The Dawn of a New Era in Cancer Screening - Dr. Josh Ofman | 1149 | Dave Asprey

They said, okay, we know that DNA is being shed into the blood. We know we can find that DNA. What is the best way to interrogate that DNA to find a signal of cancer? And they studied all of them. Mutations, chromosomal changes, fragment lengths, you know, proteins, rna, and methylation, which is the epigenetic changes. Those are those little molecules that attach to the DNA that turn genes on and off, but they don't change the code. And when that study was completed, Grail determined that these methylation changes were the most powerful way to find cancer signals. And they're the most specific.

You're listening to the Human Upgrade with Dave Asprey. You're listening to the human Upgrade with Dave Asprey. Today is an interview about what's going on inside your cells. In the last, oh, four or so years, there has been a surprising and unprecedented surge in the speed of some types of cancer proliferation that I've been hearing about from a variety of friends in the field. And cancer is one of the big four killers. If you've read Superhuman, which is my big book on longevity, that sort of set a framework that a lot of longevity books are using now, there's four things to do to not die, and then there's a bunch of other things you do to support the systems that are in your body. And not getting cancer, or at least surviving cancer because you detected it early is one of the biggest things you could do to live a long time. So that's easier said than done. Support metabolic health. Don't expose yourself to toxins. You know, don't have too much sugar, and don't do a bunch of other things that are not so good for you. But how do you know if it's working? Well, I've got a guest for you who has spent a long time, about 15 years, working in biotech. He's a faculty member at the UCLA School of medicine. And we're going to talk about multi cancer early detection or something called a grail test, something I first did almost, I want to say, seven, eight years ago, because regular cancer screenings are part of my longevity strategy. It used to be just sort of a scary thing. Wait till you see a lump, which means it's really big. Or get a blood test and see what happens if you can detect something way before you could see it. And let's talk with the world's expert on this kind of stuff, Dr. Often, welcome to the show.

Thank you very much for having me. And I'm with a company called Grail.

Grail's been around for how many years now?

It was founded in 2016, so it's been around for about a little short of eight years now. And it was spun out from a company called Illumina, which is a sequencing company. And we've been independent now for about. Since then. Since 2016.

Well, I am grateful because being able to know whether you have cancer or not can be a huge source of. Lack. A source of relief for people, especially if you had some sort of cancer in your family, which is not really common. You're saying, well, do I have higher risk? Is it genetic? Is it environmental? We don't really know. Or I used to smoke. How many types of cancer can you detect now with the grail test?

So, you know, just to take a step back for a minute, and you. You mentioned this in your introduction. You know, cancer is soon to become the number one killer of men and women worldwide. And why is that? Well, it's because we're finding most cancers too late. So the way traditionally in healthcare, we have screened for cancer is by looking at one cancer at a time. So for women, we look for breast cancer, cervical cancer, colon cancer, and if she happens to be a smoker, also lung cancer. And we're looking for those single cancers. So we call those single cancer screening tests. Right. A pap smear or a psych. Well, grail was invented and kind of founded some really breakthrough technology that looks at DNA that is being shed by cancer cells into your blood. And we figured out a way to combine genomics and artificial intelligence and machine learning to read a pattern in that DNA that you see very commonly in many different kinds of cancer, and importantly, that you almost never see in patients without cancer. So so far, this pattern recognition technology has enabled us to find well over 50 different types of cancer.

Wow.

And we're grouping them so we know it's well over that. We know, you know, probably 60 to 70 already. And because we're not looking for any particular cancer, we're looking at whatever cancer the individual may have, because there's a shared signal in that DNA that we're reading. And. And then we can localize that signal to where in the body that signal comes from to tell the doctor where to go look to find that cancer, if it exists.

I've read that there isn't a lot of genetic overlap. You take two different pituitary tumors, and they could have entirely different genetics in them.

How.

How do you know what cancer DNA looks like, given that a lot of cancer looks like it might not be DNA caused, you know, when most people.

