Embedding Ethics to Accelerate Discovery

Elizabeth Christopherson is President and Chief Executive Officer of the Rita Allen Foundation. Cynthia Friend is President and Chief Executive Officer of The Kavli Foundation. Both foundations are Civic Science Fellows funding partners and members of the Civic Science Funders Collaborative.

Cynthia Friend: Dame Carol, your work is very fundamental, basic research, but nevertheless it has significant impact in many fields, including healthcare and medicine. I’d appreciate if you’d take the time to explain the significance of your work and talk about some of the potential applications.

Dame Carol Robinson: If you think about a protein, it’s folded because it’s surrounded by solution. If you put it into the atmosphere, it starts to unfold and then you lose all the information. But very early in my career, I worked out that if we could keep it folded, then it could come with its partners, and then we would learn something about biology that no one had seen before. I’ve always found that so exciting, because typically proteins are studied in X-ray crystallography or more recently in cryo-EM. Studying them in the gas phase was considered quite controversial. But I always thought if we can do this, we will learn something. I’m not sure what, but we’re going to learn something. And I think that’s for me the excitement about basic research. You don’t actually know quite what you’re going to find, but you will find something, and it will be important.

Cynthia Friend: That must have taken some technical machinations, trying to keep those water molecules in the solution around the protein. Could you elaborate on how you came to do that and also how you were able to continue to do that work when people were skeptical?

Dame Carol Robinson: Early in my career when I wasn’t very well known, people would say, oh, that poor girl, why is she doing this? It’s never going to work, girl. I thought it was particularly patronizing. However, now many people look at proteins in the gas phase and try to understand their structure. The breakthrough moments with the instruments were quite interesting because I started in mass spectrometry from the age of 16, so I had no fear of the instrument. When I started it was very new, and I’d taken it apart. I had rebuilt it. I really got to know it. And so when I knew what I wanted to do with it, I wasn’t scared to pull it apart until I got the conditions that I really needed.

It took some courage and determination. I always think, well, if you don’t do what you want to do, then you really shouldn’t be in science. You need to do what you feel compelled to do. I was very passionate about what I was doing, and I was determined it was going to work.

Elizabeth Christopherson: Where does the civic element and where does the ethical element come in? When do you have to go beyond the knowledge that you have to start thinking about who else has to be engaged and how?

Dame Carol Robinson: Other work in our laboratory focuses on the human brain and how the receptors and transporters might be communicating. This topic has a huge amount of ethical importance and questions. We are asking the question, is there a difference in the wiring of receptors in the brains of people who die by suicide? The thing that I found but hadn’t anticipated, and this is why you should think about ethics before you do things, not afterwards, was the amount of pressure that we would experience from the families to find something. The ethics piece there is, okay, maybe we find nothing and that’s also fine.

The first thing we looked at was the excitatory neurotransmitter. You might imagine if you’re depressed, you don’t have much excitation coming through with your transporter. So, we looked at that and there was no difference. But then we looked at how the neurotransmitters are sensed by their receptors, and we saw a definite difference in their organization. Now we are engaging with a patient group who suffer from major depressive disorder. That again leads us to all sorts of ethical issues.

The very best thing about having Mackenzie Graham in the institute, as our lead in the ethics program Kavli very generously sponsored for us, is that he gets me to talk about it and to find the right language. For a long time, I got tied up, and then I would start to feel very uncomfortable. I didn’t like giving the talk even. I was thinking, I need the tools to find out what the public finds acceptable and how that becomes ethical.

During a difficult personal time, a student in our group expressed a bit of discomfort with our using dead people’s brains in our research. And I said, well, it’s just a tissue. But it’s not just tissue, is it? It’s much deeper. For me, that was a big ethical dilemma that I wasn’t trained to address. I’m a chemist. A plus B gives us this. We don’t talk really about ethics.

Now Mackenzie comes in and we see him, we have coffee, we have lunch with him. It becomes more of a norm to talk to him. It’s not, oh, the ethics guy’s in today, what are we going to talk about? He’s just there. If you have a problem, talk to him. Making the time for him is important. And he’s trying to do it in a low-key way. He asks, would you like to come for pizza? And many of the students say, this is quite interesting. They thought it was going to be boring, a lot of people talking about philosophy all the time, but they said, no, it was actually really interesting. I want them to think of it as a kind of resource, particularly for students who worry about these things.

Cynthia Friend: Along those lines, the research you discussed as having ethical implications is shaded more toward the translational side, because it has a specific medical issue you’re trying to address. But what about really basic research? Do you think there’s a place long before you ever get to an application for bringing in ethical considerations?

Dame Carol Robinson: For basic science, I think what we need is to know more about, what does the public think? What does the public think we’re doing? Because if they think it’s somehow unethical, then we haven’t really considered it properly.

Researchers in our group tell the story where they went to the market to buy a pig brain at the meat market. This is in Oxford, and there was a little boy in the shop and he said, “What are you doing?” And the researcher said, “Oh, just buying a pig brain.” The boy said, “What for?” The man behind the counter said, “Don’t eat it.” The researcher said, “No, we’re going to do experiments.” And the little boy in the shop started. He was quite traumatized by some sort of weird experimental scientist with a pig’s brain. To me, I hadn’t thought that anyone would think that. I thought they would think it is material for experiments. But clearly the public think that it is a bit weird or unethical even.

