Tag Archives: NIH

Melting body fat with a microneedle patch

For many people this may seem like a dream come true but there is a proviso. So far researchers have gotten to the in vivo testing (mice)  with no word about human clinical trials, which means it could be quite a while, assuming human clinical trials go well, before any product comes to market. With that in mind, here’s more from a Sept.15, 2017 news item on Nanowerk,

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders like obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

A Sept. 15, 2017 Columbia University Medical Center news release on EurekAlert, which originated the news item, describes the research further,

Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat–a process named browning–which can happen naturally when the body is exposed to cold temperatures–as a treatment for obesity and diabetes.

“There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology and cell biology at CUMC. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.”

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter–too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

“The nanoparticles were designed to effectively hold the drug and then gradually collapse, releasing it into nearby tissue in a sustained way instead of spreading the drug throughout the body quickly,” said patch designer and study co-leader Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The new treatment approach was tested in obese mice by loading the nanoparticles with one of two compounds known to promote browning: rosiglitazone (Avandia) or beta-adrenergic receptor agonist (CL 316243) that works well in mice but not in humans. Each mouse was given two patches–one loaded with drug-containing nanoparticles and another without drug–that were placed on either side of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were also given two empty patches.

Mice treated with either of the two drugs had a 20 percent reduction in fat on the treated side compared to the untreated side. They also had significantly lower fasting blood glucose levels than untreated mice.

Tests in normal, lean mice revealed that treatment with either of the two drugs increased the animals’ oxygen consumption (a measure of overall metabolic activity) by about 20 percent compared to untreated controls.

Genetic analyses revealed that the treated side contained more genes associated with brown fat than on the untreated side, suggesting that the observed metabolic changes and fat reduction were due to an increase in browning in the treated mice.

“Many people will no doubt be excited to learn that we may be able to offer a noninvasive alternative to liposuction for reducing love handles,” says Dr. Qiang. “What’s much more important is that our patch may provide a safe and effective means of treating obesity and related metabolic disorders such as diabetes.” [emphasis mine]

The patch has not been tested in humans. The researchers are currently studying which drugs, or combination of drugs, work best to promote localized browning and increase overall metabolism.

The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health (1UL1TR001111, R00DK97455, and P30DK063608).

Notice the emphasis on health and that the funding does not seem to be from industry (the National Institutes of Health is definitely a federal US agency but I’m not familiar with the North Carolina Translational and Clinical Sciences Institute).

Getting back to the research, here’s an animation featuring the work,

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

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment by Yuqi Zhang†, Qiongming Liu, Jicheng Yu†, Shuangjiang Yu, Jinqiang Wang, Li Qiang, and Zhen Gu. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b04348 Publication Date (Web): September 15, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

I would imagine that Qiang and his colleagues will find a number of business entities will be lining up to fund their work. While the researchers may be focused primarily on health issues, I imagine business types will be seeing dollar signs (very big ones with many zeroes).

The US White House and its Office of Science and Technology Policy (OSTP)

It’s been a while since I first wrote this but I believe this situation has not changed.

There’s some consternation regarding the US Office of Science and Technology Policy’s (OSTP) diminishing size and lack of leadership. From a July 3, 2017 article by Bob Grant for The Scientist (Note: Links have been removed),

Three OSTP staffers did leave last week, but it was because their prearranged tenures at the office had expired, according to an administration official familiar with the situation. “I saw that there were some tweets and what-not saying that it’s zero,” the official tells The Scientist. “That is not true. We have plenty of PhDs that are still on staff that are working on science. All of the work that was being done by the three who left on Friday had been transitioned to other staffers.”

At least one of the tweets that the official is referring to came from Eleanor Celeste, who announced leaving OSTP, where she was the assistant director for biomedical and forensic sciences. “science division out. mic drop,” she tweeted on Friday afternoon.

The administration official concedes that the OSTP is currently in a state of “constant flux” and at a “weird transition period” at the moment, and expects change to continue. “I’m sure that the office will look even more different in three months than it does today, than it did six months ago,” the official says.

Jeffrey Mervis in two articles for Science Magazine is able to provide more detail. From his July 11, 2017 article,

OSTP now has 35 staffers, says an administration official who declined to be named because they weren’t authorized to speak to the media. Holdren [John Holdren], who in January [2017] returned to Harvard University, says the plunge in staff levels is normal during a presidential transition. “But what’s shocking is that, this far into the new administration, the numbers haven’t gone back up.”

The office’s only political appointee is Michael Kratsios, a former aide to Trump confidant and Silicon Valley billionaire Peter Thiel. Kratsios is serving as OSTP’s deputy chief technology officer and de facto OSTP head. Eight new detailees have arrived from other agencies since the inauguration.

Although there has been no formal reorganization of OSTP, a “smaller, more collaborative staff” is now grouped around three areas—science, technology, and national security—according to the Trump aide. Three holdovers from Obama’s OSTP are leading teams focused on specific themes—Lloyd Whitman in technology, Chris Fall in national security, and Deerin Babb-Brott in environment and energy. They report to Kratsios and Ted Wackler, a career civil servant who was Holdren’s deputy chief of staff and who joined OSTP under former President George W. Bush.

“It’s a very flat structure,” says the Trump official, consistent with the administration’s view that “government should be looking for ways to do more with less.” Ultimately, the official adds, “the goal is [for OSTP] to have “probably closer to 50 [people].”

A briefing book prepared by Obama’s outgoing OSTP staff may be a small but telling indication of the office’s current status. The thick, three-ring binder, covering 100 issues, was modeled on one that Holdren received from John “Jack” Marburger, Bush’s OSTP director. “Jack did a fabulous job of laying out what OSTP does, including what reports it owes Congress, so we decided to do likewise,” Holdren says. “But nobody came [from Trump’s transition team] to collect it until a week before the inauguration.”

That person was Reed Cordish, the 43-year-old scion of billionaire real estate developer David Cordish. An English major in college, Reed Cordish was briefly a professional tennis player before joining the family business. He “spent an hour with us and took the book away,” Holdren says. “He told us, ‘This is an important operation and I’ll do my best to see that it flourishes.’ But we don’t know … whether he has the clout to make that happen.”

Cordish is now assistant to the president for intragovernmental and technology initiatives. He works in the new Office of American Innovation led by presidential son-in-law Jared Kushner. That office arranged a recent meeting with high-tech executives, and is also leading yet another White House attempt to “reinvent” government.

Trump has renewed the charter of the National Science and Technology Council, a multiagency group that carries out much of the day-to-day work of advancing the president’s science initiatives. … Still pending is the status of the President’s Council of Advisors on Science and Technology [emphasis mine], a body of eminent scientists and high-tech industry leaders that went out of business at the end of the Obama administration.

Mervis’ July 12, 2017 article is in the form of a Q&A (question and answer) session with the previously mentioned John Holdren, director of the OSTP in Barack Obama’s administration,

Q: Why did you have such a large staff?

A: One reason was to cover the bases. We knew from the start that the Obama administration thought cybersecurity would be an important issue and we needed to be capable in that space. We also knew we needed people who were capable in climate change, in science and technology for economic recovery and job creation and sustained economic growth, and people who knew about advanced manufacturing and nanotechnology and biotechnology.