Are talking about DNA, they're talking about mu mutations, you know, changes in the code of the DNA. And you're exactly right, Dave. You and I may have some changes to our code or mutations that are exactly the same mutations that you see in cancer, but we don't have cancer. So that does happen. And you can be fooled. Mutations are uncommon. They occur in cancer and non cancer. And they fooled by clonal hematopoiesis and other things. We're not looking at that. We did a very. What Grail did very uniquely, which is quite interesting, is they asked a very unbiased question. They said, okay, we know that DNA is being shed into the blood. We know we can find that DNA. What is the best way to interrogate that DNA to find a signal of cancer? And they studied all of them. Mutations, chromosomal changes, fragment lengths, you know, proteins, rna, and methylation, which is the epigenetic changes. Those are those little molecules that attach to the DNA that turn genes on and off, but they don't change the code. And when that study was completed, Grail determined that these methylation changes were the most powerful way to find cancer signals. And. And they're the most specific.

It's interesting, other colleagues, both at UCLA and other schools, are using DNA methylation for something a lot of listeners know about, which is DNA methylation, aging tests. You can see speed of aging or aging clocks. Steve Horvath's work.

Yep.

And so these are really the same sets of genes. You just have a different lens to look at them, right?

Yeah, they're. They're molecules, basically. When from the time you're an embryo, these little molecules, they're called methyl groups, are attaching to the DNA and they're actually regulating the DNA. So the genes are actually the codes within the DNA, but these molecules turn those genes on and off. And so when you want, when you're an embryo and a certain type of cell says, I now need to go become a liver cell, it's usually those methylation markers that are telling the genes to differentiate those cells into liver cells. So there's a little fingerprint that's always left on those cells to tell you where in the body they are. And so we read that fingerprint, but we read a much broader pattern also that in cancer, those molecules are in and around tumor promoter and tumor suppressor genesis, turning them on and off. And so in cancer, you see this hyper methylation of those tumor promoter and suppressor genes and kind of a global hypomethylation of other informative genes around cancer. And that pattern is what we're reading.

How do people go about getting a grail test?

The grail test is called gallery and you can get it in two ways. Right now it's, it's been on the market for about since mid 21 and it's right now can be ordered by a physician. It must be ordered by a physician. So someone could go to their doctor and say I would like grail's gallery test or the gallery test. And it's usually because it's not covered by most insurance yet, usually an out of pocket expense at this point. Or they can go on the gallery.com website and order it through a telemedicine provider. And the kit, it's a small kit with two tubes, will get shipped to their home and they can go to any Quest Labs or any local lab or have a phlebotomist come to their home and draw the blood and then they'll get their results in about seven to 10 days.

And what's the cost when you go to the website?

A retail cost is $949. And obviously if you're part of an insurance company or a self insured employer or a life insurer that offers the test, it'll be, you know, far less than that. And some of the prices are discounted in certain health systems and other provider organizations and we have line of sight to getting those costs down over time with future versions.

People can also use in the US anyway FSA and HSA where you can set aside some pre tax dollars for this.

That's right.

Which basically saves you 300 bucks in taxes or something when you do it. And just thank you for making it direct to consumer. Right now we're seeing this. What I think is a really powerful shift where you used to have to go to the doctor and say what test do I need doc? And now people are saying well you know, I just want to do this so I know what's going on in there. And it's not because I'm sick, it's because I'm going to not get sick. And sometimes you just need to go online and order what you want and get your own data and then call a doctor if you need it. So the telehealth way is I think a way of reducing friction for people to have access to their own data.

Couldn't agree more. We have a breakthrough device designation with the fda. We are seeking FDA approval, but before that, you know, we don't really do direct to consumer advertising or marketing. We we do a awareness raising, and then a physician does need to prescribe it, whether it's a telemedicine provider or a provider in an office. But what's beautiful about this is, is that gallery is a really important proactive tool. It gives people the power to be more proactive about their health, because the only chance that we have to bend the cancer mortality curve is to find many, many more cancers much earlier, before symptoms present. By the time symptoms are present, most cancers have already spread. And if you can find it in an asymptomatic state, generally at an earlier stage, you know, most cancers are very treatable, and they're often quite curable. So we have already found, you know, in many of our studies, and in the real world, we are finding early stage of the deadliest cancers. And surgeons are saying things like, I've never seen a gastric cancer this early or a pancreatic cancer this early. And they're undergoing curative intent treatments.

How does the grail test compare with whole body MRI for cancer screening?

