Tag Archives: in silico

University of Toronto, ebola epidemic, and artificial intelligence applied to chemistry

Leave a reply

It’s hard to tell much from the Nov. 5, 2014 University of Toronto news release by Michael Kennedy (also on EurekAlert but dated Nov. 10, 2014) about in silico drug testing focused on finding a treatment for ebola,

The University of Toronto, Chematria and IBM are combining forces in a quest to find new treatments for the Ebola virus.

Using a virtual research technology invented by Chematria, a startup housed at U of T’s Impact Centre, the team will use software that learns and thinks like a human chemist to search for new medicines. Running on Canada’s most powerful supercomputer, the effort will simulate and analyze the effectiveness of millions of hypothetical drugs in just a matter of weeks.

“What we are attempting would have been considered science fiction, until now,” says Abraham Heifets (PhD), a U of T graduate and the chief executive officer of Chematria. “We are going to explore the possible effectiveness of millions of drugs, something that used to take decades of physical research and tens of millions of dollars, in mere days with our technology.”

The news release makes it all sound quite exciting,

Chematria’s technology is a virtual drug discovery platform based on the science of deep learning neural networks and has previously been used for research on malaria, multiple sclerosis, C. difficile, and leukemia. [emphases mine]

Much like the software used to design airplanes and computer chips in simulation, this new system can predict the possible effectiveness of new medicines, without costly and time-consuming physical synthesis and testing. [emphasis mine] The system is driven by a virtual brain that teaches itself by “studying” millions of datapoints about how drugs have worked in the past. With this vast knowledge, the software can apply the patterns it has learned to predict the effectiveness of hypothetical drugs, and suggest surprising uses for existing drugs, transforming the way medicines are discovered.

My understanding is that Chematria’s is not the only “virtual drug discovery platform based on the science of deep learning neural networks” as is acknowledged in the next paragraph. In fact, there’s widespread interest in the medical research community as evidenced by such projects as Seurat-1’s NOTOX* and others. Regarding the research on “malaria, multiple sclerosis, C. difficile, and leukemia,” more details would be welcome, e.g., what happened?

A Nov. 4, 2014 article for Mashable by Anita Li does offer a new detail about the technology,

Now, a team of Canadian researchers are hunting for new Ebola treatments, using “groundbreaking” artificial-intelligence technology that they claim can predict the effectiveness of new medicines 150 times faster than current methods.

With the quotes around the word, groundbreaking, Li suggests a little skepticism about the claim.

Here’s more from Li where she seems to have found some company literature,

Chematria describes its technology as a virtual drug-discovery platform that helps pharmaceutical companies “determine which molecules can become medicines.” Here’s how it works, according to the company:

The system is driven by a virtual brain, modeled on the human visual cortex, that teaches itself by “studying” millions of datapoints about how drugs have worked in the past. With this vast knowledge, Chematria’s brain can apply the patterns it perceives, to predict the effectiveness of hypothetical drugs, and suggest surprising uses for existing drugs, transforming the way medicines are discovered.

I was not able to find a Chematria website or anything much more than this brief description on the University of Toronto website (from the Impact Centre’s Current Companies webpage),

Chematria makes software that helps pharmaceutical companies determine which molecules can become medicines. With Chematria’s proprietary approach to molecular docking simulations, pharmaceutical researchers can confidently predict potent molecules for novel biological targets, thereby enabling faster drug development for a fraction of the price of wet-lab experiments.

Chematria’s Ebola project is focused on drugs already available but could be put to a new use (from Li’s article),

In response to the outbreak, Chematria recently launched an Ebola project, using its algorithm to evaluate molecules that have already gone through clinical trials, and have proven to be safe. “That means we can expedite the process of getting the treatment to the people who need it,” Heifets said. “In a pandemic situation, you’re under serious time pressure.”

He cited Aspirin as an example of proven medicine that has more than one purpose: People take it for headaches, but it’s also helpful for heart disease. Similarly, a drug that’s already out there may also hold the cure for Ebola.

I recommend reading Li’s article in its entirety.

The University of Toronto news release provides more detail about the partners involved in this ebola project,

… The unprecedented speed and scale of this investigation is enabled by the unique strengths of the three partners: Chematria is offering the core artificial intelligence technology that performs the drug research, U of T is contributing biological insights about Ebola that the system will use to search for new treatments and IBM is providing access to Canada’s fastest supercomputer, Blue Gene/Q.

