Tag Archives: bioethics

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.

…

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.

Need to improve oversight on chimeric human-animal research

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It seems chimeras are of more interest these days. In all likelihood that has something to do with the fellow who received a transplant of a pig’s heart in January 2022 (he died in March 2022).

For those who aren’t familiar with the term, a chimera is an entity with two different DNA (deoxyribonucleic acid) identities. In short, if you get a DNA sample from the heart, it’s different from a DNA sample obtained from a cheek swab. This contrasts with a hybrid such as a mule (donkey/horse) whose DNA samples show a consisted identity throughout its body.

A December 12, 2022 The Hastings Center news release (also on EurekAlert) announces a special report,

A new report on the ethics of crossing species boundaries by inserting human cells into nonhuman animals – research surrounded by debate – makes recommendations clarifying the ethical issues and calling for improved oversight of this work.

The report, “Creating Chimeric Animals — Seeking Clarity On Ethics and Oversight,” was developed by an interdisciplinary team, with funding from the National Institutes of Health. Principal investigators are Josephine Johnston and Karen Maschke, research scholars at The Hastings Center, and Insoo Hyun, director of the Center for Life Sciences and Public Learning at the Museum of Life Sciences in Boston, formerly of Case Western Reserve University.

Advances in human stem cell science and gene editing enable scientists to insert human cells more extensively and precisely into nonhuman animals, creating “chimeric” animals, embryos, and other organisms that contain a mix of human and nonhuman cells.

Many people hope that this research will yield enormous benefits, including better models of human disease, inexpensive sources of human eggs and embryos for research, and sources of tissues and organs suitable for transplantation into humans. 

But there are ethical concerns about this type of research, which raise questions such as whether the moral status of nonhuman animals is altered by the insertion of human stem cells, whether these studies should be subject to additional prohibitions or oversight, and whether this kind of research should be done at all.

The report found that:

Animal welfare is a primary ethical issue and should be a focus of ethical and policy analysis as well as the governance and oversight of chimeric research.

Chimeric studies raise the possibility of unique or novel harms resulting from the insertion and development of human stem cells in nonhuman animals, particularly when those cells develop in the brain or central nervous system.

Oversight and governance of chimeric research are siloed, and public communication is minimal. Public communication should be improved, communication between the different committees involved in oversight at each institution should be enhanced, and a national mechanism created for those involved in oversight of these studies. 

Scientists, journalists, bioethicists, and others writing about chimeric research should use precise and accessible language that clarifies rather than obscures the ethical issues at stake. The terms “chimera,” which in Greek mythology refers to a fire-breathing monster, and “humanization” are examples of ethically laden, or overly broad language to be avoided.

The Research Team

The Hastings Center

• Josephine Johnston
• Karen J. Maschke
• Carolyn P. Neuhaus
• Margaret M. Matthews
• Isabel Bolo

Case Western Reserve University
• Insoo Hyun (now at Museum of Science, Boston)
• Patricia Marshall
• Kaitlynn P. Craig

The Work Group

• Kara Drolet, Oregon Health & Science University
• Henry T. Greely, Stanford University
• Lori R. Hill, MD Anderson Cancer Center
• Amy Hinterberger, King’s College London
• Elisa A. Hurley, Public Responsibility in Medicine and Research
• Robert Kesterson, University of Alabama at Birmingham
• Jonathan Kimmelman, McGill University
• Nancy M. P. King, Wake Forest University School of Medicine
• Geoffrey Lomax, California Institute for Regenerative Medicine
• Melissa J. Lopes, Harvard University Embryonic Stem Cell Research Oversight Committee
• P. Pearl O’Rourke, Harvard Medical School
• Brendan Parent, NYU Grossman School of Medicine
• Steven Peckman, University of California, Los Angeles
• Monika Piotrowska, State University of New York at Albany
• May Schwarz, The Salk Institute for Biological Studies
• Jeff Sebo, New York University
• Chris Stodgell, University of Rochester
• Robert Streiffer, University of Wisconsin-Madison
• Lorenz Studer, Memorial Sloan Kettering Cancer Center
• Amy Wilkerson, The Rockefeller University

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

Creating Chimeric Animals: Seeking Clarity on Ethics and Oversight edited by Karen J. Maschke, Margaret M. Matthews, Kaitlynn P. Craig, Carolyn P. Neuhaus, Insoo Hyun, Josephine Johnston, The Hastings Center Report Volume 52, Issue S2 (Special Report), November‐December 2022 First Published: 09 December 2022

This report is open access.

