Nova Scotia’s low incidence of COVID-19 has endowed a short-term, province-wide wastewater surveillance project with the ability to act as an early warning system for clinical caseload surges.

That capability sets the Nova Scotia program apart from other wastewater sampling initiatives across the country, monitoring for the virus that causes the disease, according to Dr. Graham Gagnon, who co-leads the surveillance project with Dr. Amina Stoddart, both from Dalhousie University’s Faculty of Engineering.

Dr. Gagnon, who is also the University Research Professor and Director of the Centre for Water Resources Studies, explained, “in regions of high caseloads, the viral signal is expected to be seen in the wastewater and can be monitored for increasing or decreasing trends.

“What’s interesting about our program is that while we expect the viral signal in wastewater to be low when cases are few, a notable increase in the signal could indicate the presence of the virus before new cases are reported.

“When used in this way, our research has the potential to provide us with an early warning signal for the re-occurrence of COVID-19 in our communities.”

As talk of a third pandemic wave grows, advance warning could give Nova Scotia Public Health officials a distinct advantage to take mitigating measures ahead of a viral outbreak and reduce its potential impact.

“Another notable feature of our program,” said Dr. Gagnon, “is that in addition to wastewater testing, we are incorporating primary solids testing, as well as passive sampling in targeted locations for a more comprehensive monitoring strategy.”

Wastewater surveillance exploits a quirk of SARS-CoV-2, the virus that causes COVID-19. Its genetic material survives longer in the gastrointestinal tract than in the respiratory system where it causes most of its havoc. That factor makes it possible to detect the virus, via its RNA, when excreted in human waste by individuals who may be asymptomatic, pre-symptomatic or symptomatic.

With the mass vaccination program against COVID-19 under way, Public Health worries have shifted to the infiltration of variants of concern and their potential to show resistance to the antibodies generated by the new vaccines and the natural immunity acquired from having had COVID-19. In some cases, variants first detected in the U.K., Brazil and South Africa seem to be more transmissible and, to cause more serious disease, than the wild form of the virus – the non-mutated form we are more familiar with.

Responding to these developments, Project Manager, Dr. Crystal Sweeney, noted the Nova Scotia team’s detection method targets the N2 gene on the viral RNA to identify the presence of SARS-CoV-2 in wastewater samples.

“Since the mutations identified in the variants of concern do not involve the N2 gene,” she said, “our method is able to detect the variants, if present, but we cannot identify whether the viral signal is from the wild-type SARS-CoV-2 or a variant.

“However, we are working with a laboratory here at Dalhousie University to sequence RNA extracted from our wastewater samples to determine whether variants of concern are present in the environmental samples.”

Dr. Sweeney is confident RNA fragments from SARS-CoV-2 cannot easily elude the sensitivity of the team’s testing method. “Through strategic and targeted monitoring, along with innovative method advances, we have demonstrated the ability to detect the viral signal in wastewater when there were only nine active cases in the entire province,” she said.

Data collection and assembly have been organized for fast, accurate retrieval and distribution, with a dashboard that displays the latest sample collection and analysis data. Dr. Sweeney said, “We have also prepared consolidated reports for wastewater testing results at each sampling site so that a complete sampling and data history can be provided for any site at any time.”

Wastewater sampling for pathogens is not new to public health. It was widely used in the past to uncover Poliovirus 1, for instance.  Many countries, most of them in the context of research, are using wastewater sampling for SARS-CoV-2 detection, and Dr. Gagnon said, “We view our work as a research program that builds upon the active body of research that is happening in the field of wastewater surveillance across the globe.”

The current Dalhousie-led project is the successor to a Genome Atlantic-funded pilot in which Dr. Gagnon’s team succeeded in finding evidence of SARS-CoV-2 in Wolfville’s municipal wastewater system, last year. The province’s Public Health officials responded by expanding capacity at the town’s primary COVID-19 assessment centre and opening pop-up rapid testing sites in the community. It was a demonstration of how wastewater surveillance and Public Health officials can work together to mitigate the spread of COVID-19.

Dr. Gagnon recounted, “Genome Atlantic’s support allowed us to get some small laboratory equipment and to bridge a research assistant into this much larger project.” The funding helped finalize some lab testing and demonstrated the potential of the wastewater sampling method on environmental specimens.

