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    December 22, 2021

    Spotlight Interview with Dr. Stephen Husbands, Professor of Medicinal Chemistry, University of Bath

    This is an interview with Professor Stephen Husbands from the University of Bath. Dr. Husbands is a Professor of Medicinal Chemistry at the Department of Pharmacy & Pharmacology, Centre for Therapeutic Innovation, Addiction and Mental Health Group (AIM).

    stephen husbands

    Professor Husbands, many thanks for your time. Can you tell us more about how you chose a scientific career? Where did all start?

    It was a combination of subjects that appealed to me and particularly inspiring teachers, so chemistry was the thing that got me early on and took me to do chemistry at the University of Strathclyde. I lived near Glasgow, it was sort of traditional then to go to the local university, and Strathclyde was about as close as I could get. So I started university at 17!

    Very young, indeed. So, can you tell us more about your initial research field?

    I was inspired by and got on well with Professor Colin Suckling during my undergraduate years. He worked in medicinal chemistry. I went on and did a PhD with him, and so he got me interested in applied medicinal chemistry. Then, I joined the University of Bristol Chemistry Department and the Psychopharmacology Unit with Prof. John W. Lewis. During his time in industry he was responsible for bringing Buprenorphine to market. The Bristol group was built up to better understand and improve the pharmacological characteristics of this compound, Buprenorphine, which is an opioid partial agonist useful for treating opioid use disorders. So, I joined the team as a postdoc, which started my research in CNS disorders in general and drug use disorders in particular.

    Drug use disorders are a complex issue involving personality and physiological aspects. What are the main challenges in the area?

    Indeed, any sort of neuropsychiatric disorders is complex. We've got this sort of black-box type problem of the brain because you can't easily just take a little piece out to have a look at it. So, actually working out what's wrong with any particular individual that you're trying to treat is not a simple matter at all. In addition, although there is a lot of heterogeneity amongst the population, we still tend to lump people with, for instance, depression altogether. We are happy these days, thinking that cancer is a lot of different diseases that need to be treated differently and ultimately, I guess we'll end up doing something like that for depression. But the problem is how do you stratify and group patients because we have no suitable means of doing so. There's a lack of knowledge of the diseases we're trying to treat. We have broad ideas, but we don't know the details. And then, for us in the drug use area, it's all further complicated by the difficulties of using controlled drugs in research and clinical trials. So, from the research point of view, recreational drugs like MDMA should make ideal drugs to study if you're trying to help people's mental health, but there is push back against using these as potential treatment agents.

    It's a fascinating area of research, for sure, especially because of the complexity and the multifactorial nature of the same.

    It's getting a little better, I guess. There are a few trials with the MDMA and ketamine for PTSD, depression and alcoholism. These show promise, so hopefully, we can keep moving in the right direction.

    We've seen a lot of cannabinoid research resurgence. What do you think of the field?

    Yes, this is an area that I'm personally interested in. There is work in Bath on the involvement of the cannabinoid system in inflammatory diseases and specifically, endocannabinoid secretion into the intestinal lumen and how this system can be modulated to treat inflammatory bowel disease. That's been a real eye-opener to me because I've always tended to think of cannabinoids in terms of CNS activity.

    It is interesting to look at the development of (illicit) synthetic cannabinoid receptor agonists. So, we hear about the sort of "spice" type compounds. There are so many new compounds appearing on the street, and therefore being used by people on a very regular basis. There are hundreds of these, not one, which we don't know much about, for example, even their basic pharmacology, certainly nothing about safety, but suddenly they are being taken by people. So that's, the whole area is interesting, including their detection. We're involved in a project developing a point of care detection device for synthetic cannabinoids. It'll pick up the series of novel synthetic cannabinoids used by people and help direct the care patients receive.

    In relation to your research, you have new bioactive compounds with promising safety profile compounds in the area. What are now the challenges to progress your compounds?

    Being in academia, there is an issue. There is a sort of well-known valley of death between developing novel and interesting potential therapeutics and having means and resources to translate those into any clinical program or even development programs.

