What do glaucoma, oil sands tailings ponds and solar cells have in common? They all appear in the resumé of Dr. Vikramaditya Yadav, MCIC, a chemical engineering professor whose pursuit of bio-inspired tools for carrying out critical chemical transformations has taken him to some unexpected places.
One of those places is Alberta, where each day more than 120 oil sands projects ship 2.6 million barrels of bitumen, diluted with light crude oil and other chemicals, into the United States. Most of this bitumen is found deep within the ground and can only be extracted via the costly process of steam injection. But some — about 20 per cent — lies closer to the surface, allowing for open pit mining. These account for much of what has been extracted so far.
Open pit mines leave behind tailings ponds containing water as well as sand, silt, and clay. In all, tailings ponds in Alberta house about 1.3 trillion litres of water – the equivalent of 500,000 Olympic swimming pools. Significantly, the water also contains small amounts of residual bitumen and various chemicals, such as naphthenic acids, polycyclic aromatic hydrocarbons (PAHs), as well as metals such as cadmium, lead, and arsenic at levels that are toxic to fish, birds, and other wildlife. When tailings ponds leak, they contaminate nearby water sources such as the Athabasca River, which Indigenous peoples have historically relied upon as a water and food source. And on top of everything is the price tag: future taxpayers will be footing an estimated $27 billion cleanup bill, according to the Alberta Energy Regulator.
“The biggest challenge to dealing with tailings ponds is their scale,” says Yadav, an associate professor in the Department of Chemical and Biological Engineering at the University of British Columbia (UBC). Straightforward, common-sense approaches, such as filtering the water to remove contaminants, are hard to scale up to the level required. In wastewater treatment, UV radiation is often used to break down contaminants; however, UV rays can’t penetrate the great dark depths of tailings ponds. Some researchers have considered using additives like titanium dioxide, which would accelerate the breakdown of certain species, or adding sorbents such as activated carbon. But these may not provide the broad-spectrum cleaning power to remove the wide range of contaminants and they leave behind solid waste that still requires treatment.
Yadav believes that the solution may lie in what he calls “getting the ponds to treat themselves.” Despite their toxic nature, tailings ponds are still home to microbes that eke out a living by breaking down some of the toughest organic contaminants. Shaped by the power of evolution, these microbes are accomplishing what humans currently cannot. Learning their tricks could offer a way forward.
As Yadav points out, there is plenty of precedent for this approach. Many of our modern pharmaceuticals are derived from natural sources.
“The plant world is filled with remarkable molecules,” he says. His team is targeting the biochemical machinery by which living organisms break down some molecules and build up others. The research, which has applications ranging from industrial bioremediation to biomedicine, is carried out via metabolic and enzyme engineering, a branch of synthetic biology.
Yadav and his students pursue both theoretical and experimental strategies, using mathematical models to understand how enzymes work and manipulate their amino acids sequences to improve their activity, stability, or product specificity. These tools can be used not only for the simplest organisms, such as bacteria, but on higher organisms like plants and human stem cells, looking “to nature for wonderful chemical reactions.”
In the past few years, Yadav and his colleagues at the UBC’s Biofoundry, which customizes biosynthetic enzymes in collaboration with Vancouver-based Metabolik Technologies and Alberta’s Suncor Energy. The team identified a number of bacterial strains capable of “eating up” naphthenic acids, then subjected these microbes to elaborate genetic and metabolic experiments to find out which enzymes in the bacteria are responsible for consumption of the acids. This work is now improving the ability of the natural microbes to degrade naphthenic acids by, among other approaches, introducing extra copies of the genes that encode the enzymes into the bacteria to boost enzyme production.
Yadav has high hopes for this project: while native bacteria can consume about 15 percent of the naphthenic acids over a 30-day period, Yadav predicts that within a couple of years, this collaboration will net a bacterial strain that “eats up 99 per cent” of naphthenic acids, using these toxic waste chemicals to extract energy for such normal metabolic activities as cellular repair and the creation of additional biomass.
If successful, the strains will need to be manufactured and deployed at an industrial scale, which is Metabolik’s forte. The company specializes in process engineering, conceiving and delivering large-scale wastewater treatment projects that are currently being pilot-tested in Alberta.
“We extracted the natural bacteria from oil-sands water and tweaked certain genes,” says Yadav, adding that early tests indicate that the naphthenic acids-mitigated water is no longer toxic. “It’s still the native bacteria, with some genetic elements changed to improve the degradation rate. Essentially you’re using the innate ability of the pond to treat the pond.”
Yadav and his colleagues are currently working with Innotech Alberta, the provincially-funded R&D corporation that replaced the Alberta Research Council in 2016. Indoor testing of the microbes got underway this fall and he is looking forward to an expanded, outdoor trial next summer that will use of actual tailings pond water. He adds that the first generation of microbes used in this work are reducing the concentrations of naphthenic acids to levels that are permitted by government regulations. Generation 2, which is under development now, “will ideally hit the 99 per cent level.”
