Malte Gather and Seok Hyun Yun are a pair of absurdly smart scientists from the Wellman Center for Photomedicine in Boston, and they recently published research showing how they created the world's first biological lasers made from single cells. Their work was picked up all over the Internet, and now they've effectively become rock stars of the light sciences world.
How did they bring this sci-fi fantasy to fruition? By inserting genes for the expression of green fluorescent protein from bioluminescent jellyfish into human embryonic kidney cells, which are then sandwiched in a pair of tiny mirrors and bathed in a blue light, naturally. This light triggers the cells to flash a green fluorescent pulse, which is shaped by the mirrors into a laser beam. It's absolutely brilliant, and has an enormous amount of potential in applied medicine.
I called Gather to chat about the future of biological lasers, the silly controversy over his research, and whether he just unlocked the key to creating a zombie army with laser eyes.
This is crazy stuff. What are the applications?
Everyone is asking this. Honestly, when we started this, it was more for scientific curiosity. We didn't start with an application in mind. It was more to see if we can build lasers that are completely in the biological realm because we knew that lasers don't appear in nature per se, so we wanted to gather an idea of the fundamentals for that.
Of course, as the project progressed and it seemed it would be quite successful we started to think about applications and I think I can mention maybe two or three that we are currently interested in but that might not definitely be what it is used for in the end because other people are starting to think about this as well.
What are you able to mention?
Well, I think the one that's closest to any real use is the following: when we looked at the output of our lighted cells, we realized that the beam that comes out of the cell is not just a circular beam like what you would see, for example, if you were using a laser pointer. It's this relatively complex pattern; you might have seen the one picture that's all over the world now that's a complexly shaped laser spot. And we realized that this pattern captured information about the shape and inside structures of the cell.
The thing, is we haven't quite worked out yet how the two relate so we are unable to decode the pattern to learn things about the inside of the cell but we are quite confident that there is information in this pattern, and we are hoping to use it as a very quick screening tool to look at a very large population of cells. The way this would work is you would take a vial of say a million cells and pop them through this pair of mirrors in very quick succession so that each of these cells produced one or a few laser pulses and you would record the spatial pattern or just the spectrum of these laser pulses and analyze that in order to learn something about the composition of your sample.
Whats's interesting is the laser pulse is relatively high intensity, so it's easy to measure, and the laser pulse is inherently very short so you get a nanosecond pulse. For that reason you can look at many cells in a short period of time.
How powerful are these lasers exactly? Are they something that could damage the surrounding cells, or are they gentle, but directed light?
I guess, at the moment, the latter. We haven't actually been able to quantify the output power as of now, purely for technical reasons. We just didn't have the right detector in the lab. But we have taken all of these pictures, so what I can say is it's readily detectable with a camera. Of course, that's not a good way to quantify it, so I'm actually working on a way to get a quantifiable number.
That means that it's not high power. If it was, it would be easier to measure. It's not something that will ever damage or cut an organic material.
Is it scalable? Could you do this with a series of cells to make it more powerful?
You could definitely do that. The very reason it's low power is because a single cell is very small, so the volume in which you generate the light is just tiny. You can definitely scale that. At the beginning we worked with just a solution of this protein that forms the heart of all these lasers, and at that time we used a lot bigger structure, couple of millimeter-long laser structures. From there the power can go up considerably, and I think you can even reach millijoules of energy per pulse.
Can the laser beam be directed, or does it just shoot wherever it wants?
Right now we can only change the orientation of the mirror pair, so it will always be perpendicular to surface of the mirror. But we are working at ways to shrink this mirror pair such that we can implant it into the cell. At that time it probably won't be a pair of mirrors but another resonator structure. Once we do that we can control the direction of the output if we wanted to.
If you could implant these structures into the cell, could you implant them within the cells of an organism?
Yeah, we could do that. It's obviously a little bit in the future [laughs]. We think there's no fundamental reason stopping us from doing this.
Is any of this applicable to human therapies, like maybe for sight?
Many of the applications of light and medicine could benefit from this, because a lot of time getting the light into the body is an issue. Also oftentimes it's advantageous to use laser light because it's monochromatic.
One thing we thinking about is a technique called photodynamic therapy, or PTD, where you treat cancer or some other inflammation by applying a drug. This drug doesn't do anything until it's activated by light, and then it will start to fight the tumor. The good thing about this is if you can then only activate the drug where the tumor is, and not have the drug affect the rest of the body. This has already been used clinically. It would be nice then to have the laser source to make the drug act more specifically because of the monochromatic output. If we found a way for the laser to run completely on its own, it would also become easier to expose regions to light that are not accessible from the outside of your body. Right now how it works is you have to surgically open the body to expose these regions to light.
So in the future will I be able to shoot laser beams out of my eyeballs?
I've read some comments about the freaking sharks with lasers on their head invented by Dr. Evil and all this stuff. Actually, I don't really think so. It's interesting to think about, high-powered generation of light in biological structures. But it's fairly difficult to do. The lasers out of your eyeballs might not have immediate applications, but I think there actually might be other applications for biological systems generating light in higher power and higher quantity. I'm definitely interested in this, but I think that will be a long way away because generation of light is not that efficient in biological systems.
What's next with your research?
In general, I think we will look into the shrinking of these lasers to see if we can actually plug the lasers into the cells. The other thing we always wanted to really prove is that these lasers are self-healing. It's obvious that the cells generate or produce this green fluorescent protein all the time. Once you start using them as a laser you of course begin to bleach the protein over time, so you actually destroy some of the material. We are pretty sure that the cells can produce sufficient amounts of new GFP so that you can heal the laser. An actual demonstration of this is still to come.
If these are self-healing, are you worried about zombie laser cells getting out?
Not really. Of course in the public there have been a few comments that we were doing very unethical research. There was also a big misunderstanding about the type of cells we are using. These are called human embryonic kidney cells, so people were accusing us of killing innocent babies to do this research, which is of course not the case. This is a cell line that was created forty years ago, in the seventies I believe, that has been passed on and is used by thousands of scientists every day.
The cells wouldn't live more than a couple of hours outside of the lab, so there isn't really a risk there, but it is interesting to speculate about the zombie army with lasers coming out of their eyes. It's something people are interested in, and it's totally fine. We were kind of expecting some reaction like that.