Category Archives: science

October 31, 2023 data analysis and visualization workshop for science writers

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Thanks to the Science Media Centre of Canada for the notice about this upcoming workshop for science writers, (from the Data Analysis and Visualization Tools for Science Writers page on eventbrite.com), Note: There is a fee of $125 (I assume this is US currency) and a limited number of discounts are available (keep reading either here or on the event page for details about the discounts),

[downloaded from https://www.eventbrite.com/e/data-analysis-and-visualization-tools-for-science-writers-tickets-692049688247]

Also from the event page,

This workshop will focus on reporting & producing data stories about science topics, highlighting free tools for analysis & visualization.

Date and time

Tuesday, October 31 · 12:30 – 2pm PDT

Location

Online

Refund Policy

Contact the organizer to request a refund.Eventbrite’s fee is nonrefundable.

About this event

1 hour 30 minutes Mobile eTicket

Science writers are used to encountering data, whether we’re reading through dense scientific papers or trying to figure out what a statistic means for our readers. But sometimes, datasets themselves can be sources for stories—and they have led to some of the most widely read science stories of the last few years, from El Pais’ visualization of coronavirus spread to ProPublica’s investigation of burning sugar cane. Datasets can help us make complex topics accessible, visualize patterns from research, or even investigate instances of wrongdoing.

A science writer interested in pursuing stories like these could find a wide variety of resources to help them get started on a data project. But the growing data journalism field can be overwhelming: you might not be sure how to pick an initial project, which online course to try, which tools to use, or whether you need to learn how to code first. (Spoiler alert: you don’t!)

This 90-minute hands-on workshop from The Open Notebook, building on the instructor’s TON article about this topic [TON = The Open Notebook], will provide a crash course in data reporting basics. It’s designed for science writers who are interested in pursuing data stories but aren’t quite sure how to get started, and for editors who are interested in working with writers on these stories.

You’ll get an introduction to all of the steps of reporting and producing a data story, from finding story ideas to editing and fact-checking. The workshop will include an interactive tutorial showcasing two common tools that you can start using immediately.

You will learn how to:

Recognize potential data stories on your beat
Search for public datasets that you can use
Use free tools for data analysis and visualization
Work with a data team or independently as a freelancer
Make your data stories accessible

The workshop will be recorded and made available to registered participants for three months following the workshop.

Instructor

Betsy Ladyzhets is an independent science, health, and data journalist focused on COVID-19 and the future of public health. She runs the COVID-19 Data Dispatch, a publication that provides news, resources, and original reporting on COVID-19 data. Recently, she was a journalism fellow at MuckRock, where she contributed to award-winning COVID-19 investigations. She also previously managed the Science & Health vertical at Stacker and volunteered at the COVID Tracking Project. Her freelance work has appeared in Science News, The Atlantic, STAT, FiveThirtyEight, MIT Technology Review, and other national publications.

Registration Fee

The registration fee is $125.

About our discounted rates: Our goal at The Open Notebook is to support the advancement of science journalists around the world. In particular, we want to ensure that the resources we provide are accessible to those who have experienced higher-than-average barriers to entry in our field. A limited number of discounted slots are available on a first-come, first-served basis to individuals who are members of communities that have historically been underrepresented in science journalism or whose economic circumstances would make the full cost of the workshops a financial strain. To use this discount, add the promo code TON_70DISCOUNT for a 70 percent discount. (The promo code box is above the workshops listing on the sign-up page.)

I found out a little more about The Open Notebook, from their About tab Mission page,

Our Mission

The Open Notebook is a 501(c)(3) non-profit organization that is widely regarded as the leading online source of training and educational materials for journalists who cover science. We are dedicated to fostering a supportive, diverse, and inclusive global community that enables reporters and editors who cover science to learn and thrive. Through our comprehensive library of articles on the craft of science journalism and our extensive training and mentoring programs, we empower journalists at all experience levels, around the world, to tell impactful, engaging stories about science.

…

Why We’re Here

At no other time in human history has the meaning of what constitutes a fact—a valid piece of knowledge—been more at risk than it is today. Journalists’ ability to report stories about science clearly, accurately, and engagingly has never been more critical for public understanding of science and for a well-functioning democracy. Journalists who cover science play a crucial and demanding role in society—they must not only explain the newest advances in scientific research, but also provide critical context and analysis on issues ranging from climate change to infectious disease to artificial intelligence; shed light on the human beings behind the research; and serve as watchdogs to help ensure the continued freedom and integrity of the scientific enterprise.

To fulfill such a role takes skill. And the skills that science journalists need are endangered. Only a fraction of working science journalists are trained in formal journalism programs. And with the shrinking number of traditional staff jobs available, science journalism is fast moving toward a “gig economy” that relies on freelancers to produce work once done by staffers. One effect of that shift is that fewer journalists have the opportunity to master skills through the natural mentoring that takes place in newsrooms. In addition, science journalists who are from historically underrepresented communities face formidable barriers to entry and participation in the field. The Open Notebook is dedicated to helping journalists cultivate fundamental skills necessary for covering science and to helping foster a more inclusive community of voices covering science.

What We Do

Since The Open Notebook was founded in 2010, more than a million people from around the world have visited the site. Thousands of journalists have taken part in our courses, workshops, and mentoring programs. Below is a summary of our major programs.

…

There you have it.

Study on skepticism towards such scientific innovations as nanotechnology, AI, and human gene editing

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A September 26, 2023 CORDIS* press release announces a new study, Note: Links have been removed,

A new study looks at political beliefs, religion and spirituality to identify what makes people sceptical [sic] about new scientific developments.

Scientists supported by the EU-funded PSYDISC project carried out a study to gain a better understanding of people’s scepticism [sic] towards scientific innovations. They found that people who identify as spiritual are highly sceptical [sic] about advances in three scientific fields.

