UC Davis CRISPR Mtg: Vital Role of Language in CRISPR

Here is another of my blog posts from yesterday’s CRISPR ethics, science, and policy symposium held here at UC Davis.

You can read the others here, here, and here.

Note as with the other posts, since I was taking notes as listening and on the fly, this post is a stream of consciousness on what the speakers said so it is rough and there are some fragments.
Michael Zerbe, UC Davis CRISPR

The next panel at the UC Davis CRISPR meeting included these speakers: Michael J. Zerbe, PhD, York College of Pennsylvania, Sarah Perrault, PhD, University Writing Program, UC Davis, Meaghan O’Keefe, PhD, Department of Religious Studies, UC Davis with Moderator: Jodi Halpern, MD, PhD, UC Berkeley.

Sarah started the panel discussing CRISPR metaphors. We use metaphors to help explain something unfamiliar using something familiar such as the editing metaphor. The metaphors and language that we use to frame discussion of CRISPR can have a strong impact. Sarah and some of my other UC Davis colleagues published an excellent piece on the metaphor of “gene editing” in AJOB, which I highly recommend, and this paper was discussed at the meeting. Sarah and I both graduated from Reed College. Hearing Sarah’s talk now sort of took me back to Reed in a way in terms of the eloquent and powerful language. She reminds me of some of my wonderful Reed professors.

Michael spoke next. He is as Associate Professor English so that brought a unique, valuable perspective. He discussed the language of CRISPR with a title of “DNA as language.” or protolanguage.  He cited the “CRISPR Heroes” article by Lander and CRISPR, The Disruptor article in Nature.

He proposed a double major idea, such as in English (or history, etc.) and Biology. Why the separation of “The Two Cultures”? DNA is a language, not a code. The body is the text. It’s clear that he doesn’t like “editing” as a metaphor. Why? He mentioned one reason as being that editing also implies there are authors and experts.

When he said, “We don’t have native speakers of DNA” that kind of hit home. He also said that learning DNA is like learning Klingon. Finally, he asked, “How will we know when we become fluent in DNA?”

FYI: I’m going to do a separate post on another one of Michael’s most provocative points as I think it deserves more depth. Stay tuned.

Meaghan spoke next. She talked about The Cannon of Invention. She asked about all those who could be affected by CRISPR and she argued that we need to ask expansive questions. Further we need structured pragmatic ways of asking questions with CRISPR.

As someone myself who has in the past couple years publicly asked a lot of questions about CRISPR policy, Meaghan’s talk got me thinking about how sometimes when I have asked such questions, certain parties didn’t like it and have even in some cases let me know that. There’s pushback on that kind of rigorous questioning of dogma and language about CRISPR and other scientific trends. It’s not always easy being the one asking the questions.

Overall I thought this was an outstanding panel with great contributions from each participant and a nice Q&A afterwards.

UC Davis CRISPR Meeting Panel: A View from the Trenches on Human Disease

The second session at our CRISPR meeting was really powerful.

As with other posts from the UC Davis CRISPR meeting, since I was taking notes on the fly during this session, this post is a stream of bits from the different talks, often trying to capture the essence of key questions or ideas as the speakers talked so forgive the format.

Overall from this session, the potential future somatic-gene therapy kind of use of CRISPR for catastrophic, fatal diseases such as Huntington’s Disease is something that needs special attention and discussion. More data is needed to know how this will play out.

CRISPR meeting panel

Jacob Corn is a pioneering CRISPR scientist at IGI at Berkeley. I thought it was really cool that he passed a model of CRISPR-Cas9 around for audience. He made the analogy that what we are doing as a field is kind of like driving a car while still working on the car. It was striking when he pointed out the massive increase in publications on CRISPR-Cas9 going from 1 original paper in something like a year to start to now an average of 6 papers per day.CRISPR Model Jacob Corn

Kyle Fink. Kyle is a Huntington’s Disease (HD) researcher here at UC Davis, focusing on genetic approaches to HD including using CRISPR for somatic targeting. He gave an overview of HD and discussed targeting CAG repeats. A team could target the mutant HD DNA, RNA or the toxic protein itself. Targeting DNA could be more effective. Can we truncate the CAG repeats with CRISPR or other similar methods? Or could we silence the expression of the mutant allele specifically. We could use a combo of stem cell and gene therapy. I was impressed by the work he’s doing.

