Tag Archives: CRISPR

Xenotransplantation—organs for transplantation in human patients—it’s a business and a science

The last time (June 18, 2018 post) I mentioned xenotransplantation (transplanting organs from one species into another species; see more here), it was in the context of an art/sci (or sciart) event coming to Vancouver (Canada).,

Patricia Piccinini’s Curious Imaginings Courtesy: Vancouver Biennale [downloaded from http://dailyhive.com/vancouver/vancouver-biennale-unsual-public-art-2018/]

The latest edition of the Vancouver Biennale was featured in a June 6, 2018 news item on the Daily Hive (Vancouver),

Melbourne artist Patricia Piccinini’s Curious Imaginings is expected to be one of the most talked about installations of the exhibit. Her style of “oddly captivating, somewhat grotesque, human-animal hybrid creature” is meant to be shocking and thought-provoking.

Piccinini’s interactive [emphasis mine] experience will “challenge us to explore the social impacts of emerging biotechnology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.”

Piccinini’s work will be displayed in the 105-year-old Patricia Hotel in Vancouver’s Strathcona neighbourhood. The 90-day ticketed exhibition [emphasis mine] is scheduled to open this September [2018].

(The show opens on Sept. 14, 2018.)

At the time, I had yet to stumble across Ingfei Chen’s thoughtful dive into the topic in her May 9, 2018 article for Slate.com,

In the United States, the clock is ticking for more than 114,700 adults and children waiting for a donated kidney or other lifesaving organ, and each day, nearly 20 of them die. Researchers are devising a new way to grow human organs inside other animals, but the method raises potentially thorny ethical issues. Other conceivable futuristic techniques sound like dystopian science fiction. As we envision an era of regenerative medicine decades from now, how far is society willing to go to solve the organ shortage crisis?

I found myself pondering this question after a discussion about the promises of stem cell technologies veered from the intriguing into the bizarre. I was interviewing bioengineer Zev Gartner, co-director and research coordinator of the Center for Cellular Construction at the University of California, San Francisco, about so-called organoids, tiny clumps of organlike tissue that can self-assemble from human stem cells in a Petri dish. These tissue bits are lending new insights into how our organs form and diseases take root. Some researchers even hope they can nurture organoids into full-size human kidneys, pancreases, and other organs for transplantation.

Certain organoid experiments have recently set off alarm bells, but when I asked Gartner about it, his radar for moral concerns was focused elsewhere. For him, the “really, really thought-provoking” scenarios involve other emerging stem cell–based techniques for engineering replacement organs for people, he told me. “Like blastocyst complementation,” he said.

Never heard of it? Neither had I. Turns out it’s a powerful new genetic engineering trick that researchers hope to use for growing human organs inside pigs or sheep—organs that could be genetically personalized for transplant patients, in theory avoiding immune-system rejection problems. The science still has many years to go, but if it pans out, it could be one solution to the organ shortage crisis. However, the prospect of creating hybrid animals with human parts and killing them to harvest organs has already raised a slew of ethical questions. In 2015, the National Institutes of Health placed a moratorium on federal funding of this nascent research area while it evaluated and discussed the issues.

As Gartner sees it, the debate over blastocyst complementation research—work that he finds promising—is just one of many conversations that society needs to have about the ethical and social costs and benefits of future technologies for making lifesaving transplant organs. “There’s all these weird ways that we could go about doing this,” he said, with a spectrum of imaginable approaches that includes organoids, interspecies organ farming, and building organs from scratch using 3D bioprinters. But even if it turns out we can produce human organs in these novel ways, the bigger issue, in each technological instance, may be whether we should.

Gartner crystallized things with a downright creepy example: “We know that the best bioreactor for tissues and organs for humans are human beings,” he said. Hypothetically, “the best way to get you a new heart would be to clone you, grow up a copy of yourself, and take the heart out.” [emphasis mine] Scientists could probably produce a cloned person with the technologies we already have, if money and ethics were of no concern. “But we don’t want to go there, right?” he added in the next breath. “The ethics involved in doing it are not compatible with who we want to be as a society.”

This sounds like Gartner may have been reading some science fiction, specifically, Lois McMaster Bujold and her Barrayar series where she often explored the ethics and possibilities of bioengineering. At this point, some of her work seems eerily prescient.

As for Chen’s article, I strongly encourage you to read it in its entirety if you have the time.

Medicine, healing, and big money

At about the same time, there was a May 31, 2018 news item on phys.org offering a perspective from some of the leaders in the science and the business (Note: Links have been removed),

Over the past few years, researchers led by George Church have made important strides toward engineering the genomes of pigs to make their cells compatible with the human body. So many think that it’s possible that, with the help of CRISPR technology, a healthy heart for a patient in desperate need might one day come from a pig.

“It’s relatively feasible to change one gene in a pig, but to change many dozens—which is quite clear is the minimum here—benefits from CRISPR,” an acronym for clustered regularly interspaced short palindromic repeats, said Church, the Robert Winthrop Professor of Genetics at Harvard Medical School (HMS) and a core faculty member of Harvard’s Wyss Institute for Biologically Inspired Engineering. Xenotransplantation is “one of few” big challenges (along with gene drives and de-extinction, he said) “that really requires the ‘oomph’ of CRISPR.”

To facilitate the development of safe and effective cells, tissues, and organs for future medical transplantation into human patients, Harvard’s Office of Technology Development has granted a technology license to the Cambridge biotech startup eGenesis.

Co-founded by Church and former HMS doctoral student Luhan Yang in 2015, eGenesis announced last year that it had raised $38 million to advance its research and development work. At least eight former members of the Church lab—interns, doctoral students, postdocs, and visiting researchers—have continued their scientific careers as employees there.

