A chat with scientists Roger Olsson and Magnus Berggren
We might all remember, from our elementary school science class, how to make a circuit that transports electricity. With conductive material, if we form a closed loop, we can transport electrical charge from one place to another. This usually happens with the help of metal, a highly conductive material.
Over the years, this basic concept has been used to develop some cutting-edge technologies able to save people’s lives. For example, deep-brain stimulation, in which doctors implant electrodes in people’s brains — little plugs able to transmit electrical impulses from a conductive material to one that doesn’t naturally conduce electricity — to transmit signals to neurons responsible for conditions such as Parkinson's or epilepsy.
This is great but quite invasive.
Enter Magnus Berggren, professor of organic electronics at Linköping University and one of the pioneers in the field of making bio-electrical devices, aka devices that blend the living and the electronic. With his colleague Roger Olsson, professor of nanoscience and semiconductor technology at Lund University, their team may have found a non-invasive work around the issue.
They created a gel that, once injected into a living animal, can create an electrically conductive structure inside the organism without harming it, according to a new paper in the journal Science. Scholars had managed something similar a couple of years ago in worms, but they had needed to carry out some genetic engineering. In this case, all you need is a little prick.
I’m a science journalist, and my work — which has appeared in the New York Times, Guardian, BBC, and National Geographic — is all about telling stories of how the mind works. I had the pleasure of chatting with Berggren and Olsson for my ITM column called “Behind the Science”, where I unpack the behind-the-scenes of science that’s changing the way we think about the world.
A collage of images made by Sofia Quaglia
Can you tell me a little bit about the research you do, and the questions you’ve been trying to answer for the past couple of years?
Magnus Berggren: For the past 20 years my team has been working to develop “organic electronic devices”. Devices to both stimulate and record signals in biological organisms — everything from plants to mammals. But making organic electronic devices isn’t easy. Whenever we get too close to biological organisms, it's basically like taking to it with a knife. Even though organic electronic devices are flexible and soft, it's like using a knife: you have to damage a lot of the tissue to penetrate into the organs and install the devices.
Then, some time ago, we realized we could form organic electronic devices such as electrodes in plants: the chemical energy and the enzymes within the plants could be used to create something like wires for electricity. That’s when Roger Olsson read my research and got in touch, to see if we could do this in neuronal systems in animals.
Roger Olsson: Exactly. I've been in the pharmaceutical industry for 20 years, so I'm a trained organic chemist and work with chemistry in zebrafish specifically. But since plant and animal cells are quite different, we needed to start changing the formula used to make conductive materials in plants to make it helpful for animals. At least because some parts of the formula that we use for plants could be toxic to the living brain. So, we put a lot of energy into that for it to work.
And I know there were a lot of hurdles and challenges to making this work, and for a year it almost seemed like the project wasn't really moving anywhere, right?
Magnus Berggren: In plants, the enzymes that are needed to create electric conductivity already exist, to some extent, and they help convert sugar or other compounds into a chemical energy that we can use to polymerize — basically when molecules arrange to create three-dimensional networks which can then, in turn, be used for conducting electricity . To replicate that in a living organism, that doesn’t have those enzymes, we had a long wish-list, like a recipe, to create a concoction of chemicals that could kickstart that process for us. For example, it must be dispensed as a fluid, otherwise, you cannot get it into the organ and distribute it. It had to be made of non-toxic compounds, homogeneous, and long-term stable… and more. All this is like a Christmas wish list for the perfect “invivo manufactured electrode”. And through trial and error, and thanks to the effort of very talented researchers in our laboratory, such as Xenofon Strakosas and Hanne Biesmans, we were able to put all these components together and come up with the right chemical cocktail: one containing a category of molecules called oxidases that have the ability to react with the sugars already naturally inside the living tissue.
You had this list of all the boxes that you needed to tick off for this to work. After months of trying to see how to change the initial cocktail formula that had worked for plants to make it work for living cells, you basically managed to manufacture this polymerizing gel. But how do you know it works?