We also recruited to carry out specific initiatives, like in precision medicine, or combating antibiotic resistance, or the BRAIN [Brain Research through Advancing Innovative Neurotechnologies] initiative. Most of the work will go on in the departments and agencies, but you need someone to oversee it.

The reason we ended up with 135 people at our peak, which was twice the number during its previous peak in the Clinton administration’s second term, was that this president was so interested in knowing what science could do to advance his agenda, on economic recovery, or energy and climate change, or national intelligence. He got it. He didn’t need to be tutored on why science and technology matters.

I feel I’ve been given undue credit for [Obama] being a science geek. It wasn’t me. He came that way. He was constantly asking what we could do to move the needle. When the first flu epidemic, H1N1, came along, the president immediately turned to me and said, “OK, I want [the President’s Council of Advisors on Science and Technology] to look in depth on this, and OSTP, and NIH [National Institutes of Health], and [the Centers for Disease Control and Prevention].” And he told us to coordinate my effort on this stuff—inform me on what can be done and assemble the relevant experts. It was the same with Ebola, with the Macondo oil spill in the Gulf, with Fukushima, where the United States stepped up to work with the Japanese.

It’s not that we had all the expertise. But our job was to reach out to those who did have the relevant expertise.

Q: OSTP now has 35 people. What does that level of staffing say to you?

A: I have to laugh.

Q: Why?

A: When I left, on 19 January [2017], we were down to 30 people. And a substantial fraction of the 30 were people who, in a sense, keep the lights on. They were the OSTP general counsel and deputy counsel, the security officer and deputy, the budget folks, the accounting folks, the executive director of NSTC [National Science and Technology Council].

There are some scientists left, and there are some scientists there still. But on 30 June the last scientist in the science division left.

Somebody said OSTP has shut down. But that’s not quite it. There was no formal decision to shut anything down. But they did not renew the contract of the last remaining science folks in the science division.

I saw somebody say, “Well, we still have some Ph.D.s left.” And that’s undoubtedly true. There are still some science Ph.D.s left in the national security and international affairs division. But because [OSTP] is headless, they have no direct connection to the president and his top advisers.

I don’t want to disparage the top people there. The top people there now are Michael Kratsios, who they named the deputy chief technology officer, and Ted Wackler, who was my deputy chief of staff and who was [former OSTP Director] Jack Marberger’s deputy, and who I kept because he’s a fabulously effective manager. And I believe that they are doing everything they can to make sure that OSTP, at the very least, does the things it has to do. … But right now I think OSTP is just hanging on.

Q: Why did some people choose to stay on?

A: A large portion of OSTP staff are borrowed from other agencies, and because the White House is the White House, we get the people we need. These are dedicated folks who want to get the job done. They want to see science and technology applied to advance the public interest. And they were willing to stay and do their best despite the considerable uncertainty about their future.

But again, most of the detailees, and the reason we went from 135 to 30 almost overnight, is that it’s pretty standard for the detailees to go back to their home agencies and wait for the next administration to decide what set of detailees it wants to advance their objects.

So there’s nothing shocking that most of the detailees went back to their home agencies. The people who stayed are mostly employed directly by OSTP. What’s shocking is that, this far into the new administration, that number hasn’t gone back up. That is, they have only five more people than they had on January 20 [2017].

As I had been wondering about the OSTP and about the President’s Council of Advisors on Science and Technology (PCAST), it was good to get an update.

On a more parochial note, we in Canada are still waiting for an announcement about who our Chief Science Advisor might be.

Hopes for nanocellulose in the fields of medicine and green manufacturing

Initially this seemed like an essay extolling the possibilities for nanocellulose but it is also a research announcement. From a Nov. 7, 2016 news item on Nanowerk,

What if you could take one of the most abundant natural materials on earth and harness its strength to lighten the heaviest of objects, to replace synthetic materials, or use it in scaffolding to grow bone, in a fast-growing area of science in oral health care?

This all might be possible with cellulose nanocrystals, the molecular matter of all plant life. As industrial filler material, they can be blended with plastics and other synthetics. They are as strong as steel, tough as glass, lightweight, and green.

“Plastics are currently reinforced with fillers made of steel, carbon, Kevlar, or glass. There is an increasing demand in manufacturing for sustainable materials that are lightweight and strong to replace these fillers,” said Douglas M. Fox, associate professor of chemistry at American University.
“Cellulose nanocrystals are an environmentally friendly filler. If there comes a time that they’re used widely in manufacturing, cellulose nanocrystals will lessen the weight of materials, which will reduce energy.”

A Nov. 7, 2016 American University news release on EurekAlert, which originated the news item, continues into the research,

Fox has submitted a patent for his work with cellulose nanocrystals, which involves a simple, scalable method to improve their performance. Published results of his method can be found in the chemistry journal ACS Applied Materials and Interfaces. Fox’s method could be used as a biomaterial and for applications in transportation, infrastructure and wind turbines.

The power of cellulose

Cellulose gives stems, leaves and other organic material in the natural world their strength. That strength already has been harnessed for use in many commercial materials. At the nano-level, cellulose fibers can be broken down into tiny crystals, particles smaller than ten millionths of a meter. Deriving cellulose from natural sources such as wood, tunicate (ocean-dwelling sea cucumbers) and certain kinds of bacteria, researchers prepare crystals of different sizes and strengths.

For all of the industry potential, hurdles abound. As nanocellulose disperses within plastic, scientists must find the sweet spot: the right amount of nanoparticle-matrix interaction that yields the strongest, lightest property. Fox overcame four main barriers by altering the surface chemistry of nanocrystals with a simple process of ion exchange. Ion exchange reduces water absorption (cellulose composites lose their strength if they absorb water); increases the temperature at which the nanocrystals decompose (needed to blend with plastics); reduces clumping; and improves re-dispersal after the crystals dry.

Cell growth

Cellulose nanocrystals as a biomaterial is yet another commercial prospect. In dental regenerative medicine, restoring sufficient bone volume is needed to support a patient’s teeth or dental implants. Researchers at the National Institute of Standards and Technology [NIST], through an agreement with the National Institute of Dental and Craniofacial Research of the National Institutes of Health, are looking for an improved clinical approach that would regrow a patient’s bone. When researchers experimented with Fox’s modified nanocrystals, they were able to disperse the nanocrystals in scaffolds for dental regenerative medicine purposes.

“When we cultivated cells on the cellulose nanocrystal-based scaffolds, preliminary results showed remarkable potential of the scaffolds for both their mechanical properties and the biological response. This suggests that scaffolds with appropriate cellulose nanocrystal concentrations are a promising approach for bone regeneration,” said Martin Chiang, team leader for NIST’s Biomaterials for Oral Health Project.

Another collaboration Fox has is with Georgia Institute of Technology and Owens Corning, a company specializing in fiberglass insulation and composites, to research the benefits to replace glass-reinforced plastic used in airplanes, cars and wind turbines. He also is working with Vireo Advisors and NIST to characterize the health and safety of cellulose nanocrystals and nanofibers.

“As we continue to show these nanomaterials are safe, and make it easier to disperse them into a variety of materials, we get closer to utilizing nature’s chemically resistant, strong, and most abundant polymer in everyday products,” Fox said.

