A long-term, international collaboration between researchers at the University of Manitoba and the Leiden University Medical Centre in the Netherlands has uncovered vital information about the porcine reproductive and respiratory syndrome virus (PRRSV). This pathogen causes severe disease in pigs, leading to significant economic losses for pork producers across the globe.
“This disease in pigs is important worldwide and is economically fairly significant,” says Marjolein Kikkert, Associate Professor of Virology at Leiden University Medical Centre. “The aim of the project was to improve vaccines for this disease, and it turned out that it was very difficult.” It’s estimated that PRRS costs the Canadian pork industry $130M annually.
Kikkert and collaborator Brian Mark, Dean of the Faculty of Science at the University of Manitoba, looked at targeting a type of protein called a protease. PRRSV uses these proteins to suppress a host’s immune system, causing severe illness. By changing the structure, researchers can design altered viruses upon which to base new vaccines.
With the help of the Canadian Light Source (CLS) at the University of Saskatchewan (USask), Mark and Kikkert were able to visualize the unique structure of the PRRSV protease. What they learned in their study is valuable for developing new vaccines against PRRSV and also helps inform development of vaccines against emerging human viruses.
The team has conducted similar research on coronaviruses —which also use proteases to suppress human and animal immune systems — and has successfully designed new vaccines.
“The trick and hypothesis we had for improving the PRRSV vaccine didn’t quite work.” Says Kikkert. “However, we did learn a lot about how these viruses work. And it may certainly be a basis for further work into possibilities for improving vaccines against these viruses and coronaviruses.”
The team’s findings also unlock new doors to understanding how viruses like PRRSV use proteins to replicate, making this a significant academic discovery.
“The Canadian Light Source provided the technology we needed to determine the structures of these proteases, and this knowledge has provided tremendous insight into the biochemistry of these viruses, which is the cornerstone of modern vaccine development,” says Mark.
A research project into growing vaccines in edible plants has been funded at the University of California at Riverside (UCR) according a September 16, 2021 news item on Nanowerk,
The future of vaccines may look more like eating a salad than getting a shot in the arm. UC Riverside scientists are studying whether they can turn edible plants like lettuce into mRNA vaccine factories.
Messenger RNA or mRNA technology, used in COVID-19 vaccines, works by teaching our cells to recognize and protect us against infectious diseases.
One of the challenges with this new technology is that it must be kept cold to maintain stability during transport and storage. If this new project is successful, plant-based mRNA vaccines — which can be eaten — could overcome this challenge with the ability to be stored at room temperature.
The project’s goals, made possible by a $500,000 grant from the National Science Foundation, are threefold: showing that DNA containing the mRNA vaccines can be successfully delivered into the part of plant cells where it will replicate, demonstrating the plants can produce enough mRNA to rival a traditional shot, and finally, determining the right dosage.
“Ideally, a single plant would produce enough mRNA to vaccinate a single person,” said Juan Pablo Giraldo, an associate professor in UCR’s Department of Botany and Plant Sciences who is leading the research, done in collaboration with scientists from UC San Diego and Carnegie Mellon University.
“We are testing this approach with spinach and lettuce and have long-term goals of people growing it in their own gardens,” Giraldo said. “Farmers could also eventually grow entire fields of it.”
Key to making this work are chloroplasts — small organs in plant cells that convert sunlight into energy the plant can use. “They’re tiny, solar-powered factories that produce sugar and other molecules which allow the plant to grow,” Giraldo said. “They’re also an untapped source for making desirable molecules.”
In the past, Giraldo has shown that it is possible for chloroplasts to express genes that aren’t naturally part of the plant. He and his colleagues did this by sending foreign genetic material into plant cells inside a protective casing. Determining the optimal properties of these casings for delivery into plant cells is a specialty of Giraldo’s laboratory.
For this project Giraldo teamed up with Nicole Steinmetz, a UC San Diego professor of nanoengineering, to utilize nanotechnologies engineered by her team that will deliver genetic material to the chloroplasts.
“Our idea is to repurpose naturally occurring nanoparticles, namely plant viruses, for gene delivery to the plants,” Steinmetz said. “Some engineering goes into this to make the nanoparticles go to the chloroplasts and also to render them non-infectious toward the plants.”
For Giraldo, the chance to develop this idea with mRNA is the culmination of a dream. “One of the reasons I started working in nanotechnology was so I could apply it to plants and create new technology solutions. Not just for food, but for high-value products as well, like pharmaceuticals,” Giraldo said.
He is also co-leading a related project using nanomaterials to deliver nitrogen, a fertilizer, directly to chloroplasts, where plants need it most.
Nitrogen is limited in the environment, but plants need it to grow. Most farmers apply nitrogen to the soil. As a result, roughly half of it ends up in groundwater, contaminating waterways, causing algae blooms, and interacting with other organisms. It also produces nitrous oxide, another pollutant.
This alternative approach would get nitrogen into the chloroplasts through the leaves and control its release, a much more efficient mode of application that could help farmers and improve the environment.
The National Science Foundation has granted Giraldo and his colleagues $1.6 million to develop this targeted nitrogen delivery technology.
“I’m very excited about all of this research,” Giraldo said. “I think it could have a huge impact on peoples’ lives.”
Here’s the company’s president and CEO [chief executive officer], Dr. Thomas Madden explaining his company’s delivery system (from Acuitas’ news and events webpage),
For anyone who might find a textual description about the vaccine helpful, I have a Nov. 9, 2020 article by Adele Peters for Fast Company,
… a handful of small biotech companies began scrambling to develop vaccines using an as-yet-unproven technology platform that relies on something called messenger RNA [ribonucleic acid], usually shortened to mRNA …
Like other vaccines, mRNA vaccines work by training the immune system to recognize a threat like a virus and begin producing antibodies to protect itself. But while traditional vaccines often use inactivated doses of the organisms that cause disease, mRNA vaccines are designed to make the body produce those proteins itself. Messenger RNA—a molecule that contains instructions for cells to make DNA—is injected into cells. In the case of COVID-19, mRNA vaccines provide instructions for cells to start producing the “spike” protein of the new coronavirus, the protein that helps the virus get into cells. On its own, the spike protein isn’t harmful. But it triggers the immune system to begin a defensive response. As Bill Gates, who has supported companies like Moderna and BioNTech through the Gates Foundation, has described it, “you essentially turn your body into its own manufacturing unit.”
