Here is the full transcript of immunologist Drew Weissman’s talk titled “How A Xerox Machine Saved Lives And Won Me A Nobel Prize” at TEDxPenn 2025 conference.
Listen to the audio version here:
DREW WEISSMAN: Thank you very much. It’s an honor to be here. So, I can honestly say I am the only Nobel Laureate who has ever thanked a photocopying machine in their Nobel speech. You young folks can ask the older folks what a photocopy machine is.
A Chance Meeting at the Copy Machine
Kati Kariko and I started working together in 1997. That’s when I came to Penn from the National Institutes of Health from Tony Fauci’s lab. You’ve probably heard of him and a few other things. So, when I came over, Kati and I, the only way you could read a journal article back then was to photocopy it. So, we would wait for each other and talk. And mostly Kati talked and I got a few words in here and there. But we talked about our interests and what we were doing and what we wanted to work on.
Kati worked on RNA and she would deliver RNA to any kind of cells, any kind of cell line and ask, is protein made? I had worked in HIV pathogenesis and I worked on dendritic cells. So, I’m not going to overwhelm you with science, but dendritic cells are the cell that starts all immune reactions. And what that means is that dendritic cells are the critical cell for making a vaccine.
So, my interest was, I wanted to get mRNA to load dendritic cells. And here I am bumping into somebody at a copy machine who makes RNA and gives it the cells. It was a serendipitous moment. Again, you’ll have to ask an older person what that means. But we started working together and we spent eight years fighting our way in the lab, figuring out what was going on and how do we get RNA to work better. And that led us to our paper in 2005 that allowed us to identify a critical change that was needed in mRNA to get it to work better.
When Everyone Else Gave Up
So, if you look back in the late 90s, many people, many labs, many pharmaceutical companies were working with RNA. It went into clinical trials, it went into people trials and it failed. Everybody at that point in time gave up on it. They said it’s too hard to work with, it’s too fragile, it’s too difficult, it doesn’t make enough protein, it doesn’t work. And they gave up on it. And that was it. RNA was dead.
So, when Kati and I investigated this, we found that we could modify the RNA and make it more stable, make it produce much more protein. And that’s what went into the first two COVID vaccines that were approved and helped to stem the tide of the pandemic.
This is just a calculation of what effect the vaccines had on the COVID-19 pandemic. And what it’s noting is both the up and down nature of the pandemic, but importantly, once vaccines were introduced, the number of deaths from COVID-19 greatly dropped by enormous amounts. It’s been calculated the vaccine saved between 15 and 20 million lives.
So, Kati and I spent 25 years working on mRNA, trying to turn it into something useful. And it finally became useful in a vaccine. Now, neither of us thinking back from 1997, when we first met, ever thought that the vaccine would be proven in a century pandemic of the entire world. But that’s life.
Overcoming Disbelief
Looking back, and many of the people that have spoke before me talk about the roadblocks to getting to where we are nowadays. The roadblocks that Kati and I ran into were disbelief. So, we would submit papers to journals and they wouldn’t publish them because they said, nobody cares about RNA. We would submit grants and we would get them back and they would say, we’re not going to fund RNA. It’ll never work. Why bother?
I would go to meetings and I’m an HIV researcher. So, I would go to HIV meetings where I would meet and talk with friends, mentors, and I would tell them about the work we were doing with RNA. They would sit there and they would smile and they would nod and they would often finish by saying, “Drew, you know, you really should give up on RNA. You’re wasting your time. It’s never going to be a useful therapeutic. Nobody cares about it. Why don’t you do something useful with your career?” And I would try not to get upset and try not to fight back with them. But here we are nowadays. It’s now RNA is a well-accepted therapeutic in most people’s minds and we can talk about that later.
The Vast Potential of mRNA
I always look forward when I think about new research, new therapeutics, new treatments for people. RNA is not just a COVID-19 vaccine. It has enormous potential for unmeasurable number of diseases. This is a very short list of everything that it could potentially be used for. The list goes on and on. But this covers just about every medical problem you can think of from cancer to infectious diseases, autoimmunity, immunotherapy, heart disease, neurodegeneration. The list goes on and on. The potential for RNA is really enormous.
Revolutionizing CAR-T Cell Therapy
One of the things that we’re very interested in, CAR-T cells were clinically developed at Penn. The first two were developed at Penn and FDA licensed. What a CAR-T cell is, it’s a way of priming our immune systems to kill cancer. So in the old days, we would give chemotherapy, which are agents that break DNA, that damage DNA. And the hope is you damage the DNA of the cancer faster than you do your normal cells. But everybody who gets chemotherapy gets sick because it doesn’t really work that well.
The chemotherapy was effective. Back in the old days, 20% of people with cancer survived.
But CAR-T cells changed that paradigm. What they did is they now took our own immune systems and primed them, built them to kill the cancer cells. They’re 60 to 70% effective against leukemia and lymphomas. A CAR is a T cell receptor, which a T cell uses to kill cancer cells. And it’s manipulated so it recognizes a tumor antigen instead of a peptide.
The problem is that to make a CAR-T cell requires this kind of procedure. You have to leukapherese a patient, that means sticking them on a machine that takes their blood out, spins it around, takes out the white cells and gives everything back for two hours. That takes out around 2 billion cells. You then have to infect those cells with a virus that delivers the CAR gene. You then have to spend 10 days to two weeks expanding those cells, increasing their numbers into the trillions. You then have to give the patient chemotherapy, and then you give the T cells back. And this is all done in very expensive, very high tech hospital facilities. It costs nearly half a million dollars a dose.
