Tag Archives: RSC

DARPA (US Defense Advanced Research Projects Agency), nanoparticles, and your traumatized brain

According to the May 10, 2013 news item on Nanowerk,

DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections.

Led by Professor Michael J. Sailor, Ph.D., from the University of California San Diego [UC San Diego], the award brings together a multi-disciplinary team of renowned experts in laboratory research, translational investigation and clinical medicine, including Erkki Ruoslahti, M.D., Ph.D. of Sanford-Burnham Medical Research Institute, Sangeeta N. Bhatia, M.D., Ph.D. of Massachusetts Institute of Technology and Clark C. Chen, M.D., Ph.D. of UC San Diego School of Medicine.

Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.

“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said Chen, a neurosurgeon with UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.

The May 9, 2013 UC San Diego news release by Susan Brown, which originated the news item, describes the reasons why DARPA wants to use nanoparticles in therapies for people suffering from traumatic brain injury,

Under normal conditions, the brain is protected from infection by a physiological system called the blood-brain barrier. “Unfortunately, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold,” said Chen, associate professor and vice-chair of research in the Division of Neurosurgery at UC San Diego School of Medicine.

DARPA hopes to meet these challenges with nanotechnology. The agency awarded this grant under its In Vivo Nanoplatforms for Therapeutics program to construct nanoparticles that can find and treat infections and other damage associated with traumatic brain injuries.

“Our approach is focused on porous nanoparticles that contain highly effective therapeutics on the inside and targeting molecules on the outside,” said Sailor, the UC San Diego materials chemist who leads the team. “When injected into the blood stream, we have found that these silicon-based particles can target certain tissues very effectively.”

Several types of nanoparticles have already been approved for clinical use in patients, but none for treatment of trauma or diseases in the brain. This is due in part to the inability of nanoparticle formulations to cross the blood-brain barrier and reach their intended targets.

“Poor penetration into tissues limits the application of nanoparticles to the treatment of many types of diseases,” said Ruoslahti, distinguished professor at Sanford-Burnham and partner in the research. “We are trying to overcome this limitation using targeting molecules that activate tissue-specific transport pathways to deliver nanoparticles.”

There is another major hurdle for treating brain injuries (from the news release),

Treating brain infections is becoming more difficult as drug-resistant strains of viruses and bacteria have emerged. Because drug-resistant strains mutate and evolve rapidly, researchers must constantly adjust their approach to treatment.

In an attempt to hit this moving target, the team is making their systems modular, so they can be reconfigured “on-the-fly” with the latest therapeutic advances.

Nanocomplexes that contain genetic material known as short interfering RNA, or siRNA, developed by Bhatia’s research group at MIT, will be key to this aspect of the team’s approach.

“The function of this type of RNA is that it specifically intereferes with processes in a diseased cell. The advantage of RNA therapies are that they can be quickly and easily modified when a new disease target emerges,” said Bhatia, a bioengineering professor at MIT and partner in the research.

But effective delivery of siRNA-based therapeutics in the body has proven to be a challenge because the negative charge and chemical structure of naked siRNA makes it very unstable in the body and it has difficulty crossing into diseased cells. To solve these problems, Bhatia has developed nanoparticles that form a protective coating around siRNA.

“The nanocomplexes we are developing shield the negative charge of RNA and protect it from nucleases that would normally destroy it. Adding Erkki’s tissue homing and cell-penetrating peptides allows the nanocomplex to transport deep into tissue and enter the diseased cells,” she said.

Bhatia has previously used the cell-penetrating nanocomplex to deliver siRNA to a tumor cell and shut down its protein production machinery. Although her group’s effort has focused on cancer, the team is now going after two other hard-to-treat cell types: drug-resistant bacteria and inflammatory cells in the brain.

“The work proposed by this multi-disciplinary team should provide new tools to mitigate the debilitating effects of penetrating brain injuries and offer our warfighters the best chance of meaningful recovery,” Chen said. [emphasis mine]

BTW, the term ‘warfighters’ is new to me; are we replacing the word ‘soldier’?