Science is advancing at a rapid pace, with novel technologies having the potential to eradicate disease and bring about many other advancements in medicine and areas such as food production and climate protection. Despite the benefits of such developments, concerns about their side effects have given rise to heated debates worldwide. To discover why some people are so sceptical [sic] about certain scientific innovations, the researchers surveyed 614 people from the Netherlands about their opinions on human genome editing, nanotechnology and AI. Their findings were published in the journal ‘Science Communication’.

Not really a matter of religion or politics

The team looked beyond the influence of political and religious beliefs, also examining the role played by spirituality. Growing rapidly in western Europe, spirituality – also known as New Age or post-Christian spirituality – is a range of beliefs and practices that reflect a dismissive attitude towards religious and scientific sources of authority. People who identify as spiritual emphasise [emphasize?] personal experience as a source of knowledge as opposed to trust in scientific methods. “As such, spirituality can be a driving force behind scepticism [sic] towards certain domains of science and technology,” reports a news item posted on the website of PSYDISC project coordinator University of Amsterdam.

According to study co-author Dr Bastiaan Rutjens: “Political ideology and religiosity are usually not the primary factors contributing to scepticism [sic] about specific topics such as nanotechnology and AI.” He goes on to explain: “Other aspects of a person’s worldview and beliefs, like spirituality, moral concerns and general trust in science, play a larger role.”

The study revealed clear evidence that individuals who identify as spiritual are more sceptical [sic] in the three areas investigated, namely AI, nanotechnology and human genome editing. “Generally, spiritual individuals have less trust in science,” observes Dr Rutjens.

Unsurprisingly, religious people were also found to be rather sceptical [sic] about human genome editing and, to a lesser degree, about nanotechnology. People who are averse to tampering with nature also expressed scepticism [sic] about genetic manipulation. However, political ideology was shown to have no influence on people’s scepticism [sic] towards scientific advancements.

A person’s religion, spirituality and the way they view nature are what appear to influence their attitude towards scientific innovations. “It is therefore important to make a distinction between religious and spiritual beliefs if we want to understand why people reject certain forms of science,” remarks Dr Rutjens.

The PSYDISC (Developing and Testing the Psychological Distance to Science Model) study highlights the need for a more in-depth look at the world views that shape these attitudes, especially in western Europe, where spirituality is on the rise and religion on the decline.

Here’s a link to and a citation for the study,

Who Is Skeptical About Scientific Innovation? Examining Worldview Predictors of Artificial Intelligence, Nanotechnology, and Human Gene Editing Attitudes by Bojana Većkalov, Aart van Stekelenburg, Frenk van Harreveld, and Bastiaan T. Rutjens. Science Communication Volume 45, Issue DOI: https://doi.org/10.1177/10755470231184203 First published online: July 19, 2023

This paper is open access.

You can find Project II: PSYDISC here. It is a project that’s being funded by the ERC (European Research Council) and is administered by the PsiSci Lab which is ’embedded’ in the University of Amsterdam’s faculty of Social and Behavioural sciences.

*According to its Wikipedia entry, CORDIS, “The Community Research and Development Information Service (CORDIS) is the European Commission’s primary public repository and portal to disseminate information on all European Union (EU) funded research projects and their results in the broadest sense.” Note: Links have been removed.

Simon Fraser University’s (SFU; Canada) Café Scientifique Fall 2023 events: first event is Sept. 26, 2023

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From a September 7, 2023 SFU Café Scientifique announcement of their Fall 2023 event schedule (received via email),

We hope you had a great summer and are all excited for a brand new fall line-up:

SFU Café Scientifique lectures and discussions on Zoom 

Tuesdays from 5:00-6:30pm, Zoom invites are sent to those who register.

Email cafe_scientifique@sfu.ca for inquires.

Sept 26, 2023 Vance Williams, Chemistry

Title: (Un)Natural Beauty: Art, Science and Technology

Description: While art is often described in opposition to science and technology, in reality, these disciplines are mutually supporting and reinforcing explorations of the natural and constructed world. In this presentation, I will examine the intersection of art and science and the often blurry distinction between the scientist and the artist.

[Register here for September 26, 2023 event]

October 24, 2023 Ailene MacPherson, Mathematics

Title: Who, What, Where, When, and Why: the power of genomics in public health

Description: Within days of first being identified the full genome sequence of SARS Cov-2 was published online. Here we discuss the extraordinary power and limitations of genomics for understanding disease spread and for designing effective public health interventions.

[Register here for October 24, 2023 event]

November 28, 2023 Dustin King, Molecular Biology and Biochemistry

Title: Decoding how life senses and responds to carbon dioxide gas.

Description: Dustin King’s Indigenous background is central to his work and relationship with the biochemical research he conducts. He brings Indigenous ways of knowing and a two-eye seeing approach to critical questions about humanity’s impact upon the natural world. 

Join Dr. King on a microscopic journey into intricate cellular systems, which make use of CO2 in incredible ways. The presence of CO2 on Earth has given rise to a diverse evolutionary tree, with plants and animals developing ingenious methods for harnessing and using CO2 in their unique habitats. We travel from the depths of the ocean floor to the air we breathe, to understand the implications of increasing CO2 levels in nature and in daily human life.

[Register here for November 28, 2023 event]

I wouldn’t have thought art/science or, as it sometimes called, sciart was a particularly obscure concept these days but it’s a good reminder that much depends on the community from which you draw your audience.

Synthetic human embryos—what now? (2 of 2)

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The term they’re using in the Weizmann Institute of Science’s (Israel) announcement is “a generally accurate human embryo model.” This is in contrast to previous announcements including the one from the University of Cambridge team highlighted in Part 1.