Revival of dead pig brains raises moral questions about life and death

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The line between life and death may not be what we thought it was according to some research that was reported in April 2019. Ed Wong’s April 17, 2019 article (behind a paywall) for The Atlantic was my first inkling about the life-death questions raised by some research performed at Yale University, (Note: Links have been removed)

The brain, supposedly, cannot long survive without blood. Within seconds, oxygen supplies deplete, electrical activity fades, and unconsciousness sets in. If blood flow is not restored, within minutes, neurons start to die in a rapid, irreversible, and ultimately fatal wave.

But maybe not? According to a team of scientists led by Nenad Sestan at Yale School of Medicine, this process might play out over a much longer time frame, and perhaps isn’t as inevitable or irreparable as commonly believed. Sestan and his colleagues showed this in dramatic fashion—by preserving and restoring signs of activity in the isolated brains of pigs that had been decapitated four hours earlier.

The team sourced 32 pig brains from a slaughterhouse, placed them in spherical chambers, and infused them with nutrients and protective chemicals, using pumps that mimicked the beats of a heart. This system, dubbed BrainEx, preserved the overall architecture of the brains, preventing them from degrading. It restored flow in their blood vessels, which once again became sensitive to dilating drugs. It stopped many neurons and other cells from dying, and reinstated their ability to consume sugar and oxygen. Some of these rescued neurons even started to fire. “Everything was surprising,” says Zvonimir Vrselja, who performed most of the experiments along with Stefano Daniele.

…

… “I don’t see anything in this report that should undermine confidence in brain death as a criterion of death,” says Winston Chiong, a neurologist at the University of California at San Francisco. The matter of when to declare someone dead has become more controversial since doctors began relying more heavily on neurological signs, starting around 1968, when the criteria for “brain death” were defined. But that diagnosis typically hinges on the loss of brainwide activity—a line that, at least for now, is still final and irreversible. After MIT Technology Review broke the news of Sestan’s work a year ago, he started receiving emails from people asking whether he could restore brain function to their loved ones. He very much cannot. BrainEx isn’t a resurrection chamber.

“It’s not going to result in human brain transplants,” adds Karen Rommelfanger, who directs Emory University’s neuroethics program. “And I don’t think this means that the singularity is coming, or that radical life extension is more possible than before.”

So why do the study? “There’s potential for using this method to develop innovative treatments for patients with strokes or other types of brain injuries, and there’s a real need for those kinds of treatments,” says L. Syd M Johnson, a neuroethicist at Michigan Technological University. The BrainEx method might not be able to fully revive hours-dead brains, but Yama Akbari, a critical-care neurologist at the University of California at Irvine, wonders whether it would be more successful if applied minutes after death. Alternatively, it could help to keep oxygen-starved brains alive and intact while patients wait to be treated. “It’s an important landmark study,” Akbari says.

…

Yong notes that the study still needs to be replicated in his article which also probes some of the ethical issues associated with the latest neuroscience research.

Nature published the Yale study,

Restoration of brain circulation and cellular functions hours post-mortem by Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, André M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman & Nenad Sestan. Nature 568, 336–343 (2019) DOI: https://doi.org/10.1038/s41586-019-1099-1 Published 17 April 2019 Issue Date 18 April 2019

This paper is behind a paywall.

Two neuroethicists had this to say (link to their commentary in Nature follows) as per an April 71, 2019 news release from Case Western Reserve University (also on EurekAlert), Note: Links have been removed,

The brain is more resilient than previously thought. In a groundbreaking experiment published in this week’s issue of Nature, neuroscientists created an artificial circulation system that successfully restored some functions and structures in donated pig brains–up to four hours after the pigs were butchered at a USDA food processing facility. Though there was no evidence of restored consciousness, brains from the pigs were without oxygen for hours, yet could still support key functions provided by the artificial system. The result challenges the notion that mammalian brains are fully and irreversibly damaged by a lack of oxygen.

