\n<\/p>\n
Kendra Pierre-Louis: For Scientific American\u2019s Science Quickly, I\u2019m Kendra Pierre-Louis, in for Rachel Feltman.<\/p>\n
Cancer: it\u2019s a diagnosis that most of us have learned to fear. On the one hand decades of medical advancements have increased treatment and survival rates. A number of people who in the past might have died from cancer now go on to live long, full lives without recurrence.<\/p>\n
But not everyone is so lucky. For certain kinds of cancers, including cancer of the pancreas, effective treatments largely remain elusive, so increasingly, researchers are looking to a perhaps unexpected tool for help: vaccines.<\/p>\n
If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.<\/p>\n
It turns out that before mRNA vaccines became a key tool to protect people against COVID-19, researchers were initially eyeing them as a way to target cancer. That work continues.<\/p>\n
To learn more about how mRNA vaccines can help battle cancer we\u2019re talking to reporter Rowan Moore Gerety. He covered this topic for the December edition of Scientific American. <\/p>\n
What inspired you to write this story?<\/p>\n
Rowan Moore Gerety: When this first came on my radar about a year ago, partly, I was just surprised to be reading kind of frank mentions of cancer vaccines because, you know, growing up we think of vaccines as one of these miraculous interventions in public health that can basically eradicate a disease, right? So it\u2019s important to note that, in the cancer context, these are therapeutic vaccines, so it\u2019s not about providing immunity on the level of the population. But all the same it\u2019s the same kind of mechanism, and so I was just really interested to understand, \u201cWow, like, this is an approach that is seeming like it may be viable for cancer.\u201d<\/p>\n
That seemed like kind of a paradigm shift to me because my father\u2019s a cancer survivor. I have, as we all have, grew up hearing of people becoming gravely ill and dying with different forms of cancer, and it often just seems like a roll of the dice. To some extent it still is. But just the notion that there are interventions that might have, what I guess in my sort of layperson\u2019s brain, like, a vaccine level of effectiveness seemed kind of astounding. And so I was really interested to learn more.<\/p>\n
Pierre-Louis: Before we get into sort of, like, what makes these vaccines so unique, I think kind of on the, like, the specter of cancer and, like, the living with cancer, in the story you talk to Barbara Brigham, a woman who has been in remission from pancreatic cancer for four years. And that\u2019s a disease where most people don\u2019t make it five years. What was that kind of, like talking to someone who, absent this treatment, should be dead?<\/p>\n
Moore Gerety: It was really inspiring. I mean, she is a very rye personality; this maybe came across a little bit in the piece. She has what I associate with a kind of grandmotherly wisdom and very sort of upbeat spirit. But I think, if you have known anybody who gets a pancreatic cancer diagnosis, often it\u2019s something that is sort of diagnosed as a terminal illness. There is nothing to do but sort of treat it and see, \u201cCan we get a few more months\u2014or a few weeks, even?\u201d<\/p>\n
And as I note in the story, you know, she has been able to do quite a lot: She welcomed a new grandchild. She got to see all these volleyball games of her other grandchildren. She saw one grandchild get married and another start graduate work. And she lives on Shelter Island, which is near the tip of Long Island, and she sort of has had a very active and full social life, partly, not necessarily as, like, a cancer-survivor support group, but the way she explained her\u2014she has these weekly get-togethers where they play mah-jongg and eat dessert together, which sounds just lovely.<\/p>\n
But she\u2019s in her late 70s. The people around her, I think, are [in] their late 70s or 80s or even, in some cases, 90s. And so there\u2019s a little bit of a quality of support group to, I think, any socializing you do in that phase of life. Everybody has lost spouses, siblings; parents are long gone. And so I think it has been really meaningful for her to be able to convene a group of people and talk about surviving and talk about enjoying life on a day-to-day level. One thing I love that she said to me was her mother said you should try to have a little bit of adventure every single day. And she\u2019s adopted that as kind of a maxim over these last four years, and I think it\u2019s really served her well.<\/p>\n
Pierre-Louis: I also like that, like, the thing that is ailing her the most right now, at least that you put in the piece, is, like, her touch of arthritis. Meanwhile [laughs], she had pancreatic cancer. And it\u2019s funny that, like, the thing that she\u2019s like, \u201cAh, the arthritis,\u201d you know? [Laughs.]<\/p>\n
Moore Gerety: And she also survived breast cancer, actually, I should note …<\/p>\n
Pierre-Louis: Oh, wow.<\/p>\n
Moore Gerety: In the interim. This did not make it into the story. While she\u2019s been in remission from pancreatic cancer she has fought off a bout of breast cancer, as I understand it. That actually was communicated to us since I spoke to her.<\/p>\n
Yeah, she has gone through a lot and, obviously, has maintained a kind of positive point of view.<\/p>\n