The current $852,000 wastewater surveillance project, sponsored by Research Nova Scotia, has more than 15 wastewater sampling sites around the province. Weekly sentinel sampling for sustained monitoring in vulnerable locations is done at wastewater treatment facilities in the Halifax Regional Municipality, Sydney, Antigonish and Wolfville. Specimens are also collected up to three times a week from targeted sewersheds in surrounding areas designated for intense and frequent monitoring.  

The research team’s affiliation with a wastewater research program initiated with Halifax Water and NSERC, said Dr. Gagnon, facilitated sample collection, access to sewersheds and the ability to build the sampling programs critical to the project.

Samples are analysed by the 18-member project team within three to four hours of arrival at a lab. The team uses the new internationally deployed rapid and direct SARS-CoV-2 RNA extraction method, recently developed by Dr. Gagnon and his research group, in partnership with LuminUltra Technologies, an international biotech company based in Fredericton, N.B.  

The company is a key partner in the program along with Halifax Water, which is a co-investigator in the project along with Acadia University, Cape Breton University and St. Francis Xavier University.

It is worth pointing out that although detection of the SARS-CoV-2 signal involves the amplification of RNA fragments, Dr. Sweeney said, “the virus itself may not be in the infectious state.” She added, “although no cases of transmission through contact with sewage or contaminated water have been reported to our knowledge, and studies conducted with these matrices have not detected infectious viruses, it is important to apply the precautionary principle when handling samples.”

The surveillance program is expected to continue until July, with a final report due in November.

Genome Atlantic is helping the newly formed Atlantic Tree Improvement Council, known as AtlanTIC, get up and running with an initial $6 million, five-year regional tree improvement program for long-term forest sustainability.

Among AtlanTIC’s “big objectives,” said Stefan Richard, Executive Director of the new regional non-profit, is to leverage “the genetic gains we get from tree improvement to fight and adapt to a changing climate – to make sure we’re planting the right kind of trees now for harvest in 35-50 years.” To do that AtlanTIC intends to facilitate and coordinate the region’s tree improvement breeding programs in order to respond to threats to commercial woodlands.

“For example,” said Mr. Richard, “if areas of New Brunswick are predicted to warm more due to climate change, perhaps some of the trees from the southern part of Nova Scotia will become more important, because genetically they evolved to grow in warmer temperatures.”

Genomics is set to have a starring role in the organization’s selective tree breeding program. Dr. Richard Donald, an Associate with Genome Atlantic’s business development team who has been closely involved in AtlanTIC’s gestation, cited program activities such as collecting germplasm, the seeds or living tissue from which new plants can be grown; conducting field trials in selected locations with different tree species; and doing data collection and analysis.

For Atlantic Canada’s forest industry, genomics offers new possibilities for developing commercial species with better growth rates, pest resistance, climate resilience and wood quality. That means more sustainable woodland, greater plantation productivity, and a competitive advantage for the industry.

Where conventional tree breeding methods take up to 30 years to verify the inherited traits in a new generation, Dr. Donald pointed out, genomic selection methods require only a few years. Traits can be confirmed in the genetic composition of the tree seeds, making the genomic route to commercial breeding faster, cheaper and more effective.  

The first regional tree development program undertaken by AtlanTIC will expand coordinated progeny testing throughout Atlantic Canada. Data will figure prominently in the initiative and the plan is to develop a database ontology in which relationships among collected data are described. Data collection methods will be standardized, and the latest big data statistical methods region-wide will be used. Also, on the agenda is integrating genomics technologies to improve tree breeding program outcomes, improving training and development of regional expertise, and ensuring knowledge transfers are made to AtlanTIC’s membership.

An estimated $4.7 million will be raised for AtlanTIC’s planned tree improvement activities through member contributions. The Nova Scotia Forestry Innovation Transition Trust recently awarded $315,000 to Genome Atlantic for AtlanTIC’s planned tree improvement work in Nova Scotia. Applications to other funding agencies are being considered.  

