“My name is Kristoffer Johansen, I’m a researcher at University of Glasgow and I’m trying to cure cancer with sound”.
I met Kristoffer a few weeks ago at an event at UoG. Very quickly he struck me as an interesting character with a lot to say on a wide range of subjects. Here we discuss his work utilizing the power of bubbles, the pros and cons of doing a PhD, what Orwell might’ve had to say about modern science, the possibility of an AI revolution also being an artistic revolution and much more besides. Enjoy!
KJ: The project, funded by the European Research Council, is called Theracav, which aims to harness cavitation for therapeutic and industrial processes. Now, what is cavitation? Cavitation is bubbles. Basically, in a High Intensity Focused Ultrasound field we can create bubbles with sound. We want to show that we can control these bubbles, and if we can control the bubbles, we can operate on people non-invasively. Promising papers have already been published on this, and as physicists working on this problem, we’re trying to understand why it works, how we can do it better and how we can do it safely.
C&Q: Can you explain a little bit more about the cavitation process?
KJ: Okay, so you could create it in multiple ways. For example on a ship propeller which is rotating fast in a liquid, you could have cavitation on the end of the propeller, which is due to the negative pressure from the propeller. The more negative the pressure, the more likely it is you’re going to have cavitation.
C&J: So you’re basically blowing the water apart.
KJ: Exactly, and once you’re able to nucleate [give structure to] the gas pocket, the bubble will be driven by the sound field and it will oscillate very non-linearly. That’s a key word. It’s an extremely non-linear process.
C&Q: And by non-linear you mean chaotic, would that be fair to say?
KJ: Yes, one would say the process is highly chaotic. The equations used to describe bubble dynamics deal in deterministic chaos.
C&Q: So, complex but predictable?
KJ: Yes, and all sorts of fascinating things can happen. Shockwaves can split up into multiple bubbles, they can attract each other, attract cells. Cells are attracted by bubbles, depending on how you look at it. They eject through themselves with forces able to penetrate metal and they can also create light through sound, which is known as sonoluminescence.
C&Q: You mentioned when we met that the process is not unlike a combustion engine.
KJ: Yes, it can behave that way. When the bubble collapses from outside pressure, the gas gets heated up dramatically, some estimates putting it in the area of tens of thousands of kelvin [C&Q – the surface of the sun is only about 7000 kelvin] inside the bubble during the collapse. It’s quite violent.
C&Q: How is this process used for medical purposes?
KJ: So previously bubbles have been used in medical ultrasound as a contrast agent, and recently it has been suggested that the same bubbles that are being used for better imaging quality in medical ultrasound, could also have a therapeutic application. This is achieved through a mechanism known as sonoporation, where the bubble oscillation, forced by the acoustic field, is creating transient pores in the cell membrane. These holes in the cell membrane allows for enhanced drug uptake into cells, and targeting of drug delivery if required.
The point is that if you give chemo without bubbles, you are simply hoping that the chemo will kill more cancer cells than healthy cells. This is what is known as a systemic side effect. Now such side effects can be averted or decreased by using bubbles. When the bubbles open up transient pours in the cell membrane, the chemo becomes more effective as the drug uptake is increased in the cells affected by bubbles. And the important point here is that you will always only aim sound in the region where you have cancer, hence, increased drug uptake is achieved for a targeted diseased region of tissue.
This technique can be expended to loading the bubbles with chemo or genes, such that chemo or genes are only delivered to sick cells. If we learn to control the bubbles, the more effectively we can target cancer cells over healthy cells.
C&Q: Can you tell us a little about the process of producing the bubbles in the lab?
KJ: Okay, so we’re mainly interested in the interactions between cavitation clouds, so clouds full of bubbles that are mostly interacting in this focused sound field. We create the bubbles by firing a relatively high energy laser into the sound field so that we’re able to nucleate a single cloud. Our setup is quite unique in the world in that we’re able to study single clouds. That’s a big deal if you speak to anyone in the community (yes, I know, all these strange things in science (laughs)). The benefit of being able to study a single cloud is we can see more clearly what’s going on. Otherwise if we have many, is what we’re seeing because we have many clouds or one? It makes it all the more chaotic, even harder to analyse and understand, so one makes it easier to devise a way to harness cavitation for a brain operation, for example.
Why a cloud? They’re naturally created. We fire our laser and form a bubble. The bubble grows during the observation and is composed of tens of thousands of component bubbles, which are very strongly-interacting, and we can see from the morphology and behaviour that it’s not one structure, but a multi-structured thingy. Clouds are what you would expect in the human body and a single bubble is the special case.
C&Q: You mentioned sonoluminescence, creating light from sound. What are the possible causes?
