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While the field of chemistry is known for synthesizing new molecules with a desired function, proponents of green chemistry have long pointed out that chemists need to understand toxicology to be able to truly design safer chemicals and products. That's why at the 29th Annual Green Chemistry & Engineering Conference, which will focus on Good Health & Well-Being through Sustainable Chemistry, we are featuring a panel of toxicologists for a keynote presentation.
“I think that this focus on Good Health and Well-Being and how that naturally links to toxicology is not something that's typical of the GC&E conferences. I'm happy to see this coming up, because I think this integration of an understanding of toxicology is really key to being able to make truly safer and more sustainable chemicals,” says Carla Ng, conference co-chair and moderator of the panel. Read more to hear from the panelists about how they came to be passionate about the field of toxicology and to hear their thoughts on the importance of the intersection between sustainability, toxicology and environmental chemistry.
Make sure to check out Part 1 to meet keynote speaker Louise Proud, and stay tuned for the announcement of the keynote panelists for the third keynote talk of the conference.
Could you tell me about your career path and how you became passionate about your work?
Jamie: I'm an environmental toxicologist who found toxicology by accident after I graduated from undergrad. I didn't know what I wanted to do, but I worked in health and safety and learned about toxicology that way. I'd always been passionate about the environment, so it just made sense because it was a field that combines basic science and a lot of policy interactions.
I worked on PFAS for several years while I was a postdoc, and I've continued to work on it in my lab. But I didn't really start to get passionate about PFAS until I started to meet people in communities who had been exposed to PFAS in their drinking water and had become advocates for their communities and activists for public and environmental health. That's when I realized that the work that I do has the potential to have very real impacts on people's lives, in a different way than basic science does.
Carla: I'm a chemical engineer by training. I got into engineering because I really liked the way that it could use math and physics to explain phenomena all around us.
When I started my postdoc, I was working on pesticides for a while, and then I wanted a challenge. I liked bioaccumulation research I had done in grad school, but I wanted to work on chemicals that didn't act like your normal chemical. I was trying to decide what to work on, and I stumbled onto PFAS because that's what other people in my group were looking at.
They were pretty unique in their behavior in the environment and in the body, and so that got me fascinated to understand why they distribute the way they do, why their toxicokinetics are the way they are. After working on many classes of chemicals and looking at their toxicities, that really got me interested in the sustainability and green chemistry aspect of it, thinking about how we can design these terrible properties out of chemicals so that we don't keep making these same mistakes over and over again.
Jakub: As a computational/theoretical chemist I was largely discouraged to step outside the mainstream of my field when considering my postgraduate steps many years ago. I feel this is still the shared sentiment by many, who would consider such career moves to be betrayals of the perceived rigor and tradition. Unfortunately, such thinking and mentoring misses many great opportunities that reside at the crossroads of disciplines and puts most scientists in a 'dog-eat-dog' fight for the razor-slim spotlight of the cutting-edge part of the field. It also makes us scientifically siloed, which, while helpful in pushing the frontiers of traditional fields, ignores unintended consequences of our work.
My passion has always been to link seemingly disconnected things, to establish relationships that others might have missed. I am also a contrarian by nature, so I like to go against the flow. Lastly, I am realistic about my own abilities, which has made me recognize that I am much more likely to have a positive impact in cross-disciplinary translation and adaptation of methods rather than in pushing the theoretical boundaries within my traditional field. Seeing your work have a clear and tangible impact on the way we do things has always been the biggest motivation for the professional choices I have made, and this is what brought me to toxicology and green computational chemistry.
Carrie: For as long as I can remember I've been really passionate about the environment and motivated to have a positive impact on the Earth. This has been a common thread for me even while I've worked in many different fields. I got a bachelor's in chemistry, Ph.D. in oceanography, and then I was a postdoc and early faculty in environmental engineering before returning to a chemistry department, but in all of these roles I was studying how synthetic chemicals interact with the environment and living things.
For those who might be unfamiliar with toxicology's role in green chemistry, could you describe how toxicology is related to designing safer chemicals and pharmaceuticals?
Jamie: Toxicology and green chemistry need to work together more closely. Right now, toxicology often comes after the chemical has been designed. And it really should be a component of the design process.