From a September 6, 2023 news item on phys.org, Note: A link has been removed,

A research team headed by Prof. Jacob Hanna at the Weizmann Institute of Science has created complete models of human embryos from stem cells cultured in the lab—and managed to grow them outside the womb up to day 14. As reported today [September 6, 2023] in Nature, these synthetic embryo models had all the structures and compartments characteristic of this stage, including the placenta, yolk sac, chorionic sac and other external tissues that ensure the models’ dynamic and adequate growth.

Cellular aggregates derived from human stem cells in previous studies could not be considered genuinely accurate human embryo models, because they lacked nearly all the defining hallmarks of a post-implantation embryo. In particular, they failed to contain several cell types that are essential to the embryo’s development, such as those that form the placenta and the chorionic sac. In addition, they did not have the structural organization characteristic of the embryo and revealed no dynamic ability to progress to the next developmental stage.

Given their authentic complexity, the human embryo models obtained by Hanna’s group may provide an unprecedented opportunity to shed new light on the embryo’s mysterious beginnings. Little is known about the early embryo because it is so difficult to study, for both ethical and technical reasons, yet its initial stages are crucial to its future development. During these stages, the clump of cells that implants itself in the womb on the seventh day of its existence becomes, within three to four weeks, a well-structured embryo that already contains all the body organs.

“The drama is in the first month, the remaining eight months of pregnancy are mainly lots of growth,” Hanna says. “But that first month is still largely a black box. Our stem cell–derived human embryo model offers an ethical and accessible way of peering into this box. It closely mimics the development of a real human embryo, particularly the emergence of its exquisitely fine architecture.”

…

A stem cell–derived human embryo model at a developmental stage equivalent to that of a day 14 embryo. The model has all the compartments that define this stage: the yolk sac (yellow) and the part that will become the embryo itself, topped by the amnion (blue) – all enveloped by cells that will become the placenta (pink) Courtesy: Weizmann Institute of Science

A September 6, 2023 Weizmann Institute of Science press release, which originated the news item, offers a wealth of detail, Note: Links have been removed,

Letting the embryo model say “Go!”

Hanna’s team built on their previous experience in creating synthetic stem cell–based models of mouse embryos. As in that research, the scientists made no use of fertilized eggs or a womb. Rather, they started out with human cells known as pluripotent stem cells, which have the potential to differentiate into many, though not all, cell types. Some were derived from adult skin cells that had been reverted to “stemness.” Others were the progeny of human stem cell lines that had been cultured for years in the lab.

The researchers then used Hanna’s recently developed method to reprogram pluripotent stem cells so as to turn the clock further back: to revert these cells to an even earlier state – known as the naïve state – in which they are capable of becoming anything, that is, specializing into any type of cell. This stage corresponds to day 7 of the natural human embryo, around the time it implants itself in the womb. Hanna’s team had in fact been the first to start describing methods to generate human naïve stem cells, back in 2013; they continued to improve these methods, which stand at the heart of the current project, over the years.

The scientists divided the cells into three groups. The cells intended to develop into the embryo were left as is. The cells in each of the other groups were treated only with chemicals, without any need for genetic modification, so as to turn on certain genes, which was intended to cause these cells to differentiate toward one of three tissue types needed to sustain the embryo: placenta, yolk sac or the extraembryonic mesoderm membrane that ultimately creates the chorionic sac.

Soon after being mixed together under optimized, specifically developed conditions, the cells formed clumps, about 1 percent of which self-organized into complete embryo-like structures. “An embryo is self-driven by definition; we don’t need to tell it what to do – we must only unleash its internally encoded potential,” Hanna says. “It’s critical to mix in the right kinds of cells at the beginning, which can only be derived from naïve stem cells that have no developmental restrictions. Once you do that, the embryo-like model itself says, ‘Go!’”

The stem cell–based embryo-like structures (termed SEMs) developed normally outside the womb for 8 days, reaching a developmental stage equivalent to day 14 in human embryonic development. That’s the point at which natural embryos acquire the internal structures that enable them to proceed to the next stage: developing the progenitors of body organs.

Complete human embryo models match classic diagrams in terms of structure and cell identity

When the researchers compared the inner organization of their stem cell–derived embryo models with illustrations and microscopic anatomy sections in classical embryology atlases from the 1960s, they found an uncanny structural resemblance between the models and the natural human embryos at the corresponding stage. Every compartment and supporting structure was not only there, but in the right place, size and shape. Even the cells that make the hormone used in pregnancy testing were there and active: When the scientists applied secretions from these cells to a commercial pregnancy test, it came out positive.

In fact, the study has already produced a finding that may open a new direction of research into early pregnancy failure. The researchers discovered that if the embryo is not enveloped by placenta-forming cells in the right manner at day 3 of the protocol (corresponding to day 10 in natural embryonic development), its internal structures, such as the yolk sac, fail to properly develop.

“An embryo is not static. It must have the right cells in the right organization, and it must be able to progress – it’s about being and becoming,” Hanna says. “Our complete embryo models will help researchers address the most basic questions about what determines its proper growth.”

This ethical approach to unlocking the mysteries of the very first stages of embryonic development could open numerous research paths. It might help reveal the causes of many birth defects and types of infertility. It could also lead to new technologies for growing transplant tissues and organs. And it could offer a way around experiments that cannot be performed on live embryos – for example, determining the effects of exposure to drugs or other substances on fetal development.

For people who are visually inclined, there are two videos embedded in the September 6, 2023 Weizmann Institute of Science press release.

Here’s a link to and a citation for the paper,

Complete human day 14 post-implantation embryo models from naïve ES cells by Bernardo Oldak, Emilie Wildschutz, Vladyslav Bondarenko, Mehmet-Yunus Comar, Cheng Zhao, Alejandro Aguilera-Castrejon, Shadi Tarazi, Sergey Viukov, Thi Xuan Ai Pham, Shahd Ashouokhi, Dmitry Lokshtanov, Francesco Roncato, Eitan Ariel, Max Rose, Nir Livnat, Tom Shani, Carine Joubran, Roni Cohen, Yoseph Addadi, Muriel Chemla, Merav Kedmi, Hadas Keren-Shaul, Vincent Pasque, Sophie Petropoulos, Fredrik Lanner, Noa Novershtern & Jacob H. Hanna. Nature (2023) DOI: https://doi.org/10.1038/s41586-023-06604-5 Published: 06 September 2023

This paper is behind a paywall.

