Tag Archives: George Church

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Medicine, healing, and big money

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Infections from pigs

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This paper is open access.

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

What is it to be human?

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

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

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

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

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

Why don’t you CRISPR yourself?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Canadian content*

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Nucleic acid-based memory storage

We’re running out of memory. To be more specific, there are two problems: the supply of silicon and a limit to how much silicon-based memory can store. An April 27, 2016 news item on Nanowerk announces a nucleic acid-based approach to solving the memory problem,

A group of Boise State [Boise State University in Idaho, US] researchers, led by associate professor of materials science and engineering and associate dean of the College of Innovation and Design Will Hughes, is working toward a better way to store digital information using nucleic acid memory (NAM).

An April 25, 2016 Boise State University news release, which originated the news item, expands on the theme of computer memory and provides more details about the approach,

It’s no secret that as a society we generate vast amounts of data each year. So much so that the 30 billion watts of electricity used annually by server farms today is roughly equivalent to the output of 30 nuclear power plants.

And the demand keeps growing. The global flash memory market is predicted to reach $30.2 billion this year, potentially growing to $80.3 billion by 2025. Experts estimate that by 2040, the demand for global memory will exceed the projected supply of silicon (the raw material used to store flash memory). Furthermore, electronic memory is rapidly approaching its fundamental size limits because of the difficulty in storing electrons in small dimensions.

Hughes, with post-doctoral researcher Reza Zadegan and colleagues Victor Zhirnov (Semiconductor Research Corporation), Gurtej Sandhun (Micron Technology Inc.) and George Church (Harvard University), is looking to DNA molecules to solve the problem. Nucleic acid — the “NA” in “DNA” — far surpasses electronic memory in retention time, according to the researchers, while also providing greater information density and energy of operation.

Their conclusions are outlined in an invited commentary in the prestigious journal Nature Materials published earlier this month.

“DNA is the data storage material of life in general,” said Hughes. “Because of its physical and chemical properties, it also may become the data storage material of our lives.” It may sound like science fiction, but Hughes will participate in an invitation-only workshop this month at the Intelligence Advanced Research Projects Activity (IARPA) Agency to envision a portable DNA hard drive that would have 500 Terabytes of searchable data – that’s about the the size of the Library of Congress Web Archive.

“When information bits are encoded into polymer strings, researchers and manufacturers can manage and manipulate physical, chemical and biological information with standard molecular biology techniques,” the paper [in Nature Materials?] states.

Cost-competitive technologies to read and write DNA could lead to real-world applications ranging from artificial chromosomes, digital hard drives and information-management systems, to a platform for watermarking and tracking genetic content or next-generation encryption tools that necessitate physical rather than electronic embodiment.

Here’s how it works. Current binary code uses 0’s and 1’s to represent bits of information. A computer program then accesses a specific decoder to turn the numbers back into usable data. With nucleic acid memory, 0’s and 1’s are replaced with the nucleotides A, T, C and G. Known as monomers, they are covalently bonded to form longer polymer chains, also known as information strings.

Because of DNA’s superior ability to store data, DNA can contain all the information in the world in a small box measuring 10 x 10 x 10 centimeters cubed. NAM could thus be used as a sustainable time capsule for massive, scientific, financial, governmental, historical, genealogical, personal and genetic records.

Better yet, DNA can store digital information for a very long time – thousands to millions of years. Currently, usable information has been extracted from DNA in bones that are 700,000 years old, making nucleic acid memory a promising archival material. And nucleic acid memory uses 100 million times less energy than storing data electronically in flash, and the data can live on for generations.

At Boise State, Hughes and Zadegan are examining DNA’s stability under extreme conditions. DNA strands are subjected to temperatures varying from negative 20 degrees Celsius to 100 degrees Celsius, and to a variety of UV exposures to see if they can still retain their information. What they’re finding is that much less information is lost with NAM than with the current state of the industry.