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

Simultaneously Tailoring Surface Energies and Thermal Stabilities of Cellulose Nanocrystals Using Ion Exchange: Effects on Polymer Composite Properties for Transportation, Infrastructure, and Renewable Energy Applications by Douglas M. Fox, Rebeca S. Rodriguez, Mackenzie N. Devilbiss, Jeremiah Woodcock, Chelsea S. Davis, Robert Sinko, Sinan Keten, and Jeffrey W. Gilman. ACS Appl. Mater. Interfaces, 2016, 8 (40), pp 27270–27281 DOI: 10.1021/acsami.6b06083 Publication Date (Web): September 14, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Canada has a nanotechnology industry? and an overview of the US situation

It’s always interesting to get some insight into how someone else sees the nanotechnology effort in Canada.

First, there have been two basic approaches internationally. Some countries have chosen to fund nanotechnology/nanoscience research through a national initiative/project/council/etc. Notably the US, the UK, China, and Russia, amongst others, have followed this model. For example, the US National Nanotechnology Initiative (NNI)  (a type of hub for research, communication, and commercialization efforts) has been awarded a portion of the US budget every year since 2000. The money is then disbursed through the National Science Foundation.

Canada and its nanotechnology industry efforts

By contrast, Canada has no such line item in its national budget. There is a National Institute of Nanotechnology (NINT) but it is one of many institutes that help make up Canada’s National Research Council. I’m not sure if this is still true but when it was first founded, NINT was funded in part by the federal government and in part by the province of Alberta where it is located (specifically, in Edmonton at the University of Alberta). They claim the organization has grown since its early days although it looks like it’s been shrinking. Perhaps some organizational shuffles? In any event, support for the Canadian nanotechnology efforts are more provincial than federal. Alberta (NINT and other agencies) and Québec (NanoQuébec, a provincially funded nano effort) are the standouts, with Ontario (nano Ontario, a self-organized not-for-profit group) following closely. The scene in Canada has always seemed fragmented in comparison to the countries that have nanotechnology ‘hubs’.

Patrick Johnson in a Dec. 22, 2015 article for Geopolitical Monitor offers a view which provides an overview of nanotechnology in the US and Canada,  adds to the perspective offered here, and, at times, challenges it (Note: A link has been added),

The term ‘nanotechnology’ entered into the public vernacular quite suddenly around the turn of the century, right around the same time that, when announcing the US National Nanotechnology Initiative (NNI) in 2001 [2000; see the American Association for the Advancement of Science webpage on Historical Trends in Federal R&D, scroll down to the National Nanotechnology Initiative and click on the Jpg or Excel links], President Bill Clinton declared that it would one day build materials stronger than steel, detect cancer at its inception, and store the vast records of the Library of Congress in a device the size of a sugar cube. The world of science fiction took matters even further. In his 2002 book Prey, Michael Creighton [Michael Crichton; see Wikipedia entry] wrote of a cloud of self-replicating nanorobots [also known as, nanobots or self-assemblers] that terrorize the good people of Nevada when a science experiment goes terribly wrong.

Back then the hype was palpable. Federal money was funneled to promising nanotech projects as not to fall behind in the race to master this new frontier of science. And industry analysts began to shoot for the moon in their projections. The National Science Foundation famously predicted that the nanotechnology industry would be worth $1 trillion by the year 2015.

Well here we are in 2015 and the nanotechnology market was worth around $26 billion in [sic] last year, and there hasn’t even been one case of a murderous swarm of nanomachines terrorizing the American heartland. [emphasis mine]

Is this a failure of vision? No. If anything it’s only a failure of timing.

The nanotechnology industry is still well on its way to accomplishing the goals set out at the founding of the NNI, goals which at the time sounded utterly quixotic, and this fact is increasingly being reflected in year-on-year growth numbers. In other words, nanotechnology is still a game-changer in global innovation, it’s just taking a little longer than first expected.

The Canadian Connection

Although the Canadian government is not among the world’s top spenders on nanotechnology research, the industry still represents a bright spot in the future of the Canadian economy. The public-private engine [emphasis mine] at the center of Canada’s nanotech industry, the National Institute for Nanotechnology (NINT), was founded in 2001 with the stated goal of “increasing the competitiveness of Canadian companies; creating technology solutions to meet the needs of society; expanding training programs for researchers and entrepreneurs; and enhancing Canada’s stature in the world of nanotechnology.” This ambitious mandate that NINT set out for itself was to be accomplished over the course of two broad stages: first a ‘seeding’ phase of attracting promising personnel and coordinating basic research, and the then a ‘harvesting’ phase of putting the resulting nanotechnologies to the service of Canadian industry.

Recent developments in Canadian nanotechnology [emphasis mine] show that we have already entered that second stage where the concept of nanotechnology transitions from hopeful hypothetical to real-world economic driver

I’d dearly like to know which recent developments indicate Canada’s industry has entered a serious commercialization phase. (It’s one of the shortcomings of our effort that communication is not well supported.) As well, I’d like to know more about the  “… public-private engine at the center of Canada’s nanotech industry …” as Johnson seems to be referring to the NINT, which is jointly funded (I believe) by the federal government and the province of Alberta. There is no mention of private funding on their National Research Council webpage but it does include the University of Alberta as a major supporter.

I am intrigued and I hope there is more information to come.

US and its nanotechnology industry efforts

Dr. Ambika Bumb has written a Dec. 23, 2015 article for Tech Crunch which reflects on her experience as a researcher and entrepreneur in the context of the US NNI effort and includes a plea for future NNI funding [Note: One link added and one link removed],

Indeed, I am fortunate to be the CEO of a nanomedicine technology developer that extends the hands of doctors and scientists to the cellular and molecular level.

The first seeds of interest in bringing effective nano-tools into the hands of doctors and patients were planted in my mind when I did undergrad research at Georgia Tech.  That initial interest led to me pursuing a PhD at Oxford University to develop a tri-modal nanoparticle for imaging a variety of diseases ranging from cancers to autoimmune disorders.

My graduate research only served to increase my curiosity so I then did a pair of post-doctoral fellowships at the National Cancer Institute and the National Heart Lung and Blood Institute.  When it seemed that I was a shoe-in for a life-long academic career, our technology garnered much attention and I found myself in the Bay Area founding the now award-winning Bikanta [bikanta.com].

Through the National Nanotechnology Initiative (NNI) and Nanotechnology Research and Development Act of 2003, our federal government has invested $20 billion in nanoresearch in the past 13 years.  The return on that investment has resulted in 628 agency‐to‐agency collaborations, hundreds of thousands of publications, and more than $1 trillion in revenue generated from nano‐enabled products. [emphasis mine]

Given that medical innovations take a minimum of 10 years before they translate into a clinical product, already realizing a 50X return is an astounding achievement.  Slowing down would be counter-intuitive from an academic and business perspective.

Yet, that is what is happening.  Federal funding peaked half a decade ago in 2010.  [emphasis mine] NNI investments went from $1.58B in 2010 to $1.170B in 2015 (in constant dollars), a 26% drop.  The number of nano-related papers published in the US were roughly 25 thousand in 2013, while the EU and China produced 33 and 35 thousand, respectively.