“The Church Lab is well known for its relentless pursuit of scientific achievements so ambitious they seem improbable—and, indeed, [for] its track record of success,” said Isaac Kohlberg, Harvard’s chief technology development officer and senior associate provost. “George deserves recognition too for his ability to inspire passion and cultivate a strong entrepreneurial drive among his talented research team.”

The license from Harvard OTD covers a powerful set of genome-engineering technologies developed at HMS and the Wyss Institute, including access to foundational intellectual property relating to the Church Lab’s 2012 breakthrough use of CRISPR, led by Yang and Prashant Mali, to edit the genome of human cells. Subsequent innovations that enabled efficient and accurate editing of numerous genes simultaneously are also included. The license is exclusive to eGenesis but limited to the field of xenotransplantation.

A May 30, 2018 Harvard University news release by Caroline Petty, which originated the news item, explores some of the issues associated with incubating humans organs in other species,

The prospect of using living, nonhuman organs, and concerns over the infectiousness of pathogens either present in the tissues or possibly formed in combination with human genetic material, have prompted the Food and Drug Administration to issue detailed guidance on xenotransplantation research and development since the mid-1990s. In pigs, a primary concern has been that porcine endogenous retroviruses (PERVs), strands of potentially pathogenic DNA in the animals’ genomes, might infect human patients and eventually cause disease. [emphases mine]

That’s where the Church lab’s CRISPR expertise has enabled significant advances. In 2015, the lab published important results in the journal Science, successfully demonstrating the use of genome engineering to eliminate all 62 PERVs in porcine cells. Science later called it “the most widespread CRISPR editing feat to date.”

In 2017, with collaborators at Harvard, other universities, and eGenesis, Church and Yang went further. Publishing again in Science, they first confirmed earlier researchers’ fears: Porcine cells can, in fact, transmit PERVs into human cells, and those human cells can pass them on to other, unexposed human cells. (It is still unknown under what circumstances those PERVs might cause disease.) In the same paper, they corrected the problem, announcing the embryogenesis and birth of 37 PERV-free pigs. [Note: My July 17, 2018 post features research which suggests CRISPR-Cas9 gene editing may cause greater genetic damage than had been thought.]

“Taken together, those innovations were stunning,” said Vivian Berlin, director of business development in OTD, who manages the commercialization strategy for much of Harvard’s intellectual property in the life sciences. “That was the foundation they needed, to convince both the scientific community and the investment community that xenotransplantation might become a reality.”

“After hundreds of tests, this was a critical milestone for eGenesis — and the entire field — and represented a key step toward safe organ transplantation from pigs,” said Julie Sunderland, interim CEO of eGenesis. “Building on this study, we hope to continue to advance the science and potential of making xenotransplantation a safe and routine medical procedure.”

Genetic engineering may undercut human diseases, but also could help restore extinct species, researcher says. [Shades of the Jurassic Park movies!]

It’s not, however, the end of the story: An immunological challenge remains, which eGenesis will need to address. The potential for a patient’s body to outright reject transplanted tissue has stymied many previous attempts at xenotransplantation. Church said numerous genetic changes must be achieved to make porcine organs fully compatible with human patients. Among these are edits to several immune functions, coagulation functions, complements, and sugars, as well as the PERVs.

“Trying the straight transplant failed almost immediately, within hours, because there’s a huge mismatch in the carbohydrates on the surface of the cells, in particular alpha-1-3-galactose, and so that was a showstopper,” Church explained. “When you delete that gene, which you can do with conventional methods, you still get pretty fast rejection, because there are a lot of other aspects that are incompatible. You have to take care of each of them, and not all of them are just about removing things — some of them you have to humanize. There’s a great deal of subtlety involved so that you get normal pig embryogenesis but not rejection.

“Putting it all together into one package is challenging,” he concluded.

In short, it’s the next big challenge for CRISPR.

Not unexpectedly, there is no mention of the CRISPR patent fight between Harvard/MIT’s (Massachusetts Institute of Technology) Broad Institute and the University of California at Berkeley (UC Berkeley). My March 15, 2017 posting featured an outcome where the Broad Institute won the first round of the fight. As I recall, it was a decision based on the principles associated with King Solomon, i.e., the US Patent Office, divided the baby and UCBerkeley got the less important part of the baby. As you might expect the decision has been appealed. In an April 30, 2018 piece, Scientific American reprinted an article about the latest round in the fight written by Sharon Begley for STAT (Note: Links have been removed),

All You Need to Know for Round 2 of the CRISPR Patent Fight

It’s baaaaack, that reputation-shredding, stock-moving fight to the death over key CRISPR patents. On Monday morning in Washington, D.C., the U.S. Court of Appeals for the Federal Circuit will hear oral arguments in University of California v. Broad Institute. Questions?

How did we get here? The patent office ruled in February 2017 that the Broad’s 2014 CRISPR patent on using CRISPR-Cas9 to edit genomes, based on discoveries by Feng Zhang, did not “interfere” with a patent application by UC based on the work of UC Berkeley’s Jennifer Doudna. In plain English, that meant the Broad’s patent, on using CRISPR-Cas9 to edit genomes in eukaryotic cells (all animals and plants, but not bacteria), was different from UC’s, which described Doudna’s experiments using CRISPR-Cas9 to edit DNA in a test tube—and it was therefore valid. The Patent Trial and Appeal Board concluded that when Zhang got CRISPR-Cas9 to work in human and mouse cells in 2012, it was not an obvious extension of Doudna’s earlier research, and that he had no “reasonable expectation of success.” UC appealed, and here we are.

