Tag Archives: multiple sclerosis

Trojan horse nanoparticle for asthma

A brand new technique for dealing with asthma is being proposed by researchers at Northwestern University (US), according to an April 18, 2016 news item on ScienceDaily,

In an entirely new approach to treating asthma and allergies, a biodegradable nanoparticle acts like a Trojan horse, hiding an allergen in a friendly shell, to convince the immune system not to attack it, according to new Northwestern Medicine research. As a result, the allergic reaction in the airways is shut down long- term and an asthma attack prevented.

The technology can be applied to food allergies as well. The nanoparticle is currently being tested in a mouse model of peanut allergy, similar to food allergy in humans.

“The findings represent a novel, safe and effective long-term way to treat and potentially ‘cure’ patients with life-threatening respiratory and food allergies,” said senior author Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “This may eliminate the need for life-long use of medications to treat lung allergy.”

An April 18, 2016 Northwestern University news release (also on EurekAlert) by Marla Paul, which originated the news item, expands on the theme,

It’s the first time this method for creating tolerance in the immune system has been used in allergic diseases. The approach has been used in autoimmune diseases including multiple sclerosis and celiac disease in previous preclinical Northwestern research.

The asthma allergy study was in mice, but the technology is progressing to clinical trials in autoimmune disease. The nanoparticle technology is being developed commercially by Cour Pharmaceuticals Development Co., which is working with Miller to bring this new approach to patients. A clinical trial using the nanoparticles to treat celiac disease is in development.

“It’s a universal treatment,” Miller said. “Depending on what allergy you want to eliminate, you can load up the nanoparticle with ragweed pollen or a peanut protein.”

The nanoparticles are composed of an FDA-approved biopolymer called PLGA that includes lactic acid and glycolic acid.

Also a senior author is Lonnie Shea, adjunct professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and of obstetrics and gynecology at Feinberg, and chair of biomedical engineering at the University of Michigan.

When the allergen-loaded nanoparticle is injected into the bloodstream of mice, the immune system isn’t concerned with it because it sees the particle as innocuous debris. Then the nanoparticle and its hidden cargo are consumed by a macrophage, essentially a vacuum-cleaner cell.

“The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” Miller said. The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.

The allergen, in this case egg protein, was administered into the lungs of mice who have been pretreated to be allergic to the protein and already had antibodies in their blood against it. So when they were re-exposed to it, they responded with an allergic response like asthma. After being treated with the nanoparticle, they no longer had an allergic response to the allergen.

The approach also has a second benefit. It creates a more normal, balanced immune system by increasing the number of regulatory T cells, immune cells important for recognizing the airway allergens as normal. This method turns off the dangerous Th2 T cell that causes the allergy and expands the good, calming regulatory T cells.

If I understand this rightly, they’re rebalancing the immune system so it doesn’t treat innocuous material (dust, mould, etc.) as an allergen.

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

Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization by Charles B. Smarr, Woon Teck Yap, Tobias P. Neef, Ryan M. Pearson, Zoe N. Hunter, Igal Ifergan, Daniel R. Getts, Paul J. Bryce, Lonnie D. Shea, and Stephen D. Miller. PNAS 2016 doi: 10.1073/pnas.1505782113 Published ahead of print April 18, 2016,

This paper is behind a paywall.

Nanotechnology delivery system for skin disease therapies

A Feb. 29, 2016 news item on ScienceDaily announces a new development concerning free radicals that may be helpful with skin diseases and pathologies,

Researchers at The Hebrew University of Jerusalem have developed a nanotechnology-based delivery system containing a protective cellular pathway inducer that activates the body’s natural defense against free radicals efficiently, a development that could control a variety of skin pathologies and disorders.

A Feb. 29, 2016 Hebrew University of Jerusalem press release on EurekAlert, which originated the news item, expands on the theme,

The human skin is constantly exposed to various pollutants, UV rays, radiation and other stressors that exist in our day-to-day environment. When they filter into the body they can create Reactive Oxygen Species (ROS) – oxygen molecules known as Free Radicals, which are able to damage and destroy cells, including lipids, proteins and DNA.

In the skin – the largest organ of the body – an excess of ROS can lead to various skin conditions, including inflammatory diseases, pigmenting disorders, wrinkles and some types of skin cancer, and can also affect internal organs. This damage is known as Oxidative Stress.

The body is naturally equipped with defense mechanisms to counter oxidative stress. It has anti-oxidants and, more importantly, anti-oxidant enzymes that attack the ROS before they cause damage.