Encoding new expressions
Tailings pond mitigation is one of a string of innovations that Yadav has achieved throughout a remarkable career, one that resulted in the Canadian Society for Chemical Engineering (CSChE) acknowledging him in 2017 as one of its emerging leaders. He also chairs the Biotechnology Division of the Chemical Institute of Canada.
Yadav credits liberal, educated parents — his mother, a chemical engineer, runs a pharmaceutical manufacturing company in Mumbai, India — for a childhood “filled with escapades and experiments.” He first entered the computer engineering program for his undergrad degree at the University of Waterloo in Ontario but quickly switched to chemical engineering, enthused by the prospect of “being able to work on topics that span scientific boundaries.”
Rather than join his mother in Mumbai, Yadav forged his own path, focusing on an area of science where North America leads the global research pack: synthetic biology. He attained his PhD at Massachusetts Institute of Technology, followed by post-doctoral studies at Harvard University, then chose UBC as his home for research, drawn to its status as one of the top universities in the world in environmental and life sciences. (UBC has been rated by the Times Higher Education as the world leader in education and research in environmental and sustainability sciences.)
According to Yadav, Canada “is a leader in science and engineering and we consistently punch above our weight. It’s high time we start acknowledging that we are a force in research.”
At its simplest, genetic engineering is introducing a new gene into an organism in order to encode a new expression or behaviour. Metabolic engineering is using these tools for processes connected with the production of desired molecules, or conversely, the destruction of undesired ones.
Yadav had early success working with light-harvesting molecules produced by bacteria, including a discovery that he admits came about by happy accident. One of Yadav’s post-doc students, a materials scientist, decided to undertake some novel tests on lycopene, a photo-active molecule that gives tomatoes its characteristic red colour.
Lycopene strongly absorbs key wavelengths of solar radiation, a property that makes it attractive to those researching dye-sensitized solar cells. Unlike traditional silicon solar cells, which require bright sunlight for maximum efficiency, dye-sensitized solar cells are designed to make the most of low-light environments; even on cloudy days they provide a reliable base level of power.
“That’s where it trumps a conventional solar cell,” explains Yadav.
Unfortunately, lycopene has a high degradation rate, especially under bright light, which has so far rendered it impractical for use. Sarvesh Srivastava, a researcher from the Technical University of Denmark who is working with Yadav, subsequently ‘pasted’ titanium dioxide on the lycopene-producing bacteria and sintered this material to create an extremely porous, high-surface area conducting electrodes filled with lycopene. The resulting dye-sensitized solar cell showed enough promise that Yadav is now collaborating with Dr. David Wilkinson, who holds the Canadian Research Chair in Clean Energy and Electrochemical Technologies at UBC, to further develop the technology.
Yadav’s research is also applicable to the creation of new medicines. Alongside his other projects, Yadav has looked at the medical potential of cannabis, which has been used in the treatment of neurodegenerative maladies. Aside from the well-known hallucinogen tetrahydrocannabinol, the dominant cannabinoid produced within the cannabis plant, there are at least 100 other molecules made via similar metabolic pathways. Early-stage research has suggested that some of these may have potential as possible treatments for conditions such as Huntington’s disease or breast cancer.
Synthetic biology allows Yadav to select the enzymes used to make these minor molecules and dial their levels up or down, creating customized strains of cannabis. On this project, Yadav and his team are collaborating with Vancouver-based InMed Pharmaceuticals. InMed has created algorithms to predict which molecules are likely to be of interest, while the genetic engineering is carried out in Yadav’s laboratories.
One example is the non-psychoactive cannabinoid, cannabigerolic acid, or CBGA, which may be capable of relieving some of the symptoms of glaucoma. Yadav argues that that finding such a promising new medical molecule is only 10 per cent of the solution: much of the rest has to do with getting it to work in the human body. “It needs to be delivered to the site of action, have good absorption and you don’t want side effects,” he says.
To enhance the effectiveness of drug delivery, Yadav moved into an area outside his expertise: polymer synthesis.
“Liquid glaucoma medications are inadequate as 95 percent runs off the eye, preventing the drug from doing its job,” he says. Instead, Yadav and his team have devised a polymer hydrogel filled with nanoparticles containing CBGA, which was well absorbed and helped relieve glaucoma symptoms in test animals. Yadav has filed patents on the discovery and says he will be working with InMed to take it to market.
Whether the challenge is cleaning up contaminated environments or providing relief from complex medical conditions, Yadav sees great potential for synthetic biology to augment the traditional chemistry-based approaches.
“Nature is filled with these wonderful chemical reactions,” he concludes. “If we can identify them, we can mass produce that one chemical reaction to, say, eliminate plastics. We need to bring enough creative people into the room, focus on the technology, and deliver meaningful solutions.”