CRISPR-y critters: Cute pics of Cas9 gene edited animals

As CRISPR-Cas9 gene editing technology has advanced in the last few years, the number of genetically modified animals made with this system has steadily increased. Some are very interesting and useful for science.

At the same time especially when they are little, they can be very cute.


A nickname is going around for these CRISPR’d animals: CRISPR-y critters.

CRISPR pigsIt turns out that there used be a breakfast cereal called Crispy Critters. It had a very odd looking mascot named Crispy with fuzzy antennae and a voice like Jimmy Durante.

Ironically enough this cereal had some unusual animals in there including some that one might almost imagine were genetically modified. RFP bunny? CFP camel?

The mascot Crispy sure looks like some kind of GMO as well.

So what are the real and of course cutest CRISPR-y critters out there currently?

There are CRISPR-Cas9 edited pigs (see piglets the pic above) and these little guys have the bonus of also being clones.

Piglets are so cute!

Then we have the strange but hilarious, satirical cartoon of CRISPR below. It is illustrated with a focus on pork products.CRISPR bacon

The bacon is the DNA in question being targeted by the Cas9 and gRNA. I wish they had made the Cas9 into a knife though to go with the theme better.

This one gives a whole another somewhat disturbing twist to the crisp name here giving the involvement of potentially crispy bacon. Rhesus CRISPR

Efforts are also underway to make hornless cattle via CRISPR-Cas9 technology. This would actually be very significant because currently the horns have to be cut off apparently, which is pretty terrible.

CRISPR wormThen there are CRISPR’d primates including these super cute GM Rhesus monkeys above.

A CRISPR’d worm may not be seen as particularly cute by many, but I think it looks very cool nonetheless.

It still counts as a CRISPR-y critter too.

What else is out there?

There are CRISPR-y flies, rats, fish, and much much more including bunnies.CRISPR mouse

The little mousling (yeah, probably not the correct term, but sounds cute) shown below is adorable.

It is a founder from a CRISPR approach at the UC Irvine Transgenic Mouse Facility.

Talk about cute!

These animals have been made for scientific research to advance knowledge of development and disease. There are other possible reasons to make CRISPR-y critters too.

Given the advent and sale of the first GMO pets in the form of Glofish (not made with CRISPR), we can expect cute CRISPR-y critters to be coming to our homes in the future as pets.

What are your favorite CRISPR-y critters?

DIY human ‘upgrades’ via biohacking

Heritable human genetic modification has been the topic of the year so far, but another trend is edgy and interesting: non-heritable, but cutting edge forms of human modification that in some ways fall into the class of biohacking.


Biohackers are into do-it-yourself (DIY) forms of biology including self-modification.

Sure, people have been modifying themselves for thousands of years. Tattoos, hair changes, cosmetic surgery, tooth fillings and crowns, pacemakers and other medical implants. However, changing up one’s body has gone high-tech and DIY to include integration of the human body with computer chips for example (see image at right from here).

Meet Seth Wahle, who has an implant in his hand that allows him to hack your iPhone just by holding it. Wahle is a biohacker. According to a fun read piece by Rose Eveleth:

Wahle’s implant is an RFID chip, a tiny device that can hold small amounts of data and communicate with devices nearby.

The US military is very interested in high-tech implants of this kind for their soldiers, but biohackers bring it out into the wide world.

Some biohackers want to become cyborgs. See the above video, which is somewhat mind-boggling.

Biohacking can also involve garage-based or rented lab space-based biological experiments not involving oneself. Biohacking also intersects with the transhumanism movement, which seeks to promote the transcendence of humanity to a new, better plane where we are beyond human. Another element of transhumanism is self-editing where you change-up your own genetics via a kind of gene therapy.

I find biohacking to be very cool, but it also raises some possibly complicated ethical questions.

For example, if a friend were to make a type of mosquito in her garage that has firefly genes to make them glow in the dark so we can see them easier (before one bites us), and that friend releases (or there is accidental release of) the new type of mosquitos in fertile forms into the wild without any kind of regulatory approval, community notification, etc., what might happen?

Or she makes a fertile glow in the dark type of fish, which gets into a local stream or glowing birds fly out into the backyard trees?

If you think this kind of stuff couldn’t happen, you are mistaken.

