Scientific panel loosens ’14-day rule’ limiting how long human embryos can be grown in the lab

Andrew Joseph

STATnews.com

Originally posted 26 May 2021

An influential scientific panel cracked open the door on Wednesday to growing human embryos in the lab for longer periods of time than currently allowed, a step that could enable the plumbing of developmental mysteries but that also raises thorny questions about whether research that can be pursued should be.

For decades, scientists around the world have followed the “14-day rule,” which stipulates that they should let human embryos develop in the lab for only up to two weeks after fertilization. The rule — which some countries (though not the United States) have codified into law — was meant to allow researchers to conduct inquiries into the early days of embryonic development, but not without limits. And for years, researchers didn’t push that boundary, not just for legal and ethical reasons, but for technical ones as well: They couldn’t keep the embryos growing in lab dishes that long.

More recently, however, scientists have refined their cell-culture techniques, finding ways to sustain embryos up to that deadline. Those advances — along with other leaps in the world of stem cell research, with scientists now transmogrifying cells into blobs that resemble early embryos or injecting human cells into animals — have complicated ethical debates about how far biomedical research should go in its quest for knowledge and potential treatments.

Now, in the latest updates to its guidelines, the International Society for Stem Cell Research has revised its view on studies that would take human embryos beyond 14 days, moving such experiments from the “absolutely not” category to a “maybe” — but only if lots of conditions are first met.

“We’ve relaxed the guidelines in that respect, we haven’t abandoned them,” developmental biologist Robin Lovell-Badge of the Francis Crick Institute, who chaired the ISSCR’s guidelines task force, said at a press briefing.

The info is here.

The Moral Choices on CRISPR Babies

Sheldon Krimsky
The American Journal of Bioethics
Published online September 26, 2019

In late November 2018, Chinese scientist Dr. He Jiankui announced at the Second International Summit on Human Genome Editing in Hong Kong that he had used CRISPR/Cas 9 gene editing on two female embryos that were brought to term through an in vitro fertilization (IVF) pregnancy. The world scientific community was ill-prepared for the announcement since the moral issues surrounding the editing of human embryos were under discussion but hardly resolved. The recommendation of the 12-member organizing committee of the 2015 International Summit on Human Gene Editing in Washington, DC, stated that it would be irresponsible to undertake any clinical use of germline editing unless and until the safety and efficacy issues were resolved and there was a broad consensus on the specific application, and that such use could proceed only under appropriate regulatory oversight (International Summit on Human Genome Editing 2015). Similar recommendations were made by the National Academies of Sciences, Engineering, and Medicine. This editorial gives two reasons for genetically modifying embryos and three reasons against it.

The summary of arguments for and against genetically modifying embryos is here.

Debate ethics of embryo models from stem cells

Nicolas Rivron, Martin Pera, Janet Rossant, Alfonso Martinez Arias, and others
Nature
Originally posted December 12, 2018

Here are some excerpts:

Four questions

Future progress depends on addressing now the ethical and policy issues that could arise.

Ultimately, individual jurisdictions will need to formulate their own policies and regulations, reflecting their values and priorities. However, we urge funding bodies, along with scientific and medical societies, to start an international discussion as a first step. Bioethicists, scientists, clinicians, legal and regulatory specialists, patient advocates and other citizens could offer at least some consensus on an appropriate trajectory for the field.

Two outputs are needed. First, guidelines for researchers; second, a reliable source of information about the current state of the research, its possible trajectory, its potential medical benefits and the key ethical and policy issues it raises. Both guidelines and information should be disseminated to journalists, ethics committees, regulatory bodies and policymakers.

Four questions in particular need attention.

Should embryo models be treated legally and ethically as human embryos, now or in the future?

Which research applications involving human embryo models are ethically acceptable?

How far should attempts to develop an intact human embryo in a dish be allowed to proceed?

Does a modelled part of a human embryo have an ethical and legal status similar to that of a complete embryo?

The info is here.

