We Should Resist Making “Synthetic Embryos” Too Realistic
Ethics needs context. So does science – specifically, science that aims to create bioengineered models of early human embryo development in a dish (hereafter synthetic embryos). Even the term "synthetic embryos" begs for an explanation. What are these? And why would anyone want to create them?
"This knowledge may help scientists understand how certain birth defects are formed and why miscarriages often occur."
First the research context. Synthetic embryos are stem cell-derived simulations of human post-implantation embryos that are designed to mimic a stage of early development called gastrulation. That's the stage—around 14-15 days after fertilization – when embryos begin to form a very primitive body plan (basic dorsal-ventral and anterior-posterior axes, and distinct cell lineages). Researchers are starting to create synthetic embryos in the lab – albeit imperfect and incomplete versions – to learn how gastrulation might unfold in real human embryos embedded unseen in the womb. This knowledge may help scientists understand how certain birth defects are formed and why miscarriages often occur soon after implantation. As such, synthetic embryos are meant to be models of human embryo development, not themselves actually embryos. But will synthetic embryos ever get to the point where they are practically the same thing as "natural" human embryos? That is my concern and why I think researchers should avoid creating synthetic embryos capable of doing everything natural embryos can do.
It may not be too difficult to prevent this slide from synthetic to real. Synthetic embryos must be created using sophisticated 3D culture systems that mimic the complex architecture of human embryos. These complex culture systems also have to incorporate precise microinjection systems to chemically trigger the symmetry-breaking events involved in early body plan formation. In short, synthetic embryos need a heavy dose of engineering to get their biological processes going and to help keep them going. And like most engineered entities, designs can be built into the system early to serve well-considered goals – in our case, the goal of not wanting to create synthetic embryos that are too realistic.
"If one wants to study how car engines work, one can model an engine without also modeling the wheels, transmission, and every other car part together."
A good example of this point is found a report published in Nature Communications where scientists created a human stem cell-based 3D model that faithfully recapitulates the biological events around post-implantation amniotic sac development. Importantly, however, the embryo model they developed lacked several key structures and therefore – despite its partial resemblance to an early human embryo – did not have complete human form and potential. While fulfilling their model's aim of revealing a previously inaccessible early developmental event, the team intentionally did not recreate the entire post-implantation human embryo because they did not want to provoke any ethical concerns, as the lead author told me personally. Besides, creating a complete synthetic embryo was not necessary or scientifically justified for the research question they were pursuing. This example goes to show that researchers can create a synthetic embryo to model specific developmental events they want to study without modeling every aspect of a developing embryo. Likewise – to use a somewhat imprecise but instructive analogy – if one wants to study how car engines work, one can model an engine without also modeling the wheels, transmission, and every other car part together.
A representative "synthetic embryo," which in some ways resembles a post-implantation embryo around 14 days after fertilization.
(Courtesy of Yue Shao)
But why should researchers resist creating complete synthetic embryos? To answer this, we need some policy context. Currently there is an embryo research rule in place – a law in many nations, in others a culturally accepted agreement – that intact human embryos must not be grown for research in the lab for longer than 14 consecutive days after fertilization or the formation of the primitive streak (a faint embryonic band that signals the start of gastrulation). This is commonly referred to as the 14-day rule. It was established in the UK decades ago to carve out a space for meritorious human embryo research while simultaneously assuring the public that researchers won't go too far in cultivating embryos to later developmental stages before destroying them at the end of their studies. Many citizens accepting of pre-implantation stage human embryo research would not have tolerated post-implantation stage embryo use. The 14-day rule was a line in the sand, drawn to protect the advancement of embryo research, which otherwise might have been stifled without this clear stopping point. To date, the 14-day rule has not been revoked anywhere in the world, although new research in extended natural embryo cultivation is starting to put some pressure on it.
"Perhaps the day will come when scientists don't have to apply for research funding under such a dark cloud of anti-science sentiment."
Why does this policy context matter? The creation of complete synthetic embryos could raise serious questions (some of them legal) about whether the 14-day rule applies to these lab entities. Although they can be constructed in far fewer than 14 days, they would, at least in theory, be capable of recapitulating all of a natural embryo's developmental events at the gastrulation stage, thus possibly violating the spirit of the 14-day rule. Embryo research laws and policies worldwide are not ready yet to tackle this issue. Furthermore, professional guidelines issued by the International Society for Stem Cell Research prohibit the culture of any "organized embryo-like cellular structures with human organismal potential" to be cultured past the formation of the primitive streak. Thus, researchers should wait until there is greater clarity on this point, or until the 14-day rule is revised through proper policy-making channels to explicitly exclude complete synthetic embryos from its reach.
I should be clear that I am not basing my recommendations on any anti-embryo-research position per se, or on any metaphysical position regarding the positive moral status of synthetic embryos. Rather, I am concerned about the potential backlash that research on complete synthetic embryos might bring to embryo research in general. I began this essay by saying that ethics needs context. The ethics of synthetic embryo research needs to be considered within the context of today's fraught political environment. Perhaps the day will come when scientists don't have to apply for research funding under such a dark cloud of anti-science sentiment. Until then, however, it is my hope that scientists can fulfill their research aims by working on an array of different but each purposefully incomplete synthetic embryo models to generate, in the aggregate of their published work, a unified portrait of human development such that biologically complete synthetic embryo models will not be necessary.
Editor's Note: Read a different viewpoint here written by a leading New York fertility doctor/researcher.
When a patient is diagnosed with early-stage breast cancer, having surgery to remove the tumor is considered the standard of care. But what happens when a patient can’t have surgery?
Whether it’s due to high blood pressure, advanced age, heart issues, or other reasons, some breast cancer patients don’t qualify for a lumpectomy—one of the most common treatment options for early-stage breast cancer. A lumpectomy surgically removes the tumor while keeping the patient’s breast intact, while a mastectomy removes the entire breast and nearby lymph nodes.
Fortunately, a new technique called cryoablation is now available for breast cancer patients who either aren’t candidates for surgery or don’t feel comfortable undergoing a surgical procedure. With cryoablation, doctors use an ultrasound or CT scan to locate any tumors inside the patient’s breast. They then insert small, needle-like probes into the patient's breast which create an “ice ball” that surrounds the tumor and kills the cancer cells.
Cryoablation has been used for decades to treat cancers of the kidneys and liver—but only in the past few years have doctors been able to use the procedure to treat breast cancer patients. And while clinical trials have shown that cryoablation works for tumors smaller than 1.5 centimeters, a recent clinical trial at Memorial Sloan Kettering Cancer Center in New York has shown that it can work for larger tumors, too.
In this study, doctors performed cryoablation on patients whose tumors were, on average, 2.5 centimeters. The cryoablation procedure lasted for about 30 minutes, and patients were able to go home on the same day following treatment. Doctors then followed up with the patients after 16 months. In the follow-up, doctors found the recurrence rate for tumors after using cryoablation was only 10 percent.
For patients who don’t qualify for surgery, radiation and hormonal therapy is typically used to treat tumors. However, said Yolanda Brice, M.D., an interventional radiologist at Memorial Sloan Kettering Cancer Center, “when treated with only radiation and hormonal therapy, the tumors will eventually return.” Cryotherapy, Brice said, could be a more effective way to treat cancer for patients who can’t have surgery.
“The fact that we only saw a 10 percent recurrence rate in our study is incredibly promising,” she said.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”