KJ: Ya, so if you seed your liquid with a noble gas like helium, xenon, argon, you get a much brighter flash, but you can also get sonoluminescence from pure water. I’m tempted to say that it has to do with plasma formation. When we study cavitation, we have this really nice high-speed camera with which we can image sound fields at ten million frames per second. We’re able to see shockwaves and everything. It gives you a real peek into the process and when there’s plasma, we can see it.
C&Q: So, plasma confirmed? What about hydroxide and ionised hydrogen from the water being split apart? I imagine the recombination would create some photons.
KJ: Plasma confirmed, no doubt, no doubt. I believe that the generation of a plasma during strong collapses is a strong candidate, however, it is also possible that radical formation is a contributing process. It depends on the proportion. Whoever solves it fully will almost certainly win the Nobel Prize.
C&Q: It’s thought that cavitation might actually get much hotter, maybe even the temperature of the sun’s core [about 15 million kelvin]. D’you think we’ll ever see bubble fusion?
KJ: (Laughs). I don’t think you’re going to get fusion in a normal cavitation experiment. It’s not impossible, but you’d have to try really hard. It’s all to do with the strength of the collapse, and in certain configurations it’s been shown that you can get some really crazy cavitation if you increase the ambient pressure. I wouldn’t bet on it though, it wouldn’t be easy.
C&Q: (Laughs) So, improbable, but not impossible?
KJ: (Smiles) It’s plausible!
C&Q: Going more into science in general, how did you decide to become a scientist? Did something or someone inspire you in particular?
KJ: There are multiple sides to that question. Like many people in science will tell you, they had a good teacher during high school. I myself had a brilliant teacher. He was a farmer, a fisherman, a world champion in skiing, he also ran marathons and was a little bit of a superhuman and he just decided, ‘Ya, Physics, why not?’ (we both laugh).
C&Q: How did he find the time? I’m picturing him reading books on quantum mechanics while sliding down mountains.
KJ: Ya, I don’t know, it’s baffling. He was an extraordinary man. But also, at that time in Norway, it was very ‘in’ to push kids into engineering because of course Norway needed a lot of engineers to get the oil out of the ground, right? I myself didn’t want to go down that path, because if anything it’s limiting you in what you can do. It frames your career. ‘You are a construction engineer, that’s what you do’. You don’t do anything else. That was never very appealing, but if you know physics, you can be an engineer of everything! (we both laugh). It’s much easier to teach a physicist how to be an engineer than an engineer to be a physicist, I think. Kids should choose either math, computer science or physics. That’s what you need. Everything comes from that.
C&Q: D’you think the increase in emphasis on these technical skills will further push out the arts?
KJ: Actually, I think the arts are going to come back in a big way. Machine learning and artificial intelligence will take over hundreds of thousands of jobs, and they’re never going to come back.
C&Q: And by coincidence we’re seeing experiments with universal basic income. We could enjoy the fruits of artificial intelligence.
KJ: Yes, and people need something to do. Humanities are not always the most useful, but they can certainly be interesting. That’s a possible outcome, but of course it’s hard to tell. The future is always difficult.
C&Q: I think art is important. It can inspire in ways that science doesn’t always.
KJ: So, when I go to a gallery and I see a beautiful painting, it moves me in a similar way as when I see beautiful physics. When you see a magnificent derivation and it’s all there, that can move you in absolutely the same way as a great painting, or great art.
C&Q: So what then is the need for art, if science can do it all?
KJ: (Laughs) Well ya, they’re certainly not the same in every respect. I’m not sure.
C&Q: For me, taking music as the example that inspires me most in art, when I listen to a beautiful piece of music, I derive what seems like a more raw form of inspiration. What I then do with that energy and spark of inspiration is up to me. When I see a beautiful equation or learn a beautiful concept in physics or mathematics, I’m inspired largely to do more physics and mathematics. Perhaps then art has a more broad application, or maybe I’m doing it wrong (laughs).
KJ: Hmm, actually, I would agree! I feel the same way I think.
C&Q: When last we spoke you talked about the pros and cons of doing a PhD. Is it for everyone?
KJ: I think people should be going into a PhD not for the title, but because they love science and the search for knowledge. If you don’t, it’s going to be… challenging. Difficult and challenging.
I’ve always been fascinated with what’s going down in CERN, which is basically just physics for the sake of physics and at the same time you’re doing a bit of peace work, where all the nations of the world are collaborating on a project, which is great. It’s just a hunt for knowledge. Now Theracav, my project, we’re just trying to figure out the structure of the universe, but at the same time because the funding is medical, there’s always a medical angle. It’s a multi-physics topic. You can do it just for studying how the universe functions, but also have both economical and health benefits for the world. I think it’s fantastic that such projects are funded.
C&Q: What’re some of the best and worst things about moving away for research? Are you enjoying Glasgow? Missing Norway?
