Tag Archives: Harvard Medical School

Need to improve oversight on chimeric human-animal research

It seems chimeras are of more interest these days. In all likelihood that has something to do with the fellow who received a transplant of a pig’s heart in January 2022 (he died in March 2022).

For those who aren’t familiar with the term, a chimera is an entity with two different DNA (deoxyribonucleic acid) identities. In short, if you get a DNA sample from the heart, it’s different from a DNA sample obtained from a cheek swab. This contrasts with a hybrid such as a mule (donkey/horse) whose DNA samples show a consisted identity throughout its body.

A December 12, 2022 The Hastings Center news release (also on EurekAlert) announces a special report,

A new report on the ethics of crossing species boundaries by inserting human cells into nonhuman animals – research surrounded by debate – makes recommendations clarifying the ethical issues and calling for improved oversight of this work.

The report, “Creating Chimeric Animals — Seeking Clarity On Ethics and Oversight,” was developed by an interdisciplinary team, with funding from the National Institutes of Health. Principal investigators are Josephine Johnston and Karen Maschke, research scholars at The Hastings Center, and Insoo Hyun, director of the Center for Life Sciences and Public Learning at the Museum of Life Sciences in Boston, formerly of Case Western Reserve University.

Advances in human stem cell science and gene editing enable scientists to insert human cells more extensively and precisely into nonhuman animals, creating “chimeric” animals, embryos, and other organisms that contain a mix of human and nonhuman cells.

Many people hope that this research will yield enormous benefits, including better models of human disease, inexpensive sources of human eggs and embryos for research, and sources of tissues and organs suitable for transplantation into humans. 

But there are ethical concerns about this type of research, which raise questions such as whether the moral status of nonhuman animals is altered by the insertion of human stem cells, whether these studies should be subject to additional prohibitions or oversight, and whether this kind of research should be done at all.

The report found that:

Animal welfare is a primary ethical issue and should be a focus of ethical and policy analysis as well as the governance and oversight of chimeric research.

Chimeric studies raise the possibility of unique or novel harms resulting from the insertion and development of human stem cells in nonhuman animals, particularly when those cells develop in the brain or central nervous system.

Oversight and governance of chimeric research are siloed, and public communication is minimal. Public communication should be improved, communication between the different committees involved in oversight at each institution should be enhanced, and a national mechanism created for those involved in oversight of these studies. 

Scientists, journalists, bioethicists, and others writing about chimeric research should use precise and accessible language that clarifies rather than obscures the ethical issues at stake. The terms “chimera,” which in Greek mythology refers to a fire-breathing monster, and “humanization” are examples of ethically laden, or overly broad language to be avoided.

The Research Team

The Hastings Center

• Josephine Johnston
• Karen J. Maschke
• Carolyn P. Neuhaus
• Margaret M. Matthews
• Isabel Bolo

Case Western Reserve University
• Insoo Hyun (now at Museum of Science, Boston)
• Patricia Marshall
• Kaitlynn P. Craig

The Work Group

• Kara Drolet, Oregon Health & Science University
• Henry T. Greely, Stanford University
• Lori R. Hill, MD Anderson Cancer Center
• Amy Hinterberger, King’s College London
• Elisa A. Hurley, Public Responsibility in Medicine and Research
• Robert Kesterson, University of Alabama at Birmingham
• Jonathan Kimmelman, McGill University
• Nancy M. P. King, Wake Forest University School of Medicine
• Geoffrey Lomax, California Institute for Regenerative Medicine
• Melissa J. Lopes, Harvard University Embryonic Stem Cell Research Oversight Committee
• P. Pearl O’Rourke, Harvard Medical School
• Brendan Parent, NYU Grossman School of Medicine
• Steven Peckman, University of California, Los Angeles
• Monika Piotrowska, State University of New York at Albany
• May Schwarz, The Salk Institute for Biological Studies
• Jeff Sebo, New York University
• Chris Stodgell, University of Rochester
• Robert Streiffer, University of Wisconsin-Madison
• Lorenz Studer, Memorial Sloan Kettering Cancer Center
• Amy Wilkerson, The Rockefeller University

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

Creating Chimeric Animals: Seeking Clarity on Ethics and Oversight edited by Karen J. Maschke, Margaret M. Matthews, Kaitlynn P. Craig, Carolyn P. Neuhaus, Insoo Hyun, Josephine Johnston, The Hastings Center Report Volume 52, Issue S2 (Special Report), November‐December 2022 First Published: 09 December 2022

This report is open access.

Use Gene Editing to Make Better Babies (a February 17, 2022 livestreamed debate from 05:00 PM − 06:30 PM EST)

I have high hopes for this debate on gene edited babies. Intelligence Squared US convenes good debates. (I watched their ‘de-extinction’ debate back in 2019, which coincidentally, featured George Church, one of the debaters in this event.) Not ‘good’ in that I necessarily agree or am interested in the topics but good as in thoughtful. Here’s more from the organization’s mission on their What is IQ2US? webpage,

A nonpartisan, nonprofit organization, Intelligence Squared U.S. addresses a fundamental problem in America: the extreme polarization of our nation and our politics.

Our mission is to restore critical thinking, facts, reason, and civility to American public discourse.

More about the upcoming debate can be found on the Use Gene Editing to Make Better Babies event page,

Use Gene Editing to Make Better Babies
Hosted By John Donvan

Thursday, February 17, 2022
05:00 PM − 06:30 PM EST

A genetic disease runs in your family. Your doctor tells you that, should you wish to have a child, that child is likely to also carry the disease. But a new gene-editing technology could change your fate. It could ensure that your baby is — and remains — healthy. Even more, it could potentially make sure your grandchildren are also free of the disease. What do you do? Now, imagine it’s not a rare genetic disorder, but general illness, or eye color, or cognitive ability, or athleticism. Do you opt into this new world of genetically edited humans? And what if it’s not just you. What your friends, neighbors, and colleagues are also embracing this genetic revolution? Right now, science doesn’t give you that choice. But huge advancements in CRISPR [clustered regularly interspaced short palindromic repeats] technology are making human gene editing a reality. In fact, in 2018, a Chinese scientist announced the first genetically modified babies; twin girls made to resist HIV, smallpox, and malaria. The promise of this technology is clear. But gene editing is not without its perils. Its critics say the technology is destined to exacerbate inequality, pressure all parents (and nations) into editing their children to stay competitive, and meddling with the most basic aspect of our humanity. In this context, we ask the question: Should we use gene editing to make better babies?

Main Points

The use of gene editing allows for couples to have children when they might otherwise have that option unavailable for them. It also allows for less to be left to chance during the pregnancy.

Gene editing will allow for babies to be born with reduced or eliminated chances of inheriting and passing on genes linked to diseases. We have a moral imperative to use technology that will improve the quality of life.

It is only a matter of time before gene editing becomes a widespread technology, potentially used by competitors and rivals on the international stage. If we have the technology, we should use it to our advantage to remain competitive.

The use of gene editing to create “better” outcomes in children will inherently create social stratification based on any gene editing, likely reflecting existing socioeconomic status. Additionally, the term ‘better’ is arbitrary and potentially short-sighted and dangerous.

Currently, there exist reasonable alternatives to gene editing for every condition for which gene editing can be used. 

The technology is still developing, and the long-term effects of any gene-editing could be potentially dangerous with consequences echoing throughout the gene environment. 

A February 8, 2022 Intelligence Squared U.S. news release about the upcoming debate (received via email) provides details about the debaters,

FOR THE MOTION – BIOS

* George Church, Geneticist & Founder, Personal Genome Project 
George Church is one of the nation’s leading geneticists and scholars. He is a professor of genetics at Harvard Medical School and MIT. In 1984, he developed the first direct genomic sequencing method, which resulted in the first genome sequence. He also helped initiate the Human Genome Project in 1984 and the Personal Genome Project in 2005. Church also serves as the director of the National Institutes of Health Center of Excellence in Genomic Science.  

* Amy Webb, Futurist & Author, “The Genesis Machine”  
Amy Webb is an award-winning author and futurist. She is the founder and CEO of the Future Today Institute and was named one of five women changing the world by Forbes. Her new book, “The Genesis Machine,” explores the future of synthetic biology, including human gene editing. Webb is a professor of strategic foresight at New York University’s Stern School of Business and has been elected a life member of the Council on Foreign Relations.  

AGAINST THE MOTION – BIOS

* Marcy Darnovsky, Policy Advocate & Executive Director, Center for Genetics and Society 
Marcy Darnovsky is a policy advocate and one of the most prominent voices on the politics of human biotechnology. As executive director of the Center for Genetics and Society, Darnovsky is focused on the social justice and public interest implications of gene editing. This work is informed by her background as an organizer and advocate in a range of environmental and progressive political movements.    

* Françoise Baylis, Philosopher & Author, “Altered Inheritance”  
Françoise Baylis is a philosopher whose innovative work in bioethics, at the intersection of policy and practice, has stretched the very boundaries of the field. She is the author of “Altered Inheritance: CRISPR and the Ethics of Human Genome Editing,” which explores the scientific, ethical, and political implications of human genome editing. Baylis is a research professor at Dalhousie University and a fellow of the Canadian Academy of Health Sciences. In 2017, she was awarded the Canadian Bioethics Society Lifetime Achievement Award. 