Returning to the matter at hand, I found DARPA’s In Vivo Nanoplatforms for Therapeutics program which is described this way on its home page,

Disease limits soldier readiness and creates healthcare costs and logistics burdens. Diagnosing and treating disease faster can help limit its impact. [emphasis mine] Current technologies and products for diagnosing disease are principally relegated to in vitro (in the lab) medical devices, which are often expensive, bulky and fragile.

DARPA’s In Vivo Nanoplatforms (IVN) program seeks to develop new classes of adaptable nanoparticles for persistent, distributed, unobtrusive physiologic and environmental sensing as well as the treatment of physiologic abnormalities, illness and infectious disease.

The IVN Diagnostics (IVN:Dx) program effort aims to develop a generalized in vivo platform that provides continuous physiological monitoring for the warfighter. [emphasis mine] Specifically, IVN:Dx will investigate technologies that may provide:

  • Implantable nanoplatforms using bio-compatible and nontoxic materials
  • In vivo sensing of small and large molecules of biological interest
  • Multiplexed detection of analytes at clinically relevant concentrations
  • External interrogation of the nanoplatform free from any implanted communications electronics
  • Complete system demonstration in a large animal

The IVN Therapeutics (IVN:Tx) program effort will seek unobtrusive nanoplatforms for rapidly treating disease in warfighters.

(I see DARPA is using both soldier and warfighter’.)

This team is not the only one wishing to deliver drug therapies in a targeted fashion to the brain. My Feb. 19, 2013 posting mentioned Chad Mirkin (Northwestern University) and his team’s efforts with spherical nucleic acids (SNAs), from the posting,

Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine. (originally excerpted from this the Feb. 15, 2013 news release on EurekAlert)

Coincidentally, Mirkin has just been named ‘Chemistry World Entrepreneur of the Year’ by the UK’s Royal Society of Chemistry, from the May 10, 2013 news item on Nanowerk,

Northwestern University scientist Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has been named 2013 Chemistry World Entrepreneur of the Year by the Royal Society of Chemistry (RSC). The award recognizes an individual’s contribution to the commercialization of research.

The RSC is honoring Mirkin for his invention of spherical nucleic acids (SNAs), new globular forms of DNA and RNA. These structures form the basis for more than 300 products commercialized by licensees of the technology.

I’m never quite sure what to make of researchers who receive public funding then patent and license the results of that research.

Getting back to soldiers/warfighters, I’m glad to see this research being pursued. Years ago, a physician mentioned to me that soldiers in Iraq were surviving injuries that would have killed them in previous conflicts. The problem is that the same protective gear which insulates soldiers against many injuries makes them vulnerable to abusive head trauma (same principle as ‘shaken baby syndrome’). For example, imagine having a high velocity bullet hit your helmet. You’re protected from the bullet but the impact shakes your head so violently, your brain is injured.

Council of Canadian Academies tries to answer question: What is the state of Canada’s science culture?

The Council of Canadian Academies is an organization designed to answer questions about science in Canada. From the Council’s About Us webpage on their website,

The Council is an independent, not-for-profit corporation that supports science-based, expert assessments (studies) to inform public policy development in Canada. The Council began operation in 2005 and consists of a Board of Governers, a Scientific Advisory Committee and Secretariat. The Council draws upon the intellectual capital that lies within its three Member Academies the Royal Society of Canada (RSC); the Canadian Academy of Engineering;  and the Canadian Academy of Health Sciences.

Our mission is to contribute to the shaping of evidence-based public policy that is in the public interest. This is achieved by appointing independent, multidisciplinary panels of expert volunteers. The Council’s work encompasses a broad definition of science, incorporating the natural, social and health sciences as well as engineering and the humanities.

