Tag Archives: #arseniclife

Immune to CRISPR?

I guess if you’re going to use bacteria as part of your gene editing technology (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9) then, you might half expect the body’s immune system may have developed some defenses. A Jan. 9, 2018 article by Sarah Zhang for The Atlantic provides some insight into what the new research suggests (Note: Links have been removed),

2018 is supposed to be the year of CRISPR in humans. The first U.S. and European clinical trials that test the gene-editing tool’s ability to treat diseases—such as sickle-cell anemia, beta thalassemia, and a type of inherited blindness—are slated to begin this year.

But the year has begun on a cautionary note. On Friday [January 5, 2018], Stanford researchers posted a preprint (which has not been peer reviewed) to the website biorXiv highlighting a potential obstacle to using CRISPR in humans: Many of us may already be immune to it. That’s because CRISPR actually comes from bacteria that often live on or infect humans, and we have built up immunity to the proteins from these bacteria over our lives.

Not all CRISPR therapies in humans will be doomed. “We don’t think this is the end of the story. This is the start of the story,” says Porteus [Matthew Porteus, a pediatrician and stem-cell researcher at Stanford]. There are likely ways around the problem of immunity to CRISPR proteins, and many of the early clinical trials appear to be designed around this problem.

Porteus and his colleagues focused on two versions of Cas9, the bacterial protein mostly commonly used in CRISPR gene editing. One comes from Staphylococcus aureus, which often harmlessly lives on skin but can sometimes causes staph infections, and another from Streptococcus pyogenes, which causes strep throat but can also become “flesh-eating bacteria” when it spreads to other parts of the body. So yeah, you want your immune system to be on guard against these bacteria.

The human immune system has a couple different ways of recognizing foreign proteins, and the team tested for both. First, they looked to see if people have molecules in their blood called antibodies that can specifically bind to Cas9. Among 34 people they tested, 79 percent had antibodies against the staph Cas9 and 65 percent against the strep Cas9.

The Stanford team only tested for preexisting immunity against Cas9, but anytime you inject a large bacterial protein into the human body, it can provoke an immune response. After all, that’s how the immune system learns to fight off bacteria it’s never seen before. (Preexisting immunity can make the response faster and more robust, though.)

The danger of the immune system turning on a patient’s body hangs over a lot of research into correcting genes. In the late 1990s and 2000s, research into gene therapy was derailed by the death of 18-year-old Jesse Gelsinger, who died from an immune reaction to the virus used to deliver the corrected gene. This is the worst-case scenario that the CRISPR world hopes to avoid.

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

Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans by Carsten Trevor Charlesworth, Priyanka S Deshpande, Daniel P Dever, Beruh Dejene, Natalia Gomez-Ospina, Sruthi Mantri, Mara Pavel-Dinu, Joab Camarena, Kenneth I Weinberg, Matthew H Porteus. bioRxiv posted January 5, 2018 doi: https://doi.org/10.1101/243345

This article is a preprint and has not been peer-reviewed …

This preprint (not yet published paper) is open access and open for feedback.

Meanwhile, the year of CRISPR takes off (from a January 10, 2018 American Chemical Society news release on EurekAlert),

This year could be a defining one for CRISPR, the gene editing technique, which has been hailed as an important breakthrough in laboratory research. That’s because the first company-sponsored clinical studies will be conducted to see if it can help treat diseases in humans, according to an article in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society.

C&EN Assistant Editor Ryan Cross reports that a big push is coming from industry, specifically from three companies that are each partly founded by one of the three inventors of the method. They are zeroing in on the blood diseases called sickle-cell anemia and β-thalassemia, mostly because their precise cause is known. In these diseases, hemoglobin doesn’t function properly, leading to severe health issues in some people. Crispr Therapeutics and Intellia Therapeutics plan to test the technique to boost levels of an alternative version of healthy hemoglobin. Editas Medicine, however, will also use CRISPR to correct mutations in the faulty hemoglobin gene. Labs led by university researchers are also joining the mix, starting or continuing clinical trials with the approach in 2018.