Getting back to the Use Gene Editing to Make Better Babies event page, there are a few options,

Request a Ticket

Have a question? Ask us

There’s also an option to Vote For or Against the Motion but you’ll have to go to the Use Gene Editing to Make Better Babies event page.

Two of the debaters have been mentioned on this blog before, George Church and Françoise Baylis. There are several references to Church including this mention with regard to Dr. He Jiankui and his CRISPR twins (July 28, 2020 posting). Françoise Baylis features in four 2019 postings with the most recent being this October 17, 2019 piece.

For anyone curious about the ‘de-extinction’ debate, it was described here in a January 18, 2019 posting prior to the event.

mRNA, COVID-19 vaccines, treating genetic diseases before birth, and the scientist who started it all

This post was going to be about new research into fetal therapeutics and mRNA.But, since I’ve been very intrigued by the therapeutic agent, mRNA, which has been a big part of the COVID-19 vaccine story; this seemed like a good opportunity to dive a little more deeply into that topic at the same time.

It’s called messenger ribonucleic acid (mRNA) and until seeing this video I had only the foggiest idea of how it works, which is troubling since at least two COVID-19 vaccines are based on this ‘new’ technology. From a November 10, 2020 article by Damian Garde for STAT,

Garde’s article offers detail about mRNA along with fascinating insight into how science and entreneurship works.

mRNA—it’s in the details, plus, the loneliness of pioneer researchers, a demotion, and squabbles

Garde’s November 10, 2020 article provides some explanation about how mRNA vaccines work and it takes a look at what can happen to pioneering scientists (Note: A link has been removed),

For decades, scientists have dreamed about the seemingly endless possibilities of custom-made messenger RNA, or mRNA.

Researchers understood its role as a recipe book for the body’s trillions of cells, but their efforts to expand the menu have come in fits and starts. The concept: By making precise tweaks to synthetic mRNA and injecting people with it, any cell in the body could be transformed into an on-demand drug factory. [emphasis mine]

But turning scientific promise into medical reality has been more difficult than many assumed. Although relatively easy and quick to produce compared to traditional vaccine-making, no mRNA vaccine or drug has ever won approval [until 2021].

Whether mRNA vaccines succeed or not, their path from a gleam in a scientist’s eye to the brink of government approval has been a tale of personal perseverance, eureka moments in the lab, soaring expectations — and an unprecedented flow of cash into the biotech industry.

Before messenger RNA was a multibillion-dollar idea, it was a scientific backwater. And for the Hungarian-born scientist behind a key mRNA discovery, it was a career dead-end.

Katalin Karikó spent the 1990s collecting rejections. Her work, attempting to harness the power of mRNA to fight disease, was too far-fetched for government grants, corporate funding, and even support from her own colleagues.

It all made sense on paper. In the natural world, the body relies on millions of tiny proteins to keep itself alive and healthy, and it uses mRNA to tell cells which proteins to make. If you could design your own mRNA, you could, in theory, hijack that process and create any protein you might desire — antibodies to vaccinate against infection, enzymes to reverse a rare disease, or growth agents to mend damaged heart tissue.

In 1990, researchers at the University of Wisconsin managed to make it work in mice. Karikó wanted to go further.

The problem, she knew, was that synthetic RNA was notoriously vulnerable to the body’s natural defenses, meaning it would likely be destroyed before reaching its target cells. And, worse, the resulting biological havoc might stir up an immune response that could make the therapy a health risk for some patients.

It was a real obstacle, and still may be, but Karikó was convinced it was one she could work around. Few shared her confidence.

“Every night I was working: grant, grant, grant,” Karikó remembered, referring to her efforts to obtain funding. “And it came back always no, no, no.”

By 1995, after six years on the faculty at the University of Pennsylvania, Karikó got demoted. She had been on the path to full professorship, but with no money coming in to support her work on mRNA, her bosses saw no point in pressing on.

She was back to the lower rungs of the scientific academy.

“Usually, at that point, people just say goodbye and leave because it’s so horrible,” Karikó said.

There’s no opportune time for demotion, but 1995 had already been uncommonly difficult. Karikó had recently endured a cancer scare, and her husband was stuck in Hungary sorting out a visa issue. Now the work to which she’d devoted countless hours was slipping through her fingers.

“I thought of going somewhere else, or doing something else,” Karikó said. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”

In time, those better experiments came together. After a decade of trial and error, Karikó and her longtime collaborator at Penn — Drew Weissman, an immunologist with a medical degree and Ph.D. from Boston University — discovered a remedy for mRNA’s Achilles’ heel.

The stumbling block, as Karikó’s many grant rejections pointed out, was that injecting synthetic mRNA typically led to that vexing immune response; the body sensed a chemical intruder, and went to war. The solution, Karikó and Weissman discovered, was the biological equivalent of swapping out a tire.

Every strand of mRNA is made up of four molecular building blocks called nucleosides. But in its altered, synthetic form, one of those building blocks, like a misaligned wheel on a car, was throwing everything off by signaling the immune system. So Karikó and Weissman simply subbed it out for a slightly tweaked version, creating a hybrid mRNA that could sneak its way into cells without alerting the body’s defenses.

“That was a key discovery,” said Norbert Pardi, an assistant professor of medicine at Penn and frequent collaborator. “Karikó and Weissman figured out that if you incorporate modified nucleosides into mRNA, you can kill two birds with one stone.”

That discovery, described in a series of scientific papers starting in 2005, largely flew under the radar at first, said Weissman, but it offered absolution to the mRNA researchers who had kept the faith during the technology’s lean years. And it was the starter pistol for the vaccine sprint to come.

Entrepreneurs rush in

Garde’s November 10, 2020 article shifts focus from Karikó, Weissman, and specifics about mRNA to the beginnings of what might be called an entrepreneurial gold rush although it starts sedately,

Derrick Rossi [emphasis mine], a native of Toronto who rooted for the Maple Leafs and sported a soul patch, was a 39-year-old postdoctoral fellow in stem cell biology at Stanford University in 2005 when he read the first paper. Not only did he recognize it as groundbreaking, he now says Karikó and Weissman deserve the Nobel Prize in chemistry.

“If anyone asks me whom to vote for some day down the line, I would put them front and center,” he said. “That fundamental discovery is going to go into medicines that help the world.”

But Rossi didn’t have vaccines on his mind when he set out to build on their findings in 2007 as a new assistant professor at Harvard Medical School running his own lab.

He wondered whether modified messenger RNA might hold the key to obtaining something else researchers desperately wanted: a new source of embryonic stem cells [emphasis mine].

In a feat of biological alchemy, embryonic stem cells can turn into any type of cell in the body. That gives them the potential to treat a dizzying array of conditions, from Parkinson’s disease to spinal cord injuries.

But using those cells for research had created an ethical firestorm because they are harvested from discarded embryos.

Rossi thought he might be able to sidestep the controversy. He would use modified messenger molecules to reprogram adult cells so that they acted like embryonic stem cells.

He asked a postdoctoral fellow in his lab to explore the idea. In 2009, after more than a year of work, the postdoc waved Rossi over to a microscope. Rossi peered through the lens and saw something extraordinary: a plate full of the very cells he had hoped to create.

Rossi excitedly informed his colleague Timothy Springer, another professor at Harvard Medical School and a biotech entrepreneur. Recognizing the commercial potential, Springer contacted Robert Langer, the prolific inventor and biomedical engineering professor at the Massachusetts Institute of Technology.

On a May afternoon in 2010, Rossi and Springer visited Langer at his laboratory in Cambridge. What happened at the two-hour meeting and in the days that followed has become the stuff of legend — and an ego-bruising squabble.

Langer is a towering figure in biotechnology and an expert on drug-delivery technology. At least 400 drug and medical device companies have licensed his patents. His office walls display many of his 250 major awards, including the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers.

As he listened to Rossi describe his use of modified mRNA, Langer recalled, he realized the young professor had discovered something far bigger than a novel way to create stem cells. Cloaking mRNA so it could slip into cells to produce proteins had a staggering number of applications, Langer thought, and might even save millions of lives.

“I think you can do a lot better than that,” Langer recalled telling Rossi, referring to stem cells. “I think you could make new drugs, new vaccines — everything.”

Within several months, Rossi, Langer, Afeyan [Noubar Afeyan, venture capitalist, founded and runs Flagship Ventures], and another physician-researcher at Harvard formed the firm Moderna — a new word combining modified and RNA.

Springer was the first investor to pledge money, Rossi said. In a 2012 Moderna news release, Afeyan said the firm’s “promise rivals that of the earliest biotechnology companies over 30 years ago — adding an entirely new drug category to the pharmaceutical arsenal.”

But although Moderna has made each of the founders hundreds of millions of dollars — even before the company had produced a single product — Rossi’s account is marked by bitterness. In interviews with the [Boston] Globe in October [2020], he accused Langer and Afeyan of propagating a condescending myth that he didn’t understand his discovery’s full potential until they pointed it out to him.