As for the question I asked in the head “what now?” I have absolutely no idea.

Synthetic human embryos—what now? (1 of 2)

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Usually, there’s a rough chronological order to how I introduce the research, but this time I’m looking at the term used to describe it, following up with the various news releases and commentaries about the research, and finishing with a Canadian perspective.

After writing this post (but before it was published), the Weizmann Institute of Science (Israel) made their September 6, 2023 announcement and things changed a bit. That’s in Part two.

Say what you really mean (a terminology issue)

First, it might be useful to investigate the term, ‘synthetic human embryos’ as Julian Hitchcock does in his June 29, 2023 article on Bristows website (h/t Mondaq’s July 5, 2023 news item), Note: Links have been removed,

“Synthetic Embryos” are neither Synthetic nor Embryos. So why are editors giving that name to stem cell-based models of human development?

One of the less convincing aspects of the last fortnight’s flurry of announcements about advances in simulating early human development (see here) concerned their name. Headlines galore (in newspapers and scientific journals) referred to “synthetic embryos“.

But embryo models, however impressive, are not embryos. To claim that the fundamental stages of embryo development that we learnt at school – fertilisation, cleavage and compaction – could now be bypassed to achieve the same result would be wrong. Nor are these objects “synthesised”: indeed, their interest to us lies in the ways in which they organise themselves. The researchers merely place the stem cells in a matrix in appropriate conditions, then stand back and watch them do it. Scientists were therefore unhappy about this use of the term in news media, and relieved when the International Society for Stem Cell Research (ISSCR) stepped in with a press release:

“Unlike some recent media reports describing this research, the ISSCR advises against using the term “synthetic embryo” to describe embryo models, because it is inaccurate and can create confusion. Integrated embryo models are neither synthetic nor embryos. While these models can replicate aspects of the early-stage development of human embryos, they cannot and will not develop to the equivalent of postnatal stage humans. Further, the ISSCR Guidelines prohibit the transfer of any embryo model to the uterus of a human or an animal.”

Although this was the ISSCR’s first attempt to put that position to the public, it had already made that recommendation to the research community two years previously. Its 2021 Guidelines for Stem Cell Research and Clinical Translation had recommended researchers to “promote accurate, current, balanced, and responsive public representations of stem cell research”. In particular:

“While organoids, chimeras, embryo models, and other stem cell-based models are useful research tools offering possibilities for further scientific progress, limitations on the current state of scientific knowledge and regulatory constraints must be clearly explained in any communications with the public or media. Suggestions that any of the current in vitro models can recapitulate an intact embryo, human sentience or integrated brain function are unfounded overstatements that should be avoided and contradicted with more precise characterizations of current understanding.”

…

Here’s a little bit about Hitchcock from his Bristows profile page,

  • Diploma Medical School, University of Birmingham (1975-78)
  • LLB, University of Wolverhampton
  • Diploma in Intellectual Property Law & Practice, University of Bristol
  • Qualified 1998

Following an education in medicine at the University of Birmingham and a career as a BBC science producer, Julian has focused on the law and regulation of life science technologies since 1997, practising in England and Australia. He joined Bristows with Alex Denoon in 2018.

…

Hitchcock’s June 29, 2023 article comments on why this term is being used,

…

I have a lot of sympathy with the position of the science writers and editors incurring the scientists’ ire. First, why should journalists have known of the ISSCR’s recommendations on the use of the term “synthetic embryo”? A journalist who found Recommendation 4.1 of the ISSCR Guidelines would probably not have found them specific enough to address the point, and the academic introduction containing the missing detail is hard to find. …

My second reason for being sympathetic to the use of the terrible term is that no suitable alternative has been provided, other than in the Stem Cell Reports paper, which recommends the umbrella terms “embryo models” or “stem cell based embryo models”. …

When asked why she had used the term “synthetic embryo”, the journalist I contacted remarked that, “We’re still working out the right language and it’s something we’re discussing and will no doubt evolve along with the science”.

It is absolutely in the public’s interest (and in the interest of science), that scientific research is explained in terms that the public understands. There is, therefore, a need, I think, for the scientific community to supply a name to the media or endure the penalties of misinformation …

In such an intensely competitive field of research, disagreement among researchers, even as to names, is inevitable. In consequence, however, journalists and their audiences are confronted by a slew of terms which may or may not be synonymous or overlapping, with no agreed term [emphasis mine] for the overall class of stem cell based embryo models. We cannot blame them if they make up snappy titles of their own [emphasis mine]. …

The announcement

The earliest date for the announcement at the International Society for Stem Cell Researh meeting that I can find is Hannah Devlin’s June 14, 2023 article in The Guardian newspaper, Note: A link has been removed,

Scientists have created synthetic human embryos using stem cells, in a groundbreaking advance that sidesteps the need for eggs or sperm.

Scientists say these model embryos, which resemble those in the earliest stages of human development, could provide a crucial window on the impact of genetic disorders and the biological causes of recurrent miscarriage.

However, the work also raises serious ethical and legal issues as the lab-grown entities fall outside current legislation in the UK and most other countries.

The structures do not have a beating heart or the beginnings of a brain, but include cells that would typically go on to form the placenta, yolk sac and the embryo itself.

Prof Magdalena Żernicka-Goetz, of the University of Cambridge and the California Institute of Technology, described the work in a plenary address on Wednesday [June 14, 2023] at the International Society for Stem Cell Research’s annual meeting in Boston.