History has shown repeatedly how the United States has lost an early competitive advantage in developing high‐value technologies to international competition when commercialization infrastructure was not adequately supported.

Examples include semiconductors, advanced batteries for vehicles, and cement‐based construction materials, all of which were originally developed in the United States, but are now manufactured elsewhere.

It is now time for a second era – NNI 2.0.  A return to higher and sustained investment, the purpose of NNI 2.0 should be not just foundational research but also necessary support for rapid commercialization of nanotechnology. The translation of bench science into commercial reality requires the partnership of academic, industrial, federal, and philanthropic players.

I’m not sure why there’s a difference between Johnson’s ” … worth around $26 billion in [sic] last year …] and Bumb’s “… return on that investment has resulted … more than $1 trillion in revenue generated from nano‐enabled products.” I do know there is some controversy as to what should or should not be included when estimating the value of the ‘nanotechnology enterprise’, for example, products that are only possible due to nanotechnology as opposed to products that already existed, such as golf clubs, but are enhanced by nanotechnology.

Bumb goes on to provide a specific example from her own experience to support the plea,

When I moved from the renowned NIH [US National Institutes of Health] on the east coast to the west coast to start Bikanta, one of the highest priority concerns was how we were going to develop nanodiamond technology without access to high-end characterization instrumentation to analyze the quality of our material.  Purchasing all that equipment was not financially viable or even wise for a startup.

We were extremely lucky because our proposal was accepted by the Molecular Foundry, one of five DOE [US Department of Energy]-funded nanoscience user facilities.  While the Foundry primarily facilitates basic nanoscience projects from academic and national laboratory users, Fortune 500 companies and startups like ours also take advantage of its capabilities to answer fundamental questions and conduct proof of concept studies (~10%).

Disregarding the dynamic intellectual community for a minute, there is probably more than $150M worth of instrumentation at the Foundry.  An early startup would never be able to dream of raising a first round that large.

One of the factors of Bikanta’s success is that the Molecular Foundry enabled us to make tremendous strides in R&D in just months instead of years.  More user facilities, incubator centers, and funding for commercializing nanotech are greatly needed.

Final comments

I have to thank Dr. Bumb for pointing out that 2010 was the peak for NNI funding (see the American Association for the Advancement of Science webpage on Historical Trends in Federal R&D, scroll down to the National Nanotechnology Initiative and click on the Jpg or Excel links). I erroneously believed (although I don’t appear to have written up my belief; if you find any such statement, please let me know so I can correct it) that the 2015 US budget was the first time the NNI experienced a drop in funding.

While I found Johnson’s article interesting I wasn’t able to determine the source for his numbers and some of his material had errors that can be identified immediately, e.g., Michael Creighton instead of Michael Crichton.

North Carolina universities go beyond organ-on-a-chip

The researchers in the North Carolina universities involved in this project have high hopes according to an Oct. 9, 2015 news item on Nanowerk,

A team of researchers from the University of North Carolina at Chapel Hill and NC State University has received a $5.3 million, five-year Transformative Research (R01) Award from the National Institutes of Health (NIH) to create fully functioning versions of the human gut that fit on a chip the size of a dime.

Such “organs-on-a-chip” have become vital for biomedical research, as researchers seek alternatives to animal models for drug discovery and testing. The new grant will fund a technology that represents a major step forward for the field, overcoming limitations that have mired other efforts.

The technology will use primary cells derived directly from human biopsies, which are known to provide more relevant results than the immortalized cell lines used in current approaches. In addition, the device will sculpt these cells into the sophisticated architecture of the gut, rather than the disorganized ball of cells that are created in other miniature organ systems.

“We are building a device that goes far beyond the organ-on-a-chip,” said Nancy L. Allbritton, MD, PhD, professor and chair of the UNC-NC State joint department of biomedical engineering and one of four principle investigators on the NIH grant. “We call it a ‘simulacrum,’ [emphasis mine] a term used in science fiction to describe a duplicate. The idea is to create something that is indistinguishable from your own gut.”

I’ve come across the term ‘simulacrum’ in relation to philosophy so it’s a bit of a surprise to find it in a news release about an organ-on-a-chip where it seems to have been redefined somewhat. Here’s more from the Simulacrum entry on Wikipedia (Note: Links have been removed),

A simulacrum (plural: simulacra from Latin: simulacrum, which means “likeness, similarity”), is a representation or imitation of a person or thing.[1] The word was first recorded in the English language in the late 16th century, used to describe a representation, such as a statue or a painting, especially of a god. By the late 19th century, it had gathered a secondary association of inferiority: an image without the substance or qualities of the original.[2] Philosopher Fredric Jameson offers photorealism as an example of artistic simulacrum, where a painting is sometimes created by copying a photograph that is itself a copy of the real.[3] Other art forms that play with simulacra include trompe-l’œil,[4] pop art, Italian neorealism, and French New Wave.[3]

Philosophy

The simulacrum has long been of interest to philosophers. In his Sophist, Plato speaks of two kinds of image making. The first is a faithful reproduction, attempted to copy precisely the original. The second is intentionally distorted in order to make the copy appear correct to viewers. He gives the example of Greek statuary, which was crafted larger on the top than on the bottom so that viewers on the ground would see it correctly. If they could view it in scale, they would realize it was malformed. This example from the visual arts serves as a metaphor for the philosophical arts and the tendency of some philosophers to distort truth so that it appears accurate unless viewed from the proper angle.[5] Nietzsche addresses the concept of simulacrum (but does not use the term) in the Twilight of the Idols, suggesting that most philosophers, by ignoring the reliable input of their senses and resorting to the constructs of language and reason, arrive at a distorted copy of reality.[6]

Postmodernist French social theorist Jean Baudrillard argues that a simulacrum is not a copy of the real, but becomes truth in its own right: the hyperreal. Where Plato saw two types of representation—faithful and intentionally distorted (simulacrum)—Baudrillard sees four: (1) basic reflection of reality; (2) perversion of reality; (3) pretence of reality (where there is no model); and (4) simulacrum, which “bears no relation to any reality whatsoever”.[7] In Baudrillard’s concept, like Nietzsche’s, simulacra are perceived as negative, but another modern philosopher who addressed the topic, Gilles Deleuze, takes a different view, seeing simulacra as the avenue by which an accepted ideal or “privileged position” could be “challenged and overturned”.[8] Deleuze defines simulacra as “those systems in which different relates to different by means of difference itself. What is essential is that we find in these systems no prior identity, no internal resemblance”.[9]

Getting back to the proposed research, an Oct. (?), 2015 University of North Carolina news release, which originated the news item, describes the proposed work in more detail,

Allbritton is an expert at microfabrication and microengineering. Also on the team are intestinal stem cell expert Scott T. Magness, associate professor of medicine, biomedical engineering, and cell and molecular physiology in the UNC School of Medicine; microbiome expert Scott Bultman, associate professor of genetics in the UNC School of Medicine; and bioinformatics expert Shawn Gomez, associate professor of biomedical engineering in UNC’s College of Arts and Sciences and NC State.

