As a subject of research, an unusual degree of consensus appears to exist among scientists, politicians and the public about human embryos being deserving of special considerations. But what those special considerations should be is less clear. And this is where the subject becomes contentious and opinions diverge because, somewhat surprisingly, what really represents a human embryo has so far not been resolved.
"Prior to implantation, embryos must be given a different level of reverence than after implantation."
In 2002, Howard W. Jones Jr., widely considered the "father" of in vitro fertilization (IVF) in the U.S., argued in a widely acclaimed article titled "What is an embryo?" that a precondition for the definition of a human embryo was successful implantation. Only once implantation established a biological unit between embryo and mother, could a relatively small number of human cells be considered a human embryo.
Because he felt strongly that human embryos, indeed, deserve special considerations, and should receive those during IVF, he pointed out that, even inside a woman's body, most human embryos (in contrast to other species) never implant and, therefore, are never given a chance at human life. Consequently, he reasoned that prior to implantation, embryos must be given a different level of reverence than after implantation.
"One cannot help but wonder about the fog of misconceptions and misrepresentations that still surrounds what an embryo is."
This difference, he felt, should also be reflected in scientific language, proposing that embryos prior to implantation in daily IVF practice be called "pre-embryos," with the term "embryo" reserved for post-implantation-stage embryos. Then still unknown to Jones, recent research findings support this viewpoint, since genetic profiles of pre- and post-implantation stage embryos greatly differ.
In an analogy to nature, which in humans allows implantation of only a small minority of naturally generated pre-embryos, IVF centers around the world routinely discard large numbers of pre-embryos, judged inadequate for producing normal pregnancies. Jones' suggestion that only post-implantation embryos should be considered embryos deserving of special considerations, therefore, not only appears prescient and considerate of current IVF practices, but grounded in scientific reality. One, therefore, cannot help but wonder about the fog of misconceptions and misrepresentations that still surrounds what an embryo is.
"Much of the regulatory environment surrounding research on human embryos is guided by emotions rather than science and logical thinking."
In 1984, a British ethics committee issued the Warnock Report, which still today prohibits scientists worldwide from studying human embryos in a lab beyond 14 days from fertilization or past formation of the so-called primitive streak, whichever comes first. Well-meaning in its day, its intent was to apply special considerations to human pre-embryos by protecting them from the potential of "feeling pain," once the primitive streak arose on day-15 of development. Formation of the primitive streak signifies a process known as gastrulation, when a subset of cells from the inner cell mass of the pre-embryo are transformed into the three germ layers that comprise all tissues of the developing embryo: The ectoderm, which gives rise to the nervous system; the mesoderm, which gives rise to the circulatory system, muscle, and kidneys; and the endoderm which gives rise to the interior lining of the digestive and respiratory tracts, among other tissues.
That pre-embryos may feel pain at that stage of development was far-fetched in 1984; in view of what we have learned about early human embryology in the 33 years since, it remains untenable today. And, yet, scientists all over the world remain bound by the ethical constraints imposed by the Warnock Report.
A similar ethical paradox exists today for guidelines affecting huge numbers of so-called "abandoned" cryopreserved embryos, often stored ad infinitum in IVF centers all over the world. These are pre-embryos, whose "parents" are no longer responsive to queries from their IVF centers. Current U.S. guidelines allow the disposal of such pre-embryos but prohibit their use in research that may benefit mankind. One, however, wonders whether disposal of huge numbers of abandoned embryos is really more ethical than their use in potentially life-saving human research?
That much of the regulatory environment surrounding research on human embryos is, indeed, guided by emotions rather than science and logical thinking, is also demonstrated by recently expressed concern about so-called "artificial" or "synthetic" embryos. Though both of these terms suggest impending ability to create human embryos from synthetic building blocks, this is not what these terms are meant to describe (such abilities also are not on the horizon). They also do not describe abilities to create gametes (i.e., eggs and sperm) from somatic cells by reprogramming adult peripheral cells, which has already been successfully done in mice by Japanese investigators, leading to the creation of healthy embryos and births and three generations of healthy pubs. Such an approach is at least conceivable as an upcoming infertility treatment.
"A team of biologists and engineers at the University of Michigan recently received media attention after creating organoids from embryonic stem cells that resembled human embryos."