“The assumptions have always been that after a couple minutes of anoxia, or no oxygen, the brain is ‘dead,'” says Stuart Youngner, MD, who co-authored a commentary accompanying the study with Insoo Hyun, PhD, both professors in the Department of Bioethics at Case Western Reserve University School of Medicine. “The system used by the researchers begs the question: How long should we try to save people?”

In the pig experiment, researchers used an artificial perfusate (a type of cell-free “artificial blood”), which helped brain cells maintain their structure and some functions. Resuscitative efforts in humans, like CPR, are also designed to get oxygen to the brain and stave off brain damage. After a period of time, if a person doesn’t respond to resuscitative efforts, emergency medical teams declare them dead.

The acceptable duration of resuscitative efforts is somewhat uncertain. “It varies by country, emergency medical team, and hospital,” Youngner said. Promising results from the pig experiment further muddy the waters about the when to stop life-saving efforts.

At some point, emergency teams must make a critical switch from trying to save a patient, to trying to save organs, said Youngner. “In Europe, when emergency teams stop resuscitation efforts, they declare a patient dead, and then restart the resuscitation effort to circulate blood to the organs so they can preserve them for transplantation.”

The switch can involve extreme means. In the commentary, Youngner and Hyun describe how some organ recovery teams use a balloon to physically cut off blood circulation to the brain after declaring a person dead, to prepare the organs for transplantation.

The pig experiment implies that sophisticated efforts to perfuse the brain might maintain brain cells. If technologies like those used in the pig experiment could be adapted for humans (a long way off, caution Youngner and Hyun), some people who, today, are typically declared legally dead after a catastrophic loss of oxygen could, tomorrow, become candidates for brain resuscitation, instead of organ donation.

Said Youngner, “As we get better at resuscitating the brain, we need to decide when are we going to save a patient, and when are we going to declare them dead–and save five or more who might benefit from an organ.”

Because brain resuscitation strategies are in their infancy and will surely trigger additional efforts, the scientific and ethics community needs to begin discussions now, says Hyun. “This study is likely to raise a lot of public concerns. We hoped to get ahead of the hype and offer an early, reasoned response to this scientific advance.”

Both Youngner and Hyun praise the experiment as a “major scientific advancement” that is overwhelmingly positive. It raises the tantalizing possibility that the grave risks of brain damage caused by a lack of oxygen could, in some cases, be reversible.
“Pig brains are similar in many ways to human brains, which makes this study so compelling,” Hyun said. “We urge policymakers to think proactively about what this line of research might mean for ongoing debates around organ donation and end of life care.”

Here’s a link to and a citation to the Nature commentary,

Pig experiment challenges assumptions around brain damage in people by Stuart Youngner and Insoo Hyun. Nature 568, 302-304 (2019) DOI: 10.1038/d41586-019-01169-8 April 17, 2019

This paper is open access.

I was hoping to find out more about BrainEx, but this April 17, 2019 US National Institute of Mental Health news release is all I’ve been able to find in my admittedly brief online search. The news release offers more celebration than technical detail.

Quick comment

Interestingly, there hasn’t been much of a furor over this work. Not yet.

BRAIN and ethics in the US with some Canucks (not the hockey team) participating (part two of five)

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The Brain research, ethics, and nanotechnology (part one of five) May 19, 2014 post kicked off a series titled ‘Brains, prostheses, nanotechnology, and human enhancement’ which brings together a number of developments in the worlds of neuroscience*, prosthetics, and, incidentally, nanotechnology in the field of interest called human enhancement. Parts one through four are an attempt to draw together a number of new developments, mostly in the US and in Europe. Due to my language skills which extend to English and, more tenuously, French, I can’t provide a more ‘global perspective’. Part five features a summary.

Before further discussing the US Presidential Commission for the Study of Bioethical Issues ‘brain’ meetings mentioned in part one, I have some background information.