…

The (UK) Science Media Centre made expert comments available in a June 14, 2023 posting “expert reaction to Guardian reporting news of creation of synthetic embryos using stem cells.”

Two days later, this June 16, 2023 essay by Kathryn MacKay, Senior Lecturer in Bioethics, University of Sydney (Australia), appeared on The Conversation (h/t June 16, 2023 news item on phys.org), Note: Links have been removed,

Researchers have created synthetic human embryos using stem cells, according to media reports. Remarkably, these embryos have reportedly been created from embryonic stem cells, meaning they do not require sperm and ova.

This development, widely described as a breakthrough that could help scientists learn more about human development and genetic disorders, was revealed this week in Boston at the annual meeting of the International Society for Stem Cell Research.

The research, announced by Professor Magdalena Żernicka-Goetz of the University of Cambridge and the California Institute of Technology, has not yet been published in a peer-reviewed journal. But Żernicka-Goetz told the meeting these human-like embryos had been made by reprogramming human embryonic stem cells.

So what does all this mean for science, and what ethical issues does it present?

MacKay goes on to answer her own questions, from the June 16, 2023 essay, Note: A link has been removed,

…

One of these quandaries arises around whether their creation really gets us away from the use of human embryos.

Robin Lovell-Badge, the head of stem cell biology and developmental genetics at the Francis Crick Institute in London UK, reportedly said that if these human-like embryos can really model human development in the early stages of pregnancy, then we will not have to use human embryos for research.

At the moment, it is unclear if this is the case for two reasons.

First, the embryos were created from human embryonic stem cells, so it seems they do still need human embryos for their creation. Perhaps more light will be shed on this when Żernicka-Goetz’s research is published.

Second, there are questions about the extent to which these human-like embryos really can model human development.

…

Professor Magdalena Żernicka-Goetz’s research is published

Almost two weeks later the research from the Cambridge team (there are other teams and countries also racing; see Part two for the news from Sept. 6, 2023) was published, from a June 27, 2023 news item on ScienceDaily,

Cambridge scientists have created a stem cell-derived model of the human embryo in the lab by reprogramming human stem cells. The breakthrough could help research into genetic disorders and in understanding why and how pregnancies fail.

Published today [Tuesday, June 27, 2023] in the journal Nature, this embryo model is an organised three-dimensional structure derived from pluripotent stem cells that replicate some developmental processes that occur in early human embryos.

Use of such models allows experimental modelling of embryonic development during the second week of pregnancy. They can help researchers gain basic knowledge of the developmental origins of organs and specialised cells such as sperm and eggs, and facilitate understanding of early pregnancy loss.

…

A June 27, 2023 University of Cambridge press release (also on EurekAlert), which originated the news item, provides more detail about the work,

“Our human embryo-like model, created entirely from human stem cells, gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb,” said Professor Magdalena Zernicka-Goetz in the University of Cambridge’s Department of Physiology, Development and Neuroscience, who led the work.

She added: “This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will let us test the function of specific factors, which is difficult to do in the natural embryo.”

In natural human development, the second week of development is an important time when the embryo implants into the uterus. This is the time when many pregnancies are lost.

The new advance enables scientists to peer into the mysterious ‘black box’ period of human development – usually following implantation of the embryo in the uterus – to observe processes never directly observed before.

Understanding these early developmental processes holds the potential to reveal some of the causes of human birth defects and diseases, and to develop tests for these in pregnant women.

Until now, the processes could only be observed in animal models, using cells from zebrafish and mice, for example.

Legal restrictions in the UK currently prevent the culture of natural human embryos in the lab beyond day 14 of development: this time limit was set to correspond to the stage where the embryo can no longer form a twin. [emphasis mine]

Until now, scientists have only been able to study this period of human development using donated human embryos. This advance could reduce the need for donated human embryos in research.

Zernicka-Goetz says the while these models can mimic aspects of the development of human embryos, they cannot and will not develop to the equivalent of postnatal stage humans.

Over the past decade, Zernicka-Goetz’s group in Cambridge has been studying the earliest stages of pregnancy, in order to understand why some pregnancies fail and some succeed.

In 2021 and then in 2022 her team announced in Developmental Cell, Nature and Cell Stem Cell journals that they had finally created model embryos from mouse stem cells that can develop to form a brain-like structure, a beating heart, and the foundations of all other organs of the body.

The new models derived from human stem cells do not have a brain or beating heart, but they include cells that would typically go on to form the embryo, placenta and yolk sac, and develop to form the precursors of germ cells (that will form sperm and eggs).

Many pregnancies fail at the point when these three types of cells orchestrate implantation into the uterus begin to send mechanical and chemical signals to each other, which tell the embryo how to develop properly.

There are clear regulations governing stem cell-based models of human embryos and all researchers doing embryo modelling work must first be approved by ethics committees. Journals require proof of this ethics review before they accept scientific papers for publication. Zernicka-Goetz’s laboratory holds these approvals.

“It is against the law and FDA regulations to transfer any embryo-like models into a woman for reproductive aims. These are highly manipulated human cells and their attempted reproductive use would be extremely dangerous,” said Dr Insoo Hyun, Director of the Center for Life Sciences and Public Learning at Boston’s Museum of Science and a member of Harvard Medical School’s Center for Bioethics.

Zernicka-Goetz also holds position at the California Institute of Technology and is NOMIS Distinguished Scientist and Scholar Awardee.

The research was funded by the Wellcome Trust and Open Philanthropy.

(There’s more about legal concerns further down in this post.)

Here’s a link to and a citation for the paper,

Pluripotent stem cell-derived model of the post-implantation human embryo by Bailey A. T. Weatherbee, Carlos W. Gantner, Lisa K. Iwamoto-Stohl, Riza M. Daza, Nobuhiko Hamazaki, Jay Shendure & Magdalena Zernicka-Goetz. Nature (2023) DOI: https://doi.org/10.1038/s41586-023-06368-y Published: 27 June 2023

This paper is open access.

