Tag Archives: Massachusetts Institute of Technology

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

I found it at the movies: a commentary on/review of “Films from the Future”

Kudos to anyone who recognized the reference to Pauline Kael (she changed film criticism forever) and her book “I Lost it at the Movies.” Of course, her book title was a bit of sexual innuendo, quite risqué for an important film critic in 1965 but appropriate for a period (the 1960s) associated with a sexual revolution. (There’s more about the 1960’s sexual revolution in the US along with mention of a prior sexual revolution in the 1920s in this Wikipedia entry.)

The title for this commentary is based on an anecdote from Dr. Andrew Maynard’s (director of the Arizona State University [ASU] Risk Innovation Lab) popular science and technology book, “Films from the Future: The Technology and Morality of Sci-Fi Movies.”

The ‘title-inspiring’ anecdote concerns Maynard’s first viewing of ‘2001: A Space Odyssey, when as a rather “bratty” 16-year-old who preferred to read science fiction, he discovered new ways of seeing and imaging the world. Maynard isn’t explicit about when he became a ‘techno nerd’ or how movies gave him an experience books couldn’t but presumably at 16 he was already gearing up for a career in the sciences. That ‘movie’ revelation received in front of a black and white television on January 1,1982 eventually led him to write, “Films from the Future.” (He has a PhD in physics which he is now applying to the field of risk innovation. For a more detailed description of Dr. Maynard and his work, there’s his ASU profile webpage and, of course, the introduction to his book.)

The book is quite timely. I don’t know how many people have noticed but science and scientific innovation is being covered more frequently in the media than it has been in many years. Science fairs and festivals are being founded on what seems to be a daily basis and you can now find science in art galleries. (Not to mention the movies and television where science topics are covered in comic book adaptations, in comedy, and in standard science fiction style.) Much of this activity is centered on what’s called ’emerging technologies’. These technologies are why people argue for what’s known as ‘blue sky’ or ‘basic’ or ‘fundamental’ science for without that science there would be no emerging technology.

Films from the Future

Isn’t reading the Table of Contents (ToC) the best way to approach a book? (From Films from the Future; Note: The formatting has been altered),

Table of Contents
Chapter One
In the Beginning 14
Beginnings 14
Welcome to the Future 16
The Power of Convergence 18
Socially Responsible Innovation 21
A Common Point of Focus 25
Spoiler Alert 26
Chapter Two
Jurassic Park: The Rise of Resurrection Biology 27
When Dinosaurs Ruled the World 27
De-Extinction 31
Could We, Should We? 36
The Butterfly Effect 39
Visions of Power 43
Chapter Three
Never Let Me Go: A Cautionary Tale of Human Cloning 46
Sins of Futures Past 46
Cloning 51
Genuinely Human? 56
Too Valuable to Fail? 62
Chapter Four
Minority Report: Predicting Criminal Intent 64
Criminal Intent 64
The “Science” of Predicting Bad Behavior 69
Criminal Brain Scans 74
Machine Learning-Based Precognition 77
Big Brother, Meet Big Data 79
Chapter Five
Limitless: Pharmaceutically-enhanced Intelligence 86
A Pill for Everything 86
The Seduction of Self-Enhancement 89
Nootropics 91
If You Could, Would You? 97
Privileged Technology 101
Our Obsession with Intelligence 105
Chapter Six
Elysium: Social Inequity in an Age of Technological
Extremes 110
The Poor Shall Inherit the Earth 110
Bioprinting Our Future Bodies 115
The Disposable Workforce 119
Living in an Automated Future 124
Chapter Seven
Ghost in the Shell: Being Human in an
Augmented Future 129
Through a Glass Darkly 129
Body Hacking 135
More than “Human”? 137
Plugged In, Hacked Out 142
Your Corporate Body 147
Chapter Eight
Ex Machina: AI and the Art of Manipulation 154
Plato’s Cave 154
The Lure of Permissionless Innovation 160
Technologies of Hubris 164
Superintelligence 169
Defining Artificial Intelligence 172
Artificial Manipulation 175
Chapter Nine
Transcendence: Welcome to the Singularity 180
Visions of the Future 180
Technological Convergence 184
Enter the Neo-Luddites 190
Techno-Terrorism 194
Exponential Extrapolation 200
Make-Believe in the Age of the Singularity 203
Chapter Ten
The Man in the White Suit: Living in a Material World 208
There’s Plenty of Room at the Bottom 208
Mastering the Material World 213
Myopically Benevolent Science 220
Never Underestimate the Status Quo 224
It’s Good to Talk 227
Chapter Eleven
Inferno: Immoral Logic in an Age of
Genetic Manipulation 231
Decoding Make-Believe 231
Weaponizing the Genome 234
Immoral Logic? 238
The Honest Broker 242
Dictating the Future 248
Chapter Twelve
The Day After Tomorrow: Riding the Wave of
Climate Change 251
Our Changing Climate 251
Fragile States 255
A Planetary “Microbiome” 258
The Rise of the Anthropocene 260
Building Resiliency 262
Geoengineering the Future 266
Chapter Thirteen
Contact: Living by More than Science Alone 272
An Awful Waste of Space 272
More than Science Alone 277
Occam’s Razor 280
What If We’re Not Alone? 283
Chapter Fourteen
Looking to the Future 288
Acknowledgments 293

The ToC gives the reader a pretty clue as to where the author is going with their book and Maynard explains how he chose his movies in his introductory chapter (from Films from the Future),

“There are some quite wonderful science fiction movies that didn’t make the cut because they didn’t fit the overarching narrative (Blade Runner and its sequel Blade Runner 2049, for instance, and the first of the Matrix trilogy). There are also movies that bombed with the critics, but were included because they ably fill a gap in the bigger story around emerging and converging technologies. Ultimately, the movies that made the cut were chosen because, together, they create an overarching narrative around emerging trends in biotechnologies, cybertechnologies, and materials-based technologies, and they illuminate a broader landscape around our evolving relationship with science and technology. And, to be honest, they are all movies that I get a kick out of watching.” (p. 17)

Jurassic Park (Chapter Two)

Dinosaurs do not interest me—they never have. Despite my profound indifference I did see the movie, Jurassic Park, when it was first released (someone talked me into going). And, I am still profoundly indifferent. Thankfully, Dr. Maynard finds meaning and a connection to current trends in biotechnology,

Jurassic Park is unabashedly a movie about dinosaurs. But it’s also a movie about greed, ambition, genetic engineering, and human folly—all rich pickings for thinking about the future, and what could possibly go wrong. (p. 28)

What really stands out with Jurassic Park, over twenty-five years later, is how it reveals a very human side of science and technology. This comes out in questions around when we should tinker with technology and when we should leave well enough alone. But there is also a narrative here that appears time and time again with the movies in this book, and that is how we get our heads around the sometimes oversized roles mega-entrepreneurs play in dictating how new tech is used, and possibly abused. These are all issues that are just as relevant now as they were in 1993, and are front and center of ensuring that the technologyenabled future we’re building is one where we want to live, and not one where we’re constantly fighting for our lives.  (pp. 30-1)

He also describes a connection to current trends in biotechnology,

De-Extinction

In a far corner of Siberia, two Russians—Sergey Zimov and his son Nikita—are attempting to recreate the Ice Age. More precisely, their vision is to reconstruct the landscape and ecosystem of northern Siberia in the Pleistocene, a period in Earth’s history that stretches from around two and a half million years ago to eleven thousand years ago. This was a time when the environment was much colder than now, with huge glaciers and ice sheets flowing over much of the Earth’s northern hemisphere. It was also a time when humans
coexisted with animals that are long extinct, including saber-tooth cats, giant ground sloths, and woolly mammoths.

The Zimovs’ ambitions are an extreme example of “Pleistocene rewilding,” a movement to reintroduce relatively recently extinct large animals, or their close modern-day equivalents, to regions where they were once common. In the case of the Zimovs, the
father-and-son team believe that, by reconstructing the Pleistocene ecosystem in the Siberian steppes and elsewhere, they can slow down the impacts of climate change on these regions. These areas are dominated by permafrost, ground that never thaws through
the year. Permafrost ecosystems have developed and survived over millennia, but a warming global climate (a theme we’ll come back to in chapter twelve and the movie The Day After Tomorrow) threatens to catastrophically disrupt them, and as this happens, the impacts
on biodiversity could be devastating. But what gets climate scientists even more worried is potentially massive releases of trapped methane as the permafrost disappears.

Methane is a powerful greenhouse gas—some eighty times more effective at exacerbating global warming than carbon dioxide— and large-scale releases from warming permafrost could trigger catastrophic changes in climate. As a result, finding ways to keep it in the ground is important. And here the Zimovs came up with a rather unusual idea: maintaining the stability of the environment by reintroducing long-extinct species that could help prevent its destruction, even in a warmer world. It’s a wild idea, but one that has some merit.8 As a proof of concept, though, the Zimovs needed somewhere to start. And so they set out to create a park for deextinct Siberian animals: Pleistocene Park.9

Pleistocene Park is by no stretch of the imagination a modern-day Jurassic Park. The dinosaurs in Hammond’s park date back to the Mesozoic period, from around 250 million years ago to sixty-five million years ago. By comparison, the Pleistocene is relatively modern history, ending a mere eleven and a half thousand years ago. And the vision behind Pleistocene Park is not thrills, spills, and profit, but the serious use of science and technology to stabilize an increasingly unstable environment. Yet there is one thread that ties them together, and that’s using genetic engineering to reintroduce extinct species. In this case, the species in question is warm-blooded and furry: the woolly mammoth.

The idea of de-extinction, or bringing back species from extinction (it’s even called “resurrection biology” in some circles), has been around for a while. It’s a controversial idea, and it raises a lot of tough ethical questions. But proponents of de-extinction argue
that we’re losing species and ecosystems at such a rate that we can’t afford not to explore technological interventions to help stem the flow.