The US launched its self-explanatory BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative (originally called BAM; Brain Activity Map) in 2013. (You can find more about the history and details in this Wikipedia entry.)

From the beginning there has been discussion about how nanotechnology will be of fundamental use in the US BRAIN initiative and the European Union’s 10 year Human Brain Project (there’s more about that in my Jan. 28, 2013 posting). There’s also a 2013 book (Nanotechnology, the Brain, and the Future) from Springer, which, according to the table of contents, presents an exciting (to me) range of ideas about nanotechnology and brain research,

I. Introduction and key resources

1. Nanotechnology, the brain, and the future: Anticipatory governance via end-to-end real-time technology assessment by Jason Scott Robert, Ira Bennett, and Clark A. Miller
2. The complex cognitive systems manifesto by Richard P. W. Loosemore
3. Analysis of bibliometric data for research at the intersection of nanotechnology and neuroscience by Christina Nulle, Clark A. Miller, Harmeet Singh, and Alan Porter
4. Public attitudes toward nanotechnology-enabled human enhancement in the United States by Sean Hays, Michael Cobb, and Clark A. Miller
5. U.S. news coverage of neuroscience nanotechnology: How U.S. newspapers have covered neuroscience nanotechnology during the last decade by Doo-Hun Choi, Anthony Dudo, and Dietram Scheufele
6. Nanoethics and the brain by Valerye Milleson
7. Nanotechnology and religion: A dialogue by Tobie Milford

II. Brain repair

8. The age of neuroelectronics by Adam Keiper
9. Cochlear implants and Deaf culture by Derrick Anderson
10. Healing the blind: Attitudes of blind people toward technologies to cure blindness by Arielle Silverman
11. Ethical, legal and social aspects of brain-implants using nano-scale materials and techniques by Francois Berger et al.
12. Nanotechnology, the brain, and personal identity by Stephanie Naufel

III. Brain enhancement

13. Narratives of intelligence: the sociotechnical context of cognitive enhancement by Sean Hays
14. Towards responsible use of cognitive-enhancing drugs by the healthy by Henry T. Greeley et al.
15. The opposite of human enhancement: Nanotechnology and the blind chicken debate by Paul B. Thompson
16. Anticipatory governance of human enhancement: The National Citizens’ Technology Forum by Patrick Hamlett, Michael Cobb, and David Guston
a. Arizona site report
b. California site report
c. Colorado site reportd. Georgia site report
e. New Hampshire site report
f. Wisconsin site report

IV. Brain damage

17. A review of nanoparticle functionality and toxicity on the central nervous system by Yang et al.
18. Recommendations for a municipal health and safety policy for nanomaterials: A Report to the City of Cambridge City Manager by Sam Lipson
19. Museum of Science Nanotechnology Forum lets participants be the judge by Mark Griffin
20. Nanotechnology policy and citizen engagement in Cambridge, Massachusetts: Local reflexive governance by Shannon Conley

Thanks to David Bruggeman’s May 13, 2014 posting on his Pasco Phronesis blog, I stumbled across both a future meeting notice and documentation of the  Feb. 2014 meeting of the Presidential Commission for the Study of Bioethical Issues (Note: Links have been removed),

Continuing from its last meeting (in February 2014), the Presidential Commission for the Study of Bioethical Issues will continue working on the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative in its June 9-10 meeting in Atlanta, Georgia.  An agenda is still forthcoming, …

…

In other developments, Commission staff are apparently going to examine some efforts to engage bioethical issues through plays.  I’d be very excited to see some of this happen during a Commission meeting, but any little bit is interesting.  The authors of these plays, Karen H. Rothenburg and Lynn W. Bush, have published excerpts in their book The Drama of DNA: Narrative Genomics.  …

The Commission also has a YouTube channel …

Integrating a theatrical experience into the reams of public engagement exercises that technologies such as stem cell, GMO (genetically modified organisms), nanotechnology, etc. tend to spawn seems a delightful idea.

