Tag Archives: gene editing

First CRISPR gene-edited babies? Ethics and the science story

Scientists, He Jiankui and Michael Deem, may have created the first human babies born after being subjected to CRISPR (clustered regularly interspaced short palindromic repeats) gene editing.  At this point, no one is entirely certain that these babies  as described actually exist since the information was made public in a rather unusual (for scientists) fashion.

The news broke on Sunday, November 25, 2018 through a number of media outlets none of which included journals associated with gene editing or high impact journals such as Cell, Nature, or Science.The news broke in MIT Technology Review and in Associated Press. Plus, this all happened just before the Second International Summit on Human Genome Editing (Nov. 27 – 29, 2018) in Hong Kong. He Jiankui was scheduled to speak today, Nov. 27, 2018.

Predictably, this news has caused quite a tizzy.

Breaking news

Antonio Regalado broke the news in a November 25, 2018  article for MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

According to Chinese medical documents posted online this month (here and here), a team at the Southern University of Science and Technology, in Shenzhen, has been recruiting couples in an effort to create the first gene-edited babies. They planned to eliminate a gene called CCR5 in hopes of rendering the offspring resistant to HIV, smallpox, and cholera.

The clinical trial documents describe a study in which CRISPR is employed to modify human embryos before they are transferred into women’s uteruses.

The scientist behind the effort, He Jiankui, did not reply to a list of questions about whether the undertaking had produced a live birth. Reached by telephone, he declined to comment.

However, data submitted as part of the trial listing shows that genetic tests have been carried out on fetuses as late as 24 weeks, or six months. It’s not known if those pregnancies were terminated, carried to term, or are ongoing.

Apparently He changed his mind because Marilynn Marchione in a November 26, 2018 article for the Associated Press confirms the news,

A Chinese researcher claims that he helped make the world’s first genetically edited babies — twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.

If true, it would be a profound leap of science and ethics.

A U.S. scientist [Dr. Michael Deem] said he took part in the work in China, but this kind of gene editing is banned in the United States because the DNA changes can pass to future generations and it risks harming other genes.

Many mainstream scientists think it’s too unsafe to try, and some denounced the Chinese report as human experimentation.

There is no independent confirmation of He’s claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it Monday [November 26, 2018] in Hong Kong to one of the organizers of an international conference on gene editing that is set to begin Tuesday [November 27, 2018], and earlier in exclusive interviews with The Associated Press.

“I feel a strong responsibility that it’s not just to make a first, but also make it an example,” He told the AP. “Society will decide what to do next” in terms of allowing or forbidding such science.

Some scientists were astounded to hear of the claim and strongly condemned it.

It’s “unconscionable … an experiment on human beings that is not morally or ethically defensible,” said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert and editor of a genetics journal.

“This is far too premature,” said Dr. Eric Topol, who heads the Scripps Research Translational Institute in California. “We’re dealing with the operating instructions of a human being. It’s a big deal.”

However, one famed geneticist, Harvard University’s George Church, defended attempting gene editing for HIV, which he called “a major and growing public health threat.”

“I think this is justifiable,” Church said of that goal.

h/t Cale Guthrie Weissman’s Nov. 26, 2018 article for Fast Company.

Diving into more detail

Ed Yong in a November 26, 2018 article for The Atlantic provides more details about the claims (Note: Links have been removed),

… “Two beautiful little Chinese girls, Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago,” He said in the first of five videos, posted yesterday {Nov. 25, 2018] to YouTube [link provided at the end of this section of the post]. “The girls are home now with their mom, Grace, and dad, Mark.” The claim has yet to be formally verified, but if true, it represents a landmark in the continuing ethical and scientific debate around gene editing.

Late last year, He reportedly enrolled seven couples in a clinical trial, and used their eggs and sperm to create embryos through in vitro fertilization. His team then used CRISPR to deactivate a single gene called CCR5 in the embryos, six of which they then implanted into mothers. CCR5 is a protein that the HIV virus uses to gain entry into human cells; by deactivating it, the team could theoretically reduce the risk of infection. Indeed, the fathers in all eight couples were HIV-positive.

Whether the experiment was successful or not, it’s intensely controversial. Scientists have already begun using CRISPR and other gene-editing technologies to alter human cells, in attempts to treat cancers, genetic disorders, and more. But in these cases, the affected cells stay within a person’s body. Editing an embryo [it’s often called, germline editing] is very different: It changes every cell in the body of the resulting person, including the sperm or eggs that would pass those changes to future generations. Such work is banned in many European countries, and prohibited in the United States. “I understand my work will be controversial, but I believe families need this technology and I’m willing to take the criticism for them,” He said.

“Was this a reasonable thing to do? I would say emphatically no,” says Paula Cannon of the University of Southern California. She and others have worked on gene editing, and particularly on trials that knock out CCR5 as a way to treat HIV. But those were attempts to treat people who were definitively sick and had run out of other options. That wasn’t the case with Nana and Lulu.

“The idea that being born HIV-susceptible, which is what the vast majority of humans are, is somehow a disease state that requires the extraordinary intervention of gene editing blows my mind,” says Cannon. “I feel like he’s appropriating this potentially valuable therapy as a shortcut to doing something in the sphere of gene editing. He’s either very naive or very cynical.”

“I want someone to make sure that it has happened,” says Hank Greely, an ethicist at Stanford University. If it hasn’t, that “would be a pretty bald-faced fraud,” but such deceptions have happened in the past. “If it is true, I’m disappointed. It’s reckless on safety grounds, and imprudent and stupid on social grounds.” He notes that a landmark summit in 2015 (which included Chinese researchers) and a subsequent major report from the National Academies of Science, Engineering, and Medicine both argued that “public participation should precede any heritable germ-line editing.” That is: Society needs to work out how it feels about making gene-edited babies before any babies are edited. Absent that consensus, He’s work is “waving a red flag in front of a bull,” says Greely. “It provokes not just the regular bio-Luddites, but also reasonable people who just wanted to talk it out.”

Societally, the creation of CRISPR-edited babies is a binary moment—a Rubicon that has been crossed. But scientifically, the devil is in the details, and most of those are still unknown.

CRISPR is still inefficient. [emphasis mine] The Chinese teams who first used it to edit human embryos only did so successfully in a small proportion of cases, and even then, they found worrying levels of “off-target mutations,” where they had erroneously cut parts of the genome outside their targeted gene. He, in his video, claimed that his team had thoroughly sequenced Nana and Lulu’s genomes and found no changes in genes other than CCR5.

That claim is impossible to verify in the absence of a peer-reviewed paper, or even published data of any kind. “The paper is where we see whether the CCR5 gene was properly edited, what effect it had at the cellular level, and whether [there were] any off-target effects,” said Eric Topol of the Scripps Research Institute. “It’s not just ‘it worked’ as a binary declaration.”

In the video, He said that using CRISPR for human enhancement, such as enhancing IQ or selecting eye color, “should be banned.” Speaking about Nana and Lulu’s parents, he said that they “don’t want a designer baby, just a child who won’t suffer from a disease that medicine can now prevent.”

But his rationale is questionable. Huang [Junjiu Huang of Sun Yat-sen University ], the first Chinese researcher to use CRISPR on human embryos, targeted the faulty gene behind an inherited disease called beta thalassemia. Mitalipov, likewise, tried to edit a gene called MYBPC3, whose faulty versions cause another inherited disease called hypertrophic cardiomyopathy (HCM). Such uses are still controversial, but they rank among the more acceptable applications for embryonic gene editing as ways of treating inherited disorders for which treatments are either difficult or nonexistent.

In contrast, He’s team disableda normal gene in an attempt to reduce the risk of a disease that neither child had—and one that can be controlled. There are already ways of preventing fathers from passing HIV to their children. There are antiviral drugs that prevent infections. There’s safe-sex education. “This is not a plague for which we have no tools,” says Cannon.

As Marilynn Marchione of the AP reports, early tests suggest that He’s editing was incomplete [emphasis mine], and at least one of the twins is a mosaic, where some cells have silenced copies of CCR5 and others do not. If that’s true, it’s unlikely that they would be significantly protected from HIV. And in any case, deactivating CCR5 doesn’t confer complete immunity, because some HIV strains can still enter cells via a different protein called CXCR4.

Nana and Lulu might have other vulnerabilities. …

It is also unclear if the participants in He’s trial were fully aware of what they were signing up for. [emphasis mine] The team’s informed-consent document describes their work as an “AIDS vaccine development project,” and while it describes CRISPR gene editing, it does so in heavily technical language. It doesn’t mention any of the risks of disabling CCR5, and while it does note the possibility of off-target effects, it also says that the “project team is not responsible for the risk.”

He owns two genetics companies, and his collaborator, Michael Deem of Rice University,  [emphasis mine] holds a small stake in, and sits on the advisory board of, both of them. The AP’s Marchione reports, “Both men are physics experts with no experience running human clinical trials.” [emphasis mine]

Yong’s article is well worth reading in its entirety. As for YouTube, here’s The He Lab’s webpage with relevant videos.

Reactions

Gina Kolata, Sui-Lee Wee, and Pam Belluck writing in a Nov. 26, 2018 article for the New York Times chronicle some of the response to He’s announcement,

It is highly unusual for a scientist to announce a groundbreaking development without at least providing data that academic peers can review. Dr. He said he had gotten permission to do the work from the ethics board of the hospital Shenzhen Harmonicare, but the hospital, in interviews with Chinese media, denied being involved. Cheng Zhen, the general manager of Shenzhen Harmonicare, has asked the police to investigate what they suspect are “fraudulent ethical review materials,” according to the Beijing News.

The university that Dr. He is attached to, the Southern University of Science and Technology, said Dr. He has been on no-pay leave since February and that the school of biology believed that his project “is a serious violation of academic ethics and academic norms,” according to the state-run Beijing News.

In a statement late on Monday, China’s national health commission said it has asked the health commission in southern Guangdong province to investigate Mr. He’s claims.

“I think that’s completely insane,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. Dr. Mitalipov broke new ground last year by using gene editing to successfully remove a dangerous mutation from human embryos in a laboratory dish. [I wrote a three-part series about CRISPR, which included what was then the latest US news, Mitalipov’s announcement, along with a roundup of previous work in China. Links are at the end of this section.’