Well, whole body MRI for cancer, we don't know. We know there's never been a formal study of MRI for cancer screening compared to other forms of cancer screening. So I can't. I think there have been some studies done outside the United States, and. And those studies did not look particularly favorable. MRI, whole body imaging is, is an interesting technique. It can find early cancer, asymptomatic cancer, but it doesn't visualize, you know, some of the areas very well, like the hematologic compartment, for example, and it doesn't visualize inside, you know, your GI tract very well. So there are limitations. And the other problem with mri, although it's a very good test, is that you find all kinds of things in the body that people don't really know what to do with that aren't suspicious of cancer. But there are other things that you find. And so that's been a challenge. But I think, you know, it is in use, and I think we're hearing more about whole body mri, but there's no, there's no direct comparison that I'm aware of, because I don't know the performance of whole body MRI for early cancer detection.

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Both are useful and I think, you know, time will tell about cancer detection. The other thing we know is that, you know, we're getting. What's unique about the innovation that that grail has developed here in the test call gallery is that it's, it's highly specific for cancer. As you know, it's got a false positive rate of less than. It's about 0.5%. That's an order of magnitude better than anything that's ever been seen in cancer screening before.

Wow.

And it also is very accurate in telling you where in the body that signal is coming from, which is tremendous. And it's very sensitive for the deadliest cancers. The, the issue with, you know, after you get a positive gallery test, if it says so, Dave, let's say we did the test on you and it said gall, you know, cancer signal detected, predicted origin, liver or pancreas or stomach. You know, imaging is imperfect. Right. We've already had many cases where imaging didn't detect the cancer that was there. I'll give you an example. A woman got a positive gallery test. It said gallbladder is the predicted location. MRI of the liver and the gallbladder showed a gallbladder that looked fairly normal, but it was filled with gallstones. So the doctor didn't want to do anything. The woman was asymptomatic. She insisted on having her gallbladder removed. And the first surgeon didn't want to do it because she wasn't having any symptoms. The second surgeon did it, and when they went in there, the gallbladder was stuck to the liver. And when they took the gallbladder out and opened it up, there was a cancer inside the gallbladder. Wow. That was being obstructed by all the stones. And so imaging missed it. And we've had many, many cases like that. And so what we use, what we're used to using for cancer screening is we're used to using shadows, images, you know, and directly visualizing tissue with either a, you know, a Pap smear or a colonoscopy or a upper endoscopy. And, you know, we know that those are not perfect. Now what we're seeing are direct biological signals being shed directly from the cancers. And that's teaching us a lot about cancer.

That means that we'll be able to see it earlier and earlier. The more data we have coming in from people as well, right?

Yeah. The more data we have, the more we'll be able to teach our machine learning algorithms to get better and better, to get more biological noise out of the assay so that we can detect smaller and smaller amounts of this tumor DNA that's being shed into blood. Now, there are some tumors that just don't shed DNA into the blood. Brain tumors, for example, are protected from the blood by the blood brain barrier. Very early melanomas, they're too superficial to access the bloodstream. The slow growing tumors, like encapsulated prostate cancers, are not shedding a lot of DNA into the bloodstream. So not all cancers can be detected this way. But many, many cancers can. And importantly, 80% of the cancer deaths today, okay. Are caused by cancers we are not looking for. And so this gives us an opportunity now to look for all those cancers that are causing the vast majority of cancer deaths that we are not screening for today.

That's incredible. So, retail price about 950ish dollars. It's almost like if you looked at some of the $160 billion that the government sent overseas. If you took the number of people in the country and multiplied times $960, assuming no volume discounts, it looks like we could have afforded many times over to do early cancer detection for the entire population of the U.S. including anyone who is in the country, whether or not they're a citizen or not, green card holders and everyone else. And if we did that, our 1.4 trillion dollar or whatever it is, national spend on healthcare would drop precipitously. Right, because the amount of money you spent on cancer is insane.

Yeah, we do. Late stage cancer is very expensive to treat and isn't very effective. Early stage cancer obviously much easier to treat and much more effective and much less costly, often 5 to 10 times less costly to treat early stage cancer and late stage cancer. The other thing that's really important to know is that, you know, so often, you know, we, we get asked the question, is this affordable? By the time this gets to population wide screening, the cost of this test will be much lower than they are today. But remember, all the screening we're doing today, we spend about $25 billion a year screening for these five cancers. Okay. And most of that money is being spent on working up all the false positives. So, you know, we find those cancers are fi. Those screening tests are only finding about 14% of the incident cancers in elevated risk adults. And we look at risk, age is the most important risk factor. And that's not enough cancer. We're not going to bend the cancer mortality curve finding so few cancers and they're generating an enormous number of false positives and that's what's consuming all the money. We're suggesting that Galleri be added to those standard of care single cancer screening tests. And we can create a much more effective and efficient cancer screening system to find way more than just those five cancers, but all the other cancers that people are dying from. And to do it with a much lower false positive rate.