Pierre-Louis: Can we talk a little bit about how mRNAs work against some cancers and how that sets them apart from existing treatments or existing understanding of, like, how cancer works?<\/p>\n
Moore Gerety: So one of the things that makes cancer unique among diseases, or relatively unusual, is that it\u2019s not like a virus, where, you know, you have this pathogen that\u2019s introduced into the body and the body goes, \u201cOh, my God, you look really, really different. I better go after you and attack you with all my might.\u201d Cancer, because it arises from these genetic mutations in our own cells, a tumor\u2019s genetics end up looking quite similar to the rest of your body\u2019s genetics. And so it creates a kind of a quandary for the immune system of figuring out, \u201cWhere is that line?\u201d<\/p>\n
Researchers talk about \u201cself\u201d versus \u201cnot self,\u201d and one of the kind of riddles of cancer treatment for a very long time has been how the body manages to make that distinction and how we can kind of put our thumb on the scales with medical interventions to accelerate immune responses to cancer.<\/p>\n
The earliest interventions into cancer were major surgery, right: \u201cLet\u2019s just cut out much of the organ, or all of the organ, that\u2019s being affected. And to some extent that still happens. And then you have chemotherapy and radiation, which are targeting still pretty broad parts of the body, or systems within the body. And so naturally, through all those things, there\u2019s a lot of collateral consequences. If you\u2019ve ever talked to somebody who\u2019s going through chemotherapy, they\u2019re really tired. It\u2019s, like, an extremely exhausting, taxing process. And part of that\u2019s because, like, you are absorbing these chemicals into your body that are pretty toxic. Like, so these are not things that you would do to yourself absent having a life-threatening disease.<\/p>\n
What is different about mRNA vaccines\u2014and in this they\u2019re kind of part of this newer generation of treatments that are called immunotherapy\u2014is that they are trying to leverage that immune response.<\/p>\n
And there\u2019s one more distinction to draw here, which is that about 30 years ago researchers started to have success with something called checkpoint inhibitors. So in our body we are always fighting off pathogens of one kind or another. And the body\u2019s always deciding, like, \u201cDo I need to pay attention to you, or, oh, is this thing over here more serious?\u201d And so part of what controls that immune response is a group of proteins called checkpoint proteins, and cancers can actually kind of trick the body using those checkpoint proteins to say, \u201cHey, don\u2019t worry about me. It\u2019s all good over here. We can turn off your T cells,\u201d those killer cells that would normally come after a tumor, \u201cand instead just let the tumor grow.\u201d So checkpoint inhibitors are a class of drugs that has been around for 20, 25 years that act on that capacity that tumors have to sort of shut off your T cells using checkpoint proteins.<\/p>\n
And so that\u2019s sort of the basic hallmark of immunotherapies: they\u2019re trying to intervene in the immune response. But in order to intervene there has to be an immune response. And what\u2019s new about mRNA vaccines is that mRNA is really just a set of genetic instructions. And so rather than your body needing to know, \u201cHey, this is what your cancer looks like,\u201d the mRNA vaccine can actually tell your body, \u201cHey, this is what your cancer looks like.\u201d And in that way it can help your body form what people call a de novo, or a brand-new, immune response rather than just amplifying the existing immune response, which is what earlier forms of immunotherapy have done.<\/p>\n
Pierre-Louis: And my understanding is researchers who are using the mRNA, it\u2019s not, like, a standalone thing. You don\u2019t just get a one-and-done shot, and you\u2019re on your merry way. It\u2019s, like, used in conjunction with other immuno treatments.<\/p>\n
Moore Gerety: That\u2019s right. So because cancer\u2019s so serious, and I think because of, you know, the Hippocratic injunction \u201cDo no harm,\u201d you can\u2019t just say, \u201cWell, to find out if this works we\u2019re gonna withhold the cancer treatments that we know work a little bit and just give you the shot and kind of see what happens.\u201d<\/p>\n
So the people who participate in early studies, or really any study, of mRNA vaccines\u2014and this is now quite a huge area; there are 50-some-odd trials going on right now. All of those people are getting kind of state-of-the-art treatment, whether it\u2019s chemotherapy and immunotherapy, surgery or radiation and immunotherapy, right\u2014whatever the sort of cocktail of interventions that researchers determine is, like, the best treatment for that form of cancer\u2014and then they\u2019re also getting these shots over the course of a few months or a year.<\/p>\n
Pierre-Louis: One of the [things] that surprised me in your piece was that, you know, for most of the world, and I think for most people in the U.S., mRNAs are sort of synonymous with the COVID vaccine; that\u2019s the thing that we think of. But we\u2019re kind of thinking of it a little bit backwards, which is they were tinkering with this treatment in order to treat cancer, and then the COVID pandemic broke out, and they were like, \u201cHey, we actually think we can use this as an inoculate against this, you know, very deadly virus.\u201d<\/p>\n