Public polling on human genetic modification: mixed, but favor moratorium

Many of us scientists, ethicists, and legal scholars are working on educational outreach to the public on the potential use of gene editing technologies to genetically modify human beings, but clearly there’s a long way to go and much more to do on this front.Hart Poll CRISPR

The future use of CRISPR to edit the human genome in a heritable manner could be imminent or many years away, but clearly there is a move in that direction technologically and there are advocates of human modification such as some transhumanists and ethicists.

How does the public feel about all this?

A new Hart Research poll, “Public Attitudes Regarding New Technology for Editing DNA” provides a fresh look at public opinion. About six months ago, Pew did polling that suggested the public in the US was equally split on the idea of using genetic modification to try to prevent/cure genetic diseases, but there was strong opposition to the use for enhancement (e.g. designer babies). That poll also did not include the context of the concerns that have arisen in the last 4-5 months.

The new Hart poll is notable not only for its freshness (conducted May 14-17, 2015), but also for specifically talking about new technology, heritability, and asking about a potential moratorium.Hart Poll CRISPR Moratorium

Most people who took the poll were of mixed feelings, which I think makes good sense given that there’s not a lot of information out there on this yet for the public and there are both up and downsides to this technology.

Even when the pollsters pushed the “not sure” folks to include leaners, the respondents were still mostly of mixed opinions. Interestingly, this mixed sentiment overall reflects my sense of what many of us scientists are feeling too.

When asked about a moratorium on clinical use in humans, people answering the poll were generally supportive of a moratorium, which I think also is good common sense. There is a kind of “let’s hold off on taking this drastic step of genetically modifying people until we all can learn more and get more clarity” sentiment.

It’s not clear what the public feels about genetic modification of human embryos in the lab only with no clinical component.

This polling reinforces the idea that more engagement is needed and makes a case for more inclusion of the public in the dialogue on the use of CRISPR (or TALENs, etc.) in humans.

Hat tip to Antonio Regalado

Guest Post by Christopher Thomas Scott–The Great CRISPR Controversy: What’s Next?

Christopher Thomas Scott

Stanford Center for Biomedical Ethics

Director, Program on Stem Cells in Society


A decade ago I wrote an article in the journal Nature Biotechnology about the rise of a new gene editing technology called zinc finger nucleases (ZNF). It was one of those “drumbeat” discoveries: at the time, my sense was it would revolutionize how we deliver genes to cells and tissues, and profoundly change the way we think about gene therapy.

I was partially right. Although ZNFs are now well along in clinical trials for HIV, successive advances in precision gene editing now include transcription activator-like effector nuclease (TALENS), and most recently, clustered regularly interspaced short palindromic repeats (CRISPR-Cas9). Of the three methods, CRISPR-Cas9 has clear advantages. It’s cheaper, faster, more efficient, and can target multiple genes simultaneously.

CRISPR primatesRecently, experiments using the CRISPR-Cas9 system have provoked a firestorm of controversy, raising old fears about gene therapies and “designer babies.” Things began to heat up in 2014 when a Chinese team successfully used CRISPR-Cas9 to edit the germline of monkeys. Live, engineered monkeys were born (here’s a photo of the cute little guys). It was only a matter of time before someone attempted the system using a human embryo—doing controversial germline research.

In anticipation of that experiment, two recent essays in Science and Nature outlined policies for the use of precision germline editing. The scientists in each group are experts in ZFN (Nature) and CRISPR (Science) and also have commercial interests in companies developing the technology. In the papers, the authors describe the risks of human germline modification and the limitations of the technology, while promoting research that would better understand safety and efficacy, including off target effects. Both groups would ban using the technology to make babies, but are split on whether to continue research in the laboratory under existing ethical guidelines (Science = yes; Nature = no).

Just weeks after the essays appeared, a second Chinese team announced it had used CRISPR-Cas9 to edit non-viable (three sets chromosomes) embryos, a byproduct of vitro fertilization (IVF). The paper, published in a little known journal Protein & Cell, targeted a human disease. It modified the endogenous beta-globin gene (HBB): a mutated form of HBB causes Beta-thalassemia. Reportedly, the paper had been rejected at Science and Nature “in part because of ethical reasons.” The researchers reported three results: 1) low efficiency: only about half of the embryos were edited; 2) mosaicism: the embryo started dividing before all the cells were edited; and importantly, 3) significant numbers of off-target mutations. The last result is especially worrisome, because off-target problems plagued early gene transfer technologies, inserting genes into the genome in unintended places. For example, a wayward insertion could turn on a cancer-causing gene.