In a review article published in the journal Cosmetics, a PhD student from The Hebrew University of Jerusalem, working in collaboration with researchers at the Technion – Israel Institute of Technology, suggested an innovative way to invigorate the body to produce antioxidant enzymes, while maintaining skin cell redox balance – a gentle equilibrium between Reactive Oxygen Species and their detoxification.

“The approach of using the body’s own defense system is very effective. We showed that activation of the body’s defense system with the aid of a unique delivery system is feasible, and may leverage dermal cure,” said Hebrew University researcher Maya Ben-Yehuda Greenwald.

Ben-Yehuda Greenwald showed that applying nano-size droplets of microemulsion liquids containing a cellular protective pathway inducer into the skin activates the natural skin defense systems.

“Currently, there are many scientific studies supporting the activation of the body’s defense mechanisms. However, none of these studies has demonstrated the use of a nanotechnology-based delivery system to do so,” Ben-Yehuda Greenwald said.

Production of antioxidant enzymes in the body is signaled in the DNA by activation of Nrf2 – a powerful protein that exists in every cell in our body. This Nrf2 cellular-protective signaling pathway is a major intersection of many other signaling pathways affecting each other and determining cell functionality and fate. Nrf2 is capable of coordinating the cellular response to internal as well as external stressors by tight regulation of phase-II protective enzymes, such as the antioxidant enzymes.

Ben-Yehuda Greenwald has also discovered a new family of compounds capable of activating the Nrf2 pathway. Moreover, by incorporating them into the unique delivery system she has developed, she managed to efficiently stimulate the activation of the Nrf2 pathway and mimic the activity of the body’s’ natural way of coping with a variety of stress conditions.

“The formula we have created could be used in topical medication for treating skin conditions. Our formula could be used both as preventive means and for treatment of various skin conditions, such as infections, over-exposure to UV irradiation, inflammatory conditions, and also internal disease,” she said.

While the researchers focused on the skin, the formulation could prove to be effective in enhancing the body’s natural protection against the damaging effects of ROS in other parts of the body, such as inflammation in cardiovascular diseases, heart attack, cancer, multiple sclerosis and Alzheimer’s.

Here’s an image provided by Ben-Yehuda Greenwald illustrating the team’s work,

Caption: These are the consequences of skin exposure to stressors. Credit: Maya Ben-Yehuda Greenwald

Caption: These are the consequences of skin exposure to stressors. Credit: Maya Ben-Yehuda Greenwald

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

Skin Redox Balance Maintenance: The Need for an Nrf2-Activator Delivery System by Maya Ben-Yehuda Greenwald, Shmuel Ben-Sasson, Havazelet Bianco-Peled, and Ron Kohen. Cosmetics 2016, 3(1), 1; doi:10.3390/cosmetics3010001 Published: 15 January 2016

This paper appears to be open access.

Parvus Therapeutics (Calgary, Canada) and reprogramming immune cells

An international collaboration of Canadian, Spanish, and US scientists has announced a new therapeutic approach which could reverse autoimmune diseases in a Feb. 17, 2016 news item on Nanotechnology Now,

• Nanotechnology Approach Restores Glucose Regulation and Motor Function in In Vivo Preclinical Models of Diabetes and Multiple Sclerosis, Respectively; Joint Swelling and Destruction Resolved in In Vivo Model of Rheumatoid Arthritis
• Parvus’ Approach Can Be Tailored to Treat Diverse Diseases

A Feb. 17, 2016 Parvus Therapeutics news release (also on EurekAlert), which originated the news item, provides more detail and a strong orientation to marketing communication,

Parvus Therapeutics today announced the publication in Nature of a seminal paper describing the discovery and applications of a novel therapeutic approach employing nanomedicines, referred to as “Navacims”TM, to reprogram white blood cells to become regulatory cells capable of blunting autoimmune responses and restoring the equilibrium of the immune system. Navacims are nanoparticles (NPs) coated with disease-relevant peptide-major histocompatibility complexes (pMHCs) that alter the behavior of pathogenic T lymphocytes by binding directly to their antigen receptors. The peer-reviewed article, titled “Expanding antigen-specific regulatory networks to treat autoimmunity” reports on a body of work, including results in multiple in vivo disease models, built on more than eight years of research by Parvus Founder and Chief Scientific Officer, Pere Santamaria, M.D., Ph.D.

Dr. Santamaria commented, “Autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, are extraordinarily complex responses of our immune system against some of our own tissues (e.g. pancreas, brain and joints, respectively), leading to chronic organ inflammation, organ dysfunction, and, in some cases, premature death. Blunting these incompletely understood immune responses without suppressing the normal components of our immune system that protect us against infection and cancer is not currently possible.”