Amy Judd’s Nov. 9, 2020 article for Global news online explains (or you can just take another look at the video to refresh your memory) how the Acuitas technology fits into the vaccine picture,
Vancouver-based Acuitas Therapeutics, a biotechnology company, is playing a key role through a technology known as lipid nanoparticles, which deliver messenger RNA into cells.
“The technology we provide to our partners is lipid nanoparticles and BioNTech and Pfizer are developing a vaccine that’s using a messenger RNA that tells our cells how to make a protein that’s actually found in the COVID-19 virus,” Dr. Thomas Madden, president and CEO of Acuitas Therapeutics, told Global News Monday [Nov. 9, 2020].
“But the messenger RNA can’t work by itself, it needs a delivery technology to protect this after it’s administered and then to carry it into the cells where it can be expressed and give rise to an immune response.”
Madden said they like to think of the lipid nanoparticles as protective wrapping around a fragile glass ornament [emphasis mine] being shipped to your house online. That protective wrapping would then make sure the ornament made it to your house, through your front door, then unwrap itself and leave in your hallway, ready for you to come and grab it when you came home.
Acuitas Therapeutics employs 29 people and Madden said he believes everyone is feeling very proud of their work.
“Not many people are aware of the history of this technology and the fact that it originated in Vancouver,” he added.
“Dr. Pieter Cullis was one of the key scientists who brought together a team to develop this technology many, many years ago. UBC and Vancouver and companies associated with those scientists have been at the global centre of this technology for many years now.
“I think we’ve been looking for a light at the end of the tunnel for quite some time. I think everybody has been hoping that a vaccine would be able to provide the protection we need to move out of our current situation and I think this is now a confirmation that this hope wasn’t misplaced.”
Nanomedicine in Vancouver
For anyone who’s curious about the Canadian nanomedicine scene, you can find out more about it on Canada’s NanoMedicines Innovation Network (NMIN) website. They recently held a virtual event (Vancouver Nanomedicine Day) on Sept. 17, 2020 (see my Sept. 11, 2020 posting for details), which featured a presentation about Aquitas’ technology.
Happily, the organizers have posted videos for most of the sessions. Dr. Ying Tam of Acuitas made this presentation (about 22 mins. running time) “A Novel Vaccine Approach Using Messenger RNA‐Lipid Nanoparticles: Preclinical and Clinical Perspectives.” If you’re interested in that video or any of the others go to the NanoMedicines Innovation Network’s Nanomedicine Day 2020 webpage.
One of the major problems with vaccines is that they need to be refrigerated. (The Nanopatch, which additionally wouldn’t require needles or syringes, is my favourite proposed solution and it comes from Australia.) This latest research into making vaccines more long-lasting is from the UK and takes a different approach to the problem.
Vaccines are notoriously difficult to transport to remote or dangerous places, as they spoil when not refrigerated. Formulations are safe between 2°C and 8°C, but at other temperatures the proteins start to unravel, making the vaccines ineffective. As a result, millions of children around the world miss out on life-saving inoculations.
However, scientists have now found a way to prevent warmed-up vaccines from degrading. By encasing protein molecules in a silica shell, the structure remains intact even when heated to 100°C, or stored at room temperature for up to three years.
The technique for tailor-fitting a vaccine with a silica coat—known as ensilication—was developed by a Bath [University] team in collaboration with the University of Newcastle. This pioneering technology was seen to work in the lab two years ago, and now it has demonstrated its effectiveness in the real world too.
Here’s the lead researcher describing her team’s work
In their latest study, published in the journal Scientific Reports, the researchers sent both ensilicated and regular samples of the tetanus vaccine from Bath to Newcastle by ordinary post (a journey time of over 300 miles, which by post takes a day or two). When doses of the ensilicated vaccine were subsequently injected into mice, an immune response was triggered, showing the vaccine to be active. No immune response was detected in mice injected with unprotected doses of the vaccine, indicating the medicine had been damaged in transit.
Dr Asel Sartbaeva, who led the project from the University of Bath’s Department of Chemistry, said: “This is really exciting data because it shows us that ensilication preserves not just the structure of the vaccine proteins but also the function – the immunogenicity.”
“This project has focused on tetanus, which is part of the DTP (diphtheria, tetanus and pertussis) vaccine given to young children in three doses. Next, we will be working on developing a thermally-stable vaccine for diphtheria, and then pertussis. Eventually we want to create a silica cage for the whole DTP trivalent vaccine, so that every child in the world can be given DTP without having to rely on cold chain distribution.”
Cold chain distribution requires a vaccine to be refrigerated from the moment of manufacturing to the endpoint destination.
Silica is an inorganic, non-toxic material, and Dr Sartbaeva estimates that ensilicated vaccines could be used for humans within five to 15 years. She hopes the technology to silica-wrap proteins will eventually be adopted to store and transport all childhood vaccines, as well as other protein-based products, such as antibodies and enzymes.
“Ultimately, we want to make important medicines stable so they can be more widely available,” she said. “The aim is to eradicate vaccine-preventable diseases in low income countries by using thermally stable vaccines and cutting out dependence on cold chain.”
Currently, up to 50% of vaccine doses are discarded before use due to exposure to suboptimal temperatures. According to the World Health Organisation (WHO), 19.4 million infants did not receive routine life-saving vaccinations in 2018.
I tend to lose track as a science gets closer to commercialization since the science news becomes business news and I almost never scan that sector. It’s been about two-and-half years since I featured research that suggested Nanopatch provided more effective polio vaccination than the standard needle and syringe method in a December 20, 2017 post. The latest bits of news have an interesting timeline.