“Our team is focusing on the mechanism Ebola uses to latch on to the cells it infects,” said Dr. Jeffrey Lee of the University of Toronto. “If we can interrupt that process with a new drug, it could prevent the virus from replicating, and potentially work against other viruses like Marburg and HIV that use the same mechanism.”

…

The initiative may also demonstrate an alternative approach to high-speed medical research. While giving drugs to patients will always require thorough clinical testing, zeroing in on the best drug candidates can take years using today’s most common methods. Critics say this slow and prohibitively expensive process is one of the key reasons that finding treatments for rare and emerging diseases is difficult.

“If we can find promising drug candidates for Ebola using computers alone,” said Heifets, “it will be a milestone for how we develop cures.”

I hope this effort along with all the others being made around the world prove helpful with Ebola. it’s good to see research into drugs (chemical formulations) that are familiar to the medical community and can be used for a different purpose than originally intended. Drugs that are ‘repurposed’ should be cheaper than new ones and we already have data about side effects.

As for the “milestone for how we develop cures,” this team’s work along with all the international research on this front and on how we assess toxicity should certainly make that milestone possible.

* Full disclosure: I came across Seurat-1’s NOTOX project when I attended (at Seurat-1’s expense) the 9th World Congress on Alternatives to Animal Testing held in Aug. 2014 in Prague.

Deadline extension (travel grants and poster abstracts) for alternate testing strategies (ATS) of nanomaterials workshop

Leave a reply

It seems there have been a couple of deadline extensions (to August 1, 2014) for the September 15-16, 2014 ‘Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials’ in Washington, DC (first mentioned in my July 10, 2014 posting featuring a description of the workshop). You can go here to submit a poster abstract (from any country) and you can go here if you’re a student or young professional (from any country) in search of a $500 travel award.

I managed to speak to one of the organizers, Lorraine Sheremeta, (Assistant Director, Ingenuity Lab, University of Alberta and co-author a July 9, 2014 Nanowerk Spotlight article about the workshop). Lorraine (Lori) kindly spoke to me about the upcoming workshop, which she described as an academic conference,.

As I understand what she told me, the hosts for the September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC want to attract a multidisciplinary group of people to grapple with a few questions. First, they want to establish a framework for establishing which are the best test methods for nanomaterials. Second, they are trying to move away from animal testing and want to establish which methods are equal to or better than animal testing. Thirdly, they want to discuss what they are going to do with the toxicological data  that we have  been collecting on nanomaterials for years now.

Or, as she and her colleague from the Society of Risk Analysis (Jo Anne Shatkin) have put in it in their Nanowerk Spotlight article:

… develop a report on the State of the Science for ATS for nanomaterials, catalogue of existing and emerging ATS [alternate testing strategies] methods in a database; and develop a case study to inform workshop deliberations and expert recommendations

The collaborative team behind this event includes, the University of Alberta’s Ingenuity Lab, the Society for Risk Analysis, Environment Canada, Health Canada, and the Organization for Economic Co-operation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN) .

The speaker lineup isn’t settled at this time although they have confirmed Vicki Stone of Heriot-Watt University in Scotland (from her university bio page),

Vicki Stone, Professor of Toxicology, studies the effects of nanomaterials on humans and environmentally relevant species.  Current research projects investigate the mechanism of toxicity of a range of nanomaterials in cells of the immune system (macrophages and neutrophils), liver (hepatocytes) , gastrointestinal tract, blood vessels (endothelium) and lung.  She is interested in interactions between nanomaterials, proteins and lipids, and how this influences subsequent toxicity.  Current projects also develop in vitro alternatives using microfluidics as well as high resolution imaging of individual nanomaterials in 3D and over time.  In addition Vicki collaborates with ecotoxicologists to investigate the impacts of nanomaterials on aquatic organisms. Vicki coordinated a European project to identify the research priorities to develop an intelligent testing strategy for nanomaterials (www.its-nano.eu).

Vicki is Director of the Nano Safety Research Group at Heriot-Watt University, Edinburgh, and Director of Toxicology for SAFENANO (www.safenano.org). She has acted as the Editor-in-chief of the journal Nanotoxicology (http://informahealthcare.com/nan) for 6 years (2006-2011). Vicki has also published over 130 publications pertaining to particle toxicology over the last 16 years and has provided evidence for the government commissioned reports published by the Royal Society (2003) and the on Environmental Pollution (2008).  Vicki was previously a member of the UK Government Committee on the Medical Effects of Air Pollution (COMEAP) and an advisory board member for the Center for the Environmental Implications of NanoTechnology (CEINT; funded by the US Environmental Protection Agency)).