For anyone who may not realize what the stakes are for these institutions, Linda Williams in a March 16, 1999 article for the LA Times had this to say about universities, patents, and money,

The University of Florida made about $2 million last year in royalties on a patent for Gatorade Thirst Quencher, a sports drink that generates some $500 million to $600 million a year in revenue for Quaker Oats Co.

The payments place the university among the top five in the nation in income from patent royalties.

Oh, but if some people on the Gainesville, Fla., campus could just turn back the clock. “If we had done Gatorade right, we would be getting $5 or $6 million (a year),” laments Donald Price, director of the university’s office of corporate programs. “It is a classic example of how not to handle a patent idea,” he added.

Gatorade was developed in 1965 when many universities were ill equipped to judge the commercial potential of ideas emerging from their research labs. Officials blew the university’s chance to control the Gatorade royalties when they declined to develop a professor’s idea.

The Gatorade story does not stop there and, even though it’s almost 20 years old, this article stands the test of time. I strongly encourage you to read it if the business end of patents and academia interest you or if you would like to develop more insight into the Broad Institute/UC Berkeley situation.

Getting back to the science, there is that pesky matter of diseases crossing over from one species to another. While, Harvard and eGenesis claim a victory in this area, it seems more work needs to be done.

Infections from pigs

An August 29, 2018 University of Alabama at Birmingham news release (also on EurekAlert) by Jeff Hansen, describes the latest chapter in the quest to provide more organs for transplantion,

A shortage of organs for transplantation — including kidneys and hearts — means that many patients die while still on waiting lists. So, research at the University of Alabama at Birmingham and other sites has turned to pig organs as an alternative. [emphasis mine]

Using gene-editing, researchers have modified such organs to prevent rejection, and research with primates shows the modified pig organs are well-tolerated.

An added step is needed to ensure the safety of these inter-species transplants — sensitive, quantitative assays for viruses and other infectious microorganisms in donor pigs that potentially could gain access to humans during transplantation.

The U.S. Food and Drug Administration requires such testing, prior to implantation, of tissues used for xenotransplantation from animals to humans. It is possible — though very unlikely — that an infectious agent in transplanted tissues could become an emerging infectious disease in humans.

In a paper published in Xenotransplantation, Mark Prichard, Ph.D., and colleagues at UAB have described the development and testing of 30 quantitative assays for pig infectious agents. These assays had sensitivities similar to clinical lab assays for viral loads in human patients. After validation, the UAB team also used the assays on nine sows and 22 piglets delivered from the sows through caesarian section.

“Going forward, ensuring the safety of these organs is of paramount importance,” Prichard said. “The use of highly sensitive techniques to detect potential pathogens will help to minimize adverse events in xenotransplantation.”

“The assays hold promise as part of the screening program to identify suitable donor animals, validate and release transplantable organs for research purposes, and monitor transplant recipients,” said Prichard, a professor in the UAB Department of Pediatrics and director of the Department of Pediatrics Molecular Diagnostics Laboratory.

The UAB researchers developed quantitative polymerase chain reaction, or qPCR, assays for 28 viruses sometimes found in pigs and two groups of mycoplasmas. They established reproducibility, sensitivity, specificity and lower limit of detection for each assay. All but three showed features of good quantitative assays, and the lower limit of detection values ranged between one and 16 copies of the viral or bacterial genetic material.

Also, the pig virus assays did not give false positives for some closely related human viruses.

As a start to understanding the infectious disease load in normal healthy animals and ensuring the safety of pig tissues used in xenotransplantation research, the researchers then screened blood, nasal swab and stool specimens from nine adult sows and 22 of their piglets delivered by caesarian section.

Mycoplasma species and two distinct herpesviruses were the most commonly detected microorganisms. Yet 14 piglets that were delivered from three sows infected with either or both herpesviruses were not infected with the herpesviruses, showing that transmission of these viruses from sow to the caesarian-delivery piglet was inefficient.

Prichard says the assays promise to enhance the safety of pig tissues for xenotransplantation, and they will also aid evaluation of human specimens after xenotransplantation.

The UAB researchers say they subsequently have evaluated more than 300 additional specimens, and that resulted in the detection of most of the targets. “The detection of these targets in pig specimens provides reassurance that the analytical methods are functioning as designed,” said Prichard, “and there is no a priori reason some targets might be more difficult to detect than others with the methods described here.”

As is my custom, here’s a link to and a citation for the paper,

Xenotransplantation panel for the detection of infectious agents in pigs by Caroll B. Hartline, Ra’Shun L. Conner, Scott H. James, Jennifer Potter, Edward Gray, Jose Estrada, Mathew Tector, A. Joseph Tector, Mark N. Prichard. Xenotransplantaion Volume 25, Issue 4 July/August 2018 e12427 DOI: https://doi.org/10.1111/xen.12427 First published: 18 August 2018

This paper is open access.

All this leads to questions about chimeras. If a pig is incubating organs with human cells it’s a chimera but then means the human receiving the organ becomes a chimera too. (For an example, see my Dec. 22, 2013 posting where there’s mention of a woman who received a trachea from a pig. Scroll down about 30% of the way.)

What is it to be human?

A question much beloved of philosophers and others, the question seems particularly timely with xenotransplantion and other developments such neuroprosthetics (cyborgs) and neuromorphic computing (brainlike computing).

As I’ve noted before, although not recently, popular culture offers a discourse on these issues. Take a look at the superhero movies and the way in which enhanced humans and aliens are presented. For example, X-Men comics and movies present mutants (humans with enhanced abilities) as despised and rejected. Video games (not really my thing but there is the Deus Ex series which has as its hero, a cyborg also offer insight into these issues.

