounds. In fewer than 10 days in indoor agricultural farms, "we grow large slabs of mycelium that are many feet wide and long," he says. "We are not confined to the shape or geometry of an animal," so there's a much lower scrap rate.
Decreasing the scrap rate is a major selling point. "Our customers can order the pieces to the way that they want them, and there is almost no waste in the processing," explains Ross of MycoWorks. "We can make ours thinner or thicker," depending on a client's specific needs. Growing materials locally also results in a reduction in transportation, shipping and other supply chain costs, he says.
Yet another advantage to making things out of mycelium is its biodegradability at the end of an item's lifecycle. When a pair of old sneakers lands in a compost pile or landfill, it decomposes thanks to microbial processes that, once again, involve fungi. "It is cool to think that the same organism used to create a product can also be what recycles it, perhaps building something else useful in the same act," says biologist Schilling. That amounts to "more than a nice business model—it is a window into how sustainability works in nature."
A product can be called "sustainable" if it's biodegradable, leaves a minimal carbon footprint during production, and is also profitable, says Preeti Arya, an assistant professor at the Fashion Institute of Technology in New York City and faculty adviser to a student club of the American Association of Textile Chemists and Colorists.
On the opposite end of the spectrum, products composed of petroleum-based polymers don't biodegrade—they break down into smaller pieces or even particles. These remnants pollute landfills, oceans and rivers, contaminating edible fish and eventually contributing to the growth of benign and cancerous tumors in humans, Arya says.
Commending the steps a few designers have taken toward bringing more environmentally conscious merchandise to consumers, she says, "I'm glad that they took the initiative because others also will try to be part of this competition toward sustainability." And consumers will take notice. "The more people become aware, the more these brands will start acting on it."
A further shift toward mycelium-based products has the capability to reap tremendous environmental dividends, says Drew Endy, associate chair of bioengineering at Stanford University and president of the BioBricks Foundation, which focuses on biotechnology in the public interest.
The continued development of "leather surrogates on a scaled and sustainable basis will provide the greatest benefit to the greatest number of people, in perpetuity," Endy says. "Transitioning the production of leather goods from a process that involves the industrial-scale slaughter of vertebrate mammals to a process that instead uses renewable fungal-based manufacturing will be more just."
Amy Bitterman, who teaches at Rutgers Law School in Newark, gets enormous pleasure from her three mixed-breed rescue cats, Spike, Dee, and Lucy. To manage her chronically stuffy nose, three times a week she takes Allegra D, which combines the antihistamine fexofenadine with the decongestant pseudoephedrine. Amy's dog allergy is rougher--so severe that when her sister launched a business, Pet Care By Susan, from their home in Edison, New Jersey, they knew Susan would have to move elsewhere before she could board dogs. Amy has tried to visit their brother, who owns a Labrador Retriever, taking Allegra D beforehand. But she began sneezing, and then developed watery eyes and phlegm in her chest.
"It gets harder and harder to breathe," she says.
Animal lovers have long dreamed of "hypo-allergenic" cats and dogs. Although to date, there is no such thing, biotechnology is beginning to provide solutions for cat-lovers. Cats are a simpler challenge than dogs. Dog allergies involve as many as seven proteins. But up to 95 percent of people who have cat allergies--estimated at 10 to 30 percent of the population in North America and Europe--react to one protein, Fel d1. Interestingly, cats don't seem to need Fel d1. There are cats who don't produce much Fel d1 and have no known health problems.
The current technologies fight Fel d1 in ingenious ways. Nestle Purina reached the market first with a cat food, Pro Plan LiveClear, launched in the U.S. a year and a half ago. It contains Fel d1 antibodies from eggs that in effect neutralize the protein. HypoCat, a vaccine for cats, induces them to create neutralizing antibodies to their own Fel d1. It may be available in the United States by 2024, says Gary Jennings, chief executive officer of Saiba Animal Health, a University of Zurich spin-off. Another approach, using the gene-editing tool CRISPR to create a medication that would splice out Fel d1 genes in particular tissues, is the furthest from fruition.
"Our goal was to ensure that whatever we do has no negative impact on the cat."
Customer demand is high. "We already have a steady stream of allergic cat owners contacting us desperate to have access to the vaccine or participate in the testing program," Jennings said. "There is a major unmet medical need."