Early approaches to bringing species back from the dead have involved selective breeding. The idea was simple—if you have modern ancestors of a recently extinct species, selectively breeding specimens that have a higher genetic similarity to their forebears can potentially help reconstruct their genome in living animals. This approach is being used in attempts to bring back the aurochs, an ancestor of modern cattle.10 But it’s slow, and it depends on
the fragmented genome of the extinct species still surviving in its modern-day equivalents.

An alternative to selective breeding is cloning. This involves finding a viable cell, or cell nucleus, in an extinct but well-preserved animal and growing a new living clone from it. It’s definitely a more appealing route for impatient resurrection biologists, but it does mean getting your hands on intact cells from long-dead animals and devising ways to “resurrect” these, which is no mean feat. Cloning has potential when it comes to recently extinct species whose cells have been well preserved—for instance, where the whole animal has become frozen in ice. But it’s still a slow and extremely limited option.

Which is where advances in genetic engineering come in.

The technological premise of Jurassic Park is that scientists can reconstruct the genome of long-dead animals from preserved DNA fragments. It’s a compelling idea, if you think of DNA as a massively long and complex instruction set that tells a group of biological molecules how to build an animal. In principle, if we could reconstruct the genome of an extinct species, we would have the basic instruction set—the biological software—to reconstruct
individual members of it.

The bad news is that DNA-reconstruction-based de-extinction is far more complex than this. First you need intact fragments of DNA, which is not easy, as DNA degrades easily (and is pretty much impossible to obtain, as far as we know, for dinosaurs). Then you
need to be able to stitch all of your fragments together, which is akin to completing a billion-piece jigsaw puzzle without knowing what the final picture looks like. This is a Herculean task, although with breakthroughs in data manipulation and machine learning,
scientists are getting better at it. But even when you have your reconstructed genome, you need the biological “wetware”—all the stuff that’s needed to create, incubate, and nurture a new living thing, like eggs, nutrients, a safe space to grow and mature, and so on. Within all this complexity, it turns out that getting your DNA sequence right is just the beginning of translating that genetic code into a living, breathing entity. But in some cases, it might be possible.

In 2013, Sergey Zimov was introduced to the geneticist George Church at a conference on de-extinction. Church is an accomplished scientist in the field of DNA analysis and reconstruction, and a thought leader in the field of synthetic biology (which we’ll come
back to in chapter nine). It was a match made in resurrection biology heaven. Zimov wanted to populate his Pleistocene Park with mammoths, and Church thought he could see a way of
achieving this.

What resulted was an ambitious project to de-extinct the woolly mammoth. Church and others who are working on this have faced plenty of hurdles. But the technology has been advancing so fast that, as of 2017, scientists were predicting they would be able to reproduce the woolly mammoth within the next two years.

One of those hurdles was the lack of solid DNA sequences to work from. Frustratingly, although there are many instances of well preserved woolly mammoths, their DNA rarely survives being frozen for tens of thousands of years. To overcome this, Church and others
have taken a different tack: Take a modern, living relative of the mammoth, and engineer into it traits that would allow it to live on the Siberian tundra, just like its woolly ancestors.

Church’s team’s starting point has been the Asian elephant. This is their source of base DNA for their “woolly mammoth 2.0”—their starting source code, if you like. So far, they’ve identified fifty plus gene sequences they think they can play with to give their modern-day woolly mammoth the traits it would need to thrive in Pleistocene Park, including a coat of hair, smaller ears, and a constitution adapted to cold.

The next hurdle they face is how to translate the code embedded in their new woolly mammoth genome into a living, breathing animal. The most obvious route would be to impregnate a female Asian elephant with a fertilized egg containing the new code. But Asian elephants are endangered, and no one’s likely to allow such cutting edge experimentation on the precious few that are still around, so scientists are working on an artificial womb for their reinvented woolly mammoth. They’re making progress with mice and hope to crack the motherless mammoth challenge relatively soon.

It’s perhaps a stretch to call this creative approach to recreating a species (or “reanimation” as Church refers to it) “de-extinction,” as what is being formed is a new species. … (pp. 31-4)

This selection illustrates what Maynard does so very well throughout the book where he uses each film as a launching pad for a clear, readable description of relevant bits of science so you understand why the premise was likely, unlikely, or pure fantasy while linking it to contemporary practices, efforts, and issues. In the context of Jurassic Park, Maynard goes on to raise some fascinating questions such as: Should we revive animals rendered extinct (due to obsolescence or inability to adapt to new conditions) when we could develop new animals?

General thoughts

‘Films for the Future’ offers readable (to non-scientific types) science, lively writing, and the occasional ‘memorish’ anecdote. As well, Dr. Maynard raises the curtain on aspects of the scientific enterprise that most of us do not get to see.  For example, the meeting  between Sergey Zimov and George Church and how it led to new ‘de-extinction’ work’. He also describes the problems that the scientists encountered and are encountering. This is in direct contrast to how scientific work is usually presented in the news media as one glorious breakthrough after the next.

Maynard does discuss the issues of social inequality and power and ownership. For example, who owns your transplant or data? Puzzlingly, he doesn’t touch on the current environment where scientists in the US and elsewhere are encouraged/pressured to start up companies commercializing their work.

Nor is there any mention of how universities are participating in this grand business experiment often called ‘innovation’. (My March 15, 2017 posting describes an outcome for the CRISPR [gene editing system] patent fight taking place between Harvard University’s & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley and my Sept. 11, 2018 posting about an art/science exhibit in Vancouver [Canada] provides an update for round 2 of the Broad Institute vs. UC Berkeley patent fight [scroll down about 65% of the way.) *To read about how my ‘cultural blindness’ shows up here scroll down to the single asterisk at the end.*

There’s a foray through machine-learning and big data as applied to predictive policing in Maynard’s ‘Minority Report’ chapter (my November 23, 2017 posting describes Vancouver’s predictive policing initiative [no psychics involved], the first such in Canada). There’s no mention of surveillance technology, which if I recall properly was part of the future environment, both by the state and by corporations. (Mia Armstrong’s November 15, 2018 article for Slate on Chinese surveillance being exported to Venezuela provides interesting insight.)

The gaps are interesting and various. This of course points to a problem all science writers have when attempting an overview of science. (Carl Zimmer’s latest, ‘She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity’] a doorstopping 574 pages, also has some gaps despite his focus on heredity,)

Maynard has worked hard to give an comprehensive overview in a remarkably compact 279 pages while developing his theme about science and the human element. In other words, science is not monolithic; it’s created by human beings and subject to all the flaws and benefits that humanity’s efforts are always subject to—scientists are people too.

The readership for ‘Films from the Future’ spans from the mildly interested science reader to someone like me who’s been writing/blogging about these topics (more or less) for about 10 years. I learned a lot reading this book.

Next time, I’m hopeful there’ll be a next time, Maynard might want to describe the parameters he’s set for his book in more detail that is possible in his chapter headings. He could have mentioned that he’s not a cinéaste so his descriptions of the movies are very much focused on the story as conveyed through words. He doesn’t mention colour palates, camera angles, or, even, cultural lenses.

Take for example, his chapter on ‘Ghost in the Shell’. Focused on the Japanese animation film and not the live action Hollywood version he talks about human enhancement and cyborgs. The Japanese have a different take on robots, inanimate objects, and, I assume, cyborgs than is found in Canada or the US or Great Britain, for that matter (according to a colleague of mine, an Englishwoman who lived in Japan for ten or more years). There’s also the chapter on the Ealing comedy, The Man in The White Suit, an English film from the 1950’s. That too has a cultural (as well as, historical) flavour but since Maynard is from England, he may take that cultural flavour for granted. ‘Never let me go’ in Chapter Two was also a UK production, albeit far more recent than the Ealing comedy and it’s interesting to consider how a UK production about cloning might differ from a US or Chinese or … production on the topic. I am hearkening back to Maynard’s anecdote about movies giving him new ways of seeing and imagining the world.

There’s a corrective. A couple of sentences in Maynard’s introductory chapter cautioning that in depth exploration of ‘cultural lenses’ was not possible without expanding the book to an unreadable size followed by a sentence in each of the two chapters that there are cultural differences.

One area where I had a significant problem was with regard to being “programmed” and having  “instinctual” behaviour,

As a species, we are embarrassingly programmed to see “different” as “threatening,” and to take instinctive action against it. It’s a trait that’s exploited in many science fiction novels and movies, including those in this book. If we want to see the rise of increasingly augmented individuals, we need to be prepared for some social strife. (p. 136)

These concepts are much debated in the social sciences and there are arguments for and against ‘instincts regarding strangers and their possible differences’. I gather Dr. Maynard hies to the ‘instinct to defend/attack’ school of thought.

One final quandary, there was no sex and I was expecting it in the Ex Machina chapter, especially now that sexbots are about to take over the world (I exaggerate). Certainly, if you’re talking about “social strife,” then sexbots would seem to be fruitful line of inquiry, especially when there’s talk of how they could benefit families (my August 29, 2018 posting). Again, there could have been a sentence explaining why Maynard focused almost exclusively in this chapter on the discussions about artificial intelligence and superintelligence.

Taken in the context of the book, these are trifling issues and shouldn’t stop you from reading Films from the Future. What Maynard has accomplished here is impressive and I hope it’s just the beginning.

Final note

Bravo Andrew! (Note: We’ve been ‘internet acquaintances/friends since the first year I started blogging. When I’m referring to him in his professional capacity, he’s Dr. Maynard and when it’s not strictly in his professional capacity, it’s Andrew. For this commentary/review I wanted to emphasize his professional status.)

If you need to see a few more samples of Andrew’s writing, there’s a Nov. 15, 2018 essay on The Conversation, Sci-fi movies are the secret weapon that could help Silicon Valley grow up and a Nov. 21, 2018 article on slate.com, The True Cost of Stain-Resistant Pants; The 1951 British comedy The Man in the White Suit anticipated our fears about nanotechnology. Enjoy.