A representative from PETA (People for the Ethical Treatment of Animals) will also be speaking. I believe that will be Amy Clippinger (from the PETA website’s Regulatory Testing webpage; scroll down about 70% of the way),

Science adviser Amy Clippinger has a Ph.D. in cellular and molecular biology and genetics and several years of research experience at the University of Pennsylvania.

PETA representatives have been to at least one other conference on the topic of nano, toxicology, and animal testing as per my April 24, 2014 posting about NANOTOX 2014 in Turkey,

Writing about nanotechnology can lead you in many different directions such as the news about PETA (People for the Ethical Treatment of Animals) and its poster presentation at the NanoTox 2014 conference being held in Antalya, Turkey from April 23 – 26, 2014. From the April 22, 2014 PETA news release on EurekAlert,

PETA International Science Consortium Ltd.’s nanotechnology expert will present a poster titled “A tiered-testing strategy for nanomaterial hazard assessment” at the 7th International Nanotoxicology Congress [NanoTox 2014] to be held April 23-26, 2014, in Antalya, Turkey.

Dr. Monita Sharma will outline a strategy consistent with the 2007 report from the US National Academy of Sciences, “Toxicity Testing in the 21st Century: A Vision and a Strategy,” which recommends use of non-animal methods involving human cells and cell lines for mechanistic pathway–based toxicity studies.

There is a lot of interest internationally in improving how we test for toxicity of nanomaterials. As well, the drive to eliminate or minimize as much as possible the use of animals in testing seems to be gaining momentum.

Good luck to everyone submitting a poster abstract and/or an application for a travel grant!

In case you don’t want to scroll up, the SRA nano workshop website is here.

An upcoming alternate testing strategies (ATS) for nanomaterials workshop and the quest to reduce animal testing

Leave a reply

It’s too late to announce a call for poster abstracts or travel awards but that still leaves the possibility of attending a September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC. In a July 9, 2014 Nanowerk Spotlight article,, Jo Anne Shatkin (President, Vireo Advisors) and Lorraine Sheremeta (Assistant Director, Ingenuity Lab, University of Alberta) tout the workshop in the context of describing new approaches to nanotoxicology research (Note: A link has been removed),

Engineered nanoscale materials (ENM or ‘nanomaterials’) offer the potential to create safer and more effective products through the use of smaller quantities of improved performance materials. Currently nanomaterials are used to improve the performance of life-saving drugs and medical technologies, to make renewable energy more efficient, to make value added products from industrial waste streams, to improve food, packaging, to lightweight materials used in transportation systems, and to improve many of the personal care products that we use every day. Nanomaterial manufacture and use is expected to increase over the coming years and despite the widespread use of nanomaterials in a variety of consumer products, we are only beginning to understand the impacts of these emerging materials on our health and the environment. To this end, the University of Alberta’s Ingenuity Lab is collaborating with the Society for Risk Analysis to evaluate the potential to use alternative test strategies (ATS) to improve our ability to assess nanomaterial toxicity and environmental impact.

Shatkin and Sheremeta describe toxicology tests and explain the importance of refining and improving these tests (from the article),

Standard in vivo toxicology test methods that depend heavily on the use of animals have long been used to assess chemical safety. [emphasis mine*] Existing and novel in vitro and in silico test methods provide important alternatives to in vivo animal testing for chemicals and potentially for ENM. Genotoxicity tests, for example, are used to assess the mutagenic potential of chemicals or nanomaterials in the replication of DNA in cells. Driven in part by increasing market and regulatory requirements for safer and more sustainable products, large international infrastructure has developed for creating, testing and validating in vitro test methods, and its use is expanding to chemical and nanomaterial assessment (NSF, 2007). The goals of reducing, refining and replacing animal testing (the commonly cited ‘three Rs’) – resonate with key and diverse stakeholders including animal rights groups, the bioethics community, the pharmaceutical industry, regulatory agencies and the broader public. [emphasis mine*]

Despite nearly a decade of effort in the conduct toxicology and exposure research to inform the assessment of health and environmental risks of nanomaterials, major gaps remain in the ability to understand and quantify risks. While there is now a large body of published data on carbon nanotubes and metal oxide nanoparticles, concern has been raised that speculation about nanomaterial risk has hardened into an assumption that there are ‘as-yet-to-be-discovered risks’ that we must identify and manage (Maynard, 2014) that demands extensive testing.