What all of this noise is really about is the discovery that, as several Rockefeller University investigators recently noted, "Cells have an intrinsic ability to self-assemble and self-organize into complex and functional tissues and organs." Investigators have taken advantage of this ability by creating in the lab so-called "organoids" from accumulations of individual embryonic stem cells. They are defined by three characteristics: (i) they contain a variety of cell types and tissue layers, all typical for a given organ; (ii) these cells are organized similarly to their organization in a specific organ; and (iii) the organoid mimics functions of the organ.
Several other biologists from the Cincinnati Children Hospital Medical Center recently noted that in the last five years, quite a variety of human stem cell-derived organoids, including all three germ layers, have been generated by different research groups around the world, thereby establishing new human model systems that can be used outside the body, in a dish, to investigate otherwise difficult-to-approach organs. Interestingly, they can also be used to investigate early stages of human embryological development.
A team of biologists and engineers at the University of Michigan recently received media attention after creating organoids from embryonic stem cells that resembled human embryos and, therefore, were given the name "embroids." Though clearly not embryos (the only thing they had in common with human embryos were cell types), they were nevertheless awarded in at least one article the identity of "artificial embryos," which "no one knows how to handle." As Howard Jones so correctly noted, with the word embryo often comes undeserved reverence.
"Any association with the term "embryo" should be avoided; it is not only misleading and irresponsible but scientifically incorrect."
Artificial embryos, therefore, do not exist. Organoids that resemble embryos (i.e., "embroids"), while potentially very useful research objects in studies of early human embryonic cell organization and lineage development, are not embryos--not even pre-embryos. Special considerations for "artificial" or "synthetic" embryos, as recently advocated by some scientists, therefore, appear ethically undeserved. How misdirected and forced some of these efforts are is probably best demonstrated by a recent publication in which a group of Harvard University investigators proposed the term "synthetic human entities with embryo-like features" or SHEEFS" in place of "organoids." Preferably, however, in describing these laboratory-created entities, any association with the term "embryo" should be avoided. It is not only misleading and irresponsible but scientifically incorrect.
Clinical reproductive medicine and reproductive biology, for valid ethical reasons, but also because of myths, misperceptions and, sometimes, outright misrepresentations of facts for political reasons, are under more public scrutiny than most other science areas. Yet, at least in the realm of biomedical research, nothing appears more important than better understanding the first few days of human embryo development. A recent study involving genetic editing of human embryos, reported by British investigators in Nature, once again confirmed what biologist have known for some time: No animal model faithfully recapitulates most of human developmental origins. The most important secrets nature still has to tell us, will not be revealed through mouse or other animal studies. We will discover them only through the study of early-stage human embryos – and we, therefore, should not limit the use of lab-grown organoids to help further that research.
Understanding early human development "will not only greatly enhance the biological understanding of our species; but also will open groundbreaking new therapeutic options in all areas of medicine."
As Howard Jones intuitively noticed, words matter. Appropriate and uniformly accepted definitions and terms are not only essential for scientific communications but, within the context of human reproduction, often elicit strong emotional reactions, and are easily misappropriated by those opposed to most interventions into human reproduction.
Who does not recall the early days of IVF in the late 1970s, when even reputable news outlets raised the specter of Frankenstein monsters created through the IVF process? Millions of IVF births later, a Nobel Prize in Medicine and Physiology was in 2010 finally awarded to the biologist Robert Edwards who, together with the gynecologist Patrick Steptoe, reported the first live birth through IVF on July 25, 1978. Many more awards are still waiting for recipients who through the study of early human embryo development will discover how cell fate is determined and cells acquire highly specific functions; how rapid cell proliferation takes place and, when required, stops; why chromosomal abnormalities are so common in early stage embryos and what their function may be.
Those who will discover these and many other important answers, will not only greatly enhance the biological understanding of our species; but also will open groundbreaking new therapeutic options in all areas of medicine. Learning how to control cell proliferation, for example, will likely revolutionize cancer therapy; I started my research career in biology with a study published in 1980 of "common denominators of pregnancy and malignancy." If regulatory prohibitions are not allowed to interfere in rapidly progressing research opportunities involving organoids and pre-embryos, we will, finally, see the circle closing, with the most rewarding benefits for mankind ever achieved through biological research.