So what that means is that it can only be done in regions, United States and Europe, that have the facilities that can do this and have the funding available to be able to treat people. If you’re in sub-Saharan Africa, you’ll never get a CAR-T cell therapy. It’s unaffordable and there’s no place to make them.
So we had the idea that we could change this. We could make the CAR-T cells in the body. So what we did is using the mRNA and LNP technology, we targeted the LNPs to T cells in the body. The RNA encoded the CAR molecule. Now instead of two weeks of fancy hospital facilities, we can give people an injection, just a shot in the arm. They will make CAR-T cells in their body. They’ll be useful for cancer, for autoimmune diseases, for HIV, for a variety of different diseases. We don’t know how much it’ll cost, but it isn’t going to be half a million dollars. We’ve already proven that it works in mice and in macaques, and we’re getting ready to test this in people.
The Challenge of Global Access
That brings up another issue, which is global access. I’ve been mentioning this a bunch of times throughout my talk. The treatments that are available in the United States and Western Europe are not available around the world. And to me, that’s a major critical problem. During the pandemic, the vaccines were made in the United States and Western Europe. The vaccines were delivered to the United States and Western Europe. It took years before they were available throughout the world.
The problem is, how do you solve that problem? And that’s most critical when you think about a genetic disease like sickle cell anemia. So last month, gene therapies were approved to treat sickle cell anemia. What they involve is you take a lot of bone marrow out of a patient, you infect them with a virus, you culture them, you give the patient chemotherapy, and you give them back. They haven’t put a price tag
On that yet, but it’s probably going to be around $4 million per person. Now the issue is, 300,000 people a year are born with sickle cell anemia. They’re mainly in sub-Saharan Africa, but they’re in every country in the world. It’s a worldwide problem. This gives you the distribution of sickle cell anemia. The problem is, where the people need it aren’t where production is. The United States and Western Europe have very low rates.
So I’ve spent the past decades working on gaining access to new therapeutics across the world. And what this means is that we’ve built so far 15 GMP production sites. GMP production is the quality you need to give a drug or a vaccine to a patient. It’s very expensive, very environmentally sound, lots of rules that need to be stuck to. It costs $30 to $40 million to build one, and about $5 million a year to keep it up and running.
But we’ve now built 15 GMP sites across sub-Saharan Africa, South America, Southeast Asia, and Western Europe. And the idea is that by having access to new therapeutics, we can now go in and build research infrastructure. So we routinely train people from across the world in my lab at Penn about RNA, about how to make RNA vaccines, how to think about vaccines, how to test them, how to develop new therapeutics. With the idea that they’ll go home and now set up their own labs in their home regions, countries, areas. They now have access to GMP production. So they can do clinical processing, clinical trials in their home regions.
Local Vaccine Development During the Pandemic
We did this in Thailand starting about 10 years ago. During the pandemic, they came to me in March of 2020, and said, we don’t think if a vaccine is made in US or Western Europe, we’re concerned it’s going to be years before it ever gets to us, and it ever gets to sub-Saharan Africa. And we’re not willing to wait.
So working with Thai researchers, we made an mRNA vaccine in Thailand. And we produced it in a GMP site in Thailand. We did the clinical trials there. It’s now being distributed across all of Southeast Asia.
So now with this new infrastructure, in the event of the next pandemic, and I’m sorry, I have to say it that way, but there will be more. The next pandemic, instead of waiting for the Pfizer and BioNTech and Moderna’s in the US and Western Europe to make vaccine and make it available to the rest of the world, each of these regions can make vaccines themselves and distribute them to their local populations.
That’s also important, because we’re dealing with another issue of vaccine hesitancy, of people being nervous about taking vaccines. For many of these regions, their concerns are, we don’t like colonialists coming in here and forcing their vaccines on us. We don’t trust them. So now the vaccines, the therapeutics, whatever, is being made locally by local researchers and politicians.
It’s also important because those researchers know the diseases of their regions. They know the infection rates, they know the populations involved. They now have the ability to make vaccines that are needed for their populations. In Sub-Saharan Africa, the industries that have been built are working on malaria vaccines. In Thailand and Southeast Asia, they’re working on dengue and tularemia vaccines. These are vaccines that the whole world doesn’t need. We don’t have dengue in Philadelphia. But now they have the ability and the access to make vaccines themselves. And that’s critical for global access to new technologies.
The Future of RNA Technology
So RNA is not just the COVID-19 vaccine. That was the first therapeutic that was developed. There are going to be many, many more. There’s currently over 300 clinical trials using mRNA LNPs for vaccines, for gene therapies, for a variety of diseases. The gene therapies are the newest sort of darling of the field. So far, one disease has already been, I can’t quite say cured because we’ve only been following them for two years. But a single injection of RNA LNPs has fixed their disease for two years. And in a few more years, we’ll be able to say cured.
In a couple of years, we hope to be going to Sub-Saharan Africa or India or anywhere in the world with an igloo cooler full of RNA LNPs and giving people injections of RNA to cure their sickle cell. That can then be expanded to the thousands of other genetic diseases of the bone marrow, diseases of the livers, of heart, of lungs, of brain, of kidneys, of every organ in the body. RNA has the potential to treat these.
So we’re incredibly excited by the potential of what RNA holds. This is going to be long after I’m retired in a nursing home somewhere. But the hope is that RNA development therapeutics is going to continue for a long time and save a lot of lives. Thank you.