Other than popular culture and in the ‘bleeding edge’ arts community, I can’t recall any public discussion on these matters arising from the extraordinary set of technologies which are being deployed or prepared for deployment in the foreseeable future.

(If you’re in Vancouver (Canada) from September 14 – December 15, 2018, you may want to check out Piccinini’s work. Also, there’s ” NCSU [North Carolina State University] Libraries, NC State’s Genetic Engineering and Society (GES) Center, and the Gregg Museum of Art & Design have issued a public call for art for the upcoming exhibition Art’s Work in the Age of Biotechnology: Shaping our Genetic Futures.” from my Sept. 6, 2018 posting. Deadline: Oct. 1, 2018.)

At a guess, there will be pushback from people who have no interest in debating what it is to be human as they already know, and will find these developments, when they learn about them, to be horrifying and unnatural.

June 4, 2018 talk in Vancouver (Canada): Genetically-Engineered Food: Facts, Ethical Considerations and World Hunger

ARPICO (Society of Italian Researchers and Professionals in Western Canada) is hosting a talk on the topic of genetically modified food. Here’s more from their May 20, 2018 announcement (received via email),

Our third speaking event of the year has been scheduled for Monday, June 4th, 2018 at the Italian Cultural Centre – Museum & Art Gallery. Marie-Claude Fortin’s talk will discuss food systems derived from biotechnology (often referred to as GMO) and their comparison with traditional farming processes, both technical and ethical. You can read a summary of Marie-Claude Fortin’s lecture as well as her short professional biography at the bottom of this message.

Ahead of the speaking event, ARPICO will be holding its 2018 Annual General Meeting in the same location. We encourage everyone to participate in the AGM, have their say on ARPICO’s matters and possibly volunteer for the Board of Directors.

We look forward to seeing everyone there.

Please register for the event by visiting the EventBrite link or RSVPing to info@arpico.ca.

The evening agenda is as follows:

6:00pm to 6:45pm – Annual General Meeting
7:00 pm – Lecture by Marie-Claude Fortin
~8:00 pm – Q & A Period
Mingling & Refreshments until about 9:45 pm

If you have not yet RSVP’d, please do so on our EventBrite page.

Further details are also available at arpico.ca, our facebook page, and Eventbrite.

Genetically-Engineered Food: Facts, Ethical Considerations and World Hunger

In this lecture we will explore a part of our food system, which has received much press, but which consumers still misunderstand: food derived from biotechnology often referred to as genetically modified organisms. We will be learning about the types of plants and animals which are genetically engineered and part of our everyday food system and the reasons for which they have been transformed genetically. We will be looking at the issue from several different angles. You are encouraged to approach the topic with an open mind, and learn how the technology is being used. We will start by understanding the differences between traditional plant breeding, conventional plant breeding, transgenic technology and genome editing. The latter two processes are considered genetic engineering technologies but all of them constitute a continuum of techniques employed to improve domestic plants and animals. We will then go over the ethical paradigms related to genetically engineered food represented by the European and North American points of view. Finally, we will discuss the strengths and weaknesses associated with genetic engineering as a tool to solve world hunger.

Marie-Claude Fortin is a former Research Scientist with Agriculture and Agri-Food Canada, Associate Editor with Crop Science Society of America, Board Member of the Soil and Water Conservation Society and Adjunct Professor at the University of British Columbia (UBC) and currently responsible for the shared research infrastructure portfolio at the UBC Vice-President Research & Innovation Office. Her main areas of research expertise are crop and soil sciences with special interests in measuring and modeling crop development and various processes on agricultural land: water and nitrogen fertilizer flow through the soil profile, emissions of greenhouse gases and soil physical properties. Her research shows that sustainable crop management practices result in soil environments, which are conducive to resilient crop production and organic matter buildup, which is the process of storing carbon in soils, a most important process in this era of climate change. For the past 18 years, Marie-Claude has been teaching food systems courses at UBC [University of British Columbia], emphasizing impacts of decisions made at the corporate, national and local levels on the economic, environmental and social sustainability of the food system, including impacts of organic and industrial agriculture and adoption of genetically engineered crops and animals, on farmers and consumers.

WHEN (AGM): Monday, June 4th, 2018 at 6:00pm (doors open at 5:50pm)

WHEN (EVENT): Monday, June 4th, 2018 at 7:00pm (doors open at 6:45pm)

WHERE: Italian Cultural Centre – Museum & Art Gallery – 3075 Slocan St, Vancouver, BC, V5M 3E4

RSVP: Please RSVP at EventBrite (https://gmofoods.eventbrite.ca/) or email info@arpico.ca

Tickets are Needed

Tickets are FREE, but all individuals are requested to obtain “free-admission” tickets on EventBrite site due to limited seating at the venue. Organizers need accurate registration numbers to manage wait lists and prepare name tags.

All ARPICO events are 100% staffed by volunteer organizers and helpers, however, room rental, stationery, and guest refreshments are costs incurred and underwritten by members of ARPICO. Therefore to be fair, all audience participants are asked to donate to the best of their ability at the door or via EventBrite to “help” defray costs of the event.

FAQs

Where can I contact the organizer with any questions? info@arpico.ca

Do I have to bring my printed ticket to the event? No, you do not. Your name will be on our Registration List at the Check-in Desk.

Is my registration/ticket transferrable? If you are unable to attend, another person may use your ticket. Please send us an email at info@arpico.ca of this substitution to correct our audience Registration List and to prepare guest name tags.

Can I update my registration information? Yes. If you have any questions, contact us at info@arpico.ca

I am having trouble using EventBrite and cannot reserve my ticket(s). Can someone at ARPICO help me with my ticket reservation? Of course, simply send your ticket request to us at info@arpico.ca so we help you.