Moore Gerety: Yeah, this is a fascinating story and one that I was not familiar with through the pandemic even though, you know, I have, at this point, many mRNA shots in my arm.<\/p>\n
Pierre-Louis: [Laughs.]<\/p>\n
Moore Gerety: So two of the people who have been really critical in this history are the founders of BioNTech, which is one of the companies that came up with the first sort of viable COVID-19 vaccine right at the end of 2020. So this is a Turkish couple in Germany named Ugur Sahin and \u00d6zlem T\u00fcreci. And they first became interested in mRNA as cancer researchers 30 years ago because they were looking at precisely this question of: \u201cHow can we find a way to boost the immune response, and how can we personalize the response?\u201d<\/p>\n
So, you know, a little while ago I was talking about how cancer really looks like any other part of your body. Your cancer is gonna look more like you, perhaps, than it\u2019ll look like my cancer, and my cancer\u2019s gonna look more like me than our cancers will look like one another in some sense, right? They\u2019re mutations that arise from our own genes. And so even, you know, a generation ago the founders of BioNTech were really interested in figuring out, like, \u201cHow can we personalize treatment?\u201d And they decided to kind of bet on mRNA as a platform.<\/p>\n
And the reasons that they took this approach is that mRNA is a set of genetic instructions, and one of its real strengths is that it\u2019s very flexible. When you change between one patient and another or one disease and another you don\u2019t need to start from scratch. You can just go in and basically splice out a portion of those genetic instructions and say, \u201cOkay, now go look for this genetic mutation,\u201d and everything else in the molecule can remain the same.<\/p>\n
And so when I say everything else, what that means is the cap and tail that essentially say to the mRNA, \u201cGo to this part of the body. Try to be stable,\u201d right\u2014the body\u2019s kind of a messy place. \u201cDon\u2019t get corrupted or kind of thrown off your axis by whatever\u2019s going on inside us. And deliver your jolt,\u201d right? So they spent, like, decades, really, tinkering with that cap and tail, the rest of the mRNA molecule, in order to say, \u201cHey, how can we make this really stable? How can we make it persistent? And also, how can we make it powerful enough that it will engender a really strong immune response?\u201d<\/p>\n
When you\u2019re going after a virus your body produces antibodies, and those antibodies can then go throughout your body and sort of do their thing and go after it. When you\u2019re going after cancer it\u2019s actually the immune cells themselves that need to attack the cancer cells. And so what that means is, in terms of the demands of your body\u2019s immune response, it\u2019s much, much larger. I think they told me you have somewhere on the order of, like, tens of thousands of cells that would need to be active and creating an adequate immune response to fight off a virus, because those antibodies are always circulating, looking for the first signs of an invasion, but [for] a cancer response you might need billions of T cells to be engaged. And so in order to sort of customize the mRNA they had to figure out, \u201cHow can we make this molecule work so that it can generate a big enough immune response?\u201d<\/p>\n
So they spend decades doing this: kind of tinkering with the mRNA, finding a form they like. Along comes the pandemic, and they say, \u201cI think mRNA could really help here because it\u2019s so flexible. Each time the COVID-19 virus changes we can just tinker with that middle section and then spit out a new vaccine in a few weeks.\u201d And lo and behold that\u2019s exactly what happened, and that\u2019s what allowed us all to get boosters throughout the pandemic that were tailored to the genetic versions of the pathogen that was sort of most in evidence around the world so that when Omicron became a thing the vaccine\u2019s tailored to Omicron, and you can suppress whatever wave is happening that looks like Omicron.<\/p>\n
So then after the pandemic, again, they realized, \u201cNow we have this incredible proof of concept. All of that decades of work we did sort of pursuing mRNA vaccines as a good platform for cancer treatment, now we have shown people that it\u2019s safe, we have learned a lot about how to manufacture them effectively, and now we can kind of pivot and go back towards our original research interest.\u201d And of course, BioNTech is not the only company that was going through that journey.<\/p>\n
Pierre-Louis: You know, so far we\u2019ve been talking about this technology and how wonderful it is and how it saved lives, but there\u2019s, like, a dark side, which is kind of the combination of people more broadly becoming anti-vaccination and partly because of the rise of the Trump administration gutting the National [Institutes] of Health. This research is maybe not quite at risk but, like, potentially moving a lot more slowly and helping less people than it could otherwise. And I was wondering if you could talk more about what you\u2019ve seen in that regard, what researchers have told you. Like, what are we facing in terms of, like, actually having this technology be deployable on, like, larger scale?<\/p>\n