Interestingly, the meeting in June 2014 will coincide with the book’s release date. I dug further and found these snippets of information. The book is being published by Oxford University Press and is available in both paperback and e-book formats. The authors are not playwrights, as one might assume. From the Author Information page,

Lynn Bush, PhD, MS, MA is on the faculty of Pediatric Clinical Genetics at Columbia University Medical Center, a faculty associate at their Center for Bioethics, and serves as an ethicist on pediatric and genomic advisory committees for numerous academic medical centers and professional organizations. Dr. Bush has an interdisciplinary graduate background in clinical and developmental psychology, bioethics, genomics, public health, and neuroscience that informs her research, writing, and teaching on the ethical, psychological, and policy challenges of genomic medicine and clinical research with children, and prenatal-newborn screening and sequencing.

Karen H. Rothenberg, JD, MPA serves as Senior Advisor on Genomics and Society to the Director, National Human Genome Research Institute and Visiting Scholar, Department of Bioethics, Clinical Center, National Institutes of Health. She is the Marjorie Cook Professor of Law, Founding Director, Law & Health Care Program and former Dean at the University of Maryland Francis King Carey School of Law and Visiting Professor, Johns Hopkins Berman Institute of Bioethics. Professor Rothenberg has served as Chair of the Maryland Stem Cell Research Commission, President of the American Society of Law, Medicine and Ethics, and has been on many NIH expert committees, including the NIH Recombinant DNA Advisory Committee.

It is possible to get a table of contents for the book but I notice not a single playwright is mentioned in any of the promotional material for the book. While I like the idea in principle, it seems a bit odd and suggests that these are purpose-written plays. I have not had good experiences with purpose-written plays which tend to be didactic and dull, especially when they’re not devised by a professional storyteller.

You can find out more about the upcoming ‘bioethics’ June 9 – 10, 2014 meeting here.  As for the Feb. 10 – 11, 2014 meeting, the Brain research, ethics, and nanotechnology (part one of five) May 19, 2014 post featured Barbara Herr Harthorn’s (director of the Center for Nanotechnology in Society at the University of California at Santa Barbara) participation only.

It turns out, there are some Canadian tidbits. From the Meeting Sixteen: Feb. 10-11, 2014 webcasts page, (each presenter is featured in their own webcast of approximately 11 mins.)

Timothy Caulfield, LL.M., F.R.S.C., F.C.A.H.S.

Canada Research Chair in Health Law and Policy
Professor in the Faculty of Law
and the School of Public Health
University of Alberta

Eric Racine, Ph.D.

Director, Neuroethics Research Unit
Associate Research Professor
Institut de Recherches Cliniques de Montréal
Associate Research Professor,
Department of Medicine
Université de Montréal
Adjunct Professor, Department of Medicine and Department of Neurology and Neurosurgery,
McGill University

It was a surprise to see a couple of Canucks listed as presenters and I’m grateful that the Presidential Commission for the Study of Bioethical Issues is so generous with information. in addition to the webcasts, there is the Federal Register Notice of the meeting, an agenda, transcripts, and presentation materials. By the way, Caulfield discussed hype and Racine discussed public understanding of science with regard to neuroscience both fitting into the overall theme of communication. I’ll have to look more thoroughly but it seems to me there’s no mention of pop culture as a means of communicating about science and technology.

Links to other posts in the Brains, prostheses, nanotechnology, and human enhancement five-part series:

Part one: Brain research, ethics, and nanotechnology (May 19, 2014 post)

Part three: Gray Matters: Integrative Approaches for Neuroscience, Ethics, and Society issued May 2014 by US Presidential Bioethics Commission (May 20, 2014)

Part four: Brazil, the 2014 World Cup kickoff, and a mind-controlled exoskeleton (May 20, 2014)

Part five: Brains, prostheses, nanotechnology, and human enhancement: summary (May 20, 2014)

* ‘neursocience’ corrected to ‘neuroscience’ on May 20, 2014.

Thinking about nanotechnology, synthetic biology, body hacking, corporate responsibility, and zombies

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In the wake of Craig Venter’s announcement (last week) of the creation of a synthetic organism (or most of one), Barack Obama, US President, has requested a special study (click here to see the letter to Dr. Amy Gutmann of the Presidential Commission for the Study of Bioethical Issues). From Andrew Maynard’s 2020 Science blog (May 26, 2010) posting,

It’s no surprise therefore that, hot on the heels of last week’s announcement, President Obama called for an urgent study to identify appropriate ethical boundaries and minimize possible risks associated with the breakthrough.