Expert Panels directly address the question and sub-questions referred to them. Panel assessments may also identify: emerging issues, gaps in knowledge, Canadian strengths, and international trends and practices. Upon completion, assessments provide government decision-makers, academia and stakeholders with high-quality information required to develop informed and innovative public policy.

Several months ago, Gary Goodyear, Canada’s Minister of State (Science and Technology), requested on behalf of the Canada Science and Technology Museums Corporation (CSTMC), Natural Resources Canada, and Industry Canada an assessment of science culture in Canada. From the State of Canada’s Science Culture webpage on the Council of Canadian Academies website,

Over the past 30 years, public interest and debate has been steadily growing in Canada and abroad over the need to foster a science culture as part of the national science and technology agenda. In this period, significant government and private investments have contributed to the development of hundreds of individual science culture programs and institutions.

Now more than ever the volume of programs and data support the need for a national examination of issues, such as the performance indicators that best reflect the vitality of Canada’s science culture, and a need to understand where Canada ranks internationally. The expert panel will be asked to consider these and other questions such as what factors influence an interest in science among youth; what are the key components of the informal system that supports science culture; and what strengths and weaknesses exist in the Canadian system.

Assessments of science culture can focus either on science in the general culture, or the culture among scientists. This assessment will focus principally on the former, with additional interest in understanding the underlying connections among entrepreneurship, innovation and science. …

The full assessment process includes a rigorous peer review exercise to ensure the report is objective, balanced and evidence-based. Following the review and approval by the Council’s Board of Governors, the complete report will be made available on the Council’s website in both official languages. …

Question

What is the state of Canada’s science culture?

Sub-questions:

  1. What is the state of knowledge regarding the impacts of having a strong science culture?
  2. What are the indicators of a strong science culture? How does Canada compare with other countries against these indicators? What is the relationship between output measures and major outcome measures?
  3. What factors (e.g., cultural, economic, age, gender) influence interest in science, particularly among youth?
  4. What are the critical components of the informal system that supports science culture (roles of players, activities, tools and programs run by science museums, science centres, academic and not-for-profit organizations and the private sector)? What strengths and weaknesses exist in Canada’s system?
  5. What are the effective practices that support science culture in Canada and in key competitor countries?

Hopefully, the expert panel will have a definition of some kind for “science culture.”

After waiting what seems to be an unusually long period, the Council announced the chair for the  “science culture” expert panel (from the CCA Dec. 19, 2012 news release),

Arthur Carty to Serve as Expert Panel Chair on the State of Canada’s Science Culture

The Council is pleased to announce the appointment of Dr. Arthur Carty, O.C., as Chair of the Expert Panel on the State of Canada’s Science Culture. In 2011, the Minister of State (Science and Technology) on behalf of the Canada Science and Technology Museums Corporation (CSTMC), Natural Resources Canada, and Industry Canada requested the Council conduct an in-depth, evidence-based assessment on the state of Canada’s science culture.

As Chair of the Council’s Expert Panel, Dr. Carty will work with a multidisciplinary group of experts, to be appointed by the Council, to address the following question: What is the state of Canada’s science culture?

Dr. Carty is currently the Executive Director of the Waterloo Institute for Nanotechnology at the University of Waterloo. Dr. Carty also serves as Special Advisor to the President on international science and technology collaboration, and as Research Professor in the Department of Chemistry. Prior to this, Dr. Carty served as Canada’s first National Science Advisor to the Prime Minister and to the Government of Canada from 2004-2007 and as President of the National Research Council Canada from 1994-2004.

You can find out more on Carty’s biography webpage, on the CCA website,

Arthur Carty is the Executive Director of the Waterloo Institute for Nanotechnology at the University of Waterloo, Special Advisor to the President on international science and technology collaboration, and Research Professor in the Department of Chemistry

From 2004-2008, Dr. Carty served as Canada’s first National Science Advisor to the Prime Minister and to the Government of Canada. Prior to this appointment, he was President of the National Research Council Canada for 10 years. Before this, he spent 2 years at Memorial University and then 27 years at the University of Waterloo, where he was successively Professor of Chemistry, Director of the Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Chair of the Department of Chemistry, and Dean of Research.