Dr. Mitalipov said that unlike his own work, which focuses on editing out mutations that cause serious diseases that cannot be prevented any other way, Dr. He did not do anything medically necessary. There are other ways to prevent H.I.V. infection in newborns.

Just three months ago, at a conference in late August on genome engineering at Cold Spring Harbor Laboratory in New York, Dr. He presented work on editing the CCR₅ gene in the embryos of nine couples.

At the conference, whose organizers included Jennifer Doudna, one of the inventors of Crispr technology, Dr. He gave a careful talk about something that fellow attendees considered squarely within the realm of ethically approved research. But he did not mention that some of those embryos had been implanted in a woman and could result in genetically engineered babies.

“What we now know is that as he was talking, there was a woman in China carrying twins,” said Fyodor Urnov, deputy director of the Altius Institute for Biomedical Sciences and a visiting researcher at the Innovative Genomics Institute at the University of California. “He had the opportunity to say ‘Oh and by the way, I’m just going to come out and say it, people, there’s a woman carrying twins.’”

“I would never play poker against Dr. He,” Dr. Urnov quipped.

Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology, who co-led an advisory group on human gene editing for the National Academy of Sciences and the National Academy of Medicine, said that group and a similar organization in Britain had determined that if human genes were to be edited, the procedure should only be done to address “serious unmet needs in medical treatment, it had to be well monitored, it had to be well followed up, full consent has to be in place.”

It is not clear why altering genes to make people resistant to H.I.V. is “a serious unmet need.” Men with H.I.V. do not infect embryos. …

Dr. He got his Ph.D., from Rice University, in physics and his postdoctoral training, at Stanford, was with Stephen Quake, a professor of bioengineering and applied physics who works on sequencing DNA, not editing it.

Experts said that using Crispr would actually be quite easy for someone like Dr. He.

After coming to Shenzhen in 2012, Dr. He, at age 28, established a DNA sequencing company, Direct Genomics, and listed Dr. Quake on its advisory board. But, in a telephone interview on Monday, Dr. Quake said he was never associated with the company.

Deem, the US scientist who worked in China with He is currently being investigated (from a Nov. 26, 2018 article by Andrew Joseph in STAT),

Rice University said Monday that it had opened a “full investigation” into the involvement of one of its faculty members in a study that purportedly resulted in the creation of the world’s first babies born with edited DNA.

Michael Deem, a bioengineering professor at Rice, told the Associated Press in a story published Sunday that he helped work on the research in China.

Deem told the AP that he was in China when participants in the study consented to join the research. Deem also said that he had “a small stake” in and is on the scientific advisory boards of He’s two companies.

Megan Molteni in a Nov. 27, 2018 article for Wired admits she and her colleagues at the magazine may have dismissed CRISPR concerns about designer babies prematurely while shedding more light on this  latest development (Note: Links have been removed),

We said “don’t freak out,” when scientists first used Crispr to edit DNA in non-viable human embryos. When they tried it in embryos that could theoretically produce babies, we said “don’t panic.” Many years and years of boring bench science remain before anyone could even think about putting it near a woman’s uterus. Well, we might have been wrong. Permission to push the panic button granted.

Late Sunday night, a Chinese researcher stunned the world by claiming to have created the first human babies, a set of twins, with Crispr-edited DNA….

What’s perhaps most strange is not that He ignored global recommendations on conducting responsible Crispr research in humans. He also ignored his own advice to the world—guidelines that were published within hours of his transgression becoming public.

On Monday, He and his colleagues at Southern University of Science and Technology, in Shenzhen, published a set of draft ethical principles “to frame, guide, and restrict clinical applications that communities around the world can share and localize based on religious beliefs, culture, and public-health challenges.” Those principles included transparency and only performing the procedure when the risks are outweighed by serious medical need.

The piece appeared in the The Crispr Journal, a young publication dedicated to Crispr research, commentary, and debate. Rodolphe Barrangou, the journal’s editor in chief, where the peer-reviewed perspective appeared, says that the article was one of two that it had published recently addressing the ethical concerns of human germline editing, the other by a bioethicist at the University of North Carolina. Both papers’ authors had requested that their writing come out ahead of a major gene editing summit taking place this week in Hong Kong. When half-rumors of He’s covert work reached Barrangou over the weekend, his team discussed pulling the paper, but ultimately decided that there was nothing too solid to discredit it, based on the information available at the time.

Now Barrangou and his team are rethinking that decision. For one thing, He did not disclose any conflicts of interest, which is standard practice among respectable journals. It’s since become clear that not only is He at the helm of several genetics companies in China, He was actively pursuing controversial human research long before writing up a scientific and moral code to guide it.“We’re currently assessing whether the omission was a matter of ill-management or ill-intent,” says Barrangou, who added that the journal is now conducting an audit to see if a retraction might be warranted. …

“There are all sorts of questions these issues raise, but the most fundamental is the risk-benefit ratio for the babies who are going to be born,” says Hank Greely, an ethicist at Stanford University. “And the risk-benefit ratio on this stinks. Any institutional review board that approved it should be disbanded if not jailed.”

Reporting by Stat indicates that He may have just gotten in over his head and tried to cram a self-guided ethics education into a few short months. The young scientist—records indicate He is just 34—has a background in biophysics, with stints studying in the US at Rice University and in bioengineer Stephen Quake’s lab at Stanford. His resume doesn’t read like someone steeped deeply in the nuances and ethics of human research. Barrangou says that came across in the many rounds of edits He’s framework went through.

… China’s central government in Beijing has yet to come down one way or another. Condemnation would make He a rogue and a scientific outcast. Anything else opens the door for a Crispr IVF cottage industry to emerge in China and potentially elsewhere. “It’s hard to imagine this was the only group in the world doing this,” says Paul Knoepfler, a stem cell researcher at UC Davis who wrote a book on the future of designer babies called GMO Sapiens. “Some might say this broke the ice. Will others forge ahead and go public with their results or stop what they’re doing and see how this plays out?”

Here’s some of the very latest information with the researcher attempting to explain himself.

What does He have to say?

After He’s appearance at the Second International Summit on Human Genome Editing today, Nov. 27, 2018, David Cyranoski produced this article for Nature,

He Jiankui, the Chinese scientist who claims to have helped produce the first people born with edited genomes — twin girls — appeared today at a gene-editing summit in Hong Kong to explain his experiment. He gave his talk amid threats of legal action and mounting questions, from the scientific community and beyond, about the ethics of his work and the way in which he released the results.

He had never before presented his work publicly outside of a handful of videos he posted on YouTube. Scientists welcomed the fact that he appeared at all — but his talk left many hungry for more answers, and still not completely certain that He has achieved what he claims.

“There’s no reason not to believe him,” says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. “I’m just not completely convinced.”

Lovell-Badge, like others at the conference, says that an independent body should confirm the test results by performing an in-depth comparison of the parents’ and childrens’ genes.

Many scientists faulted He for a lack of transparency and the seemingly cavalier nature in which he embarked on such a landmark, and potentially risky, project.

“I’m happy he came but I was really horrified and stunned when he described the process he used,” says Jennifer Doudna, a biochemist at the University of California, Berkeley and a pioneer of the CRISPR/Cas-9 gene-editing technique that He used. “It was so inappropriate on so many levels.”

He seemed shaky approaching the stage and nervous during the talk. “I think he was scared,” says Matthew Porteus, who researches genome-editing at Stanford University in California and co-hosted a question-and-answer session with He after his presentation. Porteus attributes this either to the legal pressures that He faces or the mounting criticism from the scientists and media he was about to address.

He’s talk leaves a host of other questions unanswered, including whether the prospective parents were properly informed of the risks; why He selected CCR5 when there are other, proven ways to prevent HIV; why he chose to do the experiment with couples in which the fathers have HIV, rather than mothers who have a higher chance of passing the virus on to their children; and whether the risks of knocking out CCR5 — a gene normally present in people, which could have necessary but still unknown functions — outweighed the benefits in this case.

In the discussion following He’s talk, one scientist asked why He proceeded with the experiments despite the clear consensus among scientists worldwide that such research shouldn’t be done. He didn’t answer the question.

He’s attempts to justify his actions mainly fell flat. In response to questions about why the science community had not been informed of the experiments before the first women were impregnated, he cited presentations that he gave last year at meetings at the University of California, Berkeley, and at the Cold Spring Harbor Laboratory in New York. But Doudna, who organized the Berkeley meeting, says He did not present anything that showed he was ready to experiment in people. She called his defence “disingenuous at best”.

He also said he discussed the human experiment with unnamed scientists in the United States. But Porteus says that’s not enough for such an extraordinary experiment: “You need feedback not from your two closest friends but from the whole community.” …

Pressure was mounting on He ahead of the presentation. On 27 November, the Chinese national health commission ordered the Guangdong health commission, in the province where He’s university is located, to investigate.

On the same day, the Chinese Academy of Sciences issued a statement condemning his work, and the Genetics Society of China and the Chinese Society for Stem Cell Research jointly issued a statement saying the experiment “violates internationally accepted ethical principles regulating human experimentation and human rights law”.

The hospital cited in China’s clinical-trial registry as the that gave ethical approval for He’s work posted a press release on 27 November saying it did not give any approval. It questioned the signatures on the approval form and said that the hospital’s medical-ethics committee never held a meeting related to He’s research. The hospital, which itself is under investigation by the Shenzhen health authorities following He’s revelations, wrote: “The Company does not condone the means of the Claimed Project, and has reservations as to the accuracy, reliability and truthfulness of its contents and results.”

He has not yet responded to requests for comment on these statements and investigations, nor on why the hospital was listed in the registry and the claim of apparent forged signatures.

Alice Park’s Nov. 26, 2018 article for Time magazine includes an embedded video of He’s Nov. 27, 2018 presentation at the summit meeting.

What about the politics?

Mara Hvistendahl’s Nov. 27, 2018 article about this research for Slate.com poses some geopolitical questions (Note: Links have been removed),

The informed consent agreement for He Jiankui’s experiment describes it as an “AIDS vaccine development project” and used highly technical language to describe the procedure that patients would undergo. If the reality for some Chinese patients is that such agreements are glossed over, densely written, or never read, the reality for some researchers working in the country is that the appeal of cutting-edge trials is too great to resist. It is not just Chinese scientists who can be blinded by the lure of quick breakthroughs. Several of the most notable breaches of informed consent on the mainland have involved Western researchers or co-authors. … When people say that the usual rules don’t apply in China, they are really referring to authoritarian science, not some alternative communitarian ethics.

For the many scientists in China who adhere to recognized international standards, the incident comes as a disgrace. He Jiankui now faces an ethics investigation from provincial health authorities, and his institution, Southern University of Science and Technology, was quick to issue a statement noting that He was on unpaid leave. …

It would seem that US scientists wanting to avoid pesky ethics requirements in the US have found that going to China could be the answer to their problems. I gather it’s not just big business that prefers deregulated environments.

Guillaume Levrier’s  (he’ studying for a PhD at the Universté Sorbonne Paris Cité) November 16, 2018 essay for The Conversation sheds some light on political will and its impact on science (Note: Links have been removed),

… China has entered a “genome editing” race among great scientific nations and its progress didn’t come out of nowhere. China has invested heavily in the natural-sciences sector over the past 20 years. The Ninth Five-Year Plan (1996-2001) mentioned the crucial importance of biotechnologies. The current Thirteenth Five-Year Plan is even more explicit. It contains a section dedicated to “developing efficient and advanced biotechnologies” and lists key sectors such as “genome-editing technologies” intended to “put China at the bleeding edge of biotechnology innovation and become the leader in the international competition in this sector”.

Chinese embryo research is regulated by a legal framework, the “technical norms on human-assisted reproductive technologies”, published by the Science and Health Ministries. The guidelines theoretically forbid using sperm or eggs whose genome have been manipulated for procreative purposes. However, it’s hard to know how much value is actually placed on this rule in practice, especially in China’s intricate institutional and political context.

In theory, three major actors have authority on biomedical research in China: the Science and Technology Ministry, the Health Ministry, and the Chinese Food and Drug Administration. In reality, other agents also play a significant role. Local governments interpret and enforce the ministries’ “recommendations”, and their own interpretations can lead to significant variations in what researchers can and cannot do on the ground. The Chinese National Academy of Medicine is also a powerful institution that has its own network of hospitals, universities and laboratories.

Another prime actor is involved: the health section of the People’s Liberation Army (PLA), which has its own biomedical faculties, hospitals and research labs. The PLA makes its own interpretations of the recommendations and has proven its ability to work with the private sector on gene editing projects. …

One other thing from Levrier’s essay,

… And the media timing is just a bit too perfect, …

Do read the essay; there’s a twist at the end.

Final thoughts and some links

If I read this material rightly, there are suspicions there may be more of this work being done in China and elsewhere. In short, we likely don’t have the whole story.

As for the ethical issues, this is a discussion among experts only, so far. The great unwashed (thee and me) are being left at the wayside. Sure, we’ll be invited to public consultations, one day,  after the big decisions have been made.

Anyone who’s read up on the history of science will tell you this kind of breach is very common at the beginning. Richard Holmes’  2008 book, ‘The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science’ recounts stories of early scientists (European science) who did crazy things. Some died, some shortened their life spans; and, some irreversibly damaged their health.  They also experimented on other people. Informed consent had not yet been dreamed up.

In fact, I remember reading somewhere that the largest human clinical trial in history was held in Canada. The small pox vaccine was highly contested in the US but the Canadian government thought it was a good idea so they offered US scientists the option of coming here to vaccinate Canadian babies. This was in the 1950s and the vaccine seems to have been administered almost universally. That was a lot of Canadian babies. Thankfully, it seems to have worked out but it does seem mind-boggling today.

For all the indignation and shock we’re seeing, this is not the first time nor will it be the last time someone steps over a line in order to conduct scientific research. And, that is the eternal problem.

Meanwhile I think some of the real action regarding CRISPR and germline editing is taking place in the field (pun!) of agriculture:

My Nov. 27, 2018 posting titled: ‘Designer groundcherries by CRISPR (clustered regularly interspaced short palindromic repeats)‘ and a more disturbing Nov. 27, 2018 post titled: ‘Agriculture and gene editing … shades of the AquAdvantage salmon‘. That second posting features a company which is trying to sell its gene-editing services to farmers who would like cows that  never grow horns and pigs that never reach puberty.

Then there’s this ,

The Genetic Revolution‘, a documentary that offers relatively up-to-date information about gene editing, which was broadcast on Nov. 11, 2018 as part of The Nature of Things series on CBC (Canadian Broadcasting Corporation).

My July 17, 2018 posting about research suggesting that scientists hadn’t done enough research on possible effects of CRISPR editing titled: ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle’.

My 2017 three-part series on CRISPR and germline editing:

CRISPR and editing the germline in the US (part 1 of 3): In the beginning

CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

There you have it.

Added on November 30, 2018: David Cyanowski has written one final article (Nov. 30, 2018 for Nature) about He and the Second International Summit on Human Genome Editing. He did not make his second scheduled appearance at the summit, returning to China before the summit concluded. He was rebuked in a statement produced by the Summit’s organizing committee at the end of the three-day meeting. The situation with regard to his professional status in China is ambiguous. Cyanowski ends his piece with the information that the third summit will take place in London (likely in the UK) in 2021. I encourage you to read Cyanowski’s Nov. 30, 2018 article in its entirety; it’s not long.

Added on Dec. 3, 2018: The story continues. Ed Yong has written a summary of the issues to date in a Dec. 3, 2018 article for The Atlantic (even if you know the story ift’s eyeopening to see all the parts put together.

J. Benjamin Hurlbut, Associate Professor of Life Sciences at Arizona State University (ASU) and Jason Scott Robert, Director of the Lincoln Center for Applied Ethics at Arizona State University have written a provocative (and true) Dec. 3, 2018 essay titled, CRISPR babies raise an uncomfortable reality – abiding by scientific standards doesn’t guarantee ethical research, for The Conversation. h/t phys.org

Agriculture and gene editing … shades of the AquAdvantage salmon

Salmon are not the only food animals being genetically altered (more about that later in this post) we can now add cows, pigs, and more.

This November 15, 2018 article by Candice Choi on the Huffington Post website illustrates some of the excitement and terror associated with gene editing farm animals,

A company wants to alter farm animals by adding and subtracting genetic traits in a lab. It sounds like science fiction, but Recombinetics sees opportunity for its technology in the livestock industry.

But first, it needs to convince regulators that gene-edited animals are no different than conventionally bred ones. To make the technology appealing and to ease any fears that it may be creating Franken-animals, [emphasis mine] Recombinetics isn’t starting with productivity. Instead, it’s introducing gene-edited traits as a way to ease animal suffering.

“It’s a better story to tell,” said Tammy Lee, CEO of the St. Paul, Minnesota-based company.

For instance, animal welfare advocates have long criticized the way farmers use caustic paste or hot irons to dehorn dairy cows so the animals don’t harm each other. Recombinetics snips out the gene for growing horns so the procedure is unnecessary. [emphases mine]

Last year, a bull gene-edited by Recombinetics to have the dominant hornless trait sired several offspring. All were born hornless as expected, and are being raised at the University of California, Davis. Once the female offspring starts lactating, its milk will be tested for any abnormalities.

Another Recombinetics project: castration-free pigs.

When male piglets go through puberty, their meat can take on an unpleasant odour, something known as “boar taint.” To combat it, farmers castrate pigs, a procedure animal welfare advocates say is commonly performed without painkillers. Editing genes so that pigs never go through puberty would make castration unnecessary.

Also in development are dairy cows that could withstand higher temperatures, so the animals don’t suffer in hotter climates. [emphasis mine]

..

Before food from gene-edited animals can land on dinner tables, however, Recombinetics has to overcome any public unease about the technology.

Beyond worries about “playing God,” it may be an uncomfortable reminder of how modern food production already treats animals, said Paul Thompson, a professor of agriculture at Michigan State University.

“There’s an ethical question that’s been debated for at least the last 20 years, of whether you need to change the animal or change the system,” Thompson said.

Support for gene editing will also likely depend on how the technology is used: whether it’s for animal welfare, productivity or disease resistance. In August, a Pew study found 43 per cent of Americans supported genetically engineered animals for more nutritious meat.

Choi has written an interesting article, which includes a picture of the hornless cows embedded in the piece. One note: Choi makes reference to a milk glut. As far as I’m aware that’s not the case in Canada (at this time) but it is a problem in the US where in 2015 (?) farmers dumped some 43  million gallons of milk (October 12, 2016 article by Martha C. White for Money magazine).

As for the salmon, I’ve covered that story a few times during its journey to being approved for human consumption i Canada (my May 20, 2016 posting) to the discovery in 2017 that the genetically modified product, AquAdvantage salmon, had been introduced into the market, (from my Sept. 13, 2017 posting; scroll down about 40R of the way),

“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 …”

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. [Prince Edward Island; a province in Canada], which is currently being expanded, and then they’re shipped to Panama where the fish are raised.

….

There was a bit of a kerfuffle about the whole affair but it seems Canadians have gone on to embrace the genetically modified product. At least that’s Christine Blank’s perspective in her Sept. 13, 2018 article (Canada, US embrace AquAdvantage GMO salmon, Brazil and China may be next) for the Genetic Literacy Project website,

Genetically modified salmon firm AquaBounty has found “very enthusiastic” buyers in Canada, according to president and CEO Ronald Stotish.

The first sale of the Maynard, Massachusetts, U.S.A.-based firm’s AquAdvantage salmon was made last June [2017], when unnamed buyers in Canada bought five metric tons at the going rate of traditional farmed Atlantic salmon, according to the company. Since then, AquaBounty has sold 10 additional metric tons of its AquAdvantage salmon to buyers in Canada

Meanwhile, Stotish revealed that AquAdvantage will be sold in the U.S. through established distributors.

“Once [AquaBounty salmon] is established in the market, the option for branding as a ‘sustainably produced’ food item can be considered,” he told investors.

Alex Gillis’ June 5, 2018 article for Macleans magazine suggests that Canadians may be a bit more doubtful about GM (genetically modified) salmon than Stotish seems to be believe,

An Ipsos Reid poll conducted for the Canadian Biotechnology Action Network in 2015 suggested that Canadians are concerned about GM foods, in spite of government assurances that they’re safe. About 60 per cent of respondents opposed genetically modifying crops and animals for food; nearly half supported a ban on all GM food. More than 20 years of surveys indicate that the vast majority of Canadians want to know when they’re eating GMOs. Fully 88 per cent of those polled in the 2015 survey said they want mandatory labelling.

Their concern hasn’t escaped the notice of those who raise and sell much of the salmon consumed in this country. Five years ago, Marine Harvest, one of the world’s largest producers of farmed salmon, called for labelling of GMOs. Today, it says that it doesn’t grow, sell or research GM salmon, a policy it shares with major salmon producers in Canada. And most big grocery retailers have stated they don’t want GM salmon. When contacted by Maclean’s for this story, Metro, Sobeys, Wal-Mart and Loblaws—four of Canada’s five largest food retailers—declared that none of AquaBounty’s GM salmon from 2017 was sold in their stores, saying neither Sea Delight Canada nor Montreal Fish Co. supplied them with Atlantic salmon at the time.

“I’m happy to report that we don’t source salmon from these two companies,” says Geneviève Grégoire, communications adviser with Metro Richelieu Inc., which operates or supplies 948 food stores in Quebec and Ontario, including Metro, Super C, Food Basics, Adonis and Première Moisson. “As we said before, we didn’t and will not sell GM Atlantic salmon.”

If you’re looking for a more comprehensive and critical examination of the issue, read Lucy Sharratt’s Sept. 1, 2018 article for the Canadian Centre for Policy Alternatives (CCPA).

Designer groundcherries by CRISPR (clustered regularly interspaced short palindromic repeats)

I love the little things.. Groundcherries are just the right combination of sweet and tart.

Courtesy of Boyce Thompson Institute

They’re not in the stores very often and I wondered about that. Luckily, an  October 1, 2018 Boyce Thompson Institute news release by Mike Carroll (also on EurekAlert) explains why that is and how scientists are trying to overcome the difficulties,

You might not have heard of the groundcherry, or at least, never tasted one. But that could soon change thanks to research from the Van Eck Laboratory at Boyce Thompson Institute (BTI).

The groundcherry (Physalis pruinosa) is approximately the same size as a cherry tomato, but with a much sweeter flavor. The tropical-tasting fruit is also a powerhouse in terms of nutritional value. Packed with Vitamin C, Vitamin B, beta-carotene, phytosterols, and antioxidants, plus anti-inflammatory and medicinal properties, this tiny fruit might just be the next superfood.

“We feel there is potential for these to become a specialty fruit crop and to be grown on a larger scale in the US,” said Joyce Van Eck, associate professor at BTI.

However, even with their delicious flavor and nutritional value, groundcherries remain an underutilized crop in the United States. Several characteristics make them unsuitable for large-scale agriculture. [emphasis mine] In the October 1, 2018 issue of Nature Plants, Van Eck and colleagues present research which could change that and make groundcherries a common household name thanks to the genome editing tool CRISPR.

CRISPR has great promise for increasing crop productivity, especially for orphan crops such as groundcherries, which often contain undesirable characteristics resembling wild relatives. Leveraging knowledge from model crops (such as the tomato) can improve plant architecture (growth habit), flower production, fruit size, and more.

Selections for mutations in tomatoes have led to improvements in yield and Van Eck and her collaborator, Zach Lippman, at the Cold Spring Harbor Laboratory hypothesized that groundcherry genes could be similarly modified for immediate improvements. One concern with the groundcherry is its weedy growth habit. Genetic alterations have led to changes in the hormone that regulates flowering, producing plants which are more compact with fruit in clusters. They also targeted ways to increase fruit size and weight [emphases mine] through a CRISPR-generated mutation, leading to fifty-percent more fruit along a given stem and more seedy sections in each fruit.

“It’s exciting that we can take what we have learned in tomato and apply it to distantly related species,” said Van Eck.

Van Eck is also focused on fixing problems caused by fruit drop. [emphasis mine] Groundcherries drop to the ground, often before fully ripening.

This puts the fruit at risk for damage and creates a labor-intensive harvest process. In addition, fruit having to be gathered up from the ground causes concerns for food safety with potential for foodborne illness. A jointless mutation in tomatoes could provide the inspiration for using gene-editing to stop fruit drop in groundcherries.

“Physalis is the perfect candidate for looking at getting the fruit to not drop,” said Van Eck. “Gene editing might be the only way to fix this in the groundcherry.”

This study represents the first step towards improving the groundcherry and this work could be extended to target additional genes benefiting a range of consumer desirable traits.

Veronique Greenwood wrote an October 6, 2018 article for the New York Times about the scientists and the work featured in the October 1, 2018 issue of ‘Nature Plants’ and two scientists from Van Eck’s lab, Nathan T. Reem and Esperanza Shenstone, have written a November 14, 2018 essay about the work for The Conversation (h/t phys.org).

Here’s a link to and a citation for the research paper,

Rapid improvement of domestication traits in an orphan crop by genome editing by Zachary H. Lemmon, Nathan T. Reem, Justin Dalrymple, Sebastian Soyk, Kerry E. Swartwood, Daniel Rodriguez-Leal, Joyce Van Eck, & Zachary B. Lippman. Nature Plants volume 4, pages766–770 (2018) DOI: https://doi.org/10.1038/s41477-018-0259-x Published: 01 October 2018

This paper is behind a paywall.

All about gene editing, sexual reproduction, and the arts (an October 27, 2018 ArtSci Salon event in Toronto, Canada)

This ArtSci Salon event is part of the third world congress, GeNeDis (Genetics, Geriatrics, and Neurodegenerative Diseases Research). GeNeDis 2018 was organized by The Laboratory of Bioinformatics and Human Electrophysiology, Department of Informatics of the Ionian University (Corfu Greece) in cooperation with the Fields Institute (for Research in Mathematical Sciences) at the University of Toronto (Ontario, Canada) and Wilfrid Laurier University (Waterloo Ontario).

The ArtSci Salon will be presenting (from the ArtSci Salon GeNeDis event page) Note: Read carefully as this is a multi-pronged event,

GeNeDis Panel and Exhibition – Gene Editing, sexual reproduction and the arts: Oct 27, 2018

ArtSci salon is proud to present an event to explore the entangled issues of sex and sexual fantasy, sexual reproduction and sexual regulation, fertility and sexual technologies. We invited artists and scholars to address these themes using their preferred approach: the result is a thought provoking series which interrogates and imagines these issues through human/non-human sexual fantasies, interrogates them by means of modified gynaecological instruments, rewrites potential scenarios as enhanced and/or elderly humans, or offers unexpected ways to hack sex right here, right now.

Our goal is not just to imagine how media, technological enhancement, gene editing and medical treatments will transform our idea of sex and our sexuality as human beings and as part of the wide non-human world that surrounds us. It is also to think of how creative/critical initiatives may facilitate a sustained dialogue to help us cope with unresolved issues in the present. Interdisciplinary so!

The event will be accompanied by an exhibition on display Oct 18-Nov.8 in the Koffler Students Centre Cabinets, University of Toronto

Panel discussion

Gene editing, sexual reproduction and the arts: the present, the future and the imagined

ArtSci Salon will participate in the scientific conference GeNeDis (Genetics, Geriatrics, and Neurodegenerative Diseases Research) with a special panel addressing the topic of gene editing and sexual reproduction from a sciart perspective. The discussion will be preceded by the official opening of an exhibition illustrating how present issues in gynaecology and sexual regulation, hormonal management, human enhancement and sexual and cultural identity may be addressed, redressed, hacked and reimagined through the arts.

The Panel will be followed by a reception

Chair: Roberta Buiani, ArtSci Salon, Fields Institute
Speakers: Byron Rich, Samira Daneshvar, Adam Zaretsky & Dolores Steinman.

Saturday, Oct 27,
18:00-19:30

Lennox Hall
77 Adelaide Street W.

please, RSVP here 

For a little more detail about the event, you can check an Oct. 19, 2018 news item in Clot magazine,

On October 27th [2018], interdisciplinary group ArtSci Salon will present a panel discussion addressing the topic of gene editing and sexual reproduction from a sciart perspective. Preceding the discussion will be the official opening of an exhibition featuring the work of four of the speakers; a show that reimagines issues relating to gynaecology, sexual regulation, hormonal management and cultural identity through the arts.

During the conversation itself, the panel will focus on the current status of genome editing, presenting a nuanced alternative to sensationalist media narratives that often frame genome editing as a set of dichotomized future predictions, either utopian or dystopian. Stepping back into the present, the speakers will rethink the implications of genome editing through a creative lens, exploring the intersection of scientific and artistic interventions as they relate to human enhancement. Both panel and exhibition will approach these topics with an emphasis on their social implications, exploring in particular issues relating to sexual reproduction, fertility and sexual technologies – simultaneously raising awareness of sexual politics and the medicalization of the body.

The news item goes on to briefly describe the panelists.

The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle

Setting the stage

Not unexpectedly, CRISPR-Cas9  or clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 can be dangerous as these scientists note in a July 16, 2018 news item on phys.org,

Scientists at the Wellcome Sanger Institute have discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.

Reported today (16 July 2018) in the journal Nature Biotechnology, the study also revealed that standard tests for detecting DNA changes miss finding this genetic damage, and that caution and specific testing will be required for any potential gene therapies.

This CRISPR-Cas9 image reminds me of popcorn,

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)[ downloaded from https://phys.org/news/2018-07-genome-crisprcas9-gene-higher-thought.html#jCp]

A July 16, 2018 Wellcome Sanger Institute press release (also on EurekAlert), which originated the news item, offers a little more explanation,

CRISPR/Cas9 is one of the newest genome editing tools. It can alter sections of DNA in cells by cutting at specific points and introducing changes at that location. Already extensively used in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene, or correct a genetic mutation. However, any potential treatments would have to prove that they were safe.

Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. To investigate this further the researchers carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations, but at a greater distance from the target site.

The researchers found many of the cells had large genetic rearrangements such as DNA deletions and insertions. These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies. In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods.

Prof Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute, said: “This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects.”

Michael Kosicki, the first author from the Wellcome Sanger Institute, said: “My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true.”

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.

Prof Maria Jasin, an independent researcher from Memorial Slone Kettering Cancer Centre, New York, who was not involved in the study said: “This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site. While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically.”

For anyone who’d like to better understand the terms gene editing and CRISPR-Cas9, the Wellcome Sanger Institute provides these explanatory webpages, What is genome editing? and What is CRISPR-Cas9?

For the more advanced, here’s a link and a citation for the paper,

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements by Michael Kosicki, Kärt Tomberg, & Allan Bradley. Nature Biotechnology DOI: https://doi.org/10.1038/nbt.4192 Published 16 July 2018

This paper appears to be open access.

The kerfuffle

It seems this news has affected the CRISPR market. From a July 16, 2018 article by Cale Guthrie Weissman for Fast Company,

… CRISPR could unknowingly delete or alter non-targeted genes, which could lead to myriad unintended consequences. This is especially frightening, since the technology is going to be used in human clinical trials.

Meanwhile, other scientists working with CRISPR are trying to downplay the findings, telling STAT [a life sciences and business journalism website] that there have been no reported adverse effects similar to what the study describes. The news, however, has brought about a market reaction–at least three publicly traded companies that focus on CRISPR-based therapies are in stock nosedive. Crispr Therapeutics is down by over 6%; Editas fell by over 3%; and Intellia Therapeutics dropped by over 5%. [emphasis mine]

Damage control

Gaetan Burgio (geneticist, Australian National University)  in a July 16, 2018 essay on phys.org (originating from The Conversation) suggests some calm (Note: Links have been removed),

But a new study has called into question the precision of the technique [CRISPR gene editing technology].

The hope for gene editing is that it will be able to cure and correct diseases. To date, many successes have been reported, including curing deafness in mice, and in altering cells to cure cancer.

Some 17 clinical trials in human patients are registered [emphasis mine] testing gene editing on leukaemias, brain cancers and sickle cell anaemia (where red blood cells are misshaped, causing them to die). Before implementing CRISPR technology in clinics to treat cancer or congenital disorders, we must address whether the technique is safe and accurate.

There are a few options for getting around this problem. One option is to isolate the cells we wish to edit from the body and reinject only the ones we know have been correctly edited.

For example, lymphocytes (white blood cells) that are crucial to killing cancer cells could be taken out of the body, then modified using CRISPR to heighten their cancer-killing properties. The DNA of these cells could be sequenced in detail, and only the cells accurately and specifically gene-modified would be selected and delivered back into the body to kill the cancer cells.

While this strategy is valid for cells we can isolate from the body, some cells, such as neurons and muscles, cannot be removed from the body. These types of cells might not be suitable for gene editing using Cas9 scissors.

Fortunately, researchers have discovered other forms of CRISPR systems that don’t require the DNA to be cut. Some CRISPR systems only cut the RNA, not the DNA (DNA contains genetic instructions, RNA convey the instructions on how to synthesise proteins).

As RNA [ribonucleic acid] remains in our cells only for a specific period of time before being degraded, this would allow us to control the timing and duration of the CRISPR system delivery and reverse it (so the scissors are only functional for a short period of time).

This was found to be successful for dementia in mice. Similarly, some CRISPR systems simply change the letters of the DNA, rather than cutting them. This was successful for specific mutations causing diseases such as hereditary deafness in mice.

I agree with Burgio’s conclusion (not included here) that we have a lot more to learn and I can’t help wondering why there are 17 registered human clinical trials at this point.

Yes! Art, genetic modifications, gene editing, and xenotransplantation at the Vancouver Biennale (Canada)

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

Up to this point, I’ve been a little jealous of the Art/Sci Salon’s (Toronto, Canada) January 2018 workshops for artists and discussions about CRISPR ((clustered regularly interspaced short palindromic repeats))/Cas9 and its social implications. (See my January 10, 2018 posting for more about the events.) Now, it seems Vancouver may be in line for its ‘own’ discussion about CRISPR and the implications of gene editing. The image you saw (above) represents one of the installations being hosted by the 2018 – 2020 edition of the Vancouver Biennale.

While this posting is mostly about the Biennale and Piccinini’s work, there is a ‘science’ subsection featuring the science of CRISPR and xenotransplantation. Getting back to the Biennale and Piccinini: A major public art event since 1988, the Vancouver Biennale has hosted over 91 outdoor sculptures and new media works by more than 78 participating artists from over 25 countries and from 4 continents.

Quickie description of the 2018 – 2020 Vancouver Biennale

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

The Vancouver Biennale will be bringing new —and unusual— works of public art to the city beginning this June.

The theme for this season’s Vancouver Biennale exhibition is “re-IMAGE-n” and it kicks off on June 20 [2018] in Vanier Park with Saudi artist Ajlan Gharem’s Paradise Has Many Gates.

Gharem’s architectural chain-link sculpture resembles a traditional mosque, the piece is meant to challenge the notions of religious orthodoxy and encourages individuals to image a space free of Islamophobia.

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].

Given that this blog is focused on nanotechnology and other emerging technologies such as CRISPR, I’m focusing on Piccinini’s work and its art/science or sci-art status. This image from the GOMA Gallery where Piccinini’s ‘Curious Affection‘ installation is being shown from March 24 – Aug. 5, 2018 in Brisbane, Queensland, Australia may give you some sense of what one of her installations is like,

Courtesy: Queensland Art Gallery | Gallery of Modern Art (QAGOMA)

I spoke with Serena at the Vancouver Biennale office and asked about the ‘interactive’ aspect of Piccinini’s installation. She suggested the term ‘immersive’ as an alternative. In other words, you won’t be playing with the sculptures or pressing buttons and interacting with computer screens or robots. She also noted that the ticket prices have not been set yet and they are currently developing events focused on the issues raised by the installation. She knew that 2018 is the 200th anniversary of the publication of Mary Shelley’s Frankenstein but I’m not sure how the Biennale folks plan (or don’t plan)  to integrate any recognition of the novle’s impact on the discussions about ‘new’ technologies .They expect Piccinini will visit Vancouver. (Note 1: Piccinini’s work can  also be seen in a group exhibition titled: Frankenstein’s Birthday Party at the Hosfselt Gallery in San Francisco (California, US) from June 23 – August 11, 2018.  Note 2: I featured a number of international events commemorating the 200th anniversary of the publication of Mary Shelley’s novel, Frankenstein, in my Feb. 26, 2018 posting. Note 3: The term ‘Frankenfoods’ helped to shape the discussion of genetically modified organisms and food supply on this planet. It was a wildly successful campaign for activists affecting legislation in some areas of research. Scientists have not been as enthusiastic about the effects. My January 15, 2009 posting briefly traces a history of the term.)

The 2018 – 2020 Vancouver Biennale and science

A June 7, 2018 Vancouver Biennale news release provides more detail about the current series of exhibitions,

The Biennale is also committed to presenting artwork at the cutting edge of discussion and in keeping with the STEAM (science, technology, engineering, arts, math[ematics]) approach to integrating the arts and sciences. In August [2018], Colombian/American visual artist Jessica Angel will present her monumental installation Dogethereum Bridge at Hinge Park in Olympic Village. Inspired by blockchain technology, the artwork’s design was created through the integration of scientific algorithms, new developments in technology, and the arts. This installation, which will serve as an immersive space and collaborative hub for artists and technologists, will host a series of activations with blockchain as the inspirational jumping-off point.

In what is expected to become one of North America’s most talked-about exhibitions of the year, Melbourne artist Patricia Piccinini’s Curious Imaginings will see the intersection of art, science, and ethics. For the first time in the Biennale’s fifteen years of creating transformative experiences, and in keeping with the 2018-2020 theme of “re-IMAGE-n,” the Biennale will explore art in unexpected places by exhibiting in unconventional interior spaces.  The hyperrealist “world of oddly captivating, somewhat grotesque, human-animal hybrid creatures” will be the artist’s first exhibit in a non-museum setting, transforming a wing of the 105-year-old Patricia Hotel. Situated in Vancouver’s oldest neighbourbood of Strathcona, Piccinini’s interactive experience will “challenge us to explore the social impacts of emerging bio-technology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.” In this intimate hotel setting located in a neighborhood continually undergoing its own change, Curious Imaginings will empower visitors to personally consider questions posed by the exhibition, including the promises and consequences of genetic research and human interference. …

There are other pieces being presented at the Biennale but my special interest is in the art/sci pieces and, at this point, CRISPR.

Piccinini in more depth

You can find out more about Patricia Piccinini in her biography on the Vancouver Biennale website but I found this Char Larsson April 7, 2018 article for the Independent (UK) more informative (Note: A link has been removed),

Patricia Piccinini’s sculptures are deeply disquieting. Walking through Curious Affection, her new solo exhibition at Brisbane’s Gallery of Modern Art, is akin to entering a science laboratory full of DNA experiments. Made from silicone, fibreglass and even human hair, her sculptures are breathtakingly lifelike, however, we can’t be sure what life they are like. The artist creates an exuberant parallel universe where transgenic experiments flourish and human evolution has given way to genetic engineering and DNA splicing.

Curious Affection is a timely and welcome recognition of Piccinini’s enormous contribution to reaching back to the mid-1990s. Working across a variety of mediums including photography, video and drawing, she is perhaps best known for her hyperreal creations.

As a genre, hyperrealism depends on the skill of the artist to create the illusion of reality. To be truly successful, it must convince the spectator of its realness. Piccinini acknowledges this demand, but with a delightful twist. The excruciating attention to detail deliberately solicits our desire to look, only to generate unease, as her sculptures are imbued with a fascinating otherness. Part human, part animal, the works are uncannily familiar, but also alarmingly “other”.

Inspired by advances in genetically modified pigs to generate replacement organs for humans [also known as xenotransplantation], we are reminded that Piccinini has always been at the forefront of debates concerning the possibilities of science, technology and DNA cloning. She does so, however, with a warm affection and sense of humour, eschewing the hysterical anxiety frequently accompanying these scientific developments.

Beyond the astonishing level of detail achieved by working with silicon and fibreglass, there is an ethics at work here. Piccinini is asking us not to avert our gaze from the other, and in doing so, to develop empathy and understanding through the encounter.

I encourage anyone who’s interested to read Larsson’s entire piece (April 7, 2018 article).

According to her Wikipedia entry, Piccinini works in a variety of media including video, sound, sculpture, and more. She also has her own website.

Gene editing and xenotransplantation

Sarah Zhang’s June 8, 2018 article for The Atlantic provides a peek at the extraordinary degree of interest and competition in the field of gene editing and CRISPR ((clustered regularly interspaced short palindromic repeats))/Cas9 research (Note: A link has been removed),

China Is Genetically Engineering Monkeys With Brain Disorders

Guoping Feng applied to college the first year that Chinese universities reopened after the Cultural Revolution. It was 1977, and more than a decade’s worth of students—5.7 million—sat for the entrance exams. Feng was the only one in his high school to get in. He was assigned—by chance, essentially—to medical school. Like most of his contemporaries with scientific ambitions, he soon set his sights on graduate studies in the United States. “China was really like 30 to 50 years behind,” he says. “There was no way to do cutting-edge research.” So in 1989, he left for Buffalo, New York, where for the first time he saw snow piled several feet high. He completed his Ph.D. in genetics at the State University of New York at Buffalo.

Feng is short and slim, with a monk-like placidity and a quick smile, and he now holds an endowed chair in neuroscience at MIT, where he focuses on the genetics of brain disorders. His 45-person lab is part of the McGovern Institute for Brain Research, which was established in 2000 with the promise of a $350 million donation, the largest ever received by the university. In short, his lab does not lack for much.

Yet Feng now travels to China several times a year, because there, he can pursue research he has not yet been able to carry out in the United States. [emphasis mine] …

Feng had organized a symposium at SIAT [Shenzhen Institutes of Advanced Technology], and he was not the only scientist who traveled all the way from the United States to attend: He invited several colleagues as symposium speakers, including a fellow MIT neuroscientist interested in tree shrews, a tiny mammal related to primates and native to southern China, and Chinese-born neuroscientists who study addiction at the University of Pittsburgh and SUNY Upstate Medical University. Like Feng, they had left China in the ’80s and ’90s, part of a wave of young scientists in search of better opportunities abroad. Also like Feng, they were back in China to pursue a type of cutting-edge research too expensive and too impractical—and maybe too ethically sensitive—in the United States.

Here’s what precipitated Feng’s work in China, (from Zhang’s article; Note: Links have been removed)

At MIT, Feng’s lab worked on genetically engineering a monkey species called marmosets, which are very small and genuinely bizarre-looking. They are cheaper to keep due to their size, but they are a relatively new lab animal, and they can be difficult to train on lab tasks. For this reason, Feng also wanted to study Shank3 on macaques in China. Scientists have been cataloging the social behavior of macaques for decades, making it an obvious model for studies of disorders like autism that have a strong social component. Macaques are also more closely related to humans than marmosets, making their brains a better stand-in for those of humans.

The process of genetically engineering a macaque is not trivial, even with the advanced tools of CRISPR. Researchers begin by dosing female monkeys with the same hormones used in human in vitro fertilization. They then collect and fertilize the eggs, and inject the resulting embryos with CRISPR proteins using a long, thin glass needle. Monkey embryos are far more sensitive than mice embryos, and can be affected by small changes in the pH of the injection or the concentration of CRISPR proteins. Only some of the embryos will have the desired mutation, and only some will survive once implanted in surrogate mothers. It takes dozens of eggs to get to just one live monkey, so making even a few knockout monkeys required the support of a large breeding colony.

The first Shank3 macaque was born in 2015. Four more soon followed, bringing the total to five.

To visit his research animals, Feng now has to fly 8,000 miles across 12 time zones. It would be a lot more convenient to carry out his macaque research in the United States, of course, but so far, he has not been able to.

He originally inquired about making Shank3 macaques at the New England Primate Research Center, one of eight national primate research centers then funded by the National Institutes of Health in partnership with a local institution (Harvard Medical School, in this case). The center was conveniently located in Southborough, Massachusetts, just 20 miles west of the MIT campus. But in 2013, Harvard decided to shutter the center.

The decision came as a shock to the research community, and it was widely interpreted as a sign of waning interest in primate research in the United States. While the national primate centers have been important hubs of research on HIV, Zika, Ebola, and other diseases, they have also come under intense public scrutiny. Animal-rights groups like the Humane Society of the United States have sent investigators to work undercover in the labs, and the media has reported on monkey deaths in grisly detail. Harvard officially made its decision to close for “financial” reasons. But the announcement also came after the high-profile deaths of four monkeys from improper handling between 2010 and 2012. The deaths sparked a backlash; demonstrators showed up at the gates. The university gave itself two years to wind down their primate work, officially closing the center in 2015.

“They screwed themselves,” Michael Halassa, the MIT neuroscientist who spoke at Feng’s symposium, told me in Shenzhen. Wei-Dong Yao, another one of the speakers, chimed in, noting that just two years later CRISPR has created a new wave of interest in primate research. Yao was one of the researchers at Harvard’s primate center before it closed; he now runs a lab at SUNY Upstate Medical University that uses genetically engineered mouse and human stem cells, and he had come to Shenzhen to talk about restarting his addiction research on primates.

Here’s comes the competition (from Zhang’s article; Note: Links have been removed),

While the U.S. government’s biomedical research budget has been largely flat, both national and local governments in China are eager to raise their international scientific profiles, and they are shoveling money into research. A long-rumored, government-sponsored China Brain Project is supposed to give neuroscience research, and primate models in particular, a big funding boost. Chinese scientists may command larger salaries, too: Thanks to funding from the Shenzhen local government, a new principal investigator returning from overseas can get 3 million yuan—almost half a million U.S. dollars—over his or her first five years. China is even finding success in attracting foreign researchers from top U.S. institutions like Yale.

In the past few years, China has seen a miniature explosion of genetic engineering in monkeys. In Kunming, Shanghai, and Guangzhou, scientists have created monkeys engineered to show signs of Parkinson’s, Duchenne muscular dystrophy, autism, and more. And Feng’s group is not even the only one in China to have created Shank3 monkeys. Another group—a collaboration primarily between researchers at Emory University and scientists in China—has done the same.

Chinese scientists’ enthusiasm for CRISPR also extends to studies of humans, which are moving much more quickly, and in some cases under less oversight, than in the West. The first studies to edit human embryos and first clinical trials for cancer therapies using CRISPR have all happened in China. [emphases mine]

Some ethical issues are also covered (from Zhang’s article),

Parents with severely epileptic children had asked him if it would be possible to study the condition in a monkey. Feng told them what he thought would be technically possible. “But I also said, ‘I’m not sure I want to generate a model like this,’” he recalled. Maybe if there were a drug to control the monkeys’ seizures, he said: “I cannot see them seizure all the time.”

But is it ethical, he continued, to let these babies die without doing anything? Is it ethical to generate thousands or millions of mutant mice for studies of brain disorders, even when you know they will not elucidate much about human conditions?

Primates should only be used if other models do not work, says Feng, and only if a clear path forward is identified. The first step in his work, he says, is to use the Shank3 monkeys to identify the changes the mutations cause in the brain. Then, researchers might use that information to find targets for drugs, which could be tested in the same monkeys. He’s talking with the Oregon National Primate Research Center about carrying out similar work in the United States. ….[Note: I have a three-part series about CRISPR and germline editing* in the US, precipitated by research coming out of Oregon, Part 1, which links to the other parts, is here.]

Zhang’s June 8, 2018 article is excellent and I highly recommend reading it.

I touched on the topic of xenotransplanttaion in a commentary on a book about the science  of the television series, Orphan Black in a January 31,2018 posting (Note: A chimera is what you use to incubate a ‘human’ organ for transplantation or, more accurately, xenotransplantation),

On the subject of chimeras, the Canadian Broadcasting Corporation (CBC) featured a January 26, 2017 article about the pig-human chimeras on its website along with a video,

The end

I am very excited to see Piccinini’s work come to Vancouver. There have been a number of wonderful art and art/science installations and discussions here but this is the first one (I believe) to tackle the emerging gene editing technologies and the issues they raise. (It also fits in rather nicely with the 200th anniversary of the publication of Mary Shelley’s Frankenstein which continues to raise issues and stimulate discussion.)

In addition to the ethical issues raised in Zhang’s article, there are some other philosophical questions:

  • what does it mean to be human
  • if we are going to edit genes to create hybrid human/animals, what are they and how do they fit into our current animal/human schema
  • are you still human if you’ve had an organ transplant where the organ was incubated in a pig

There are also going to be legal issues. In addition to any questions about legal status, there are also fights about intellectual property such as the one involving Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley (March 15, 2017 posting)..

While I’m thrilled about the Piccinini installation, it should be noted the issues raised by other artworks hosted in this version of the Biennale are important. Happily, they have been broached here in Vancouver before and I suspect this will result in more nuanced  ‘conversations’ than are possible when a ‘new’ issue is introduced.

Bravo 2018 – 2020 Vancouver Biennale!

* Germline editing is when your gene editing will affect subsequent generations as opposed to editing out a mutated gene for the lifetime of a single individual.

Art/sci and CRISPR links

This art/science posting may prove of some interest:

The connectedness of living things: an art/sci project in Saskatchewan: evolutionary biology (February 16, 2018)

A selection of my CRISPR posts:

CRISPR and editing the germline in the US (part 1 of 3): In the beginning (August 15, 2017)

NOTE: An introductory CRISPR video describing how CRISPR/Cas9 works was embedded in part1.

Why don’t you CRISPR yourself? (January 25, 2018)

Editing the genome with CRISPR ((clustered regularly interspaced short palindromic repeats)-carrying nanoparticles (January 26, 2018)

Immune to CRISPR? (April 10, 2018)

CRISPR-Cas12a as a new diagnostic tool

Similar to Cas9, Cas12a is has an added feature as noted in this February 15, 2018 news item on ScienceDaily,

Utilizing an unsuspected activity of the CRISPR-Cas12a protein, researchers created a simple diagnostic system called DETECTR to analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance and also diagnose bacterial and viral infections. The scientists discovered that when Cas12a binds its double-stranded DNA target, it indiscriminately chews up all single-stranded DNA. They then created reporter molecules attached to single-stranded DNA to signal when Cas12a finds its target.

A February 15, 2018 University of California at Berkeley (UC Berkeley) news release by Robert Sanders and which originated the news item, provides more detail and history,

CRISPR-Cas12a, one of the DNA-cutting proteins revolutionizing biology today, has an unexpected side effect that makes it an ideal enzyme for simple, rapid and accurate disease diagnostics.

blood in test tube

(iStock)

Cas12a, discovered in 2015 and originally called Cpf1, is like the well-known Cas9 protein that UC Berkeley’s Jennifer Doudna and colleague Emmanuelle Charpentier turned into a powerful gene-editing tool in 2012.

CRISPR-Cas9 has supercharged biological research in a mere six years, speeding up exploration of the causes of disease and sparking many potential new therapies. Cas12a was a major addition to the gene-cutting toolbox, able to cut double-stranded DNA at places that Cas9 can’t, and, because it leaves ragged edges, perhaps easier to use when inserting a new gene at the DNA cut.

But co-first authors Janice Chen, Enbo Ma and Lucas Harrington in Doudna’s lab discovered that when Cas12a binds and cuts a targeted double-stranded DNA sequence, it unexpectedly unleashes indiscriminate cutting of all single-stranded DNA in a test tube.

Most of the DNA in a cell is in the form of a double-stranded helix, so this is not necessarily a problem for gene-editing applications. But it does allow researchers to use a single-stranded “reporter” molecule with the CRISPR-Cas12a protein, which produces an unambiguous fluorescent signal when Cas12a has found its target.

“We continue to be fascinated by the functions of bacterial CRISPR systems and how mechanistic understanding leads to opportunities for new technologies,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute investigator.

DETECTR diagnostics

The new DETECTR system based on CRISPR-Cas12a can analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance as well as diagnose bacterial and viral infections. Target DNA is amplified by RPA to make it easier for Cas12a to find it and bind, unleashing indiscriminate cutting of single-stranded DNA, including DNA attached to a fluorescent marker (gold star) that tells researchers that Cas12a has found its target.

The UC Berkeley researchers, along with their colleagues at UC San Francisco, will publish their findings Feb. 15 [2018] via the journal Science’s fast-track service, First Release.

The researchers developed a diagnostic system they dubbed the DNA Endonuclease Targeted CRISPR Trans Reporter, or DETECTR, for quick and easy point-of-care detection of even small amounts of DNA in clinical samples. It involves adding all reagents in a single reaction: CRISPR-Cas12a and its RNA targeting sequence (guide RNA), fluorescent reporter molecule and an isothermal amplification system called recombinase polymerase amplification (RPA), which is similar to polymerase chain reaction (PCR). When warmed to body temperature, RPA rapidly multiplies the number of copies of the target DNA, boosting the chances Cas12a will find one of them, bind and unleash single-strand DNA cutting, resulting in a fluorescent readout.

The UC Berkeley researchers tested this strategy using patient samples containing human papilloma virus (HPV), in collaboration with Joel Palefsky’s lab at UC San Francisco. Using DETECTR, they were able to demonstrate accurate detection of the “high-risk” HPV types 16 and 18 in samples infected with many different HPV types.

“This protein works as a robust tool to detect DNA from a variety of sources,” Chen said. “We want to push the limits of the technology, which is potentially applicable in any point-of-care diagnostic situation where there is a DNA component, including cancer and infectious disease.”

The indiscriminate cutting of all single-stranded DNA, which the researchers discovered holds true for all related Cas12 molecules, but not Cas9, may have unwanted effects in genome editing applications, but more research is needed on this topic, Chen said. During the transcription of genes, for example, the cell briefly creates single strands of DNA that could accidentally be cut by Cas12a.

The activity of the Cas12 proteins is similar to that of another family of CRISPR enzymes, Cas13a, which chew up RNA after binding to a target RNA sequence. Various teams, including Doudna’s, are developing diagnostic tests using Cas13a that could, for example, detect the RNA genome of HIV.

infographic about DETECTR system

(Infographic by the Howard Hughes Medical Institute)

These new tools have been repurposed from their original role in microbes where they serve as adaptive immune systems to fend off viral infections. In these bacteria, Cas proteins store records of past infections and use these “memories” to identify harmful DNA during infections. Cas12a, the protein used in this study, then cuts the invading DNA, saving the bacteria from being taken over by the virus.

The chance discovery of Cas12a’s unusual behavior highlights the importance of basic research, Chen said, since it came from a basic curiosity about the mechanism Cas12a uses to cleave double-stranded DNA.

“It’s cool that, by going after the question of the cleavage mechanism of this protein, we uncovered what we think is a very powerful technology useful in an array of applications,” Chen said.

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

CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity by Janice S. Chen, Enbo Ma, Lucas B. Harrington, Maria Da Costa, Xinran Tian, Joel M. Palefsky, Jennifer A. Doudna. Science 15 Feb 2018: eaar6245 DOI: 10.1126/science.aar6245

This paper is behind a paywall.

Emerging technology and the law

I have three news bits about legal issues that are arising as a consequence of emerging technologies.

Deep neural networks, art, and copyright

Caption: The rise of automated art opens new creative avenues, coupled with new problems for copyright protection. Credit: Provided by: Alexander Mordvintsev, Christopher Olah and Mike Tyka

Presumably this artwork is a demonstration of automated art although they never really do explain how in the news item/news release. An April 26, 2017 news item on ScienceDaily announces research into copyright and the latest in using neural networks to create art,

In 1968, sociologist Jean Baudrillard wrote on automatism that “contained within it is the dream of a dominated world […] that serves an inert and dreamy humanity.”

With the growing popularity of Deep Neural Networks (DNN’s), this dream is fast becoming a reality.

Dr. Jean-Marc Deltorn, researcher at the Centre d’études internationales de la propriété intellectuelle in Strasbourg, argues that we must remain a responsive and responsible force in this process of automation — not inert dominators. As he demonstrates in a recent Frontiers in Digital Humanities paper, the dream of automation demands a careful study of the legal problems linked to copyright.

An April 26, 2017 Frontiers (publishing) news release on EurekAlert, which originated the news item, describes the research in more detail,

For more than half a century, artists have looked to computational processes as a way of expanding their vision. DNN’s are the culmination of this cross-pollination: by learning to identify a complex number of patterns, they can generate new creations.

These systems are made up of complex algorithms modeled on the transmission of signals between neurons in the brain.

DNN creations rely in equal measure on human inputs and the non-human algorithmic networks that process them.

Inputs are fed into the system, which is layered. Each layer provides an opportunity for a more refined knowledge of the inputs (shape, color, lines). Neural networks compare actual outputs to expected ones, and correct the predictive error through repetition and optimization. They train their own pattern recognition, thereby optimizing their learning curve and producing increasingly accurate outputs.

The deeper the layers are, the higher the level of abstraction. The highest layers are able to identify the contents of a given input with reasonable accuracy, after extended periods of training.

Creation thus becomes increasingly automated through what Deltorn calls “the arcane traceries of deep architecture”. The results are sufficiently abstracted from their sources to produce original creations that have been exhibited in galleries, sold at auction and performed at concerts.

The originality of DNN’s is a combined product of technological automation on one hand, human inputs and decisions on the other.

DNN’s are gaining popularity. Various platforms (such as DeepDream) now allow internet users to generate their very own new creations . This popularization of the automation process calls for a comprehensive legal framework that ensures a creator’s economic and moral rights with regards to his work – copyright protection.

Form, originality and attribution are the three requirements for copyright. And while DNN creations satisfy the first of these three, the claim to originality and attribution will depend largely on a given country legislation and on the traceability of the human creator.

Legislation usually sets a low threshold to originality. As DNN creations could in theory be able to create an endless number of riffs on source materials, the uncurbed creation of original works could inflate the existing number of copyright protections.

Additionally, a small number of national copyright laws confers attribution to what UK legislation defines loosely as “the person by whom the arrangements necessary for the creation of the work are undertaken.” In the case of DNN’s, this could mean anybody from the programmer to the user of a DNN interface.

Combined with an overly supple take on originality, this view on attribution would further increase the number of copyrightable works.

The risk, in both cases, is that artists will be less willing to publish their own works, for fear of infringement of DNN copyright protections.

In order to promote creativity – one seminal aim of copyright protection – the issue must be limited to creations that manifest a personal voice “and not just the electric glint of a computational engine,” to quote Deltorn. A delicate act of discernment.

DNN’s promise new avenues of creative expression for artists – with potential caveats. Copyright protection – a “catalyst to creativity” – must be contained. Many of us gently bask in the glow of an increasingly automated form of technology. But if we want to safeguard the ineffable quality that defines much art, it might be a good idea to hone in more closely on the differences between the electric and the creative spark.

This research is and be will part of a broader Frontiers Research Topic collection of articles on Deep Learning and Digital Humanities.

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

Deep Creations: Intellectual Property and the Automata by Jean-Marc Deltorn. Front. Digit. Humanit., 01 February 2017 | https://doi.org/10.3389/fdigh.2017.00003

This paper is open access.

Conference on governance of emerging technologies

I received an April 17, 2017 notice via email about this upcoming conference. Here’s more from the Fifth Annual Conference on Governance of Emerging Technologies: Law, Policy and Ethics webpage,

The Fifth Annual Conference on Governance of Emerging Technologies:

Law, Policy and Ethics held at the new

Beus Center for Law & Society in Phoenix, AZ

May 17-19, 2017!

Call for Abstracts – Now Closed

The conference will consist of plenary and session presentations and discussions on regulatory, governance, legal, policy, social and ethical aspects of emerging technologies, including (but not limited to) nanotechnology, synthetic biology, gene editing, biotechnology, genomics, personalized medicine, human enhancement technologies, telecommunications, information technologies, surveillance technologies, geoengineering, neuroscience, artificial intelligence, and robotics. The conference is premised on the belief that there is much to be learned and shared from and across the governance experience and proposals for these various emerging technologies.

Keynote Speakers:

Gillian HadfieldRichard L. and Antoinette Schamoi Kirtland Professor of Law and Professor of Economics USC [University of Southern California] Gould School of Law

Shobita Parthasarathy, Associate Professor of Public Policy and Women’s Studies, Director, Science, Technology, and Public Policy Program University of Michigan

Stuart Russell, Professor at [University of California] Berkeley, is a computer scientist known for his contributions to artificial intelligence

Craig Shank, Vice President for Corporate Standards Group in Microsoft’s Corporate, External and Legal Affairs (CELA)

Plenary Panels:

Innovation – Responsible and/or Permissionless

Ellen-Marie Forsberg, Senior Researcher/Research Manager at Oslo and Akershus University College of Applied Sciences

Adam Thierer, Senior Research Fellow with the Technology Policy Program at the Mercatus Center at George Mason University

Wendell Wallach, Consultant, ethicist, and scholar at Yale University’s Interdisciplinary Center for Bioethics

 Gene Drives, Trade and International Regulations

Greg Kaebnick, Director, Editorial Department; Editor, Hastings Center Report; Research Scholar, Hastings Center

Jennifer Kuzma, Goodnight-North Carolina GlaxoSmithKline Foundation Distinguished Professor in Social Sciences in the School of Public and International Affairs (SPIA) and co-director of the Genetic Engineering and Society (GES) Center at North Carolina State University

Andrew Maynard, Senior Sustainability Scholar, Julie Ann Wrigley Global Institute of Sustainability Director, Risk Innovation Lab, School for the Future of Innovation in Society Professor, School for the Future of Innovation in Society, Arizona State University

Gary Marchant, Regents’ Professor of Law, Professor of Law Faculty Director and Faculty Fellow, Center for Law, Science & Innovation, Arizona State University

Marc Saner, Inaugural Director of the Institute for Science, Society and Policy, and Associate Professor, University of Ottawa Department of Geography

Big Data

Anupam Chander, Martin Luther King, Jr. Professor of Law and Director, California International Law Center, UC Davis School of Law

Pilar Ossorio, Professor of Law and Bioethics, University of Wisconsin, School of Law and School of Medicine and Public Health; Morgridge Institute for Research, Ethics Scholar-in-Residence

George Poste, Chief Scientist, Complex Adaptive Systems Initiative (CASI) (http://www.casi.asu.edu/), Regents’ Professor and Del E. Webb Chair in Health Innovation, Arizona State University

Emily Shuckburgh, climate scientist and deputy head of the Polar Oceans Team at the British Antarctic Survey, University of Cambridge

 Responsible Development of AI

Spring Berman, Ira A. Fulton Schools of Engineering, Arizona State University

John Havens, The IEEE [Institute of Electrical and Electronics Engineers] Global Initiative for Ethical Considerations in Artificial Intelligence and Autonomous Systems

Subbarao Kambhampati, Senior Sustainability Scientist, Julie Ann Wrigley Global Institute of Sustainability, Professor, School of Computing, Informatics and Decision Systems Engineering, Ira A. Fulton Schools of Engineering, Arizona State University

Wendell Wallach, Consultant, Ethicist, and Scholar at Yale University’s Interdisciplinary Center for Bioethics

Existential and Catastrophic Ricks [sic]

Tony Barrett, Co-Founder and Director of Research of the Global Catastrophic Risk Institute

Haydn Belfield,  Academic Project Administrator, Centre for the Study of Existential Risk at the University of Cambridge

Margaret E. Kosal Associate Director, Sam Nunn School of International Affairs, Georgia Institute of Technology

Catherine Rhodes,  Academic Project Manager, Centre for the Study of Existential Risk at CSER, University of Cambridge

These were the panels that are of interest to me; there are others on the homepage.

Here’s some information from the Conference registration webpage,

Early Bird Registration – $50 off until May 1! Enter discount code: earlybirdGETs50

New: Group Discount – Register 2+ attendees together and receive an additional 20% off for all group members!

Click Here to Register!

Conference registration fees are as follows:

  • General (non-CLE) Registration: $150.00
  • CLE Registration: $350.00
  • *Current Student / ASU Law Alumni Registration: $50.00
  • ^Cybsersecurity sessions only (May 19): $100 CLE / $50 General / Free for students (registration info coming soon)

There you have it.

Neuro-techno future laws

I’m pretty sure this isn’t the first exploration of potential legal issues arising from research into neuroscience although it’s the first one I’ve stumbled across. From an April 25, 2017 news item on phys.org,

New human rights laws to prepare for advances in neurotechnology that put the ‘freedom of the mind’ at risk have been proposed today in the open access journal Life Sciences, Society and Policy.

The authors of the study suggest four new human rights laws could emerge in the near future to protect against exploitation and loss of privacy. The four laws are: the right to cognitive liberty, the right to mental privacy, the right to mental integrity and the right to psychological continuity.

An April 25, 2017 Biomed Central news release on EurekAlert, which originated the news item, describes the work in more detail,

Marcello Ienca, lead author and PhD student at the Institute for Biomedical Ethics at the University of Basel, said: “The mind is considered to be the last refuge of personal freedom and self-determination, but advances in neural engineering, brain imaging and neurotechnology put the freedom of the mind at risk. Our proposed laws would give people the right to refuse coercive and invasive neurotechnology, protect the privacy of data collected by neurotechnology, and protect the physical and psychological aspects of the mind from damage by the misuse of neurotechnology.”

Advances in neurotechnology, such as sophisticated brain imaging and the development of brain-computer interfaces, have led to these technologies moving away from a clinical setting and into the consumer domain. While these advances may be beneficial for individuals and society, there is a risk that the technology could be misused and create unprecedented threats to personal freedom.

Professor Roberto Andorno, co-author of the research, explained: “Brain imaging technology has already reached a point where there is discussion over its legitimacy in criminal court, for example as a tool for assessing criminal responsibility or even the risk of reoffending. Consumer companies are using brain imaging for ‘neuromarketing’, to understand consumer behaviour and elicit desired responses from customers. There are also tools such as ‘brain decoders’ which can turn brain imaging data into images, text or sound. All of these could pose a threat to personal freedom which we sought to address with the development of four new human rights laws.”

The authors explain that as neurotechnology improves and becomes commonplace, there is a risk that the technology could be hacked, allowing a third-party to ‘eavesdrop’ on someone’s mind. In the future, a brain-computer interface used to control consumer technology could put the user at risk of physical and psychological damage caused by a third-party attack on the technology. There are also ethical and legal concerns over the protection of data generated by these devices that need to be considered.

International human rights laws make no specific mention to neuroscience, although advances in biomedicine have become intertwined with laws, such as those concerning human genetic data. Similar to the historical trajectory of the genetic revolution, the authors state that the on-going neurorevolution will force a reconceptualization of human rights laws and even the creation of new ones.

Marcello Ienca added: “Science-fiction can teach us a lot about the potential threat of technology. Neurotechnology featured in famous stories has in some cases already become a reality, while others are inching ever closer, or exist as military and commercial prototypes. We need to be prepared to deal with the impact these technologies will have on our personal freedom.”

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

Towards new human rights in the age of neuroscience and neurotechnology by Marcello Ienca and Roberto Andorno. Life Sciences, Society and Policy201713:5 DOI: 10.1186/s40504-017-0050-1 Published: 26 April 2017

©  The Author(s). 2017

This paper is open access.

Managing risks in a world of converging technology (the fourth industrial revolution)

Finally there’s an answer to the question: What (!!!) is the fourth industrial revolution? (I took a guess [wrongish] in my Nov. 20, 2015 post about a special presentation at the 2016 World Economic Forum’s IdeasLab.)

Andrew Maynard in a Dec. 3, 2015 think piece (also called a ‘thesis’) for Nature Nanotechnology answers the question,

… an approach that focuses on combining technologies such as additive manufacturing, automation, digital services and the Internet of Things, and … is part of a growing movement towards exploiting the convergence between emerging technologies. This technological convergence is increasingly being referred to as the ‘fourth industrial revolution’, and like its predecessors, it promises to transform the ways we live and the environments we live in. (While there is no universal agreement on what constitutes an ‘industrial revolution’, proponents of the fourth industrial revolution suggest that the first involved harnessing steam power to mechanize production; the second, the use of electricity in mass production; and the third, the use of electronics and information technology to automate production.)

In anticipation of the the 2016 World Economic Forum (WEF), which has the fourth industrial revolution as its theme, Andrew  explains how he sees the situation we are sliding into (from Andrew Maynard’s think piece),

As more people get closer to gaining access to increasingly powerful converging technologies, a complex risk landscape is emerging that lies dangerously far beyond the ken of current regulations and governance frameworks. As a result, we are in danger of creating a global ‘wild west’ of technology innovation, where our good intentions may be among the first casualties.

There are many other examples where converging technologies are increasing the gap between what we can do and our understanding of how to do it responsibly. The convergence between robotics, nanotechnology and cognitive augmentation, for instance, and that between artificial intelligence, gene editing and maker communities both push us into uncertain territory. Yet despite the vulnerabilities inherent with fast-evolving technological capabilities that are tightly coupled, complex and poorly regulated, we lack even the beginnings of national or international conceptual frameworks to think about responsible decision-making and responsive governance.

He also lists some recommendations,

Fostering effective multi-stakeholder dialogues.

Encouraging actionable empathy.

Providing educational opportunities for current and future stakeholders.

Developing next-generation foresight capabilities.

Transforming approaches to risk.

Investing in public–private partnerships.

Andrew concludes with this,

… The good news is that, in fields such as nanotechnology and synthetic biology, we have already begun to develop the skills to do this — albeit in a small way. We now need to learn how to scale up our efforts, so that our convergence in working together to build a better future mirrors the convergence of the technologies that will help achieve this.

It’s always a pleasure to read Andrew’s work as it’s thoughtful. I was surprised (since Andrew is a physicist by training) and happy to see the recommendation for “actionable empathy.”

Although, I don’t always agree with him on this occasion I don’t have any particular disagreements but I think that including a recommendation or two to cover the certainty we will get something wrong and have to work quickly to right things would be a good idea.  I’m thinking primarily of governments which are notoriously slow to respond with legislation for new developments and equally slow to change that legislation when the situation changes.

The technological environment Andrew is describing is dynamic, that is fast-moving and changing at a pace we have yet to properly conceptualize. Governments will need to change so they can respond in an agile fashion. My suggestion is:

Develop policy task forces that can be convened in hours and given the authority to respond to an immediate situation with oversight after the fact

Getting back to Andrew Maynard, you can find his think piece in its entirety via this link and citation,

Navigating the fourth industrial revolution by Andrew D. Maynard. Nature Nanotechnology 10, 1005–1006 (2015) doi:10.1038/nnano.2015.286 Published online 03 December 2015

This paper is behind a paywall.