This was a bold and important move on the part of the White House. But its success will lie in ensuring the debate over risks in particular is based on sound science, and not sidetracked by groundless speculation.

The new “synthetic biology” epitomized by the Venter Institute’s work – in essence the ability to design new genetic code on computers and then “download” it into living organisms – heralds a new era of potentially transformative technology innovation. As if to underline this, the US House of Representatives Committee on Energy and Commerce will be hearing testimony from Craig Venter and others on the technology’s potential on May 27th – just days after last week’s announcement.

Andrew goes on to suggest while the ethical issues are very important that safety issues should not be shortchanged,

The ethics in particular surrounding synthetic biology are far from clear; the ability to custom-design the genetic code that resides in and defines all living organisms challenges our very notions of what is right and what is acceptable. Which is no doubt why President Obama wasted no time in charging the Presidential Commission for the Study of Bioethical Issues to look into the technology.

But in placing ethics so high up the agenda, my fear is that more immediate safety issues might end up being overlooked.

Hilary Sutcliffe in an opinion piece for ethicalcorp.com (writing to promote her organization’s [MATTER] Corporate responsibility and emerging technologies conference on June 4, 2010) suggests this,

Though currently most of the attention is focused on the scientists exploring synthetic biology in universities, this will also include the companies commercialising these technologies.

In addition, many organisations may soon have to consider if and how they use the applications developed using these new technologies in their own search for sustainability.

This is definitely an issue for the ‘Futures’ area of your CSR [corporate social responsibility] strategy, but there is a new ‘ology’ which is being used in products already on the market which may need to be moved up your priority list – ‘Nanotechnology’ or (‘nanotechnologies’ to be precise) – nano for short.

What I’m doing here is drawing together synthetic biology, nanotechnology, safety, and corporate social responsibility (CSR). What follows is an example of a company that apparently embraced CSR.

In the wake of BP’s (British Petroleum) disastrous handling of the Gulf of Mexico oil spill, the notion of corporate social responsibility and  ethics and safety issues being considered and discussed seriously seems unlikely. Sure, there are some smaller companies that act on on those values but those are the values of an owner and are not often seen in action in a larger corporate entity and certainly not in a multinational enterprise such as BP.

Spinwatch offers an intriguing perspective on corporate social responsibility in an article by Tom Borelli,

To demonstrate “responsibility”, BP spent huge sums of money on an advertising campaign promoting the notion that fossil fuel emissions of carbon dioxide is to blame for global warming and its investment in renewable energy was proof the company was seeking a future that was “beyond petroleum”.

The message was clear: oil is bad for society and BP is leading the way in alternative energy.

The BP experience shows there are serious consequences when companies demagogue against its core business. …

… “If you drew up a list of companies that Americans are most disappointed in, BP would definitely feature,” said James Hoopes, professor of business ethics at Babson College, Massachusetts.

Ironically, BP’s experience delivered the exact opposite of CSR’s promise: the company’s reputation was ruined, the company is the target of government agency investigations and Congressional hearings and its stock price lags far behind its competitors and the S&P 500.

Unfortunately, in the aftermath of BP’s failures, many critics blamed corporate greed – not CSR – as the cause. They believed the profit motive forced the company to skimp on basic pipeline maintenance and worker safety.

This conclusion is far from the truth. If profit were its only goal, BP would define its role in society as a company that safely producing oil while providing jobs and energy for the economy.

This article was written in 2006 and presents a view that would never have occurred to me. I find Borelli’s approach puzzling as it seems weirdly naïve. He seems to be unaware that large companies can have competing interests and while one part of an enterprise may be pursuing genuine corporate social responsibility another part of the enterprise may be pursuing goals that are antithetical to that purpose. Another possibility is that the company was cynically pursing corporate social responsibility in the hope that it would mitigate any backlash in the event of a major accident.