That sounds like that would be, well, life, life changing for a lot of people. And that was why I wanted to have you on. Because this is a new way of thinking about cancer, right? It, it was very much an imaging game, right? Or a symptom game, like you're limping, let's find the bone cancer. But by the time you're limping, you're kind of screwed, right?

That's right. And it is very different. It is a, it's a paradigm changing type of technology to be able to transition from only looking for individual cancers now to also look at individuals for whatever cancer they may have. So let me give you an example. You're a, you're a man, you get prostate cancer screening, colon cancer screening, and let's say you use a stool based colon cancer screening test like, you know, cologuard or the Fit test. And let's say you're a smoker and you also get low dose CT of the lungs. No doctor has ever told you that. Across those three tests, your false positive rate for you, the person, not the false positive rate of the test, but for you will be almost 40%.

Wow.

Nobody would ever recommend a test like that. Right.

It's almost like you could, you could flip a coin.

Well, it's. That's at the false positive rate level. Now, if you think about positive predictive value, which is if you had a positive test, what's the likelihood you have cancer? That's going to be less than 2%. Okay. So, you know, because cancer is very uncommon, generally it's about 1% incidence. So, you know, the positive predicted value for the gallery test to look for 50 or more cancers is somewhere between 40 and 50%. So an order of magnitude higher than anything that's ever been seen before with cancer screening.

Wow. So you're finding all this stuff that nothing else can find.

That's right.

Do you have enough data over the past year since you started doing testing to look at incidents of cancer? Have you seen any, anything in the signal that says cancer is getting better, getting worse over time, or is this just. We're detecting more.

We haven't, we were. We're going to be detecting more. We haven't seen any data on any particular cancer as to whether the incidence is changing. But you know, what was good about. I joined GRAIL about four and a half years ago and they had begun investing in a, in a very large evidence program that's considered to be probably the largest clinical genomics program ever undertaken. Were studying over 380,000 individuals in all sorts of studies, including the largest randomized clinical trial ever conducted for a multicancer early detection test in England, where we randomized 140,000 adults with no signs or suspicions of cancer. And that study is fully enrolled and they've done their third consecutive screening round. And that study will weed out, you know, in, in a year or two. We've done real world interventional studies in the United States where when we added gallery to standard of care screening, we more than doubled the number of cancers found in the population. And half of the cancers we found were in stage one and two. 70% of the cancers had no recommended screening. And again, the positive predictive value, you had a positive gallery test, the likelihood you had cancer was 43%, again, order of magnitude higher than anything that's ever been seen. And we found some of the deadliest early Cancers that, that have been found in and we continue to study in the real world. We've done over 150,000 commercial tests. Now we're seeing a signal detection rate of about 1%. So about 99% of the people who take gallery will get a result that says no cancer signal detected. Please keep getting your single cancer screening tests because we don't want to replace those, we want to add to it. And about 1% will say cancer signal detected, predicted origin ovary or uterus or stomach or pancreas. And you know, they'll go, those doctors will go work them up for cancer. And we're finding those early cancers and.

Most cancers, if you detect them in stage one, are highly curable, right?

That's right. Even stage two, you know, stage one and two solid tumors are localized, they haven't spread. And so those are very well treated. There are more treatment options. And even if they're not curable, the life expectancy is much higher than it would be then in later stages. And it's, you know, often surgery with or without radiation is the treatment.

If Steve Jobs had access to the Grail Gallery test, we would have spotted that way earlier than we did, right?

Probably.

Yeah, yeah, yeah, that's what it looks like. And so people fear pancreatic cancer partly because of Steve Jobs. Plus it's just, it's a really severe, relatively fast moving and highly fatal cancer. But if you get it at stage zero, stage one, it's pretty darn treatable.

That's right.

I know 950 bucks is a lot of money for, for people right now. Half the country in the US doesn't have $1,000 for an emergency medical expense. And you may or may not have insurance. And it's not supposed to be like that in the country. And it wasn't always like that. And it won't always be like that, but it is right now. And so if you're listening to this, this is one of the things to ask your insurance company and your doctor about. And if you are someone who's in a fortunate position to say, all right, I'm spending proactively and avoiding the four killers. Don't get diabetes, don't get cancer, don't get heart disease, and don't get Alzheimer's if you can just do that. And there's so much information now about how to just reduce your risk by orders of magnitude with some simple lifestyle behavior things. And you can measure whether you're making progress. This seems like one of those things that ought to be on your list of what, every two years, how often would you do a Grail gallery test?