More than a third of Americans own a cat (while half own a dog), and pet ownership is rising. With more Americans living alone, pets may be just the right amount of company. But the number of Americans with asthma increases every year. Of that group, some 20 to 30 percent have pet allergies that could trigger a possibly deadly attack. It is not clear how many pets end up in shelters because their owners could no longer manage allergies. Instead, allergists commonly report that their patients won't give up a beloved companion.
No one can completely avoid Fel d1, which clings to clothing and lands everywhere cat-owners go, even in schools and new homes never occupied by cats. Myths among cat-lovers may lead them to underestimate their own level of risk. Short hair doesn't help: the length of cat hair doesn't affect the production of Fel d1. Bathing your cat will likely upset it and accomplish little. Washing cuts the amount on its skin and fur only for two days. In one study, researchers measured the Fel d1 in the ambient air in a small chamber occupied by a cat—and then washed the cat. Three hours later, with the cat in the chamber again, the measurable Fel d1 in the air was lower. But this benefit was gone after 24 hours.
For years, the best option has been shots for people that prompt protective antibodies. Bitterman received dog and cat allergy injections twice a week as a child. However, these treatments require up to 100 injections over three to five years, and, as in her case, the effect may be partial or wear off. Even if you do opt for shots, treating the cat also makes sense, since you could protect more than one allergic member of your household and any allergic visitors as well.
An Allergy-Neutralizing Diet
Cats produce much of their Fel d1 in their saliva, which then spreads it to their fur when they groom, observed Nestle Purina immunologist Ebenezer Satyaraj. He realized that this made saliva—and therefore a cat's mouth--an unusually effective site for change. Hens exposed to Fel d1 produce their own antibodies, which survive in their eggs. The team coated LiveClear food with a powder form of these eggs; once in a cat's mouth, the chicken antibody binds to the Fel d1 in the cat's saliva, neutralizing it.
The results are partial: In a study with 105 cats, the level of active Fel d1 in their fur had dropped on average by 47 percent after ten weeks eating LiveClear. Cats that produced more Fel d1 at baseline had a more robust response, with a drop of up to 71 percent. A safety study found no effects on cats after six months on the diet. "Our goal was to ensure that whatever we do has no negative impact on the cat," Satyaraj said. Might a dogfood that minimizes dog allergens be on the way? "There is some early work," he said.
This is a year when vaccines changed the lives of billions. Saiba's vaccine, HypoCat, delivers recombinant Fel d1 and the coat from a plant virus (the Cucumber mosaic virus) without any vital genetic information. The viral coat serves as a carrier. A cat would need shots once or twice a year to produce antibodies that neutralize Fel d1.
HypoCat works much like any vaccine, with the twist that the enemy is the cat's own protein. Is that safe? Saiba's team has followed 70 cats treated with the vaccine over two years and they remain healthy. Again the active Fel d1 doesn't disappear but diminishes. The team asked 10 people with cat allergies to report on their symptoms when they pet their vaccinated cats. Eight of them could pet their cat for nearly a half hour before their symptoms began, compared with an average of 17 minutes before the vaccine.
Jennings hopes to develop a HypoDog shot with a similar approach. However, the goal would be to target four or five proteins in one vaccine, and that increases the risk of hurting the dog. In the meantime, allergic dog-lovers considering an expensive breeder dog might think again: Independent research does not support the idea that any breed of dog produces less dander in the home. In fact, one well-designed study found that Spanish water dogs, Airedales, poodles and Labradoodles--breeds touted as hypo-allergenic--had significantly more of the most common allergen on their coat than an ordinary Lab and the control group.
One day you might be able to bring your cat to the vet once a year for an injection that would modify specific tissues so they wouldn't produce Fel d1.
Nicole Brackett, a postdoctoral scientist at Viriginia-based Indoor Biotechnologies, which specializes in manufacturing biologics for allergy and asthma, most recently has used CRISPR to identify Fel d1 genetic sequences in cells from 50 domestic cats and 24 exotic ones. She learned that the sequences vary substantially from one cat to the next. This discovery, she says, backs up the observations that Fel d1 doesn't have a vital purpose.
The next step will be a CRISPR knockout of the relevant genes in cells from feline salivary glands, a prime source of Fel d1. Although the company is considering using CRISPR to edit the genes in a cat embryo and possibly produce a Fel d1-free cat, designer cats won't be its ultimate product. Instead, the company aims to produce injections that could treat any cat.
Reducing pet allergens at home could have a compound benefit, Indoor Biotechnologies founder Martin Chapman, an immunologist, notes: "When you dampen down the response to one allergen, you could also dampen it down to multiple allergens." As allergies become more common around the world, that's especially good news.