Published the same day (June 27, 2023) is a paper (citation and link follow) also focused on studying human embryonic development using stem cells. First, there’s this from the Abstract,

Investigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In the face of these difficulties, stem cells have provided an alternative to experimentally model inaccessible stages of human development in vitro …

This time the work is from a US/German team,

Self-patterning of human stem cells into post-implantation lineages by Monique Pedroza, Seher Ipek Gassaloglu, Nicolas Dias, Liangwen Zhong, Tien-Chi Jason Hou, Helene Kretzmer, Zachary D. Smith & Berna Sozen. Nature (2023) DOI: https://doi.org/10.1038/s41586-023-06354-4 Published: 27 June 2023

The paper is open access.

Legal concerns and a Canadian focus

A July 25, 2023 essay by Françoise Baylis and Jocelyn Downie of Dalhousie University (Nova Scotia, Canada) for The Conversation (h/t July 25, 2023 article on phys.org) covers the advantages of doing this work before launching into a discussion of legislation and limits in the UK and, more extensively, in Canada, Note: Links have been removed,

…

This research could increase our understanding of human development and genetic disorders, help us learn how to prevent early miscarriages, lead to improvements in fertility treatment, and — perhaps — eventually allow for reproduction without using sperm and eggs.

Synthetic human embryos — also called embryoid bodies, embryo-like structures or embryo models — mimic the development of “natural human embryos,” those created by fertilization. Synthetic human embryos include the “cells that would typically go on to form the embryo, placenta and yolk sac, and develop to form the precursors of germ cells (that will form sperm and eggs).”

Though research involving natural human embryos is legal in many jurisdictions, it remains controversial. For some people, research involving synthetic human embryos is less controversial because these embryos cannot “develop to the equivalent of postnatal stage humans.” In other words, these embryos are non-viable and cannot result in live births.

…

Now, for a closer look at the legalities in the UK and in Canada, from the July 25, 2023 essay, Note: Links have been removed,

The research presented by Żernicka-Goetz at the ISSCR meeting took place in the United Kingdom. It was conducted in accordance with the Human Fertilization and Embryology Act, 1990, with the approval of the U.K. Stem Cell Bank Steering Committee.

U.K. law limits the research use of human embryos to 14 days of development. An embryo is defined as “a live human embryo where fertilisation is complete, and references to an embryo include an egg in the process of fertilisation.”

Synthetic embryos are not created by fertilization and therefore, by definition, the 14-day limit on human embryo research does not apply to them. This means that synthetic human embryo research beyond 14 days can proceed in the U.K.

The door to the touted potential benefits — and ethical controversies — seems wide open in the U.K.

…

While the law in the U.K. does not apply to synthetic human embryos, the law in Canada clearly does. This is because the legal definition of an embryo in Canada is not limited to embryos created by fertilization [emphasis mine].

The Assisted Human Reproduction Act (the AHR Act) defines an embryo as “a human organism during the first 56 days of its development following fertilization or creation, excluding any time during which its development has been suspended.”

Based on this definition, the AHR Act applies to embryos created by reprogramming human embryonic stem cells — in other words, synthetic human embryos — provided such embryos qualify as human organisms.

A synthetic human embryo is a human organism. It is of the species Homo sapiens, and is thus human. It also qualifies as an organism — a life form — alongside other organisms created by means of fertilization, asexual reproduction, parthenogenesis or cloning.

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Given that the AHR Act applies to synthetic human embryos, there are legal limits on their creation and use in Canada.

First, human embryos — including synthetic human embryos – can only be created for the purposes of “creating a human being, improving or providing instruction in assisted reproduction procedures.”

Given the state of the science, it follows that synthetic human embryos could legally be created for the purpose of improving assisted reproduction procedures.

Second, “spare” or “excess” human embryos — including synthetic human embryos — originally created for one of the permitted purposes, but no longer wanted for this purpose, can be used for research. This research must be done in accordance with the consent regulations which specify that consent must be for a “specific research project.”

Finally, all research involving human embryos — including synthetic human embryos — is subject to the 14-day rule. The law stipulates that: “No person shall knowingly… maintain an embryo outside the body of a female person after the fourteenth day of its development following fertilization or creation, excluding any time during which its development has been suspended.”

Putting this all together, the creation of synthetic embryos for improving assisted human reproduction procedures is permitted, as is research using “spare” or “excess” synthetic embryos originally created for this purpose — provided there is specific consent and the research does not exceed 14 days.

This means that while synthetic human embryos may be useful for limited research on pre-implantation embryo development, they are not available in Canada for research on post-implantation embryo development beyond 14 days.

The authors close with this comment about the prospects for expanding Canada’s14-day limit, from the July 25, 2023 essay,

… any argument will have to overcome the political reality that the federal government is unlikely to open up the Pandora’s box of amending the AHR Act.

It therefore seems likely that synthetic human embryo research will remain limited in Canada for the foreseeable future.

As mentioned, in September 2023 there was a new development. See: Part two.

Frog pants?

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How would you go about tracking these frogs?

Six images of tiny frogs wearing little plastic trackers attached to wire harnesses on their back legs.
Researchers have fitted tiny trackable radio-pants to three species of South American frogs to test their ability to navigate through the rainforest. (Submitted by Andrius Pašukonis)

You can see how tiny they are when you compare one of the frogs to a leaf visible in one of the images (top left or top right).

The answer to the question, as you may have guessed, are frog pants (or G-strings).

Sheena Goodyear’s June 13, 2023 article for the CBC’s (Canadian Broadcasting Corporation) As It Happens radio show explores the question and the research and includes an embedded 6:20 radio interview with researcher, Andrius Pašukonis,

How do you track a bunch of teeny-weeny frogs across the vast rainforests of South America? By putting teeny-weeny trackers on their teeny-weeny underwear, of course.