Mark Kendal (Wikipedia entry) is the researcher behind the Nanopatch. He’s interviewed in a March 5, 2020 episode (about 20 mins.) in the Pioneers Series (bankrolled by Rolex [yes, the watch company]) on Monocle.com. Coincidentally or not, a new piece of research funded by Vaxxas (the nanopatch company founded by Mark Kendall; on the website you will find a ‘front’ page and a ‘Contact us’ page only) was announced in a March 17, 2020 news item on medical.net,
Vaxxas, a clinical-stage biotechnology company commercializing a novel vaccination platform, today announced the publication in the journal PLoS Medicine of groundbreaking clinical research indicating the broad immunological and commercial potential of Vaxxas’ novel high-density microarray patch (HD-MAP). Using influenza vaccine, the clinical study of Vaxxas’ HD-MAP demonstrated significantly enhanced immune response compared to vaccination by needle/syringe. This is the largest microarray patch clinical vaccine study ever performed.
“With vaccine coated onto Vaxxas HD-MAPs shown to be stable for up to a year at 40°C [emphasis mine], we can offer a truly differentiated platform with a global reach, particularly into low and middle income countries or in emergency use and pandemic situations,” said Angus Forster, Chief Development and Operations Officer of Vaxxas and lead author of the PLoS Medicine publication. “Vaxxas’ HD-MAP is readily fabricated by injection molding to produce a 10 x 10 mm square with more than 3,000 microprojections that are gamma-irradiated before aseptic dry application of vaccine to the HD-MAP’s tips. All elements of device design, as well as coating and QC, have been engineered to enable small, modular, aseptic lines to make millions of vaccine products per week.”
The PLoS publication reported results and analyses from a clinical study involving 210 clinical subjects [emphasis mine]. The clinical study was a two-part, randomized, partially double-blind, placebo-controlled trial conducted at a single Australian clinical site. The clinical study’s primary objective was to measure the safety and tolerability of A/Singapore/GP1908/2015 H1N1 (A/Sing) monovalent vaccine delivered by Vaxxas HD-MAP in comparison to an uncoated Vaxxas HD-MAP and IM [intramuscular] injection of a quadrivalent seasonal influenza vaccine (QIV) delivering approximately the same dose of A/Sing HA protein. Exploratory outcomes were: to evaluate the immune responses to HD-MAP application to the forearm with A/Sing at 4 dose levels in comparison to IM administration of A/Sing at the standard 15 μg HA per dose per strain, and to assess further measures of immune response through additional assays and assessment of the local skin response via punch biopsy of the HD-MAP application sites. Local skin response, serological, mucosal and cellular immune responses were assessed pre- and post-vaccination.
Here’s a link to and a citation for the latest ‘nanopatch’ paper,
Two months later, Merck, an American multinational pharmaceutical company, showed some serious interest in the ‘nanopatch’. A May 28, 2020 article by Chris Newmarker for drugdelvierybusiness.com announces the news (Note: Links have been removed),
Merck has exercised its option to use Vaxxas‘ High Density Microarray Patch (HD-MAP) platform as a delivery platform for a vaccine candidate, the companies announced today [Thursday, May 28, 2020].
Also today, Vaxxas announced that German manufacturing equipment maker Harro Höfliger will help Vaxxas develop a high-throughput, aseptic manufacturing line to make vaccine products based on Vaxxas’ HD-MAP technology. Initial efforts will focus on having a pilot line operating in 2021 to support late-stage clinical studies — with a goal of single, aseptic-based lines being able to churn out 5 million vaccine products a week.
“A major challenge in commercializing microarray patches — like Vaxxas’ HD-MAP — for vaccination is the ability to manufacture at industrially-relevant scale, while meeting stringent sterility and quality standards. Our novel device design along with our innovative vaccine coating and quality verification technologies are an excellent fit for integration with Harro Höfliger’s aseptic process automation platforms. Adopting a modular approach, it will be possible to achieve output of tens-of-millions of vaccine-HD-MAP products per week,” Hoey [David L. Hoey, President and CEO of Vaxxas] said.
Vaxxas also claims that the patches can deliver vaccine more efficiently — a positive when people around the world are clamoring for a vaccine against COVID-19. The company points to a recent [March 17, 2020] clinical study in which their micropatch delivering a sixth of an influenza vaccine dose produced an immune response comparable to a full dose by intramuscular injection. A two-thirds dose by HD-MAP generated significantly faster and higher overall antibody responses.
As I noted earlier, this is an interesting timeline.
In the end, what all of this means is that there may be more than one way to deal with vaccines and medicines that deteriorate all too quickly unless refrigerated. I wish all of these researchers the best.
A May 28, 2019 news item on Nanowerk announced research targeting Langerham cells and the immune system (Note: A link has been removed),
Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam developed targeted nanoparticles that are taken up by certain immune cells of the human skin (ACS Central Science, “A specific, glycomimetic Langerin ligand for human Langerhans cell targeting”). These so-called Langerhans cells coordinate the immune response and alert the body when pathogens or tumors occur.
This new nanoparticle technology platform enables targeted drug delivery of vaccines or pharmaceuticals to Langerhans cells, triggering a controlled immune response to naturally eradicate the pathogen or tumor.
The skin is a particularly attractive place for the application of many drugs that affect the immune system, as the appropriate target cells lie directly beneath the skin. These Langerhans cells are able to elicit an immune reaction in the entire body of the patient after local application of an active substance.
Langerhans Cells – Experts of pathogen defense
To develop a targeted drug delivery system, which guides drugs directly to Langerhans cells, one can make use of their natural function: as professional, antigen-presenting cells they detect pathogens, internalize them and present components of these pathogens to effector cells of the immune system (T cells). For detection and uptake, Langerhans cells use receptors on their surface that search the environment for microbes. They especially recognize pathogens by the unique coating of sugar structures on their surface. Langerin, a protein of the C-type lectins family, is such a receptor on Langerhans cells that can detect viruses and bacteria. The specific expression of Langerin on Langerhans cells allows a targeted drug delivery encapsulated in nanoparticleswhile minimizing the side effects.