Because CRISPR is being used to cut a cell’s DNA and insert a new sequence, concerns have been raised about the potential for accidents. A cut in the wrong place could mean introducing a new mutation that could be benign — or cancerous. But according to proponents of the method, researchers are conducting extensive computer predictions and in vitro tests to help avoid this outcome.

The January 8, 2018 Chemical and Engineering News (C&EN) open access article by Ryan Cross is here.

Finally, if you are interested in how this affects research as it’s being developed, there’s University of British Columbia researcher Rosie Redfield’s January 16, 2018 posting on RRResearch blog,

Thursday’s [January 11, 2018] post described the hypothesis that bacteria might use gene transfer agent particles to inoculate other cells in the population with fragments of phage DNA, and outlined an experiment to test this.  Now I’m realizing that I need to know a lot more about the kind of immunity I should expect to see if this GTA-as-vaccine hypothesis is correct.

That should give you some idea of what I meant by “research as it’s being developed.” Redfield’s blog is not for the mildly interested.

Redfield is well-known internationally as being one of the first to refute research which suggested the existence of an ‘arsenic bacterium’ (see my Dec. 8, 2010 posting: My apologies for arsenic blooper. She’s first mentioned in the second excerpt, second paragraph.) The affair was known online as #arseniclife. There’s a May 27, 2011 essay by Carl Zimmer on Slate titled: The Discovery of Arsenic-Based Twitter: How #arseniclife changed science.

Rosie Redfield talks #arseniclife at Vancouver’s Café Scientifique tonight (April 24, 2012)

Rose Redfield seems to be everywhere in Vancouver these days. Last week (April 19, 2012) she spoke at the first ScienceOnline Vancouver Event and tonight she’s at Café Scientifique at the Railway Club, 579 Dunsmuir St. (second floor) at 7:30 pm.

Here’s the event description straight from the news release,

Our speaker for the evening will be Dr. Rosie Redfield, the biologist from UBC who was recently named one of the “10 People Who Mattered” in 2011 by Nature magazine. (http://www.nature.com/news/365-days-nature-s-10-1.9678 ).

The title and abstract for her café is:

#arseniclife and Open Science
The #arseniclife story started with a bang in late 2010, when NASA proudly announced the discovery that some bacteria could synthesize their DNA with arsenic in the backbone in place of phosphorus. But within a few days it all fell apart, as scientists used blogs and Twitter to conduct impromptu ‘post-publication peer review’. (‘#arseniclife’ is the Twitter hashtag used to identify relevant tweets.) Working with collaborators at Princeton, my lab has now shown that the key results cannot be replicated. This debacle has implications for many aspects of science, from how personal biases and funding sources affect scientific judgment to the increasing roles of social media in both the practice and public communication of science.

I hope she’s addressed that problem with overmodulation that I described in my comments about last week’s ScienceOnline Vancouver event (my April 20, 2012 posting) because she’s very interesting.

For anyone not familiar with the #arseniclife story, here’s my Dec. 8, 2012 apology  posting about it (with links to other more informed writing) and my blooper Dec. 6, 2010 posting.

Comments on ScienceOnline Vancouver’s first event

Bravo to the organizers, Catherine Anderson, Sarah Chow, and Peter Newberry of Vancouver’s (Canada) first ScienceOnline event last night (Thursday, April 19, 2012 first mentioned my April 4, 2012 posting). They attracted, by my count,  a crowd of about 75-80 people. A free event held at Science World, there were three speakers Rosie Redfield, Lisa Johnson, and Anthony Floyd. Here’s a bit more about them from the event description page,

  • Rosie Redfield – Named Nature’s most influential person of 2011, this associate professor of microbiology at UBC [University of British Columbia] hit science fame through her blog RRResearch disputing NASA’s claim life exists in arsenic.
  • Lisa Johnson – Multiplatform journalist with a keen interest in environment and science stories. She enjoys digging, storytelling, and finding context in breaking news.
  • Anthony Floyd – aerospace research engineer with a PhD in Civil Engineering from UBC. Although strictly a digital immigrant, Anthony grew up with technology as technology grew up. He is quite active in social media. Anthony’s a proud dad to two boys, year-round bike commuter, opinionated political observer, and Maritimer-in-exile.