Biologist Andrius Pašukonis and his colleagues wanted to study the navigational capabilities of poisonous frogs that are too small for most animal tracking devices.

So he designed a Speedo-like harness that wraps around their back legs and props a tiny radio tracker on their backsides. The research team dubbed the invention “frog pants” — though Pašukonis says that’s “a bit of a misnomer.”

“My French colleagues like to call it a telemetric G-string,” Pašukonis, a senior scientist at Lithuania’s Vilnius University, told As It Happens host Nil Köksal.

“It’s a lot of fine motor skills and a lot of practice in handling tiny frogs and sewing little frog harnesses. But we go find them in the rainforest, and we catch them, and we put the tags on.”

My favourite part is “… sewing little frog harnesses.” Note: The following video features a commercial and then, moves onto a 2:22 interview,

More from Goodyear’s June 13, 2023 article, Note: A link has been removed,

Pašukonis was a PhD student at the University of Vienna when he first started experimenting with the frog pants design, and later put it to use while working as a postdoctoral fellow at Stanford University in California.

He and is colleagues used the tracker pants to study the spatial skills of three frog species that range from three to five centimetres in length — diablito poison frogs in Ecuador, and brilliant-thighed poison frogs and dyeing poison frogs in French Guiana. The findings were published late last year in the journal e-Life [sic].

“The only way to study movements of animals is to be able to track them and follow them around, which nobody has managed to do or even tried to do with these tiny, tiny frogs in the rainforest,” he said.

“So that became my goal and challenge, where I spent a good part of my PhD trying different versions of different tags and different attachment methods, trial and error, to finally get to be able to put tags on and track them and study their behaviour.”

The frogs, he admits, didn’t particularly like the pants. But they didn’t seem to mind too much, and the team removed the trackers after four to six days. 

“Like any animal, they might scratch a little bit afterwards … like a dog with a new collar,” he said. “And then they just go on with their business.”

…

Other scientists have tried to track tiny frogs, from Goodyear’s June 13, 2023 article, Note: Links have been removed,

The design caught the eye of Richard Essner, a biologist at Southern Illinois University Edwardsville who studies animal locomotion, and has a particular interest in little frogs.

“Tracking small frogs with radio telemetry is not an easy thing to do,” Essner, who wasn’t involved in the Stanford research, told CBC in an email. 

About a decade ago, he says his lab attempted to use radio telemetry to track the movement of the threatened Illinois chorus frog using a transmitter attached via an elastic belt around the waist.

“Unfortunately, we had to abandon the study because we found that the transmitter apparatus was interfering with locomotion. If the belt was too tight, it caused abrasion. If it was too loose it slid down around the legs and left the frog immobilized and vulnerable to predation,” he said.

The frog pants, he says, seem to offer a solution to this conundrum. 

…

Lea Randall, a Calgary Zoo and Wilder Institute ecologist who specializes in amphibians and reptiles, ran into similar obstacles while trying to track northern leopard frogs at a reintroduction site in B.C. 

Like the Stanford researchers, her team experimented with several different designs before landing on one that worked — a belt-like attachment with some “very stylish” smooth glass beads to prevent abrasion. 

“Unfortunately, due to the weight of the radio transmitters at the time we couldn’t study smaller individuals,” she said. 

“We didn’t use leg straps, but I can see the advantages of that to help keep the transmitters in place. The creative thinking and problem solving that goes into developing these kinds of studies always amazes me.”

…

Finally, frogs may be smarter than we think, from Goodyear’s June 13, 2023 article,

When it comes to animal cognition and behaviour, Pašukonis says frogs are understudied —  and he believes, underestimated — compared to birds and mammals.

The poisonous rainforest frogs, he says, may be only a few centimetres in size, but when they breed, they carry their tadpoles between 200 to 300 metres across the rainforest to find them the perfect puddle to grow in.

Then they turn right around, and make their way home again. 

“How could a little frog — frogs typically are not thought to be very smart — learn to navigate on such a big scale? And how do they find their way around more on a fundamental scientific level?” Pašukonis said.

“We’re uncovering that overall amphibians, for example, might be smarter or have more complicated cognitive abilities than we thought.”

Here’s a link to and a citation for the paper published by Pašukonis and his colleagues,

Contrasting parental roles shape sex differences in poison frog space use but not navigational performance by Andrius Pašukonis, Shirley Jennifer Serrano-Rojas, Marie-Therese Fischer, Matthias-Claudio Loretto, Daniel A Shaykevich, Bibiana Rojas, Max Ringler, Alexandre B Roland, Alejandro Marcillo-Lara, Eva Ringler, Camilo Rodríguez, Luis A Coloma, Lauren A O’Connell. eLife DOI: https://doi.org/10.7554/eLife.80483 Version of Record Published: Nov 15, 2022

This paper appears to be open access.

CRISPR-like system found in animals

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I trust the eukaryotes will not be suing for intellectual property rights. (For anyone who’s interested in CRISPR [clustered regularly interspaced short palindromic repeats) and associated intellectual property (specifically, patent) issues, see my March 15, 2017 posting “CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now.” It’s not up-to-date but as far as I know there haven’t been any major intellectual property developments since. If I’m wrong, please let me know in the Comments section of this posting.)

A june 28, 2023 news item on phys.org announces research suggesting there are naturally occurring CRISPR-like capabilities in some species,

A team of researchers led by Feng Zhang at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT [Massachusetts Institute of Technology] has uncovered the first programmable RNA-guided system in eukaryotes—organisms that include fungi, plants, and animals.