“However, our work offers a pharmaceutical solution to this fundamental problem,” Dr. Santamaria continued. “Navacims essentially re-program disease-causing white blood cells to become disease-suppressing cells, known as regulatory cells, leading to sustained therapeutic effects in various spontaneous and experimental autoimmune diseases, as reported in our article in Nature. Essentially, we have found that Navacims can be tailored to treat a wide range of autoimmune diseases, while sharing a common structure. Importantly, they have been shown to affect human white blood cells in the same manner as they do murine cells. Furthermore, Navacims have shown promising safety findings in preclinical in vivo models. Based on our results to date, we believe Navacims represent a therapeutic platform with broad-ranging health care implications.”

Findings being reported in Nature include:

pMHC class II Navacims expanded cognate CD4+ T-cells that consistently have a TR1-like, regulatory T cell surface phenotype, transcriptional pattern and cytokine profile (mouse=human TR1 cells) systemically.

pMHC class II-Navacims designed to target T cells in newly diabetic nonobese (NOD) mice restored normoglycemia (normal blood sugar regulation) in the majority of the mice tested.

Tailored pMHC class II Navacims restored motor function to paralyzed C57BL/6 mice at the peak of Experimental Autoimmune Encephalomyelitis (a model of Multiple Sclerosis).

pMHC class II Navacims, targeting disease-causing T cells in joints, resolved joint swelling and destruction in arthritic mice.

“The findings being reported in Nature represent a scientific advance for Parvus and also a major achievement in the field of Immunology,” said Janice M. LeCocq, CEO of Parvus. “We believe that Dr. Santamaria’s work has the potential to transform the treatment of many of the more than 80 major autoimmune diseases affecting humankind, alleviating the suffering of millions of patients and their families. Over the coming year, we will be dedicating much of our in-house efforts to the advancement of our two lead programs for type 1 diabetes and multiple sclerosis.”

“Dr. Santamaria’s work to target the immune system dysfunction that causes type 1 diabetes represents the kind of innovative work that JDRF believes will eventually get us to a cure for this disease,” said Juvenile Diabetes Research Foundation Vice President of Discovery Research Julia Greenstein, Ph.D. “He and his colleagues have made exciting progress towards possibly developing a new class of drugs that could rebalance certain T-cells and ultimately provide a cure for type 1 diabetes and other autoimmune diseases as well.” The JDRF has funded the work of Dr. Santamaria and his colleagues at Parvus to explore Navacim-based treatments for diabetes.

Parvus’ strategy is to establish partnerships with major pharmaceutical companies to undertake the clinical and commercial development of many of its product pipeline candidates while also reserving rights to others suitable for its own development and commercialization. Parvus currently is engaged in late stage discussions with multiple pharmaceutical companies with regard to the type 1 diabetes (T1D) program. Manufacturing scale-up is now underway to supply upcoming preclinical and clinical studies.

The work being reported in Nature was led by Dr. Pere Santamaria and largely executed at the University of Calgary, Cumming School of Medicine (animal models of disease) and the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (humanized mouse work), with significant contributions from investigators at Institutions in Europe and the US. Further, Innovate Calgary, the technology-transfer and business-incubation center for the University of Calgary, provided early support for the transfer of the Navacims technology to and incubation of Parvus Therapeutics, which was organized as a separate entity in 2012.

It should be noted that this intervention has been tested on ‘humanized’ mice and, at this point, there don’t seem to have been any human clinical trials. At a guess I’d say we’re still several years away from this therapeutic intervention reaching the market, should it prove to be successful in humans.

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

Expanding antigen-specific regulatory networks to treat autoimmunity by Xavier Clemente Casares, Jesus Blanco, Poornima Ambalavanan, Jun Yamanouchi, Santiswarup Singha, Cesar Fandos, Sue Tsai, Jinguo Wang, Nahir Garabatos, Cristina Izquierdo, Smriti Agrawal, Michael B. Keough, V. Wee Yong, Eddie James, Anna Moore, Yang Yang, Thomas Stratmann, Pau Serra, & Pere Santamaria. Nature (2016) doi:10.1038/nature16962 Published online 17 February 2016

This paper is behind a paywall.

Herbicide nanometric sensor could help diagnose multiple sclerosis

This research into nanometric sensors and multiple sclerosis comes from Brazil. According to a June 23, 2015 news item on Nanowerk (Note: A link has been removed),

The early diagnosis of certain types of cancer, as well as nervous system diseases such as multiple sclerosis and neuromyelitis optica, may soon be facilitated by the use of a nanosensor capable of identifying biomarkers of these pathological conditions (“A Nanobiosensor Based on 4-Hydroxyphenylpyruvate Dioxygenase Enzyme for Mesotrione Detection”).