    I've been fortunate enough to work with collaborators that can take pharmacological evaluation in to primates, preclinical safety, etc. Every study requires expertise and money. From an academic point of view, it's not just the money to fund the studies, it is also the expertise, and that really means better interactions with the industry. With funding there's always a potential route forward.

    Effectively, the ideal solution is to find some industrial partners with expertise to carry forward the project.

    Some academics have the time and energy to form a startup maybe and go that way. But I think that licencing is the more straightforward available route to work with the industry. They know what they are doing.

    In terms of data, why did you implement CDD Vault?

    Because I work with many collaborators, I have got to the point where we have quite a few exciting compounds, so people are getting in touch requesting samples to test further. So, I will be getting data back from a huge range of different sources. Ultimately, I'd like to have a resource database to manage all of this data within, rather than having a whole load of different folders lying around my office with different collaborators' information. So I think being able to pull that together and really see at a glance, well, all the data that we've got on a particular compound, no matter which collaborator it comes from, is useful to me. We haven't managed to transfer everything yet. But that's the endpoint.

    You mentioned that you work in collaboration. Do you see collaborations and collaborative drug discovery research growing?

    Every project I've been involved with is collaborative. For instance, I don't have the expertise in pharmacology, and I don't really want to put in the time to try and learn to do that. I'd rather work with experts and get good data. So yes, for me, collaborations are hugely important. And I think the way science has gone; there's so much more we can do now. No individual can be an expert in all areas, so we should be willing to work with whoever. Yeah, it's certainly really important throughout the development process and in basic science. I'd much rather work with a number of experts. It has benefits in terms of the quality of data you get, but also, you're just in touch with people interested in a similar question or similar field. So, it's an excellent excuse to chat with interesting people and learn from each other. Having conversations with people is one of the best ways to come up with new ideas or think about your own projects in a different way.

    What else do you need to advance your discovery research further?

    An improvement would be if there were a little bit more stability in the funding or personnel within the academic sector. We're in a constant battle looking for funding, and when you get some funding, then almost straight away you're looking for the next set of financing for when that one stops, and that's a never-ending cycle for academics. And that's not necessarily the best use of our time because searching for funding is not the same as thinking about your research projects. So, I think having a little bit of stability and maybe distributing the funding through different mechanisms, maybe longer-term or going back to having PhD students being given to academics every few years. There's too much academic time spent searching for money and not enough time spent thinking about research.

    How did COVID impact your team, your research?

    There was an obvious extreme impact early on with the shutdown. So, even the research labs shut down during the first lockdown. But, once things worked out, the research carried on. We're in well-ventilated environments and we can work safely. However, funders, quite rightly, in a way shifted their focus towards how COVID affected their area. A significant change has been the effect on charities to scale back a lot of their funding because they don't have the income, which is an essential funding source for medical research.

    One of the longer-term effects, I think that has affected how the scientific community communicates with each other. On the positive side, I noticed that we have seminar speakers from throughout the world. So rather than just having people from the UK or maybe Northern Europe who could get here easily, we can have people from as far as Australia, the US etc. It doesn't matter where scientists are. So that's been a good thing. You know there are real positives that can be retained even when we return to regular conferences.

    I would love to know your take on what you think the future holds for science? And maybe your message to the next generation of scientists?

    Perhaps, COVID taught us, and the whole population, that pharmaceutical and pharmacological treatments, including vaccines, are essential. In my area of neuropsychiatric diseases we also need to think more broadly to include psychological therapy where appropriate. Of course, with COVID, we see other social changes, such as wearing masks in crowded places. So we have to sort of dovetail both the pharmacological approaches with other types of measures that can help treat or control diseases-so trying to think more broadly than just drug treatment.

    For the next generation of scientists, the message is that there are always new problems to address and new technology for you to embrace. And again, collaborate. Get out there. Talk to your colleagues, talk to as many people as possible, and don't be afraid to work with people. Don't be afraid to admit how little you know. Get out there and you will keep learning new things. To me that's the way to stay interested over the years and have a long life in research.

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