….

Carty’s profile page on the Waterloo Institute of Nanotechnology (WIN) website offers the same information but in more detail.

It’s difficult to divine much from the biographical information about Carty as it is very purpose-oriented to impress the reader with Carty’s international and national involvements in the field of science advice and collaboration. Carty may have extensive experience with multi-disciplinary teams and an avid interest in a science culture that includes informal science education and the arts and humanities, unfortunately, it’s not visible on either the CCA or WIN website biographies.

Hopefully,  Carty and the CCA will assemble a diverse expert panel. (Warning: blatant self-promotion ahead) If they are looking for a person of diverse personal and professional interests

  • who has an MA in Creative Writing (nonfiction and fiction) and New Media from De Montfort University in Leicester, UK and
  • a BA (Communication – Honors) from Simon Fraser University in Burnaby, Canada and
  • who has built up one of the largest and longest-running independent science blogs in the country thereby contributing to science culture in Canada,
  • neatly combining the social sciences, the humanities, and an informed perspective on science and science culture in Canada in one person,

they may want to contact me at [email protected] I have more details in the CV and can supply references.

Why does hot water sometimes freeze faster than cold—a 2300 year old question

The Mpemba effect is when hot water freezes more quickly than cold water and the question as to why was first posed, as far as we know, by Aristotle. 2300 years later we’re still looking for the answer and the UK’s Royal Society of Chemistry (RSC) has decided to pose the question to two different audiences in the hope of finally getting a solution. Brian Emsley in his June 26, 2012 posting on the Guardian Science Blogs describes the RSC’s open contest for £1000,

The Royal Society of Chemistry has decided enough is enough. In an attempt to nail the matter once and for all, we’re asking the public to come up with a convincing explanation of a phenomenon that defeated Aristotle, Francis Bacon and René Descartes. To win the £1,000 prize, you will need to make a convincing case and employ some creative thinking.

The deadline for public entries is 30 July [2012] …

You can go here to the Hermes organization website to submit your solution.

For those with any lingering questions about the competition for the general public, the June 26, 2012 RSC news release provides more information including a list of prominent theorists who have also puzzled over the question,

  • Aristotle agonized over it fruitlessly in the fourth century BC
  • Roger Bacon in the 13th century used it to advocate the scientific method in his book Opus Majus
  • Another Bacon, Francis, wrote in his 1620 Novum Organum, that “slightly tepid water freezes more easily than that which is utterly cold” but could not explain why
  • Descartes was defeated by it in the 17th century AD
  • Even perplexed 20th and 21st century scientists and intellectuals have swarmed over it without result

Now the Royal Society of Chemistry is offering £1000 to the person or team producing the best and most creative explanation of the phenomenon, known today as The Mpemba Effect.

Competition judges will be looking for an outside-the-box, inventive submission. In addition, the format of the submission should be creative and eye-catching.

Any medium or technology can be employed to make the case, including articles, illustrations or even film.

Submissions can be based on, and reference, existing research. The winning submission will be scientifically sound, and arresting in presentation and delivery.

The public has four weeks to crack the case …

Then, according to the RSC news release,

… a group of the world’s brightest young science brains take on the challenge in London as one aspect of a special science communications meeting entitled Hermes 2012.

The sharpest international postgraduate science students will travel to England from around the globe to participate in the Hermes 2012 event.

The Royal Society of Chemistry is sponsoring this visit to the UK of the hand-picked young scientists, who will gather at Cumberland Lodge in Windsor Great Park.

The organisers of Hermes 2012, based at Imperial College, chose the opening weekend of the Olympic Games for the academic event to underline the global nature of the meeting, with its temporary, multi-national community of high-achievers.