The event was titled, Where do you get your science? It was the third event I attended yesterday so maybe I was a little less tolerant than I can be. I was expecting a lively discussion about finding science what I got was Redfield and Johnson talking about the arsenic life story and their roles in that story locally and, in Redfield’s case, internationally. The only one who really talked about finding science online was Floyd.

I’m not sure if the organizers were hoping that the ‘arsenic life’ stories would somehow tie into the topic or if the two speakers just went off on their own tangents.

Redfield gave an ‘ignite’ talk, which is five minutes long with 20 slides in a timed slideshow where the speaker has to keep time with the slides. I’m sorry to say she overmodulated (used the storytime voice usually aimed at an audience of five-year olds)  for much of the talk. Johnson made the point several times that it wasn’t her fault that the story was wrong. She did admit at one point that she could have dug more deeply and, in fact, someone suggested that she talk to Rosie Redfield for advice about this story at very early stage, something she failed to do. Most valuable to me was the reminder of the constraints that journalists are under.

Note: I, too,  got caught up with my Dec. 6, 2010 posting and I subsequently apologized, Dec. 8, 2010 posting.

Floyd, as I noted earlier, did address the question, Where do you get your science?, although he did ask his audience to make a bit of a leap when he used a story about searching for information about bicycle helmets and bylaws to illustrate one of his points.

I wasn’t able to stay for the more informal discussion after the speakers finished but the organizers  did manage a good icebreaker exercise at the beginning. The audience seemed mostly to be mostly in their 20s and 30s.

It was a very technology-heavy event in that there was livestreaming, multiple computers and screens, references to tweeting and Storify, etc.

Aside: All three of the events I attended yesterday had technology issues of one kind or another. I’m not especially happy when almost all of the attention is on the technology while the live audience is left waiting or is interrupted during question period to accommodate a tweet or has to endure feedback.

I did mention Storify, the ScienceOnline Vancouver Storify ‘story’ is here and you can check #sovan on Twitter for other responses to last night’s event.

All in all, it was a very promising start, despite my nitpicks.

Sick and tired of the ‘social media is changing how science is practiced’ narrative

The whole ‘social media is changing ______’ puzzles me. You can fill in the blank with science/government/social relationships/etc. It’s always the same notion. Somehow social media is engendering changes the like of which we’ve never seen before.

  • The February 2011 overthrow of Mubarak in Egypt was all due to social media, as is the current social unrest in many Middle Eastern Countries.
  • Social relationships are being negatively impacted (nobody talks to anybody else anymore or it’s opening new avenues for relationships)
  • The practice of science is being changed by the use of social media.
  • etc.

Mostly I’m concerned with the one about science since I recently ended up on a panel where the discussion turned on this topic. I think there are a lot of things having an impact on how science is practiced and trying to establish the role social media is playing, if any, is a little premature.

We had Rosie Redfield on the panel. Rosie is a professor at the University of British Columbia who was part of the ‘arsenic life’ story that took the internet by a storm in late November/early December 2010. (Confession: I got caught up in the excitement in my Dec. 6, 2010 posting and recanted in my Dec. 8, 2010 posting.) Recently, there’s been a story about ‘arsenic life’ by Carl Zimmer for Slate magazine titled, How #arseniclife changed science. Here’s Zimmer’s set up (from the Slate article),

On November 29, NASA announced that it would soon hold a press conference to “discuss an astrobiology finding that will impact the search for evidence of extraterrestrial life.” Wild speculation ran amok—perhaps scientists had found living things on one of Saturn’s moons. At the press conference, the scientists did not unveil an actual extraterrestrial, but they did have big news. A new paper had just been published in the journal Science, they said, which described bacteria that seemed able to build their own DNA from arsenic. If that were true, it would be an historic discovery, because no such ability has ever been found among Earth’s life-forms.