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

Nucleic acid memory by Victor Zhirnov, Reza M. Zadegan, Gurtej S. Sandhu, George M. Church, & William L. Hughes. Nature Materials 15, 366–370 (2016)  doi:10.1038/nmat4594 Published online 23 March 2016

This paper is behind a paywall.

Toggling atomic switches and other talks at the Foresight Institute’s 2013 technical conference

The correct title for the conference, which took place almost one year ago (Jan. 11-13, 2013 in Palo Alto, California, US, is the 2013 Foresight Technical Conference: Illuminating Atomic Precision, and the organizers, the Foresight Institute in a Dec. 2, 2013 posting by James Lewis have announced a number of conference videos have been made available and have provided a transcript of sorts for one of the videos,

A select set of videos from the 2013 Foresight Technical Conference: Illuminating Atomic Precision, held January 11-13, 2013 in Palo Alto, have been made available on vimeo. Videos have been posted of those presentations for which the speakers have consented. Other presentations contained confidential information and will not be posted.

Here’s a listing of the 2013 conference presentations made available (click to access the videos),

  • Larry Millstein: Introductory comments at Foresight Technical Conference 2013
  • J. Fraser Stoddart: Introductory comments at Foresight Technical Conference 2013
  • Leonhard Grill: “Assembly and Manipulation of Molecules at the Atomic Scale”
  • John Randall: “Atomically Precise Manufacturing”
  • Philip Moriarty: “Mechanical Atom Manipulation: Towards a Matter Compiler?”
  • David Soloveichik: “DNA Displacement Cascades”
  • Alex Wissner-Gross: “Bringing Computational Programmability to Nanostructured Surfaces”
  • Joseph Puglisi: “Deciphering the Molecular Choreography of Translation”
  • Feynman Awards Banquet at Foresight Technical Conference 2013
  • Gerhard Klimeck: “Multi-Million Atom Simulations for Single Atom Transistor Structures”
  • William Goddard: “Nanoscale Materials, Devices, and Processing Predicted from First Principals” [Note: He’s a wearing a jaunty beret adding a note of style not usually found at technical conferences.]
  • Gerhard Klimeck: “Mythbusting Knowledge Transfer Mechanisms through Science Gateways”
  • Art Olson: “New Methods of Exploring, Analyzing, and Predicting Molecular Interactions”
  • George Church: “Regenesis: Bionano”
  • Dean Astumian: “Microscopic Reversibility: The Organizing Principle for Molecular Machines”
  • Larry Millstein: Closing comments at Foresight Technical Conference 2013

In his Foresight Institute blog posting  Lewis goes on to offer a description of Philip Moriarty’s presentation “Mechanical Atom Manipulation: Towards a Matter Compiler?,”

Prof. Moriarty presented his work with the qPlus technique of non-contact AFM of semiconductors, using chemical forces to mechanically move atoms around to structure matter, focusing on the tip of the probe—specifically how to optimize the tip structure, and how to return the tip to a previously known state. He begins with a brief review of how non-contact AFM uses a damped, driven oscillator to measure and manipulate what is happening at the level of single chemical bonds. The tip at the end of the oscillating cantilever measures the frequency shift of the cantilever as it approaches and interacts with the surface, and it maintains a constant amplitude of oscillation by pumping energy into the system. The frequency shift provides information about conservative forces acting on the tip, and the amount of energy pumped in gives a handle on non-conservative, or dissipative, forces. Before diving into the experimental details of his own work, Prof. Moriarty noted that various experimental accomplishments have vindicated Eric Drexler’s assertion that single atom chemistry could be done using purely mechanical force.

I found this description to be a beautiful piece of technical writing although I do have to admit to being distracted by thoughts of Sherlock Holmes on reading “Prof. Moriarty.” One final note, I noted the reference to Eric Drexler in the last sentence of my excerpt as Drexler was a Foresight Institute founder amongst his many other accomplishments.