The research team of Dr. Christoph Rademacher at the Max Planck Institute of Colloids and Interfaces has now been able to exploit the knowledge of the underlying detection mechanisms with atomic resolution: “Based on our insight how immune cells recognize sugars, we developed a synthetic, sugar-like substance that enables nanoparticles to specifically bind to Langerhans cells”, says Dr. Christoph Rademacher. In collaboration with a scientific team from the Laboratory for Langerhans Cell Research of the Medical University of Innsbruck, nanoparticles have been developed that can be incorporated into Langerhans cells of the human skin through this interaction. The researchers thus lay the foundation for further developments, for example to deliver vaccines directly through the skin to the immune cells. “Imagine avoiding needles for vaccination in the future or directly activating the body’s immune system against infections and maybe even cancer”, adds Dr. Christoph Rademacher. Langerhans cells are responsible for activating the immune system systemically. Based on these findings, it may be possible in the future to develop novel vaccines against infections or immunotherapies for the treatment of cancer or autoimmune diseases.
The starting points for this work were the pioneering contributions from Ralph M. Steinman (Nobel Prize 2011) and other scientists who showed the potential of dendritic cells. Langerhans cells are one subset of these cells and are able to trigger an immune response. These findings were subsequently refined for use in cancer therapy. It has been shown that an immune response can be achieved via artificially introduced antigens. Later work confirmed these findings and also demonstrated that human Langerhans cells are also able to activate the immune system, which is particularly interesting for skin vaccination. Targeted delivery of immunomodulators to Langerhans cells would thus be desirable. However, this is often hindered or even prevented by the complex environment of the skin, especially by competing phagocytes in this tissue, such as macrophages. Consequently, pharmaceuticals not taken up by the Langerhans cells, but internalized into bystander cells may lead to unwanted side effects.
Recognition through synthetic sugars
Based on insights on the interaction between Langerin and its natural sugar ligands Christoph Rademacher and his team developed a synthetic ligand, which binds specifically to the receptor on Langerhans cells. For this purpose, synthetic sugars were produced in the laboratory and their interactions with the receptor were examined by nuclear magnetic resonance spectroscopy. With this method the researchers were able to determine which atoms of the ligand interact with which parts of the receptor. By using this structure-based approach they found out that a compound can be anchored and tested on these nanoparticles. These particles are liposomes, which have been used for many years in the clinic in the absence of such targeting ligands as a carrier for various drugs. The difference with existing systems is that the sugar-like ligand now allows specific binding to Langerhans cells. The investigations on these immune cells were carried out in collaboration with the research group of Assoz. Prof. Patrizia Stoitzner at the Langerhans Cell Research Laboratory of the Medical University of Innsbruck. Together they could show that the specific uptake of liposomes is possible even in the complex environment of human skin. The scientists used different methods such as flow cytometry and confocal microscopy for their findings.
These liposomal particles may now provide a common platform for researchers at the MPI of Colloids and Interfaces to work on the development of novel vaccines in the future.
The Cultural Cognition Project is a group of scholars interested in studying how cultural values shape public risk perceptions and related policy beliefs. Cultural cognition refers to the tendency of individuals to conform their beliefs about disputed matters of fact (e.g., whether global warming is a serious threat; whether the death penalty deters murder; whether gun control makes society more safe or less) to values that define their cultural identities.Project members are using the methods of various disciplines — including social psychology, anthropology, communications, and political science — to chart the impact of this phenomenon and to identify the mechanisms through which it operates. The Project also has an explicit normative objective: to identify processes of democratic decisionmaking by which society can resolve culturally grounded differences in belief in a manner that is both congenial to persons of diverse cultural outlooks and consistent with sound public policymaking.
Disputes over science-related policy issues such as climate change or fracking often seem as intractable as other politically charged debates. But in science, at least, simple curiosity might help bridge that partisan divide, according to new research.
In a study slated for publication in the journal Advances in Political Psychology, a Yale-led research team found that people who are curious about science are less polarized in their views on contentious issues than less-curious peers.
In an experiment, they found out why: Science-curious individuals are more willing to engage with surprising information that runs counter to their political predispositions.
“It’s a well-established finding that most people prefer to read or otherwise be exposed to information that fits rather than challenges their political preconceptions,” said research team leader Dan Kahan, Elizabeth K. Dollard Professor of Law and professor of psychology at Yale Law School. “This is called the echo-chamber effect.”
But science-curious individuals are more likely to venture out of that chamber, he said.
“When they are offered the choice to read news articles that support their views or challenge them on the basis of new evidence, science-curious individuals opt for the challenging information,” Kahan said. “For them, surprising pieces of evidence are bright shiny objects — they can’t help but grab at them.”
Kahan and other social scientists previously have shown that information based on scientific evidence can actually intensify — rather than moderate — political polarization on contentious topics such as gun control, climate change, fracking, or the safety of certain vaccines. The new study, which assessed science knowledge among subjects, reiterates the gaping divide separating how conservatives and liberals view science.
Republicans and Democrats with limited knowledge of science were equally likely to agree or disagree with the statement that “there is solid evidence that global warming is caused by human activity. However, the most science-literate conservatives were much more likely to disagree with the statement than less-knowledgeable peers. The most knowledgeable liberals almost universally agreed with the statement.
“Whatever measure of critical reasoning we used, we always observed this depressing pattern: The members of the public most able to make sense of scientific evidence are in fact the most polarized,” Kahan said.
But knowledge of science, and curiosity about science, are not the same thing, the study shows.
The team became interested in curiosity because of its ongoing collaborative research project to improve public engagement with science documentaries involving the Cultural Cognition Project at Yale Law School, the Annenberg Public Policy Center of the University of Pennsylvania, and Tangled Bank Studios at the Howard Hughes Medical Institute.
They noticed that the curious — those who sought out science stories for personal pleasure — not only were more interested in viewing science films on a variety of topics but also did not display political polarization associated with contentious science issues.
The new study found, for instance, that a much higher percentage of curious liberals and conservatives chose to read stories that ran counter to their political beliefs than did their non-curious peers.
“As their science curiosity goes up, the polarizing effects of higher science comprehension dissipate, and people move the same direction on contentious policies like climate change and fracking,” Kahan said.
It is unclear whether curiosity applied to other controversial issues can minimize the partisan rancor that infects other areas of society. But Kahan believes that the curious from both sides of the political and cultural divide should make good ambassadors to the more doctrinaire members of their own groups.
“Politically curious people are a resource who can promote enlightened self-government by sharing scientific information they are naturally inclined to learn and share,” he said.
