I think we can all pretty much agree that germs are really annoying. You can take my word for this because I'm kind of an expert. Not only because I work with viruses for a living, which I do, but mainly because I have two young sons at home. They're four and two, and I swear they are germ factories. It seems like every single week they are sick with something. They have some upper respiratory, lower respiratory, diarrhea, vomiting, you name it, they've been infected. What that means is I am constantly sick. So, yes, germs are a real big pain. But luckily if it's a bacterial infection you can treat it with antibiotics, but if it's a viral infection you just kind of wait it out, right? But luckily most of the infections are not that bad and my kids will cure them in a couple of weeks. But we also know that there are a lot of other viruses that lead to more significant problems. It can range from maybe having life-long cold sores to something more serious like debilitation or even death. So in general viruses are something I want to stay away from. They're nasty. But now let me introduce you to my mom. This picture was taken in December 2008. We were visiting my brother, who lived in Hawaii at that time. My mom loves golf, her family and warm weather. Probably in that order. So Hawaii is really her paradise. We had a really great time, it was really fun. Unfortunately, when I took this picture, I didn't realize that my mom's body was in the process of betraying her. Because just six months later she was diagnosed with breast cancer. When she was diagnosed, I was pregnant with my first son. So it became this big emotionally confusing time for me. Because there I was, growing life in my body, and there she was, growing what could potentially be her death. And in addition, since I was pregnant, I was starting to appreciate the female breasts as something that provides sustenance, right? They're supposed to support life. But hers may ultimately be the source of her demise. So it was a very difficult time. In a couple months after her diagnosis, she started her cancer treatment. Chemo, surgery, radiation. It was a very difficult time. And all the things that you hear about cancer treatment, especially chemo being horrible, it's true, it is really horrible. And this is something that you will not appreciate unless you or someone you love goes through it. But we've made it. We made it through that long, intense year and at her cancer hospital there's this bell that they hung on the wall and at the end of the year you can go and ring that bell, telling everyone you're done with treatment, you're done with cancer. So we were very happy that day, but that happiness and that relief was extremely short-lived. And the worry starts to creep in. The source of that worry is because of this one word. This one word has so much power. Metastasis. Metastasis is where the cancer that originated in one part of the body spreads and moves to different parts of your body, to set up tumors elsewhere. According to the American Cancer Society, if the cancer cells are found just in your breasts, your 5-year relative survival rate is 99 percent. Which is great. But you can see that if cancer cells are found at distant metastatic sites, your survival rate drops to 24 percent. That is scary. Hence, we have one of the greatest challenges to modern medicine. Which is, how do we deliver these toxic drugs, these messages of death, if you will, just to those metastatic cancer cells? When we're talking about delivery, there are really two factors that you must consider. One is efficiency. How well can you get these drugs, these messages of death, just to the cancer cells, right? And the second is specificity. That's where you want those drugs delivered just to the cancer cells, those metastatic cancer cells, but leave all the other healthy tissues alone. And that will decrease those horrible side effects. The question is, how? In my work, the answer lies with the virus. Viruses are nature's nano-cell machines that have evolved to deliver genes, or deliver messages into those cells. They are incredibly good at their job. So what we're trying to do is engineer viruses to treat cancer. Let me introduce you now to the virus that we work on. It's called the adeno-associated virus, it's a very benign virus, it is not linked to any disease. Actually most of us, 80 to 90 percent of us sitting here today, we've already been infected by this virus. So I'm showing you here the outside shell of this virus. It is empty on the inside, so that it could carry a very small piece of DNA that encodes for that message that you would want to deliver to the cancer cells. And so when I look at images like this, of the virus, I am convinced that Mother Nature is an artist. Not only that, she is a proficient designer. The tight interlock between form and function is fundamental for design. This virus is only 25 nanometers in diameter, which is 4,000 times smaller than the width of your hair. So, in this tiny little package, Nature doesn't really have a lot of wiggle room to include things that are not important for the ultimate function of the virus. Which is to infect cells. The other thing I want to point out is that viruses are old technology. I mean, it's really, really old technology. Billions of years. What we're trying to do is to simply piggy-back on Mother Nature's work. To program these viruses to kill cancer. Our over-arching strategy, in our lab, is to program synthetic algorithms into the virus structure, in order to train it to pick out those cancer cells and to destroy them. Now, it turns out, that you can already think of viruses as nanoscopic computers. They have evolved to detect biomolecular signals in their environment, which could include biomolecular cues in our bodies, in order to have productive infections that lead to self-replication ultimately. In every step of the virus infectious process the virus detects biomolecular signals that allow the virus to do the next step of that infection, and t's actually very fascinating, because it turns out that every biomolecular signal acts upon the capsid, changing it, sometimes just a little bit, and sometimes quite dramatically. So you can think of viruses as some of the most primitive shape-shifters. In our work, we're basically taking these intrinsic properties of viruses as inspiration and we want to re-write or re-program what the virus detects and computes as biomolecular input. Here are some of the viruses that we have re-programmed in the laboratory. Just by looking at them, you actually won't be able to tell the difference between our engineered viruses and the ones that exist in Nature. But these are different. These have algorithms programmed into their structure that turns them into cancer-seeking assassins. Let me explain. The basic idea is that we want to create viruses that will be able to travel throughout the body in an inert fashion, or in a locked configuration, if you will. In this locked configuration the virus cannot deliver the message that it's carrying until it comes across some biomolecular cue, signal, represented by the key here, and that key will open up the capsid and now, in this open configuration, the virus can deliver that message to the cancer cells. The other way that I like to conceptualize our design strategy is thinking of it as if we were programming encryption into these viruses. So, the message cannot be read unless it is deciphered by the appropriate key. The next natural question is, what key? Luckily, advances in biomedical research has been answering that question for us. It turns out that if you look at tumor cells, tumor masses, there are a lot of biochemical signals, these cues, that are present at higher concentrations in the tumor, either outside of the cancer cells or within the cancer cells themselves. You can imagine all of these cues can act as the key that will open up our virus. This is a demonstration of how one of our devices work. In this black part, you don't see anything but there's an entire lawn of cells and onto this lawn we've added these viruses that we have in here, and in this case the virus is still in its locked state, its encrypted state, and as a demonstration this virus is delivering a message that, if read properly by that cell, would turn that cell green. It's a green message. You can see there's really not many cells that are able to read that green message. That's mainly because the virus is encrypted. Conversely, when the virus sees these biomolecular keys, the viruses open, that message is decyphered and these cells can now read these green messages. Let's go back to the schematic here. I told you that there's a lot of keys within the tumor mass, greater concentration in the tumor, but you may have noticed that there are also keys, present at lower concentrations, elsewhere in the body. And that represents some problem. That could lead to these non-targeted side effects, that you want to run away from. Our answer to this is trying to make these viruses open only when it detects two, both the red and the green. As shown here. And we have successfully generated one of these devices recently. Another way to think about this is to program an "AND" logic operator into this virus structure. I believe that the virus biotechnology community we are dreaming the same dream, we have the same vision. In the very near future, we want to be able to program viruses, real viruses, as we would computer programs. And we want this design process to be standardized, modular and lead to a predictable outcome. I leave you with a cliff-hanger. The big looming question is, how will these devices work in the human body? Will they actually do what we are proposing? We don't know the answers to these questions yet. But I work with a really great team, of very hard-working and passionate students on this research. So follow us and see our progress over the next several years. I invite you. Go viral with us. Thank you. (Applause)