As an added bonus, Dr. Donald said the program aligns with Nova Scotia’s Lahey report, a 2018 review of the province’s forest practices that called for designated high-production forestry areas and allowing for biodiversity and more sustainable forests. Mr. Richard explained the program will improve commercial woodland productivity and boost genetic diversity by “bringing together sources of genetic material from across all four Atlantic provinces.”

AtlanTIC’s founding was facilitated by Genome Atlantic, through the work of Dr. Donald and Britta Fiander, Director, Innovation Programs, Genome Atlantic. The organization was propelled into the convener role by its region-wide connections with government and the forestry industry, and by its genomic expertise.

Dr. Donald said Genome Atlantic’s role involved “bringing people together, figuring out how this group is going to work, developing the bylaws, developing the mission statement, hiring the executive director, coming up with the initial budget and writing funding applications.”

The recent Genome Quebec-managed and Genome Atlantic-supported FastTRAC project, which focused on genomic selection for white and red spruce in New Brunswick and Quebec, helped validate the central role of genomics in AtlanTIC’s broad-based regional program. That project, funded through the Genomic Applications Partnership Program, involved J.D. Irving Limited, Laval University and the provincial governments of Quebec and New Brunswick.

AtlanTIC’s charter members from the forest industry are J.D. Irving Limited, Northern Pulp, and Port Hawkesbury Paper, but other companies in the region are expected to join and Mr. Richard said expanding the list is a priority.

The charter group also includes Genome Atlantic as well as government forestry departments: the federal government’s Canadian Forestry Service, Natural Resources Canada; Nova Scotia’s Department of Lands and Forestry; Newfoundland and Labrador’s Department of Fisheries, Forestry and Agriculture; New Brunswick’s Department of Natural Resources and Crown Lands; and Prince Edward Island’s Department of Agriculture, Natural Resources and Industry.

Dr. Donald said membership will also be extended to universities in the region with the research capacity to engage in AtlanTIC’s tree improvement program. 

The reason for AtlanTIC’s formation lies in new and growing challenges facing the region’s forestry industry. There are increasing pressures to modernize facilities and methods, compete with off-shore competitors that have faster growing tree stock, adapt to changing social values associated with woodland, combat the harmful effects of climate change, and deal with the influx of invasive non-native pests.

Meanwhile, a consensus has grown that the region’s forestry players need to work together for shared solutions, which they cannot achieve alone or through their provincial organizations.

Mr. Richard said working together “increases the efficiency in this type of work. Whether it’s funding of research development projects, developing datasets that we require, or accessing different genetics, different species, that we need, we are much stronger as a group than we are as individual members.

 “And you get a multiplying effect,” he added. “So, for every research dollar that our members put in, we can multiply that – we can make the impact greater because we are a group working together towards the same goals.”

In March, the Government of Canada announced research support for a $4.7 Million Complex Gill Health Initiative that will focus on Complex Gill Disease (CGD), a growing health challenge for salmon farming operations in both the Pacific and North Atlantic.  This project, co-led by Genome Atlantic and Genome BC, will validate biomarkers of healthy and compromised gills of Atlantic salmon and use these to develop an early warning system for the development of gill disease on Atlantic salmon production sites across Canada. The resulting genomics-enabled tools for fish health will guide the management and intervention strategies for complex gill disease in Atlantic salmon.

Genome Atlantic congratulates the coast-to-coast research team and acknowledge the generous support of project funders the Government of Canada through Genome Canada, the federal Department of Fisheries and Oceans, Genome BC, Mitacs Canada, Memorial University, the University of Prince Edward Island, the BC Salmon Farmers Association, and industry partners Cermaq Canada, Grieg Seafood, and Cargill. 

In a world of skyrocketing drug costs, a revolutionary new business model is being trialed in Canada that promises to spur the pace of drug development and price the results within reach.

The concept will form the basis of Dr. Aled Edwards’ virtual presentation, Open Drug Discovery – A Business Model that can Discover New Medicines and Price Them Affordably, 12 p.m. April 7. The talk is part of the Centre for Genomics Enhanced Medicine (CGEM) Seminar Series, of which Genome Atlantic is a sponsor.

Dr. Edwards, a protein biochemist, based at the University of Toronto, is a leading thinker in the field of chemical biology and drug discovery. He is best known as the founding and current CEO of the Structural Genomics Consortium, or SGC, a charitable open science research organization with university-based sites in Canada, the United Kingdom, Brazil, Sweden, United States and Germany.

