Tag Archives: regenerative medicine

New wound dressings with nanofibres for tissue regeneration

The Rotary Jet-Spinning manufacturing system was developed specifically as a therapeutic for the wounds of war. The dressings could be a good option for large wounds, such as burns, as well as smaller wounds on the face and hands, where preventing scarring is important. Illustration courtesy of Michael Rosnach/Harvard University

This image really gets the idea of regeneration across to the viewer while also informing you that this is medicine that comes from the military. A March 19,2018 news item on phys.org announces the work,

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering have developed new wound dressings that dramatically accelerate healing and improve tissue regeneration. The two different types of nanofiber dressings, described in separate papers, use naturally-occurring proteins in plants and animals to promote healing and regrow tissue.

Our fiber manufacturing system was developed specifically for the purpose of developing therapeutics for the wounds of war,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at SEAS and senior author of the research. “As a soldier in Afghanistan, I witnessed horrible wounds and, at times, the healing process for those wounds was a horror unto itself. This research is a years-long effort by many people on my team to help with these problems.”

Parker is also a Core Faculty Member of the Wyss Institute.

The most recent paper, published in Biomaterials, describes a wound dressing inspired by fetal tissue.

A March 19, 2018 Harvard University John A. Paulson School of Engineering and Applied Science news release by Leah Burrows (also on EurekAlert), which originated the news item, provides some background information before launching into more detail about this latest work,

In the late 1970s, when scientists first started studying the wound-healing process early in development, they discovered something unexpected: Wounds incurred before the third trimester left no scars. This opened a range of possibilities for regenerative medicine. But for decades, researchers have struggled to replicate those unique properties of fetal skin.

Unlike adult skin, fetal skin has high levels of a protein called fibronectin, which assembles into the extracellular matrix and promotes cell binding and adhesion. Fibronectin has two structures: globular, which is found in blood, and fibrous, which is found in tissue. Even though fibrous fibronectin holds the most promise for wound healing, previous research focused on the globular structure, in part because manufacturing fibrous fibronectin was a major engineering challenge.

But Parker and his team are pioneers in the field of nanofiber engineering.

The researchers made fibrous fibronectin using a fiber-manufacturing platform called Rotary Jet-Spinning (RJS), developed by Parker’s Disease Biophysics Group. RJS works likes a cotton-candy machine — a liquid polymer solution, in this case globular fibronectin dissolved in a solvent, is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. As the solution leaves the reservoir, the solvent evaporates and the polymers solidify. The centrifugal force unfolds the globular protein into small, thin fibers. These fibers — less than one micrometer in diameter — can be collected to form a large-scale wound dressing or bandage.

“The dressing integrates into the wound and acts like an instructive scaffold, recruiting different stem cells that are relevant for regeneration and assisting in the healing process before being absorbed into the body,” said Christophe Chantre, a graduate student in the Disease Biophysics Group and first author of the paper.

In in vivo testing, the researchers found that wounds treated with the fibronectin dressing showed 84 percent tissue restoration within 20 days, compared with 55.6 percent restoration in wounds treated with a standard dressing.

The researchers also demonstrated that wounds treated with the fibronectin dressing had almost normal epidermal thickness and dermal architecture, and even regrew hair follicles — often considered one of the biggest challenges in the field of wound healing.

“This is an important step forward,” said Chantre. “Most work done on skin regeneration to date involves complex treatments combining scaffolds, cells, and even growth factors. Here we were able to demonstrate tissue repair and hair follicle regeneration using an entirely material approach. This has clear advantages for clinical translation.”

In another paper published in Advanced Healthcare Materials, the Disease Biophysics Group demonstrated a soy-based nanofiber that also enhances and promotes wound healing.

Soy protein contains both estrogen-like molecules — which have been shown to accelerate wound healing — and bioactive molecules similar to those that build and support human cells.

“Both the soy- and fibronectin-fiber technologies owe their success to keen observations in reproductive medicine,” said Parker. “During a woman’s cycle, when her estrogen levels go high, a cut will heal faster. If you do a surgery on a baby still in the womb, they have scar-less wound healing. Both of these new technologies are rooted in the most fascinating of all the topics in human biology — how we reproduce.”

In a similar way to fibronectin fibers, the research team used RJS to spin ultrathin soy fibers into wound dressings. In experiments, the soy- and cellulose-based dressing demonstrated a 72 percent increase in healing over wounds with no dressing and a 21 percent increase in healing over wounds dressed without soy protein.

“These findings show the great promise of soy-based nanofibers for wound healing,” said Seungkuk Ahn, a graduate student in the Disease Biophysics Group and first author of the paper. “These one-step, cost-effective scaffolds could be the next generation of regenerative dressings and push the envelope of nanofiber technology and the wound-care market.”

Both kinds of dressing, according to researchers, have advantages in the wound-healing space. The soy-based nanofibers — consisting of cellulose acetate and soy protein hydrolysate — are inexpensive, making them a good option for large-scale use, such as on burns. The fibronectin dressings, on the other hand, could be used for smaller wounds on the face and hands, where preventing scarring is important.

Here’s are links and citations for both papers mentioned in the news release,

Soy Protein/Cellulose Nanofiber Scaffolds Mimicking Skin Extracellular Matrix for Enhanced Wound Healing by Seungkuk Ahn, Christophe O. Chantre, Alanna R. Gannon, Johan U. Lind, Patrick H. Campbell, Thomas Grevesse, Blakely B. O’Connor, Kevin Kit Parker. Advanced Healthcare Materials https://doi.org/10.1002/adhm.201701175 First published: 23 January 2018

Production-scale fibronectin nanofibers promote wound closure and tissue repair in a dermal mouse model by Christophe O. Chantre, Patrick H. Campbell, Holly M. Golecki, Adrian T. Buganza, Andrew K. Capulli, Leila F. Deravi, Stephanie Dauth, Sean P. Sheehy, Jeffrey A.Paten. KarlGledhill, Yanne S. Doucet, Hasan E.Abaci, Seungkuk Ahn, Benjamin D.Pope, Jeffrey W.Ruberti, Simon P.Hoerstrup, Angela M.Christiano, Kevin Kit Parker. Biomaterials Volume 166, June 2018, Pages 96-108 https://doi.org/10.1016/j.biomaterials.2018.03.006 Available online 5 March 2018

Both papers are behind paywalls although you may want to check with ResearchGate where many researchers make their papers available for free.

One last comment, I noticed this at the end of Burrows’ news release,

The Harvard Office of Technology Development has protected the intellectual property relating to these projects and is exploring commercialization opportunities.

It reminded me of the patent battle between the Broad Institute (a Harvard University and Massachusetts Institute of Technology joint venture) and the University of California at Berkeley over CRISPR (clustered regularly interspaced short palindromic repeats) technology. (My March 15, 2017 posting describes the battle’s outcome.)

Lest we forget, there could be major financial rewards from this work.

“Living” bandages made from biocompatible anti-burn nanofibers

A February 16, 2018 news item on Nanowerk announces research from a Russian team about their work on “living” bandages,

In regenerative medicine, and particularly in burn therapy, the effective regeneration of damaged skin tissue and the prevention of scarring are usually the main goals. Scars form when skin is badly damaged, whether through a cut, burn, or a skin problem such as acne or fungal infection.

Scar tissue mainly consists of irreversible collagen and significantly differs from the tissue it replaces, having reduced functional properties. For example, scars on skin are more sensitive to ultraviolet radiation, are not elastic, and the sweat glands and hair follicles are not restored in the area.

The solution of this medical problem was proposed by the researchers from the NUST MISIS [National University of Science and Technology {formerly Moscow Institute of Steel and Alloys State Technological University})] Inorganic Nanomaterials Laboratory, led by PhD Anton Manakhov, a senior researcher. The team of nanotechnology scientists has managed to create multi-layer ‘bandages’ made of biodegradable fibers and multifunctional bioactive nanofilms, which [the bandages] prevent scarring and accelerate tissue regeneration.

A February 14, 2018 NUST MISIS press release, which originated the news item, provides more detail,

The addition of the antibacterial effect by the introduction of silver nanoparticles or joining antibiotics, as well as the increase of biological activity to the surface of hydrophilic groups (-COOH) and the blood plasma proteins have provided unique healing properties to the material.