The authors describe ATS (alternative test strategies) in greater detail,

ATS approaches are regarded by many to have the potential for rapid screening of large numbers and types of materials. They can include a breadth of techniques including high throughput screening methods (HTS), high content screening, computational approaches, toxicogenomics, cell-based methods, in vitro assays and non-mammalian whole animal models. The emergence of ATS raises questions about how the results of these methods may be used for assessing the potential risks of ENM. For instance, ATS could be used in combination in a multiple models approach to evaluate new ENM in a number of rapid assays and compare with well-studied substances using in vivo testing; thereby identifying ENM for additional testing in a more strategic fashion than is possible through conventional testing approaches.

They also describe the current state of affairs with ATS,

In the United States, the U.S. ToxCast program has, as part of their 21st century toxicity screening program (NRC, 2007), tested 29 NMs with 62 in vitro test methods (Wang et al. 2013). Many researchers, including several from the University of Alberta, have proposed and developed ATS to include a variety of methods, some which are standardized for chemicals, and others which take advantage of developments including advanced biological mechanistic understanding, genomics, metabolomics, automation and informatics. However, these existing as well as emerging ATS have a short history with nanomaterials, and have not yet proven to be reliable for quantitative estimation of ENM risk. Still, several international efforts have developed ATS that have potential to be used for screening purposes, and to guide further testing priorities for regulatory decision making. The goal of the September [2014] workshop by the Society for Risk Analysis is to explore ways in which distinct ATS may be used for screening and prioritizing the need for more extensive testing of novel ENM.

The parties (including the authors of the article) involved in developing this risk workshop are listed, also mentioned are members of the international testing scene,

Lori Sheremeta, the Assistant Director of Ingenuity Lab in Edmonton Alberta and past Chair of the Society for Risk Analysis (SRA) Emerging Nanoscale Materials Specialty Group (ENMSG), is collaborating with U.S.-based nanomaterials risk expert Jo Anne Shatkin (an SRA Councilor and co-founder of the SRA ENMSG), Environment Canada, Health Canada, the SRA ENMSG and others on a Pilot Project with the Organization for Economic Co-operation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN) to develop a report on the State of the Science for ATS for nanomaterials, catalogue of existing and emerging ATS methods in a database; and develop a case study to inform workshop deliberations and expert recommendations.

…

There are many international efforts to develop, as well as to validate and standardize, these methods for chemicals, including organizations such as the US National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (ICCVAM), the European Union Reference Laboratory European Centre for the Validation of Alternative Methods (EURL ECVAM), the Japanese Center for the Validation of Alternative Methods (JacVAM), the Korean Centre for the Validation of Alternative Methods (KoCVAM) and the OECD. There is wide recognition that the diversity of NMs renders it impractical to use traditional animal testing to evaluate safety, hence there is significant interest in assessing the performance of both existing and emerging alternative testing strategies for NMs. Further, the EU directive REACH (Directive 2006/121/EC) requires replacing in vivo testing, and there is widespread popular agreement about the desire to limit animal testing. Finally, there is a need for more biologically informative toxicology methods (Hartung, 2010; Silbergeld et al, 2011; Landsiedel et al, 2009).

A list of the workshop objectives is offered  in the article,

The main objectives of the workshop are to:

assess the state of the science on HTS and ATS from a ‘multiple models’ perspective to identify areas of common findings from differing approaches, areas of greatest uncertainty, and priorities for follow up in applied research toward risk assessment of ENM;
evaluate the ability to use data from ATS/HTS methods for screening purposes – combining suites of assays and comparing well-studied substances to novel ones;

assess the ability to use a suite of ATS methods to amplify the Weight of Evidence;

characterize uncertainty associated with predictive relationships and propose strategies to address uncertainties;

elicit the perspectives of diverse stakeholders about the use of HTS/ATS for screening purposes in risk analysis of ENM; and

develop a set of recommendations for these alternative approaches to become more widely adopted for environmental, health and safety decision making about ENM across the product life cycle. The output of the workshop holds potential for transformation through risk screening approaches that promote safer and more sustainable material and technology development.

You can find more about the September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC here.

The text in the article is a bit rough. Some of the ideas and topics don’t follow each other logically. So, be prepared to spend a little time reading, Happily, there are references included with the article.

I last mentioned Jo Anne Shatkin here in the context of a 2013 paper on alternative test strategies (ATS) in an Aug. 22, 2013 posting. I think the most recent mention of Lorraine Sheremeta here is in a Jan. 11, 2010 posting about Canada, nanotechnology, and food.

Final note, I am hoping to get some more information about the workshop and ATS scene from Lorraine Sheremeta to be published in a subsequent posting.

* I added the emphases at 0830 hours PDT July 10, 2014.