In Bilbao’s Casco Viejo, where crews had to stop txikiteo for months because of the pandemic, no one stops Drew Weissman (Lexington, Massachusetts, 62 years old) to ask him for a selfie. However, it’s likely that these Bilbaois, who love close socializing and open-mouthed, and who are famed for their somewhat boastful generosity, would start a popular collection if they recognized him to give him a statue in one of the seven downtown streets dedicate.
Weissman, a prudent looking man, is one of the scientists who has enabled us to regain much of the life stolen by Covid, which has calmed the fears of the most vulnerable and relieved Ucis and morgues. His collaboration with researcher Katalin Karikó at the University of Pennsylvania (USA) made therapies based on messenger RNA possible. Vaccines from Pfizer or Moderna embody him and would not exist without his vision.
RNA is an essential molecule for life. Synthesized in the cell nucleus, it reads the instructions written in the DNA and separates from them so that the organism’s factories produce everything necessary for life. In the 1990s, Karikó came up with the idea of using this messenger substance to heal the sick. If the right piece of RNA were introduced into his cells, he speculated, they would produce the missing protein that causes anemia, or ignite an immune response to fight infection or even cancer. Weissman wanted to make better vaccines, and he also suspected that the answer might lie in the fragile molecule.
One of the reasons why the solution seemed impractical was that the RNA injections provoked an intolerable immune response. That changed from the early 2000s, when Weissman and Karikó began talking at a photocopier in their apartment, where they copied magazine articles that updated them on the latest scientific findings. Together they discovered a modification in the RNA sequence that suppressed inflammation and enabled the protein to be produced in large quantities. In a 2005 article, they published the results of a revolution that their peers were slow to assimilate.
Recognizing this decades-long effort and its tremendous impact on millions of people, Weissman is in the capital of Biscay this week to join Karikó and Robert Langer, a chemical engineer who accepted the BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine System, today to encapsulate the RNA so it can be injected.
“We are preparing a universal vaccine to prevent future pandemics”
Questions. Her work has had a huge impact on the lives of many people and has made her famous. What did this celebrity mean to you?
Answer. It’s actually a bit awkward because I’m very shy and I’m happy when they let me work alone. Now I’m in the spotlight, I see my photos being posted in New York and it’s disturbing. But it’s positive to be able to reach a lot of people, to talk to them about science, to explain to them what RNA vaccines are, why they are safe and why they should be given to them.
P The scientific community has been slow to appreciate the importance of what you and Karikó published in 2005. Is this inevitable when it comes to major innovations, or can something be done to accelerate the acceptance of new discoveries by society and scientists?
R I don’t think there is a solution. When we published our article in 2005, we thought everyone would want to use our discovery to make RNA therapies, but they weren’t interested and we didn’t understand why. It was another five years before interest came. This is life.
Drew Weissman during the interview. Javier Hernandez
P The pandemic has accelerated the development of vaccines and RNA therapies. What would have happened if it hadn’t happened?
R We started testing vaccines on humans even before Covid, but now everything is accelerating and an atmosphere conducive to the use of RNA has been created around the world. Regulatory agencies are keen to approve vaccines and therapeutics, and RNA has become a household term.
P Now we’re talking about the Pfizer or Moderna vaccine and not Karikós or Weissmans or any of the other researchers who made them possible. Do you think the merits and benefits of new drugs are shared fairly between big pharma and basic researchers?
R We need to focus on funding basic research and governments need to fund it better. What people don’t understand is that almost every drug that is developed, every new therapy, is made in academic laboratories. pharmaceutical companies don’t. The companies go into the laboratories and say: This is a great drug that we want to develop. That means I don’t want my name on a vaccine.
P Before working on this type of vaccine, he devoted himself to research into HIV. Almost 40 years after its discovery there is no vaccine, but for the coronavirus it was achieved in a few months. Why?
R We have been working on HIV vaccines for many years and now we have some clinical trials of RNA vaccines and we believe that in the next 6 or 7 years we will have an effective HIV vaccine. People need to understand that some vaccines are easier than others; the Covid vaccine is easy and the HIV vaccine is very difficult. They are not the same. But we are working on vaccines for HIV, malaria, tuberculosis and many other diseases and the probability of success of these projects has increased with the success of the projects for Covid.
“New drugs come from academic labs, not drug companies”
P What other vaccines and therapies can we expect thanks to new technologies that use RNA?
R For example with CAR-T, one of the latest therapies against cancer [consiste en extraer células inmunitarias del propio paciente, modificarlas para que detecten las células tumorales y volvérselas a inyectar]. They were very successful but difficult to manufacture. They take two weeks of lab work and cost almost half a million dollars. Using RNA, we were able to modify two types of immune cells in mice and make these CAR-Ts to cure them of cardiac fibrosis. And we bring it to the people. We believe we can cure sickle cell anemia with a single RNA injection and that’s important because every year 200,000 people are born with this disease, mostly in Africa and India, and now to cure it you need treatments with Cell therapies that cost a million dollars.
P Are we better prepared for the next pandemic thanks to this new vaccine?
R On the one hand, we are preparing a universal vaccine against coronaviruses and other viruses that have the potential to jump from animals to humans, thus preventing future pandemics. We do the same with the flu. We also make vaccines against malaria, one of the greatest scourges of mankind, and against viruses like Ebola or Nipah. I believe that RNA will allow us to create new vaccines very quickly, effectively and safely for the next possible pandemics and also avoid having to have souvenir punctures every few months.
P He talks about the production of RNA vaccines against tuberculosis, HIV and malaria. They are three of the top-killing diseases in the world, but they mostly affect poor countries. With Covid we have seen vaccines arrive very quickly in the developed world but the same has not happened in the poor.
R That’s what I’ve worked on my whole career. For example, we started developing a vaccine with laboratories in Thailand in spring 2020. Also, we have set up a production center that conforms to good manufacturing regulations [GMP, de sus siglas en inglés] so they can make vaccines for humans, and it’s already working. The Thai vaccine is in the final stages of clinical trials and will soon be available across Southeast Asia. We have also set up another GMP laboratory in South Africa, which enables local production of the vaccine. And when Covid is over, they can start producing vaccines for malaria. And in Thailand they will start with vaccines against dengue or other diseases specific to the region that pharmaceutical companies have no interest in producing.
P When applied to cancer, can universal therapies also be considered to some extent, or is the disease too complex to consider this possibility?
R In fact, it’s an incredibly complex disease. People tend to think that all breast cancers are the same, which is not the case. Therefore, it is very difficult to create an effective vaccine for everyone. But we are working on it and I hope we will have something in the future. I believe that cancer vaccines will be one of many therapies in development that can alter cancer prognosis.
P Aside from cancer or infectious diseases, what other therapies can be developed from RNA technology?
R Vaccines against autoimmune diseases such as lupus or rheumatoid arthritis, against food or environmental allergies are being worked on… RNA will be used in more and more therapies.
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