A significant acceleration of the healing process, the successful regeneration of normal skin covering tissue, and the prevention of scarring on the site of burnt or damaged skin have been observed when applying these bandages made of the developed material to an injured area. The antibacterial components of multifunctional nanofibers decrease inflammation, and the blood plasma with an increased platelet level — vital and multi-purposed for every element in the healing process — stimulates the regeneration of tissues. The bandages should not be removed or changed during treatment as it may cause additional pain to the patient. After a certain period of time, the biodegradable fiber simply “dissolves” without any side effects.

“With the help of chemical bonds, we were able to create a stable layer containing blood plasma components (growth factors, fibrinogens, and other important proteins that promote cell growth) on a polycaprolactone base. The base fibers were synthesized by electroforming. Then, with the help of plasma treatment, to increase the material`s hydrophilic properties, a polymer layer containing carboxyl groups was applied to the surface. The resulting layer was enriched with antibacterial and protein components”, noted Elizabeth Permyakova, one of the project members and laboratory scientists.

The researchers have made images of their work available including this one,

Courtesy NUST MISS [downloaded from http://en.misis.ru/university/news/science/2018-02/5219/]

There is doesn’t appear to be an accompanying published paper.

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

Taking up from where I left off with my comments on Competing in a Global Innovation Economy: The Current State of R and D in Canada or as I prefer to call it the Third assessment of Canadas S&T (science and technology) and R&D (research and development). (Part 1 for anyone who missed it).

Is it possible to get past Hedy?

Interestingly (to me anyway), one of our R&D strengths, the visual and performing arts, features sectors where a preponderance of people are dedicated to creating culture in Canada and don’t spend a lot of time trying to make money so they can retire before the age of 40 as so many of our start-up founders do. (Retiring before the age of 40 just reminded me of Hollywood actresses {Hedy] who found and still do find that work was/is hard to come by after that age. You may be able but I’m not sure I can get past Hedy.) Perhaps our business people (start-up founders) could take a leaf out of the visual and performing arts handbook? Or, not. There is another question.

Does it matter if we continue to be a ‘branch plant’ economy? Somebody once posed that question to me when I was grumbling that our start-ups never led to larger businesses and acted more like incubators (which could describe our R&D as well),. He noted that Canadians have a pretty good standard of living and we’ve been running things this way for over a century and it seems to work for us. Is it that bad? I didn’t have an  answer for him then and I don’t have one now but I think it’s a useful question to ask and no one on this (2018) expert panel or the previous expert panel (2013) seems to have asked.

I appreciate that the panel was constrained by the questions given by the government but given how they snuck in a few items that technically speaking were not part of their remit, I’m thinking they might have gone just a bit further. The problem with answering the questions as asked is that if you’ve got the wrong questions, your answers will be garbage (GIGO; garbage in, garbage out) or, as is said, where science is concerned, it’s the quality of your questions.

On that note, I would have liked to know more about the survey of top-cited researchers. I think looking at the questions could have been quite illuminating and I would have liked some information on from where (geographically and area of specialization) they got most of their answers. In keeping with past practice (2012 assessment published in 2013), there is no additional information offered about the survey questions or results. Still, there was this (from the report released April 10, 2018; Note: There may be some difference between the formatting seen here and that seen in the document),

3.1.2 International Perceptions of Canadian Research
As with the 2012 S&T report, the CCA commissioned a survey of top-cited researchers’ perceptions of Canada’s research strength in their field or subfield relative to that of other countries (Section 1.3.2). Researchers were asked to identify the top five countries in their field and subfield of expertise: 36% of respondents (compared with 37% in the 2012 survey) from across all fields of research rated Canada in the top five countries in their field (Figure B.1 and Table B.1 in the appendix). Canada ranks fourth out of all countries, behind the United States, United Kingdom, and Germany, and ahead of France. This represents a change of about 1 percentage point from the overall results of the 2012 S&T survey. There was a 4 percentage point decrease in how often France is ranked among the top five countries; the ordering of the top five countries, however, remains the same.

When asked to rate Canada’s research strength among other advanced countries in their field of expertise, 72% (4,005) of respondents rated Canadian research as “strong” (corresponding to a score of 5 or higher on a 7-point scale) compared with 68% in the 2012 S&T survey (Table 3.4). [pp. 40-41 Print; pp. 78-70 PDF]

Before I forget, there was mention of the international research scene,

Growth in research output, as estimated by number of publications, varies considerably for the 20 top countries. Brazil, China, India, Iran, and South Korea have had the most significant increases in publication output over the last 10 years. [emphases mine] In particular, the dramatic increase in China’s output means that it is closing the gap with the United States. In 2014, China’s output was 95% of that of the United States, compared with 26% in 2003. [emphasis mine]

Table 3.2 shows the Growth Index (GI), a measure of the rate at which the research output for a given country changed between 2003 and 2014, normalized by the world growth rate. If a country’s growth in research output is higher than the world average, the GI score is greater than 1.0. For example, between 2003 and 2014, China’s GI score was 1.50 (i.e., 50% greater than the world average) compared with 0.88 and 0.80 for Canada and the United States, respectively. Note that the dramatic increase in publication production of emerging economies such as China and India has had a negative impact on Canada’s rank and GI score (see CCA, 2016).

As long as I’ve been blogging (10 years), the international research community (in particular the US) has been looking over its shoulder at China.

Patents and intellectual property

As an inventor, Hedy got more than one patent. Much has been made of the fact that  despite an agreement, the US Navy did not pay her or her partner (George Antheil) for work that would lead to significant military use (apparently, it was instrumental in the Bay of Pigs incident, for those familiar with that bit of history), GPS, WiFi, Bluetooth, and more.

Some comments about patents. They are meant to encourage more innovation by ensuring that creators/inventors get paid for their efforts .This is true for a set time period and when it’s over, other people get access and can innovate further. It’s not intended to be a lifelong (or inheritable) source of income. The issue in Lamarr’s case is that the navy developed the technology during the patent’s term without telling either her or her partner so, of course, they didn’t need to compensate them despite the original agreement. They really should have paid her and Antheil.

The current patent situation, particularly in the US, is vastly different from the original vision. These days patents are often used as weapons designed to halt innovation. One item that should be noted is that the Canadian federal budget indirectly addressed their misuse (from my March 16, 2018 posting),

Surprisingly, no one else seems to have mentioned a new (?) intellectual property strategy introduced in the document (from Chapter 2: Progress; scroll down about 80% of the way, Note: The formatting has been changed),

Budget 2018 proposes measures in support of a new Intellectual Property Strategy to help Canadian entrepreneurs better understand and protect intellectual property, and get better access to shared intellectual property.

What Is a Patent Collective?
A Patent Collective is a way for firms to share, generate, and license or purchase intellectual property. The collective approach is intended to help Canadian firms ensure a global “freedom to operate”, mitigate the risk of infringing a patent, and aid in the defence of a patent infringement suit.

Budget 2018 proposes to invest $85.3 million over five years, starting in 2018–19, with $10 million per year ongoing, in support of the strategy. The Minister of Innovation, Science and Economic Development will bring forward the full details of the strategy in the coming months, including the following initiatives to increase the intellectual property literacy of Canadian entrepreneurs, and to reduce costs and create incentives for Canadian businesses to leverage their intellectual property:

  • To better enable firms to access and share intellectual property, the Government proposes to provide $30 million in 2019–20 to pilot a Patent Collective. This collective will work with Canada’s entrepreneurs to pool patents, so that small and medium-sized firms have better access to the critical intellectual property they need to grow their businesses.
  • To support the development of intellectual property expertise and legal advice for Canada’s innovation community, the Government proposes to provide $21.5 million over five years, starting in 2018–19, to Innovation, Science and Economic Development Canada. This funding will improve access for Canadian entrepreneurs to intellectual property legal clinics at universities. It will also enable the creation of a team in the federal government to work with Canadian entrepreneurs to help them develop tailored strategies for using their intellectual property and expanding into international markets.
  • To support strategic intellectual property tools that enable economic growth, Budget 2018 also proposes to provide $33.8 million over five years, starting in 2018–19, to Innovation, Science and Economic Development Canada, including $4.5 million for the creation of an intellectual property marketplace. This marketplace will be a one-stop, online listing of public sector-owned intellectual property available for licensing or sale to reduce transaction costs for businesses and researchers, and to improve Canadian entrepreneurs’ access to public sector-owned intellectual property.