Actually, we're recommending gallery be used annually. Annually, because what we're learning about the rate of growth, the pace of change of these cancers is faster than what most people have come to understand because now we're looking at this biological signal being shed from the cancer itself. And so, you know, most of these deadly invasive cancers are moving really quickly. And so if you don't do it annually, you run the risk of, of missing that early stage detection. Most of our studies are, are with annual testing. In fact, Medicare has just worked, you know, to approve a study that we are doing called the Gallery Medicare study or the reach study of 50,000 Medicare beneficiaries who will get tested for three consecutive years. And Medicare will pay for the test and the workup. And so we're going to, we're going to really study this in the Medicare population. And it's, you know, again, an annual test. And to your point, you know, $949 is a lot for Americans right now. But we're in a transitional period. We have every intention of getting FDA approval as soon as possible and then payer coverage and payer reimbursement will occur so that patients won't have to bear the burden of that cost and we can get to population wide screening much faster.

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No, it is not available. The only place right now where it's available is in England as part of that study. And the UK government is going to think about whether they would do an early implementation pilot in a million Englanders over the next couple years. And we'll hear about that probably over the summer whether they're going to do that or not.

I was just down at UC San Diego at, at Dr. Patel's office looking at mitochondrial biology and he's getting amazing results from just getting blood on, you know, dry blood samples now. And I've seen so many companies with mini lancets, and it seems like there's a big revolution of not having to go into Quester LabCorp to get liquid blood. Are you guys close to being able to use better sampling so that the cost could go down?

You know, the sampling is not a huge part of the cost, but right now, no, we. We need two tubes of blood.

You do. Okay.

We run the test on one tube, and then we keep a backup tube in case it's needed.

Okay.

And, you know, we're always looking for ways of improving our test, and we may come to something like that, but for now, you know, we're trying to collect two tubes of blood on every individual who takes. We want to make sure we have that extra tube in case something happens.

So you could rerun the test. That makes sense. And do you mix all the blood up at the end itself to vampires? Just checking.

No, no, but we, you know, the way our test works is. Is pretty straightforward. You know, we isolate the DNA out from the plasma. So we spin down the blood, get the plasma, isolate the DNA, amplify that DNA, and then. And then sequence it using bisulfite sequencing. A very proprietary chemistry that gives us that ability to see the methylation pattern. And it's that. That the machine learning classifier is taught on. And then if there's a signal scene, it goes through a second machine learning classifier to pinpoint where in the body that signal came from, because there's that little. Yeah.

Wow. This is groundbreaking stuff. Another question for you. The history of medicine, at least in all the 1900s, has been, let's do it on college age. Mostly white dudes, because that's who's going to college. So you look back in 70s, 80s, and even early 90s, there was way more sampling of men, but the population is 51% women, at least in the West. And it's a little bit stilted to have less women in some parts of Asia, mostly because of birth practices. So that means that you're sampling, though, now, is it an equivalent? Are you getting 51% women samples, 49% men? And is there a difference in the way you have to analyze cancer in women versus cancer in men?

It's a great question. No, we're not. We're trying in our studies to get as representative a population as possible. Ethnic representation, racial representation, and socioeconomic representation. So, you know, traditionally. So the Medicare reach study is a good example where we're really aiming to get into those populations that are traditionally underserved. The UK trial that I mentioned in England is very well represented with a diverse and a socioeconomically deprived population. So we're trying to get as broad a population as possible. We know that age is the most important risk factor for cancer. So the studies are typically done in adults over the age of 50. And we know that adults over the age of 50 have about a 13 times higher incidence of cancer than adults under the age of 50. But there are younger populations like a 35 year old smoker or a 35 year old cancer survivor or a 30 year old who may have a hereditary cancer syndrome or carry a germline mutation. They're also at that elevated risk of cancer. So in clinical commercial use it's being applied to all of those elevated risk groups. But our studies are typically in, in, in adults over the age of 50.

Makes sense. I feel like if I was to just apply what I know about the world, I would guess that the second biggest predictor after age would probably be poverty level.