The paper made headline news and generated heated discussion. Media reports were very uneven—the main points of confusion being whether this experiment edited a viable human embryo (it did not), that the experiment was unethical (it appears to be conducted ethically), and that familiar problem at the intersection of science, technology and society: drawing conclusions that designer babies were at our doorstep (not anytime soon, if ever).

In my reading of things, the current controversy centers on:

1) Whether experiments like the Protein & Cell paper should be permitted; 2) the reasoning (ethical? scientific? both?) behind Nature and Science’s rejection of the paper; 3) the speed of the peer-review (at only two days, some believe that the paper was rushed to press); 4) the defense of publishing the paper by the journal’s editor-in-chief (see the quote below and definitely worth a read); and most recently, 5) whether the research was important (scientists are divided on this point).

CRISPR embryo paper editorial

Where does this leave us?  The experiment appears to be ethically sound. The Chinese group used non-viable embryos and disclosed the research had an ethical review. The group was clearly addressing the need for “further research” and the rationale for the study centers on safety and efficacy. The editors’ reasons for publishing the paper, though late in the process and quite interesting, seem reasonable.

More public discussion will attempt to sort these questions out. Along these lines, I recently participated in a panel discussion at Stanford with Hank Greely, Lynn Westphal, Paul Knoeplfer, and Marcy Darnovsky (Paul’s excellent summary of the panel can be found here). The biggest question I took home from our panel is “what now”? Should we allow laboratory germline-editing research to go forward? I think we should. The technology could help scientists uncover problems behind infertility or reveal insights into failures of early human development. Scientists are divided on the issue whether the Protein & Cell paper was important or groundbreaking. This raises the question whether journals should publish controversial research just to demonstrate the technical feat, rather than research that moves science ahead in meaningful and important ways. Other interesting questions include the obligations of researchers and journal editors to explain the ethical and social significance of the research they publish—in my view, the Protein & Cell example laid bare how far we have to go to clearly justify why this research is important, and how deeply we have thought through the ethical and social implications of human germline research. On this last topic, stay tuned for a commentary I’ve written with a Stanford researcher, Arun Sharma, in the June issue of Nature Biotechnology. The next few months will be interesting times for scientists and policymakers as they attempt to sort these questions out.

Report from Stanford Event: Human Germline Modification: Medicine, Science, Ethics, & Law

Greely_HankLast Thursday I participated in a meeting at Stanford Law School on human germline genetic modification hosted by Hank Greely (pictured at left), Professor of Law and Genetics at Stanford.

The meeting was entitled, “Human Germline Modification: Medicine, Science, Ethics, and Law”. The panel included in addition to Hank and me, the following speakers: Marcy Darnovsky, Executive Director of the Center for Genetics and Society (CGS); Christopher (Chris) Thomas Scott, Stanford Center for Biomedical Ethics, and Lynn M. Westphal, Professor of Obstetrics and Gynecology, Stanford University Medical School.

We each spoke for about 10-15 minutes, followed by a rousing discussion with the audience of about 50 people and between us panelists. The audience asked great questions. The meeting was videotaped and hopefully in the future that video will become available at which time I will either embed here or do a fresh blog post.MarcyDarnovsky_2012

I’m just going to blog here focusing on my impressions of the meeting and I’m in no way speaking for the other panelists. I hope that if they have other ideas about how the meeting went or their own views in response to my post that they will weigh in as well. I want to thank Hank for the invitation to participate and the other panelists for a great meeting. I came away having learned some important new things and with a broader perspective on human embryo editing.

Part of what made this meeting so interesting to me was the wide range of views on human  modification of the participants and the audience. My sense was that Marcy (picture above right) has the strongest concerns about heritable human genetic modification amongst us speakers. CGS, her organization, just last week I think outlined 7 reasons on their website to “just say no to human genetic modification” and she articulated some of her concerns at the meeting. I share some of her concerns, but don’t feel quite as strongly about human embryo editing and I favor allowing in vitro research under some conditions. Marcy and I also disagreed on whether human germline modification is inevitable. I think it is, while she doesn’t. I got the sense that she is concerned that talk of inevitability could discourage efforts to restrict the technology.