The nanobiosensor was developed at the Federal University of São Carlos (UFSCar), Sorocaba, in partnership with the São Paulo Federal Institute of Education, Science & Technology (IFSP), Itapetininga, São Paulo State, Brazil. It was originally designed to detect herbicides, heavy metals and other pollutants.

A June 23, 2015 Fundação de Amparo à Pesquisa do Estado de São Paulo news release on EurekAlert, which originated the news item, describes the sensor as it was originally used and explains its new function as a diagnostic tool for multiple sclerosis and other diseases,

“It’s a highly sensitive device, which we developed in collaboration with Alberto Luís Dario Moreau, a professor at IFSP. “We were able to increase sensitivity dramatically by going down to the nanometric scale,” said physicist Fábio de Lima Leite, a professor at UFSCar and the coordinator of the research group.

The nanobiosensor consists of a silicon nitride (Si3N4) or silicon (Si) nanoprobe with a molecular-scale elastic constant and a nanotip coupled to an enzyme, protein or other molecule.

When this molecule touches a target of interest, such as an antibody or antigen, the probe bends as the two molecules adhere. The deflection is detected and measured by the device, enabling scientists to identify the target.

“We started by detecting herbicides and heavy metals. Now we’re testing the device for use in detecting target molecules typical of nervous system diseases, in partnership with colleagues at leading centers of research on demyelinating diseases of the central nervous system”

The migration from herbicide detection to antibody detection was motivated mainly by the difficulty of diagnosing demyelinating diseases, cancer and other chronic diseases before they have advanced beyond an initial stage.

The criteria for establishing a diagnosis of multiple sclerosis or neuromyelitis optica are clinical (supplemented by MRI scans), and patients do not always present with a characteristic clinical picture. More precise diagnosis entails ruling out several other diseases.

The development of nanodevices will be of assistance in identifying these diseases and reducing the chances of false diagnosis.

The procedure can be as simple as placing a drop of the patient’s cerebrospinal fluid on a glass slide and observing its interaction with the nanobiosensor.

“If the interaction is low, we’ll be able to rule out multiple sclerosis with great confidence,” Leite said. “High interaction will indicate that the person is very likely to have the disease.” In this case, further testing would be required to exclude the possibility of a false positive.

“Different nervous system diseases have highly similar symptoms. Multiple sclerosis and neuromyelitis optica are just two examples. Even specialists experience difficulties or take a long time to diagnose them. Our technique would provide a differential diagnostic tool,” Leite said.

The next step for the group is to research biomarkers for these diseases that have not been completely mapped, including antibodies and antigens, among others. The group has begun tests for the detection of head and neck cancer.

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

A Nanobiosensor Based on 4-Hydroxyphenylpyruvate Dioxygenase Enzyme for Mesotrione Detection by P. Soto Garcia, A.L.D Moreau, J.C. Magalhaes Ierich,  A.C Araujo Vig, A.M. Higa, G.S. Oliveira, F. Camargo Abdalla, M. Hausen, & F.L. Leite. Sensors Journal, IEEE  (Volume:15 ,  Issue: 4) pp. 2106 – 2113 Date of Publication: 20 November 2014 Date of Current Version: 27 January 2015 Issue Date: April 2015  DOI 10.1109/JSEN.2014.2371773

This paper is behind a paywall.

Multiple sclerosis stopped by a biodegradable nanoparticle?

Researchers at Northwestern University (Chicago, Illinois) have halted the progress of multiple sclerosis in mice. The Nov. 18, 2012 Northwestern University news release on EurekAlert provides more details,

In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.

In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.

The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.

“This is a highly significant breakthrough in translational immunotherapy,” said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that’s delivered.”

“The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin,” Miller added. “Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact.”

The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and Applied Science.

There are human clinical trials taking place now (from the news release),

The study’s method is the same approach now being tested in multiple sclerosis patients in a phase I/II clinical trial — with one key difference. The trial uses a patient’s own white blood cells — a costly and labor intensive procedure — to deliver the antigen. The purpose of the new study was to see if nanoparticles could be as effective as the white blood cells as delivery vehicles. They were.

For interested parties, here’s the full citation for the article and a link,

Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis” by Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael . Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Zunrong Luo, Nicholas JC King, Lonnie D Shea and Stephen D Miller in Nature Biotechnology (2012) doi:10.1038/nbt.2434

The article is behind a paywall.  I found these details  in the news release about how the antigen and nanoparticles work with the immune system particularly interesting,

In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

“The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system,” said Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the National Institutes of Health, which supported the research.