Vicki Wheelock. Dr. Wheelock is a UC Davis physician who cares for HD patients and also conducts research. She provided a very powerful perspective. HD manifests earlier than other neurodevelopmental diseases, typically in 30s and 40s at the peak of life. There are 30,000 cases in the US, but ripple effect affects a lot more people negatively. HD has many, diverse, and often tragic symptoms via the striatum being injured in HD. All treatments are now palliative. Stem cell therapies bring hope for replacement therapy such as MSCs with BDNF (which is taken out by HD). Another example is anti-sense oligo (ASO), which is the basis of a trial via spinal taps in Canada now. But ASO is not specific to mutant HD allele so need data on safety. She highlighted the huge unmet need. I learned something else new about HD in this talk in that HD families went underground during the eugenics movement. There is a stigma, but fortunately that is decreasing. Still a need for other new technologies such as CRISPR.

Judy Roberson. Judy is a wonderful patient advocate for the HD community for over 20 years and has served for 5 years on an FDA advisory panel. She was the first voting HD advocate on that panel. Part of the title of her talk was “HD: The Perfect First Model for CRISPR.” She gave a very moving talk.

She talked about how HD hit her family like a ton of bricks. Her MIL was affected in 30s. Took a long time for diagnosis and died at age 55. She and her husband Tim have 4 children. Tim’s brother Joe died of HD at 52. Judy’s husband was diagnosed at 39 and died in his early 50s. People with HD are often underground and there are worries about genetic discrimination. The stigma remains.

Judy talked about the unique HD program at UC Davis that has more than 500 patients. Some patients move here to be part of the program.

I was impressed with her guts and bluntness. For instance, she criticized the FDA for a number of reasons including lack of listening to patients and their overly conservative approach.

She also had some words for CIRM. “I love CIRM”, she said, but they urgently need some changes including more transparency and more of a role for patient advocates at each step. Judy wrapped up by invoking CRISPR as a “magic scissors” to tackle the mutant HD allele.

The panel also answered questions after they each spoke. For instance, I asked them about the potential use of CRISPR in human embryos to prevent HD.

UC Davis CRISPR Meeting: Big Picture from Ben Hurlbut

The CRISPR meeting has started off wonderfully with a talk by Ben Hurlbut. His talk was entitled, “The Demands of CRISPR’s World: Imagination, Deliberation and Governance”. Since I took notes and listened this post is somewhat freeform.

I liked how Ben asked a lot of questions.

What is “CRISPR’s world” as Science Magazine called it?

How do we want to use the capability of CRISPR?

Ben made a comparison to nuclear physics and the development and use of atomic bombs. He quoted throughout his talk the words of Robert Oppenheimer as well with great effect.

Oppenheimer quote

Ben talked about David Baltimore’s words from the National Academy of Sciences D.C. Summit of Human Gene Editing. He quoted Baltimore that “we are initiating the process of taking responsibility”, but who is this “we” that makes the decisions and takes the responsibilities?

Who gets to imagine the future?

He said that predicting risk is one way to imagine the future.

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Blogging UC Davis CRISPR Science & Bioethics Meeting

There’s a great meeting going on today here at UC Davis starting soon on CRISPR, focused on the intersection of the science with bioethical and legal issues.

CRISPR meeting UC Davis

I’ve been helping to organize this meeting, but kudos and thanks go to my colleague Mark Yarborough who took the lead in organizing the meeting and did most of the work.

I’m hoping as time permits to do a few semi-live blog posts on the meeting as it goes along. If things are too busy, I will blog over the weekend or early next week on it, but I’m hoping to do some today.

We have a wonderful line up of speakers. I’ve placed a screenshot of the top of the flyer in this post.

Stay tuned!

NgAgo a-go-go: top 5 bullet points on upstart CRISPR challenger

NgAgoThe gene editing technology CRISPR has been arguably the top story in the biomedical world in the last two years, but going forward there is a CRISPR challenger in upstart gene editing technology NgAgo.

For more background on NgAgo and the key first published paper on its genetic modification characteristics see my post here. 

In the comments on that post and in discussions I’ve had with other researchers, some key points have crystalized on NgAgo versus CRISPR at this time. As a possible CRISPR challenger, how does NgAgo fare?

Broader possible applicability. The lack of a PAM site requirement for NgAgo means it is almost certain that for some specific gene editing applications, NgAgo will work and CRISPR won’t. Design of NgAgo guides seems to be a simpler matter too because no PAM is needed (more on guides below). In that first NgAgo paper they reported effective editing of 8 different genes with good efficiency so it’s unlikely there is a strongly required DNA sequence context needed for NgAgo. However, it is still formally possible that NgAgo in some contexts will have some kind of preference for certain DNA sequences.  Further study will help resolve this more concretely, but so far this is looking like a major plus for NgAgo.

DNA guides should be a lot easier. The use of DNA-based guides will make gene editing easier as opposed to RNA-based guides. At the very least you eliminate a cloning step and you can just order oligos, which you can phosphorylate in your lab to use as guides by transfection.

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