Here’s my standard link to and citation for the paper,
Science Curiosity and Political Information Processing by Dan M. Kahan, Asheley R Landrum, Katie Carpenter, Laura Helft, and Kathleen Hall Jamieson. Political Psychology Volume 38, Issue Supplement S1 February 2017 Pages 179–199 DOI: 10.1111/pops.12396View First published: 26 January 2017
This paper is open and it can also be accessed here.
I last mentioned Kahan and The Cultural Cognition Project in an April 10, 2014 posting (scroll down about 45% of the way) about responsible science.
Slate.com is dedicating a month (January 2017) to Frankenstein. This means there were will be one or more essays each week on one aspect or another of Frankenstein and science. These essays are one of a series of initiatives jointly supported by Slate, Arizona State University, and an organization known as New America. It gets confusing since these essays are listed as part of two initiatives: Futurography and Future Tense.
The really odd part, as far as I’m concerned, is that there is no mention of Arizona State University’s (ASU) The Frankenstein Bicentennial Project (mentioned in my Oct. 26, 2016 posting). Perhaps they’re concerned that people will think ASU is advertising the project?
Getting back to the essays, a Jan. 3, 2017 article by Jacob Brogan explains, by means of a ‘Question and Answer’ format article, why the book and the monster maintain popular interest after two centuries (Note: We never do find out who or how many people are supplying the answers),
OK, fine. I get that this book is important, but why are we talking about it in a series about emerging technology?
Though people still tend to weaponize it as a simple anti-scientific screed, Frankenstein, which was first published in 1818, is much richer when we read it as a complex dialogue about our relationship to innovation—both our desire for it and our fear of the changes it brings. Mary Shelley was just a teenager when she began to compose Frankenstein, but she was already grappling with our complex relationship to new forces. Almost two centuries on, the book is just as propulsive and compelling as it was when it was first published. That’s partly because it’s so thick with ambiguity—and so resistant to easy interpretation.
Is it really ambiguous? I mean, when someone calls something frankenfood, they aren’t calling it “ethically ambiguous food.”
It’s a fair point. For decades, Frankenstein has been central to discussions in and about bioethics. Perhaps most notably, it frequently crops up as a reference point in discussions of genetically modified organisms, where the prefix Franken- functions as a sort of convenient shorthand for human attempts to meddle with the natural order. Today, the most prominent flashpoint for those anxieties is probably the clustered regularly interspaced short palindromic repeats, or CRISPR, gene-editing technique [emphasis mine]. But it’s really oversimplifying to suggest Frankenstein is a cautionary tale about monkeying with life.
As we’ll see throughout this month on Futurography, it’s become a lens for looking at the unintended consequences of things like synthetic biology, animal experimentation, artificial intelligence, and maybe even social networking. Facebook, for example, has arguably taken on a life of its own, as its algorithms seem to influence the course of elections. Mark Zuckerberg, who’s sometimes been known to disavow the power of his own platform, might well be understood as a Frankensteinian figure, amplifying his creation’s monstrosity by neglecting its practical needs.
But this book is almost 200 years old! Surely the actual science in it is bad.
Shelley herself would probably be the first to admit that the science in the novel isn’t all that accurate. Early in the novel, Victor Frankenstein meets with a professor who castigates him for having read the wrong works of “natural philosophy.” Shelley’s protagonist has mostly been studying alchemical tomes and otherwise fantastical works, the sort of things that were recognized as pseudoscience, even by the standards of the day. Near the start of the novel, Frankenstein attends a lecture in which the professor declaims on the promise of modern science. He observes that where the old masters “promised impossibilities and performed nothing,” the new scientists achieve far more in part because they “promise very little; they know that metals cannot be transmuted and that the elixir of life is a chimera.”
Is it actually about bad science, though?
Not exactly, but it has been read as a story about bad scientists.
Ultimately, Frankenstein outstrips his own teachers, of course, and pulls off the very feats they derided as mere fantasy. But Shelley never seems to confuse fact and fiction, and, in fact, she largely elides any explanation of how Frankenstein pulls off the miraculous feat of animating dead tissue. We never actually get a scene of the doctor awakening his creature. The novel spends far more dwelling on the broader reverberations of that act, showing how his attempt to create one life destroys countless others. Read in this light, Frankenstein isn’t telling us that we shouldn’t try to accomplish new things, just that we should take care when we do.
This speaks to why the novel has stuck around for so long. It’s not about particular scientific accomplishments but the vagaries of scientific progress in general.
Does that make it into a warning against playing God?
It’s probably a mistake to suggest that the novel is just a critique of those who would usurp the divine mantle. Instead, you can read it as a warning about the ways that technologists fall short of their ambitions, even in their greatest moments of triumph.
Look at what happens in the novel: After bringing his creature to life, Frankenstein effectively abandons it. Later, when it entreats him to grant it the rights it thinks it deserves, he refuses. Only then—after he reneges on his responsibilities—does his creation really go bad. We all know that Frankenstein is the doctor and his creation is the monster, but to some extent it’s the doctor himself who’s made monstrous by his inability to take responsibility for what he’s wrought.
I encourage you to read Brogan’s piece in its entirety and perhaps supplement the reading. Mary Shelley has a pretty interesting history. She ran off with Percy Bysshe Shelley who was married to another woman, in 1814 at the age of seventeen years. Her parents were both well known and respected intellectuals and philosophers, William Godwin and Mary Wollstonecraft. By the time Mary Shelley wrote her book, her first baby had died and she had given birth to a second child, a boy. Percy Shelley was to die a few years later as was her son and a third child she’d given birth to. (Her fourth child born in 1819 did survive.) I mention the births because one analysis I read suggests the novel is also a commentary on childbirth. In fact, the Frankenstein narrative has been examined from many perspectives (other than science) including feminism and LGBTQ studies.
Getting back to the science fiction end of things, the next part of the Futurography series is titled “A Cheat-Sheet Guide to Frankenstein” and that too is written by Jacob Brogan with a publication date of Jan. 3, 2017,
Marilyn Butler: Butler, a literary critic and English professor at the University of Cambridge, authored the seminal essay “Frankenstein and Radical Science.”
Jennifer Doudna: A professor of chemistry and biology at the University of California, Berkeley, Doudna helped develop the CRISPR gene-editing technique [emphasis mine].