Editor's Note: Read a different viewpoint here written by one of the world's top experts on the ethics of stem cell research.
On the morning of April 12, 1955, newsrooms across the United States inked headlines onto newsprint: the Salk Polio vaccine was "safe, effective, and potent." This was long-awaited news. Americans had limped through decades of fear, unaware of what caused polio or how to cure it, faced with the disease's terrifying, visible power to paralyze and kill, particularly children.
The announcement of the polio vaccine was celebrated with noisy jubilation: church bells rang, factory whistles sounded, people wept in the streets. Within weeks, mass inoculation began as the nation put its faith in a vaccine that would end polio.
Today, most of us are blissfully ignorant of child polio deaths, making it easier to believe that we have not personally benefited from the development of vaccines. According to Dr. Steven Pinker, cognitive psychologist and author of the bestselling book Enlightenment Now, we've become blasé to the gifts of science. "The default expectation is not that disease is part of life and science is a godsend, but that health is the default, and any disease is some outrage," he says.
The Rise and Fall of Public Trust<p>When the polio vaccine was released in 1955, "we were nearing an all-time high point in public trust," says Matt Baum, Harvard Kennedy School professor and lead author of <a href="http://www.kateto.net/covid19/COVID19%20CONSORTIUM%20REPORT%2013%20TRUST%20SEP%202020.pdf" target="_blank" rel="noopener noreferrer"><u>several</u></a> <a href="https://shorensteincenter.org/wp-content/uploads/2020/09/COVID19-CONSORTIUM-REPORT-14-MISINFO-SEP-2020.pdf" target="_blank" rel="noopener noreferrer"><u>reports</u></a> measuring public trust and vaccine confidence. Baum explains that the U.S. was experiencing a post-war boom following the Allied triumph in WWII, a popular Roosevelt presidency, and the rapid innovation that elevated the country to an international superpower.</p><p> The 1950s witnessed the emergence of nuclear technology, a space program, and unprecedented medical breakthroughs, adds Emily Brunson, Texas State University anthropologist and co-chair of the Working Group on Readying Populations for COVID-19 Vaccine. "Antibiotics were a game changer," she states. While before, people got sick with pneumonia for a month, suddenly they had access to pills that accelerated recovery. </p><p>During this period, science seemed to hold all the answers; people embraced the idea that we could "come to know the world with an absolute truth," Brunson explains. Doctors were portrayed as unquestioned gods, so Americans were primed to trust experts who told them the polio vaccine was safe. </p>
The Shift in How We Consume Information<p>In the 1950s, the media created an informational consensus. The fundamental ideas the public consumed about the state of the world were unified. "People argued about the best solutions, but didn't fundamentally disagree on the factual baseline," says Baum. Indeed, the messaging around the polio vaccine was centralized and consistent, led by President Roosevelt's successful <a href="https://files.eric.ed.gov/fulltext/EJ978264.pdf" target="_blank" rel="noopener noreferrer"><u>March of Dimes crusade</u></a>. People of lower socioeconomic status with limited access to this information were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551508/?page=3" target="_blank" rel="noopener noreferrer"><u>less likely to have confidence</u></a> in the vaccine, but most people consumed <a href="https://www.c-span.org/video/?506891-1/a-special-report-polio" target="_blank" rel="noopener noreferrer"><u>media that assured them</u></a> of the vaccine's safety and <a href="https://www.cbsnews.com/news/the-salk-polio-vaccine-greatest-public-health-experiment-in-history/" target="_blank" rel="noopener noreferrer"><u>mobilized them</u></a> to receive it. </p><p>Today, the information we consume is no longer centralized—in fact, just the opposite. "When you take that away, it's hard for people to know what to trust and what not to trust," Baum explains. We've witnessed an increase in polarization and the technology that makes it easier to give people what they want to hear, reinforcing the human tendencies to vilify the other side and reinforce our preexisting ideas. When information is engineered to further an agenda, each choice and risk calculation made while navigating the COVID-19 pandemic <a href="https://www.nytimes.com/2020/12/19/opinion/sunday/coronavirus-science.html?referringSource=articleShare" target="_blank" rel="noopener noreferrer"><u>is deeply politicized</u></a>. </p><p>This polarization maps onto a rise in socioeconomic inequality and economic uncertainty. These factors, associated with a sense of lost control, prime people