Artificial embryo tech reported in Science: how big is this?

Can you make an artificial embryo?

Developmental biologist Magdalena Zernicka-Goetz has long been on the trail of this seemingly almost uncatchable quarry.

With her team’s publication in Science today they took a big step forward on this path even if some major hurdles remain. You can see her discussion of the research in the YouTube video above along with interesting comments from her graduate student, Sarah Harrison who was the first author. Congrats to both.

The paper, Harrison, et al, is entitled “Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro”. The murine embryo-like structures are referred to as ETS-embryos since they are derived from both Embryonic stem cells and Trophoblast Stem cells.

The potential applications of this artificial ETS-embryo technology moving forward are broad, but there are some limits to the current version of the method. For instance, not all germ layers are represented. New Scientist quoted Robin Lovell-Badge about these limitations:

Robin Lovell-Badge at the Francis Crick Institute in London says that the embryos lack two other types of cell layer required to develop the bodies’ organs: ectoderm, which forms skin and the central nervous system, and endoderm, which makes our internal organs.”

artificial embryos

Figure 2 Series of images showing the development of ETS-embryos over a period of 5 days. Trophoblast-derived cells are stained with a DNA marker only and ESC-derived cells stained with Oct4

The team hopes to address that with future versions.

Could one ever create ‘real” living mouse embryos this way?

From New Scientist:

“We’re not planning to make a mouse in the lab using stem cells,” says Zernicka-Goetz. But she is hopeful that adding yolk sac stem cells will allow these artificial embryos to survive long enough to study the beginnings of organs like the heart.”

Another provocative open question that Harrison calls “the elephant in the room” in the video is whether this type of technology could work with human cells to make human embryo-like structures. If that is possible, a great deal of innovative research could be catalyzed, but of course huge ethical questions would emerge along the way. Harrison highlighted differences in mouse and human embryogenesis that could also be a challenge.

Of course one can more simply make early embryos through IVF, but a new perhaps tractable system like ETS-embryos may enable more flexible studies involving use CRISPR for instance. Would it bypass ethical concerns in the human context if someone went down that path? It all depends on how one defines an embryo.

Disclosure: Cell Guidance Systems, an advertiser on this blog, has licensed the embryo technology and conducted the interview in the video, but this is not a sponsored post.

CRISPR embryo OK signals ongoing liberal UK trend on human modification

Kathy Niakan

Dr. Kathy Niakan, Francis Crick Institute Photo

With the approval today of the use of CRISPR in human embryos, the UK continues its recent trend toward a more permissive regulatory policy on human genetic modification. There are both risks and scientific benefits that come along with this trend.

Last year the UK approved an experimental technology with the goal of preventing the transmission of mitochondrial disease. The approach would try to prevent this terrible genetic disease but in the process would also create genetically modified babies. I lobbied the UK Parliament to not approve this technology (variously called 3-person IVF, mitochondrial transfer, and more controversially “3-parent babies”) at this time.

My view was that there wasn’t even close to enough data to support its safety and efficacy at present, but in the future we might know more that tells us it is wise to proceed. I still feel that way today and I’ve heard rumors that the UK scientists even now with the 3-person IVF approval are taking a relatively slow-go approach on its implementation. If correct, I think that’s wise of them. The 3-person IVF technology could do more harm than good. We just don’t know.

With a green light now for CRISPR’ing human embryos at the request of Kathy Niakan, a biologist at Francis Crick Institute, the UK continues its broader trend toward being more open to genetic modification on the human front. The stated goal of the UK CRISPR research on human embryos is not to make designer babies, but rather to advance our understanding of human development, which remains poorly understood:

“I promise you she has no intention of the embryos ever being put back into a woman for development,” Robin Lovell-Badge, group leader at the Crick Institute, told TIME. “That wouldn’t be the point. The point is to understand things about basic human biology.”

Dr. Lovell-Badge is right on this research potentially teaching us very important things about human biology and I can’t imagine that Dr. Niakan has any interest in designer baby research. I’m not worried about that and I’m excited about the research potential here.

It’s frustrating for us biologists that we still know more about the development of other animals (e.g. mice or fruit flies) than that of our own species. CRISPR could change that and I believe it could do it in a big way. So with the appropriate oversight, bioethics training, and transparency, I could support this CRISPR work in the UK. I need time to read up on what exactly they have planned. Also, see my ABCD plan on human germline modification.

However, at the same time we have to be clear that thing aren’t so simple in terms of keeping control of technologies and there are big risks here at a more global level. Collectively we are walking a fine line in this area. All it would take is someone going rogue by taking the same CRISPR’d embryos and implanting them in a surrogate for the field to find itself in a very dangerous situation.

The UK is heading in a more permissive direction on human modification. That may be appropriate to some extent and worth some risk, but how far should it go? What about the US, China, and other countries? We need more talk (meaning dialogue, debate, etc.) to go along with the increasing action (research) in this area.