Christopher Thomas ScottOn the other side, it seemed to me that Lynn was perhaps more open to the possibility of modification being used in the future if deemed safe, particularly if it could help infertile couples have their own genetically related children. I found it very interesting to hear about Lynn’s experience as a physician on the medical frontline interacting with couples dealing with infertility or genetic problems including mitochondrial disorders. In communicating with Chris afterwards he mentioned that he was struck by the way in which Lynn indicated that there could well be pressures from patients for therapeutic embryo editing. My sense too was that Lynn wouldn’t be shocked if clinical application of human editing technology was eventually attempted by fertility doctors.

Hank and Chris seemed relatively less concerned than Marcy about human germline modification overall and more confident that it can be regulated appropriately. Chris, pictured above left, also did an excellent job explaining the science behind CRISPR and highlighting what makes it so important and unusual compared to past technologies. Like Chris, I’m more inclined to let some in vitro research (conduced with appropriate ethical and institutional approval and oversight) on human germline modification proceed (see my ABCD plan) and I got the sense that is Hank’s view as well. But there should be a compelling, logical rationale for doing the work in embryos rather than cells.

My impression was that we all could agree that for dealing with most genetic disorders preimplantation genetic diagnosis (PGD) would be far preferable to trying to make a genetic correction in a human embryo.

Hank pointed out three scenarios where PGD likely wouldn’t work to correct a problematic genetic situation and hence gene editing could be needed:

  • 1. Dominant genetic disease with one parent being homozygous
  • 2. Both parents have some kind of mutation in the same gene
  • 3. Certain kinds of mitochondrial disease

I know a lot of people have been trying to think through possible situations where gene editing might be needed and PGD wouldn’t solve a particular problem so it was great to hear Hank articulate how these three fit into that category. Hank and others mentioned how these would be very rare circumstances, but not entirely unheard of so in principle at least there could be a unique role for editing over PGD in humans if proven safe and effective. It is also possible that some rare sex-linked disorders could not be resolvable by PGD.Lynn M. Westphal

Lynn, pictured at right, also added in importantly I thought that for some couples there are so few embryos that PGD is unlikely to work to find one lacking a mutation. I wondered aloud: how many human embryos might take to get CRISPR to work for editing too? It might take quite a few.

We had a good discussion of the example of potential genetic modification of a human embryo for the correction of a BRCA1 breast/ovarian cancer-associated gene mutation. It was pointed out by several that this mutation is not a “causal” mutation in the sense of always leading to disease, but only a predisposition to disease.

If it were decided that human editing for BRCA1 is acceptable, then I suggested that other weaker genetic predispositions might be considered legitimate as well. This could create somewhat of a gray area whereby human genetic modification becomes considered appropriate simply for predispositions including some that might be viewed as only moderate such as say a 30% increased risk of Alzheimer’s or cognitive disability in children. There’s could end up being a bit of blurring there where we could see enhancements occurring too. I felt that there wouldn’t always been a clear, bright line between medical use and enhancements with human germline editing.

I thought Chris raised some great points about issues related to scientific publishing and human germline modification. Why did the journal Protein & Cell, which published the first human embryo editing paper just a few weeks ago, only come out with an editorial days later explaining why they decided to publish the paper rather than having an editorial accompanying the actual research article? To me it definitely seemed reactionary and in response to critical questions raised about the embryo editing paper rather than with forethought about how it would be important to place this publication in an appropriate context right from the beginning.

Chris also pointed out that a key question still open for debate is whether this embryo editing paper should have been published at all. To me it seems like not a whole lot was gained specifically by doing this CRISPR’ing in actual human embryos rather than cell lines.

Some of the questions from the audience included asking about how human modification might change the relationship between parents and children as well as how commercialization could impact the evolution of human editing via CRISPR-Cas9. Another point that came up during the discussion was the concern over potential strong negative impact of gene editing of animals (not humans) either for us as novelty pets or in the wild.

Overall it was a wonderful, very useful meeting that advanced the discussion of human modification forward. I hope that these types of meetings continue and that there is more discussion of this kind involving diverse stakeholders as well as the public.