Garde goes on to explain how BioNTech came into the mRNA picture and contrasts the two companies’ approaches to biotechnology as a business. It seems BioNTech has not cashed in the same way as has Moderna. (For some insight into who’s making money from COVID-19 check out Giacomo Tognini’s December 23, 2020 article (Meet The 50 Doctors, Scientists And Healthcare Entrepreneurs Who Became Pandemic Billionaires In 2020) for Forbes.)

Garde ends his November 10, 2020 article on a mildly cautionary note,

“You have all these odd clinical and pathological changes caused by this novel bat coronavirus [emphasis mine], and you’re about to meet it with all of these vaccines with which you have no experience,” said Paul Offit, an infectious disease expert at Children’s Hospital of Philadelphia and an authority on vaccines.

What happened to Katalin Karikó?

Matthew Rosza’s January 25, 2021 article about Karikó and her pioneering work features an answer to my question and some advice,

“I want young people to feel — if my example, because I was demoted, rejected, terminated, I was even subject for deportation one point — [that] if they just pursue their thing, my example helps them to wear rejection as a badge,” Karikó, who today is a senior vice president at BioNTech RNA Pharmaceuticals, told Salon last month when discussing her story. “‘Okay, well, I was rejected. I know. Katalin was rejected and still [succeeded] at the end.’ So if it helps them, then it helps them.”

Despite her demotion, Karikó continued with her work and, along with a fellow immunologist named Dr. Drew Weissman, penned a series of influential articles starting in 2005. These articles argued that mRNA vaccines would not be neutralized by the human immune system as long as there were specific modifications to nucleosides, a compound commonly found in RNA.

By 2013, Karikó’s work had sufficiently impressed experts that she left the University of Pennsylvania for BioNTech RNA Pharmaceuticals.

Karikó tells Salon that the experience taught her one important lesson: In life there will be people who, for various reasons, will try to hold you back, and you can’t let them get you down.

“People that are in power, they can help you or block you,” Karikó told Salon. “And sometimes people select to make your life miserable. And now they cannot be happy with me because now they know that, ‘Oh, you know, we had the confrontation and…’ But I don’t spend too much time on these things.”

Before moving onto the genetic research which prompted this posting, I have an answer to the following questions:

Could an mRNA vaccine affect your DNA (deoxyribonucleic acid) and how do mRNA vaccines differ from the traditional ones?

No, DNA is not affected by the COVID-19 mRNA vaccines, according to a January 5, 2021 article by Jason Murdock for Newsweek,

The type of vaccines used against COVID-19 do not interact with or alter human genetic code, also known as DNA, scientists say.

In traditional vaccines, a piece of a virus, known as an “antigen,” would be injected into the body to force the immune system to make antibodies to fight off future infection. But mRNA-based methods do not use a live virus, and cannot give someone COVID.

Instead, mRNA vaccines give cells the instructions to make a “spike” protein also found on the surface of the virus that causes COVID. The body kickstarts its immune response by creating the antibodies needed to combat those specific virus proteins.

Once the spike protein is created, the cell breaks down the instructions provided by the mRNA molecule, leaving the human immune system prepared to combat infection. The mRNA vaccines are not a medicine—nor a cure—but a preventative measure.

Gavi, a vaccine alliance partnered with the World Health Organization (WHO), has said that mRNA instructions will become degraded in approximately 72 hours.

It says mRNA strands are “chemical intermediaries” between DNA in our chromosomes and the “cellular machinery that produces the proteins we need to function.”

But crucially, while mRNA vaccines will give the human body the blueprints on how to assemble proteins, the alliance said in a fact-sheet last month that “mRNA isn’t the same as DNA, and it can’t combine with our DNA to change our genetic code.”

It explained: “Some viruses like HIV can integrate their genetic material into the DNA of their hosts, but this isn’t true of all viruses… mRNA vaccines don’t carry these enzymes, so there is no risk of the genetic material they contain altering our DNA.”

The [US] Centers for Disease Control and Prevention (CDC) says on its website that mRNA vaccines that are rolling out don’t “interact with our DNA in any way,” and “mRNA never enters the nucleus of the cell, which is where our DNA (genetic material) is kept.”

Therapeutic fetal mRNA treatment

Rossi’s work on mRNA and embryonic stem cells bears a relationship of sorts to this work focusing on prebirth therapeutics. (From a January 13, 2021 news item on Nanowerk), Note: A link has been removed,

Researchers at Children’s Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy.

The proof-of-concept study, published in Science Advances (“Ionizable Lipid Nanoparticles for In Utero mRNA Delivery”), engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

A January 13, 2021 Children’s Hospital of Philadelphia (CHOP) news release (also on EurekAlert), which originated the news item, delves further into the research,

“This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. “These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing.”

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Of the potential vehicles for introducing therapeutic protein replacement, mRNA is distinct from other nucleic acids, such as DNA, because it does not need to enter the nucleus and can use the body’s own machinery to produce the desired proteins. Currently, the common methods of nucleic acid delivery include viral vectors and nonviral approaches. Although viral vectors may be well-suited to gene therapy, they come with the potential risk of unwanted integration of the transgene or parts of the viral vector in the recipient genome. Thus, there is an important need to develop safe and effective nonviral nucleic acid delivery technologies to treat prenatal diseases.

In order to identify potential nonviral delivery systems for therapeutic mRNA, the researchers engineered a library of lipid nanoparticles, small particles less than 100 nanometers in size that effectively enter cells in mouse fetal recipients. Each lipid nanoparticle formulation was used to encapsulate mRNA, which was administered to mouse fetuses. The researchers found that several of the lipid nanoparticles enabled functional mRNA delivery to fetal livers and that some of those lipid nanoparticles also delivered mRNA to the fetal lungs and intestines. They also assessed the lipid nanoparticles for toxicity and found them to be as safe or safer than existing formulations.

Having identified the lipid nanoparticles that were able to accumulate within fetal livers, lungs, and intestines with the highest efficiency and safety, the researchers also tested therapeutic potential of those designs by using them to deliver erythropoietin (EPO) mRNA, as the EPO protein is easily trackable. They found that EPO mRNA delivery to liver cells in mouse fetuses resulted in elevated levels of EPO protein in the fetal circulation, providing a model for protein replacement therapy via the liver using these lipid nanoparticles.

“A central challenge in the field of gene therapy is the delivery of nucleic acids to target cells and tissues, without causing side effects in healthy tissue. This is difficult to achieve in adult animals and humans, which have been studied extensively. Much less is known in terms of what is required to achieve in utero nucleic acid delivery,” said Mitchell. “We are very excited by the initial results of our lipid nanoparticle technology to deliver mRNA in utero in safe and effective manner, which could open new avenues for lipid nanoparticles and mRNA therapeutics to treat diseases before birth.”

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

Ionizable lipid nanoparticles for in utero mRNA delivery by Rachel S. Riley, Meghana V. Kashyap, Margaret M. Billingsley, Brandon White, Mohamad-Gabriel Alameh, Sourav K. Bose, Philip W. Zoltick, Hiaying Li, Rui Zhang, Andrew Y. Cheng, Drew Weissman, William H. Peranteau, Michael J. Mitchell. Science Advances 13 Jan 2021: Vol. 7, no. 3, eaba1028 DOI: 10.1126/sciadv.aba1028

This paper appears to be open access. BTW, I noticed Drew Weissman’s name as one of the paper’s authors and remembered him as one of the first to recognize Karikó’s pioneering work. I imagine that when he co-authored papers with Karikó he was risking his reputation.

Funny how a despised field of research has sparked a ‘gold rush’ for research and for riches, yes?.

Colo(u)r-changing bandage for better compression

This is a structural colo(u)r story, from a May 29, 2018 news item on Nanowerk,

Compression therapy is a standard form of treatment for patients who suffer from venous ulcers and other conditions in which veins struggle to return blood from the lower extremities. Compression stockings and bandages, wrapped tightly around the affected limb, can help to stimulate blood flow. But there is currently no clear way to gauge whether a bandage is applying an optimal pressure for a given condition.

Now engineers at MIT {Massachusetts Institute of Technology] have developed pressure-sensing photonic fibers that they have woven into a typical compression bandage. As the bandage is stretched, the fibers change color. Using a color chart, a caregiver can stretch a bandage until it matches the color for a desired pressure, before, say, wrapping it around a patient’s leg.

The photonic fibers can then serve as a continuous pressure sensor — if their color changes, caregivers or patients can use the color chart to determine whether and to what degree the bandage needs loosening or tightening.

A May 29, 2018 MIT news release (also on EurekAlert), which originated the news item, provides more detail,

“Getting the pressure right is critical in treating many medical conditions including venous ulcers, which affect several hundred thousand patients in the U.S. each year,” says Mathias Kolle, assistant professor of mechanical engineering at MIT. “These fibers can provide information about the pressure that the bandage exerts. We can design them so that for a specific desired pressure, the fibers reflect an easily distinguished color.”

Kolle and his colleagues have published their results in the journal Advanced Healthcare Materials. Co-authors from MIT include first author Joseph Sandt, Marie Moudio, and Christian Argenti, along with J. Kenji Clark of the Univeristy of Tokyo, James Hardin of the United States Air Force Research Laboratory, Matthew Carty of Brigham and Women’s Hospital-Harvard Medical School, and Jennifer Lewis of Harvard University.