The impetus for the “organ-on-chip” movement comes largely from the failings of the pharmaceutical industry. For just a single drug to go through the discovery, testing, and approval process can take as many as 15 years and as much as $5 billion dollars. Animal models are expensive to work with and often don’t respond to drugs and diseases the same way humans do. Human cells grown in flat sheets on Petri dishes are also a poor proxy. Three-dimensional “organoids” are an improvement, but these hollow balls are made of a mishmash of cells that doesn’t accurately mimic the structure and function of the real organ.

Basically, the human gut is a 30-foot long hollow tube made up of a continuous single-layer of specialized cells. Regenerative stem cells reside deep inside millions of small pits or “crypts” along the tube, and mature differentiated cells are linked to the pits and live further out toward the surface. The gut also contains trillions of microbes, which are estimated to outnumber human cells by ten to one. These diverse microbial communities – collectively known as the microbiota – process toxins and pharmaceuticals, stimulate immunity, and even release hormones to impact behavior.

To create a dime-sized version of this complex microenvironment, the UNC-NC State team borrowed fabrication technologies from the electronics and microfluidics world. The device is composed of a polymer base containing an array of imprinted or shaped “hydrogels,” a mesh of molecules that can absorb water like a sponge. These hydrogels are specifically engineered to provide the structural support and biochemical cues for growing cells from the gut. Plugged into the device will be various kinds of plumbing that bring in chemicals, fluids, and gases to provide cues that tell the cells how and where to differentiate and grow. For example, the researchers will engineer a steep oxygen gradient into the device that will enable oxygen-loving human cells and anaerobic microbes to coexist in close proximity.

“The underlying concept – to simply grow a piece of human tissue in a dish – doesn’t seem that groundbreaking,” said Magness. “We have been doing that for a long time with cancer cells, but those efforts do not replicate human physiology. Using native stem cells from the small intestine or colon, we can now develop gut tissue layers in a dish that contains stem cells and all the differentiated cells of the gut. That is the thing stem cell biologists and engineers have been shooting for, to make real tissue behave properly in a dish to create better models for drug screening and cell-based therapies. With this work, we made a big leap toward that goal.”

Right now, the team has a working prototype that can physically and chemically guide mouse intestinal stem cells into the appropriate structure and function of the gut. For several years, Magness has been isolating and banking human stem cells from samples from patients undergoing routine colonoscopies at UNC Hospitals.

As part of the grant, he will work with the rest of the team to apply these stem cells to the new device and create “simulacra” that are representative of each patient’s individual gut. The approach will enable researchers to explore in a personalized way how both the human and microbial cells of the gut behave during healthy and diseased states.

“Having a system like this will advance microbiota research tremendously,” said Bultman. “Right now microbiota studies involve taking samples, doing sequencing, and then compiling an inventory of all the microbes in the disease cases and healthy controls. These studies just draw associations, so it is difficult to glean cause and effect. This device will enable us to probe the microbiota, and gain a better understanding of whether changes in these microbial communities are the cause or the consequence of disease.”

I wish them good luck with their work and to end on another interesting note, the concept of organs-on-a-chip won a design award. From a June 22, 2015 article by Oliver Wainwright for the Guardian (Note: Links have been removed),

Meet the Lung-on-a-chip, a simulation of the biological processes inside the human lung, developed by the Wyss Institute for Biologically Inspired Engineering at Harvard University – and now crowned Design of the Year by London’s Design Museum.

Lined with living human cells, the “organs-on-chips” mimic the tissue structures and mechanical motions of human organs, promising to accelerate drug discovery, decrease development costs and potentially usher in a future of personalised medicine.

“This is the epitome of design innovation,” says Paola Antonelli, design curator at New York’s Museum of Modern Art [MOMA], who nominated the project for the award and recently acquired organs-on-chips for MoMA’s permanent collection. “Removing some of the pitfalls of human and animal testing means, theoretically, that drug trials could be conducted faster and their viable results disseminated more quickly.”

Whodathunkit? (Tor those unfamiliar with slang written in this form: Who would have thought it?)

A pragmatic approach to alternatives to animal testing

Retitled and cross-posted from the June 30, 2015 posting (Testing times: the future of animal alternatives) on the International Innovation blog (a CORDIS-listed project dissemination partner for FP7 and H2020 projects).

Maryse de la Giroday explains how emerging innovations can provide much-needed alternatives to animal testing. She also shares highlights of the 9th World Congress on Alternatives to Animal Testing.

‘Guinea pigging’ is the practice of testing drugs that have passed in vitro and in vivo tests on healthy humans in a Phase I clinical trial. In fact, healthy humans can make quite a bit of money as guinea pigs. The practice is sufficiently well-entrenched that there is a magazine, Guinea Pig Zero, devoted to professionals. While most participants anticipate some unpleasant side effects, guinea pigging can sometimes be a dangerous ‘profession’.

HARMFUL TO HEALTH

One infamous incident highlighting the dangers of guinea pigging occurred in 2006 at Northwick Park Hospital outside London. Volunteers were offered £2,000 to participate in a Phase I clinical trial to test a prospective treatment – a monoclonal antibody designed for rheumatoid arthritis and multiple sclerosis. The drug, called TGN1412, caused catastrophic systemic organ failure in participants. All six individuals receiving the drug required hospital treatment. One participant reportedly underwent amputation of fingers and toes. Another reacted with symptoms comparable to John Merrick, the Elephant Man.

The root of the disaster lay in subtle immune system differences between humans and cynomolgus monkeys – the model animal tested prior to the clinical trial. The drug was designed for the CD28 receptor on T cells. The monkeys’ receptors closely resemble those found in humans. However, unlike these monkeys, humans have other immune cells that carry CD28. The trial participants received a starting dosage that was 0.2 per cent of what the monkeys received in their final tests, but failure to take these additional receptors into account meant a dosage that was supposed to occupy 10 per cent of the available CD28 receptors instead occupied 90 per cent. After the event, a Russian inventor purchased the commercial rights to the drug and renamed it TAB08. It has been further developed by Russian company, TheraMAB, and TAB08 is reportedly in Phase II clinical trials.

HUMAN-ON-A-CHIP AND ORGANOID PROJECTS

While animal testing has been a powerful and useful tool for determining safe usage for pharmaceuticals and other types of chemicals, it is also a cruel and imperfect practice. Moreover, it typically only predicts 30-60 per cent of human responses to new drugs. Nanotechnology and other emerging innovations present possibilities for reducing, and in some cases eliminating, the use of animal models.

People for the Ethical Treatment of Animals (PETA), still better known for its publicity stunts, maintains a webpage outlining a number of alternatives including in silico testing (computer modelling), and, perhaps most interestingly, human-on-a-chip and organoid (tissue engineering) projects.

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

Another interesting alternative for animal testing is organoids – a feature in regenerative medicine that can function as test sites. Engineers based at Cornell University recently published a paper on their functional, synthetic immune organ. Inspired by the lymph node, the organoid is comprised of gelatin-based biomaterials, which are reinforced with silicate nanoparticles (to keep the tissue from melting when reaching body temperature) and seeded with cells allowing it to mimic the anatomical microenvironment of a lymphatic node. It behaves like its inspiration converting B cells to germinal centres which activate, mature and mutate antibody genes when the body is under attack. The engineers claim to be able to control the immune response and to outperform 2D cultures with their 3D organoid. If the results are reproducible, the organoid could be used to develop new therapeutics.