All in all, this seems a gentler approach to the disease.

More than the “Emperor’s New Clothes” insight

Happy 2010 to all! I’ve taken some time out as I have moved locations and it’s taken longer to settle down that I hoped. (sigh) I still have loads to do but can get back to posting regularly (I hope).

New Year’s Eve I came across a very interesting article about how scientists think thanks to a reference on the Foresight Institute website. The article, Accept Defeat: The Neuroscience of Screwing Up, by Jonah Lehrer for Wired Magazine uses a story about a couple of astronomers and their investigative frustrations to illustrate research on how scientists (and the rest of us, as it turns out) think.

Before going on about the article I’m going to arbitrarily divide beliefs about scientific thinking/processes into two schools. In the first there’s the scientific method with its belief in objectivity and incontrovertible truths waiting to be discovered and validated. Later in university I was introduced to the 2nd belief about scientific thinking with the notion that scientific facts are social creations and that objectivity does not exist. From the outside it appears that scientists tend to belong to the first school and social scientists to the second but, as the Wired article points out, things are a little more amorphous than that when you dig down into the neuroscience of it all.

From the article,

The reason we’re so resistant to anomalous information — the real reason researchers automatically assume that every unexpected result is a stupid mistake — is rooted in the way the human brain works. Over the past few decades, psychologists [and other social scientists] have dismantled the myth of objectivity. The fact is, we carefully edit our reality, searching for evidence that confirms what we already believe. Although we pretend we’re empiricists — our views dictated by nothing but the facts — we’re actually blinkered, especially when it comes to information that contradicts our theories. The problem with science, then, isn’t that most experiments fail — it’s that most failures are ignored.

The DLPFC [dorsolateral prefrontal cortex] is constantly censoring the world, erasing facts from our experience. If the ACC  [anterior cingulate cortex, typically associated with errors and contradictions]] is the “Oh shit!” circuit, the DLPFC is the Delete key. When the ACC and DLPFC “turn on together, people aren’t just noticing that something doesn’t look right,” [Kevin] Dunbar says. “They’re also inhibiting that information.”

Disregarding evidence is something I’ve noticed (in others more easily than in myself) and have wondered about the implications. As noted in the article, ignoring scientific failure stymies research and ultimately more effective applications for the research. For example, there’s been a lot of interest in a new surgical procedure (still being tested) for patients with multiple sclerosis (MS). The procedure was developed by an Italian surgeon who (after his wife was stricken with the disease) reviewed literature on the disease going back 100 years and found a line of research that wasn’t being pursued actively and was a radical departure from current accepted beliefs about the nature of MS. (You can read more about the MS work here in the Globe and Mail story or here in the CBC story.) Btw, there are a couple of happy endings. The surgeon’s wife is much better and a promising new procedure is being examined.

Innovation and new research can be so difficult to pursue it’s amazing that anyone ever succeeds. Kevin Dunbar, the researcher mentioned previously, arrived at a rather interesting conclusion in his investigation on how scientists think and how they get around the ACC/DLFPC action: other people.  He tells a story about two lab groups who each had a meeting,

Dunbar watched how each of these labs dealt with their protein problem. The E. coli group took a brute-force approach, spending several weeks methodically testing various fixes. “It was extremely inefficient,” Dunbar says. “They eventually solved it, but they wasted a lot of valuable time.”The diverse lab, in contrast, mulled the problem at a group meeting. None of the scientists were protein experts, so they began a wide-ranging discussion of possible solutions. At first, the conversation seemed rather useless. But then, as the chemists traded ideas with the biologists and the biologists bounced ideas off the med students, potential answers began to emerge. “After another 10 minutes of talking, the protein problem was solved,” Dunbar says. “They made it look easy.”

When Dunbar reviewed the transcripts of the meeting, he found that the intellectual mix generated a distinct type of interaction in which the scientists were forced to rely on metaphors and analogies [my emphasis] to express themselves. (That’s because, unlike the E. coli group, the second lab lacked a specialized language that everyone could understand.) These abstractions proved essential for problem-solving, as they encouraged the scientists to reconsider their assumptions. Having to explain the problem to someone else forced them to think, if only for a moment, like an intellectual on the margins, filled with self-skepticism.

As Dunbar notes, we usually need more than an outsider to experience a Eureka moment (the story about Italian surgeon notwithstanding and it should be noted that he was an MS outsider); we need metaphors and analogies. (I’ve taken it a bit further than Dunbar likely would but I am a writer, after all.)

If you are interested in Dunbar’s work, he’s at the University of Toronto with more information here.