NAS Meeting on Human Germline Modification Taking Shape

The US National Academy of Sciences (NAS) will hold a meeting on heritable human genetic modification on December 1-3, 2015 in Washington, D.C. Invitations to the NAS meeting to individuals starting going out last week.

The upcoming NAS meeting seeks to address these issues and discuss the possibility of a moratorium on clinical use of genetic modification technology. It could play a crucial role in shaping both national and global policy on human genetic modification.NAS gene editing

The meeting was sparked in part by rising concerns over the possibility that some scientists may race ahead to clinical use of new gene editing technologies such as CRISPR-Cas9. Such clinical use of human genetic modification technology could pose serious risks to both individuals and to science. Others have the opposite view and favor allowing heritable human editing to proceed as a natural course of science delineated only by existing regulations rather than a moratorium. An international meeting would have the goal to reach consensus on prudent policy in this area, just as the 1975 Asilomar meeting did on genetic engineering.

The NAS has announced that both the Royal Society and the Chinese Academy of Sciences are partnering on the new 2015 meeting. This is a positive step as it will increase the diverse, global views on the key issues. Leaders of both the new partners indicated their enthusiasm for the meeting:

“Human gene editing offers great promise for improving human health and well-being but it also raises significant ethical and societal issues,” said Royal Society President Paul Nurse.  “It is vital that we have a well-informed international debate about the potential benefits and risks, and this summit can hopefully set the tone for that discussion.”

Chinese Academy of Sciences President Chunli Bai said, “Both Chinese scientists and the government are aware of the pros and cons of human gene editing.  CAS scientists have organized a panel discussion and coordinated with related government agencies for regulatory policies on this issue.  We would like to work together with international communities for the proper regulation and application of such technology.”

One issue, however, is whether it could be a challenge for a meeting with such a broad spectrum of views and constituents to reach a focused consensus.

Details on the meeting are starting to come out on social media too.

Bioethicist Tetsuya Ishii tweeted about his invite to the meeting.

From the NAS website here are the meeting organizers:

  • David Baltimore (chair), president emeritus and Robert Andrews Millikan Professor of Biology, California Institute of Technology, Pasadena United States
  • Françoise Baylis, professor and Canada Research Chair in Bioethics and Philosophy, Dalhousie University, Nova Scotia Canada
  • Paul Berg, Robert W. and Vivian K. Cahill Professor Emeritus and director emeritus, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, Calif. United States
  • George Q. Daley, Samuel E. Lux IV Professor of Hematology and Oncology, and director, Stem Cell Transplantation Program, Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston United States
  • Jennifer A. Doudna, investigator, Howard Hughes Medical Institute; and professor, department of molecular and cell biology, Lawrence Berkeley National Laboratory, and department of chemistry, University of California, Berkeley United States
  • Eric S. Lander, president and director, The Broad Institute of Harvard and MIT, Cambridge, Mass. United States
  • Robin Lovell-Badge, group leader and head, division of stem cell biology and developmental genetics, The Francis Crick Institute, London United Kingdom
  • Pilar Ossorio, professor of law and bioethics, University of Wisconsin; and ethics scholar, Morgridge Institute for Research, Madison United States
  • Duanqing Pei, professor and director general, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou China
  • Adrian Thrasher, professor of paediatric immunology, University College London United Kingdom
  • Ernst-Ludwig Winnacker, professor emeritus and director emeritus, Gene Center, Ludwig-Maximilians University, Munich Germany
  • Qi Zhou, professor and deputy director, Institute of Zoology, Chinese Academy of Sciences, Beijing China

Are babies from same-sex couples really possible?

Since Shinya Yamanaka reprogrammed first mouse and then human ordinary cells into powerful pluripotent stem cells, termed induced pluripotent stem (iPS) cells, back in 2006-2007 many new research avenues have opened up.

The impossible suddenly seemed a lot more possible with the report of iPS cells (aka IPSC). People started asking many more creative questions, The biomedical sciences now had more potential to make the seemingly impossible become reality.

One question that has come up: could same sex couples have their own biological children?

There’s been a lot of hype on this question in the media in the last week including these headlines and stories:

One article claimed that same sex parents could have their own biological offspring within 2 years. That’s just total baloney. However, in the long run within 1-2 decades this very well could be achieved. The excitement and over-exuberance in some cases with the media over this issue stems from recent work published in Cell from the labs of Drs. Azim Surani and Jacob Hanna on a more efficient way to produce human primordial germ cells (PGCs) via iPS cell-related methods.

Hanna was quoted thusly by Newsweek:

“This is very exciting biology,” says Dr Hanna. “We have succeeded in the first and most important step of the process, where we have reached the progenitor cell state for sperm and egg. We have not yet achieved mature sperm and eggs. So we are now focusing on completing the second half of this process.”

stem cell gametesThere’s no doubt that this is important work in this paper, but it’s a long, complicated road to get from the point A of the state of this research today to point B, where it could actually be used to produce human babies.

Still, what is so different now is that one can see a roadmap how to possibly get to that new reality.