Natural inspiration

The color of the photonic fibers arises not from any intrinsic pigmentation, but from their carefully designed structural configuration. Each fiber is about 10 times the diameter of a human hair. The researchers fabricated the fiber from ultrathin layers of transparent rubber materials, which they rolled up to create a jelly-roll-type structure. Each layer within the roll is only a few hundred nanometers thick.

In this rolled-up configuration, light reflects off each interface between individual layers. With enough layers of consistent thickness, these reflections interact to strengthen some colors in the visible spectrum, for instance red, while diminishing the brightness of other colors. This makes the fiber appear a certain color, depending on the thickness of the layers within the fiber.

“Structural color is really neat, because you can get brighter, stronger colors than with inks or dyes just by using particular arrangements of transparent materials,” Sandt says. “These colors persist as long as the structure is maintained.”

The fibers’ design relies upon an optical phenomenon known as “interference,” in which light, reflected from a periodic stack of thin, transparent layers, can produce vibrant colors that depend on the stack’s geometric parameters and material composition. Optical interference is what produces colorful swirls in oily puddles and soap bubbles. It’s also what gives peacocks and butterflies their dazzling, shifting shades, as their feathers and wings are made from similarly periodic structures.

“My interest has always been in taking interesting structural elements that lie at the origin of nature’s most dazzling light manipulation strategies, to try recreating and employing them in useful applications,” Kolle says.

A multilayered approach

The team’s approach combines known optical design concepts with soft materials, to create dynamic photonic materials.

While a postdoc at Harvard in the group of Professor Joanna Aizenberg, Kolle was inspired by the work of Pete Vukusic, professor of biophotonics at the University of Exeter in the U.K., on Margaritaria nobilis, a tropical plant that produces extremely shiny blue berries. The fruits’ skin is made up of cells with a periodic cellulose structure, through which light can reflect to give the fruit its signature metallic blue color.

Together, Kolle and Vukusic sought ways to translate the fruit’s photonic architecture into a useful synthetic material. Ultimately, they fashioned multilayered fibers from stretchable materials, and assumed that stretching the fibers would change the individual layers’ thicknesses, enabling them to tune the fibers’ color. The results of these first efforts were published in Advanced Materials in 2013.

When Kolle joined the MIT faculty in the same year, he and his group, including Sandt, improved on the photonic fiber’s design and fabrication. In their current form, the fibers are made from layers of commonly used and widely available transparent rubbers, wrapped around highly stretchable fiber cores. Sandt fabricated each layer using spin-coating, a technique in which a rubber, dissolved into solution, is poured onto a spinning wheel. Excess material is flung off the wheel, leaving a thin, uniform coating, the thickness of which can be determined by the wheel’s speed.

For fiber fabrication, Sandt formed these two layers on top of a water-soluble film on a silicon wafer. He then submerged the wafer, with all three layers, in water to dissolve the water-soluble layer, leaving the two rubbery layers floating on the water’s surface. Finally, he carefully rolled the two transparent layers around a black rubber fiber, to produce the final colorful photonic fiber.

Reflecting pressure

The team can tune the thickness of the fibers’ layers to produce any desired color tuning, using standard optical modeling approaches customized for their fiber design.

“If you want a fiber to go from yellow to green, or blue, we can say, ‘This is how we have to lay out the fiber to give us this kind of [color] trajectory,'” Kolle says. “This is powerful because you might want to have something that reflects red to show a dangerously high strain, or green for ‘ok.’ We have that capacity.”

The team fabricated color-changing fibers with a tailored, strain-dependent color variation using the theoretical model, and then stitched them along the length of a conventional compression bandage, which they previously characterized to determine the pressure that the bandage generates when it’s stretched by a certain amount.

The team used the relationship between bandage stretch and pressure, and the correlation between fiber color and strain, to draw up a color chart, matching a fiber’s color (produced by a certain amount of stretching) to the pressure that is generated by the bandage.

To test the bandage’s effectiveness, Sandt and Moudio enlisted over a dozen student volunteers, who worked in pairs to apply three different compression bandages to each other’s legs: a plain bandage, a bandage threaded with photonic fibers, and a commercially-available bandage printed with rectangular patterns. This bandage is designed so that when it is applying an optimal pressure, users should see that the rectangles become squares.

Overall, the bandage woven with photonic fibers gave the clearest pressure feedback. Students were able to interpret the color of the fibers, and based on the color chart, apply a corresponding optimal pressure more accurately than either of the other bandages.

The researchers are now looking for ways to scale up the fiber fabrication process. Currently, they are able to make fibers that are several inches long. Ideally, they would like to produce meters or even kilometers of such fibers at a time.

“Currently, the fibers are costly, mostly because of the labor that goes into making them,” Kolle says. “The materials themselves are not worth much. If we could reel out kilometers of these fibers with relatively little work, then they would be dirt cheap.”

Then, such fibers could be threaded into bandages, along with textiles such as athletic apparel and shoes as color indicators for, say, muscle strain during workouts. Kolle envisions that they may also be used as remotely readable strain gauges for infrastructure and machinery.

“Of course, they could also be a scientific tool that could be used in a broader context, which we want to explore,” Kolle says.

Here’s what the bandage looks like,

Caption: Engineers at MIT have developed pressure-sensing photonic fibers that they have woven into a typical compression bandage. Credit Courtesy of the researchers

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

Stretchable Optomechanical Fiber Sensors for Pressure Determination in Compressive Medical Textiles by Joseph D. Sandt, Marie Moudio, J. Kenji Clark, James Hardin, Christian Argenti, Matthew Carty, Jennifer A. Lewis, Mathias Kolle. Advanced Healthcare Materials https://doi.org/10.1002/adhm.201800293 First published: 29 May 2018

This paper is behind a paywall.

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

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

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

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

Quickie description of the 2018 – 2020 Vancouver Biennale

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

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

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

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

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

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

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

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

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

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

The 2018 – 2020 Vancouver Biennale and science

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

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

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

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

Piccinini in more depth

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

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

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

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

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

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

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

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

Gene editing and xenotransplantation

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

China Is Genetically Engineering Monkeys With Brain Disorders

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The end

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

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

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

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

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

Bravo 2018 – 2020 Vancouver Biennale!

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

Art/sci and CRISPR links

This art/science posting may prove of some interest:

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

A selection of my CRISPR posts:

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

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

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

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

Immune to CRISPR? (April 10, 2018)

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.

The Hedy Lamarr of international research: Canada’s Third assessment of The State of Science and Technology and Industrial Research and Development in Canada (1 of 2)

Before launching into the assessment, a brief explanation of my theme: Hedy Lamarr was considered to be one of the great beauties of her day,

“Ziegfeld Girl” Hedy Lamarr 1941 MGM *M.V.
Titles: Ziegfeld Girl
People: Hedy Lamarr
Image courtesy mptvimages.com [downloaded from https://www.imdb.com/title/tt0034415/mediaviewer/rm1566611456]

Aside from starring in Hollywood movies and, before that, movies in Europe, she was also an inventor and not just any inventor (from a Dec. 4, 2017 article by Laura Barnett for The Guardian), Note: Links have been removed,

Let’s take a moment to reflect on the mercurial brilliance of Hedy Lamarr. Not only did the Vienna-born actor flee a loveless marriage to a Nazi arms dealer to secure a seven-year, $3,000-a-week contract with MGM, and become (probably) the first Hollywood star to simulate a female orgasm on screen – she also took time out to invent a device that would eventually revolutionise mobile communications.

As described in unprecedented detail by the American journalist and historian Richard Rhodes in his new book, Hedy’s Folly, Lamarr and her business partner, the composer George Antheil, were awarded a patent in 1942 for a “secret communication system”. It was meant for radio-guided torpedoes, and the pair gave to the US Navy. It languished in their files for decades before eventually becoming a constituent part of GPS, Wi-Fi and Bluetooth technology.

(The article goes on to mention other celebrities [Marlon Brando, Barbara Cartland, Mark Twain, etc] and their inventions.)

Lamarr’s work as an inventor was largely overlooked until the 1990’s when the technology community turned her into a ‘cultish’ favourite and from there her reputation grew and acknowledgement increased culminating in Rhodes’ book and the documentary by Alexandra Dean, ‘Bombshell: The Hedy Lamarr Story (to be broadcast as part of PBS’s American Masters series on May 18, 2018).

Canada as Hedy Lamarr

There are some parallels to be drawn between Canada’s S&T and R&D (science and technology; research and development) and Ms. Lamarr. Chief amongst them, we’re not always appreciated for our brains. Not even by people who are supposed to know better such as the experts on the panel for the ‘Third assessment of The State of Science and Technology and Industrial Research and Development in Canada’ (proper title: Competing in a Global Innovation Economy: The Current State of R&D in Canada) from the Expert Panel on the State of Science and Technology and Industrial Research and Development in Canada.

A little history

Before exploring the comparison to Hedy Lamarr further, here’s a bit more about the history of this latest assessment from the Council of Canadian Academies (CCA), from the report released April 10, 2018,

This assessment of Canada’s performance indicators in science, technology, research, and innovation comes at an opportune time. The Government of Canada has expressed a renewed commitment in several tangible ways to this broad domain of activity including its Innovation and Skills Plan, the announcement of five superclusters, its appointment of a new Chief Science Advisor, and its request for the Fundamental Science Review. More specifically, the 2018 Federal Budget demonstrated the government’s strong commitment to research and innovation with historic investments in science.