Stephen Jay Gould: Gould is an evolutionary biologist and has written in defense of Frankenstein’s scientific ambitions, arguing that hubris wasn’t the doctor’s true fault.
Seán Ó hÉigeartaigh: As executive director of the Center for Existential Risk at the University of Cambridge, hÉigeartaigh leads research into technologies that threaten the existience of our species.
Jim Hightower: This columnist and activist helped popularize the term frankenfood to describe genetically modified crops.
Mary Shelley: Shelley, the author of Frankenstein, helped create science fiction as we now know it.
J. Craig Venter: A leading genomic researcher, Venter has pursued a variety of human biotechnology projects.
‘Franken’ and CRISPR
The first essay is in a Jan. 6, 2016 article by Kay Waldman focusing on the ‘franken’ prefix (Note: links have been removed),
In a letter to the New York Times on June 2, 1992, an English professor named Paul Lewis lopped off the top of Victor Frankenstein’s surname and sewed it onto a tomato. Railing against genetically modified crops, Lewis put a new generation of natural philosophers on notice: “If they want to sell us Frankenfood, perhaps it’s time to gather the villagers, light some torches and head to the castle,” he wrote.
William Safire, in a 2000 New York Times column, tracked the creation of the franken- prefix to this moment: an academic channeling popular distrust of science by invoking the man who tried to improve upon creation and ended up disfiguring it. “There’s no telling where or how it will end,” he wrote wryly, referring to the spread of the construction. “It has enhanced the sales of the metaphysical novel that Ms. Shelley’s husband, the poet Percy Bysshe Shelley, encouraged her to write, and has not harmed sales at ‘Frank’n’Stein,’ the fast-food chain whose hot dogs and beer I find delectably inorganic.” Safire went on to quote the American Dialect Society’s Laurence Horn, who lamented that despite the ’90s flowering of frankenfruits and frankenpigs, people hadn’t used Frankensense to describe “the opposite of common sense,” as in “politicians’ motivations for a creatively stupid piece of legislation.”
A year later, however, Safire returned to franken- in dead earnest. In an op-ed for the Times avowing the ethical value of embryonic stem cell research, the columnist suggested that a White House conference on bioethics would salve the fears of Americans concerned about “the real dangers of the slippery slope to Frankenscience.”
All of this is to say that franken-, the prefix we use to talk about human efforts to interfere with nature, flips between “funny” and “scary” with ease. Like Shelley’s monster himself, an ungainly patchwork of salvaged parts, it can seem goofy until it doesn’t—until it taps into an abiding anxiety that technology raises in us, a fear of overstepping.
Waldman’s piece hints at how language can shape discussions while retaining a rather playful quality.
Since its publication nearly 200 years ago, Shelley’s gothic novel has been read as a cautionary tale of the dangers of creation and experimentation. James Whale’s 1931 film took the message further, assigning explicitly the hubris of playing God to the mad scientist. As his monster comes to life, Dr. Frankenstein, played by Colin Clive, triumphantly exclaims: “Now I know what it feels like to be God!”
The admonition against playing God has since been ceaselessly invoked as a rhetorical bogeyman. Secular and religious, critic and journalist alike have summoned the term to deride and outright dismiss entire areas of research and technology, including stem cells, genetically modified crops, recombinant DNA, geoengineering, and gene editing. As we near the two-century commemoration of Shelley’s captivating story, we would be wise to shed this shorthand lesson—and to put this part of the Frankenstein legacy to rest in its proverbial grave.
The trouble with the term arises first from its murkiness. What exactly does it mean to play God, and why should we find it objectionable on its face? All but zealots would likely agree that it’s fine to create new forms of life through selective breeding and grafting of fruit trees, or to use in-vitro fertilization to conceive life outside the womb to aid infertile couples. No one objects when people intervene in what some deem “acts of God,” such as earthquakes, to rescue victims and provide relief. People get fully behind treating patients dying of cancer with “unnatural” solutions like chemotherapy. Most people even find it morally justified for humans to mete out decisions as to who lives or dies in the form of organ transplant lists that prize certain people’s survival over others.
So what is it—if not the imitation of a deity or the creation of life—that inspires people to invoke the idea of “playing God” to warn against, or even stop, particular technologies? A presidential commission charged in the early 1980s with studying the ethics of genetic engineering of humans, in the wake of the recombinant DNA revolution, sheds some light on underlying motivations. The commission sought to understand the concerns expressed by leaders of three major religious groups in the United States—representing Protestants, Jews, and Catholics—who had used the phrase “playing God” in a 1980 letter to President Jimmy Carter urging government oversight. Scholars from the three faiths, the commission concluded, did not see a theological reason to flat-out prohibit genetic engineering. Their concerns, it turned out, weren’t exactly moral objections to scientists acting as God. Instead, they echoed those of the secular public; namely, they feared possible negative effects from creating new human traits or new species. In other words, the religious leaders who called recombinant DNA tools “playing God” wanted precautions taken against bad consequences but did not inherently oppose the use of the technology as an act of human hubris.
She presents an interesting argument and offers this as a solution,
The lesson for contemporary science, then, is not that we should cease creating and discovering at the boundaries of current human knowledge. It’s that scientists and technologists ought to steward their inventions into society, and to more rigorously participate in public debate about their work’s social and ethical consequences. Frankenstein’s proper legacy today would be to encourage researchers to address the unsavory implications of their technologies, whether it’s the cognitive and social effects of ubiquitous smartphone use or the long-term consequences of genetically engineered organisms on ecosystems and biodiversity.
Some will undoubtedly argue that this places an undue burden on innovators. Here, again, Shelley’s novel offers a lesson. Scientists who cloister themselves as Dr. Frankenstein did—those who do not fully contemplate the consequences of their work—risk later encounters with the horror of their own inventions.
At a guess, Venkataraman seems to be assuming that if scientists communicate and make their case that the public will cease to panic with reference moralistic and other concerns. My understanding is that social scientists have found this is not the case. Someone may understand the technology quite well and still oppose it.