****Added at 1700 hours on Nov. 22, 2018: You can purchase Films from the Future here.

*Nov. 23, 2018: I should have been more specific and said ‘academic scientists’. In Canada, the great percentage of scientists are academic. It’s to the point where the OECD (Organization for Economic Cooperation and Development) has noted that amongst industrialized countries, Canada has very few industrial scientists in comparison to the others.

Café Scientifique Vancouver (Canada) talk on October 30th, 2018: Solving some of Canada’s grandest challenges with synthetic biology

From an October 16, 2018 Café Scientifique Vancouver announcement (received via email),

Our next café will happen on TUESDAY, OCTOBER 30TH at 7:30PM in the
back room at YAGGER’S DOWNTOWN (433 W Pender). Our speaker for the
evening will be DR. VIKRAMADITYA G. YADAV. His topic will be:

SOLVING SOME OF CANADA’S GRANDEST CHALLENGES WITH SYNTHETIC BIOLOGY

A warming climate, unrepressed mining and logging, contamination of our
water resources, the uncertain price and tight supply of crude oil and
the growing threat of epidemics are having a profound, negative impact
on the well-being of Canadians. There is an urgent need to develop and
implement sustainable manufacturing technologies that can not only meet
our material and energy needs, but also sustain our quality of life.
Romantic and unbelievable as it sounds, Nature posses all the answer to
our challenges, and the coming decades in science and engineering will
be typified by our attempts to mimic or recruit biology to address our
needs. This talk will present a vivid snapshot of current and emerging
research towards this goal and highlight some cutting-edge technologies
under development at the University of British Columbia [UBC].

When he joined the University of Waterloo as an undergraduate student in
chemical engineering, Dr. Vikramaditya G. Yadav coveted a career in
Alberta’s burgeoning petrochemical sector. He even interned at Imperial
Oil during his first summer break from university. Then, one fine
evening during second year, he stumbled upon a copy of Juan Enríquez’s
As the Future Catches You in the library and became instantly captivated
with biological engineering. His journey over the past few years has
taken him to Sanofi Pasteur [vaccines division of the multinational
pharmaceutical
company Sanofi], the Massachusetts Institute of Technology [MIT],
Harvard University, and finally, the University of British Columbia,
where he now leads a wonderful group of researchers working on
wide-ranging topics at the interface of biology, chemistry, engineering,
medicine and economics.

We hope to see you there!

Oftentimes, the speaker is asked to write up a description of their talk and assuming that’s the case and based on how it’s written, I’d say the odds are good that this will be a lively, engaging talk.

For more proof, you can check out Dr. Yadav’s description of his research interests on his UBC profile page. BTW, his research group is called The Biofoundry (at UBC).

A 3D printed eye cornea and a 3D printed copy of your brain (also: a Brad Pitt connection)

Sometimes it’s hard to keep up with 3D tissue printing news. I have two news bits, one concerning eyes and another concerning brains.

3D printed human corneas

A May 29, 2018 news item on ScienceDaily trumpets the news,

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today [May 29, 2018] in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a ‘bio-ink’.

Here are the proud researchers with their cornea,

Caption: Dr. Steve Swioklo and Professor Che Connon with a dyed cornea. Credit: Newcastle University, UK

A May 30,2018 Newcastle University press release (also on EurekAlert but published on May 29, 2018), which originated the news item, adds more details,

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture – or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

“Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

“This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”

The scientists, including first author and PhD student Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient’s unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient’s eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: “Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

“However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage.”

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

3D bioprinting of a corneal stroma equivalent by Abigail Isaacson, Stephen Swioklo, Che J. Connon. Experimental Eye Research Volume 173, August 2018, Pages 188–193 and 2018 May 14 pii: S0014-4835(18)30212-4. doi: 10.1016/j.exer.2018.05.010. [Epub ahead of print]

This paper is behind a paywall.

A 3D printed copy of your brain

I love the title for this May 30, 2018 Wyss Institute for Biologically Inspired Engineering news release: Creating piece of mind by Lindsay Brownell (also on EurekAlert),

What if you could hold a physical model of your own brain in your hands, accurate down to its every unique fold? That’s just a normal part of life for Steven Keating, Ph.D., who had a baseball-sized tumor removed from his brain at age 26 while he was a graduate student in the MIT Media Lab’s Mediated Matter group. Curious to see what his brain actually looked like before the tumor was removed, and with the goal of better understanding his diagnosis and treatment options, Keating collected his medical data and began 3D printing his MRI [magnetic resonance imaging] and CT [computed tomography] scans, but was frustrated that existing methods were prohibitively time-intensive, cumbersome, and failed to accurately reveal important features of interest. Keating reached out to some of his group’s collaborators, including members of the Wyss Institute at Harvard University, who were exploring a new method for 3D printing biological samples.

“It never occurred to us to use this approach for human anatomy until Steve came to us and said, ‘Guys, here’s my data, what can we do?” says Ahmed Hosny, who was a Research Fellow with at the Wyss Institute at the time and is now a machine learning engineer at the Dana-Farber Cancer Institute. The result of that impromptu collaboration – which grew to involve James Weaver, Ph.D., Senior Research Scientist at the Wyss Institute; Neri Oxman, [emphasis mine] Ph.D., Director of the MIT Media Lab’s Mediated Matter group and Associate Professor of Media Arts and Sciences; and a team of researchers and physicians at several other academic and medical centers in the US and Germany – is a new technique that allows images from MRI, CT, and other medical scans to be easily and quickly converted into physical models with unprecedented detail. The research is reported in 3D Printing and Additive Manufacturing.

“I nearly jumped out of my chair when I saw what this technology is able to do,” says Beth Ripley, M.D. Ph.D., an Assistant Professor of Radiology at the University of Washington and clinical radiologist at the Seattle VA, and co-author of the paper. “It creates exquisitely detailed 3D-printed medical models with a fraction of the manual labor currently required, making 3D printing more accessible to the medical field as a tool for research and diagnosis.”

Imaging technologies like MRI and CT scans produce high-resolution images as a series of “slices” that reveal the details of structures inside the human body, making them an invaluable resource for evaluating and diagnosing medical conditions. Most 3D printers build physical models in a layer-by-layer process, so feeding them layers of medical images to create a solid structure is an obvious synergy between the two technologies.

However, there is a problem: MRI and CT scans produce images with so much detail that the object(s) of interest need to be isolated from surrounding tissue and converted into surface meshes in order to be printed. This is achieved via either a very time-intensive process called “segmentation” where a radiologist manually traces the desired object on every single image slice (sometimes hundreds of images for a single sample), or an automatic “thresholding” process in which a computer program quickly converts areas that contain grayscale pixels into either solid black or solid white pixels, based on a shade of gray that is chosen to be the threshold between black and white. However, medical imaging data sets often contain objects that are irregularly shaped and lack clear, well-defined borders; as a result, auto-thresholding (or even manual segmentation) often over- or under-exaggerates the size of a feature of interest and washes out critical detail.

The new method described by the paper’s authors gives medical professionals the best of both worlds, offering a fast and highly accurate method for converting complex images into a format that can be easily 3D printed. The key lies in printing with dithered bitmaps, a digital file format in which each pixel of a grayscale image is converted into a series of black and white pixels, and the density of the black pixels is what defines the different shades of gray rather than the pixels themselves varying in color.

Similar to the way images in black-and-white newsprint use varying sizes of black ink dots to convey shading, the more black pixels that are present in a given area, the darker it appears. By simplifying all pixels from various shades of gray into a mixture of black or white pixels, dithered bitmaps allow a 3D printer to print complex medical images using two different materials that preserve all the subtle variations of the original data with much greater accuracy and speed.

The team of researchers used bitmap-based 3D printing to create models of Keating’s brain and tumor that faithfully preserved all of the gradations of detail present in the raw MRI data down to a resolution that is on par with what the human eye can distinguish from about 9-10 inches away. Using this same approach, they were also able to print a variable stiffness model of a human heart valve using different materials for the valve tissue versus the mineral plaques that had formed within the valve, resulting in a model that exhibited mechanical property gradients and provided new insights into the actual effects of the plaques on valve function.

“Our approach not only allows for high levels of detail to be preserved and printed into medical models, but it also saves a tremendous amount of time and money,” says Weaver, who is the corresponding author of the paper. “Manually segmenting a CT scan of a healthy human foot, with all its internal bone structure, bone marrow, tendons, muscles, soft tissue, and skin, for example, can take more than 30 hours, even by a trained professional – we were able to do it in less than an hour.”

The researchers hope that their method will help make 3D printing a more viable tool for routine exams and diagnoses, patient education, and understanding the human body. “Right now, it’s just too expensive for hospitals to employ a team of specialists to go in and hand-segment image data sets for 3D printing, except in extremely high-risk or high-profile cases. We’re hoping to change that,” says Hosny.

In order for that to happen, some entrenched elements of the medical field need to change as well. Most patients’ data are compressed to save space on hospital servers, so it’s often difficult to get the raw MRI or CT scan files needed for high-resolution 3D printing. Additionally, the team’s research was facilitated through a joint collaboration with leading 3D printer manufacturer Stratasys, which allowed access to their 3D printer’s intrinsic bitmap printing capabilities. New software packages also still need to be developed to better leverage these capabilities and make them more accessible to medical professionals.

Despite these hurdles, the researchers are confident that their achievements present a significant value to the medical community. “I imagine that sometime within the next 5 years, the day could come when any patient that goes into a doctor’s office for a routine or non-routine CT or MRI scan will be able to get a 3D-printed model of their patient-specific data within a few days,” says Weaver.

Keating, who has become a passionate advocate of efforts to enable patients to access their own medical data, still 3D prints his MRI scans to see how his skull is healing post-surgery and check on his brain to make sure his tumor isn’t coming back. “The ability to understand what’s happening inside of you, to actually hold it in your hands and see the effects of treatment, is incredibly empowering,” he says.