We look forward to seeing you there.
www.arpico.ca

I wonder if they’re going to be discussing AquAdvantage salmon, which was first mentioned here in a Dec. 4, 2015 post (scroll down about 40% of the way), again, in a May 20, 2016 posting (AquAdvantage salmon (genetically modified) approved for consumption in Canada), and, most recently, in a Sept. 13, 2017 posting where I was critiquing a couple of books (scroll down to the ‘Fish’ subtitle). Allegedly the fish were allegedly sold in the Canadian market,

Since the 2016 approval, AquAdvantage salmon, 4.5M tonnes has been sold in Canada according to an Aug. 8, 2017 article by Sima Shakeri for Huffington Post (Note: Links have been removed),

After decades of trying to get approval by in North America, genetically modified Atlantic salmon has been sold to consumers in Canada.

AquaBounty Technologies, an American company that produces the Atlantic salmon, confirmed it had sold 4.5 tonnes of the modified fish on August 4 [2017], the Scientific American reported.

The fish have been engineered with a growth hormone gene from Chinook salmon to grow faster than regular salmon and require less food. They take about 18 months to reach market size, which is much quicker than the 30 months or so for conventional salmon.

The Washington Post wrote AquaBounty’s salmon also contains a gene from the ocean pout that makes the salmon produce the growth hormone gene all-year-round.

The company produces the eggs in a facility in P.E.I., which is currently being expanded, and then they’re shipped to Panama where the fish are raised.

Health Canada assessed the AquAdvantage salmon and concluded it “did not pose a greater risk to human health than salmon currently available on the Canadian market,” and that it would have no impact on allergies nor a difference in nutritional value compared to other farmed salmon.

Because of that, the AquAdvantage product is not required to be specially labelled as genetically modified, and is up to the discretion of retailers.

As for gene editing, I don’t follow everything in that area of endeavour but I have (more or less) kept track of CRISPR ((clustered regularly interspaced short palindromic repeat). Just use CRISPR as the search term for the blog search function to find what’s here.

This looks to be a very interesting talk and good for ARPICO for tackling a ‘difficult’ topic. I hope they have a lively, convivial, and open discussion.

Alan Copperman and Amanda Marcotte have a very US-centric discussion about CRISPR and germline editing (designer babies?)

For anyone who needs more information, I ran a three part series on CRISPR germline editing on August 15, 2017:

Part 1 opens the series with a basic description of CRISPR and the germline research that occasioned the series along with some of the ethical issues and patent disputes that are arising from this new technology. CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

The news about CRISPR and germline editing by a US team made a bit of a splash even being mentioned on Salon.com, which hardly ever covers any science news (except for some occasional climate change pieces). In a Sept. 4, 2017 salon.com item (an excerpt from the full interview) Amanda Marcotte talks with Dr. Alan Copperman director of the division of reproductive endocrinology and infertility at Mount Sinai Medical Center about the technology and its implications.  As noted in the headline, it’s a US-centric discussion where assumptions are made about who will be leading discussions about the future of the technology.

It’s been a while since I’ve watched it but I believe they do mention in passing that Chinese scientists published two studies about using CRISPR to edit the germline (i think there’s a third Chinese paper in the pipeline) before the American team announced its accomplishment in August 2017. By the way, the first paper by the Chinese caused quite the quandary in April 2015. (My May 14, 2015 posting covers some of the ethical issues; scroll down about 50% of the way for more about the impact of the published Chinese research.)

Also, you might want notice just how smooth Copperman’s responses are almost always emphasizing the benefits of the technology before usually answering the question. He’s had media training and he’s good at this.

They also talk about corn and CRISPR just about the time that agricultural research was announced. Interesting timing, non? (See my Oct. 11, 2017 posting about CRISPR edited corn coming to market in 2020.)

For anyone who wants to skip to the full Marcotte/Cooperman interview, go here on Facebook.

CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now

I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.

It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,

After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).

According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.

Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),

It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.

The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.

Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.

But the fight for patent rights to CRISPR technology is by no means over. Here are four reasons why.

1. Berkeley can appeal the ruling

2. European patents are still up for grabs

3. Other parties are also claiming patent rights on CRISPR–Cas9

4. CRISPR technology is moving beyond what the patents cover

As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.

Once you’ve read Distor’s and Ledford’s articles, you may want to check out Adam Rogers’ and Eric Niiler’s Feb. 16, 2017 CRISPR patent article for Wired,

The fight over who owns the most promising technique for editing genes—cutting and pasting the stuff of life to cure disease and advance scientific knowledge—has been a rough one. A team on the West Coast, at UC Berkeley, filed patents on the method, Crispr-Cas9; a team on the East Coast, based at MIT and the Broad Institute, filed their own patents in 2014 after Berkeley’s, but got them granted first. The Berkeley group contended that this constituted “interference,” and that Berkeley deserved the patent.

At stake: millions, maybe billions of dollars in biotech money and licensing fees, the future of medicine, the future of bioscience. Not nothing. Who will benefit depends on who owns the patents.

On Wednesday [Feb. 15, 2017], the US Patent Trial and Appeal Board kind of, sort of, almost began to answer that question. Berkeley will get the patent for using the system called Crispr-Cas9 in any living cell, from bacteria to blue whales. Broad/MIT gets the patent in eukaryotic cells, which is to say, plants and animals.

It’s … confusing. “The patent that the Broad received is for the use of Crispr gene-editing technology in eukaryotic cells. The patent for the University of California is for all cells,” says Jennifer Doudna, the UC geneticist and co-founder of Caribou Biosciences who co-invented Crispr, on a conference call. Her metaphor: “They have a patent on green tennis balls; we have a patent for all tennis balls.”