'Should we even consider this?' WHO starts work on gene editing ethics

Agence France-Presse
Originally published 3 Dec 2018

The World Health Organization is creating a panel to study the implications of gene editing after a Chinese scientist controversially claimed to have created the world’s first genetically edited babies.

“It cannot just be done without clear guidelines,” Tedros Adhanom Ghebreyesus, the head of the UN health agency, said in Geneva.

The organisation was gathering experts to discuss rules and guidelines on “ethical and social safety issues”, added Tedros, a former Ethiopian health minister.

Tedros made the comments after a medical trial, which was led by Chinese scientist He Jiankui, claimed to have successfully altered the DNA of twin girls, whose father is HIV-positive, to prevent them from contracting the virus.

His experiment has prompted widespread condemnation from the scientific community in China and abroad, as well as a backlash from the Chinese government.

The info is here.

As China Seeks Scientific Greatness, Some Say Ethics Are an Afterthought

Sui-Lee Wee and Elsie Chen
The New York Times
Originally published November 30, 2018

First it was a proposal to transplant a head to a new body. Then it was the world’s first cloned primates. Now it is genetically edited babies.

Those recent scientific announcements, generating reactions that went from unease to shock, had one thing in common: All involved scientists from China.

China has set its sights on becoming a leader in science, pouring millions of dollars into research projects and luring back top Western-educated Chinese talent. The country’s scientists are accustomed to attention-grabbing headlines by their colleagues as they race to dominate their fields.

But when He Jiankui announced on Monday that he had created the world’s first genetically edited babies, Chinese scientists — like those elsewhere — denounced it as a step too far. Now many are asking whether their country’s intense focus on scientific achievement has come at the expense of ethical standards.

The info is here.

Japan Set to Allow Gene Editing in Human Embryos

David Cyranoski
Scientific American
Originally posted on October 3, 2018

Japan has issued draft guidelines that allow the use of gene-editing tools in human embryos. The proposal was released by an expert panel representing the country’s health and science ministries on 28 September.

Although the country regulates the use of human embryos for research, there have been no specific guidelines on using tools such as CRISPR–Cas9 to make precise modifications in their DNA until now.

Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, says that before the draft guidelines were issued, Japan’s position on gene editing in human embryos was neutral. The proposal now encourages this kind of research, he says.

But if adopted, the guidelines would restrict the manipulation of human embryos for reproduction, although this would not be legally binding.

Manipulating DNA in embryos could reveal insights into early human development. Researchers also hope that in the long term, these tools could be used to fix genetic mutations that cause diseases, before they are passed on.

The info is here.

Double time limit for embryo research, say ethics experts

Science News
August 7, 2018

Currently, research on embryos is limited in many countries to a maximum period of 14 days after their fertilisation in the lab.

But ethicists Dr John Appleby of Lancaster University with Professor Dr Annelien Bredenoord of University Medical Center Utrecht believe the current limit is "no longer adequate for current scientific developments."

Dr Appleby and Professor Dr Bredenoord said: "The 14 day rule has been a very successful example of international science regulation, but it should not become a dogma in itself and it should be revisited when no longer fit to purpose."

Until recently, scientists have not been able to culture and sustain embryos in vitro as long as (or beyond) 14 days but this has now changed.

"There are both scientific and ethical reasons to extent the 14 day rule to for example 28 days. Extending the window for embryo research to 28 days would allow scientists to reveal a new in-depth chapter of knowledge about the developmental processes that take place in embryos."

The info is here.

Deadly gene mutations removed from human embryos in landmark study

Ian Sample
The Guardian
Originally published August 2, 2017

Scientists have modified human embryos to remove genetic mutations that cause heart failure in otherwise healthy young people in a landmark demonstration of the controversial procedure.

It is the first time that human embryos have had their genomes edited outside China, where researchers have performed a handful of small studies to see whether the approach could prevent inherited diseases from being passed on from one generation to the next.