“Curiosity is one of the biggest drivers of innovation and change for the greater good, especially when it involves exploring questions across disciplines and institutions. The Wyss Institute is proud to be a space where this kind of cross-field innovation can flourish,” says Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Here’s an image illustrating the work,

Caption: This 3D-printed model of Steven Keating’s skull and brain clearly shows his brain tumor and other fine details thanks to the new data processing method pioneered by the study’s authors. Credit: Wyss Institute at Harvard University

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

From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets by Ahmed Hosny , Steven J. Keating, Joshua D. Dilley, Beth Ripley, Tatiana Kelil, Steve Pieper, Dominik Kolb, Christoph Bader, Anne-Marie Pobloth, Molly Griffin, Reza Nezafat, Georg Duda, Ennio A. Chiocca, James R.. Stone, James S. Michaelson, Mason N. Dean, Neri Oxman, and James C. Weaver. 3D Printing and Additive Manufacturing http://doi.org/10.1089/3dp.2017.0140 Online Ahead of Print:May 29, 2018

This paper appears to be open access.

A tangential Brad Pitt connection

It’s a bit of Hollywood gossip. There was some speculation in April 2018 that Brad Pitt was dating Dr. Neri Oxman highlighted in the Wyss Institute news release. Here’s a sample of an April 13, 2018 posting on Laineygossip (Note: A link has been removed),

It took him a long time to date, but he is now,” the insider tells PEOPLE. “He likes women who challenge him in every way, especially in the intellect department. Brad has seen how happy and different Amal has made his friend (George Clooney). It has given him something to think about.”

While a Pitt source has maintained he and Oxman are “just friends,” they’ve met up a few times since the fall and the insider notes Pitt has been flying frequently to the East Coast. He dropped by one of Oxman’s classes last fall and was spotted at MIT again a few weeks ago.

Pitt and Oxman got to know each other through an architecture project at MIT, where she works as a professor of media arts and sciences at the school’s Media Lab. Pitt has always been interested in architecture and founded the Make It Right Foundation, which builds affordable and environmentally friendly homes in New Orleans for people in need.

“One of the things Brad has said all along is that he wants to do more architecture and design work,” another source says. “He loves this, has found the furniture design and New Orleans developing work fulfilling, and knows he has a talent for it.”

It’s only been a week since Page Six first broke the news that Brad and Dr Oxman have been spending time together.

I’m fascinated by Oxman’s (and her colleagues’) furniture. Rose Brook writes about one particular Oxman piece in her March 27, 2014 posting for TCT magazine (Note: Links have been removed),

MIT Professor and 3D printing forerunner Neri Oxman has unveiled her striking acoustic chaise longue, which was made using Stratasys 3D printing technology.

Oxman collaborated with Professor W Craig Carter and Composer and fellow MIT Professor Tod Machover to explore material properties and their spatial arrangement to form the acoustic piece.

Christened Gemini, the two-part chaise was produced using a Stratasys Objet500 Connex3 multi-colour, multi-material 3D printer as well as traditional furniture-making techniques and it will be on display at the Vocal Vibrations exhibition at Le Laboratoire in Paris from March 28th 2014.

An Architect, Designer and Professor of Media, Arts and Science at MIT, Oxman’s creation aims to convey the relationship of twins in the womb through material properties and their arrangement. It was made using both subtractive and additive manufacturing and is part of Oxman’s ongoing exploration of what Stratasys’ ground-breaking multi-colour, multi-material 3D printer can do.

Brook goes on to explain how the chaise was made and the inspiration that led to it. Finally, it’s interesting to note that Oxman was working with Stratasys in 2014 and that this 2018 brain project is being developed in a joint collaboration with Statasys.

That’s it for 3D printing today.

Santiago Ramón y Cajal and the butterflies of the soul

The Cajal exhibit of drawings was here in Vancouver (Canada) this last fall (2017) and I still carry the memory of that glorious experience (see my Sept. 11, 2017 posting for more about the show and associated events). It seems Cajal’s drawings had a similar response in New York city, from a January 18, 2018 article by Roberta Smith for the New York Times,

It’s not often that you look at an exhibition with the help of the very apparatus that is its subject. But so it is with “The Beautiful Brain: The Drawings of Santiago Ramón y Cajal” at the Grey Art Gallery at New York University, one of the most unusual, ravishing exhibitions of the season.

The show finished its run on March 31, 2018 and is now on its way to the Massachusetts Institute of Technology (MIT) in Boston, Massachusetts for its opening on May 3, 2018. It looks like they have an exciting lineup of events to go along with the exhibit (from MIT’s The Beautiful Brain: The Drawings of Santiago Ramón y Cajal exhibit and event page),

SUMMER PROGRAMS

ONGOING

Spotlight Tours
Explorations led by local and Spanish scientists, artists, and entrepreneurs who will share their unique perspectives on particular aspects of the exhibition. (2:00 pm on select Tuesdays and Saturdays)

Tue, May 8 – Mark Harnett, Fred and Carole Middleton Career Development Professor at MIT and McGovern Institute Investigator Sat, May 26 – Marion Boulicault, MIT Graduate Student and Neuroethics Fellow in the Center for Sensorimotor Neural Engineering Tue, June 5 – Kelsey Allen, Graduate researcher, MIT Center for Brains, Minds, and Machines Sat, Jun 23 – Francisco Martin-Martinez, Research Scientist in MIT’s Laboratory for Atomistic & Molecular Mechanics and President of the Spanish Foundation for Science and Technology Jul 21 – Alex Gomez-Marin, Principal Investigator of the Behavior of Organisms Laboratory in the Instituto de Neurociencias, Spain Tue, Jul 31– Julie Pryor, Director of Communications at the McGovern Institute for Brain Research at MIT Tue, Aug 28 – Satrajit Ghosh, Principal Research Scientist at the McGovern Institute for Brain Research at MIT, Assistant Professor in the Department of Otolaryngology at Harvard Medical School, and faculty member in the Speech and Hearing Biosciences and Technology program in the Harvard Division of Medical Sciences

Idea Hub
Drop in and explore expansion microscopy in our maker-space.

Visualizing Science Workshop
Experiential learning with micro-scale biological images. (pre-registration required)

Gallery Demonstrations
Researchers share the latest on neural anatomy, signal transmission, and modern imaging techniques.

EVENTS

Teen Science Café: Mindful Matters
MIT researchers studying the brain share their mind-blowing findings.

Neuron Paint Night
Create a painting of cerebral cortex neurons and learn about the EyeWire citizen science game.

Cerebral Cinema Series
Hear from researchers and then compare real science to depictions on the big screen.

Brainy Trivia
Test your brain power in a night of science trivia and short, snappy research talks.

Come back to see our exciting lineup for the fall!

If you don’t have a chance to see the show or if you’d like a preview, I encourage you to read Smith’s article as it has embedded several Cajal drawings and rendered them exceptionally well.

For those who like a little contemporary (and related) science with their art, there’s a March 30, 2018 Harvard Medical Schoo (HMS)l news release by Kevin Jang (also on EurekAlert), Note: All links save one have been removed,

Drawing of the cells of the chick cerebellum by Santiago Ramón y Cajal, from “Estructura de los centros nerviosos de las aves,” Madrid, circa 1905

 

Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries.

His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks.

As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species?

At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron—one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the “butterflies of the soul.”

Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism and intellectual disability.

Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out.

Now, in a study published in the March 22 [2018] issue of Nature, researchers from Harvard Medical School, New York Genome Center, New York University and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.

Using single-cell analysis—a technology that allows scientists to track cellular behavior one cell at a time—the team traced the lineage of interneurons from their earliest precursor states to their mature forms in mice. The researchers identified key genetic programs that determine the fate of developing interneurons, as well as when these programs are switched on or off.

The findings serve as a guide for efforts to shed light on interneuron function and may help inform new treatment strategies for disorders involving their dysfunction, the authors said.

“We knew more than 100 years ago that this huge diversity of morphologically interesting cells existed in the brain, but their specific individual roles in brain function are still largely unclear,” said co-senior author Gordon Fishell, HMS professor of neurobiology and a faculty member at the Stanley Center for Psychiatric Research at the Broad.

“Our study provides a road map for understanding how and when distinct interneuron subtypes develop, giving us unprecedented insight into the biology of these cells,” he said. “We can now investigate interneuron properties as they emerge, unlock how these important cells function and perhaps even intervene when they fail to develop correctly in neuropsychiatric disease.”

A hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative CommonsA hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative Commons

Origins and Fates

In collaboration with co-senior author Rahul Satija, core faculty member of the New York Genome Center, Fishell and colleagues analyzed brain regions in developing mice known to contain precursor cells that give rise to interneurons.

Using Drop-seq, a single-cell sequencing technique created by researchers at HMS and the Broad, the team profiled gene expression in thousands of individual cells at multiple time points.

This approach overcomes a major limitation in past research, which could analyze only the average activity of mixtures of many different cells.

In the current study, the team found that the precursor state of all interneurons had similar gene expression patterns despite originating in three separate brain regions and giving rise to 14 or more interneuron subtypes alone—a number still under debate as researchers learn more about these cells.

“Mature interneuron subtypes exhibit incredible diversity. Their morphology and patterns of connectivity and activity are so different from each other, but our results show that the first steps in their maturation are remarkably similar,” said Satija, who is also an assistant professor of biology at New York University.

“They share a common developmental trajectory at the earliest stages, but the seeds of what will cause them to diverge later—a handful of genes—are present from the beginning,” Satija said.

As they profiled cells at later stages in development, the team observed the initial emergence of four interneuron “cardinal” classes, which give rise to distinct fates. Cells were committed to these fates even in the early embryo. By developing a novel computational strategy to link precursors with adult subtypes, the researchers identified individual genes that were switched on and off when cells began to diversify.

For example, they found that the gene Mef2c—mutations of which are linked to Alzheimer’s disease, schizophrenia and neurodevelopmental disorders in humans—is an early embryonic marker for a specific interneuron subtype known as Pvalb neurons. When they deleted Mef2c in animal models, Pvalb neurons failed to develop.