The Government will also consider further measures, including through legislation, in support of the new intellectual property strategy.

Helping All Canadians Harness Intellectual Property
Intellectual property is one of our most valuable resources, and every Canadian business owner should understand how to protect and use it.

To better understand what groups of Canadians are benefiting the most from intellectual property, Budget 2018 proposes to provide Statistics Canada with $2 million over three years to conduct an intellectual property awareness and use survey. This survey will help identify how Canadians understand and use intellectual property, including groups that have traditionally been less likely to use intellectual property, such as women and Indigenous entrepreneurs. The results of the survey should help the Government better meet the needs of these groups through education and awareness initiatives.

The Canadian Intellectual Property Office will also increase the number of education and awareness initiatives that are delivered in partnership with business, intermediaries and academia to ensure Canadians better understand, integrate and take advantage of intellectual property when building their business strategies. This will include targeted initiatives to support underrepresented groups.

Finally, Budget 2018 also proposes to invest $1 million over five years to enable representatives of Canada’s Indigenous Peoples to participate in discussions at the World Intellectual Property Organization related to traditional knowledge and traditional cultural expressions, an important form of intellectual property.

It’s not wholly clear what they mean by ‘intellectual property’. The focus seems to be on  patents as they are the only intellectual property (as opposed to copyright and trademarks) singled out in the budget. As for how the ‘patent collective’ is going to meet all its objectives, this budget supplies no clarity on the matter. On the plus side, I’m glad to see that indigenous peoples’ knowledge is being acknowledged as “an important form of intellectual property” and I hope the discussions at the World Intellectual Property Organization are fruitful.

As for the patent situation in Canada (from the report released April 10, 2018),

Over the past decade, the Canadian patent flow in all technical sectors has consistently decreased. Patent flow provides a partial picture of how patents in Canada are exploited. A negative flow represents a deficit of patented inventions owned by Canadian assignees versus the number of patented inventions created by Canadian inventors. The patent flow for all Canadian patents decreased from about −0.04 in 2003 to −0.26 in 2014 (Figure 4.7). This means that there is an overall deficit of 26% of patent ownership in Canada. In other words, fewer patents were owned by Canadian institutions than were invented in Canada.

This is a significant change from 2003 when the deficit was only 4%. The drop is consistent across all technical sectors in the past 10 years, with Mechanical Engineering falling the least, and Electrical Engineering the most (Figure 4.7). At the technical field level, the patent flow dropped significantly in Digital Communication and Telecommunications. For example, the Digital Communication patent flow fell from 0.6 in 2003 to −0.2 in 2014. This fall could be partially linked to Nortel’s US$4.5 billion patent sale [emphasis mine] to the Rockstar consortium (which included Apple, BlackBerry, Ericsson, Microsoft, and Sony) (Brickley, 2011). Food Chemistry and Microstructural [?] and Nanotechnology both also showed a significant drop in patent flow. [p. 83 Print; p. 121 PDF]

Despite a fall in the number of parents for ‘Digital Communication’, we’re still doing well according to statistics elsewhere in this report. Is it possible that patents aren’t that big a deal? Of course, it’s also possible that we are enjoying the benefits of past work and will miss out on future work. (Note: A video of the April 10, 2018 report presentation by Max Blouw features him saying something like that.)

One last note, Nortel died many years ago. Disconcertingly, this report, despite more than one reference to Nortel, never mentions the company’s demise.

Boxed text

While the expert panel wasn’t tasked to answer certain types of questions, as I’ve noted earlier they managed to sneak in a few items.  One of the strategies they used was putting special inserts into text boxes including this (from the report released April 10, 2018),

Box 4.2
The FinTech Revolution

Financial services is a key industry in Canada. In 2015, the industry accounted for 4.4%

of Canadia jobs and about 7% of Canadian GDP (Burt, 2016). Toronto is the second largest financial services hub in North America and one of the most vibrant research hubs in FinTech. Since 2010, more than 100 start-up companies have been founded in Canada, attracting more than $1 billion in investment (Moffatt, 2016). In 2016 alone, venture-backed investment in Canadian financial technology companies grew by 35% to $137.7 million (Ho, 2017). The Toronto Financial Services Alliance estimates that there are approximately 40,000 ICT specialists working in financial services in Toronto alone.

AI, blockchain, [emphasis mine] and other results of ICT research provide the basis for several transformative FinTech innovations including, for example, decentralized transaction ledgers, cryptocurrencies (e.g., bitcoin), and AI-based risk assessment and fraud detection. These innovations offer opportunities to develop new markets for established financial services firms, but also provide entry points for technology firms to develop competing service offerings, increasing competition in the financial services industry. In response, many financial services companies are increasing their investments in FinTech companies (Breznitz et al., 2015). By their own account, the big five banks invest more than $1 billion annually in R&D of advanced software solutions, including AI-based innovations (J. Thompson, personal communication, 2016). The banks are also increasingly investing in university research and collaboration with start-up companies. For instance, together with several large insurance and financial management firms, all big five banks have invested in the Vector Institute for Artificial Intelligence (Kolm, 2017).

I’m glad to see the mention of blockchain while AI (artificial intelligence) is an area where we have innovated (from the report released April 10, 2018),

AI has attracted researchers and funding since the 1960s; however, there were periods of stagnation in the 1970s and 1980s, sometimes referred to as the “AI winter.” During this period, the Canadian Institute for Advanced Research (CIFAR), under the direction of Fraser Mustard, started supporting AI research with a decade-long program called Artificial Intelligence, Robotics and Society, [emphasis mine] which was active from 1983 to 1994. In 2004, a new program called Neural Computation and Adaptive Perception was initiated and renewed twice in 2008 and 2014 under the title, Learning in Machines and Brains. Through these programs, the government provided long-term, predictable support for high- risk research that propelled Canadian researchers to the forefront of global AI development. In the 1990s and early 2000s, Canadian research output and impact on AI were second only to that of the United States (CIFAR, 2016). NSERC has also been an early supporter of AI. According to its searchable grant database, NSERC has given funding to research projects on AI since at least 1991–1992 (the earliest searchable year) (NSERC, 2017a).

The University of Toronto, the University of Alberta, and the Université de Montréal have emerged as international centres for research in neural networks and deep learning, with leading experts such as Geoffrey Hinton and Yoshua Bengio. Recently, these locations have expanded into vibrant hubs for research in AI applications with a diverse mix of specialized research institutes, accelerators, and start-up companies, and growing investment by major international players in AI development, such as Microsoft, Google, and Facebook. Many highly influential AI researchers today are either from Canada or have at some point in their careers worked at a Canadian institution or with Canadian scholars.

As international opportunities in AI research and the ICT industry have grown, many of Canada’s AI pioneers have been drawn to research institutions and companies outside of Canada. According to the OECD, Canada’s share of patents in AI declined from 2.4% in 2000 to 2005 to 2% in 2010 to 2015. Although Canada is the sixth largest producer of top-cited scientific publications related to machine learning, firms headquartered in Canada accounted for only 0.9% of all AI-related inventions from 2012 to 2014 (OECD, 2017c). Canadian AI researchers, however, remain involved in the core nodes of an expanding international network of AI researchers, most of whom continue to maintain ties with their home institutions. Compared with their international peers, Canadian AI researchers are engaged in international collaborations far more often than would be expected by Canada’s level of research output, with Canada ranking fifth in collaboration. [p. 97-98 Print; p. 135-136 PDF]

The only mention of robotics seems to be here in this section and it’s only in passing. This is a bit surprising given its global importance. I wonder if robotics has been somehow hidden inside the term artificial intelligence, although sometimes it’s vice versa with robot being used to describe artificial intelligence. I’m noticing this trend of assuming the terms are synonymous or interchangeable not just in Canadian publications but elsewhere too.  ’nuff said.