KJ: (Laughs) I’m enjoying Glasgow, I’m missing Norway. No matter where you go, you’re going to miss the people of your old place. Not necessarily the place, it’s the people that you miss. No matter where you go, because a PhD is such hard work and such a huge responsibility, it can be difficult finding the time to find new people. Thankfully the cultures are quite the same (laughs). Glasgow has so much to offer. I really like it.
Something people should know, is that as a PhD student in the UK, you’re considered a student and not an employee, so if something goes wrong, it’s your problem and you fix it. In the rest of Europe you’re an employee, which means that you have rights and people have your back. An important part of coming to Scotland was that I’d just finished my MSc on anti-bubbles (yes, anti-bubbles, with a fluid core. Everything is better if you put ‘anti-‘ in front of it (laughs))…
C&Q: I have some googling to do when I get home!
KJ: (Laughs) I know, it’s crazy, right? So I was interested in doing more with bubbles and in all honesty, industry was down. I started my PhD when oil prices were falling and not a lot was happening, so I was offered a PhD-ship in Scotland and I thought, ‘yeah, why not? I have no children, I have no mortgage’ (laughs).
C&Q: I read an article on the train here about what it was like to be a British PhD student in the 1840s. For one, many British scientists were apprentices rather than graduates. They had to travel all the way to Germany to train. One, John Tyndall who eventually succeeded Michael Faraday at the Royal Institution, laid out a typical day in a letter – up at 5, learn German until 7.30 for breakfast, physics and chemistry lectures from 8-10, in the lab all day, maths from 4-5, tea at 6 then bed at 10, more or less every day for two years. Has the PhD experience changed much since then?
KJ: (Laughs). Well, usually a PhD is 3 or 4 years now, and many people struggle to complete within the time. It depends on how engaged the candidate is with the project. If you’re giving it an honest go, it should sound something like that but without the German and without the modules. You wake up in the morning, then it’s research until you go to bed, then you wake up again. Repeat for a few years.
C&Q: So if you take a break to watch a film, you’re still doing research in the back of your mind?
KJ: Well… yes! (Laughs). All the time. In all honesty, it’s always going, it’s always ticking. You read so many papers, you have at least three projects going simultaneously, maybe five. All linked, so not crazy different, but you’re thinking all the time of problems that you’re facing or knowing that you have to deal with.
C&Q: I’ve been reading about phenomena in psychology recently – harmonious and obsessive passion. The former deals with being one and in flow with an undertaking, while the latter involves undertaking something without true love for the task. Is harmonious passion necessary for a necessary PhD, d’you think?
KJ: I don’t think it’s necessary for a PhD. You can brute force it if you want, but you’re going to have a terrible time (laughs). It’s a lot of work. It’s a LOT of work. Harmony is preferable, but in the end, nothing in life is quite simple and what is really good with a PhD is that it builds character. People say they never give up, but during a PhD you learn just what that really means! (Huge, bellowing laugh). You continue, even though it hurts. Sometimes you make it, sometimes you don’t. It feels great when you do make it.
C&Q: And for those aspiring to be more scientifically minded, or even enter into science themselves, what are the key traits necessary to develop a scientific mindset?
KJ: To be able to give any effort or experience any harmony, you have to be curious. Intrinsically curious. It is important to have some intelligence, it helps to be smart, but it’s not the biggest factor in success or failure. You have to show devotion, you have to be a dog with a bone. You need to see what you want and to run after it until you have it. That combined with passion, a touch of intelligence, some people skills so that you’re able to both collaborate with and benefit from the people around you so that you’re not just constantly having to reinvent the wheel, because you see that in research. People are just reinventing the wheel all the time and it’s just a waste of effort. Doing the same thing as someone else takes quite a bit of time and they could just get it from someone else.
Also, if you need something, a tool of some kind, or help with some kind of mathematical derivation, ask someone who knows the fucking subject! (pardon my language). Don’t spend weeks and months on something you have no clue on. That’s just bad time management and you’re being irresponsible. It’s not a grown-up thing to do. That’s a side note, but yeah, a mix of these buzz words: motivation, devotion, persistence.
C&Q: (Laughs) Great. Any last words?
KJ: Yeah. In the words of George Orwell, ‘people know the price of everything but the value of nothing’. That is a bit how I feel about how science is going at the moment, where you have papers coming out in every direction all the time. It’s impossible to stay on top of any field, because there are just hundreds and hundreds of papers coming out every month and most of those papers are not great. They will not be remembered. Good, real research which actually makes a difference for mankind is not being valued. The system does not reward it. It’s a real mess.
C&Q: I think that’s a great place to close the interview. Thanks, Kristoffer!
KJ: (Laughs) Thank you, thanks!
You can find out more about Kristoffer’s research and cavitation in general at these links:
For the article I mentioned on PhDs in the 1840s and more on The Royal Institution, see here: