Tag Archives: The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science

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

Why don’t you CRISPR yourself?

It must have been quite the conference. Josiah Zayner plunged a needle into himself and claimed to have changed his DNA (deoxyribonucleic acid) while giving his talk. (*Segue: There is some Canadian content if you keep reading.*) From an Oct. 10, 2017 article by Adele Peters for Fast Company (Note: A link has been removed),

“What we’ve got here is some DNA, and this is a syringe,” Josiah Zayner tells a room full of synthetic biologists and other researchers. He fills the needle and plunges it into his skin. “This will modify my muscle genes and give me bigger muscles.”

Zayner, a biohacker–basically meaning he experiments with biology in a DIY lab rather than a traditional one–was giving a talk called “A Step-by-Step Guide to Genetically Modifying Yourself With CRISPR” at the SynBioBeta conference in San Francisco, where other presentations featured academics in suits and the young CEOs of typical biotech startups. Unlike the others, he started his workshop by handing out shots of scotch and a booklet explaining the basics of DIY [do-it-yourwelf] genome engineering.

If you want to genetically modify yourself, it turns out, it’s not necessarily complicated. As he offered samples in small baggies to the crowd, Zayner explained that it took him about five minutes to make the DNA that he brought to the presentation. The vial held Cas9, an enzyme that snips DNA at a particular location targeted by guide RNA, in the gene-editing system known as CRISPR. In this case, it was designed to knock out the myostatin gene, which produces a hormone that limits muscle growth and lets muscles atrophy. In a study in China, dogs with the edited gene had double the muscle mass of normal dogs. If anyone in the audience wanted to try it, they could take a vial home and inject it later. Even rubbing it on skin, Zayner said, would have some effect on cells, albeit limited.

Peters goes on to note that Zayner has a PhD in molecular biology and biophysics and worked for NASA (US National Aeronautics and Space Administration). Zayner’s Wikipedia entry fills in a few more details (Note: Links have been removed),

Zayner graduated from the University of Chicago with a Ph.D. in biophysics in 2013. He then spent two years as a researcher at NASA’s Ames Research Center,[2] where he worked on Martian colony habitat design. While at the agency, Zayner also analyzed speech patterns in online chat, Twitter, and books, and found that language on Twitter and online chat is closer to how people talk than to how they write.[3] Zayner found NASA’s scientific work less innovative than he expected, and upon leaving in January 2016, he launched a crowdfunding campaign to provide CRISPR kits to let the general public experiment with editing bacterial DNA. He also continued his grad school business, The ODIN, which sells kits to let the general public experiment at home. As of May 2016, The ODIN had four employees and operates out of Zayner’s garage.[2]

He refers to himself as a biohacker and believes in the importance in letting the general public participate in scientific experimentation, rather than leaving it segregated to labs.[2][4][1] Zayner found the biohacking community exclusive and hierarchical, particularly in the types of people who decide what is “safe”. He hopes that his projects can let even more people experiment in their homes. Other scientists responded that biohacking is inherently privileged, as it requires leisure time and money, and that deviance from the safety rules of concern would lead to even harsher regulations for all.[5] Zayner’s public CRISPR kit campaign coincided with wider scrutiny over genetic modification. Zayner maintained that these fears were based on misunderstandings of the product, as genetic experiments on yeast and bacteria cannot produce a viral epidemic.[6][7] In April 2015, Zayner ran a hoax on Craigslist to raise awareness about the future potential of forgery in forensics genetics testing.[8]

In February 2016, Zayner performed a full body microbiome transplant on himself, including a fecal transplant, to experiment with microbiome engineering and see if he could cure himself from gastrointestinal and other health issues. The microbiome from the donors feces successfully transplanted in Zayner’s gut according to DNA sequencing done on samples.[2] This experiment was documented by filmmakers Kate McLean and Mario Furloni and turned into the short documentary film Gut Hack.[9]

In December 2016, Zayner created a fluorescent beer by engineering yeast to contain the green fluorescent protein from jellyfish. Zayner’s company, The ODIN, released kits to allow people to create their own engineered fluorescent yeast and this was met with some controversy as the FDA declared the green fluorescent protein can be seen as a color additive.[10] Zayner, views the kit as a way that individual can use genetic engineering to create things in their everyday life.[11]

I found the video for Zayner’s now completed crowdfunding campaign,

I also found The ODIN website (mentioned in the Wikipedia essay) where they claim to be selling various gene editing and gene engineering kits including the CRISPR editing kits mentioned in Peters’ article,

In 2016, he [Zayner] sold $200,000 worth of products, including a kit for yeast that can be used to brew glowing bioluminescent beer, a kit to discover antibiotics at home, and a full home lab that’s roughly the cost of a MacBook Pro. In 2017, he expects to double sales. Many kits are simple, and most buyers probably aren’t using the supplies to attempt to engineer themselves (many kits go to classrooms). But Zayner also hopes that as people using the kits gain genetic literacy, they experiment in wilder ways.

Zayner sells a full home biohacking lab that’s roughly the cost of a MacBook Pro. [Photo: The ODIN]

He questions whether traditional research methods, like randomized controlled trials, are the only way to make discoveries, pointing out that in newer personalized medicine (such as immunotherapy for cancer, which is personalized for each patient), a sample size of one person makes sense. At his workshop, he argued that people should have the choice to self-experiment if they want to; we also change our DNA when we drink alcohol or smoke cigarettes or breathe in dirty city air. Other society-sanctioned activities are more dangerous. “We sacrifice maybe a million people a year to the car gods,” he said. “If you ask someone, ‘Would you get rid of cars?’–no.” …

US researchers both conventional and DIY types such as Zayner are not the only ones who are editing genes. The Chinese study mentioned in Peters’ article was written up in an Oct. 19, 2015 article by Antonio Regalado for the MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

Scientists in China say they are the first to use gene editing to produce customized dogs. They created a beagle with double the amount of muscle mass by deleting a gene called myostatin.

The dogs have “more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications,” Liangxue Lai, a researcher with the Key Laboratory of Regenerative Biology at the Guangzhou Institutes of Biomedicine and Health, said in an e-mail.

Lai and 28 colleagues reported their results last week in the Journal of Molecular Cell Biology, saying they intend to create dogs with other DNA mutations, including ones that mimic human diseases such as Parkinson’s and muscular dystrophy. “The goal of the research is to explore an approach to the generation of new disease dog models for biomedical research,” says Lai. “Dogs are very close to humans in terms of metabolic, physiological, and anatomical characteristics.”

Lai said his group had no plans breed to breed the extra-muscular beagles as pets. Other teams, however, could move quickly to commercialize gene-altered dogs, potentially editing their DNA to change their size, enhance their intelligence, or correct genetic illnesses. A different Chinese Institute, BGI, said in September it had begun selling miniature pigs, created via gene editing, for $1,600 each as novelty pets.

People have been influencing the genetics of dogs for millennia. By at least 36,000 years ago, early humans had already started to tame wolves and shape the companions we have today. Charles Darwin frequently cited dog breeding in The Origin of Species to demonstrate how evolution gradually occurs by a process of selection. With CRISPR, however, evolution is no longer gradual or subject to chance. It is immediate and under human control.

It is precisely that power that is stirring wide debate and concern over CRISPR. Yet at least some researchers think that gene-edited dogs could put a furry, friendly face on the technology. In an interview this month, George Church, a professor at Harvard University who leads a large effort to employ CRISPR editing, said he thinks it will be possible to augment dogs by using DNA edits to make them live longer or simply make them smarter.

Church said he also believed the alteration of dogs and other large animals could open a path to eventual gene editing of people. “Germline editing of pigs or dogs offers a line into it,” he said. “People might say, ‘Hey, it works.’ ”

In the meantime, Zayner’s ideas are certainly thought provoking. I’m not endorsing either his products or his ideas but it should be noted that early science pioneers such as Humphrey Davy and others experimented on themselves. For anyone unfamiliar with Davy, (from the Humphrey Davy Wikipedia entry; Note: Links have been removed),

Sir Humphry Davy, 1st Baronet PRS MRIA FGS (17 December 1778 – 29 May 1829) was a Cornish chemist and inventor,[1] who is best remembered today for isolating a series of substances for the first time: potassium and sodium in 1807 and calcium, strontium, barium, magnesium and boron the following year, as well as discovering the elemental nature of chlorine and iodine. He also studied the forces involved in these separations, inventing the new field of electrochemistry. Berzelius called Davy’s 1806 Bakerian Lecture On Some Chemical Agencies of Electricity[2] “one of the best memoirs which has ever enriched the theory of chemistry.”[3] He was a Baronet, President of the Royal Society (PRS), Member of the Royal Irish Academy (MRIA), and Fellow of the Geological Society (FGS). He also invented the Davy lamp and a very early form of incandescent light bulb.

Canadian content*

A Nov. 11, 2017 posting on the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks blog notes that self-experimentation has a long history and goes on to describe Zayner’s and others biohacking exploits before describing the legality of biohacking in Canada,

With biohackers entering into the space traditionally held by scientists and clinicians, it begs questions. Professor Timothy Caulfield, a Canada research chair in health, law and policy at the University of Alberta, says when he hears of somebody giving themselves biohacked gene therapy, he wonders: “Is this legal? Is this safe? And if it’s not safe, is there anything that we can do about regulating it? And to be honest with you that’s a tough question and I think it’s an open question.”

In Canada, Caulfield says, Health Canada focuses on products. “You have to have something that you are going to regulate or you have to have something that’s making health claims. So if there is a product that is saying I can cure X, Y, or Z, Health Canada can say, ‘Well let’s make sure the science really backs up that claim.’ The problem with these do-it-yourself approaches is there isn’t really a product. You know these people are experimenting on themselves with something that may or may not be designed for health purposes.”

According to Caufield, if you could buy a gene therapy kit that was being marketed to you to biohack yourself, that would be different. “Health Canada could jump in. But right here that’s not the case,” he says.

There are places in the world that do regulate biohacking, says Caulfield. “Germany, for example, they have specific laws for it. And here in Canada we do have a regulatory framework that says that you cannot do gene therapy that will alter the germ line. In other words, you can’t do gene therapy or any kind of genetic editing that will create a change that you will pass on to your offspring. So that would be illegal, but that’s not what’s happening here. And I don’t think there’s a regulatory framework that adequately captures it.”

Infectious disease and policy experts aren’t that concerned yet about the possibility of a biohacker unleashing a genetically modified super germ into the population.

“I think in the future that could be a problem,”says Caulfield, “but this isn’t something that would be easy to do in your garage. I think it’s complicated science. But having said that, the science is moving quickly. We need to think about how we are going to control the potential harms.”

You can find out more about the ‘wild’ people (mostly men) of early science in Richard Holmes’ 2008 book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science.

Finally, should you be interested in connecting with synthetic biology enthusiasts, entrepreneurs, and others, SynBioBeta is more than a conference; it’s also an activity hub.

ETA January 25, 2018 (five minutes later): There are some CRISPR/CAS9 events taking place in Toronto, Canada on January 24 and 25, 2018. One is a workshop with Portuguese artist, Marta de Menezes, and the other is a panel discussion. See my January 10, 2018 posting for more details.

*’Segue: There is some Canadian content if you keep reading.’ and ‘Canadian content’ added January 25, 2018 six minutes after first publication.

ETA February 20, 2018: Sarah Zhang’s Feb. 20, 2018 article for The Atlantic revisits Josiah Zayner’s decision to inject himself with CRISPR,

When Josiah Zayner watched a biotech CEO drop his pants at a biohacking conference and inject himself with an untested herpes treatment, he realized things had gone off the rails.

Zayner is no stranger to stunts in biohacking—loosely defined as experiments, often on the self, that take place outside of traditional lab spaces. You might say he invented their latest incarnation: He’s sterilized his body to “transplant” his entire microbiome in front of a reporter. He’s squabbled with the FDA about selling a kit to make glow-in-the-dark beer. He’s extensively documented attempts to genetically engineer the color of his skin. And most notoriously, he injected his arm with DNA encoding for CRISPR that could theoretically enhance his muscles—in between taking swigs of Scotch at a live-streamed event during an October conference. (Experts say—and even Zayner himself in the live-stream conceded—it’s unlikely to work.)

So when Zayner saw Ascendance Biomedical’s CEO injecting himself on a live-stream earlier this month, you might say there was an uneasy flicker of recognition.

“Honestly, I kind of blame myself,” Zayner told me recently. He’s been in a soul-searching mood; he recently had a kid and the backlash to the CRISPR stunt in October [2017] had been getting to him. “There’s no doubt in my mind that somebody is going to end up hurt eventually,” he said.

Yup, it’s one of the reasons for rules; people take things too far. The trick is figuring out how to achieve balance between risk taking and recklessness.

Essays on Frankenstein

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

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

Introductions

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

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

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

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

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

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

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

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

Is it actually about bad science, though?

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

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

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

Does that make it into a warning against playing God?

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

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

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

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

Key Players

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

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

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

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

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

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

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

Lingo

….

Debates

Popular Culture

Further Reading

….

‘Franken’ and CRISPR

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

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

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

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

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

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

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

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

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

Playing God

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

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

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

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

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

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

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

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

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

Frankenstein and anti-vaxxers

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

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

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

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

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

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

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

The end of this piece

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

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

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

The dangers of metaphors when applied to science

Metaphors can be powerful in both good ways and bad. I once read that there was a ‘lighthouse’ metaphor used to explain a scientific concept to high school students which later caused problems for them when they were studying the biological sciences as university students.  It seems there’s research now to back up the assertion about metaphors and their powers. From an Oct. 7, 2016 news item on phys.org,

Whether ideas are “like a light bulb” or come forth as “nurtured seeds,” how we describe discovery shapes people’s perceptions of both inventions and inventors. Notably, Kristen Elmore (Bronfenbrenner Center for Translational Research at Cornell University) and Myra Luna-Lucero (Teachers College, Columbia University) have shown that discovery metaphors influence our perceptions of the quality of an idea and of the ability of the idea’s creator. The research appears in the journal Social Psychological and Personality Science.

While the metaphor that ideas appear “like light bulbs” is popular and appealing, new research shows that discovery metaphors influence our understanding of the scientific process and perceptions of the ability of inventors based on their gender. [downloaded from http://www.spsp.org/news-center/press-release/metaphors-bias-perception]

While the metaphor that ideas appear “like light bulbs” is popular and appealing, new research shows that discovery metaphors influence our understanding of the scientific process and perceptions of the ability of inventors based on their gender. [downloaded from http://www.spsp.org/news-center/press-release/metaphors-bias-perception]

An Oct. 7, 2016  Society for Personality and Social Psychology news release (also on EurekAlert), which originated the news item, provides more insight into the work,

While those involved in research know there are many trials and errors and years of work before something is understood, discovered or invented, our use of words for inspiration may have an unintended and underappreciated effect of portraying good ideas as a sudden and exceptional occurrence.

In a series of experiments, Elmore and Luna-Lucero tested how people responded to ideas that were described as being “like a light bulb,” “nurtured like a seed,” or a neutral description. 

According the authors, the “light bulb metaphor implies that ‘brilliant’ ideas result from sudden and spontaneous inspiration, bestowed upon a chosen few (geniuses) while the seed metaphor implies that ideas are nurtured over time, ‘cultivated’ by anyone willing to invest effort.”

The first study looked at how people reacted to a description of Alan Turing’s invention of a precursor to the modern computer. It turns out light bulbs are more remarkable than seeds.

“We found that an idea was seen as more exceptional when described as appearing like a light bulb rather than nurtured like a seed,” said Elmore.

But this pattern changed when they used these metaphors to describe a female inventor’s ideas. When using the “like a light bulb” and “nurtured seed” metaphors, the researchers found “women were judged as better idea creators than men when ideas were described as nurtured over time like seeds.”

The results suggest gender stereotypes play a role in how people perceived the inventors.

In the third study, the researchers presented participants with descriptions of the work of either a female (Hedy Lamarr) or a male (George Antheil) inventor, who together created the idea for spread-spectrum technology (a precursor to modern wireless communications). Indeed, the seed metaphor “increased perceptions that a female inventor was a genius, while the light bulb metaphor was more consistent with stereotypical views of male genius,” stated Elmore.

Elmore plans to expand upon their research on metaphors by examining the interactions of teachers and students in real world classroom settings.

“The ways that teachers and students talk about ideas may impact students’ beliefs about how good ideas are created and who is likely to have them,” said Elmore. “Having good ideas is relevant across subjects—whether students are creating a hypothesis in science or generating a thesis for their English paper—and language that stresses the role of effort rather than inspiration in creating ideas may have real benefits for students’ motivation.”

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

Light Bulbs or Seeds? How Metaphors for Ideas Influence Judgments About Genius by Kristen C. Elmore and Myra Luna-Lucero. Social Psychological and Personality Science doi: 10.1177/1948550616667611 Published online before print October 7, 2016

This paper is behind a paywall.

While Elmore and Luna-Lucero are focused on a nuanced analysis of specific metaphors, Richard Holmes’s book, ‘The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science’, notes that the ‘Eureka’  (light bulb) moment for scientific discovery and the notion of a ‘single great man’ (a singular genius) as the discoverer has its roots in romantic (Shelley, Keats, etc.) poetry.