Maryse de la Giroday is a science communications consultant and writer.

Full disclosure: Maryse de la Giroday received transportation and accommodation for the 9th World Congress on Alternatives to Animal Testing from SEURAT-1, a European Union project, making scientific inquiries to facilitate the transition to animal testing alternatives, where possible.

ETA July 1, 2015: I would like to acknowledge more sources for the information in this article,

Sources:

The guinea pigging term, the ‘professional aspect, the Northwick Park story, and the Guinea Pig Zero magazine can be found in Carl Elliot’s excellent 2006 story titled ‘Guinea-Pigging’ for New Yorker magazine.

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

Information about the drug used in the Northwick Park Hospital disaster, the sale of the rights to a Russian inventor, and the June 2015 date for the current Phase II clinical trials were found in this Wikipedia essay titled, TGN 1412.

http://en.wikipedia.org/wiki/TGN1412

Additional information about the renamed drug, TAB08 and its Phase II clinical trials was found on (a) a US government website for information on clinical trials, (b) in a Dec. 2014 (?) TheraMAB  advertisement in a Nature group magazine and a Jan. 2014 press release,

https://www.clinicaltrials.gov/ct2/show/NCT01990157?term=TAB08_RA01&rank=1

http://www.theramab.ru/TheraMAB_NAture.pdf

http://theramab.ru/en/news/phase_II

An April 2015 article (Experimental drug that injured UK volunteers resumes in human trials) by Owen Dyer for the British Medical Journal also mentioned the 2015 TheraMab Phase II clinical trials and provided information about the information about Macaque (cynomolgus) monkey tests.

http://www.bmj.com.proxy.lib.sfu.ca/content/350/bmj.h1831

BMJ 2015; 350 doi: http://dx.doi.org.proxy.lib.sfu.ca/10.1136/bmj.h1831 (Published 02 April 2015) Cite this as: BMJ 2015;350:h1831

A 2009 study by Christopher Horvath and Mark Milton somewhat contradicts the Dyer article’s contention that a species Macaque monkey was used as an animal model. (As the Dyer article is more recent and the Horvath/Milton analysis is more complex covering TGN 1412 in the context of other MAB drugs and their precursor tests along with specific TGN 1412 tests, I opted for the simple description.)

The TeGenero Incident [another name for the Northwick Park Accident] and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? by Christopher J. Horvath and Mark N. Milton. Published online before print February 24, 2009, doi: 10.1177/0192623309332986 Toxicol Pathol April 2009 vol. 37 no. 3 372-383

http://tpx.sagepub.com/content/37/3/372.full

Philippa Roxbuy’s May 24, 2013 BBC news online article provided confirmation and an additional detail or two about the Northwick Park Hospital accident. It notes that other models, in addition to animal models, are being developed.

http://www.bbc.com/news/health-22556736

Anne Ju’s excellent June 10,2015 news release about the Cornell University organoid (synthetic immune organ) project was very helpful.

http://www.news.cornell.edu/stories/2015/06/engineers-synthetic-immune-organ-produces-antibodies

There will also be a magazine article in International Innovation, which will differ somewhat from the blog posting, due to editorial style and other requirements.

ETA July 22, 2015: I now have a link to the magazine article.

Nanomedicine living up to its promise?

Michael Berger has written a March 10, 2015 Nanowerk spotlight article reviewing nanomedicine’s  progress or lack thereof (Note: Links have been removed),

In early 2003, the European Science Foundation launched its Scientific Forward Look on Nanomedicine, a foresight study (report here ;pdf) and in 2004, the U.S. National Institute[s] of Health (NIH) published its Roadmap (now Common Fund) of the Nanomedicine Initiative. This program began in 2005 with a national network of eight Nanomedicine Development Centers. Now, in the second half of this 10-year program, the four centers best positioned to effectively apply their findings to translational studies were selected to continue receiving support.

A generally accepted definition of nanomedicine refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve.

Much of Berger’s article is based on Subbu Venkatraman’s, Director of the NTU (Nanyang Technological University)-Northwestern Nanomedicine Institute in Singapore, paper, Has nanomedicine lived up to its promise?, 2014 Nanotechnology 25 372501 doi:10.1088/0957-4484/25/37/372501 (Note: Links have been removed),

… Historically, the approval of Doxil as the very first nanotherapeutic product in 1995 is generally regarded as the dawn of nanomedicine for human use. Since then, research activity in this area has been frenetic, with, for example, 2000 patents being generated in 2003, in addition to 1200 papers [2]. In the same time period, a total of 207 companies were involved in developing nanomedicinal products in diagnostics, imaging, drug delivery and implants. About 38 products loosely classified as nanomedicine products were in fact approved by 2004. Out of these, however, a number of products (five in all) were based on PEG-ylated proteins, which strictly speaking, are not so much nanomedicine products as molecular therapeutics. Nevertheless, the promise of nanomedicine was being translated into funding for small companies, and into clinical success, so that by 2013, the number of approved products had reached 54 in all, with another 150 in various stages of clinical trials [3]. The number of companies and institutions had risen to 241 (including research centres that were working on nanomedicine). A PubMed search on articles relating to nanomedicine shows 7400 hits over 10 years, of which 1874 were published in 2013 alone. Similarly, the US patent office database shows 409 patents (since 1976) that were granted in nanomedicine, with another 679 applications awaiting approval. So judging by research activity and funding the field of nanomedicine has been very fertile; however, when we use the yardstick of clinical success and paradigm shifts in treatment, the results appear more modest.

Both Berger’s spotlight article and Venkatraman’s review provide interesting reading and neither is especially long.

Nanotechnology, tobacco plants, and the Ebola virus

Before presenting information about the current Ebola crisis and issues with vaccines and curatives, here’s a description of the disease from its Wikipedia entry,

Ebola virus disease (EVD) or Ebola hemorrhagic fever (EHF) is a disease of humans and other primates caused by an ebola virus. Symptoms start two days to three weeks after contracting the virus, with a fever, sore throat, muscle pain, and headaches. Typically nausea, vomiting, and diarrhea follow, along with decreased functioning of the liver and kidneys. Around this time, affected people may begin to bleed both within the body and externally. [1]

As for the current crisis in countries situated on the west coast of the African continent, there’s this from an Aug. 14, 2014 news item on ScienceDaily,

The outbreak of Ebola virus disease that has claimed more than 1,000 lives in West Africa this year poses a serious, ongoing threat to that region: the spread to capital cities and Nigeria — Africa’s most populous nation — presents new challenges for healthcare professionals. The situation has garnered significant attention and fear around the world, but proven public health measures and sharpened clinical vigilance will contain the epidemic and thwart a global spread, according to a new commentary by Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Dr. Fauci’s Aug. 13, 2014 commentary (open access) in the New England Journal of Medicine provides more detail (Note: A link has been removed),

An outbreak of Ebola virus disease (EVD) has jolted West Africa, claiming more than 1000 lives since the virus emerged in Guinea in early 2014 (see figure) Ebola Virus Cases and Deaths in West Africa (Guinea, Liberia, Nigeria, and Sierra Leone), as of August 11, 2014 (Panel A), and Over Time (Panel B).). The rapidly increasing numbers of cases in the African countries of Guinea, Liberia, and Sierra Leone have had public health authorities on high alert throughout the spring and summer. More recent events including the spread of EVD to Nigeria (Africa’s most populous country) and the recent evacuation to the United States of two American health care workers with EVD have captivated the world’s attention and concern. Health professionals and the general public are struggling to comprehend these unfolding dynamics and to separate misinformation and speculation from truth.