to embrace misinformation, explains Baum, especially when the situation is difficult to comprehend. "The beauty of conspiratorial thinking is that it provides answers to all these questions," he says. Today's insidious fragmentation of news media accelerates the circulation of mis- and disinformation, reaching more people faster, regardless of veracity or motivation. In the case of vaccines, skepticism around their origin, safety, and motivation is intensified. </p><p>Alongside the rise in polarization, Pinker says "the emotional tone of the news has gone downward since the 1940s, and journalists consider it a professional responsibility to cover the negative." Relentless focus on everything that goes wrong further erodes public trust and paints a picture of the world getting worse. "Life saved is not a news story," says Pinker, but perhaps it should be, he continues. "If people were more aware of how much better life was generally, they might be more receptive to improvements that will continue to make life better. These improvements don't happen by themselves."</p>
The Future Depends on Vaccine Confidence<p>So far, the U.S. has been unable to mitigate the catastrophic effects of the pandemic through social distancing, testing, and contact tracing. President Trump has <a href="https://www.washingtonpost.com/politics/bob-woodward-rage-book-trump/2020/09/09/0368fe3c-efd2-11ea-b4bc-3a2098fc73d4_story.html" target="_blank" rel="noopener noreferrer"><u>downplayed the effects and threat of the virus</u></a>, <a href="https://www.washingtonpost.com/outlook/2020/07/14/cdc-directors-trump-politics/" target="_blank" rel="noopener noreferrer"><u>censored experts and scientists</u></a>, <a href="https://www.theatlantic.com/science/archive/2020/06/america-giving-up-on-pandemic/612796/" target="_blank" rel="noopener noreferrer"><u>given up on containing the spread</u></a>, and <a href="https://www.nytimes.com/2020/09/16/world/covid-coronavirus.html" target="_blank" rel="noopener noreferrer"><u>mobilized his base to protest masks</u></a>. The Trump Administration failed to devise a national plan, so our national plan has defaulted to hoping for the <a href="https://www.politico.com/news/2020/08/26/nation-of-miracles-pence-coronavirus-vaccine-rnc-402949" target="_blank" rel="noopener noreferrer"><u>"miracle" of a vaccine</u></a>. And they are "something of a miracle," Pinker says, describing vaccines as "the most benevolent invention in the history of our species." In record-breaking time, three vaccines have arrived. But their impact will be weakened unless we achieve mass vaccination. As Brunson notes, "The technology isn't the fix; it's people taking the technology."</p><p> Significant challenges remain, including facilitating widespread access and supporting on-the-ground efforts to allay concerns and build trust with <a href="https://www.newyorker.com/news/daily-comment/african-american-resistance-to-the-covid-19-vaccine-reflects-a-broader-problem" target="_blank" rel="noopener noreferrer"><u>specific populations with historic reasons for distrust</u></a>, says Brunson. Baum predicts continuing delays as well as deaths from other causes that will be linked to the vaccine. </p><p> Still, there's every reason for hope. The new administration "has its eyes wide open to these challenges. These are the kind of problems that are amenable to policy solutions if we have the will," Baum says. He forecasts widespread vaccination by late summer and a bounce back from the economic damage, a "Good News Story" that will bolster vaccine acceptance in the future. And Pinker reminds us that science, medicine, and public health have greatly extended our lives in the last few decades, a trend that can only continue if we're willing to roll up our sleeves. </p>
Imagine this scenario: you get an annoying cough and a bit of a fever. When you wake up the next morning you lose your sense of taste and smell. That sounds familiar, so you head to a doctor's office for a Covid test, which comes back positive.
Your next step? An anti-Covid nasal spray of course, a "trickster drug" that will clear the once-dangerous and deadly virus out of the body. The drug works by tricking the coronavirus with decoy receptors that appear to be just like those on the surface of our own cells. The virus latches onto the drug's molecules "thinking" it is breaking into human cells, but instead it flushes out of your system before it can cause any serious damage.
This may sounds like science fiction, but several research groups are already working on such trickster coronavirus drugs, with some candidates close to clinical trials and possibly even becoming available late this year. The teams began working on them when the pandemic arrived, and continued in lockdown.
Biochemist David Baker, pictured in his lab at the University of Washington.