Elizabeth Christopherson: What sort of opportunities do you think would better prepare scientists to be thinking about ethics and engagement as they’re getting started with this work?

Dame Carol Robinson: The earlier you start the conversation, the better it is. Because as I said, I gave these talks, and I was very unprepared. To me it’s a triangle. It’s the scientists, it’s the public, and it’s the ethics. The public’s views are important in helping to guide our thinking about what is ethical. Because we think if we start to shock somebody, then that’s not good. I think you’ve got to gain the trust of that person and then start to talk about it.

Cynthia Friend: If there’s kind of a check-the-box compliance exercise requiring a lot of paperwork, let’s say, to get a grant, it’s not really what we’re talking about here. What we’re talking about is thinking about how to make your research better. People have the mentality that ethics and engagement are going to make it harder for them to do their work instead of making it better, which is the goal.

You have done some really interesting work with translating your fundamental research into applications. In fact, you founded OMass Therapeutics. What is your perspective on how that was achieved, how fundamental research can go from the lab to being scaled into an industrial setting, and what the responsibilities and opportunities are for scientists in that process?

Dame Carol Robinson: I think about the ethics of it a lot more now than I did at the time. There was some pushback from people. They didn’t like the idea of making money from research: “This is research, it’s basic research. You shouldn’t really be trying to commercialize it.” But for me, I was thinking, if I can find a drug that cures something, then surely that’s amazing. I’ll be so delighted that my research has led to something. We have something going into the clinic soon for clinical trials, which is very exciting to me.

Elizabeth Christopherson: One of the exciting things here is that we’re trying to continue to widen the lens as we talk about ethics and the public and civics. If we think of team science or cross-sectoral sciences, how and when do we have the ethicists and the public voices included in some of the research?

I think there’s a great hunger from our philanthropic colleagues on what we can do to invest in the future, to make science stronger and to make the benefits broader and stronger too. If you were talking to the philanthropic community, what would be on your wish list? What advice would you give?

Dame Carol Robinson: Basic science can lead to something really important, but you don’t necessarily know. If I could, I would persuade philanthropy to invest in basic science and know it will pay back. You can’t always be sure how, but you’ll see something different because you have a different view. That’s why I think it’s good to compare a healthy and a disease state, for example, and then see how they differ.

Engaging people earlier is also very important. Wellcome Trust encouraged me to talk to patients in depression. They said, you could go off trying to do something, and then the patients might not be interested. In the first engagement I had with a young woman, she said, “I don’t want any more drugs. Don’t find me any drugs.” I thought she would like a drug, but she doesn’t.

I realized she would consider a nutritional supplement, which is a nutraceutical, as we call it, but not a pharmaceutical. And actually, we found a lipid that was missing in the brains of these patients. Then I saw that in Chinese traditional medicine, the lipid we found is used as a treatment for depression. That was one of those amazing circles of things. If she could take that lipid, which actually she probably would, it might help. Who knows? That’s one theory. And people have been taking it for years in Chinese traditional medicine for major depressive disorders.

Cynthia Friend: I was going to pick up on the thread, because I would think there’s an opportunity for philanthropy to bet on people with ideas that may be a little bit out of the scope of what might typically be funded. I also want to come back to your background, because I think it makes the point that philanthropy can make a difference. We have an opportunity to look for people who are not necessarily on the traditional path to science. If you could just share your personal story, which I think is beautiful, I’d appreciate it.

Dame Carol Robinson: Pfizer was about 20 miles away from my house, and it used to run a company bus. I was thinking, I need to work there because I can’t drive. I’m too young. So this is how my whole life changed.

I got on the bus, and I didn’t know what I was going to do. I tried NMR, mass spec, IR spectroscopy, all of these different chemical things. And then I just loved the mass spec.

One of my supervisors said, “Why did you leave school at 16?” I said, well, that’s what we did. My brother had done the same. He said I should have gone to university. And I said, well, it’s probably a bit late now. He said, nope, I’m going to make you go to evening classes after work and see how that goes. And then I did seven years part-time study, so quite a long hard course.

Then I got to Cambridge, which was an unbelievable thing for me. I often tell this big imposter syndrome story, because you come there and people ask, “How did you get in? You worked. You don’t have a proper degree.” I did a degree, but it was part-time, so that was an unusual thing. But I did get a lot of hands-on experience, which allowed me to not be scared of the mass spectrometer and to really own it and take it apart and rebuild it. In some ways it can help you having a different background.

In Cambridge, there was a person who said, I’ll just fund your research, and you do what you want with the funding. To me, that was amazing because most funding you get it is tied to something or someone. I was able to support people who were a bit different, like me, which I like to do.

That sort of philanthropic funding, without too much telling you what to do with it, was really good for me. And then with creating The Kavli Institute for Nanoscience Discovery, again, I got this opportunity to create the place where I’d always wanted to work. I know how good institutes could be, and I know how they can be quite tough as well. We owe it to everybody to make it not like that. Otherwise, too many people leave science and give up. That’s a very important ethical piece. It should be a better world for everybody in science.

Read the original story here: Civic Science Funders Collaborative Advisory Series: Prof. Dame Carol Robinson