In early 2014, EVD emerged in a remote region of Guinea near its borders with Sierra Leone and Liberia. Since then, the epidemic has grown dramatically, fueled by several factors. First, Guinea, Sierra Leone, and Liberia are resource-poor countries already coping with major health challenges, such as malaria and other endemic diseases, some of which may be confused with EVD. Next, their borders are porous, and movement between countries is constant. Health care infrastructure is inadequate, and health workers and essential supplies including personal protective equipment are scarce. Traditional practices, such as bathing of corpses before burial, have facilitated transmission. The epidemic has spread to cities, which complicates tracing of contacts. Finally, decades of conflict have left the populations distrustful of governing officials and authority figures such as health professionals. Add to these problems a rapidly spreading virus with a high mortality rate, and the scope of the challenge becomes clear.

Although the regional threat of Ebola in West Africa looms large, the chance that the virus will establish a foothold in the United States or another high-resource country remains extremely small. Although global air transit could, and most likely will, allow an infected, asymptomatic person to board a plane and unknowingly carry Ebola virus to a higher-income country, containment should be readily achievable. Hospitals in such countries generally have excellent capacity to isolate persons with suspected cases and to care for them safely should they become ill. Public health authorities have the resources and training necessary to trace and monitor contacts. Protocols exist for the appropriate handling of corpses and disposal of biohazardous materials. In addition, characteristics of the virus itself limit its spread. Numerous studies indicate that direct contact with infected bodily fluids — usually feces, vomit, or blood — is necessary for transmission and that the virus is not transmitted from person to person through the air or by casual contact. Isolation procedures have been clearly outlined by the Centers for Disease Control and Prevention (CDC). A high index of suspicion, proper infection-control practices, and epidemiologic investigations should quickly limit the spread of the virus.

Fauci’s article makes it clear that public concerns are rising in the US and I imagine that’s true of Canada too and many other parts of the world, not to mention the countries currently experiencing the EVD outbreak. In the midst of all this comes a US Food and Drug Administration (FDA) warning as per an Aug. 15, 2014 news item (originated by Reuters reporter Toni Clarke) on Nanowerk,

The U.S. Food and Drug Administration said on Thursday [Aug. 14, 2014] it has become aware of products being sold online that fraudulently claim to prevent or treat Ebola.

The FDA’s warning comes on the heels of comments by Nigeria’s top health official, Onyebuchi Chukwu, who reportedly said earlier Thursday [Aug. 14, 2014] that eight Ebola patients in Lagos, the country’s capital, will receive an experimental treatment containing nano-silver.

Erica Jefferson, a spokeswoman for the FDA, said she could not provide any information about the product referenced by the Nigerians.

The Aug. 14,  2014 FDA warning reads in part,

The U.S. Food and Drug Administration is advising consumers to be aware of products sold online claiming to prevent or treat the Ebola virus. Since the outbreak of the Ebola virus in West Africa, the FDA has seen and received consumer complaints about a variety of products claiming to either prevent the Ebola virus or treat the infection.

There are currently no FDA-approved vaccines or drugs to prevent or treat Ebola. Although there are experimental Ebola vaccines and treatments under development, these investigational products are in the early stages of product development, have not yet been fully tested for safety or effectiveness, and the supply is very limited. There are no approved vaccines, drugs, or investigational products specifically for Ebola available for purchase on the Internet. By law, dietary supplements cannot claim to prevent or cure disease.

As per the FDA’s reference to experimental vaccines, an Aug. 6, 2014 article by Caroline Chen, Mark Niquette, Mark Langreth, and Marie French for Bloomberg describes the ZMapp vaccine/treatment (Note: Links have been removed),

On a small plot of land incongruously tucked amid a Kentucky industrial park sit five weather-beaten greenhouses. At the site, tobacco plants contain one of the most promising hopes for developing an effective treatment for the deadly Ebola virus.

The plants contain designer antibodies developed by San Diego-based Mapp Biopharmaceutical Inc. and are grown in Kentucky by a unit of Reynolds American Inc. Two stricken U.S. health workers received an experimental treatment containing the antibodies in Liberia last week. Since receiving doses of the drug, both patients’ conditions have improved.

Tobacco plant-derived medicines, which are also being developed by a company whose investors include Philip Morris International Inc., are part of a handful of cutting edge plant-based treatments that are in the works for everything from pandemic flu to rabies using plants such as lettuce, carrots and even duckweed. While the technique has existed for years, the treatments have only recently begun to reach the marketplace.

Researchers try to identify the best antibodies in the lab, before testing them on mice, then eventually on monkeys. Mapp’s experimental drug, dubbed ZMapp, has three antibodies, which work together to alert the immune system and neutralize the Ebola virus, she [Erica Ollman Saphire, a molecular biologist at the Scripps Research Institute,] said.

This is where the tobacco comes in: the plants are used as hosts to grow large amounts of the antibodies. Genes for the desired antibodies are fused to genes for a natural tobacco virus, Charles Arntzen, a plant biotechnology expert at Arizona State University, said in an Aug. 4 [2014] telephone interview.

The tobacco plants are then infected with this new artificial virus, and antibodies are grown inside the plant. Eventually, the tobacco is ground up and the antibody is extracted, Arntzen said.

The process of growing antibodies in mammals risks transferring viruses that could infect humans, whereas “plants are so far removed, so if they had some sort of plant virus we wouldn’t get sick because viruses are host-specific,” said Qiang Chen, a plant biologist at Arizona State University in Tempe, Arizona, in a telephone interview.

There is a Canadian (?) company working on a tobacco-based vaccines including one for EVD but as the Bloomberg writers note the project is highly secret,

Another tobacco giant-backed company working on biotech drugs grown in tobacco plants is Medicago Inc. in Quebec City, which is owned by Mitsubishi Tanabe Pharma Corp. and Philip Morris. [emphasis mine]

Medicago is working on testing a vaccine for pandemic influenza and has a production greenhouse facility in North Carolina, said Jean-Luc Martre, senior director for government affairs at Medicago. Medicago is planning a final stage trial of the pandemic flu vaccine for next year, he said in a telephone interview.

The plant method is flexible and capable of making antibodies and vaccines for numerous types of viruses, said Martre. In addition to influenza, the company’s website says it is in early stages of testing products for rabies and rotavirus.

Medicago ‘‘is currently closely working with partners for the production of an Ebola antibody as well as other antibodies that are of interest for bio-defense,” he said in an e-mail. He would not disclose who the partners were. [emphasis mine]

I have checked both the English and French language versions of Medicago’s website and cannot find any information about their work on ebola. (The Bloomberg article provides a good overview of the ebola situation and more. I recommend reading it and/or the Aug. 15, 2014 posting on CTV [Canadian Television Network] which originated from an Associated Press article by Malcolm Ritter).

