Sharing Our Current Thinking: Models Containing Aspects of Human Embryos

Understanding early human development helps scientists study causes of miscarriage and search for therapies and preventions for developmental disorders. As I’ve explained before on this blog, NIH is prohibited from funding research that creates or destroys human embryos. However, models of various aspects of human embryo development represent promising alternatives.

Readers of this blog may recall that in 2019, I wrote about how NIH, as a steward of public funds, carefully considers whether the agency can support proposed research using these models on a case-by-case basis. We at NIH have been following the progress of these various research approaches, and last year my office sponsored a state of the science workshop on these model systems at the National Academies of Sciences, Engineering, and Medicine. At the workshop, leaders of the field presented their findings and future research plans with models that vary in shape and composition and mimic different aspects of actual embryos and time points in development. The researchers explained how they use these models to investigate how cells differentiate into specific cell types and organize themselves and what signals coordinate key changes during embryonic development. Models range from rings of different cell types in a single-cell monolayer to more spherical models of particular features of the human embryo. (See diagrams of several models below.)

With these new tools developed and further refinements on the horizon, I thought it would be a good time to share our latest thoughts on how we decide what research we can legally support. When NIH considers whether the agency can support a specific research proposal, we ask ourselves (and sometimes the applicants!) a number of questions. These may include:

  • What stage, or aspect, of embryonic development is being modeled?
  • What cell types, structures, and functions are present in the model? For example,
    • Does the model contain all components of the epiblast lineage (i.e. the three “germ layers” that collectively form the embryo)?
    • Does the model contain any extraembryonic lineage cell types (i.e. cells that contribute to the yolk sac, placenta, or other tissues that support development of the embryo)?
    • Are there other materials or growth factors present that might substitute for the functions of the extraembryonic lineages?
  • Is the spatial orientation of the components similar to, or different from, an actual embryo?
    • Are the cells in a single monolayer or in a more complex structure?
    • How is the shape similar to or different from that of the embryo?
  • Can the model maintain its organizational structure? Does it change to look like the next stage in normal development?
  • Would the researcher watch for any unanticipated events, such as the unexpected appearance of other cell types or structures?

Ultimately, NIH considers what is the likely developmental potential of the model. This is of course a tricky question, since the ultimate test of the potential of a model would be to study its growth in a uterine environment–an experiment that NIH would never support. Yet we know what structures and functions of an embryo and extraembryonic tissue are critical for development, so we have a framework to address this question.

Personally, it has been fascinating to witness the advancements in this field. As an agency, NIH will continue to consider applications on a case-by-case basis, and do our best to be a responsible steward of public funds.

Summary of Stem Cell Models of the Mouse and Human Embryo
From Shahbazi et al., Science 364, 948–951 (2019). Reprinted with permission from AAAS.

Parenting in a Time of COVID

Next week marks the one-year anniversary of NIH shifting to maximum telework in response to the COVID-19 pandemic. Like employers and employees across the country, overnight we needed to adapt our entire enterprise and reinvent our jobs in the virtual workplace. Coincidentally, next week is also when with a deep breath and a big hug, I send my six year old back to school in person, masked up and excited to meet his 1st grade teacher in person for the first time. So it seems like a good time to reflect on what the past year has been like, juggling the demands of serving in the leadership of a government agency square in the middle of COVID response with the needs of two young children during this nationwide experiment in virtual schooling.

Over the past year, I have gotten expert at the hand-over-the-mouth side conversations with my kids while muted on videoconference. There are good days and there are bad days. Like when my already prone-to-anxiety fifth grader gets hysterical because there are technology glitches and is panicked he’s missed something. Or when my first grader breaks down into tears because he’s had to sit in front of a computer for hours and is confused by something being asked of him. Inevitably, these moments occur when I’m in the middle of a critical meeting. I’ve accidentally come off mute while in the middle of alternately yelling at and bribing my children to behave so I can just pay attention to this conversation. I long for five minutes to just pay sole attention to the work I am doing and not have to think about snack time or lunch options or whether trombone is starting to whether a Chromebook is charged. I struggle to feel smart and competent as either a mother or as a professional when the unrelenting demands of one are constantly competing with the other.

Much to the entertainment of my colleagues, I have found my six year old does best when I am working nearby, which means he is constantly in the background of my WebEx or Zoom – fidgeting, coloring, doing jumping jacks – as I try to provide intelligent advice on agency policy with a song about counting frogs in one ear. I have been caught frozen in moments of indecision, as my children come running up in hysterical tears for help with one thing or another, but I have an upcoming item on the agenda to speak to. And that’s the curated account – not delving into the darker moments when I break down in tears or lose my temper because I reached the limits of my emotional wherewithal and snap at my kids in a voice I barely recognize as my own. Or those days when I have trouble caring about what’s going on at work or just turn my children over to electronic devices for a moment of peace. I worry all the time that having my children continually visible in my workspace, demonstrating my constant state of distraction, will cause my (primarily older and male) colleagues to take me less seriously.

The media has offered extensive coverage of how truly difficult this balancing act has been, the disproportionate effect it is having on women or individuals whose jobs do not support telework, such as healthcare workers or front-line service providers, and the agonizing choice faced by many parents struggling with impossible dilemmas of keeping themselves or their loved ones safe from a deadly disease while trying to do what’s best for their child’s well-being and education. The wrench the pandemic has thrown into the everyday tension of work-life balance just doesn’t affect women, of course. In my own household, my husband has taken on more childcare responsibilities than ever, as the pandemic has increased my workload, and a recent Pew study seems to indicate this is happening all over the country1. But evidence has long shown that women bear a disproportionate burden of household and dependent care responsibilities2, and the early data on the negative impact of the pandemic on the productivity of women in science is truly alarming3. There is recognition across the biomedical enterprise that the long-term impact of the pandemic could entail a devastating setback for women and others with dependent care responsibilities, and there are a lot of discussions of strategies to minimize that risk.

In a world currently experiencing staggering loss of life and economic misfortune due to COVID-19, my challenges pale by comparison. My family has been able to stay safe, we are healthy, we are employed… and yet still it is a struggle. Even as it feels like hope is on the horizon, in the form of vaccine and falling hospitalization rates and opening of schools, we must recognize not just the toll the past year has taken on working women and parents, but also not lose sight of the bright light the pandemic has cast on this balancing act. The challenge of balancing work and caregiving doesn’t go away just because it isn’t visible on Zoom. We need to create an environment that feels safe for caregivers, particularly women, to talk about their real-world dilemmas and ask for help or just feel empathy from their peers, without feeling like revealing this diminishes us as professionals. I thought long and hard about writing such a personal blog post, but I worry that by not talking candidly and honestly about how difficult juggling this all is, I am serving as a bad role model. The working mom dilemma exists in the best of time, as author Amy Westfield describes it “We expect women to work like they don’t have children, and raise children as if they don’t work.”

I am not going to end this blog post with a pithy solution that diminishes the complexity of the problem or suggests I personally have this all figured out. The next few years will undoubtedly be dominated by a “lessons learned” conversation about COVID 19, and I plan to use my seat at the table of scientific leadership to make sure we haven’t squandered a crisis for women in science.  I hope other leaders, both men and women, will do the same.




Posted by Dr. Carrie D. Wolinetz, March 8, 2021