The paper was published online in late November and attracted a great deal of discussion and criticism almost immediately on blogs (Rosie Redfield’s RRResearch amongst them) and on twitter via the hash tag topic, #arseniclife. The print version of the paper, along with critical letters, will appear in the June 3, 2011 issue of Science.

Here’s Zimmer’s take on what makes this particular scientific dust-up different,

For those of us who have been tracking #arseniclife since last Thanksgiving, however, today comes as an anticlimax. There’s not much in the letters to Science that we haven’t read before. In the past, scientists might have kept their thoughts to themselves, waiting for journals to decide when and how they could debate the merits of a study. But this time, they started talking right away, airing their criticisms on the Internet. In fact, the true significance of the aliens-that-weren’t will be how it helped change the way scientists do science.

Zimmer goes on to describe this new practice,

Redfield and her colleagues are starting to carry out a new way of doing science, known as post-publication peer review. Rather than leaving the evaluation of new studies to a few anonymous scientists, researchers now debate the merit of papers after they have been published. The collective decision they come to stays open to revision.

Post-publication peer review—and open science in general—is attracting a growing number of followers in the scientific community. But some critics have argued that it’s been more successful in theory than in practice. The #arseniclife affair is one of the first cases in which the scientific community openly vetted a high-profile paper, and influenced how the public at large thought about it.

Post-publication peer review existed before social media as per ‘cold fusion’ (Wikipedia essay). I remember it because I wasn’t particularly interested in science at the time but this was everywhere and it went on for months. There was the initial excitement and enthusiasm (the ‘cold fusion’ scientists were featured on the cover of Times or Newsweek or maybe both in the days when those magazines were powerhouse publications). Then, as the initial enthusiasm died down, the storm of scientific criticism started (those other scientists may not have had social media but they made themselves felt). The story took place over eight to 10 months and achieved public awareness in a way that scientists can only fantasize about these days.  By comparison, the arsenic story blew up and disappeared from public consciousness within roughly two weeks, if that.

Social media may yet change how science is practiced but I wouldn’t use Zimmer’s story about #arsencilife to support that belief, in fact, I think it could support another idea altogether.

The ‘arsenic’ story was, by comparison, with ‘cold fusion’ greatly truncated and most members of the public never really heard about it and, as a consequence, were not exposed to the furious debate and discussion as they were with  ‘cold fusion’.  They did not get exposed to how science ‘really works and therein lies a problem because they did not see the uncertainties, the mistakes, and revised ideas.

As for what factors may be having an impact on scientific practice, I’d suggest reading Identifying good scientists and keeping them honest on The Black Hole blog by David Kent. Here’s an excerpt,

In a February 2011 interview with Lab Times, Cambridge scientist Peter Lawrence1 reflects on his own career and complains that “the heart of research is sick” as he charts the changes in the way in which science is pursued.  Briefly, he cites impact factors and the increased need to assign metrics to scientists (# of publications, H-index, etc) as main drivers of producing low quality research and unfairly squeezing out some good scientists who do not publish simply for the sake of publishing.  Impact factor fever runs deep throughout laboratories but, most damagingly, exists at the funding agency and university administrative level as well.

ETA June 17, 2011: For anyone who’d like to read some updated and contrasting discussion about the #arseniclife aftermath for scientific practice and science education there are two June 16, 2011 guest posts for Scientific American, one from Rosie Redfield and the other from Marie-Claire Shanahan. Plus, if you are interested in more details about the cold fusion story and the role electronic communication played, check out Marie-Claire Shanahan’s post,  Arsenic, cold fusion and the legitimacy of online critique, on the Boundary Vision blog.