Getting back to the matter at hand, t he report does note that patenting (technometric data) is problematic (from the report released April 10, 2018),

The limitations of technometric data stem largely from their restricted applicability across areas of R&D. Patenting, as a strategy for IP management, is similarly limited in not being equally relevant across industries. Trends in patenting can also reflect commercial pressures unrelated to R&D activities, such as defensive or strategic patenting practices. Finally, taxonomies for assessing patents are not aligned with bibliometric taxonomies, though links can be drawn to research publications through the analysis of patent citations. [p. 105 Print; p. 143 PDF]

It’s interesting to me that they make reference to many of the same issues that I mention but they seem to forget and don’t use that information in their conclusions.

There is one other piece of boxed text I want to highlight (from the report released April 10, 2018),

Box 6.3
Open Science: An Emerging Approach to Create New Linkages

Open Science is an umbrella term to describe collaborative and open approaches to
undertaking science, which can be powerful catalysts of innovation. This includes
the development of open collaborative networks among research performers, such
as the private sector, and the wider distribution of research that usually results when
restrictions on use are removed. Such an approach triggers faster translation of ideas
among research partners and moves the boundaries of pre-competitive research to
later, applied stages of research. With research results freely accessible, companies
can focus on developing new products and processes that can be commercialized.

Two Canadian organizations exemplify the development of such models. In June
2017, Genome Canada, the Ontario government, and pharmaceutical companies
invested $33 million in the Structural Genomics Consortium (SGC) (Genome Canada,
2017). Formed in 2004, the SGC is at the forefront of the Canadian open science
movement and has contributed to many key research advancements towards new
treatments (SGC, 2018). McGill University’s Montréal Neurological Institute and
Hospital has also embraced the principles of open science. Since 2016, it has been
sharing its research results with the scientific community without restriction, with
the objective of expanding “the impact of brain research and accelerat[ing] the
discovery of ground-breaking therapies to treat patients suffering from a wide range
of devastating neurological diseases” (neuro, n.d.).

This is exciting stuff and I’m happy the panel featured it. (I wrote about the Montréal Neurological Institute initiative in a Jan. 22, 2016 posting.)

More than once, the report notes the difficulties with using bibliometric and technometric data as measures of scientific achievement and progress and open science (along with its cousins, open data and open access) are contributing to the difficulties as James Somers notes in his April 5, 2018 article ‘The Scientific Paper is Obsolete’ for The Atlantic (Note: Links have been removed),

The scientific paper—the actual form of it—was one of the enabling inventions of modernity. Before it was developed in the 1600s, results were communicated privately in letters, ephemerally in lectures, or all at once in books. There was no public forum for incremental advances. By making room for reports of single experiments or minor technical advances, journals made the chaos of science accretive. Scientists from that point forward became like the social insects: They made their progress steadily, as a buzzing mass.

The earliest papers were in some ways more readable than papers are today. They were less specialized, more direct, shorter, and far less formal. Calculus had only just been invented. Entire data sets could fit in a table on a single page. What little “computation” contributed to the results was done by hand and could be verified in the same way.

The more sophisticated science becomes, the harder it is to communicate results. Papers today are longer than ever and full of jargon and symbols. They depend on chains of computer programs that generate data, and clean up data, and plot data, and run statistical models on data. These programs tend to be both so sloppily written and so central to the results that it’s [sic] contributed to a replication crisis, or put another way, a failure of the paper to perform its most basic task: to report what you’ve actually discovered, clearly enough that someone else can discover it for themselves.

Perhaps the paper itself is to blame. Scientific methods evolve now at the speed of software; the skill most in demand among physicists, biologists, chemists, geologists, even anthropologists and research psychologists, is facility with programming languages and “data science” packages. And yet the basic means of communicating scientific results hasn’t changed for 400 years. Papers may be posted online, but they’re still text and pictures on a page.

What would you get if you designed the scientific paper from scratch today? A little while ago I spoke to Bret Victor, a researcher who worked at Apple on early user-interface prototypes for the iPad and now runs his own lab in Oakland, California, that studies the future of computing. Victor has long been convinced that scientists haven’t yet taken full advantage of the computer. “It’s not that different than looking at the printing press, and the evolution of the book,” he said. After Gutenberg, the printing press was mostly used to mimic the calligraphy in bibles. It took nearly 100 years of technical and conceptual improvements to invent the modern book. “There was this entire period where they had the new technology of printing, but they were just using it to emulate the old media.”Victor gestured at what might be possible when he redesigned a journal article by Duncan Watts and Steven Strogatz, “Collective dynamics of ‘small-world’ networks.” He chose it both because it’s one of the most highly cited papers in all of science and because it’s a model of clear exposition. (Strogatz is best known for writing the beloved “Elements of Math” column for The New York Times.)

The Watts-Strogatz paper described its key findings the way most papers do, with text, pictures, and mathematical symbols. And like most papers, these findings were still hard to swallow, despite the lucid prose. The hardest parts were the ones that described procedures or algorithms, because these required the reader to “play computer” in their head, as Victor put it, that is, to strain to maintain a fragile mental picture of what was happening with each step of the algorithm.Victor’s redesign interleaved the explanatory text with little interactive diagrams that illustrated each step. In his version, you could see the algorithm at work on an example. You could even control it yourself….

For anyone interested in the evolution of how science is conducted and communicated, Somers’ article is a fascinating and in depth look at future possibilities.

Subregional R&D

I didn’t find this quite as compelling as the last time and that may be due to the fact that there’s less information and I think the 2012 report was the first to examine the Canadian R&D scene with a subregional (in their case, provinces) lens. On a high note, this report also covers cities (!) and regions, as well as, provinces.

Here’s the conclusion (from the report released April 10, 2018),

Ontario leads Canada in R&D investment and performance. The province accounts for almost half of R&D investment and personnel, research publications and collaborations, and patents. R&D activity in Ontario produces high-quality publications in each of Canada’s five R&D strengths, reflecting both the quantity and quality of universities in the province. Quebec lags Ontario in total investment, publications, and patents, but performs as well (citations) or better (R&D intensity) by some measures. Much like Ontario, Quebec researchers produce impactful publications across most of Canada’s five R&D strengths. Although it invests an amount similar to that of Alberta, British Columbia does so at a significantly higher intensity. British Columbia also produces more highly cited publications and patents, and is involved in more international research collaborations. R&D in British Columbia and Alberta clusters around Vancouver and Calgary in areas such as physics and ICT and in clinical medicine and energy, respectively. [emphasis mine] Smaller but vibrant R&D communities exist in the Prairies and Atlantic Canada [also referred to as the Maritime provinces or Maritimes] (and, to a lesser extent, in the Territories) in natural resource industries.

Globally, as urban populations expand exponentially, cities are likely to drive innovation and wealth creation at an increasing rate in the future. In Canada, R&D activity clusters around five large cities: Toronto, Montréal, Vancouver, Ottawa, and Calgary. These five cities create patents and high-tech companies at nearly twice the rate of other Canadian cities. They also account for half of clusters in the services sector, and many in advanced manufacturing.

Many clusters relate to natural resources and long-standing areas of economic and research strength. Natural resource clusters have emerged around the location of resources, such as forestry in British Columbia, oil and gas in Alberta, agriculture in Ontario, mining in Quebec, and maritime resources in Atlantic Canada. The automotive, plastics, and steel industries have the most individual clusters as a result of their economic success in Windsor, Hamilton, and Oshawa. Advanced manufacturing industries tend to be more concentrated, often located near specialized research universities. Strong connections between academia and industry are often associated with these clusters. R&D activity is distributed across the country, varying both between and within regions. It is critical to avoid drawing the wrong conclusion from this fact. This distribution does not imply the existence of a problem that needs to be remedied. Rather, it signals the benefits of diverse innovation systems, with differentiation driven by the needs of and resources available in each province. [pp.  132-133 Print; pp. 170-171 PDF]

Intriguingly, there’s no mention that in British Columbia (BC), there are leading areas of research: Visual & Performing Arts, Psychology & Cognitive Sciences, and Clinical Medicine (according to the table on p. 117 Print, p. 153 PDF).