Observers didn’t quite buy that topspin. If Caribou is playing tennis, it’s looking like Broad/MIT is Serena Williams.

“UC does not necessarily lose everything, but they’re no doubt spinning the story,” says Robert Cook-Deegan, an expert in genetic policy at Arizona State University’s School for the Future of Innovation in Society. “UC’s claims to eukaryotic uses of Crispr-Cas9 will not be granted in the form they sought. That’s a big deal, and UC was the big loser.”

UC officials said Wednesday [Feb. 15, 2017] that they are studying the 51-page decision and considering whether to appeal. That leaves members of the biotechnology sector wondering who they will have to pay to use Crispr as part of a business—and scientists hoping the outcome won’t somehow keep them from continuing their research.

….

Happy reading!

Essays on Frankenstein

Slate.com is dedicating a month (January 2017) to Frankenstein. This means there were will be one or more essays each week on one aspect or another of Frankenstein and science. These essays are one of a series of initiatives jointly supported by Slate, Arizona State University, and an organization known as New America. It gets confusing since these essays are listed as part of two initiatives:  Futurography and Future Tense.

The really odd part, as far as I’m concerned, is that there is no mention of Arizona State University’s (ASU) The Frankenstein Bicentennial Project (mentioned in my Oct. 26, 2016 posting). Perhaps they’re concerned that people will think ASU is advertising the project?

Introductions

Getting back to the essays, a Jan. 3, 2017 article by Jacob Brogan explains, by means of a ‘Question and Answer’ format article, why the book and the monster maintain popular interest after two centuries (Note: We never do find out who or how many people are supplying the answers),

OK, fine. I get that this book is important, but why are we talking about it in a series about emerging technology?

Though people still tend to weaponize it as a simple anti-scientific screed, Frankenstein, which was first published in 1818, is much richer when we read it as a complex dialogue about our relationship to innovation—both our desire for it and our fear of the changes it brings. Mary Shelley was just a teenager when she began to compose Frankenstein, but she was already grappling with our complex relationship to new forces. Almost two centuries on, the book is just as propulsive and compelling as it was when it was first published. That’s partly because it’s so thick with ambiguity—and so resistant to easy interpretation.

Is it really ambiguous? I mean, when someone calls something frankenfood, they aren’t calling it “ethically ambiguous food.”

It’s a fair point. For decades, Frankenstein has been central to discussions in and about bioethics. Perhaps most notably, it frequently crops up as a reference point in discussions of genetically modified organisms, where the prefix Franken- functions as a sort of convenient shorthand for human attempts to meddle with the natural order. Today, the most prominent flashpoint for those anxieties is probably the clustered regularly interspaced short palindromic repeats, or CRISPR, gene-editing technique [emphasis mine]. But it’s really oversimplifying to suggest Frankenstein is a cautionary tale about monkeying with life.

As we’ll see throughout this month on Futurography, it’s become a lens for looking at the unintended consequences of things like synthetic biology, animal experimentation, artificial intelligence, and maybe even social networking. Facebook, for example, has arguably taken on a life of its own, as its algorithms seem to influence the course of elections. Mark Zuckerberg, who’s sometimes been known to disavow the power of his own platform, might well be understood as a Frankensteinian figure, amplifying his creation’s monstrosity by neglecting its practical needs.

But this book is almost 200 years old! Surely the actual science in it is bad.

Shelley herself would probably be the first to admit that the science in the novel isn’t all that accurate. Early in the novel, Victor Frankenstein meets with a professor who castigates him for having read the wrong works of “natural philosophy.” Shelley’s protagonist has mostly been studying alchemical tomes and otherwise fantastical works, the sort of things that were recognized as pseudoscience, even by the standards of the day. Near the start of the novel, Frankenstein attends a lecture in which the professor declaims on the promise of modern science. He observes that where the old masters “promised impossibilities and performed nothing,” the new scientists achieve far more in part because they “promise very little; they know that metals cannot be transmuted and that the elixir of life is a chimera.”

Is it actually about bad science, though?

Not exactly, but it has been read as a story about bad scientists.

Ultimately, Frankenstein outstrips his own teachers, of course, and pulls off the very feats they derided as mere fantasy. But Shelley never seems to confuse fact and fiction, and, in fact, she largely elides any explanation of how Frankenstein pulls off the miraculous feat of animating dead tissue. We never actually get a scene of the doctor awakening his creature. The novel spends far more dwelling on the broader reverberations of that act, showing how his attempt to create one life destroys countless others. Read in this light, Frankenstein isn’t telling us that we shouldn’t try to accomplish new things, just that we should take care when we do.

This speaks to why the novel has stuck around for so long. It’s not about particular scientific accomplishments but the vagaries of scientific progress in general.

Does that make it into a warning against playing God?

It’s probably a mistake to suggest that the novel is just a critique of those who would usurp the divine mantle. Instead, you can read it as a warning about the ways that technologists fall short of their ambitions, even in their greatest moments of triumph.

Look at what happens in the novel: After bringing his creature to life, Frankenstein effectively abandons it. Later, when it entreats him to grant it the rights it thinks it deserves, he refuses. Only then—after he reneges on his responsibilities—does his creation really go bad. We all know that Frankenstein is the doctor and his creation is the monster, but to some extent it’s the doctor himself who’s made monstrous by his inability to take responsibility for what he’s wrought.