While none of the research so far has created babies from modified embryos, a move that would be illegal in many countries, the work represents a milestone in scientists’ efforts to master the technique and brings the prospect of human clinical trials one step closer.

The work focused on an inherited form of heart disease, but scientists believe the same approach could work for other conditions caused by single gene mutations, such as cystic fibrosis and certain kinds of breast cancer.

The article is here.

Genetic testing of embryos creates an ethical morass

 Andrew Joseph
STAT news
Originally published October 23, 2017

Here is an excerpt:

The issue also pokes at a broader puzzle ethicists and experts are trying to reckon with as genetic testing moves out of the lab and further into the hands of consumers. People have access to more information about their own genes — or, in this case, about the genes of their potential offspring — than ever before. But having that information doesn’t necessarily mean it can be used to inform real-life decisions.

A test can tell prospective parents that their embryo has an abnormal number of chromosomes in its cells, for example, but it cannot tell them what kind of developmental delays their child might have, or whether transferring that embryo into a womb will lead to a pregnancy at all. Families and physicians are gazing into five-day-old cells like crystal balls, seeking enlightenment about what might happen over a lifetime. Plus, the tests can be wrong.

“This is a problem that the rapidly developing field of genetics is facing every day and it’s no different with embryos than it is when someone is searching Ancestry.com,” said Judith Daar, a bioethicist and clinical professor at University of California, Irvine, School of Medicine. “We’ve learned a lot, and the technology is marvelous and can be predictive and accurate, but we’re probably at a very nascent stage of understanding the impact of what the genetic findings are on health.”

Preimplantation genetic testing, or PGT, emerged in the 1990s as a way to study the DNA of embryos before they’re transferred to a womb, and the technology has grown more advanced with time. Federal data show it has been used in about 5 percent of IVF procedures going back several years, but many experts pin the figure as high as 20 or 30 percent.

The article is here.

Human Gene Editing Marches On

bioethics.net
Originally published October 6, 2017

Here is an excerpt:

In all three cases, the main biologic approach, and the main ethical issues, are the same.  The main differences were which genes were being edited, and how the embryos were obtained.

This prompted Nature to run an editorial to say that it is “time to take stock” of the ethics of this research.  Read the editorial here.  The key points:  This is important work that should be undertaken thoughtfully.  Accordingly, donors of any embryos or cells should be fully informed of the planned research.  Only as many embryos should be created as are necessary to do the research.  Work on embryos should be preceded by work on pluripotent, or “reprogrammed,” stem cells, and if questions can be fully answered by work with those cells, then it may not be necessary to repeat the studies on whole, intact human embryos, and if that is not necessary, perhaps it should not be done.  Finally, everything should be peer reviewed.

I agree that editing work in non-totipotent cells should be at all times favored over work on intact embryos, but if one holds that an embryo is a human being that should have the benefits of protections afforded human research subjects, then Nature’s ethical principles are rather thin, little more than an extension of animal use provisions for studies in which early humans are the raw materials for the development of new medical treatments.

The article is here.

Artificial Human Embryos Are Coming, and No One Knows How to Handle Them

Antonio Regalado
MIT Tech Review
September 19, 2017

Here is an excerpt:

Scientists at Michigan now have plans to manufacture embryoids by the hundreds. These could be used to screen drugs to see which cause birth defects, find others to increase the chance of pregnancy, or to create starting material for lab-generated organs. But ethical and political quarrels may not be far behind. “This is a hot new frontier in both science and bioethics. And it seems likely to remain contested for the coming years,” says Jonathan Kimmelman, a member of the bioethics unit at McGill University, in Montreal, and a leader of an international organization of stem-cell scientists.

What’s really growing in the dish? There no easy answer to that. In fact, no one is even sure what to call these new entities. In March, a team from Harvard University offered the catch-all “synthetic human entities with embryo-like features,” or SHEEFS, in a paper cautioning that “many new varieties” are on the horizon, including realistic mini-brains.