Essentially, SGC is a public-private partnership intent on using open science, sharing data and materials fast and publicly, unencumbered by the peer review publishing process, to speed up discoveries of new therapeutic drugs. SGC’s pre-competitive research in structural biology and medicinal chemistry is funded by a range of large pharmaceutical companies, governments, charities, and Genome Canada.  

In addition, Dr. Edwards is a director of Toronto-based M4K Pharma, which also uses open science principles to partner with organizations that contribute their scientific expertise and research services.

In this case, the focus is on developing a cure for DIPG–diffuse intrinsic pontine glioma–an aggressive form of pediatric brain cancer for which there is no effective therapy for the small population of children affected by the disease. 

What makes M4K Pharma so radically different is it combines open science with reliance on regulatory exclusivity as its primary intellectual property and commercial asset instead of patents.

This new business model is attracting interest from government, foundations and individual funders that have different expectations compared with biotech, pharmaceutical companies or venture capitalists, when it comes to return on investment. Because of this difference, Dr. Edwards is convinced that therapeutics commercialized on the basis of open science and regulatory exclusivity mean discoveries can be speeded up, and the resulting drugs can be affordably priced.

Regulatory exclusivity refers to incentives awarded under many governments’ drug approval regimes. These inducements aim to stimulate the discovery of new drugs by shielding the developers from competition.

On the list is data protection for drugs with new active ingredients. This form of regulatory exclusivity effectively blocks competition from generic drug manufacturers. Some governments give regulatory exclusivity to orphan drugs developed for rare diseases, whether or not they contain new active ingredients and there are other forms of regulatory exclusivity as well.

The argument is that these forms of market protection compare quite well with the average length of patent protection, which, unlike regulatory exclusivity measures, can be costly for companies to obtain, defend and extend.

Dr. Edwards and others associated with M4K Pharma expect its success will reinforce their conclusions about the benefits of open science and regulatory exclusivity for quicker development of new affordable drugs.

M4K Pharma has been making headway dealing with DIPG, now the leading cause of death among pediatric patients with brain tumours. The company stepped in to try and come up with a drug therapy because the market for those who need it is too small and unprofitable for conventional pharmaceutical companies to direct research to the problem.

Using open science, M4K Pharma’s collaborators have already identified the ALK2 kinase receptor as a key pathway along with a potential therapeutic approach to exploit it with precision medicine.

Toronto’s Krembil Foundation has already given the given the open science – no patents approach its seal of approval with a $1.5 million donation to set up Medicines 4 Neurodegenerative Diseases, known as M4ND Pharma. The new company’s brief highlights their plan to pursue new genetic drug targets for Parkinson’s disease and Amyotrophic Lateral Sclerosis or ALS modelled on the M4K concept.

The number of attendees at Dr. Edwards’ April 7 virtual presentation is limited. Register here.

[https://www.eventbrite.com/e/virtual-cgem-seminar-series-april-7th-dr-aled-edwards-tickets-142934229127.] Dr. Edwards is a professor at the University of Toronto, and Adjunct Professor at the University of Oxford and McGill University.

When he entered medical school at Charles University, in Prague, Martin Alda, knew without a doubt, his specialty would be psychiatry. He “never had second thoughts,” he said.

“For me, it represented ‘the royal road’ to a better understanding of the human mind and brain, and their mutual relationship.“  He noted, “Psychiatry is among the most complex and yet less developed areas of medicine, and there is still much work to do.”

Today, Dr. Alda is one of the world’s leading experts in mood disorders and psychiatric genetics.

In Halifax, he holds the Killam Chair in Mood Disorders at Dalhousie University, a position he has filled since 2007, and heads of the clinical Mood Disorders Program at the Queen Elizabeth II Health Sciences Centre, while maintaining adjunct professorships at McGill University, the University of Pittsburgh, and his alma mater in Prague.

Last year he picked up the Colvin Prize for Outstanding Achievement in Mood Disorders Research and the Heinz Lehmann Award for outstanding contributions to the field of Canadian neuropsychopharmacology research – awards relegated to the top scientists in those fields.