Frankenstein and anti-vaxxers
The Jan. 16, 2017 essay by Charles Kenny is the weakest of the lot, so far (Note: Links have been removed),
In 1780, University of Bologna physician Luigi Galvani found something peculiar: When he applied an electric current to the legs of a dead frog, they twitched. Thirty-seven years later, Mary Shelley had Galvani’s experiments in mind as she wrote her fable of Faustian overreach, wherein Dr. Victor Frankenstein plays God by reanimating flesh.
And a little less than halfway between those two dates, English physician Edward Jenner demonstrated the efficacy of a vaccine against smallpox—one of the greatest killers of the age. Given the suspicion with which Romantic thinkers like Shelley regarded scientific progress, it is no surprise that many at the time damned the procedure as against the natural order. But what is surprising is how that suspicion continues to endure, even after two centuries of spectacular successes for vaccination. This anti-vaccination stance—which now infects even the White House—demonstrates the immense harm that can be done by excessive distrust of technological advance.
Kenny employs history as a framing device. Crudely, Galvani’s experiments led to Mary Shelley’s Frankenstein which is a fable about ‘playing God’. (Kenny seems unaware there are many other readings of and perspectives on the book.) As for his statement ” … the suspicion with which Romantic thinkers like Shelley regarded scientific progress … ,” I’m not sure how he arrived at his conclusion about Romantic thinkers. According to Richard Holmes (in his book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science), their relationship to science was more complex. Percy Bysshe Shelley ran ballooning experiments and wrote poetry about science, which included footnotes for the literature and concepts he was referencing; John Keats was a medical student prior to his establishment as a poet; and Samuel Taylor Coleridge (The Rime of the Ancient Mariner, etc.) maintained a healthy correspondence with scientists of the day sometimes influencing their research. In fact, when you analyze the matter, you realize even scientists are, on occasion, suspicious of science.
As for the anti-vaccination wars, I wish this essay had been more thoughtful. Yes, Andrew Wakefield’s research showing a link between MMR (measles, mumps, and rubella) vaccinations and autism is a sham. However, having concerns and suspicions about technology does not render you a fool who hasn’t progressed from 18th/19th Century concerns and suspicions about science and technology. For example, vaccines are being touted for all kinds of things, the latest being a possible antidote to opiate addiction (see Susan Gados’ June 28, 2016 article for ScienceNews). Are we going to be vaccinated for everything? What happens when you keep piling vaccination on top of vaccination? Instead of a debate, the discussion has devolved to: “I’m right and you’re wrong.”
For the record, I’m grateful for the vaccinations I’ve had and the diminishment of diseases that were devastating and seem to be making a comeback with this current anti-vaccination fever. That said, I think there are some important questions about vaccines.
Kenny’s essay could have been a nuanced discussion of vaccines that have clearly raised the bar for public health and some of the concerns regarding the current pursuit of yet more vaccines. Instead, he’s been quite dismissive of anyone who questions vaccination orthodoxy.
The end of this piece
There will be more essays in Slate’s Frankenstein series but I don’t have time to digest and write commentary for all of them.
Please use this piece as a critical counterpoint to some of the series and, if I’ve done my job, you’ll critique this critique. Please do let me know if you find any errors or want to add an opinion or add your own critique in the Comments of this blog.
ETA Jan. 25, 2017: Here’s the Frankenstein webspace on Slate’s Futurography which lists all the essays in this series. It’s well worth looking at the list. There are several that were not covered here.
Tristan Clemons has written a Nov. 9, 2016 essay for The Conversation on one of my favourite stories, the nanopatch,
Who likes getting a needle? I know I definitely don’t.
Someone else who doesn’t is Mark Kendall from the University of Queensland, winner of the Young Florey Medal 2016.
Mark’s work in developing the nanopatch has provided a clear pathway for vaccine delivery science to move beyond 160 year-old needle and syringe technology.
… There are approximately 20,000 projections per square centimeter on each patch, each around 60 to 100 micrometres in length. One micrometre is one million times smaller than a metre, so the height of these tiny spikes is approximately the width of a human hair.
The nanopatch is produced using a technique known as “deep reactive ion etching”, which essentially makes use of ions (charged atoms) in an electric field to selectively etch the surface of a material away. Controlling the electric field and the ions allows a high degree of control, so the microprojections are regularly spaced and of similar dimensions.
An added advantage of this approach is it has been used in the electronic circuit and solar energy industries for many years, and has the potential for increasing the scale of production.
The tiny projections on each nanopatch are invisible to the naked eye, but are long enough to breach the outermost skin layer, the stratum corneum. The stratum corneum is a layer of dead skin cells which acts as the first barrier in protecting us from infection and skin water loss.
The nanopatch projections penetrate through the stratum corneum to reach the living skin layers directly below, the epidermis and the dermis. In the epidermis are several types of immune cells that are vital for the vaccine to work.
Hence the nanopatch is well suited to the delivery of vaccines where targeting immune cells is vital for vaccination success. Examples include influenza, polio and cholera.
Mark Kendall and his colleagues have shown they are able to coat nanopatch microprojections with a vaccine, apply the nanopatch to the skin and achieve vaccination with one tenth to one thirtieth of the dose required using traditional needle and syringe approaches.
… it’s more than just a good idea. Mark Kendall and his colleagues are now running human clinical trials of nanopatches in Brisbane, and the WHO is planning a polio vaccine trial in Cuba in 2017.
Professor Kendall said the Nanopatch had been used to administer an inactivated Type 2 poliovirus vaccine in a rat model.
“We compared the Nanopatch to the traditional needle and syringe, and found that there is about a 40-fold improvement in delivered dose-sparing,” Professor Kendall said.
“This means about 40 times less polio vaccine was needed in Nanopatch delivery to generate a functional immune response as the needle and syringe.
“To our knowledge, this is the highest level of dose-sparing observed for an inactivated polio vaccine in rats achieved by any type of delivery technology, so this is a key breakthrough.”
The next step will be clinical testing.
Dr David Muller, first author of the research published in Scientific Reports, said the work demonstrated a key advantage of the Nanopatch.
“The Nanopatch targets the abundant immune cell populations in the skin’s outer layers; rather than muscle, resulting in a more efficient vaccine delivery system,” he said.