These early genes likely orchestrate the execution of subsequent genetic subroutines, such as ones that guide interneuron subtypes as they migrate to different locations in the brain and ones that help form unique connection patterns with other neural cell types, the authors said.

The identification of these genes and their temporal activity now provide researchers with specific targets to investigate the precise functions of interneurons, as well as how neurons diversify in general, according to the authors.

“One of the goals of this project was to address an incredibly fascinating developmental biology question, which is how individual progenitor cells decide between different neuronal fates,” Satija said. “In addition to these early markers of interneuron divergence, we found numerous additional genes that increase in expression, many dramatically, at later time points.”

The association of some of these genes with neuropsychiatric diseases promises to provide a better understanding of these disorders and the development of therapeutic strategies to treat them, a particularly important notion given the paucity of new treatments, the authors said.

Over the past 50 years, there have been no fundamentally new classes of neuropsychiatric drugs, only newer versions of old drugs, the researchers pointed out.

“Our repertoire is no better than it was in the 1970s,” Fishell said.

“Neuropsychiatric diseases likely reflect the dysfunction of very specific cell types. Our study puts forward a clear picture of what cells to look at as we work to shed light on the mechanisms that underlie these disorders,” Fishell said. “What we will find remains to be seen, but we have new, strong hypotheses that we can now test.”

As a resource for the research community, the study data and software are open-source and freely accessible online.

A gallery of the drawings of Santiago Ramón y Cajal is currently on display in New York City, and will open at the MIT Museum in Boston in May 2018.

Christian Mayer, Christoph Hafemeister and Rachel Bandler served as co-lead authors on the study.

This work was supported by the National Institutes of Health (R01 NS074972, R01 NS081297, MH071679-12, DP2-HG-009623, F30MH114462, T32GM007308, F31NS103398), the European Molecular Biology Organization, the National Science Foundation and the Simons Foundation.

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

Developmental diversification of cortical inhibitory interneurons by Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell, & Rahul Satija. Nature volume 555, pages 457–462 (22 March 2018) doi:10.1038/nature25999 Published: 05 March 2018

This paper is behind a paywall.

New path to viable memristor/neuristor?

I first stumbled onto memristors and the possibility of brain-like computing sometime in 2008 (around the time that R. Stanley Williams and his team at HP Labs first published the results of their research linking Dr. Leon Chua’s memristor theory to their attempts to shrink computer chips). In the almost 10 years since, scientists have worked hard to utilize memristors in the field of neuromorphic (brain-like) engineering/computing.

A January 22, 2018 news item on phys.org describes the latest work,

When it comes to processing power, the human brain just can’t be beat.

Packed within the squishy, football-sized organ are somewhere around 100 billion neurons. At any given moment, a single neuron can relay instructions to thousands of other neurons via synapses—the spaces between neurons, across which neurotransmitters are exchanged. There are more than 100 trillion synapses that mediate neuron signaling in the brain, strengthening some connections while pruning others, in a process that enables the brain to recognize patterns, remember facts, and carry out other learning tasks, at lightning speeds.

Researchers in the emerging field of “neuromorphic computing” have attempted to design computer chips that work like the human brain. Instead of carrying out computations based on binary, on/off signaling, like digital chips do today, the elements of a “brain on a chip” would work in an analog fashion, exchanging a gradient of signals, or “weights,” much like neurons that activate in various ways depending on the type and number of ions that flow across a synapse.

In this way, small neuromorphic chips could, like the brain, efficiently process millions of streams of parallel computations that are currently only possible with large banks of supercomputers. But one significant hangup on the way to such portable artificial intelligence has been the neural synapse, which has been particularly tricky to reproduce in hardware.

Now engineers at MIT [Massachusetts Institute of Technology] have designed an artificial synapse in such a way that they can precisely control the strength of an electric current flowing across it, similar to the way ions flow between neurons. The team has built a small chip with artificial synapses, made from silicon germanium. In simulations, the researchers found that the chip and its synapses could be used to recognize samples of handwriting, with 95 percent accuracy.

A January 22, 2018 MIT news release by Jennifer Chua (also on EurekAlert), which originated the news item, provides more detail about the research,

The design, published today [January 22, 2018] in the journal Nature Materials, is a major step toward building portable, low-power neuromorphic chips for use in pattern recognition and other learning tasks.

The research was led by Jeehwan Kim, the Class of 1947 Career Development Assistant Professor in the departments of Mechanical Engineering and Materials Science and Engineering, and a principal investigator in MIT’s Research Laboratory of Electronics and Microsystems Technology Laboratories. His co-authors are Shinhyun Choi (first author), Scott Tan (co-first author), Zefan Li, Yunjo Kim, Chanyeol Choi, and Hanwool Yeon of MIT, along with Pai-Yu Chen and Shimeng Yu of Arizona State University.

Too many paths

Most neuromorphic chip designs attempt to emulate the synaptic connection between neurons using two conductive layers separated by a “switching medium,” or synapse-like space. When a voltage is applied, ions should move in the switching medium to create conductive filaments, similarly to how the “weight” of a synapse changes.

But it’s been difficult to control the flow of ions in existing designs. Kim says that’s because most switching mediums, made of amorphous materials, have unlimited possible paths through which ions can travel — a bit like Pachinko, a mechanical arcade game that funnels small steel balls down through a series of pins and levers, which act to either divert or direct the balls out of the machine.

Like Pachinko, existing switching mediums contain multiple paths that make it difficult to predict where ions will make it through. Kim says that can create unwanted nonuniformity in a synapse’s performance.

“Once you apply some voltage to represent some data with your artificial neuron, you have to erase and be able to write it again in the exact same way,” Kim says. “But in an amorphous solid, when you write again, the ions go in different directions because there are lots of defects. This stream is changing, and it’s hard to control. That’s the biggest problem — nonuniformity of the artificial synapse.”

A perfect mismatch

Instead of using amorphous materials as an artificial synapse, Kim and his colleagues looked to single-crystalline silicon, a defect-free conducting material made from atoms arranged in a continuously ordered alignment. The team sought to create a precise, one-dimensional line defect, or dislocation, through the silicon, through which ions could predictably flow.

To do so, the researchers started with a wafer of silicon, resembling, at microscopic resolution, a chicken-wire pattern. They then grew a similar pattern of silicon germanium — a material also used commonly in transistors — on top of the silicon wafer. Silicon germanium’s lattice is slightly larger than that of silicon, and Kim found that together, the two perfectly mismatched materials can form a funnel-like dislocation, creating a single path through which ions can flow.

The researchers fabricated a neuromorphic chip consisting of artificial synapses made from silicon germanium, each synapse measuring about 25 nanometers across. They applied voltage to each synapse and found that all synapses exhibited more or less the same current, or flow of ions, with about a 4 percent variation between synapses — a much more uniform performance compared with synapses made from amorphous material.

They also tested a single synapse over multiple trials, applying the same voltage over 700 cycles, and found the synapse exhibited the same current, with just 1 percent variation from cycle to cycle.

“This is the most uniform device we could achieve, which is the key to demonstrating artificial neural networks,” Kim says.

Writing, recognized

As a final test, Kim’s team explored how its device would perform if it were to carry out actual learning tasks — specifically, recognizing samples of handwriting, which researchers consider to be a first practical test for neuromorphic chips. Such chips would consist of “input/hidden/output neurons,” each connected to other “neurons” via filament-based artificial synapses.

Scientists believe such stacks of neural nets can be made to “learn.” For instance, when fed an input that is a handwritten ‘1,’ with an output that labels it as ‘1,’ certain output neurons will be activated by input neurons and weights from an artificial synapse. When more examples of handwritten ‘1s’ are fed into the same chip, the same output neurons may be activated when they sense similar features between different samples of the same letter, thus “learning” in a fashion similar to what the brain does.

Kim and his colleagues ran a computer simulation of an artificial neural network consisting of three sheets of neural layers connected via two layers of artificial synapses, the properties of which they based on measurements from their actual neuromorphic chip. They fed into their simulation tens of thousands of samples from a handwritten recognition dataset commonly used by neuromorphic designers, and found that their neural network hardware recognized handwritten samples 95 percent of the time, compared to the 97 percent accuracy of existing software algorithms.

The team is in the process of fabricating a working neuromorphic chip that can carry out handwriting-recognition tasks, not in simulation but in reality. Looking beyond handwriting, Kim says the team’s artificial synapse design will enable much smaller, portable neural network devices that can perform complex computations that currently are only possible with large supercomputers.

“Ultimately we want a chip as big as a fingernail to replace one big supercomputer,” Kim says. “This opens a stepping stone to produce real artificial hardware.”

This research was supported in part by the National Science Foundation.

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

SiGe epitaxial memory for neuromorphic computing with reproducible high performance based on engineered dislocations by Shinhyun Choi, Scott H. Tan, Zefan Li, Yunjo Kim, Chanyeol Choi, Pai-Yu Chen, Hanwool Yeon, Shimeng Yu, & Jeehwan Kim. Nature Materials (2018) doi:10.1038/s41563-017-0001-5 Published online: 22 January 2018

This paper is behind a paywall.

For the curious I have included a number of links to recent ‘memristor’ postings here,

January 22, 2018: Memristors at Masdar

January 3, 2018: Mott memristor

August 24, 2017: Neuristors and brainlike computing

June 28, 2017: Dr. Wei Lu and bio-inspired ‘memristor’ chips

May 2, 2017: Predicting how a memristor functions

December 30, 2016: Changing synaptic connectivity with a memristor

December 5, 2016: The memristor as computing device

November 1, 2016: The memristor as the ‘missing link’ in bioelectronic medicine?

You can find more by using ‘memristor’ as the search term in the blog search function or on the search engine of your choice.

Graphite ‘gold’ rush?

