Author: Kherlen Martin

Sharing Our Current Thinking: Models Containing Aspects of Human Embryos

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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.

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Parenting in a Time of COVID

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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.

1 https://www.pewresearch.org/fact-tank/2020/10/22/fewer-mothers-and-fathers-in-u-s-are-working-due-to-covid-19-downturn-those-at-work-have-cut-hours/

2 https://www.forbes.com/sites/maggiegermano/2019/03/27/women-are-working-more-than-ever-but-they-still-take-on-most-household-responsibilities/?sh=71bbae5e52e9

3 https://www.scientificamerican.com/article/women-in-science-may-suffer-lasting-career-damage-from-covid-19/

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

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NIH’s DRAFT Data Management and Sharing Policy: We Need to Hear From You!

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Around this time last year, I wrote about a request for information (RFI) on potential key elements that could comprise a future NIH data management and sharing policy.  Not surprisingly, we received a lot of helpful feedback. Most commenters supported data sharing and the importance of prospectively planning for where, when, and how scientific data should be managed and shared.  There were, however, concerns about how one policy could fit all sizes and types of data across the biomedical research universe as well as potential burden on the research community.

Over the course of the last year, NIH has been incorporating many of these suggestions into our thinking and continuing to engage the community on their thoughts about data management and sharing. We’ve also been working with sovereign Tribal Nations through consultation sessions held across the U.S which have been vital in shaping NIH’s perspective on the potentially unique data sharing needs of those communities.

Today, NIH has released for public comment in the Federal Register a Draft NIH Policy for Data Management and Sharing along with supplement draft guidance. The draft policy furthers NIH longstanding commitment to making available the results and products of the research we fund and conduct.

To facilitate public comments, NIH has established a web-portal where folks can easily and securely provide their feedback.  The portal can be accessed by clicking here. To ensure that your comments are considered, responses must be submitted no later than January 10, 2020.

I recognize that there is a perception that a Draft policy represents a finished product, that NIH has already made up our mind. I want to assure you that this is not the case.  It is very important that we hear from the stakeholder community about what you think works and doesn’t work with respect to what we have proposed. We are also eager to hear your thoughts on the utility of the supplemental draft guidance or recommendations for any other guidance materials that would be helpful. I previously wrote a blog on best practices for public comments that you might find useful.

Finally, to further engage stakeholders, NIH will be hosting a webinar on the draft policy in the near future. Please stay tuned for the details. We look forward to hearing what you think about the draft policy and supplemental draft guidance and encourage you to broadly share its availability and our request for comments.  With your help, we can ensure that the draft policy maximizes the myriad benefits of data management and sharing while minimizing the burden to the research community.

Posted by Dr. Carrie D. Wolinetz, November 6, 2019

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Ethics is Not a Dirty Word

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When thinking about the intersection of policy and science, the notion of ‘ethical considerations’ often arises, usually in the context of ‘research should move forward while taking into account ethical considerations’. This framing can lead to strong reactions from researchers, who suggest that this will result in additional regulatory burden or bioethicists telling scientists do their jobs.  After thinking deeply about this issue, we understand where some of the confusion lies and are on a mission to try to clear it up. To many scientists, the word “ethics” appears to be code for terms like “regulation”, “oversight” – or worse – additional paperwork that does nothing to increase protections or advance science. This makes sense in a way, since the ethical principles of the Belmont report, which are the foundation for today’s human research participant protections, are actually codified through regulations like the Common Rule.

However, it is helpful to take the concept of ethics– moral principles that guide one’s behavior – back to its roots.  Ethics are more than just following the rules; it is about the abstract notion of how to “do the right thing” even in the absence of a law, regulation, or policy telling you that you have to. And here at the NIH, the world’s largest publicly funded biomedical research agency, we are always thinking about how to do the right thing.

As a publicly funded research agency, NIH has an ethical responsibility to be good stewards of those dollars invested by the public. This is reflected in the language of our agency; we are ultimately beholden to the taxpayers who collectively invest in making sure we – and the people and work we fund – behave in an ethical fashion. We have a mission to fulfill, public trust to maintain, and an imperative to ensure that we are funding the highest quality, responsibly conducted science. This IS our ethical mandate.

Now, as scientists, we completely understand the deep and urgent desire to be precise in our language. While the often imprecise nature of the term “ethics” begs further clarification from scientists, for many away from the bench, the concept is clear and its intent is crystal clear – it crops up in everyday discussions about the implications of implementing new biotechnologies, the distribution of funding across the NIH portfolio, the pros and cons of animal research, and the access of research results. When we ask scientists to ensure their experiments are rigorously designed and results are transparently presented, that is in the context of this stewardship (incidentally, it is also good for science). The flipside of that is it means poorly designed experiments could be described as unethical; and that’s the sort of framing that scientists tend to object to.

When scientists bristle against incorporating the word ethics, or the associated ethical considerations, in conversations around research, it gives the false impression that it is the rejection of the concept of ethics in the conversation. Obviously, we know this to not be true.  Many scientists hold themselves to the highest standards and think through ethical issues daily, whether it’s appropriate housing conditions for research animals, end of life issues, or privacy protections for human data.  What’s more, the conflation of ethics and regulation – and the knee jerk response it provokes from a community greatly concerned about regulatory burden – can derail the more productive conversation: how do we practically weave ethical considerations into the day to day conduct of science? For instance, neuroscientists around the globe are already self-assembling to proactively develop guides for researchers to think through potential ethical challenges early and often.

Ethics is not a static concept, nor is science. Moral principles evolve over time in society – and sometimes within ourselves – and our understanding of the world around us changes with each new discovery. At one point in history, it was considered a public good to experiment on humans regardless of their consent. By today’s standards, most would agree that principles of respect for persons, beneficence, and justice autonomy outweigh forgoing consent. In the distant past, many believed that animals were not capable of interpreting pain, whereas today we take our ethical obligations seriously to alleviate any discomfort or distress when possible. Ethical considerations are often judgment calls, thus they are not policy nor regulation nor enforceable. Consideration of ethics can sometimes be best served by asking ourselves and each other tough questions: Why are we doing this particular experiment?; Is this the best way to answer this question or is there another way?; Are the ethical issues raised by any given approach outweighed by the unique value of answering the scientific questions or do ethical issues outweigh the value of the science? Questioning the whys and hows of the ethics of science is not the same as suggesting we should not move forward. It is an opportunity for introspection, for improvement, and ultimately for reinforcing the contract we have made with the public to responsibly solve the challenges faced by us all.

This blog was co-authored by Dr. Lyric Jorgenson, Deputy Director of the NIH Office of Science Policy

Posted by Dr. Carrie D. Wolinetz, November 4, 2019

Lyric Jorgenson, PhD
NIH Associate Director for Science Policy
About Lyric
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