Katalin Karikó: It is maybe a difference that I was not much listening to what others might say, kind of. I could figure out things, that something is important, and I thought always it is important, and I tried to believe that it is doable, and not listen to those that said not so. It is like imagine something that I can have an RNA, and I have to tell you, I did not want to develop vaccine at all, and that was the reason I was looking for – with colleague Drew Weissman – how to make it nonimmunogenic, because everybody thought that the immunogenic RNA is good for vaccine, but I want to use a therapeutic. And I could imagine, like other big names like Steve Jobs, that imagined that there is something, a device, and that will be your telephone, that will be your camera, that will be all your different device in one piece. And today we take it for granted. I just imagined that there will be RNA, we are taking out from our refrigerator and put on our wound. And because the advantage of the RNA is that taken up by the cells, and locally they will produce a protein, which will be beneficial, which will be therapeutic. Otherwise, if you put the protein there and it will wash away from the blood, here is also, but it is continuously producing locally so there you have a gradient.
And I imagined that it is doable and it would be helpful for some kind of disease like healing the skin, that was my first thought, and then later when we realized that not much protein is made from the RNA, thinking about what disease model could be which small amount of protein is beneficial, and finally we ended up with treating anemia. And we come up with messenger RNA coding for erythropoietin. And because for continuously the erythropoietin mRNA, which we delivered to the animal were like four days, was continuously translated, we could see new red blood cells form, and we could see the hematopoietin increase. So it was the RNA translated to the protein, the erythropoietin, which stimulates red blood cell production, and it was functional. The RNA translated to the protein was functional and more red blood cells was made. And so, we found at least one disease where the mRNA could be beneficial. And of course, I was working on this field where Drew Weissman tried to make a vaccine and realizing when he used once this modified, nucleoside-modified, which was nonimmunogenic, that was many twists and turns. It turned out it was a better vaccine because the original RNA everybody was using turned out toxic, especially in human, and they couldn’t see as well in animals. So that was also one thing that Drew Weissman used human immune cells and we could see that the RNA, conventional RNA is inducing immune response and inflammation which was not good.