Someone in Germany (I think) is very excited about graphite, more specifically, there’s excitement around graphite flakes located in the province of Québec, Canada. Although, the person who wrote this news release might have wanted to run a search for ‘graphite’ and ‘gold rush’. The last graphite gold rush seems to have taken place in 2013.

Here’s the March 1, 2018 news release on PR Newswire (Cision), Note: Some links have been removed),

PALM BEACH, Florida, March 1, 2018 /PRNewswire/ —

MarketNewsUpdates.com News Commentary

Much like the gold rush in North America in the 1800s, people are going out in droves searching for a different kind of precious metal, graphite. The thing your third grade pencils were made of is now one of the hottest commodities on the market. This graphite is not being mined by your run-of-the-mill old-timey soot covered prospectors anymore. Big mining companies are all looking for this important resource integral to the production of lithium ion batteries due to the rise in popularity of electric cars. These players include Graphite Energy Corp. (OTC: GRXXF) (CSE: GRE), Teck Resources Limited (NYSE: TECK), Nemaska Lithium (TSX: NMX), Lithium Americas Corp. (TSX: LAC), and Cruz Cobalt Corp. (TSX-V: CUZ) (OTC: BKTPF).

These companies looking to manufacturer their graphite-based products, have seen steady positive growth over the past year. Their development of cutting-edge new products seems to be paying off. But in order to continue innovating, these companies need the graphite to do it. One junior miner looking to capitalize on the growing demand for this commodity is Graphite Energy Corp.

Graphite Energy is a mining company, that is focused on developing graphite resources. Graphite Energy’s state-of-the-art mining technology is friendly to the environment and has indicate graphite carbon (Cg) in the range of 2.20% to 22.30% with average 10.50% Cg from their Lac Aux Bouleaux Graphite Property in Southern Quebec [Canada].

Not Just Any Graphite Will Do

Graphite is one of the most in demand technology metals that is required for a green and sustainable world. Demand is only set to increase as the need for lithium ion batteries grows, fueled by the popularity of electric vehicles. However, not all graphite is created equal. The price of natural graphite has more than doubled since 2013 as companies look to maintain environmental standards which the use of synthetic graphite cannot provide due to its pollutant manufacturing process. Synthetic graphite is also very expensive to produce, deriving from petroleum and costing up to ten times as much as natural graphite. Therefore manufacturers are interested in increasing the proportion of natural graphite in their products in order to lower their costs.

High-grade large flake graphite is the solution to the environmental issues these companies are facing. But there is only so much supply to go around. Recent news by Graphite Energy Corp. on February 26th [2018] showed promising exploratory results. The announcement of the commencement of drilling is a positive step forward to meeting this increased demand.

Everything from batteries to solar panels need to be made with this natural high-grade flake graphite because what is the point of powering your home with the sun or charging your car if the products themselves do more harm than good to the environment when produced. However, supply consistency remains an issue since mines have different raw material impurities which vary from mine to mine. Certain types of battery technology already require graphite to be almost 100% pure. It is very possible that the purity requirements will increase in the future.

Natural graphite is also the basis of graphene, the uses of which seem limited only by scientists’ imaginations, given the host of new applications announced daily. In a recent study by ResearchSEA, a team from the Ocean University of China and Yunnan Normal University developed a highly efficient dye-sensitized solar cell using a graphene layer. This thin layer of graphene will allow solar panels to generate electricity when it rains.

Graphite Energy Is Keeping It Green

Whether it’s the graphite for the solar panels that will power the homes of tomorrow, or the lithium ion batteries that will fuel the latest cars, these advancements need to made in an environmentally conscious way. Mining companies like Graphite Energy Corp. specialize in the production of environmentally friendly graphite. The company will be producing its supply of natural graphite with the lowest environmental footprint possible.

From Saltwater To Clean Water Using Graphite

The world’s freshwater supply is at risk of running out. In order to mitigate this global disaster, worldwide spending on desalination technology was an estimated $16.6 billion in 2016. Due to the recent intense droughts in California, the state has accelerated the construction of desalination plants. However, the operating costs and the impact on the environment due to energy requirements for the process, is hindering any real progress in the space, until now.

Jeffrey Grossman, a professor at MIT’s [Massachusetts Institute of Technology, United States] Department of Materials Science and Engineering (DMSE), has been looking into whether graphite/graphene might reduce the cost of desalination.

“A billion people around the world lack regular access to clean water, and that’s expected to more than double in the next 25 years,” Grossman says. “Desalinated water costs five to 10 times more than regular municipal water, yet we’re not investing nearly enough money into research. If we don’t have clean energy we’re in serious trouble, but if we don’t have water we die.”

Grossman’s lab has demonstrated strong results showing that new filters made from graphene could greatly improve the energy efficiency of desalination plants while potentially reducing other costs as well.

Graphite/Graphene producers like Graphite Energy Corp. (OTC: GRXXF) (CSE: GRE) are moving quickly to provide the materials necessary to develop this new generation of desalination plants.

Potential Comparables

Cruz Cobalt Corp. (TSX-V: CUZ) (OTC: BKTPF) Cruz Cobalt Corp. is cobalt mining company involved in the identification, acquisition and exploration of mineral properties. The company’s geographical segments include the United States and Canada. They are focused on acquiring and developing high-grade Cobalt projects in politically stable, environmentally responsible and ethical mining jurisdictions, essential for the rapidly growing rechargeable battery and renewable energy.

Nemaska Lithium (TSE: NMX.TO)

Nemaska Lithium is lithium mining company. The company is a supplier of lithium hydroxide and lithium carbonate to the emerging lithium battery market that is largely driven by electric vehicles. Nemaska mining operations are located in the mining friendly jurisdiction of Quebec, Canada. Nemaska Lithium has received a notice of allowance of a main patent application on its proprietary process to produce lithium hydroxide and lithium carbonate.

Lithium Americas Corp. (TSX: LAC.TO)

Lithium Americas is developing one of North America’s largest lithium deposits in northern Nevada. It operates nearly two lithium projects namely Cauchari-Olaroz project which is located in Argentina, and the Lithium Nevada project located in Nevada. The company manufactures specialty organoclay products, derived from clays, for sale to the oil and gas and other sectors.

Teck Resources Limited (NYSE: TECK)

Teck Resources Limited is a Canadian metals and mining company.Teck’s principal products include coal, copper, zinc, with secondary products including lead, silver, gold, molybdenum, germanium, indium and cadmium. Teck’s diverse resources focuses on providing products that are essential to building a better quality of life for people around the globe.

Graphite Mining Today For A Better Tomorrow

Graphite mining will forever be intertwined with the latest advancements in science and technology. Graphite deserves attention for its various use cases in automotive, energy, aerospace and robotics industries. In order for these and other industries to become sustainable and environmentally friendly, a reliance on graphite is necessary. Therefore, this rapidly growing sector has the potential to fuel investor interest in the mining space throughout 2018. The near limitless uses of graphite has the potential to impact every facet of our lives. Companies like Graphite Energy Corp. (OTC: GRXXF); (CSE: GRE) is at the forefront in this technological revolution.

For more information on Graphite Energy Corp. (OTC: GRXXF) (CSE: GRE), please visit streetsignals.com for a free research report.

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Hopefully my insertions of ‘Canada’ and the ‘United States’ help to clarify matters. North America and the United States are not synonyms although they are sometimes used synonymously.

There is another copy of this news release on Wall Street Online (Deutschland), both in English and German.By the way, that was my first clue that there might be some German interest. The second clue was the Graphite Energy Corp. homepage. Unusually for a company with ‘headquarters’ in the Canadian province of British Columbia, there’s an option to read the text in German.

Graphite Energy Corp. seems to be a relatively new player in the ‘rush’ to mine graphite flakes for use in graphene-based applications. One of my first posts about mining for graphite flakes was a July 26, 2011 posting concerning Northern Graphite and their mining operation (Bissett Creek) in Ontario. I don’t write about them often but they are still active if their news releases are to be believed. The latest was issued February 28, 2018 and offers “financial metrics for the Preliminary Economic Assessment (the “PEA”) on the Company’s 100% owned Bissett Creek graphite project.”

The other graphite mining company mentioned here is Lomiko Metals. The latest posting here about Lomiko is a December 23, 2015 piece regarding an analysis and stock price recommendation by a company known as SeeThruEquity. Like Graphite Energy Corp., Lomiko’s mines are located in Québec and their business headquarters in British Columbia. Lomiko has a March 16, 2018 news release announcing its reinstatement for trading on the TSX (Toronto Stock Exchange),

(Vancouver, B.C.) Lomiko Metals Inc. (“Lomiko”) (“Lomiko”) (TSX-V: LMR, OTC: LMRMF, FSE: DH8C) announces it has been successful in its reinstatement application with the TSX Venture Exchange and trading will begin at the opening on Tuesday, March 20, 2018.

Getting back to the flakes, here’s more about Graphite Energy Corp.’s mine (from the About Lac Aux Bouleaux webpage),

Lac Aux Bouleaux

The Lac Aux Bouleaux Property is comprised of 14 mineral claims in one contiguous block totaling 738.12 hectares land on NTS 31J05, near the town of Mont-Laurier in southern Québec. Lac Aux Bouleaux “LAB” is a world class graphite property that borders the only producing graphite in North America [Note: There are three countries in North America, Canada, the United States, and Mexico. Québec is in Canada.]. On the property we have a full production facility already built which includes an open pit mine, processing facility, tailings pond, power and easy access to roads.

High Purity Levels

An important asset of LAB is its metallurgy. The property contains a high proportion of large and jumbo flakes from which a high purity concentrate was proven to be produced across all flakes by a simple flotation process. The concentrate can then be further purified using the province’s green and affordable hydro-electricity to be used in lithium-ion batteries.

The geological work performed in order to verify the existing data consisted of visiting approachable graphite outcrops, historical exploration and development work on the property. Large flake graphite showings located on the property were confirmed with flake size in the range of 0.5 to 2 millimeters, typically present in shear zones at the contact of gneisses and marbles where the graphite content usually ranges from 2% to 20%. The results of the property are outstanding showing to have jumbo flake natural graphite.