As I said and hinted earlier, we’ve got brains; they’re just not the kind of brains that command respect.

Final comments

My hat’s off to the expert panel and staff of the Council of Canadian Academies. Combining two previous reports into one could not have been easy. As well, kudos to their attempts to broaden the discussion by mentioning initiative such as open science and for emphasizing the problems with bibliometrics, technometrics, and other measures. I have covered only parts of this assessment, (Competing in a Global Innovation Economy: The Current State of R&D in Canada), there’s a lot more to it including a substantive list of reference materials (bibliography).

While I have argued that perhaps the situation isn’t quite as bad as the headlines and statistics may suggest, there are some concerning trends for Canadians but we have to acknowledge that many countries have stepped up their research game and that’s good for all of us. You don’t get better at anything unless you work with and play with others who are better than you are. For example, both India and Italy surpassed us in numbers of published research papers. We slipped from 7th place to 9th. Thank you, Italy and India. (And, Happy ‘Italian Research in the World Day’ on April 15, 2018, the day’s inaugural year. In Italian: Piano Straordinario “Vivere all’Italiana” – Giornata della ricerca Italiana nel mondo.)

Unfortunately, the reading is harder going than previous R&D assessments in the CCA catalogue. And in the end, I can’t help thinking we’re just a little bit like Hedy Lamarr. Not really appreciated in all of our complexities although the expert panel and staff did try from time to time. Perhaps the government needs to find better ways of asking the questions.

***ETA April 12, 2018 at 1500 PDT: Talking about missing the obvious! I’ve been ranting on about how research strength in visual and performing arts and in philosophy and theology, etc. is perfectly fine and could lead to ‘traditional’ science breakthroughs without underlining the point by noting that Antheil was a musician, Lamarr was as an actress and they set the foundation for work by electrical engineers (or people with that specialty) for their signature work leading to WiFi, etc.***

There is, by the way, a Hedy-Canada connection. In 1998, she sued Canadian software company Corel, for its unauthorized use of her image on their Corel Draw 8 product packaging. She won.

More stuff

For those who’d like to see and hear the April 10, 2017 launch for “Competing in a Global Innovation Economy: The Current State of R&D in Canada” or the Third Assessment as I think of it, go here.

The report can be found here.

For anyone curious about ‘Bombshell: The Hedy Lamarr Story’ to be broadcast on May 18, 2018 as part of PBS’s American Masters series, there’s this trailer,

For the curious, I did find out more about the Hedy Lamarr and Corel Draw. John Lettice’s December 2, 1998 article The Rgister describes the suit and her subsequent victory in less than admiring terms,

Our picture doesn’t show glamorous actress Hedy Lamarr, who yesterday [Dec. 1, 1998] came to a settlement with Corel over the use of her image on Corel’s packaging. But we suppose that following the settlement we could have used a picture of Corel’s packaging. Lamarr sued Corel earlier this year over its use of a CorelDraw image of her. The picture had been produced by John Corkery, who was 1996 Best of Show winner of the Corel World Design Contest. Corel now seems to have come to an undisclosed settlement with her, which includes a five-year exclusive (oops — maybe we can’t use the pack-shot then) licence to use “the lifelike vector illustration of Hedy Lamarr on Corel’s graphic software packaging”. Lamarr, bless ‘er, says she’s looking forward to the continued success of Corel Corporation,  …

There’s this excerpt from a Sept. 21, 2015 posting (a pictorial essay of Lamarr’s life) by Shahebaz Khan on The Blaze Blog,

6. CorelDRAW:
For several years beginning in 1997, the boxes of Corel DRAW’s software suites were graced by a large Corel-drawn image of Lamarr. The picture won Corel DRAW’s yearly software suite cover design contest in 1996. Lamarr sued Corel for using the image without her permission. Corel countered that she did not own rights to the image. The parties reached an undisclosed settlement in 1998.

There’s also a Nov. 23, 1998 Corel Draw 8 product review by Mike Gorman on mymac.com, which includes a screenshot of the packaging that precipitated the lawsuit. Once they settled, it seems Corel used her image at least one more time.

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

A transatlantic report highlighting the risks and opportunities associated with synthetic biology and bioengineering

I love e-Life, the open access journal where its editors noted that a submitted synthetic biology and bioengineering report was replete with US and UK experts (along with a European or two) but no expert input from other parts of the world. In response the authors added ‘transatlantic’ to the title. It was a good decision since it was too late to add any new experts if the authors planned to have their paper published in the foreseeable future.

I’ve commented many times here when panels of experts include only Canadian, US, UK, and, sometimes, European or Commonwealth (Australia/New Zealand) experts that we need to broaden our perspectives and now I can add: or at least acknowledge (e.g. transatlantic) that the perspectives taken are reflective of a rather narrow range of countries.

Now getting to the report, here’s more from a November 21, 2017 University of Cambridge press release,

Human genome editing, 3D-printed replacement organs and artificial photosynthesis – the field of bioengineering offers great promise for tackling the major challenges that face our society. But as a new article out today highlights, these developments provide both opportunities and risks in the short and long term.

Rapid developments in the field of synthetic biology and its associated tools and methods, including more widely available gene editing techniques, have substantially increased our capabilities for bioengineering – the application of principles and techniques from engineering to biological systems, often with the goal of addressing ‘real-world’ problems.

In a feature article published in the open access journal eLife, an international team of experts led by Dr Bonnie Wintle and Dr Christian R. Boehm from the Centre for the Study of Existential Risk at the University of Cambridge, capture perspectives of industry, innovators, scholars, and the security community in the UK and US on what they view as the major emerging issues in the field.

Dr Wintle says: “The growth of the bio-based economy offers the promise of addressing global environmental and societal challenges, but as our paper shows, it can also present new kinds of challenges and risks. The sector needs to proceed with caution to ensure we can reap the benefits safely and securely.”

The report is intended as a summary and launching point for policy makers across a range of sectors to further explore those issues that may be relevant to them.

Among the issues highlighted by the report as being most relevant over the next five years are:

Artificial photosynthesis and carbon capture for producing biofuels

If technical hurdles can be overcome, such developments might contribute to the future adoption of carbon capture systems, and provide sustainable sources of commodity chemicals and fuel.

Enhanced photosynthesis for agricultural productivity

Synthetic biology may hold the key to increasing yields on currently farmed land – and hence helping address food security – by enhancing photosynthesis and reducing pre-harvest losses, as well as reducing post-harvest and post-consumer waste.

Synthetic gene drives

Gene drives promote the inheritance of preferred genetic traits throughout a species, for example to prevent malaria-transmitting mosquitoes from breeding. However, this technology raises questions about whether it may alter ecosystems [emphasis mine], potentially even creating niches where a new disease-carrying species or new disease organism may take hold.

Human genome editing

Genome engineering technologies such as CRISPR/Cas9 offer the possibility to improve human lifespans and health. However, their implementation poses major ethical dilemmas. It is feasible that individuals or states with the financial and technological means may elect to provide strategic advantages to future generations.

Defence agency research in biological engineering

The areas of synthetic biology in which some defence agencies invest raise the risk of ‘dual-use’. For example, one programme intends to use insects to disseminate engineered plant viruses that confer traits to the target plants they feed on, with the aim of protecting crops from potential plant pathogens – but such technologies could plausibly also be used by others to harm targets.

In the next five to ten years, the authors identified areas of interest including:

Regenerative medicine: 3D printing body parts and tissue engineering

While this technology will undoubtedly ease suffering caused by traumatic injuries and a myriad of illnesses, reversing the decay associated with age is still fraught with ethical, social and economic concerns. Healthcare systems would rapidly become overburdened by the cost of replenishing body parts of citizens as they age and could lead new socioeconomic classes, as only those who can pay for such care themselves can extend their healthy years.

Microbiome-based therapies

The human microbiome is implicated in a large number of human disorders, from Parkinson’s to colon cancer, as well as metabolic conditions such as obesity and type 2 diabetes. Synthetic biology approaches could greatly accelerate the development of more effective microbiota-based therapeutics. However, there is a risk that DNA from genetically engineered microbes may spread to other microbiota in the human microbiome or into the wider environment.