Shao, who is continuing his training at MIT, dug into the ethics question and came to his own conclusions. “Very early on in our research we started to pay attention to why are we doing this? Is it really necessary? We decided yes, we are trying to grow a structure similar to part of the human early embryo that is hard otherwise to study,” says Shao. “But we are not going to generate a complete human embryo. I can’t just consider my feelings. I have to think about society.”

The article is here.

First Human Embryos Edited in U.S.

Steve Connor
MIT Technology News
Originally published July 26, 2017

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, Technology Review has learned.

The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.

Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.

The article is here.

Ethical Guidelines on Lab-Grown Embryos Beg for Revamping

Karen Weintraub
Scientific American
Originally posted on March 21, 2017

For nearly 40 years scientists have observed their self-imposed ban on doing research on human embryos in the lab beyond the first two weeks after fertilization. Their initial reasoning was somewhat arbitrary: 14 days is when a band of cells known as a primitive streak, which will ultimately give rise to adult tissues, forms in an embryo. It is also roughly the last time a human embryo can divide and create more than one person, and a few days before the nervous system begins to develop. But the so-called 14-day rule has held up all this time partly because scientists could not get an embryo to grow that long outside its mother's body.

Researchers in the U.K. and U.S. recently succeeded for the first time in growing embryos in the lab for nearly two weeks before terminating them, showing that the so-called 14-day rule is no longer a scientific limitation—although it remains a cultural one. Now, a group of Harvard University scientists has published a paper arguing that it is time to reconsider the 14-day rule because of advances in synthetic biology.

The U.S. has no law against growing embryos beyond two weeks—as long as the research is not funded with federal dollars. But most scientific journals will not publish studies that violate the 14-day rule, and the International Society for Stem Cell Research requires its members to agree to the rule in order to qualify for membership.

The article is here.

New fertility procedure may lead to 'embryo farming', warn researchers

Ian Sample
The Guardian
Originally posted January 11, 2017

A new lab procedure that could allow fertility clinics to make sperm and eggs from people’s skin may lead to “embryo farming” on a massive scale and drive parents to have only “ideal” future children, researchers warn.

Legal and medical specialists in the US say that while the procedure – known as in vitro gametogenesis (IVG) – has only been demonstrated in mice so far, the field is progressing so fast that the dramatic impact it could have on society must be planned for now.

“We try not to take a position on these issues except to point out that before too long we may well be facing them, and we might do well to start the conversation now,” said Eli Adashi, professor of medical science at Brown University in Rhode Island.

The creation of sperm and eggs from other tissues has become possible through a flurry of recent advances in which scientists have learned first to reprogram adult cells into a younger, more versatile state, and then to grow them into functioning sex cells. In October, scientists in Japan announced for the first time the birth of baby mice from eggs made with their parent’s skin.

The article is here.

Should the 14-day limit on embryo research be extended?

by Philip Ball
Prospect Magazine
Originally published December 12, 2016

Here is an excerpt:

That limit has remained in place ever since. But now some scientists believe it should be extended to 28 days. These proposals were discussed on 7th December at a meeting in London organised by charity the Progress Educational Trust. It marked the beginning of what seems likely to be a broad and extended discussion among scientists, bioethicists, fertility specialists, religious leaders and others who have a stake in the moral, legal and scientific status of the human embryo.

(cut)

So the 14-day embryo has begun the process that leads to the laying down of the human body plan—but only just. A key stage, called gastrulation, begins around day 16: this is when the embryo acquires a three-layered structure, the precursor to the appearance of different body-tissue types. So the time between day 14 and day 28 sees the embryo progress through some crucial stages of development, and understanding the details of what goes on, such as the genetic changes involved, should provide a wealth of information that might offer insights into human health, disease and malformation. Much of what we know about these stages at present comes from studies of mice—but as several of the speakers acknowledged, there are some important differences between mice and men.

This is why it looks so enticing for cell biologists and geneticists to investigate the post-14-day embryo. But should that be allowed by a change in the law?

The article is here.