Getting back to where this started, I think that nanotechnology, synthetic biology and other emerging technologies require all of the approaches to  ethics, safety rules, corporate social responsibility, regulatory frameworks, and more that we have and can dream up including this from Andrew (from May 26, 2010 posting),

Rather, scientists, policy makers and developers urgently need to consider how synthetic biology might legitimately lead to people and the environment being endangered, and how this is best avoided.

What we need is a science-based dialogue on potential emergent risks that present new challenges, the plausibility of these risks leading to adverse impacts, and the magnitude and nature of the possible harm that might result. Only then will we be able to develop a science-based foundation on which to build a safe technology.

Synthetic biology is still too young to second-guess whether artificial microbes will present new risks; whether bio-terror or bio-error will result in harmful new pathogens; or whether blinkered short-cuts will precipitate catastrophic failure. But the sheer momentum and audacity of the technology will inevitably lead to new and unusual risks emerging.

And this is precisely why the safety dialogue needs to be grounded in science now, before it becomes entrenched in speculation.

You can read more about the science behind Venter’s work in this May 22, 2010 posting by Andrew and Gregor Wolbring provides an excellent roundup of the commentary on Venter’s latest achievement.

I agree we need the discussion but grounding the safety dialogue in science won’t serve as a prophylactic treatment for public panic. I believe that there is always an underlying anxiety about science, technology, and our place in the grand scheme of things. This anxiety is played out in various horror scenarios. I don’t think it’s an accident that interest in vampires, werewolves, and zombies is so high these days.

I had a minor epiphany—a reminder of sorts—the other night watching Zombiemania ( you can read a review of this Canadian documentary here) when I heard the pioneers,  afficionados and experts comment on the political and social implications of zombie movies (full disclosure: I’m squeamish  so I had to miss parts of the documentary).This fear of losing control over nature and destroying the natural order (reversing death as zombies and vampires do) and the worry over the consequences of augmenting ourselves (werewolves, zombies and vampires are stronger than ordinary humans who become their prey) is profound.

Venter’s feat with the bacterium may or may not set off a public panic but there is no question in my mind that at least one will occur as synthetic biology, biotechnology, and nanotechnology take us closer to real life synthetic and transgenic organisms, androids and robots (artificial humans), and cyborgs (body hackers who integrate machines into their bodies).

Let’s proceed with the discussions about safety, ethics, etc. on the assumption that there will be a public panic. Let’s make another assumption, the public panic will be set off by something unexpected. For the final assumption, a public panic may be just what we need. That final comment has been occasioned by Schumpeter’s notion of ‘creative destruction’ (Wikipedia essay here). While the notion is grounded in economics, it has a remarkably useful application as a means of understanding social behaviour.

Synbio (synthetic biology) hits the big time: Venter, media storm, and synbio collaboration webcast

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Craig Venter’s and his team’s achievement is being touted widely right now. From the news item (Researchers create first self-replicating, synthetic bacterial cell) on Nanowerk,

The team synthesized the 1.08 million base pair chromosome of a modified Mycoplasma mycoides genome. The synthetic cell is called Mycoplasma mycoides JCVI-syn1.0 and is the proof of principle that genomes can be designed in the computer, chemically made in the laboratory and transplanted into a recipient cell to produce a new self-replicating cell controlled only by the synthetic genome.

This research will be published by Daniel Gibson et al in the May 20th edition of Science Express and will appear in an upcoming print issue of Science.

This has, of course, roused a discussion which is taking place in the blogosphere, in science journals, and elsewhere. Dave Bruggeman at his Pasco Phronesis blog offers a few thoughts about the achievement,

While many are hailing the replication as a significant breakthrough, others are not as impressed. For one thing, while it is described in some circles as synthetic life, the new life has a synthetic inside housed within a pre-existing bacterium shell. For another, there are related projects involving higher lifeforms that may deserve greater attention from a policy perspective.

His comments provide a bracing contrast to some of the hyperbole as per this news item (Life after the synthetic cell – opinions from eight leading synthetic-biology pundits) on Nanowerk,

In the Opinion section of Nature, eight leading synthetic-biology pundits reflect on what effect Craig Venter’s latest achievement could have on science and society.