In a study in Nature, the team describes how the system is based on a protein called Fanzor. They showed that Fanzor proteins use RNA as a guide to target DNA precisely, and that Fanzors can be reprogrammed to edit the genome of human cells. The compact Fanzor systems have the potential to be more easily delivered to cells and tissues as therapeutics than CRISPR/Cas systems, and further refinements to improve their targeting efficiency could make them a valuable new technology for human genome editing

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A june 28, 2023 Broad Institute of MIT and Harvard news release by Leah Eisenstadt (also on EurekAlert), which originated the news item, provides more context for the research,

CRISPR/Cas was first discovered in prokaryotes (bacteria and other single-cell organisms that lack nuclei) and scientists including Zhang’s lab have long wondered whether similar systems exist in eukaryotes. The new study demonstrates that RNA-guided DNA-cutting mechanisms are present across all kingdoms of life.

“CRISPR-based systems are widely used and powerful because they can be easily reprogrammed to target different sites in the genome,” said Zhang, senior author on the study and a core institute member at the Broad, an investigator at MIT’s McGovern Institute, the James and Patricia Poitras Professor of Neuroscience at MIT, and a Howard Hughes Medical Institute investigator. “This new system is another way to make precise changes in human cells, complementing the genome editing tools we already have.”

Searching the domains of life

A major aim of the Zhang lab is to develop genetic medicines using systems that can modulate human cells by targeting specific genes and processes. “A number of years ago, we started to ask, ‘What is there beyond CRISPR, and are there other RNA-programmable systems out there in nature?’” said Zhang.

Two years ago, Zhang lab members discovered a class of RNA-programmable systems in prokaryotes called OMEGAs, which are often linked with transposable elements, or “jumping genes”, in bacterial genomes and likely gave rise to CRISPR/Cas systems. That work also highlighted similarities between prokaryotic OMEGA systems and Fanzor proteins in eukaryotes, suggesting that the Fanzor enzymes might also use an RNA-guided mechanism to target and cut DNA.

In the new study, the researchers continued their study of RNA-guided systems by isolating Fanzors from fungi, algae, and amoeba species, in addition to a clam known as the Northern Quahog. Co-first author Makoto Saito of the Zhang lab led the biochemical characterization of the Fanzor proteins, showing that they are DNA-cutting endonuclease enzymes that use nearby non-coding RNAs known as ωRNAs to target particular sites in the genome. It is the first time this mechanism has been found in eukaryotes, such as animals.

Unlike CRISPR proteins, Fanzor enzymes are encoded in the eukaryotic genome within transposable elements and the team’s phylogenetic analysis suggests that the Fanzor genes have migrated from bacteria to eukaryotes through so-called horizontal gene transfer.

“These OMEGA systems are more ancestral to CRISPR and they are among the most abundant proteins on the planet, so it makes sense that they have been able to hop back and forth between prokaryotes and eukaryotes,” said Saito.

To explore Fanzor’s potential as a genome editing tool, the researchers demonstrated that it can generate insertions and deletions at targeted genome sites within human cells. The researchers found the Fanzor system to initially be less efficient at snipping DNA than CRISPR/Cas systems, but by systematic engineering, they introduced a combination of mutations into the protein that increased its activity 10-fold. Additionally, unlike some CRISPR systems and the OMEGA protein TnpB, the team found that a fungal-derived Fanzor protein did not exhibit “collateral activity,” where an RNA-guided enzyme cleaves its DNA target as well as degrading nearby DNA or RNA. The results suggest that Fanzors could potentially be developed as efficient genome editors.

Co-first author Peiyu Xu led an effort to analyze the molecular structure of the Fanzor/ωRNA complex and illustrate how it latches onto DNA to cut it. Fanzor shares structural similarities with its prokaryotic counterpart CRISPR-Cas12 protein, but the interaction between the ωRNA and the catalytic domains of Fanzor is more extensive, suggesting that the ωRNA might play a role in the catalytic reactions. “We are excited about these structural insights for helping us further engineer and optimize Fanzor for improved efficiency and precision as a genome editor,” said Xu.

Like CRISPR-based systems, the Fanzor system can be easily reprogrammed to target specific genome sites, and Zhang said it could one day be developed into a powerful new genome editing technology for research and therapeutic applications. The abundance of RNA-guided endonucleases like Fanzors further expands the number of OMEGA systems known across kingdoms of life and suggests that there are more yet to be found.

“Nature is amazing. There’s so much diversity,” said Zhang. “There are probably more RNA-programmable systems out there, and we’re continuing to explore and will hopefully discover more.”

The paper’s other authors include Guilhem Faure, Samantha Maguire, Soumya Kannan, Han Altae-Tran, Sam Vo, AnAn Desimone, and Rhiannon Macrae.

…

About Broad Institute of MIT and Harvard
Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard, Harvard-affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide.

About McGovern Institute for Brain Research at MIT
The McGovern Institute is an inclusive and collaborative community of MIT scientists, engineers, and support staff who work together to unravel the mysteries of the brain. Our researchers are committed to meeting two of the greatest challenges of modern science: understanding how the brain works and discovering new ways to prevent or treat brain disorders. To address this scientific challenge, we study the brain at many levels and collaborate with academic, clinical, and industry partners around the world.

The McGovern Institute was established in 2000 by technology entrepreneur Lore Harp McGovern and the late Patrick J. McGovern, former chairman of International Data Group (IDG). Our director is Robert Desimone, the Doris and Don Berkey Professor of Neuroscience at MIT and former head of intramural research at the National Institute of Mental Health. The McGovern Institute has grown from six founding faculty members to more than 20 distinguished investigators including one Nobel laureate and six members of the National Academy of Sciences.

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Here’s a link to and a citation for the paper,

Fanzor is a eukaryotic programmable RNA-guided endonuclease by Makoto Saito, Peiyu Xu, Guilhem Faure, Samantha Maguire, Soumya Kannan, Han Altae-Tran, Sam Vo, AnAn Desimone, Rhiannon K. Macrae & Feng Zhang. Nature (2023) DOI: https://doi.org/10.1038/s41586-023-06356-2 Published: 28 June 2023

This paper is behind a paywall.