Looking to Toxins to Understand Pain: A Chat With Australian Pain Society 2020 Rising Star Samuel Robinson

What can toxins from bees and wasps teach us about pain? Quite a lot, it turns out…. Image credit: Makrobetz/123RF Stock Photo.

Editor’s note: This interview originally appeared on the IASP Pain Research Forum and has been adapted for RELIEF.

Samuel Robinson, PhD, is a postdoctoral research fellow at the Institute for Molecular Bioscience, University of Queensland, Australia. Robinson recently won the Australian Pain Society’s Rising Star Award for 2020, which showcases up-and-coming pain researchers in Australia. Like many academic conferences, the 2020 Australian Pain Society 40th Annual Scientific Meeting, where Rising Star Award winners give a plenary presentation to showcase their work, was unable to proceed due to the COVID-19 pandemic. However, Robinson recently spoke with Lincoln Tracy, a research fellow at Monash University, via Zoom. Robinson discussed his journey to pain research, his work on plant and animal toxins and what they can teach us about the pain system, and much more. Below is an edited transcript of their conversation.

What first got you interested in science?

I guess my earliest memory of science is collecting bugs in the backyard – I was one of those kids [laughs]. So I think I’ve always been inclined that way, to an extent. I’m fortunate that I’ve turned what I used to do for fun as a four-year-old into a job.

How did you end up in pain research?

I’m passionate about biology – the study of life. When I was at university, I studied neuroscience as an undergraduate. I essentially chose neuroscience because it was the hardest course to get into – no other reason than that. I learned a lot about neuroscience during the degree and got a job in a laboratory after my honors year. During my time in the lab I was using a range of different toxins as tools to understand neurophysiology. I thought getting to use these naturally derived toxins as tools was really cool.

It was around this time that I decided I wanted to do a PhD. The toxin-related work really appealed to me and inspired me to write a proposal for a PhD. I sent my proposal around to a few labs that looked like they would accommodate this type of research. I accepted a scholarship from Monash University to do a PhD studying toxins from cone snails with Ray Norton.

Following my PhD, I did a two-year postdoc with Toto Olivera at the University of Utah, where I continued working on neurotoxins from venoms. At this point I wasn’t specifically studying pain, but a large portion of the lab’s work used mammalian sensory neurons to identify targets for the toxins the lab was working with.

Samuel Robinson

When I came back to Australia in 2017, I wanted to start my own research program. I had developed a range of neuroscience skills and knew a lot about toxins by this point, or at least I thought I did. I wanted to pursue my passion for toxin research, but I needed to find a niche. So I wrote a research program to look for toxins that cause pain. No one had been really interested in that topic because there are no direct applications for a pain-causing toxin – not in medicine, anyway.

What is the overall aim of your research?

You can probably split my research into three aims. The first is to build a library of pain-causing toxins. I’m doing this by searching animal venoms – the things that sting and that we know hurt. We know that there are different kinds of pain that people experience from these venoms, and so I want to build a library of toxins that cause pain by acting on our nervous system. The second aim is to then see how these toxins work – to figure out what they target and how they cause pain. Then, ultimately, the third aim is to understand how the targets of the toxin contribute to normal pain perception in humans as well as to pathological pain states.

How many toxins have you identified so far?

Given that there are thousands of venom-producing species and probably thousands of different chemical strategies they can use, there’s basically an infinite number of toxins to identify. I can’t look at all of them, so I’ve been focusing on Hymenopterans – bees, ants, and wasps. No one has really looked at their venom before in much detail, and there is a huge amount of diversity amongst these species. I’ve found dozens of new pain-causing toxins just from these animals.

Were there any other factors that contributed to your decision to focus on bees and wasps?

Bees and wasps are probably the best studied from a qualitative perspective, in terms of the pain that you experience. This work has primarily been done by Justin Schmidt, an American entomologist, who has spent 40 years studying Hymenopterans. During his studies he noticed that there were differences in the types of sting pain that he experienced, and he eventually started recording this information and writing descriptions of the different stings. In 2018 he published The Sting of the Wild, where he explained all these experiences. It’s a great read.

But my point is that he noticed there was a huge diversity in the experiences of the stings, which implies a diversity of chemical or pharmacological strategies being used by these animals. He had built this framework for me to start from; I just needed to go on and do the chemistry and pharmacology. That was a real drawing card. I’ve since reached out to him, and he has become an important collaborator for me.

How else can these toxins be used to improve our understanding of the human body?

When I initially came into the field of toxicology, I was using toxins to study the ion channels [specialized proteins that control the electrical excitability of cells]  involved in long-term potentiation [a strengthening of the connections between nerve cells] and memory. One of the great things about toxins is that they are often very selective, which makes them great tools for delineating specific ion channels and receptors [specialized proteins in the cell membrane]. So they can be used in neuroscience to study the central nervous system, and since many toxins target the blood or the heart, they are also used in studying the cardiovascular system. They’ve also been critical in understanding the neuromuscular junction [where nerves communicate with muscles.]

Within your line of research, what do you hope to know in five to 10 years that we don’t currently know?

My hope is that I will find that there are more – and better – pain [drug] targets than just opioid receptors [proteins to which opioids attach]. And I think we are starting to realize that this is going to be the case. We have identified a few toxins that target different ion channels and receptors, which tells us that these alternative targets are important in pain sensation.

What has been the most interesting study you have been involved with over your career?

The most interesting one was probably at the end of my PhD when I was heading over to Utah for my postdoc. I was already working with that team, and we discovered that some cone snails hunt and paralyze fish before eating them. When we looked at the venom from one species of cone snail, we came across something that looked like insulin. It turned out to be extremely similar to fish insulin. We were wondering, “What on Earth is insulin doing in there?”

We investigated this further and found an old YouTube video of an endocrinology lecture where someone dropped a fish in a bucket of insulin. The fish was knocked out and flipped belly-up straight away; it had gone into a sugar coma. When he took the fish out and put it back in normal water, it recovered.

What this said to us is that you could just apply the insulin to the local water around the fish; you didn’t even need to inject it. When we investigated the structure of the insulin, we noticed that the insulin in the cone snail toxin was structurally different from normal insulin. This difference meant that it could act on the fish straight away; there was no delay in action. This also means that it could potentially be valuable as a quick-acting drug for diabetes.

What does winning the Australian Pain Society Rising Star Award mean to you?

I hope that it will help my chances of getting fellowships and grants in the future, as this sort of award makes a big difference in those applications. It was also going to give me the fantastic opportunity to speak to a broad audience of Australian scientists in my field [before the annual conference was cancelled]. I’m hoping that I will be able to speak at next year’s meeting, so that I can still have the opportunity to share my research and out-of-the-box approach to studying pain with other scientists in Australia.

Lincoln Tracy is a postdoctoral research fellow in the School of Public Health and Preventive Medicine at Monash University and a freelance writer from Melbourne, Australia. You can find him on Twitter @lincolntracy.