Intersection of information security and bio-automation

Advancements in automation technology combined with faster and more reliable engineering techniques have resulted in the emergence of robotic ‘cloud labs’ where digital information is transformed into DNA then expressed in some target organisms. This opens the possibility of new kinds of information security threats, which could include tampering with digital DNA sequences leading to the production of harmful organisms, and sabotaging vaccine and drug production through attacks on critical DNA sequence databases or equipment.

Over the longer term, issues identified include:

New makers disrupt pharmaceutical markets

Community bio-labs and entrepreneurial startups are customizing and sharing methods and tools for biological experiments and engineering. Combined with open business models and open source technologies, this could herald opportunities for manufacturing therapies tailored to regional diseases that multinational pharmaceutical companies might not find profitable. But this raises concerns around the potential disruption of existing manufacturing markets and raw material supply chains as well as fears about inadequate regulation, less rigorous product quality control and misuse.

Platform technologies to address emerging disease pandemics

Emerging infectious diseases—such as recent Ebola and Zika virus disease outbreaks—and potential biological weapons attacks require scalable, flexible diagnosis and treatment. New technologies could enable the rapid identification and development of vaccine candidates, and plant-based antibody production systems.

Shifting ownership models in biotechnology

The rise of off-patent, generic tools and the lowering of technical barriers for engineering biology has the potential to help those in low-resource settings, benefit from developing a sustainable bioeconomy based on local needs and priorities, particularly where new advances are made open for others to build on.

Dr Jenny Molloy comments: “One theme that emerged repeatedly was that of inequality of access to the technology and its benefits. The rise of open source, off-patent tools could enable widespread sharing of knowledge within the biological engineering field and increase access to benefits for those in developing countries.”

Professor Johnathan Napier from Rothamsted Research adds: “The challenges embodied in the Sustainable Development Goals will require all manner of ideas and innovations to deliver significant outcomes. In agriculture, we are on the cusp of new paradigms for how and what we grow, and where. Demonstrating the fairness and usefulness of such approaches is crucial to ensure public acceptance and also to delivering impact in a meaningful way.”

Dr Christian R. Boehm concludes: “As these technologies emerge and develop, we must ensure public trust and acceptance. People may be willing to accept some of the benefits, such as the shift in ownership away from big business and towards more open science, and the ability to address problems that disproportionately affect the developing world, such as food security and disease. But proceeding without the appropriate safety precautions and societal consensus—whatever the public health benefits—could damage the field for many years to come.”

The research was made possible by the Centre for the Study of Existential Risk, the Synthetic Biology Strategic Research Initiative (both at the University of Cambridge), and the Future of Humanity Institute (University of Oxford). It was based on a workshop co-funded by the Templeton World Charity Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation programme.

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

A transatlantic perspective on 20 emerging issues in biological engineering by Bonnie C Wintle, Christian R Boehm, Catherine Rhodes, Jennifer C Molloy, Piers Millett, Laura Adam, Rainer Breitling, Rob Carlson, Rocco Casagrande, Malcolm Dando, Robert Doubleday, Eric Drexler, Brett Edwards, Tom Ellis, Nicholas G Evans, Richard Hammond, Jim Haseloff, Linda Kahl, Todd Kuiken, Benjamin R Lichman, Colette A Matthewman, Johnathan A Napier, Seán S ÓhÉigeartaigh, Nicola J Patron, Edward Perello, Philip Shapira, Joyce Tait, Eriko Takano, William J Sutherland. eLife; 14 Nov 2017; DOI: 10.7554/eLife.30247

This paper is open access and the editors have included their notes to the authors and the authors’ response.

You may have noticed that I highlighted a portion of the text concerning synthetic gene drives. Coincidentally I ran across a November 16, 2017 article by Ed Yong for The Atlantic where the topic is discussed within the context of a project in New Zealand, ‘Predator Free 2050’ (Note: A link has been removed),

Until the 13th century, the only land mammals in New Zealand were bats. In this furless world, local birds evolved a docile temperament. Many of them, like the iconic kiwi and the giant kakapo parrot, lost their powers of flight. Gentle and grounded, they were easy prey for the rats, dogs, cats, stoats, weasels, and possums that were later introduced by humans. Between them, these predators devour more than 26 million chicks and eggs every year. They have already driven a quarter of the nation’s unique birds to extinction.

Many species now persist only in offshore islands where rats and their ilk have been successfully eradicated, or in small mainland sites like Zealandia where they are encircled by predator-proof fences. The songs in those sanctuaries are echoes of the New Zealand that was.

But perhaps, they also represent the New Zealand that could be.

In recent years, many of the country’s conservationists and residents have rallied behind Predator-Free 2050, an extraordinarily ambitious plan to save the country’s birds by eradicating its invasive predators. Native birds of prey will be unharmed, but Predator-Free 2050’s research strategy, which is released today, spells doom for rats, possums, and stoats (a large weasel). They are to die, every last one of them. No country, anywhere in the world, has managed such a task in an area that big. The largest island ever cleared of rats, Australia’s Macquarie Island, is just 50 square miles in size. New Zealand is 2,000 times bigger. But, the country has committed to fulfilling its ecological moonshot within three decades.

In 2014, Kevin Esvelt, a biologist at MIT, drew a Venn diagram that troubles him to this day. In it, he and his colleagues laid out several possible uses for gene drives—a nascent technology for spreading designer genes through groups of wild animals. Typically, a given gene has a 50-50 chance of being passed to the next generation. But gene drives turn that coin toss into a guarantee, allowing traits to zoom through populations in just a few generations. There are a few natural examples, but with CRISPR, scientists can deliberately engineer such drives.

Suppose you have a population of rats, roughly half of which are brown, and the other half white. Now, imagine there is a gene that affects each rat’s color. It comes in two forms, one leading to brown fur, and the other leading to white fur. A male with two brown copies mates with a female with two white copies, and all their offspring inherit one of each. Those offspring breed themselves, and the brown and white genes continue cascading through the generations in a 50-50 split. This is the usual story of inheritance. But you can subvert it with CRISPR, by programming the brown gene to cut its counterpart and replace it with another copy of itself. Now, the rats’ children are all brown-furred, as are their grandchildren, and soon the whole population is brown.

Forget fur. The same technique could spread an antimalarial gene through a mosquito population, or drought-resistance through crop plants. The applications are vast, but so are the risks. In theory, gene drives spread so quickly and relentlessly that they could rewrite an entire wild population, and once released, they would be hard to contain. If the concept of modifying the genes of organisms is already distasteful to some, gene drives magnify that distaste across national, continental, and perhaps even global scales.

These excerpts don’t do justice to this thought-provoking article. If you have time, I recommend reading it in its entirety  as it provides some insight into gene drives and, with some imagination on the reader’s part, the potential for the other technologies discussed in the report.

One last comment, I notice that Eric Drexler is cited as on the report’s authors. He’s familiar to me as K. Eric Drexler, the author of the book that popularized nanotechnology in the US and other countries, Engines of Creation (1986) .

A bioengineered robot hand with its own nervous system: machine/flesh and a job opening

A November 14, 2017 news item on phys.org announces a grant for a research project which will see engineered robot hands combined with regenerative medicine to imbue neuroprosthetic hands with the sense of touch,

The sense of touch is often taken for granted. For someone without a limb or hand, losing that sense of touch can be devastating. While highly sophisticated prostheses with complex moving fingers and joints are available to mimic almost every hand motion, they remain frustratingly difficult and unnatural for the user. This is largely because they lack the tactile experience that guides every movement. This void in sensation results in limited use or abandonment of these very expensive artificial devices. So why not make a prosthesis that can actually “feel” its environment?

That is exactly what an interdisciplinary team of scientists from Florida Atlantic University and the University of Utah School of Medicine aims to do. They are developing a first-of-its-kind bioengineered robotic hand that will grow and adapt to its environment. This “living” robot will have its own peripheral nervous system directly linking robotic sensors and actuators. FAU’s College of Engineering and Computer Science is leading the multidisciplinary team that has received a four-year, $1.3 million grant from the National Institute of Biomedical Imaging and Bioengineering of the [US] National Institutes of Health for a project titled “Virtual Neuroprosthesis: Restoring Autonomy to People Suffering from Neurotrauma.”

A November14, 2017 Florida Atlantic University (FAU) news release by Gisele Galoustian, which originated the news item, goes into more detail,

With expertise in robotics, bioengineering, behavioral science, nerve regeneration, electrophysiology, microfluidic devices, and orthopedic surgery, the research team is creating a living pathway from the robot’s touch sensation to the user’s brain to help amputees control the robotic hand. A neuroprosthesis platform will enable them to explore how neurons and behavior can work together to regenerate the sensation of touch in an artificial limb.

At the core of this project is a cutting-edge robotic hand and arm developed in the BioRobotics Laboratory in FAU’s College of Engineering and Computer Science. Just like human fingertips, the robotic hand is equipped with numerous sensory receptors that respond to changes in the environment. Controlled by a human, it can sense pressure changes, interpret the information it is receiving and interact with various objects. It adjusts its grip based on an object’s weight or fragility. But the real challenge is figuring out how to send that information back to the brain using living residual neural pathways to replace those that have been damaged or destroyed by trauma.

“When the peripheral nerve is cut or damaged, it uses the rich electrical activity that tactile receptors create to restore itself. We want to examine how the fingertip sensors can help damaged or severed nerves regenerate,” said Erik Engeberg, Ph.D., principal investigator, an associate professor in FAU’s Department of Ocean and Mechanical Engineering, and director of FAU’s BioRobotics Laboratory. “To accomplish this, we are going to directly connect these living nerves in vitro and then electrically stimulate them on a daily basis with sensors from the robotic hand to see how the nerves grow and regenerate while the hand is operated by limb-absent people.”

For the study, the neurons will not be kept in conventional petri dishes. Instead, they will be placed in  biocompatible microfluidic chambers that provide a nurturing environment mimicking the basic function of living cells. Sarah E. Du, Ph.D., co-principal investigator, an assistant professor in FAU’s Department of Ocean and Mechanical Engineering, and an expert in the emerging field of microfluidics, has developed these tiny customized artificial chambers with embedded micro-electrodes. The research team will be able to stimulate the neurons with electrical impulses from the robot’s hand to help regrowth after injury. They will morphologically and electrically measure in real-time how much neural tissue has been restored.

Jianning Wei, Ph.D., co-principal investigator, an associate professor of biomedical science in FAU’s Charles E. Schmidt College of Medicine, and an expert in neural damage and regeneration, will prepare the neurons in vitro, observe them grow and see how they fare and regenerate in the aftermath of injury. This “virtual” method will give the research team multiple opportunities to test and retest the nerves without any harm to subjects.

Using an electroencephalogram (EEG) to detect electrical activity in the brain, Emmanuelle Tognoli, Ph.D., co-principal investigator, associate research professor in FAU’s Center for Complex Systems and Brain Sciences in the Charles E. Schmidt College of Science, and an expert in electrophysiology and neural, behavioral, and cognitive sciences, will examine how the tactile information from the robotic sensors is passed onto the brain to distinguish scenarios with successful or unsuccessful functional restoration of the sense of touch. Her objective: to understand how behavior helps nerve regeneration and how this nerve regeneration helps the behavior.

Once the nerve impulses from the robot’s tactile sensors have gone through the microfluidic chamber, they are sent back to the human user manipulating the robotic hand. This is done with a special device that converts the signals coming from the microfluidic chambers into a controllable pressure at a cuff placed on the remaining portion of the amputated person’s arm. Users will know if they are squeezing the object too hard or if they are losing their grip.

Engeberg also is working with Douglas T. Hutchinson, M.D., co-principal investigator and a professor in the Department of Orthopedics at the University of Utah School of Medicine, who specializes in hand and orthopedic surgery. They are developing a set of tasks and behavioral neural indicators of performance that will ultimately reveal how to promote a healthy sensation of touch in amputees and limb-absent people using robotic devices. The research team also is seeking a post-doctoral researcher with multi-disciplinary experience to work on this breakthrough project.

Here’s more about the job opportunity from the FAU BioRobotics Laboratory job posting, (I checked on January 30, 2018 and it seems applications are still being accepted.)

Post-doctoral Opportunity

Dated Posted: Oct. 13, 2017

The BioRobotics Lab at Florida Atlantic University (FAU) invites applications for a NIH NIBIB-funded Postdoctoral position to develop a Virtual Neuroprosthesis aimed at providing a sense of touch in amputees and limb-absent people.

Candidates should have a Ph.D. in one of the following degrees: mechanical engineering, electrical engineering, biomedical engineering, bioengineering or related, with interest and/or experience in transdisciplinary work at the intersection of robotic hands, biology, and biomedical systems. Prior experience in the neural field will be considered an advantage, though not a necessity. Underrepresented minorities and women are warmly encouraged to apply.

The postdoctoral researcher will be co-advised across the department of Mechanical Engineering and the Center for Complex Systems & Brain Sciences through an interdisciplinary team whose expertise spans Robotics, Microfluidics, Behavioral and Clinical Neuroscience and Orthopedic Surgery.

The position will be for one year with a possibility of extension based on performance. Salary will be commensurate with experience and qualifications. Review of applications will begin immediately and continue until the position is filled.

The application should include:

  1. a cover letter with research interests and experiences,
  2. a CV, and
  3. names and contact information for three professional references.

Qualified candidates can contact Erik Engeberg, Ph.D., Associate Professor, in the FAU Department of Ocean and Mechanical Engineering at eengeberg@fau.edu. Please reference AcademicKeys.com in your cover letter when applying for or inquiring about this job announcement.

You can find the apply button on this page. Good luck!

A cheaper way to make artificial organs

In the quest to develop artificial organs, the University of British Columbia (UBC) is the not the first research institution that comes to my mind. It seems I may need to reevaluate now that UBC (Okanagan) has announced some work on bio-inks and artificial organs in a Sept. 12, 2017 news  release (also on EurekAlert) by Patty Wellborn,,

A new bio-ink that may support a more efficient and inexpensive fabrication of human tissues and organs has been created by researchers at UBC’s Okanagan campus.

Keekyoung Kim, an assistant professor at UBC Okanagan’s School of Engineering, says this development can accelerate advances in regenerative medicine.

Using techniques like 3D printing, scientists are creating bio-material products that function alongside living cells. These products are made using a number of biomaterials including gelatin methacrylate (GelMA), a hydrogel that can serve as a building block in bio-printing. This type of bio-material—called bio-ink—are made of living cells, but can be printed and molded into specific organ or tissue shapes.

The UBC team analyzed the physical and biological properties of three different GelMA hydrogels—porcine skin, cold-water fish skin and cold-soluble gelatin. They found that hydrogel made from cold-soluble gelatin (gelatin which dissolves without heat) was by far the best performer and a strong candidate for future 3D organ printing.

“A big drawback of conventional hydrogel is its thermal instability. Even small changes in temperature cause significant changes in its viscosity or thickness,” says Kim. “This makes it problematic for many room temperature bio-fabrication systems, which are compatible with only a narrow range of hydrogel viscosities and which must generate products that are as uniform as possible if they are to function properly.”

Kim’s team created two new hydrogels—one from fish skin, and one from cold-soluble gelatin—and compared their properties to those of porcine skin GelMA. Although fish skin GelMA had some benefits, cold-soluble GelMA was the top overall performer. Not only could it form healthy tissue scaffolds, allowing cells to successfully grow and adhere to it, but it was also thermally stable at room temperature.

The UBC team also demonstrated that cold-soluble GelMA produces consistently uniform droplets at temperatures, thus making it an excellent choice for use in 3D bio-printing.

“We hope this new bio-ink will help researchers create improved artificial organs and lead to the development of better drugs, tissue engineering and regenerative therapies,” Kim says. “The next step is to investigate whether or not cold-soluble GelMA-based tissue scaffolds are can be used long-term both in the laboratory and in real-world transplants.”

Three times cheaper than porcine skin gelatin, cold-soluble gelatin is used primarily in culinary applications.