Moore Gerety: So we are in a really hopeful moment in terms of the science here. A lot of the technological advances that have made mRNA vaccines possible and practical as a form of cancer treatment in this moment are things that just weren\u2019t around five or even 10 years ago. It\u2019s now really, really cheap to do a genetic sequence of a tumor. You have all these tools, these algorithms that can predict how different kinds of proteins will appear in the body, and that\u2019s important to sort of figure out which of the different mutations in a tumor we might go after with a vaccine.<\/p>\n
So all of these exciting developments have kind of converged on this field at a moment when, all of a sudden, cancer research is kind of taking it in the chin. We saw what I think a Senate report estimated to be a [roughly] 30 percent reduction in federal funding for cancer research just in the first few months of the second Trump administration earlier this year. We have since seen cuts to major federal grant programs that supported mRNA vaccines for other diseases, so those haven\u2019t yet targeted the ongoing mRNA vaccine trials for cancer, but certainly, that is an anxiety that a number of researchers expressed to me.<\/p>\n
And I think you also have, for Americans, this new reason to question the sort of primacy of the American research establishment on a global level. And institutions that are used to getting the absolute best and brightest scientists who are up and coming from around the world flocking to New York and flocking to L.A. and Boston, wherever it may be, to, you know, go and implement their bright new ideas, those people are now starting to kind of wonder. I had a couple conversations with folks just about how different it feels to recruit young postdocs who are figuring out, \u201cWell, where does it make sense for me to start my researching life? Is the decades-long support for the kind of science I wanna do going to be there if I decide to make that choice in the U.S.?\u201d<\/p>\n
And so, as hopeful a moment as it is, I think there\u2019s a very long shadow over the field at this moment because these things take generations to develop, in some ways. Even the tissue samples in the study that developed a vaccine for Barbara Brigham, you know, the people who provided the earliest tissue samples that went into that study had, you know, died years earlier. And so there\u2019s this really long-term dimension to cancer research that is very, very important, and I think the longer the sort of interruption or pause or even just sort of uncertainty persists, the more people worry, \u201cAre we going to be able to rebuild or sustain the institutions that have made this research possible?\u201d<\/p>\n
Pierre-Louis: It also feels like, a little bit, like\u2014I don\u2019t wanna say that the people, you know, who died early on were choosing to sacrifice themselves, but it is a sort of sacrifice to say, \u201cI know that I\u2019m not gonna survive. I\u2019m gonna allow myself to be kind of poked and prodded for medical science so that, you know, the future generations can survive.\u201d And it seems like we\u2019re really at risk of kind of losing that sacrifice.<\/p>\n
Moore Gerety: A hundred percent. You need to give people a reason to feel that what they are doing is going to matter to somebody.<\/p>\n
I think it\u2019s great that people are willing to participate in studies, but as you say it\u2019s not that it\u2019s going to negatively impact their treatment, but the sales pitch is basically, \u201cHey, we don\u2019t know if this thing will work. You\u2019re at the, like, most difficult moment of your life. You may have limited time left with your family, whatever you wanna accomplish in your career. You have all kinds of new metaphysical thoughts about mortality and these things. And we\u2019re asking you to spend an extra day at the hospital, to meet with one more specialist, to allow our graduate students to be in the room, to go through a kind of selection process where we determine, \u2018Are you, in fact, eligible for this kind of new line of treatment?\u2019\u201d<\/p>\n
And so even if it does hold out a little bit of hope for improved health, it\u2019s not always, I\u2019ve gotta think, an easy trade-off. And we should really cherish people\u2019s willingness to participate in what is really a sort of an act of solidarity not only just across place, but across time, and try to support that as best we can.<\/p>\n
Pierre-Louis: That\u2019s really beautiful, and I think that\u2019s a really good place to end this, so thank you so much for your time.<\/p>\n
Moore Gerety: Thank you.<\/p>\n
Pierre-Louis: You can read Rowan\u2019s upcoming piece on ScientificAmerican.com on November 18 or check it out in the December issue of the magazine.<\/p>\n
And don\u2019t forget to tune in on Monday, when we go on a time-traveling journey with Scientific American\u2019s editor in chief David Ewalt.<\/p>\n
Science Quickly is produced by me, Kendra Pierre-Louis, along with Fonda Mwangi and Jeff DelViscio. This episode was edited by Alex Sugiura. Shayna Posses and Aaron Shattuck fact-check our show. Our theme music was composed by Dominic Smith. Subscribe to Scientific American for more up-to-date and in-depth science news.<\/p>\n
For Scientific American, this is Kendra Pierre-Louis. Have a great weekend!<\/p>\n","protected":false},"excerpt":{"rendered":"
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