Yeah, I mean it's, it's. We, we do know that socioeconomically deprived populations and ethnically less diverse, you know, diverse populations, excuse me, you know, if you're a, in a black community or a Hispanic community, that they do have a higher death rate from cancer, they get less cancer screening and they have a higher incidence of cancer. And, and so that's a sad state of affairs. The truth is, Dave, there is, there's just nothing acceptable at all today about the status quo in cancer screening. We are not finding enough cancer. We're not screening the population enough. We're not looking and screening for the cancers that are most deadly other than colon and lung. And we need to do a much better job and we have technology now that can help us get there. But we've got to get through know this period of, of pre reimbursement, you know, to get there.

It feels like when Medicaid has the ability to say, oh, you turned whatever age 50 because there's a big peak there, or when you first go on Medicaid, just you, you get a grail test automatically, they would reduce cancer care costs enormously, but they might have to pay benefits for another 10 or 20 years. So maybe it doesn't pencil for the bureaucrats, but for those of us who want our grandparents around, it pencils very, very clearly. Which is why this is, this is so critically important and why I wanted to have you on the show. If you put on your, your future Hat here you have so much data. Is there ever going to be a day where we can say, you know what, we're pretty darn sure that these three environmental things or these two food things, those are smoking guns for cancer.

Yeah, it would require quite a lot of population data. And I think still a lot is being learned about the exposures. You know, you've got, you know, first responders and firefighters, you've got in the military, people who are exposed to burn pits and, and other, you know, chemical warfare agents that we know are getting early cancer and are dying of early cancer. And so there's a lot we need to learn and a lot we can still do. But it will require novel technology like grails technology to get widespread use. If we really want to make a dent in this and to figure all of this out, but at a population level, we need to get there and it's just going to take us time. But traditionally, you know, Dave, it's taken, you know, decades from the time you had a validated technology until the time it was widely used for screening. You know, cologuard is a good example. Colonoscopy, mammography, low dose CT for the lungs. Decades from the time studies show they were good and valid to the time it was widespread. We can't afford to do that any longer. We have technology today that can find cancer in people who have no idea they have cancer. And we refuse at grail. We have a huge sense of urgency to get this into the hands of providers and their patients and we're doing everything we can to, to do that today. That's why we launched it as a lab developed test. That's why we're pursuing FDA approval. You know, Medicare, as you know, doesn't even have the authority to pay for tests like this. The only reason they pay for colonoscopies and mammograms is because special laws were introduced giving them that authority. So we're hopeful that Congress, you know, will do what's right to give Medicare the authority to pay for tests like this in the future once they're FDA approved.

It sounds to me like the grail tests should just identify as a virtual mammogram and confuse the heck out of the attorneys.

That's a great idea.

Nothing like wordplay to get bureaucrats all in a tizzy. Now when we talk about in the future, we'll have more data around cancer. Going back historically, it feels like you can see various points where cancer, there's a change in the slope of the curve. Like in the 90s, early 90s, cancer rates just went, started going through the roof and the age at which people got cancer started to go up a lot. And I've, I've seen various people say, well, there's in chemical things, there's mobile phone things, you know, there's compact fluorescent light bulbs and you know, whatever, you know, cosmic rays. There's lots of different theories about that stuff. If you had to say with, with all the disqualifiers, you could say saying, I'm not sure, but as an expert in the field, if you had to guess at, at what, what would you hypothesize? If you were just going to say, let's experiment and see if I'm right, where would you throw that dart?

That's a great question. I think what we're seeing, interestingly, is an age shift in the incidence of cancer.

For example, it started going through the roof and the age at which people got cancer started to go up a lot. And I've, I've seen colorectal cancer, as.

You'Ve seen over the last five years, seems to be showing up in younger people now.

Various people say, well, there's in chemical things, there's mobile phone things, you know, there's compact fluorescent light bulbs and you know, whatever, you know, cosmic rays. There's lots of different theories about that stuff. If you had to, we'll say with, with all the disqualifiers, you could say saying, I'm not sure, but as an.

Expert, more often than it used to, and we don't know why that is, is it food related there, the field?

If you had to guess at what would you hypothesize? If you were just going to say.

A lot of hypotheses. But you've got to suspect that if that's happening in colorectal cancer, it's probably happening in other cancers as well, right? The relationship between our exposures.

Let's experiment and see if I'm right. Where would you throw that dart?

That's a great question. I think what we're seeing in the incidence of cancer is just something, you know, maybe the National Cancer Institute, maybe people need to really take that up and help us learn a lot more about.