Moving on to more research and ebola, Dexter Johnson in an Aug. 14, 2014 posting (on his Nanoclast blog on the IEEE [Institute of Electrical and Electronics Engineers] website,) describes some work from Northeastern University (US), Note: Links have been removed,

With the Ebola virus death toll now topping 1000 and even the much publicized experimental treatment ZMapp failing to save the life of a Spanish missionary priest who was treated with it, it is clear that scientists need to explore new ways of fighting the deadly disease. For researchers at Northeastern University in Boston, one possibility may be using nanotechnology.

“It has been very hard to develop a vaccine or treatment for Ebola or similar viruses because they mutate so quickly,” said Thomas Webster, the chair of Northeastern’s chemical engineering department, in a press release. “In nanotechnology we turned our attention to developing nanoparticles that could be attached chemically to the viruses and stop them from spreading.”

Webster, along with many researchers in the nanotechnology community, have been trying to use gold nanoparticles, in combination with near-infrared light, to kill cancer cells with heat. The hope is that the same approach could be used to kill the Ebola virus.

There is also an Aug. 6, 2014 Northeastern University news release by Joe O’Connell describing the technique being used by Webster’s team,

… According to Web­ster, gold nanopar­ti­cles are cur­rently being used to treat cancer. Infrared waves, he explained, heat up the gold nanopar­ti­cles, which, in turn, attack and destroy every­thing from viruses to cancer cells, but not healthy cells.

Rec­og­nizing that a larger sur­face area would lead to a quicker heat-​​up time, Webster’s team cre­ated gold nanos­tars. “The star has a lot more sur­face area, so it can heat up much faster than a sphere can,” Web­ster said. “And that greater sur­face area allows it to attack more viruses once they absorb to the par­ti­cles.” The problem the researchers face, how­ever, is making sure the hot gold nanopar­ti­cles attack the virus or cancer cells rather than the healthy cells.

At this point, there don’t seem to be any curative measures generally available although some are available experimentally in very small quantities.

Researchers propose massive shift in science funding enterprise

The massive science funding shift that researchers are proposing won’t fundamentally change who or what research is funded so much as it will require fewer resources as described in a Jan. 8, 2014 news item on Nanowerk (Note: A link has been removed),

Researchers in the United States have suggested an alternative way to allocate science funding. The method, which is described in EMBO reports (“From funding agencies to scientific agency”), depends on a collective distribution of funding by the scientific community, requires only a fraction of the costs associated with the traditional peer review of grant proposals and, according to the authors, may yield comparable or even better results.

The Jan. 8, 2014 EMBO [European Molecular Biology Organization] news release, which originated the news item, quotes the lead author’s perspective on the current funding systems and describes the proposed solution which is meant for all science funding,

“Peer review of scientific proposals and grants has served science very well for decades. However, there is a strong sense in the scientific community that things could be improved,” said Johan Bollen, professor and lead author of the study from the School of Informatics and Computing at Indiana University. “Our most productive researchers invest an increasing amount of time, energy, and effort into writing and reviewing research proposals, most of which do not get funded. That time could be spent performing the proposed research in the first place.” He added: “Our proposal does not just save time and money but also encourages innovation.”

The new approach is possible due to recent advances in mathematics and  computer technologies. The system involves giving all scientists an annual, unconditional fixed amount of funding to conduct their research. All funded scientists are, however, obliged to donate a fixed percentage of all of the funding that they previously received to other researchers. As a result, the funding circulates through the community, converging on researchers that are expected to make the best use of it. “Our alternative funding system is inspired by the mathematical models used to search the internet for relevant information,” said Bollen. “The decentralized funding model uses the wisdom of the entire scientific community to determine a fair distribution of funding.”

The authors believe that this system can lead to sophisticated behavior at a global level. It would certainly liberate researchers from the time-consuming process of submitting and reviewing project proposals, but could also reduce the uncertainty associated with funding cycles, give researchers much greater flexibility, and allow the community to fund risky but high-reward projects that existing funding systems may overlook.

“You could think of it as a Google-inspired crowd-funding system that encourages all researchers to make autonomous, individual funding decisions towards people, not projects or proposals,” said Bollen. “All you need is a centralized web site where researchers could log-in, enter the names of the scientists they chose to donate to, and specify how much they each should receive.”

The authors emphasize that the system would require oversight to prevent misuse, such as conflicts of interests and collusion. Funding agencies may need to confidentially monitor the flow of funding and may even play a role in directing it. For example they can provide incentives to donate to specific large-scale research challenges that are deemed priorities but which the scientific community can overlook.

“The savings of financial and human resources could be used to identify new targets of funding, to support the translation of scientific results into products and jobs, and to help communicate advances in science and technology,” added Bollen. “This funding system may even have the side-effect of changing publication practices for the better: researchers will want to clearly communicate their vision and research goals to as wide an audience as possible.”

While the research is US-centric, it’s easy to see its applicabllity in many, if not all, jurisdictions around the world.

I have two links and two citations. The first is for the EMBO Reports paper,

From funding agencies to scientific agency; Collective allocation of science funding as an alternative to peer review by  Johan Bollen, David Crandall, Damion Junk, Ying Ding, & Katy Börner. Article first published online: 7 JAN 2014 DOI: 10.1002/embr.201338068

© 2014 The Authors

This paper is behind a paywall.

The second link and citation is for an earlier version of the paper on arXiv.org, which is an open access archive,

Collective allocation of science funding: from funding agencies to scientific agency
by Johan Bollen, David Crandall, Damion Junk, Ying Ding, & Katy Boerner.
(Submitted on 3 Apr 2013)

Here’s the abstract from the April 2013 version of the paper on arXiv.org,

Public agencies like the U.S. National Science Foundation (NSF) and the National Institutes of Health (NIH) award tens of billions of dollars in annual science funding. How can this money be distributed as efficiently as possible to best promote scientific innovation and productivity? The present system relies primarily on peer review of project proposals. In 2010 alone, NSF convened more than 15,000 scientists to review 55,542 proposals. [emphasis mine] Although considered the scientific gold standard, peer review requires significant overhead costs, and may be subject to biases, inconsistencies, and oversights. We investigate a class of funding models in which all participants receive an equal portion of yearly funding, but are then required to anonymously donate a fraction of their funding to peers. The funding thus flows from one participant to the next, each acting as if he or she were a funding agency themselves. Here we show through a simulation conducted over large-scale citation data (37M articles, 770M citations) that such a distributed system for science may yield funding patterns similar to existing NIH and NSF distributions, but may do so at much lower overhead while exhibiting a range of other desirable features. Self-correcting mechanisms in scientific peer evaluation can yield an efficient and fair distribution of funding. The proposed model can be applied in many situations in which top-down or bottom-up allocation of public resources is either impractical or undesirable, e.g. public investments, distribution chains, and shared resource management.

It’s interesting to note the agencies which supported the research (from the news release),

Awards from the National Science Foundation, the Andrew W. Mellon Foundation and the National Institutes of Health supported the work.

It would seem there’s an appetite for change given the National Science Foundation (NSF) and the National Institutes of Health (NIH) are the two largest science funding agencies in the US.