Clinical success and widespread use of the Nanopatch against polio could help in the current campaign to eradicate polio. It could be produced and distributed at a cheaper cost, and its ease of use would make it suitable for house-to-house vaccination efforts in endemic areas with only minimal training required.
World Health Organisation Global Polio Eradication Initiative Director Mr Michel Zaffran said only Afghanistan and Pakistan remained polio-endemic, but all countries were at risk until the disease was eradicated everywhere.
“Needle-free microneedle patches such as the Nanopatch offer great promise for reaching more children with polio vaccine as well as other antigens such as measles vaccine, particularly in hard-to-reach areas or areas with inadequate healthcare infrastructure,” Mr Zaffran said.
Nanopatch technology is being commercialised by Vaxxas Pty Ltd, which has scaled the Nanopatch from use in small models to prototypes for human use.
Vaxxas CEO Mr David Hoey said the first human vaccination studies are scheduled for this year .
“Key attributes of the Nanopatch, including its ease of use and potential to not require refrigeration, could improve the reach and efficiency of vaccination campaigns in difficult-to-reach locations, including those where polio remains endemic,” Mr Hoey said.
The work was funded by the World Health Organisation, Vaxxas, Rotary District 9630 and the Rotary Foundation.
As befitting a ‘favourite story’, I’ve been following it for a number of years starting with this April 23, 2009 posting (scroll down about 25% of the way) although you might prefer to read this more substantive July 26, 2010 posting. The last time (Aug. 3, 2011 posting) I featured the story, it was to announce an investment of AUD $15M in Vaxxas (Kendall is not listed as member of the company) in order to bring the nanopatch to market.
I like the illustration which the University of Iowa has used to illustrate work on a nanscale vaccine for dust-mite allergies,
Dust mites are tiny and ubiquitous, but they cause big allergic reactions for many people. University of Iowa researchers have created a vaccine that may provide relief to dust-mite allergies. Illustration by Austin Smoldt-Sáenz. [downloaded from http://now.uiowa.edu/2014/06/researchers-create-vaccine-dust-mite-allergies?utm_source=News&utm_medium=dustmiteallergiesvacine&utm_campaign=UI%20Home%20Page]
If you’re allergic to dust mites (and chances are you are), help may be on the way.
Researchers at the University of Iowa have developed a vaccine that can combat dust-mite allergies by naturally switching the body’s immune response. In animal tests, the nano-sized vaccine package lowered lung inflammation by 83 percent despite repeated exposure to the allergens, according to the paper, published in the AAPS (American Association of Pharmaceutical Scientists) Journal. One big reason why it works, the researchers contend, is because the vaccine package contains a booster that alters the body’s inflammatory response to dust-mite allergens.
“What is new about this is we have developed a vaccine against dust-mite allergens that hasn’t been used before,” says Aliasger Salem, professor in pharmaceutical sciences at the UI and a corresponding author on the paper.
Dust mites are ubiquitous, microscopic buggers who burrow in mattresses, sofas, and other homey spots. They are found in 84 percent of households in the United States, according to a published, national survey. Preying on skin cells on the body, the mites trigger allergies and breathing difficulties among 45 percent of those who suffer from asthma, according to some studies. Prolonged exposure can cause lung damage.
Treatment is limited to getting temporary relief from inhalers or undergoing regular exposure to build up tolerance, which is long term and holds no guarantee of success.
“Our research explores a novel approach to treating mite allergy in which specially-encapsulated miniscule particles are administered with sequences of bacterial DNA that direct the immune system to suppress allergic immune responses,” says Peter Thorne, public health professor at the UI and a contributing author on the paper. “This work suggests a way forward to alleviate mite-induced asthma in allergy sufferers.”
The UI-developed vaccine takes advantage of the body’s natural inclination to defend itself against foreign bodies. A key to the formula lies in the use of an adjuvant—which boosts the potency of the vaccine—called CpG. The booster has been used successfully in cancer vaccines but never had been tested as a vaccine for dust-mite allergies. Put broadly, CpG sets off a fire alarm within the body, springing immune cells into action. Those immune cells absorb the CpG and dispose of it.
This is important, because as the immune cells absorb CpG, they’re also taking in the vaccine, which has been added to the package, much like your mother may have wrapped a bitter pill around something tasty to get you to swallow it. In another twist, combining the antigen (the vaccine) and CpG causes the body to change its immune response, producing antibodies that dampen the damaging health effects dust-mite allergens generally cause.
In lab tests, the CpG-antigen package, at 300 nanometers in size, was absorbed 90 percent of the time by immune cells, the UI-led team reports. The researchers followed up those experiments by giving the package to mice and exposing the animals to dust-mite allergens every other day for nine days total. In analyses conducted at the UI College of Public Health, packages with CpG yielded greater production of the desirable antibodies, while lung inflammation was lower than particles that did not contain CpG, the researchers report.
“This is exactly what we were hoping for,” says Salem, whose primary appointment is in the College of Pharmacy.
The researchers will continue to test the vaccine in the hope that it can eventually be used to treat patients.
I wonder what “eventually” means. Three to five years? Five to 10? In any event, here’s a link to and a citation for the paper,
If you’ve ever struggled to read something that has scientific notations or realized that you don’t know what e=mc2 stands for, then, there’s a website that might be of interest to you. It’s called Sixty Symbols and it’s where scientists at the University of Nottingham (UK) are working with a filmmaker, Brady Haran to provide information. Together they are producing videos which explain the mysteries of formulas and symbols to lay people. Here’s an article about the site and here’s the site. At last, there’s something where I can check things out when I run across something unfamiliar or when I’ve started to question if I really do understand the symbol.
Scientists in Australia are developing a ‘nanopatch’ which would replace the use of needles for vaccinations. It sounds like they’re not exactly ‘ready for prime time’ but it does look promising according to this article in Nanowerk News. One of the great things about it besides being painfree is that the ‘nanopatch’ doesn’t require refrigeration or syringes so it’s much easier to get the vaccine to remote locations.
Now onto the University of British Columbia scientists who have discovered a molecule helpful with blood stem cell transplants. The molecule is part of a signaling system which can encourage the adoption of stem cells and, consequently, greater production of T-cells. For more details, go here.