Carla: Toxicology is hard. You’re trying to get a chemical that has a certain property that you want. And often, those properties that you want will have some implications for the way that it interacts with biological systems. Biological systems are complex, so you're just adding these unknown factors that need to be determined to get a successful product, and that pushes against trying to create chemicals or products quickly, or cheaply.
But determining toxicological effects in advance is absolutely essential because instead, we spend all the money afterwards trying to remediate environments and help people who have been harmed by these things. I think the further development of green chemistry to specifically incorporate toxicology is really critically needed.
Jakub: Toxicology and green chemistry are intrinsically linked through safer chemical design because both require the understanding and quantification of hazard. While toxicologists have traditionally focused on risk, which factors in both hazard and exposure, green chemists have been singling out hazard as the key characteristic to control.
For a safer chemical design, which requires a multi-criteria analysis, the ability to separate structural drivers of performance, hazard, environmental fate, synthetic feasibility, cost, etcetera, is essential if we want to focus solely on hazard. Computational models, particularly those that are physics-led, such as quantum-mechanical tools, are helpful here, as are modern AI approaches, which can leverage large data to figure out, for example, what novel chemicals we can make from the platform compounds currently available.
What are the gaps in models and tools that need to be filled to make progress towards implementation of safer products & processes?
Carla: We've lived, at least for industrial chemicals, in a very data poor era, where we don't know what all the chemicals are. We don't know all their structures. We don't necessarily have all of the standards that we need to evaluate them. We're trying to build models without having experimental data that is needed to train them. So I think having an understanding between the modelers and experimentalists about how to assess and evaluate data quality and applicability is really important.
Jamie: I think we have to better align what we want from a sustainable chemical with the types of toxicities that we're concerned about. For example, if our main concern for green chemistry and sustainability is lack of persistence and ability to degrade into substances that we already know and accept are safe for the environment or for people, then toxicity studies should focus on degradation, byproducts, and persistence type questions rather than a specific type of toxicity.
Jakub: Currently, regulatory frameworks are warming up to the use of in silico models to assess hazard. Globally, adoption of these tools has increased across endpoints and chemical sectors. However, we are still lacking a comprehensive translation of the full toolbox developed by computational chemists and biologists to predictive toxicology.
In particular, we need the regulators to embrace quantum mechanics as the 'third leg' of the in silico 'stool', which is currently 'wobbling' on expert systems and statistical models in a weight-of-evidence approach. It's time to add models that use quantum mechanics as an indispensable component of the testing paradigm! The proof is in the pudding, and here the pharmaceutical industry already relies on these models to assess the hazard of active pharmaceutical ingredients and intermediates internally, so we know these methods work. The perfect example, which may 'shatter the glass ceiling', is the current crisis of nitrosamine contaminants in pharmaceuticals, where in vivo models present an economically 'difficult-to-swallow' pill (pun intended), and so both the regulators and industry have to embrace quantum mechanics as part of the solution.
Carrie: A major gap I think about a lot is the gap between external chronic exposure and internal dose. In other words, if I'm exposed to a mixture of chemicals at a low level every day, what does that mean in terms of the exposure that's actually occurring at the site of action (in a cell, etc.)? I've been working to understand how to translate chronic exposures to internal doses so that when we do safety assessments and toxicological tests, we can make sure they're done using relevant mixtures.
Jamie, Carrie, and Jakub, what new perspectives do you hope attendees walk away with after your keynote discussion?
Jamie: A basic understanding of toxicology and how it has been used to inform the public, decision makers, and other scientists about hazards of particular chemicals. Also, how toxicologists work with exposure scientists to understand, predict, and characterize risks.
Jakub: Keep an open mind when considering potential solutions to new problems. We have developed a reductionist paradigm to solving scientific problems, and though helpful, this framework limits our ability to think creatively.
Carrie: An appreciation for the interdisciplinarity of this type of work. My research is informed and strengthened most by working with excellent collaborators with different areas of expertise (like Jamie). Understanding the whole story from exposure to accumulation to effect requires effective collaboration between multiple experts in different fields. It's a growing area and we need to train more students at the undergraduate and graduate level to work on safety assessment with experience in both chemistry and biology, particularly with an appreciation for the complexity of environmentally-relevant mixtures.