The CCA has a decade-long history of conducting evidence-based assessments about Canada’s research and development activities, producing seven assessments of relevance:

The State of Science and Technology in Canada (2006) [emphasis mine]
•Innovation and Business Strategy: Why Canada Falls Short (2009)
•Catalyzing Canada’s Digital Economy (2010)
•Informing Research Choices: Indicators and Judgment (2012)
The State of Science and Technology in Canada (2012) [emphasis mine]
The State of Industrial R&D in Canada (2013) [emphasis mine]
•Paradox Lost: Explaining Canada’s Research Strength and Innovation Weakness (2013)

Using similar methods and metrics to those in The State of Science and Technology in Canada (2012) and The State of Industrial R&D in Canada (2013), this assessment tells a similar and familiar story: Canada has much to be proud of, with world-class researchers in many domains of knowledge, but the rest of the world is not standing still. Our peers are also producing high quality results, and many countries are making significant commitments to supporting research and development that will position them to better leverage their strengths to compete globally. Canada will need to take notice as it determines how best to take action. This assessment provides valuable material for that conversation to occur, whether it takes place in the lab or the legislature, the bench or the boardroom. We also hope it will be used to inform public discussion. [p. ix Print, p. 11 PDF]

This latest assessment succeeds the general 2006 and 2012 reports, which were mostly focused on academic research, and combines it with an assessment of industrial research, which was previously separate. Also, this third assessment’s title (Competing in a Global Innovation Economy: The Current State of R&D in Canada) makes what was previously quietly declared in the text, explicit from the cover onwards. It’s all about competition, despite noises such as the 2017 Naylor report (Review of fundamental research) about the importance of fundamental research.

One other quick comment, I did wonder in my July 1, 2016 posting (featuring the announcement of the third assessment) how combining two assessments would impact the size of the expert panel and the size of the final report,

Given the size of the 2012 assessment of science and technology at 232 pp. (PDF) and the 2013 assessment of industrial research and development at 220 pp. (PDF) with two expert panels, the imagination boggles at the potential size of the 2016 expert panel and of the 2016 assessment combining the two areas.

I got my answer with regard to the panel as noted in my Oct. 20, 2016 update (which featured a list of the members),

A few observations, given the size of the task, this panel is lean. As well, there are three women in a group of 13 (less than 25% representation) in 2016? It’s Ontario and Québec-dominant; only BC and Alberta rate a representative on the panel. I hope they will find ways to better balance this panel and communicate that ‘balanced story’ to the rest of us. On the plus side, the panel has representatives from the humanities, arts, and industry in addition to the expected representatives from the sciences.

The imbalance I noted then was addressed, somewhat, with the selection of the reviewers (from the report released April 10, 2018),

The CCA wishes to thank the following individuals for their review of this report:

Ronald Burnett, C.M., O.B.C., RCA, Chevalier de l’ordre des arts et des
lettres, President and Vice-Chancellor, Emily Carr University of Art and Design
(Vancouver, BC)

Michelle N. Chretien, Director, Centre for Advanced Manufacturing and Design
Technologies, Sheridan College; Former Program and Business Development
Manager, Electronic Materials, Xerox Research Centre of Canada (Brampton,
ON)

Lisa Crossley, CEO, Reliq Health Technologies, Inc. (Ancaster, ON)
Natalie Dakers, Founding President and CEO, Accel-Rx Health Sciences
Accelerator (Vancouver, BC)

Fred Gault, Professorial Fellow, United Nations University-MERIT (Maastricht,
Netherlands)

Patrick D. Germain, Principal Engineering Specialist, Advanced Aerodynamics,
Bombardier Aerospace (Montréal, QC)

Robert Brian Haynes, O.C., FRSC, FCAHS, Professor Emeritus, DeGroote
School of Medicine, McMaster University (Hamilton, ON)

Susan Holt, Chief, Innovation and Business Relationships, Government of
New Brunswick (Fredericton, NB)

Pierre A. Mohnen, Professor, United Nations University-MERIT and Maastricht
University (Maastricht, Netherlands)

Peter J. M. Nicholson, C.M., Retired; Former and Founding President and
CEO, Council of Canadian Academies (Annapolis Royal, NS)

Raymond G. Siemens, Distinguished Professor, English and Computer Science
and Former Canada Research Chair in Humanities Computing, University of
Victoria (Victoria, BC) [pp. xii- xiv Print; pp. 15-16 PDF]

The proportion of women to men as reviewers jumped up to about 36% (4 of 11 reviewers) and there are two reviewers from the Maritime provinces. As usual, reviewers external to Canada were from Europe. Although this time, they came from Dutch institutions rather than UK or German institutions. Interestingly and unusually, there was no one from a US institution. When will they start using reviewers from other parts of the world?

As for the report itself, it is 244 pp. (PDF). (For the really curious, I have a  December 15, 2016 post featuring my comments on the preliminary data for the third assessment.)

To sum up, they had a lean expert panel tasked with bringing together two inquiries and two reports. I imagine that was daunting. Good on them for finding a way to make it manageable.

Bibliometrics, patents, and a survey

I wish more attention had been paid to some of the issues around open science, open access, and open data, which are changing how science is being conducted. (I have more about this from an April 5, 2018 article by James Somers for The Atlantic but more about that later.) If I understand rightly, they may not have been possible due to the nature of the questions posed by the government when requested the assessment.

As was done for the second assessment, there is an acknowledgement that the standard measures/metrics (bibliometrics [no. of papers published, which journals published them; number of times papers were cited] and technometrics [no. of patent applications, etc.] of scientific accomplishment and progress are not the best and new approaches need to be developed and adopted (from the report released April 10, 2018),

It is also worth noting that the Panel itself recognized the limits that come from using traditional historic metrics. Additional approaches will be needed the next time this assessment is done. [p. ix Print; p. 11 PDF]

For the second assessment and as a means of addressing some of the problems with metrics, the panel decided to take a survey which the panel for the third assessment has also done (from the report released April 10, 2018),

The Panel relied on evidence from multiple sources to address its charge, including a literature review and data extracted from statistical agencies and organizations such as Statistics Canada and the OECD. For international comparisons, the Panel focused on OECD countries along with developing countries that are among the top 20 producers of peer-reviewed research publications (e.g., China, India, Brazil, Iran, Turkey). In addition to the literature review, two primary research approaches informed the Panel’s assessment:
•a comprehensive bibliometric and technometric analysis of Canadian research publications and patents; and,
•a survey of top-cited researchers around the world.

Despite best efforts to collect and analyze up-to-date information, one of the Panel’s findings is that data limitations continue to constrain the assessment of R&D activity and excellence in Canada. This is particularly the case with industrial R&D and in the social sciences, arts, and humanities. Data on industrial R&D activity continue to suffer from time lags for some measures, such as internationally comparable data on R&D intensity by sector and industry. These data also rely on industrial categories (i.e., NAICS and ISIC codes) that can obscure important trends, particularly in the services sector, though Statistics Canada’s recent revisions to how this data is reported have improved this situation. There is also a lack of internationally comparable metrics relating to R&D outcomes and impacts, aside from those based on patents.

For the social sciences, arts, and humanities, metrics based on journal articles and other indexed publications provide an incomplete and uneven picture of research contributions. The expansion of bibliometric databases and methodological improvements such as greater use of web-based metrics, including paper views/downloads and social media references, will support ongoing, incremental improvements in the availability and accuracy of data. However, future assessments of R&D in Canada may benefit from more substantive integration of expert review, capable of factoring in different types of research outputs (e.g., non-indexed books) and impacts (e.g., contributions to communities or impacts on public policy). The Panel has no doubt that contributions from the humanities, arts, and social sciences are of equal importance to national prosperity. It is vital that such contributions are better measured and assessed. [p. xvii Print; p. 19 PDF]

My reading: there’s a problem and we’re not going to try and fix it this time. Good luck to those who come after us. As for this line: “The Panel has no doubt that contributions from the humanities, arts, and social sciences are of equal importance to national prosperity.” Did no one explain that when you use ‘no doubt’, you are introducing doubt? It’s a cousin to ‘don’t take this the wrong way’ and ‘I don’t mean to be rude but …’ .

Good news

This is somewhat encouraging (from the report released April 10, 2018),

Canada’s international reputation for its capacity to participate in cutting-edge R&D is strong, with 60% of top-cited researchers surveyed internationally indicating that Canada hosts world-leading infrastructure or programs in their fields. This share increased by four percentage points between 2012 and 2017. Canada continues to benefit from a highly educated population and deep pools of research skills and talent. Its population has the highest level of educational attainment in the OECD in the proportion of the population with
a post-secondary education. However, among younger cohorts (aged 25 to 34), Canada has fallen behind Japan and South Korea. The number of researchers per capita in Canada is on a par with that of other developed countries, andincreased modestly between 2004 and 2012. Canada’s output of PhD graduates has also grown in recent years, though it remains low in per capita terms relative to many OECD countries. [pp. xvii-xviii; pp. 19-20]

Don’t let your head get too big

Most of the report observes that our international standing is slipping in various ways such as this (from the report released April 10, 2018),

In contrast, the number of R&D personnel employed in Canadian businesses
dropped by 20% between 2008 and 2013. This is likely related to sustained and
ongoing decline in business R&D investment across the country. R&D as a share
of gross domestic product (GDP) has steadily declined in Canada since 2001,
and now stands well below the OECD average (Figure 1). As one of few OECD
countries with virtually no growth in total national R&D expenditures between
2006 and 2015, Canada would now need to more than double expenditures to
achieve an R&D intensity comparable to that of leading countries.