In a career largely devoted to studying and treating the highly inheritable conditions of bipolar disorder (formerly known as manic depression), schizophrenia and depression, Dr. Alda has pushed to close psychiatry’s knowledge gaps about these maladies through three lines of inquiry: mapping genes for these conditions, linking the genetic predisposition to the treatment response, and examining how genetic risk manifests in the behavioural and clinical features of the illnesses. He uses methods that run the gamut from clinical, molecular-genetic and biochemical to brain-imaging and neuropsychological techniques to study the disorders in patients and their families.

In recent years the growing possibilities of genomics to unravel the mysteries of bipolar disorder have commanded his attention.

One current project along those lines, and supported by Genome Atlantic, is Early Detection of Bipolar Disorder and Optimized Selection of Long-Term Treatment. The three-year $975,000 study, begun in 2019 by Dr. Alda and his Dalhousie psychiatry colleague, Dr. Rudolf Uher, the Canada Research Chair in Early Intervention, is exploring genetic factors in bipolar disorder which they believe could provide new clinical tools to speed up diagnosis considerably.

He describes the diagnostic tool they have in mind as “a guide for conducting a focused clinical assessment, using the information gleaned from our analyses of clinical factors and family history, together with a panel of genetic markers that can be readily combined into the risk score.”

One of the most significant advances in thinking about bipolar disorder, said Dr. Alda, has come from “a recognition that bipolar disorder starts years before the first manifestation of mania.” This realization has switched the attention of researchers and clinicians to prevention and early intervention. Faster diagnosis and treatment could substantially improve outcomes because the condition responds better to therapies when the disorder is in its early stages.

Now midway through the project, Dr. Alda said, “we have completed analyses of the clinical and genomic predictors of response to long-term lithium treatment and we are now comparing the lithium data with those on other mood stabilizers.” The results could be important.

Currently, lithium is the standard clinical mood stabilizer most often prescribed to treat bipolar disorder. With the right drug treatment, the illness’s manic and depressive episodes are preventable. However, all patients with bipolar disorder do not respond in the same way to the same treatments, and genetic predisposition appears to play a role in determining what therapies work best.

 “As well, we are collecting the largest sample of children of people with bipolar disorder and their DNA samples, most of which are now genotyped,” he said. “This cohort comes not only from our group in Halifax, but also from collaborators worldwide, and includes now over 2,000 such individuals. We expect this will allow us to differentiate, based on genetic data, which of these children are at a higher or lower risk of developing the illness in the future.”

Bipolar disorder ranks as one of the top 10 causes of death worldwide.

“Indeed, over the last several decades the rate of suicide in bipolar disorder and in psychiatric illness in general has not decreased,” said Dr. Alda. “The factors responsible are probably several. One of them is the fact that suicide risk is especially high in early stages of the illness.

“People with bipolar disorder often seek help after several years of struggle with their symptoms. They can be misdiagnosed early on, and then it takes time before their clinicians come up with the right treatment. These factors are also among those Dr. Uher and I hope to improve with our research – that is, to be able to diagnose the illness accurately and early, and shorten the time to find the effective treatment. Another factor is the societal stigma around mental illness.”

The conundrum of bipolar disorder is compounded by the fact that genetics is determinative for the condition about 80 per cent of the time, leaving environmental factors responsible for the remaining 20 per cent.  “In simple terms,” said Dr. Alda, “this amounts to an equation with two unknowns – the genes and the environment.” He is hopeful that, “Once we know the role of the genes, it will be easier to understand the contribution of the environment.”

What sparks his continuing clinical and research interest in bipolar disorder, considered one the most serious in psychiatry?  His response is surprisingly upbeat. Dr. Alda said it’s a combination of the full recoveries he has witnessed in successfully treated patients, their pleadings for a scientific look at the genetics of treatment response, and the talented and gifted nature of many of the patients themselves. This last point has been well documented and he mentioned Kay R. Jamieson’s book, Touched with Fire, as an example.

Being a psychiatric geneticist also suggests genomics may be part of what keeps him so engaged too. These days, it fuels and facilitates many of his investigations along “the royal road” he has chosen to better understand the mind-brain relationship in bipolar disorder.

News release –