An onsite mill structure, a tailing dam facility, and a historical open mining pit is already present and constructed on the property. The property is ready to be put into production based on the existing infrastructure already built. The company would hope to be able to ship by rail its mined graphite directly to Teslas Gigafactory being built in Nevada [United States] which will produce 35GWh of batteries annually by 2020.

Adjacent Properties

The property is located in a very active graphite exploration and production area, adjacent to the south of TIMCAL’s Lac des Iles graphite mine in Quebec which is a world class deposit producing 25,000 tonnes of graphite annually. There are several graphite showings and past producing mines in its vicinity, including a historic deposit located on the property.

The open pit mine in operation since 1989 with an onsite plant ranked 5th in the world production of graphite. The mine is operated by TIMCAL Graphite & Carbon which is a subsidiary of Imerys S.A., a French multinational company. The mine has an average grade of 7.5% Cg (graphite carbon) and has been producing 50 different graphite products for various graphite end users around the globe.

Canadians! We have great flakes!

Tracking artificial intelligence

Researchers at Stanford University have developed an index for measuring (tracking) the progress made by artificial intelligence (AI) according to a January 9, 2018 news item on phys.org (Note: Links have been removed),

Since the term “artificial intelligence” (AI) was first used in print in 1956, the one-time science fiction fantasy has progressed to the very real prospect of driverless cars, smartphones that recognize complex spoken commands and computers that see.

In an effort to track the progress of this emerging field, a Stanford-led group of leading AI thinkers called the AI100 has launched an index that will provide a comprehensive baseline on the state of artificial intelligence and measure technological progress in the same way the gross domestic product and the S&P 500 index track the U.S. economy and the broader stock market.

For anyone curious about the AI100 initiative, I have a description of it in my Sept. 27, 2016 post highlighting the group’s first report or you can keep on reading.

Getting back to the matter at hand, a December 21, 2017 Stanford University press release by Andrew Myers, which originated the news item, provides more detail about the AI index,

“The AI100 effort realized that in order to supplement its regular review of AI, a more continuous set of collected metrics would be incredibly useful,” said Russ Altman, a professor of bioengineering and the faculty director of AI100. “We were very happy to seed the AI Index, which will inform the AI100 as we move forward.”

The AI100 was set in motion three years ago when Eric Horvitz, a Stanford alumnus and former president of the Association for the Advancement of Artificial Intelligence, worked with his wife, Mary Horvitz, to define and endow the long-term study. Its first report, released in the fall of 2016, sought to anticipate the likely effects of AI in an urban environment in the year 2030.

Among the key findings in the new index are a dramatic increase in AI startups and investment as well as significant improvements in the technology’s ability to mimic human performance.

Baseline metrics

The AI Index tracks and measures at least 18 independent vectors in academia, industry, open-source software and public interest, plus technical assessments of progress toward what the authors call “human-level performance” in areas such as speech recognition, question-answering and computer vision – algorithms that can identify objects and activities in 2D images. Specific metrics in the index include evaluations of academic papers published, course enrollment, AI-related startups, job openings, search-term frequency and media mentions, among others.

“In many ways, we are flying blind in our discussions about artificial intelligence and lack the data we need to credibly evaluate activity,” said Yoav Shoham, professor emeritus of computer science.

“The goal of the AI Index is to provide a fact-based measuring stick against which we can chart progress and fuel a deeper conversation about the future of the field,” Shoham said.

Shoham conceived of the index and assembled a steering committee including Ray Perrault from SRI International, Erik Brynjolfsson of the Massachusetts Institute of Technology and Jack Clark from OpenAI. The committee subsequently hired Calvin LeGassick as project manager.

“The AI Index will succeed only if it becomes a community effort,” Shoham said.

Although the authors say the AI Index is the first index to track either scientific or technological progress, there are many other non-financial indexes that provide valuable insight into equally hard-to-quantify fields. Examples include the Social Progress Index, the Middle East peace index and the Bangladesh empowerment index, which measure factors as wide-ranging as nutrition, sanitation, workload, leisure time, public sentiment and even public speaking opportunities.

Intriguing findings

Among the findings of this inaugural index is that the number of active AI startups has increased 14-fold since 2000. Venture capital investment has increased six times in the same period. In academia, publishing in AI has increased a similarly impressive nine times in the last 20 years while course enrollment has soared. Enrollment in the introductory AI-related machine learning course at Stanford, for instance, has grown 45-fold in the last 30 years.

In technical metrics, image and speech recognition are both approaching, if not surpassing, human-level performance. The authors noted that AI systems have excelled in such real-world applications as object detection, the ability to understand and answer questions and classification of photographic images of skin cancer cells

Shoham noted that the report is still very U.S.-centric and will need a greater international presence as well as a greater diversity of voices. He said he also sees opportunities to fold in government and corporate investment in addition to the venture capital funds that are currently included.

In terms of human-level performance, the AI Index suggests that in some ways AI has already arrived. This is true in game-playing applications including chess, the Jeopardy! game show and, most recently, the game of Go. Nonetheless, the authors note that computers continue to lag considerably in the ability to generalize specific information into deeper meaning.

“AI has made truly amazing strides in the past decade,” Shoham said, “but computers still can’t exhibit the common sense or the general intelligence of even a 5-year-old.”

The AI Index was made possible by funding from AI100, Google, Microsoft and Toutiao. Data supporting the various metrics were provided by Elsevier, TrendKite, Indeed.com, Monster.com, the Google Trends Team, the Google Brain Team, Sand Hill Econometrics, VentureSource, Crunchbase, Electronic Frontier Foundation, EuroMatrix, Geoff Sutcliffe, Kevin Leyton-Brown and Holger Hoose.

You can find the AI Index here. They’re featuring their 2017 report but you can also find data (on the menu bar on the upper right side of your screen), along with a few provisos. I was curious as to whether any AI had been used to analyze the data and/or write the report. A very cursory look at the 2017 report did not answer that question. I’m fascinated by the failure to address what I think is an obvious question. It suggests that even very, very bright people can become blind and I suspect that’s why the group seems quite eager to get others involved, from the 2017 AI Index Report,

As the report’s limitations illustrate, the AI Index will always paint a partial picture. For this reason, we include subjective commentary from a cross-section of AI experts. This Expert Forum helps animate the story behind the data in the report and adds interpretation the report lacks.

Finally, where the experts’ dialogue ends, your opportunity to Get Involved begins [emphasis mine]. We will need the feedback and participation of a larger community to address the issues identified in this report, uncover issues we have omitted, and build a productive process for tracking activity and progress in Artificial Intelligence. (p. 8)

Unfortunately, it’s not clear how one becomes involved. Is there a forum or do you get in touch with one of the team leaders?

I wish them good luck with their project and imagine that these minor hiccups will be dealt with in near term.

The devil’s (i.e., luciferase) in the bioluminescent plant

The American Chemical Society (ACS) and the Massachusetts Institute of Technology (MIT) have both issued news releases about the latest in bioluminescence.The researchers tested their work on watercress, a vegetable that was viewed in almost sacred terms in my family; it was not easily available in Vancouver (Canada) when I was child.

My father would hunt down fresh watercress by checking out the Chinese grocery stores. He could spot the fresh stuff from across the street while driving at 30 miles or more per hour. Spotting it entailed an immediate hunt for parking (my father hated to pay so we might have go around the block a few times or more) and a dash out of the car to ensure that he got his watercress before anyone else spotted it. These days it’s much more easily available and, thankfully, my father has passed on so he won’t have to think about glowing watercress.

Getting back to bioluninescent vegetable research, the American Chemical Society’s Dec. 13, 2017 news release on EurekAlert (and as a Dec. 13, 2017 news item on ScienceDaily) makes the announcement,

The 2009 film “Avatar” created a lush imaginary world, illuminated by magical, glowing plants. Now researchers are starting to bring this spellbinding vision to life to help reduce our dependence on artificial lighting. They report in ACS’ journal Nano Letters a way to infuse plants with the luminescence of fireflies.

Nature has produced many bioluminescent organisms, however, plants are not among them. Most attempts so far to create glowing greenery — decorative tobacco plants in particular — have relied on introducing the genes of luminescent bacteria or fireflies through genetic engineering. But getting all the right components to the right locations within the plants has been a challenge. To gain better control over where light-generating ingredients end up, Michael S. Strano and colleagues recently created nanoparticles that travel to specific destinations within plants. Building on this work, the researchers wanted to take the next step and develop a “nanobionic,” glowing plant.

The team infused watercress and other plants with three different nanoparticles in a pressurized bath. The nanoparticles were loaded with light-emitting luciferin; luciferase, which modifies luciferin and makes it glow; and coenzyme A, which boosts luciferase activity. Using size and surface charge to control where the sets of nanoparticles could go within the plant tissues, the researchers could optimize how much light was emitted. Their watercress was half as bright as a commercial 1 microwatt LED and 100,000 times brighter than genetically engineered tobacco plants. Also, the plant could be turned off by adding a compound that blocks luciferase from activating luciferin’s glow.

Here’s a video from MIT detailing their research,

A December 13, 2017 MIT news release (also on EurekAlert) casts more light on the topic (I couldn’t resist the word play),

Imagine that instead of switching on a lamp when it gets dark, you could read by the light of a glowing plant on your desk.

MIT engineers have taken a critical first step toward making that vision a reality. By embedding specialized nanoparticles into the leaves of a watercress plant, they induced the plants to give off dim light for nearly four hours. They believe that, with further optimization, such plants will one day be bright enough to illuminate a workspace.

“The vision is to make a plant that will function as a desk lamp — a lamp that you don’t have to plug in. The light is ultimately powered by the energy metabolism of the plant itself,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT and the senior author of the study

This technology could also be used to provide low-intensity indoor lighting, or to transform trees into self-powered streetlights, the researchers say.

MIT postdoc Seon-Yeong Kwak is the lead author of the study, which appears in the journal Nano Letters.