A highlight of the Windsor event will be a team attempt to produce videos to explain various scientific phenomena, which will include The Mpemba Effect.

Good luck!

Hermes, by the way, was the Greek god associated with messages and communication, as well as, sports, literature, and athletics, (from the Wikipedia essay) [Note: I have removed footnotes and links],

Hermes was the herald, or messenger, of the gods to humans, sharing this role with Iris. A patron of boundaries and the travelers who cross them, he was the protector of shepherds and cowherds, thieves, orators and wit, literature and poets, athletics and sports, weights and measures, invention, and of commerce in general.

While the effect had been observed a number of times, it wasn’t considered a serious scientific question (from the RSC news release),

The problem has been around for millennia, with philosophers such as Aristotle and Descartes pondering over it.

“But this effect was reintroduced into the scientific world in 1968 by Erasto Mpemba, a young inquisitive student in Tanzania during a lab session.

“Erasto questioned a teacher on why ice cream froze more quickly when it was boiled, and was quickly told that he was wrong and had probably imagined it. It was only when the teacher performed the experiment himself that he noticed this unusual phenomenon.

“Since the discovery of the effect, scientists have been trying to find out why the phenomenon occurs but remain divided as to what the answer is. It seems that there are lots of possible answers but a conclusive explanation hasn’t been produced yet.

Canada, emerging technologies, and chemical assessments (pesticides)

The Council of Canadian Academies released a report titled, Integrating Emerging Technologies into Chemical Safety Assessment, on Jan. 12, 2012. It wasn’t what I thought it might be.

Before launching into the report, it might be helpful to know something more about the Council of Canadian Academies. (Shockingly, I can’t find a description of the group in the postings where I’ve mentioned them previously.) From the Council’s About Us page (Mar.23.12 Note: I have removed links to the Council’s Board of Governors, etc.),

The Council is an independent, not-for-profit corporation that supports science-based, expert assessments (studies) to inform public policy development in Canada. The Council began operation in 2005 and consists of a Board of Governors,  a Scientific Advisory Committee and Secretariat. The Council draws upon the intellectual capital that lies within its three Member Academies the Royal Society of Canada (RSC); the Canadian Academy of Engineering; and the Canadian Academy of Health Sciences.

Our mission is to contribute to the shaping of evidence-based public policy that is in the public interest. This is achieved by appointing independent, multidisciplinary panels of expert volunteers. The Council’s work encompasses a broad definition of science, incorporating the natural, social and health sciences as well as engineering and the humanities.

This latest report on emerging technologies and chemical assessments is in fact a report on emerging technologies for  health and safety assessment procedures of toxic chemicals using pesticides as a test case. Here’s the reasoning (from the abridged version of the report, Report in Focus; Integrating Emerging Technologies into Chemical Safety Assessment),

Protecting human health and the environment is of paramount importance to Canadians. As such, there has been an increasing demand for improved regulation of chemicals in Canada. Nevertheless, recent estimates suggest that toxicity data are lacking for over three quarters of the chemicals on the market. In fact, this paucity of data can extend to the other components within a chemical product. For example, the active ingredients in pesticides are among the most stringently regulated compounds on the market; however, the final pesticide product may also contain data-poor formulants. Added to enhance the use or increase the stability of the pesticide product, formulants are not typically subjected to the full battery of toxicity tests that the active ingredients must undergo.

The data-rich and data-poor nature of pesticide formulation is a metaphor for the dichotomy that exists for most industrial chemicals. While there are some substances for which we have an enormous amount of data, such as pesticide active ingredients, the vast majority of industrial chemicals are extremely data-poor. (p. 1)

This specific report was commissioned by the Minister of Health. From the Report in Focus; Integrating Emerging Technologies into Chemical Safety Assessment,

All levels of government in Canada play a role in regulating the sale and use of pesticides; however, the federal government is responsible for the registration of pest control products in Canada. In May 2009, the Minister of Health, on behalf of the Pest Management Regulatory Agency (PMRA), approached the Council of Canadian Academies to appoint an expert panel to answer the question:

“What is the scientific status of the use of integrated testing strategies in the human and environmental regulatory risk assessment of pesticides.”