All the commentators hail the work as highly significant — Arthur Caplan going so far as to describe it as “one of the most important scientific achievements in the history of mankind”. Beyond that they have mixed feelings about what the Mycoplasma bacterium represents.

Coincidentally (or not), the Hudson Institute is hosting its third meeting about moral issues and synthetic biology. From this news item (Moral issues raised by synthetic biology subject of Hastings Center Project) on Nanowerk,

The Hastings Center has been at the forefront of interdisciplinary research into ethical issues in emerging technology. The synthetic biology project is funded by a grant from the Alfred P. Sloan Foundation . Project participants include synthetic biologists, bioethicists, philosophers, and public policy experts. The Center’s work is part of a comprehensive look at synthetic biology by the Alfred P. Sloan Foundation. Other participants in the initiative are the J. Craig Venter Institute and the Woodrow Wilson International Center for Scholars. [emphasis mine]

Intriguingly, the Woodrow Wilson Center hosts the Synthetic Biology Project (a spinoff from their Project on Emerging Technologies [PEN]).

Last week (May 12, 2010), the SynBio Project webcast (access here) an event titled, Synbio in Society: Toward New Forms of Collaboration? which featured,

One response to society’s concerns about synthetic biology has been to institutionalize the involve­ment of social scientists in the field. There have been a series of initiatives in which ethics and biosafety approaches have been purposely incorporated into synthetic biology research and development. [emphasis mine] The collaborative Human Practices model within the NSF-funded SynBERC project was the first initiative in which social scientists were explicitly integrated into a synthetic biology research program. But these new collaborations have also flourished in the UK where four research councils have funded seven scientific networks in synthetic biology that require consideration of ethical, legal and social issues. Another example is the US-UK Synthetic Aesthetics Project, which brings together synthetic biologists, social scientists, designers and artists to explore collaborations between synthetic biology and the creative professions.

Similarly, the European Commission’s Seventh Framework Program funds a project called Synth-ethics, which “aims at discerning relevant ethical issues in close collaboration with the synthetic biology community.

I watched the webcast as it was being streamed live unaware that a big announcement would be made this week. The science community did not share my ignorance so this work has been discussed for months (Science is a peer-reviewed journal and peer review, even if expedited, is going to take more than a month).

I’m willing to bet that the webcast and the Hudson Institute meeting were timed to coincide with the announcement and that the journal Nature was given lots of time to solicit opinions from eight experts.

I have one more item of note. Science Channel will be presenting a special programme on Venter’s work,”Creating Synthetic Life, premiering Thursday, June 3, 2010, at 8PM e/p.” More from their press announcement,

Over the course of five years, only Science Channel cameras captured the failures, successes and breakthrough moments of Dr. Venter, Nobel Laureate Hamilton Smith, Dr. Clyde Hutchison and JCVI [J. Craig Venter Institute] researchers as they meticulously sought to create a synthetic single-celled organism.

What exactly does today’s news mean for the human race? Where exactly will it take us? Could the technology be used for negative purposes? What are the ethical concerns we must weigh before using it?… This one-hour special is an open forum discussion featuring Dr. Venter, leading bioethicists, top scientists and other members of the scientific community discussing the breakthrough’s ramifications and how it may change our world and the future.

Your Questions Answered allows viewers to ask the experts about how this technology will affect their lives. From now through May 26, submit your questions via Facebook, and they could be asked during the show.

Clearly, Science Channel took a calculated risk (see Venter’s bio page to understand why it was a calculated risk) when they started following Venter’s work.

In looking at all this, it’s fascinating to consider the combination of planning, calculated risk-taking, and luck that have come together to create this ‘synthetic biology moment’.

Of special interest to me, is the way that social scientists and ethicists and others have been integrated into the larger synthetic biology initiative. In my more cynical moments, I view this integration as a means of trying to allay concerns before a ‘stem cell’ or GM (genetically modified) food (aka Frankenfoods) controversy erupts. In less cynical moments, I like to think that lessons were learned and that the concerns will be heard and heeded.