Nanobionic plants

Plant nanobionics, a new research area pioneered by Strano’s lab, aims to give plants novel features by embedding them with different types of nanoparticles. The group’s goal is to engineer plants to take over many of the functions now performed by electrical devices. The researchers have previously designed plants that can detect explosives and communicate that information to a smartphone, as well as plants that can monitor drought conditions.

Lighting, which accounts for about 20 percent of worldwide energy consumption, seemed like a logical next target. “Plants can self-repair, they have their own energy, and they are already adapted to the outdoor environment,” Strano says. “We think this is an idea whose time has come. It’s a perfect problem for plant nanobionics.”

To create their glowing plants, the MIT team turned to luciferase, the enzyme that gives fireflies their glow. Luciferase acts on a molecule called luciferin, causing it to emit light. Another molecule called co-enzyme A helps the process along by removing a reaction byproduct that can inhibit luciferase activity.

The MIT team packaged each of these three components into a different type of nanoparticle carrier. The nanoparticles, which are all made of materials that the U.S. Food and Drug Administration classifies as “generally regarded as safe,” help each component get to the right part of the plant. They also prevent the components from reaching concentrations that could be toxic to the plants.

The researchers used silica nanoparticles about 10 nanometers in diameter to carry luciferase, and they used slightly larger particles of the polymers PLGA and chitosan to carry luciferin and coenzyme A, respectively. To get the particles into plant leaves, the researchers first suspended the particles in a solution. Plants were immersed in the solution and then exposed to high pressure, allowing the particles to enter the leaves through tiny pores called stomata.

Particles releasing luciferin and coenzyme A were designed to accumulate in the extracellular space of the mesophyll, an inner layer of the leaf, while the smaller particles carrying luciferase enter the cells that make up the mesophyll. The PLGA particles gradually release luciferin, which then enters the plant cells, where luciferase performs the chemical reaction that makes luciferin glow.

The researchers’ early efforts at the start of the project yielded plants that could glow for about 45 minutes, which they have since improved to 3.5 hours. The light generated by one 10-centimeter watercress seedling is currently about one-thousandth of the amount needed to read by, but the researchers believe they can boost the light emitted, as well as the duration of light, by further optimizing the concentration and release rates of the components.

Plant transformation

Previous efforts to create light-emitting plants have relied on genetically engineering plants to express the gene for luciferase, but this is a laborious process that yields extremely dim light. Those studies were performed on tobacco plants and Arabidopsis thaliana, which are commonly used for plant genetic studies. However, the method developed by Strano’s lab could be used on any type of plant. So far, they have demonstrated it with arugula, kale, and spinach, in addition to watercress.

For future versions of this technology, the researchers hope to develop a way to paint or spray the nanoparticles onto plant leaves, which could make it possible to transform trees and other large plants into light sources.

“Our target is to perform one treatment when the plant is a seedling or a mature plant, and have it last for the lifetime of the plant,” Strano says. “Our work very seriously opens up the doorway to streetlamps that are nothing but treated trees, and to indirect lighting around homes.”

The researchers have also demonstrated that they can turn the light off by adding nanoparticles carrying a luciferase inhibitor. This could enable them to eventually create plants that shut off their light emission in response to environmental conditions such as sunlight, the researchers say.

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

A Nanobionic Light-Emitting Plant by Seon-Yeong Kwak, Juan Pablo Giraldo, Min Hao Wong, Volodymyr B. Koman, Tedrick Thomas Salim Lew, Jon Ell, Mark C. Weidman, Rosalie M. Sinclair, Markita P. Landry, William A. Tisdale, and Michael S. Strano. Nano Lett., 2017, 17 (12), pp 7951–7961 DOI: 10.1021/acs.nanolett.7b04369 Publication Date (Web): November 17, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

A 3D printed ‘living’ tattoo

MIT engineers have devised a 3-D printing technique that uses a new kind of ink made from genetically programmed living cells. Courtesy of the researchers [and MIT]

If that image isn’t enough, there’s also a video abstract (I don’t think I’ve seen one of these before) for the paper,

For those who’d still like to read the text, here’s more from a December 5, 2017 MIT (Massachusetts Institute of Technology) news release (also on EurekAlert),

MIT engineers have devised a 3-D printing technique that uses a new kind of ink made from genetically programmed living cells.

The cells are engineered to light up in response to a variety of stimuli. When mixed with a slurry of hydrogel and nutrients, the cells can be printed, layer by layer, to form three-dimensional, interactive structures and devices.

The team has then demonstrated its technique by printing a “living tattoo” — a thin, transparent patch patterned with live bacteria cells in the shape of a tree. Each branch of the tree is lined with cells sensitive to a different chemical or molecular compound. When the patch is adhered to skin that has been exposed to the same compounds, corresponding regions of the tree light up in response.

The researchers, led by Xuanhe Zhao, the Noyce Career Development Professor in MIT’s Department of Mechanical Engineering, and Timothy Lu, associate professor of biological engineering and of electrical engineering and computer science, say that their technique can be used to fabricate “active” materials for wearable sensors and interactive displays. Such materials can be patterned with live cells engineered to sense environmental chemicals and pollutants as well as changes in pH and temperature.

What’s more, the team developed a model to predict the interactions between cells within a given 3-D-printed structure, under a variety of conditions. The team says researchers can use the model as a guide in designing responsive living materials.

Zhao, Lu, and their colleagues have published their results today [December 5, 2017] in the journal Advanced Materials. The paper’s co-authors are graduate students Xinyue Liu, Hyunwoo Yuk, Shaoting Lin, German Alberto Parada, Tzu-Chieh Tang, Eléonore Tham, and postdoc Cesar de la Fuente-Nunez.

A hardy alternative

In recent years, scientists have explored a variety of responsive materials as the basis for 3D-printed inks. For instance, scientists have used inks made from temperature-sensitive polymers to print heat-responsive shape-shifting objects. Others have printed photoactivated structures from polymers that shrink and stretch in response to light.

Zhao’s team, working with bioengineers in Lu’s lab, realized that live cells might also serve as responsive materials for 3D-printed inks, particularly as they can be genetically engineered to respond to a variety of stimuli. The researchers are not the first to consider 3-D printing genetically engineered cells; others have attempted to do so using live mammalian cells, but with little success.

“It turns out those cells were dying during the printing process, because mammalian cells are basically lipid bilayer balloons,” Yuk says. “They are too weak, and they easily rupture.”

Instead, the team identified a hardier cell type in bacteria. Bacterial cells have tough cell walls that are able to survive relatively harsh conditions, such as the forces applied to ink as it is pushed through a printer’s nozzle. Furthermore, bacteria, unlike mammalian cells, are compatible with most hydrogels — gel-like materials that are made from a mix of mostly water and a bit of polymer. The group found that hydrogels can provide an aqueous environment that can support living bacteria.

The researchers carried out a screening test to identify the type of hydrogel that would best host bacterial cells. After an extensive search, a hydrogel with pluronic acid was found to be the most compatible material. The hydrogel also exhibited an ideal consistency for 3-D printing.

“This hydrogel has ideal flow characteristics for printing through a nozzle,” Zhao says. “It’s like squeezing out toothpaste. You need [the ink] to flow out of a nozzle like toothpaste, and it can maintain its shape after it’s printed.”

From tattoos to living computers

Lu provided the team with bacterial cells engineered to light up in response to a variety of chemical stimuli. The researchers then came up with a recipe for their 3-D ink, using a combination of bacteria, hydrogel, and nutrients to sustain the cells and maintain their functionality.

“We found this new ink formula works very well and can print at a high resolution of about 30 micrometers per feature,” Zhao says. “That means each line we print contains only a few cells. We can also print relatively large-scale structures, measuring several centimeters.”

They printed the ink using a custom 3-D printer that they built using standard elements combined with fixtures they machined themselves. To demonstrate the technique, the team printed a pattern of hydrogel with cells in the shape of a tree on an elastomer layer. After printing, they solidified, or cured, the patch by exposing it to ultraviolet radiation. They then adhere the transparent elastomer layer with the living patterns on it, to skin.

To test the patch, the researchers smeared several chemical compounds onto the back of a test subject’s hand, then pressed the hydrogel patch over the exposed skin. Over several hours, branches of the patch’s tree lit up when bacteria sensed their corresponding chemical stimuli.

The researchers also engineered bacteria to communicate with each other; for instance they programmed some cells to light up only when they receive a certain signal from another cell. To test this type of communication in a 3-D structure, they printed a thin sheet of hydrogel filaments with “input,” or signal-producing bacteria and chemicals, overlaid with another layer of filaments of an “output,” or signal-receiving bacteria. They found the output filaments lit up only when they overlapped and received input signals from corresponding bacteria .

Yuk says in the future, researchers may use the team’s technique to print “living computers” — structures with multiple types of cells that communicate with each other, passing signals back and forth, much like transistors on a microchip.

“This is very future work, but we expect to be able to print living computational platforms that could be wearable,” Yuk says.

For more near-term applications, the researchers are aiming to fabricate customized sensors, in the form of flexible patches and stickers that could be engineered to detect a variety of chemical and molecular compounds. They also envision their technique may be used to manufacture drug capsules and surgical implants, containing cells engineered produce compounds such as glucose, to be released therapeutically over time.

“We can use bacterial cells like workers in a 3-D factory,” Liu says. “They can be engineered to produce drugs within a 3-D scaffold, and applications should not be confined to epidermal devices. As long as the fabrication method and approach are viable, applications such as implants and ingestibles should be possible.”

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

3D Printing of Living Responsive Materials and Devices by Xinyue Liu, Hyunwoo Yuk, Shaoting Lin, German Alberto Parada, Tzu-Chieh Tang, Eléonore Tham, Cesar de la Fuente-Nunez, Timothy K. Lu, and Xuanhe Zhao. Advanced Materials DOI: 10.1002/adma.201704821 Version of Record online: 5 DEC 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.