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

Comparative study of gelatin methacrylate hydrogels from different sources for biofabrication applications by Zongjie Wang, Zhenlin Tian, Fredric Menard, and Keekyoung Kim. Biofabrication, Volume 9, Number 4 Special issue on Bioinks https://doi.org/10.1088/1758-5090/aa83cf Published 21 August 2017

© 2017 IOP Publishing Ltd

This paper is behind a paywall.

‘Origami organs’ for tissue engineering

This is a different approach to tissue engineering and its the consequence of a serendipitous accident.  From an Aug. 7, 2017 Northwestern University news release (also on EurekAlert),

Northwestern Medicine scientists and engineers have invented a range of bioactive “tissue papers” made of materials derived from organs that are thin and flexible enough to even fold into an origami bird. The new biomaterials can potentially be used to support natural hormone production in young cancer patients and aid wound healing.

The tissue papers are made from structural proteins excreted by cells that give organs their form and structure. The proteins are combined with a polymer to make the material pliable.

In the study, individual types of tissue papers were made from ovarian, uterine, kidney, liver, muscle or heart proteins obtained by processing pig and cow organs. Each tissue paper had specific cellular properties of the organ from which it was made.

The article describing the tissue paper and its function will be published Aug. 7 in the journal Advanced Functional Materials.

“This new class of biomaterials has potential for tissue engineering and regenerative medicine as well as drug discovery and therapeutics,” corresponding author Ramille Shah said. “It’s versatile and surgically friendly.”

Shah is an assistant professor of surgery at the Feinberg School of Medicine and an assistant professor of materials science and engineering at McCormick School of Engineering. She also is a member of the Simpson Querrey Institute for BioNanotechnology.

For wound healing, Shah thinks the tissue paper could provide support and the cell signaling needed to help regenerate tissue to prevent scarring and accelerate healing.

The tissue papers are made from natural organs or tissues. The cells are removed, leaving the natural structural proteins – known as the extracellular matrix – that then are dried into a powder and processed into the tissue papers. Each type of paper contains residual biochemicals and protein architecture from its original organ that can stimulate cells to behave in a certain way.

In the lab of reproductive scientist Teresa Woodruff, the tissue paper made from a bovine ovary was used to grow ovarian follicles when they were cultured in vitro. The follicles (eggs and hormone-producing cells) grown on the tissue paper produced hormones necessary for proper function and maturation.

“This could provide another option to restore normal hormone function to young cancer patients who often lose their hormone function as a result of chemotherapy and radiation,” Woodruff, a study coauthor, said.

A strip of the ovarian paper with the follicles could be implanted under the arm to restore hormone production for cancer patients or even women in menopause.

Woodruff is the director of the Oncofertility Consortium and the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg.

In addition, the tissue paper made from various organs separately supported the growth of adult human stem cells. Scientists placed human bone marrow stem cells on the tissue paper, and all the stem cells attached and multiplied over four weeks.

“That’s a good sign that the paper supports human stem cell growth,” said first author Adam Jakus, who developed the tissue papers. “It’s an indicator that once we start using tissue paper in animal models it will be biocompatible.”

The tissue papers feel and behave much like standard office paper when they are dry, Jakus said. Jakus simply stacks them in a refrigerator or a freezer. He even playfully folded them into an origami bird.

“Even when wet, the tissue papers maintain their mechanical properties and can be rolled, folded, cut and sutured to tissue,” he said.

Jakus was a Hartwell postdoctoral fellow in Shah’s lab for the study and is now chief technology officer and cofounder of the startup company Dimension Inx, LLC, which was also cofounded by Shah. The company will develop, produce and sell 3-D printable materials primarily for medical applications. The Intellectual Property is owned by Northwestern University and will be licensed to Dimension Inx.

An Accidental Spill Sparked Invention

An accidental spill of 3-D printing ink in Shah’s lab by Jakus sparked the invention of the tissue paper. Jakus was attempting to make a 3-D printable ovary ink similar to the other 3-D printable materials he previously developed to repair and regenerate bone, muscle and nerve tissue. When he went to wipe up the spill, the ovary ink had already formed a dry sheet.

“When I tried to pick it up, it felt strong,” Jakus said. “I knew right then I could make large amounts of bioactive materials from other organs. The light bulb went on in my head. I could do this with other organs.”

“It is really amazing that meat and animal by-products like a kidney, liver, heart and uterus can be transformed into paper-like biomaterials that can potentially regenerate and restore function to tissues and organs,” Jakus said. “I’ll never look at a steak or pork tenderloin the same way again.”

For those who like their news in a video,

As someone who once made baklava, that does not look like filo pastry, where an individual sheet is quite thin and rips easily. Enough said.

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

“Tissue Papers” from Organ-Specific Decellularized Extracellular Matrices by Adam E. Jakus, Monica M. Laronda, Alexandra S. Rashedi, Christina M. Robinson, Chris Lee, Sumanas W. Jordan, Kyle E. Orwig, Teresa K. Woodruff, and Ramille N. Shah. Advnaced Functional Materials DOI: 10.1002/adfm.201700992 Version of Record online: 7 AUG 2017

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

This paper is behind a paywall.

A nano fabrication technique used to create next generation heart valve

I am going to have take the researchers’ word that these somehow lead to healthy heart valve tissue,

In rotary jet spinning technology, a rotating nozzle extrudes a solution of extracellular matrix (ECM) into nanofibers that wrap themselves around heart valve-shaped mandrels. By using a series of mandrels with different sizes, the manufacturing process becomes fully scalable and is able to provide JetValves for all age groups and heart sizes. Credit: Wyss Institute at Harvard University

From a May 18, 2017 news item on ScienceDaily,

The human heart beats approximately 35 million times every year, effectively pumping blood into the circulation via four different heart valves. Unfortunately, in over four million people each year, these delicate tissues malfunction due to birth defects, age-related deteriorations, and infections, causing cardiac valve disease.

Today, clinicians use either artificial prostheses or fixed animal and cadaver-sourced tissues to replace defective valves. While these prostheses can restore the function of the heart for a while, they are associated with adverse comorbidity and wear down and need to be replaced during invasive and expensive surgeries. Moreover, in children, implanted heart valve prostheses need to be replaced even more often as they cannot grow with the child.

A team lead by Kevin Kit Parker, Ph.D. at Harvard University’s Wyss Institute for Biologically Inspired Engineering recently developed a nanofiber fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofiber network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM). To achieve this, the team used the Parker lab’s proprietary rotary jet spinning technology — in which a rotating nozzle extrudes an ECM solution into nanofibers that wrap themselves around heart valve-shaped mandrels. “Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes — much faster than possible for other regenerative prostheses,” said Parker.

A May 18,2017 Wyss Institute for Biologically Inspired Engineering news release (also on EurekAlert), which originated the news item, expands on the theme of Jetvalves,

To further develop and test the clinical potential of JetValves, Parker’s team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute. As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves. In Hoerstrup’s approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an “off-the-shelf” human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue. “In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal’s heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth. While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve’s much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimizing the number of pediatric re-operations,” said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth. The team is also working towards a GMP-grade version of their customizable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Hoerstrup is Chair and Director of the University of Zurich’s Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team’s goal is to provide customized, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.

“Achieving the goal of minimally invasive, low-cost regenerating heart valves could have tremendous impact on patients’ lives across age-, social- and geographical boundaries. Once again, our collaborative team structure that combines unique and leading expertise in bioengineering, regenerative medicine, surgical innovation and business development across the Wyss Institute and our partner institutions, makes it possible for us to advance technology development in ways not possible in a conventional academic laboratory,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

This scanning electron microscopy image shows how extracellular matrix (ECM) nanofibers generated with JetValve technology are arranged in parallel networks with physical properties comparable to those found in native heart tissue. Credit: Wyss Institute at Harvard University

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

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement by Andrew K. Capulli, Maximillian Y. Emmert, Francesco S. Pasqualini, b, Debora Kehl, Etem Caliskan, Johan U. Lind, Sean P. Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Webe, Josue A. Goss. Biomaterials Volume 133, July 2017, Pages 229–241  https://doi.org/10.1016/j.biomaterials.2017.04.033

This paper is behind a paywall.