I encourage you to read Brogan’s piece in its entirety and perhaps supplement the reading. Mary Shelley has a pretty interesting history. She ran off with Percy Bysshe Shelley who was married to another woman, in 1814  at the age of seventeen years. Her parents were both well known and respected intellectuals and philosophers, William Godwin and Mary Wollstonecraft. By the time Mary Shelley wrote her book, her first baby had died and she had given birth to a second child, a boy.  Percy Shelley was to die a few years later as was her son and a third child she’d given birth to. (Her fourth child born in 1819 did survive.) I mention the births because one analysis I read suggests the novel is also a commentary on childbirth. In fact, the Frankenstein narrative has been examined from many perspectives (other than science) including feminism and LGBTQ studies.

Getting back to the science fiction end of things, the next part of the Futurography series is titled “A Cheat-Sheet Guide to Frankenstein” and that too is written by Jacob Brogan with a publication date of Jan. 3, 2017,

Key Players

Marilyn Butler: Butler, a literary critic and English professor at the University of Cambridge, authored the seminal essay “Frankenstein and Radical Science.”

Jennifer Doudna: A professor of chemistry and biology at the University of California, Berkeley, Doudna helped develop the CRISPR gene-editing technique [emphasis mine].

Stephen Jay Gould: Gould is an evolutionary biologist and has written in defense of Frankenstein’s scientific ambitions, arguing that hubris wasn’t the doctor’s true fault.

Seán Ó hÉigeartaigh: As executive director of the Center for Existential Risk at the University of Cambridge, hÉigeartaigh leads research into technologies that threaten the existience of our species.

Jim Hightower: This columnist and activist helped popularize the term frankenfood to describe genetically modified crops.

Mary Shelley: Shelley, the author of Frankenstein, helped create science fiction as we now know it.

J. Craig Venter: A leading genomic researcher, Venter has pursued a variety of human biotechnology projects.

Lingo

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Debates

Popular Culture

Further Reading

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‘Franken’ and CRISPR

The first essay is in a Jan. 6, 2016 article by Kay Waldman focusing on the ‘franken’ prefix (Note: links have been removed),

In a letter to the New York Times on June 2, 1992, an English professor named Paul Lewis lopped off the top of Victor Frankenstein’s surname and sewed it onto a tomato. Railing against genetically modified crops, Lewis put a new generation of natural philosophers on notice: “If they want to sell us Frankenfood, perhaps it’s time to gather the villagers, light some torches and head to the castle,” he wrote.

William Safire, in a 2000 New York Times column, tracked the creation of the franken- prefix to this moment: an academic channeling popular distrust of science by invoking the man who tried to improve upon creation and ended up disfiguring it. “There’s no telling where or how it will end,” he wrote wryly, referring to the spread of the construction. “It has enhanced the sales of the metaphysical novel that Ms. Shelley’s husband, the poet Percy Bysshe Shelley, encouraged her to write, and has not harmed sales at ‘Frank’n’Stein,’ the fast-food chain whose hot dogs and beer I find delectably inorganic.” Safire went on to quote the American Dialect Society’s Laurence Horn, who lamented that despite the ’90s flowering of frankenfruits and frankenpigs, people hadn’t used Frankensense to describe “the opposite of common sense,” as in “politicians’ motivations for a creatively stupid piece of legislation.”

A year later, however, Safire returned to franken- in dead earnest. In an op-ed for the Times avowing the ethical value of embryonic stem cell research, the columnist suggested that a White House conference on bioethics would salve the fears of Americans concerned about “the real dangers of the slippery slope to Frankenscience.”

All of this is to say that franken-, the prefix we use to talk about human efforts to interfere with nature, flips between “funny” and “scary” with ease. Like Shelley’s monster himself, an ungainly patchwork of salvaged parts, it can seem goofy until it doesn’t—until it taps into an abiding anxiety that technology raises in us, a fear of overstepping.

Waldman’s piece hints at how language can shape discussions while retaining a rather playful quality.

This series looks to be a good introduction while being a bit problematic in spots, which roughly sums up my conclusion about their ‘nano’ series in my Oct. 7, 2016 posting titled: Futurography’s nanotechnology series: a digest.

By the way, I noted the mention of CRISPR as it brought up an issue that they don’t appear to be addressing in this series (perhaps they will do this elsewhere?): intellectual property.

There’s a patent dispute over CRISPR as noted in this American Chemical Society’s Chemistry and Engineering News Jan. 9, 2017 video,

Playing God

This series on Frankenstein is taking on other contentious issues. A perennial favourite is ‘playing God’ as noted in Bina Venkataraman’s Jan. 11, 2017 essay on the topic,

Since its publication nearly 200 years ago, Shelley’s gothic novel has been read as a cautionary tale of the dangers of creation and experimentation. James Whale’s 1931 film took the message further, assigning explicitly the hubris of playing God to the mad scientist. As his monster comes to life, Dr. Frankenstein, played by Colin Clive, triumphantly exclaims: “Now I know what it feels like to be God!”

The admonition against playing God has since been ceaselessly invoked as a rhetorical bogeyman. Secular and religious, critic and journalist alike have summoned the term to deride and outright dismiss entire areas of research and technology, including stem cells, genetically modified crops, recombinant DNA, geoengineering, and gene editing. As we near the two-century commemoration of Shelley’s captivating story, we would be wise to shed this shorthand lesson—and to put this part of the Frankenstein legacy to rest in its proverbial grave.

The trouble with the term arises first from its murkiness. What exactly does it mean to play God, and why should we find it objectionable on its face? All but zealots would likely agree that it’s fine to create new forms of life through selective breeding and grafting of fruit trees, or to use in-vitro fertilization to conceive life outside the womb to aid infertile couples. No one objects when people intervene in what some deem “acts of God,” such as earthquakes, to rescue victims and provide relief. People get fully behind treating patients dying of cancer with “unnatural” solutions like chemotherapy. Most people even find it morally justified for humans to mete out decisions as to who lives or dies in the form of organ transplant lists that prize certain people’s survival over others.