Low and declining business R&D expenditures are the dominant driver of this
trend; however, R&D spending in all sectors is implicated. Government R&D
expenditures declined, in real terms, over the same period. Expenditures in the
higher education sector (an indicator on which Canada has traditionally ranked
highly) are also increasing more slowly than the OECD average. Significant
erosion of Canada’s international competitiveness and capacity to participate
in R&D and innovation is likely to occur if this decline and underinvestment
continue.

Between 2009 and 2014, Canada produced 3.8% of the world’s research
publications, ranking ninth in the world. This is down from seventh place for
the 2003–2008 period. India and Italy have overtaken Canada although the
difference between Italy and Canada is small. Publication output in Canada grew
by 26% between 2003 and 2014, a growth rate greater than many developed
countries (including United States, France, Germany, United Kingdom, and
Japan), but below the world average, which reflects the rapid growth in China
and other emerging economies. Research output from the federal government,
particularly the National Research Council Canada, dropped significantly
between 2009 and 2014.(emphasis mine)  [p. xviii Print; p. 20 PDF]

For anyone unfamiliar with Canadian politics,  2009 – 2014 were years during which Stephen Harper’s Conservatives formed the government. Justin Trudeau’s Liberals were elected to form the government in late 2015.

During Harper’s years in government, the Conservatives were very interested in changing how the National Research Council of Canada operated and, if memory serves, the focus was on innovation over research. Consequently, the drop in their research output is predictable.

Given my interest in nanotechnology and other emerging technologies, this popped out (from the report released April 10, 2018),

When it comes to research on most enabling and strategic technologies, however, Canada lags other countries. Bibliometric evidence suggests that, with the exception of selected subfields in Information and Communication Technologies (ICT) such as Medical Informatics and Personalized Medicine, Canada accounts for a relatively small share of the world’s research output for promising areas of technology development. This is particularly true for Biotechnology, Nanotechnology, and Materials science [emphasis mine]. Canada’s research impact, as reflected by citations, is also modest in these areas. Aside from Biotechnology, none of the other subfields in Enabling and Strategic Technologies has an ARC rank among the top five countries. Optoelectronics and photonics is the next highest ranked at 7th place, followed by Materials, and Nanoscience and Nanotechnology, both of which have a rank of 9th. Even in areas where Canadian researchers and institutions played a seminal role in early research (and retain a substantial research capacity), such as Artificial Intelligence and Regenerative Medicine, Canada has lost ground to other countries.

Arguably, our early efforts in artificial intelligence wouldn’t have garnered us much in the way of ranking and yet we managed some cutting edge work such as machine learning. I’m not suggesting the expert panel should have or could have found some way to measure these kinds of efforts but I’m wondering if there could have been some acknowledgement in the text of the report. I’m thinking a couple of sentences in a paragraph about the confounding nature of scientific research where areas that are ignored for years and even decades then become important (e.g., machine learning) but are not measured as part of scientific progress until after they are universally recognized.

Still, point taken about our diminishing returns in ’emerging’ technologies and sciences (from the report released April 10, 2018),

The impression that emerges from these data is sobering. With the exception of selected ICT subfields, such as Medical Informatics, bibliometric evidence does not suggest that Canada excels internationally in most of these research areas. In areas such as Nanotechnology and Materials science, Canada lags behind other countries in levels of research output and impact, and other countries are outpacing Canada’s publication growth in these areas — leading to declining shares of world publications. Even in research areas such as AI, where Canadian researchers and institutions played a foundational role, Canadian R&D activity is not keeping pace with that of other countries and some researchers trained in Canada have relocated to other countries (Section 4.4.1). There are isolated exceptions to these trends, but the aggregate data reviewed by this Panel suggest that Canada is not currently a world leader in research on most emerging technologies.

The Hedy Lamarr treatment

We have ‘good looks’ (arts and humanities) but not the kind of brains (physical sciences and engineering) that people admire (from the report released April 10, 2018),

Canada, relative to the world, specializes in subjects generally referred to as the
humanities and social sciences (plus health and the environment), and does
not specialize as much as others in areas traditionally referred to as the physical
sciences and engineering. Specifically, Canada has comparatively high levels
of research output in Psychology and Cognitive Sciences, Public Health and
Health Services, Philosophy and Theology, Earth and Environmental Sciences,
and Visual and Performing Arts. [emphases mine] It accounts for more than 5% of world researchin these fields. Conversely, Canada has lower research output than expected
in Chemistry, Physics and Astronomy, Enabling and Strategic Technologies,
Engineering, and Mathematics and Statistics. The comparatively low research
output in core areas of the natural sciences and engineering is concerning,
and could impair the flexibility of Canada’s research base, preventing research
institutions and researchers from being able to pivot to tomorrow’s emerging
research areas. [p. xix Print; p. 21 PDF]

Couldn’t they have used a more buoyant tone? After all, science was known as ‘natural philosophy’ up until the 19th century. As for visual and performing arts, let’s include poetry as a performing and literary art (both have been the case historically and cross-culturally) and let’s also note that one of the great physics texts, (De rerum natura by Lucretius) was a multi-volume poem (from Lucretius’ Wikipedia entry; Note: Links have been removed).

His poem De rerum natura (usually translated as “On the Nature of Things” or “On the Nature of the Universe”) transmits the ideas of Epicureanism, which includes Atomism [the concept of atoms forming materials] and psychology. Lucretius was the first writer to introduce Roman readers to Epicurean philosophy.[15] The poem, written in some 7,400 dactylic hexameters, is divided into six untitled books, and explores Epicurean physics through richly poetic language and metaphors. Lucretius presents the principles of atomism; the nature of the mind and soul; explanations of sensation and thought; the development of the world and its phenomena; and explains a variety of celestial and terrestrial phenomena. The universe described in the poem operates according to these physical principles, guided by fortuna, “chance”, and not the divine intervention of the traditional Roman deities.[16]

Should you need more proof that the arts might have something to contribute to physical sciences, there’s this in my March 7, 2018 posting,

It’s not often you see research that combines biologically inspired engineering and a molecular biophysicist with a professional animator who worked at Peter Jackson’s (Lord of the Rings film trilogy, etc.) Park Road Post film studio. An Oct. 18, 2017 news item on ScienceDaily describes the project,

Like many other scientists, Don Ingber, M.D., Ph.D., the Founding Director of the Wyss Institute, [emphasis mine] is concerned that non-scientists have become skeptical and even fearful of his field at a time when technology can offer solutions to many of the world’s greatest problems. “I feel that there’s a huge disconnect between science and the public because it’s depicted as rote memorization in schools, when by definition, if you can memorize it, it’s not science,” says Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, and Professor of Bioengineering at the Harvard Paulson School of Engineering and Applied Sciences (SEAS). [emphasis mine] “Science is the pursuit of the unknown. We have a responsibility to reach out to the public and convey that excitement of exploration and discovery, and fortunately, the film industry is already great at doing that.”

“Not only is our physics-based simulation and animation system as good as other data-based modeling systems, it led to the new scientific insight [emphasis mine] that the limited motion of the dynein hinge focuses the energy released by ATP hydrolysis, which causes dynein’s shape change and drives microtubule sliding and axoneme motion,” says Ingber. “Additionally, while previous studies of dynein have revealed the molecule’s two different static conformations, our animation visually depicts one plausible way that the protein can transition between those shapes at atomic resolution, which is something that other simulations can’t do. The animation approach also allows us to visualize how rows of dyneins work in unison, like rowers pulling together in a boat, which is difficult using conventional scientific simulation approaches.”

It comes down to how we look at things. Yes, physical sciences and engineering are very important. If the report is to be believed we have a very highly educated population and according to PISA scores our students rank highly in mathematics, science, and reading skills. (For more information on Canada’s latest PISA scores from 2015 see this OECD page. As for PISA itself, it’s an OECD [Organization for Economic Cooperation and Development] programme where 15-year-old students from around the world are tested on their reading, mathematics, and science skills, you can get some information from my Oct. 9, 2013 posting.)

Is it really so bad that we choose to apply those skills in fields other than the physical sciences and engineering? It’s a little bit like Hedy Lamarr’s problem except instead of being judged for our looks and having our inventions dismissed, we’re being judged for not applying ourselves to physical sciences and engineering and having our work in other closely aligned fields dismissed as less important.