Update: It’s also notable that Katsuhiko Hayashi and Mitinori Saitou have been able to produce living mice from stem cell-derived gametes (image above of method from one of their papers and another relevant paper to read; hat tip to Andrew Childs).

“It is probably a long way off, but it would be a way for people who have had treatment for conditions such as childhood leukaemia, which has left them infertile, to have children of their own,” Robin Lovell-Badge, head of stem-cell biology and developmental genetics at the National Institute for Medical Research, told The Sunday Times.”

I agree with Dr. Lovell-Badge on his view of this. Such technology could not only facilitate same sex couples have their own children (in the sense of genetically related to both parents), but also have a number of medical benefits such as tackling the general problem of infertility and more specifically allowing cancer patients who were treated with chemo to still have their own children later on in life as Dr. Lovell-Badge indicated. There’s great potential here even as we should be careful to note a realistic timeline and the health of children produced this way could be an issue.

IPS cell cloning

An additional cautionary note is needed as well related to cloning.

Unfortunately, there’s a ‘dual use issue’ here. This same kind of technology, if applied by some rogue scientists, could be used to clone human beings as well. This kind of technology could lead to both sperm and egg production from a single individual, which when followed by IVF, could in principle produce a human clone. See diagram above of how this could work with an individual male to be cloned (from Stem Cells: An Insider’s Guide). In theory this cloning method could work just as well with a woman too, but for male offspring somehow a Y chromosome would need to come into play. Even if it wouldn’t be easy to get this cloning to work, it might well work with enough money and effort. There are people out there who really want to clone themselves or others too so the motivation is there.

I’m not trying to freak people out, but this possibility of cloning is very possible in coming decades. It’s probably well past time for reproductive human cloning to be formally banned in the US. We still should allow therapeutic cloning of human ES cell lines. Realistically, given national politics, can we hope that politicians would be able to ban one kind of human cloning (reproductive) and still allow the other (therapeutic) to be legal in the US? I don’t know. Probably not any time soon.

As I said at the beginning of this article, amazing new things are possible that once seemed only in the realm of sci-fi, but with the good will also come some complicated baggage.

Big push for 3-parent technology in UK: some thoughts from the other side

3-parent babyA new piece came out yesterday on the Wellcome Trust Blog, strongly promoting approval of so-called “3-Parent IVF” or Mitochondrial Transfer technology by the UK Parliament.

As I written in the past (here and here), my view is that this would be a mistake at this time.

There is room for respectful disagreement on this issue between scientists, although I realize I’m up against some very prominent scientists including Drs. Peter Braude and Robin Lovell-Badge, whose past response to my open letter to the UK Parliament was one that I published on my blog here.

I believe in presenting both sides and I respect Drs. Braude and Lovell-Badge greatly.

The new Wellcome Trust blog piece includes a letter signed by a host of additional top scientists and other prominent figures encouraging parliamentary approval of 3-parent technology (see the letter at the bottom of this post).

This letter is signed by 5 Nobel Laureates and even some UK royalty.mito

Do I really want to be on the other side from those folks too?

Not really, but I need to call it like I see it and this is an important issue.

I seem to be one of the few scientists including stem cell scientists who will publicly say that I believe we need to learn a lot more about this technology before it is used on humans.

There is no doubt that mitochondrial diseases are truly terrible and need to be addressed, but if the potential outcomes from the technology are still vague, there are safety concerns, and it raises profound ethical issues such as changing the human genome heritably as is the case here, then my view is that a careful approach is both practical and logical. We cannot at this time have a reasonable expectation that this technology would be safe and effective. That may change in coming years with new knowledge. I hope so.

As strange as it may sound, although mitochondria have been studied for around 150 years, they remain in many ways still a new frontier for science with many mysteries. We are only now, for example, starting to understand how the mitochondrial genome works. There was just recently a very unexpected discovery that the mitochondrial genome produces thousands of potentially powerful non-coding RNAs with largely unknown functions. Nobody has any clue how these RNAs might behave in the context of mitochondrial transfer.

What else we will learn about mitochondria in coming years that is unexpected? I’d venture to say many mitochondrial surprises are still to come and there may well be things that we wish we knew in advance before we did human mitochondrial transfer. Science only has a very shallow depth of knowledge about mitochondria and new powerful genomics technologies are poised to change that quickly. I favor waiting until we learn more before we transfer mitochondria.

Still, since there are so many big name folks on the other side including many I greatly respect, could I be wrong?

Maybe.

Am I making a mistake publicly taking the other side?

Perhaps.

To be clear, I have no “iron in the fire” as the expression goes on this issue myself. I don’t work on this area of science or a competing area. It makes no practical difference to me whether the UK goes forward with mitochondrial transfer. If anything, my speaking out could be negative to me as I am taking what seems to be an unpopular, public stance.

The UK House of Commons will debate this issue this coming Tuesday, February 3rd.

Here’s the letter pushing for approval of this technology.

3-person technology letter