Netherlands to grow human embryos for research

By www.rt.com
Originally posted May 26, 2016

The Dutch government will allow labs to grow human embryos to be used for research in a limited number of fields, it announced on Friday. Currently scientists have to rely on a limited supply of leftover embryos from in vitro fertilization patients.

The ban on the cultivation of embryos [has] hampered research which could help with the treatment of diseases on the short to medium-long term," the government said in a statement, justifying the ethically controversial move.

The new regulations would not change the so-called “14-day rule”, which demands that any human embryo kept in a lab be destroyed no later than two weeks after fertilization.

The article is here.

Why this lab-grown human embryo has reignited an old ethical debate

By Patrick Monahan
Science
May. 4, 2016

It’s easy to obey a rule when you don’t have the means to break it. For decades, many countries have permitted human embryos to be studied in the laboratory only up to 14 days after their creation by in vitro fertilization. But—as far as anyone knows—no researcher has ever come close to the limit. The point of implantation, when the embryo attaches to the uterus about 7 days after fertilization, has been an almost insurmountable barrier for researchers culturing human embryos.

Now, two teams report growing human embryos about a week past that point. Beyond opening a new window on human biology, such work could help explain early miscarriages caused by implantation gone awry. As a result, some scientists and bioethicists contend that it’s time to revisit the so-called 14-day rule. But that won’t be welcomed by those who consider the rule to have a firm moral grounding—or by those who oppose any research on human embryos.

The article is here.

Should you edit your children’s genes?

Erika Check Hayden
Nature
Originally posted 23 February 2016

Here is an excerpt:

But emerging technologies are already testing the margins of what people deem acceptable. Parents today have unprecedented control over what they pass on to their children: they can use prenatal genetic screening to check for conditions such as Down’s syndrome, and choose whether or not to carry a fetus to term. Preimplantation genetic diagnosis allows couples undergoing in vitro fertilization to select embryos that do not have certain disease-causing mutations. Even altering the heritable genome — as might be done if CRISPR were used to edit embryos — is acceptable to some. Mitochondrial replacement therapy, which replaces a very small number of genes that a mother passes on with those from a donor, was approved last year in the United Kingdom for people who are at risk of certain genetic disorders.

Many safety, technical and legal barriers still stand in the way of editing DNA in human embryos. But some scientists and ethicists say that it is important to think through the implications of embryo editing now — before these practical hurdles are overcome. What sort of world would these procedures create for those currently living with disease and for future generations?

The article is here.

U.K. researcher details proposal for CRISPR editing of human embryos

By Erik Stokstad
Science
Originally published January 13, 2016

Here is an excerpt:

In a statement about the application, Hugh Whittall, director of the Nuffield Council on Bioethics in London noted: “The changes to DNA made for the purposes of this research could not themselves be used as part of a treatment procedure. There are, however, possible future scenarios in which a modification made in a research context—for example to correct a disease-causing genetic mutation—could, if this were to become permissible, be used in a treatment that would result in the birth of a child.  Such research, which could also be licensed under current legislation, would raise a number of significant questions that should be addressed before any such work is undertaken, including about whether, and under what circumstances, a move into treatment (which would require new legislation to be permissible in the U.K.) could be desirable.”

The article is here.

Summit fails to ban genetic engineering of human embryos

By Michael Cook
BioEdge.org
Originally published December 5, 2015

Here is an excerpt:

The most controversial item on the agenda was genetic editing of human embryos and germ cells. Chinese scientists have already done this with surplus IVF embryos, although all of them died. Unsurprisingly, the International Summit on Human Gene-Editing declared that it would be “irresponsible to proceed with any clinical use of germline editing” until the risks were better understood. But it failed to endorse even a moratorium on human germline gene-editing, let alone a blanket ban.

Gene-editing has far-reaching uses in basic and pre-clinical research and modification of somatic cells. If embryos or germ cells are edited, it might be possible to avoid severe inherited diseases or to enhance human capabilities.

The entire article is here.