Canada’s Industrial R&D: an oft-told, very sad story

Bemoaning the state of Canada’s industrial research and development efforts has been a national pastime as long as I can remember. Here’s this from the report released April 10, 2018,

There has been a sustained erosion in Canada’s industrial R&D capacity and competitiveness. Canada ranks 33rd among leading countries on an index assessing the magnitude, intensity, and growth of industrial R&D expenditures. Although Canada is the 11th largest spender, its industrial R&D intensity (0.9%) is only half the OECD average and total spending is declining (−0.7%). Compared with G7 countries, the Canadian portfolio of R&D investment is more concentrated in industries that are intrinsically not as R&D intensive. Canada invests more heavily than the G7 average in oil and gas, forestry, machinery and equipment, and finance where R&D has been less central to business strategy than in many other industries. …  About 50% of Canada’s industrial R&D spending is in high-tech sectors (including industries such as ICT, aerospace, pharmaceuticals, and automotive) compared with the G7 average of 80%. Canadian Business Enterprise Expenditures on R&D (BERD) intensity is also below the OECD average in these sectors. In contrast, Canadian investment in low and medium-low tech sectors is substantially higher than the G7 average. Canada’s spending reflects both its long-standing industrial structure and patterns of economic activity.

R&D investment patterns in Canada appear to be evolving in response to global and domestic shifts. While small and medium-sized enterprises continue to perform a greater share of industrial R&D in Canada than in the United States, between 2009 and 2013, there was a shift in R&D from smaller to larger firms. Canada is an increasingly attractive place to conduct R&D. Investment by foreign-controlled firms in Canada has increased to more than 35% of total R&D investment, with the United States accounting for more than half of that. [emphasis mine]  Multinational enterprises seem to be increasingly locating some of their R&D operations outside their country of ownership, possibly to gain proximity to superior talent. Increasing foreign-controlled R&D, however, also could signal a long-term strategic loss of control over intellectual property (IP) developed in this country, ultimately undermining the government’s efforts to support high-growth firms as they scale up. [pp. xxii-xxiii Print; pp. 24-25 PDF]

Canada has been known as a ‘branch plant’ economy for decades. For anyone unfamiliar with the term, it means that companies from other countries come here, open up a branch and that’s how we get our jobs as we don’t have all that many large companies here. Increasingly, multinationals are locating R&D shops here.

While our small to medium size companies fund industrial R&D, it’s large companies (multinationals) which can afford long-term and serious investment in R&D. Luckily for companies from other countries, we have a well-educated population of people looking for jobs.

In 2017, we opened the door more widely so we can scoop up talented researchers and scientists from other countries, from a June 14, 2017 article by Beckie Smith for The PIE News,

Universities have welcomed the inclusion of the work permit exemption for academic stays of up to 120 days in the strategy, which also introduces expedited visa processing for some highly skilled professions.

Foreign researchers working on projects at a publicly funded degree-granting institution or affiliated research institution will be eligible for one 120-day stay in Canada every 12 months.

And universities will also be able to access a dedicated service channel that will support employers and provide guidance on visa applications for foreign talent.

The Global Skills Strategy, which came into force on June 12 [2017], aims to boost the Canadian economy by filling skills gaps with international talent.

As well as the short term work permit exemption, the Global Skills Strategy aims to make it easier for employers to recruit highly skilled workers in certain fields such as computer engineering.

“Employers that are making plans for job-creating investments in Canada will often need an experienced leader, dynamic researcher or an innovator with unique skills not readily available in Canada to make that investment happen,” said Ahmed Hussen, Minister of Immigration, Refugees and Citizenship.

“The Global Skills Strategy aims to give those employers confidence that when they need to hire from abroad, they’ll have faster, more reliable access to top talent.”

Coincidentally, Microsoft, Facebook, Google, etc. have announced, in 2017, new jobs and new offices in Canadian cities. There’s a also Chinese multinational telecom company Huawei Canada which has enjoyed success in Canada and continues to invest here (from a Jan. 19, 2018 article about security concerns by Matthew Braga for the Canadian Broadcasting Corporation (CBC) online news,

For the past decade, Chinese tech company Huawei has found no shortage of success in Canada. Its equipment is used in telecommunications infrastructure run by the country’s major carriers, and some have sold Huawei’s phones.

The company has struck up partnerships with Canadian universities, and say it is investing more than half a billion dollars in researching next generation cellular networks here. [emphasis mine]

While I’m not thrilled about using patents as an indicator of progress, this is interesting to note (from the report released April 10, 2018),

Canada produces about 1% of global patents, ranking 18th in the world. It lags further behind in trademark (34th) and design applications (34th). Despite relatively weak performance overall in patents, Canada excels in some technical fields such as Civil Engineering, Digital Communication, Other Special Machines, Computer Technology, and Telecommunications. [emphases mine] Canada is a net exporter of patents, which signals the R&D strength of some technology industries. It may also reflect increasing R&D investment by foreign-controlled firms. [emphasis mine] [p. xxiii Print; p. 25 PDF]

Getting back to my point, we don’t have large companies here. In fact, the dream for most of our high tech startups is to build up the company so it’s attractive to buyers, sell, and retire (hopefully before the age of 40). Strangely, the expert panel doesn’t seem to share my insight into this matter,

Canada’s combination of high performance in measures of research output and impact, and low performance on measures of industrial R&D investment and innovation (e.g., subpar productivity growth), continue to be viewed as a paradox, leading to the hypothesis that barriers are impeding the flow of Canada’s research achievements into commercial applications. The Panel’s analysis suggests the need for a more nuanced view. The process of transforming research into innovation and wealth creation is a complex multifaceted process, making it difficult to point to any definitive cause of Canada’s deficit in R&D investment and productivity growth. Based on the Panel’s interpretation of the evidence, Canada is a highly innovative nation, but significant barriers prevent the translation of innovation into wealth creation. The available evidence does point to a number of important contributing factors that are analyzed in this report. Figure 5 represents the relationships between R&D, innovation, and wealth creation.

The Panel concluded that many factors commonly identified as points of concern do not adequately explain the overall weakness in Canada’s innovation performance compared with other countries. [emphasis mine] Academia-business linkages appear relatively robust in quantitative terms given the extent of cross-sectoral R&D funding and increasing academia-industry partnerships, though the volume of academia-industry interactions does not indicate the nature or the quality of that interaction, nor the extent to which firms are capitalizing on the research conducted and the resulting IP. The educational system is high performing by international standards and there does not appear to be a widespread lack of researchers or STEM (science, technology, engineering, and mathematics) skills. IP policies differ across universities and are unlikely to explain a divergence in research commercialization activity between Canadian and U.S. institutions, though Canadian universities and governments could do more to help Canadian firms access university IP and compete in IP management and strategy. Venture capital availability in Canada has improved dramatically in recent years and is now competitive internationally, though still overshadowed by Silicon Valley. Technology start-ups and start-up ecosystems are also flourishing in many sectors and regions, demonstrating their ability to build on research advances to develop and deliver innovative products and services.

You’ll note there’s no mention of a cultural issue where start-ups are designed for sale as soon as possible and this isn’t new. Years ago, there was an accounting firm that published a series of historical maps (the last one I saw was in 2005) of technology companies in the Vancouver region. Technology companies were being developed and sold to large foreign companies from the 19th century to present day.

Part 2

Stretchy optical materials for implants that could pulse light

An Oct. 17, 2016 Massachusetts Institute of Technology (MIT) news release (also on EurekAlert) by Emily Chu describes research that could lead to long-lasting implants offering preventive health strategies,

Researchers from MIT and Harvard Medical School have developed a biocompatible and highly stretchable optical fiber made from hydrogel — an elastic, rubbery material composed mostly of water. The fiber, which is as bendable as a rope of licorice, may one day be implanted in the body to deliver therapeutic pulses of light or light up at the first sign of disease. [emphasis mine]

The researchers say the fiber may serve as a long-lasting implant that would bend and twist with the body without breaking down. The team has published its results online in the journal Advanced Materials.

Using light to activate cells, and particularly neurons in the brain, is a highly active field known as optogenetics, in which researchers deliver short pulses of light to targeted tissues using needle-like fibers, through which they shine light from an LED source.

“But the brain is like a bowl of Jell-O, whereas these fibers are like glass — very rigid, which can possibly damage brain tissues,” says Xuanhe Zhao, the Robert N. Noyce Career Development Associate Professor in MIT’s Department of Mechanical Engineering. “If these fibers could match the flexibility and softness of the brain, they could provide long-term more effective stimulation and therapy.”

Getting to the core of it

Zhao’s group at MIT, including graduate students Xinyue Liu and Hyunwoo Yuk, specializes in tuning the mechanical properties of hydrogels. The researchers have devised multiple recipes for making tough yet pliable hydrogels out of various biopolymers. The team has also come up with ways to bond hydrogels with various surfaces such as metallic sensors and LEDs, to create stretchable electronics.

The researchers only thought to explore hydrogel’s use in optical fibers after conversations with the bio-optics group at Harvard Medical School, led by Associate Professor Seok-Hyun (Andy) Yun. Yun’s group had previously fabricated an optical fiber from hydrogel material that successfully transmitted light through the fiber. However, the material broke apart when bent or slightly stretched. Zhao’s hydrogels, in contrast, could stretch and bend like taffy. The two groups joined efforts and looked for ways to incorporate Zhao’s hydrogel into Yun’s optical fiber design.