So what is it—if not the imitation of a deity or the creation of life—that inspires people to invoke the idea of “playing God” to warn against, or even stop, particular technologies? A presidential commission charged in the early 1980s with studying the ethics of genetic engineering of humans, in the wake of the recombinant DNA revolution, sheds some light on underlying motivations. The commission sought to understand the concerns expressed by leaders of three major religious groups in the United States—representing Protestants, Jews, and Catholics—who had used the phrase “playing God” in a 1980 letter to President Jimmy Carter urging government oversight. Scholars from the three faiths, the commission concluded, did not see a theological reason to flat-out prohibit genetic engineering. Their concerns, it turned out, weren’t exactly moral objections to scientists acting as God. Instead, they echoed those of the secular public; namely, they feared possible negative effects from creating new human traits or new species. In other words, the religious leaders who called recombinant DNA tools “playing God” wanted precautions taken against bad consequences but did not inherently oppose the use of the technology as an act of human hubris.

She presents an interesting argument and offers this as a solution,

The lesson for contemporary science, then, is not that we should cease creating and discovering at the boundaries of current human knowledge. It’s that scientists and technologists ought to steward their inventions into society, and to more rigorously participate in public debate about their work’s social and ethical consequences. Frankenstein’s proper legacy today would be to encourage researchers to address the unsavory implications of their technologies, whether it’s the cognitive and social effects of ubiquitous smartphone use or the long-term consequences of genetically engineered organisms on ecosystems and biodiversity.

Some will undoubtedly argue that this places an undue burden on innovators. Here, again, Shelley’s novel offers a lesson. Scientists who cloister themselves as Dr. Frankenstein did—those who do not fully contemplate the consequences of their work—risk later encounters with the horror of their own inventions.

At a guess, Venkataraman seems to be assuming that if scientists communicate and make their case that the public will cease to panic with reference moralistic and other concerns. My understanding is that social scientists have found this is not the case. Someone may understand the technology quite well and still oppose it.

Frankenstein and anti-vaxxers

The Jan. 16, 2017 essay by Charles Kenny is the weakest of the lot, so far (Note: Links have been removed),

In 1780, University of Bologna physician Luigi Galvani found something peculiar: When he applied an electric current to the legs of a dead frog, they twitched. Thirty-seven years later, Mary Shelley had Galvani’s experiments in mind as she wrote her fable of Faustian overreach, wherein Dr. Victor Frankenstein plays God by reanimating flesh.

And a little less than halfway between those two dates, English physician Edward Jenner demonstrated the efficacy of a vaccine against smallpox—one of the greatest killers of the age. Given the suspicion with which Romantic thinkers like Shelley regarded scientific progress, it is no surprise that many at the time damned the procedure as against the natural order. But what is surprising is how that suspicion continues to endure, even after two centuries of spectacular successes for vaccination. This anti-vaccination stance—which now infects even the White House—demonstrates the immense harm that can be done by excessive distrust of technological advance.

Kenny employs history as a framing device. Crudely, Galvani’s experiments led to Mary Shelley’s Frankenstein which is a fable about ‘playing God’. (Kenny seems unaware there are many other readings of and perspectives on the book.) As for his statement ” … the suspicion with which Romantic thinkers like Shelley regarded scientific progress … ,” I’m not sure how he arrived at his conclusion about Romantic thinkers. According to Richard Holmes (in his book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science), their relationship to science was more complex. Percy Bysshe Shelley ran ballooning experiments and wrote poetry about science, which included footnotes for the literature and concepts he was referencing; John Keats was a medical student prior to his establishment as a poet; and Samuel Taylor Coleridge (The Rime of the Ancient Mariner, etc.) maintained a healthy correspondence with scientists of the day sometimes influencing their research. In fact, when you analyze the matter, you realize even scientists are, on occasion, suspicious of science.

As for the anti-vaccination wars, I wish this essay had been more thoughtful. Yes, Andrew Wakefield’s research showing a link between MMR (measles, mumps, and rubella) vaccinations and autism is a sham. However, having concerns and suspicions about technology does not render you a fool who hasn’t progressed from 18th/19th Century concerns and suspicions about science and technology. For example, vaccines are being touted for all kinds of things, the latest being a possible antidote to opiate addiction (see Susan Gados’ June 28, 2016 article for ScienceNews). Are we going to be vaccinated for everything? What happens when you keep piling vaccination on top of vaccination? Instead of a debate, the discussion has devolved to: “I’m right and you’re wrong.”

For the record, I’m grateful for the vaccinations I’ve had and the diminishment of diseases that were devastating and seem to be making a comeback with this current anti-vaccination fever. That said, I think there are some important questions about vaccines.

Kenny’s essay could have been a nuanced discussion of vaccines that have clearly raised the bar for public health and some of the concerns regarding the current pursuit of yet more vaccines. Instead, he’s been quite dismissive of anyone who questions vaccination orthodoxy.

The end of this piece

There will be more essays in Slate’s Frankenstein series but I don’t have time to digest and write commentary for all of them.

Please use this piece as a critical counterpoint to some of the series and, if I’ve done my job, you’ll critique this critique. Please do let me know if you find any errors or want to add an opinion or add your own critique in the Comments of this blog.

ETA Jan. 25, 2017: Here’s the Frankenstein webspace on Slate’s Futurography which lists all the essays in this series. It’s well worth looking at the list. There are several that were not covered here.