In response to this question, the Council assembled a multidisciplinary panel of 15 eminent experts from Canada and the United States. (p. 3)

Here’s a list of the members of the Expert Panel (from the Executive Summary; Integrating Emerging Technologies into Chemical Safety Assessment),

The Expert Panel on the Integrated Testing of Pesticides

Leonard Ritter (Chair) Executive Director, Canadian Network of Toxicology Centres; and Professor of Toxicology, University of Guelph (Guelph, ON)

Christopher P. Austin Director, Chemical Genomics Center, National Institutes of Health (Bethesda, MD)

John R. (Jack) Bend Distinguished University Professor, Departments of Pathology; Physiology and Pharmacology; and Paediatrics in the Schulich School of Medicine and Dentistry, University of Western Ontario (London, ON)

Conrad G. Brunk Professor of Philosophy, University of Victoria (Victoria, BC)

Timothy Caulfield, FRSC, FCAHS Professor, Faculty of Law and School of Public Health; Research Director, Health Law Institute; and Canada Research Chair in Health Law and Policy, University of Alberta (Edmonton, AB)

Vicki L. Dellarco Science Advisor, Office of Pesticide Programs, United States Environmental Protection Agency (Washington, DC)

Paul A. Demers Director, School of Environmental Health, College for Interdisciplinary Studies; and Professor, School of Population & Public Health, Faculty of Medicine, University of British Columbia (Vancouver, BC)

Warren Foster Professor, Department of Obstetrics and Gynaecology; and Director, Centre for Reproductive Care, McMaster University Health Sciences Centre (Hamilton, ON)

Claire Infante-Rivard Professor, Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University (Montréal, QC)

Catherine Jumarie Professor, Department of Biological Sciences, Université du Québec à Montréal (Montréal, QC)

Sam Kacew Associate Director of Toxicology, R. Samuel McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa (Ottawa, ON)

Robert J. Kavlock Director, National Center for Computational Toxicology, United States Environmental Protection Agency (Durham, NC)

Daniel Krewski Director, R. Samuel McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa (Ottawa, ON)

Paul G. Mezey Canada Research Chair in Scientific Modelling and Simulation, Memorial University of Newfoundland (St. John’s, NL)

Terry W. Schultz Emeritus Professor, Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee (Knoxville, TN) (p. 7)

Getting to the point (from the Executive Summary),

“The issues inherent in the current approach to chemical testing are two-fold: to address the lack of toxicity data for the vast majority of industrial chemicals and to recognize that regulatory decisions must be based on the best available science. The Panel believes that these challenges can be best met by adopting an Integrated Approach to Testing and Assessment (IATA).” – Leonard Ritter, Chair of the Expert Panel (p. 4)

As for what that means,

Integrated Approaches to Testing and Assessment (IATA) represent a pragmatic approach that will move toxicology away from describing what happens towards an explanation of how it happens. Toxicity testing will no longer depend on the one-size-fits-all hazard-based checklist of tests currently used but rather be based on a refined and focused testing strategy tailored to the toxicity profile and intended use of the chemical in question. An IATA strategy uses a tiered approach to help categorize and prioritize higher risk chemicals; all of the existing data on a substance are compiled at the start of the testing process in order to evaluate what data gaps exist and what testing approaches would be most appropriate to understand the precise toxicological profile of that substance.

Given my interest in the toxicological impacts of nanomaterials and concerns about responding to uncertainty and risk in a timely and appropriate fashion, this approach seems promising. Of course, the recommendations may or may not be accepted and, even then, there’s no telling what implementation would look like. Still, I am encouraged.

You can find a full list of all the documents (Report, Report in Focus, Executive Summary, etc.) here.