Yun’s design consists of a core material encased in an outer cladding. To transmit the maximum amount of light through the core of the fiber, the core and the cladding should be made of materials with very different refractive indices, or degrees to which they can bend light.

“If these two things are too similar, whatever light source flows through the fiber will just fade away,” Yuk explains. “In optical fibers, people want to have a much higher refractive index in the core, versus cladding, so that when light goes through the core, it bounces off the interface of the cladding and stays within the core.”

Happily, they found that Zhao’s hydrogel material was highly transparent and possessed a refractive index that was ideal as a core material. But when they tried to coat the hydrogel with a cladding polymer solution, the two materials tended to peel apart when the fiber was stretched or bent.

To bond the two materials together, the researchers added conjugation chemicals to the cladding solution, which, when coated over the hydrogel core, generated chemical links between the outer surfaces of both materials.

“It clicks together the carboxyl groups in the cladding, and the amine groups in the core material, like molecular-level glue,” Yuk says.

Sensing strain

The researchers tested the optical fibers’ ability to propagate light by shining a laser through fibers of various lengths. Each fiber transmitted light without significant attenuation, or fading. They also found that fibers could be stretched over seven times their original length without breaking.

Now that they had developed a highly flexible and robust optical fiber, made from a hydrogel material that was also biocompatible, the researchers began to play with the fiber’s optical properties, to see if they could design a fiber that could sense when and where it was being stretched.

They first loaded a fiber with red, green, and blue organic dyes, placed at specific spots along the fiber’s length. Next, they shone a laser through the fiber and stretched, for instance, the red region. They measured the spectrum of light that made it all the way through the fiber, and noted the intensity of the red light. They reasoned that this intensity relates directly to the amount of light absorbed by the red dye, as a result of that region being stretched.

In other words, by measuring the amount of light at the far end of the fiber, the researchers can quantitatively determine where and by how much a fiber was stretched.

“When you stretch a certain portion of the fiber, the dimensions of that part of the fiber changes, along with the amount of light that region absorbs and scatters, so in this way, the fiber can serve as a sensor of strain,” Liu explains.

“This is like a multistrain sensor through a single fiber,” Yuk adds. “So it can be an implantable or wearable strain gauge.”

The researchers imagine that such stretchable, strain-sensing optical fibers could be implanted or fitted along the length of a patient’s arm or leg, to monitor for signs of improving mobility.

Zhao envisions the fibers may also serve as sensors, lighting up in response to signs of disease.

“We may be able to use optical fibers for long-term diagnostics, to optically monitor tumors or inflammation,” he says. “The applications can be impactful.”

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

Highly Stretchable, Strain Sensing Hydrogel Optical Fibers by Jingjing Guo, Xinyue Liu, Nan Jiang, Ali K. Yetisen, Hyunwoo Yuk, Changxi Yang, Ali Khademhosseini, Xuanhe Zhao, and Seok-Hyun Yun. Advanced Materials DOI: 10.1002/adma.201603160 Version of Record online: 7 OCT 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Café Scientifique (Vancouver, Canada) October 18, 2016 talk: At the intersection of Space and Genetics

Vancouver’s (Canada) Café Scientifique seems to have settled in at Yagger’s Downtown (433 W. Pender), which is hosting (for the third time in four months) an upcoming 2016 Café Scientifique talk. From the October 17, 2016 notice received via email,

We are pleased to announce that this month’s event will be a collaboration with the American Society of Human Genetics (ASHG).  The café will be held tomorrow (Tuesday October 18th) at 7:30pm in the back room at Yagger’s Downtown, 433 W Pender.  Please note that this date is one week earlier than usual to coincide with the ASHG Annual Meeting.  Our speaker for the evening will be Dr. Ting Wu, from the Department of Genetics at Harvard Medical School. The title of her talk is:

At the intersection of Space and Genetics

Ting (C.-ting) Wu, Ph.D., is a Professor of Genetics at Harvard Medical School. She is also the Director of the Consortium for Space Genetics, the Director of the Personal Genetics Education (pgEd.org) Project, and a recipient of an NIH Director’s Pioneer Award. Her laboratory investigates how chromosome organization influences genome function, inventing and applying technologies for imaging the genome as well as studying how a very puzzling set of sequences, called ultraconserved elements (UCEs), have managed to resist change for a stunning 300 million years. These studies have led her group to consider the potential of their findings for protecting astronauts from the extreme conditions of long-term travel in space. The Wu laboratory also houses the Personal Genetics Education Project, which works to raise public awareness and discourse regarding personal genetics, aiming to make that awareness equal across all communities, regardless of socioeconomic, ethnic, educational, and religious influences.

Have a lovely time!

Nanotechnology, math, cancer, and a boxing metaphor

Violent metaphors in medicine are not unusual although the reference is often to war rather than boxing as it is in this news from the University of Waterloo (Canada). Still, it seems counter-intuitive to closely link violence with healing but the practice is well entrenched and it seems attempts to counteract it are a ‘losing battle’ (pun intended).

Credit: Gabriel Picolo "2-in-1 punch." Courtesy: University of Waterloo

Credit: Gabriel Picolo “2-in-1 punch.” Courtesy: University of Waterloo

A June 23, 2016 news item on ScienceDaily describes a new approach to cancer therapy,

Math, biology and nanotechnology are becoming strange, yet effective bed-fellows in the fight against cancer treatment resistance. Researchers at the University of Waterloo and Harvard Medical School have engineered a revolutionary new approach to cancer treatment that pits a lethal combination of drugs together into a single nanoparticle.

Their work, published online on June 3, 2016 in the leading nanotechnology journal ACS Nano, finds a new method of shrinking tumors and prevents resistance in aggressive cancers by activating two drugs within the same cell at the same time.

A June 23, 2016 University of Waterloo news release (also on EurekAlert), which originated the news item, provides more information,

Every year thousands of patients die from recurrent cancers that have become resistant to therapy, resulting in one of the greatest unsolved challenges in cancer treatment. By tracking the fate of individual cancer cells under pressure of chemotherapy, biologists and bioengineers at Harvard Medical School studied a network of signals and molecular pathways that allow the cells to generate resistance over the course of treatment.

Using this information, a team of applied mathematicians led by Professor Mohammad Kohandel at the University of Waterloo, developed a mathematical model that incorporated algorithms that define the phenotypic cell state transitions of cancer cells in real-time while under attack by an anticancer agent. The mathematical simulations enabled them to define the exact molecular behavior and pathway of signals, which allow cancer cells to survive treatment over time.

They discovered that the PI3K/AKT kinase, which is often over-activated in cancers, enables cells to undergo a resistance program when pressured with the cytotoxic chemotherapy known as Taxanes, which are conventionally used to treat aggressive breast cancers. This revolutionary window into the life of a cell reveals that vulnerabilities to small molecule PI3K/AKT kinase inhibitors exist, and can be targeted if they are applied in the right sequence with combinations of other drugs.

Previously theories of drug resistance have relied on the hypothesis that only certain, “privileged” cells can overcome therapy. The mathematical simulations demonstrate that, under the right conditions and signaling events, any cell can develop a resistance program.

“Only recently have we begun to appreciate how important mathematics and physics are to understanding the biology and evolution of cancer,” said Professor Kohandel. “In fact, there is now increasing synergy between these disciplines, and we are beginning to appreciate how critical this information can be to create the right recipes to treat cancer.”

Although previous studies explored the use of drug combinations to treat cancer, the one-two punch approach is not always successful. In the new study, led by Professor Aaron Goldman, a faculty member in the division of Engineering in Medicine at Brigham and Women’s Hospital, the scientists realized a major shortcoming of the combination therapy approach is that both drugs need to be active in the same cell, something that current delivery methods can’t guarantee.

“We were inspired by the mathematical understanding that a cancer cell rewires the mechanisms of resistance in a very specific order and time-sensitive manner,” said Professor Goldman. “By developing a 2-in-1 nanomedicine, we could ensure the cell that was acquiring this new resistance saw the lethal drug combination, shutting down the survival program and eliminating the evidence of resistance. This approach could redefine how clinicians deliver combinations of drugs in the clinic.”

The approach the bioengineers took was to build a single nanoparticle, inspired by computer models, that exploit a technique known as supramolecular chemistry. This nanotechnology enables scientists to build cholesterol-tethered drugs together from “tetris-like” building blocks that self-assemble, incorporating multiple drugs into stable, individual nano-vehicles that target tumors through the leaky vasculature. This 2-in-1 strategy ensures that resistance to therapy never has a chance to develop, bringing together the right recipe to destroy surviving cancer cells.

Using mouse models of aggressive breast cancer, the scientists confirmed the predictions from the mathematical model that both drugs must be deterministically delivered to the same cell.

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

Rationally Designed 2-in-1 Nanoparticles Can Overcome Adaptive Resistance in Cancer by Aaron Goldman, Ashish Kulkarni, Mohammad Kohandel, Prithvi Pandey, Poornima Rao, Siva Kumar Natarajan, Venkata Sabbisetti, and Shiladitya Sengupta. ACS Nano, Article ASAP DOI: 10.1021/acsnano.6b00320 Publication Date (Web): June 03, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

The researchers have made this illustration of their work available,

Courtesy: American Chemical Society

Courtesy: American Chemical Society