Roger Olsson: One good thing is that when this gel is injected and it polymerizes, becoming conductive, it turns dark blue. So, you can see it with your naked eye. We started to test it with the zebrafish tail fin and in a short timeframe, you a dark blue color starts forming. That’s how we know we’re getting polymerization. After that, we started going further, focusing on the fin, the heart, and the brain of the animal. And it worked just like in the zebrafish tail, it turned darker.
Magnus Berggren: The next step is to verify, is it conducting? Can you pass the current through it? Can we transport charge from this part to this part, and basically make this to become like a deep tissue electrode? We took the zebrafish brain and sliced it up and run a charge through it and you can see it conducting from here to there, and so on. And we can then monitor this with technological equipment. From the results, we could not only see that it is conductive, but it is also highly conducted.
Can you tell me a little bit about when you first realized this was happening and the conductivity was working?
Roger Olsson: I mean, if you think about it, what we did is take a mixture of chemicals, and when we inject it into a brain structure, it basically self-assembled to make a conductive structure. That for me as a chemist was very exciting, even just to be able to do that was very “high level”. Usually the body defends itself, but to get a gel that can arrange itself around the neurons… I was kind of surprised that we managed to do that.
Magnus Berggren: There’s almost like a philosophical beauty to this. We can use the energy system of an animal and use that energy to power and fuel polymerization. We always need energy to make materials, and normally we get energy for polymerization to make materials from, say, electricity, or very harsh chemicals.
Here, we can use the naturally available sugar inside living tissue as the sole origin of energy to power up molecules, to make a scaffold that has the power of conductivity. We sort of elegantly managed to tap into just a tiny portion of the energy that is available naturally in the body and that has never been done before.
And you can use this gel not just to create conductive structures around an organ, but also around a cell, correct?
Magnus Berggren: Here we show that the material can not only form around organs, or around structures, or within cavities, but actually inside the cell. So, can we start to build up device structures at cell level? That’s one of the pathways of research that we’re going to have to start exploring.
This sounds very invasive though, no?
Roger Olsson: No actually. For the zebrafish, we’re using a very thin capillary to inject the gel, one the size of a human hair, and after two days the initial inflammation of that area was gone. And there’s no inflammation from the polymer itself, inside the tissue.
So, you’ve tested this in fish, but what is the likelihood that this is going to work in other kinds of organisms? And ultimately humans?
Roger Olsson: Actually, I think we made one of the more difficult decisions to work with a fish. To scale up this kind of work to animals such as rats or non-human primates is easier, because, with those animals, we can do everything in a larger scale. So, we met this challenge directly. We did an animal that is in water, and we had to do different techniques to keep the fish alive during the injection. So adding the compound to, say, rodents, will be much easier because that is the standard format. So I think upscaling to other animals will be easier.
So now that you’ve tested it works, what exactly can you do with this new conductive gel for live tissue? What can we use it for, realistically?
Magnus Berggren: Let’s take deep brain electrodes, for example. They are used for deep-brain stimulation to treat neurological conditions such as epilepsy and Parkinson's disease. This is how they work today: you penetrate through the scalp, you go deep into the brain tissue, and you reach the glial cells — the cells that help the functioning of neurons. But this process basically creates scar tissue around the cells, and over time, it lowers the efficacy and precision of the treatment. We hope that by injecting this and creating electrodes that are mixed within the neural system, we don't kill any of the neurons and we don't produce any ugly scar tissue. I think we have done one more major step towards something that could, for a deep brain stimulation electrode, get into much closer proximity to the neurons, and maybe even have the neurons embedded within the electrode.
Roger Olsson: Electrostimulation is used for Parkinson's disease, there are some studies of its use for chronic pain, for example, Alzheimer's. We would like to go and replace those solid electrodes used for this therapy with these liquid electrodes that are moving with the brain, in unison. But this can take many many years, I’ve been involved in getting drugs to the market, and it can take a long time.
*This article includes some heavily paraphrased information, under the guidance of interviewees*