Golden Retriever Lifetime Study - Update From Morris Animal Foundation

Got this poignant email from Morris Animal Foundation today: 

As we approach the 15th year of the Golden Retriever Lifetime Study, we are entering a new, exciting stage every pet owner will appreciate. To date, 386 of our dogs have lived to age 13 or older, including three who have reached the remarkable milestone of 15 years. As a lifelong golden retriever owner, it warms my heart to see these dogs thrive. As a veterinarian and epidemiologist, I am eager to leverage this unique dataset to understand what sets these “super-seniors” apart. After all, that is our ultimate goal: we don’t just want dogs to avoid cancer, we want dogs that remain healthy and vibrant well into their golden years.

To capture the shifting challenges these dogs may face as they age, the Study utilizes supplemental surveys that participants can opt into every six months. These provide vital data on mobility and cognition. This initiative began when most dogs in the Study were approximately 8 years old and is rapidly becoming a robust dataset that will aid researchers for decades. Current research suggests dogs fall into two categories: "cognitive maintainers" and "cognitive decliners." Our data is uniquely positioned to help us identify the specific factors that contribute to prolonged cognitive health.

Because the Golden Retriever Lifetime Study is longitudinal, scientific interest has accelerated alongside the Study’s progress. While we have sadly said goodbye to 1,780 heroes, the information they contributed from puppyhood onward is of historic importance. As I write this, more than 100 studies have leveraged our data to investigate a wide variety of health topics. We recently closed our annual call for canine research proposals, and of the 142 pre-proposals submitted, 21 plan to incorporate Study data.

While the Study’s evolution into aging is exciting, our primary objective — to make progress against canine cancer — remains unchanged. The Foundation recently invested in two cancer studies that showed promising initial results. Both successfully identified genetic regions related to hemangiosarcoma and histiocytic sarcoma, respectively. Researchers are now building on these findings using Study data, which could lead to life-saving genetic tests. These are just two examples of the many promising studies currently underway that have the potential to change the future of canine health.

From all of us at Morris Animal Foundation, thank you for making this work possible and supporting the research that will help dogs run, play and be with us to create more memories well into their golden years.

Please keep up the good work; your team will always have wishes from Max and I.  

I said this when Max had cancer and I am saying this now - a lot of insights will come from this study and the Dog Aging Project which will help Sapiens although my moronic species refuse to give data. 

Researchers need a lot of data from healthy people to understand what it looks like not having cancer - a fundamental machine learning common sense. 

Theories To Old Truth - Roots of Cancer

Strictly speaking, genetics do not play a known role in human cancer,” says Carlos Sonnenschein, MD, a professor of integrative physiology and immunology at Tufts University School of Medicine. “Most, if not all, cancers are due to environmental factors.

Those factors, Sonnenschein explained by email, include things we have some control over and things we don’t, from what we eat and drink to whether we smoke, where and how we live, how much physical activity we get, plus societal factors such as pollution and exposure to hormone-disrupting chemicals found in pesticides, plastics and processed foods.

- More here and I told you so. 

I lost Max because of this. 

Humans never take responsibility for their actions. Some "magic" caused x and some "magic" y will fix x while I sip my beer, play golf, and go for vacation in sunny weather (hey I work hard you know). 

For the past few years since Max left me, I don't feel any emotions for someone who is willfully ignorant and gets a deadly disease. I just say, sorry to hear and they are out of my mind.

On the other hand, I will do everything I can for someone who regrets their choices they made, and they are paying the price. I am yet to meet one in person.

Bubba Becomes First Fish To Survive Chemotherapy

38 years ago, an anonymous donor dragged a large, sloshing bucket to the Shedd Aquarium in Chicago, USA, dropped it at the reception desk, and disappeared. When staff pried open the lid, they discovered Bubba – a giant grouper fish, presumably caught and determined too big to take care of. A note attached to the lid asked for the fish to get to a good home.

Upon deeper examination, doctors learned more about the Epinephelus lanceolatus. At the time, she was only 10 in long, and was a Queensland grouper – a species fast disappearing in nature. The "super grouper" needed treatment, so they nursed Bubba back to health and found her a new home in a tank in the coral fish exhibit, where the predator happily swelled to 4.5 ft (1.37 m) and a whopping 69.3 kilos (150 lbs).

While there, she became a popular attraction, as visitors marvelled at her mysterious origin story and compassionate change in circumstances. And when she was briefly removed from exhibition in 1998, fans were distraught.

"That's when we found out how popular [s]he was," said Shedd spokesman Roger Germann, to the Washington Post, "because we started getting letters from people saying they couldn't find Bubba on their last visit and wanted to know what had happened."

Midway though the 1990s, Bubba underwent her second big life change as she transitioned to male, as groupers often do. This is a common reproductive strategy in fish species, whereby the larger female fish in a tank change sex to male, while the smaller fish remain female – and since Bubba was so big, scientists weren’t exactly surprised!

But scientists were shocked to find in 2001 that Bubba, their beloved grouper, had cancer. 

While this usually is a sure sign of a fish’s demise, because of Bubba’s size, scientists decided to take the unprecedented step of treating him with chemotherapy. This was never attempted before on a fish, but groupers can live 30 to 50 years, so if successful, they would be making advances in cancer treatments, while giving Bubba years of his life back.

Luckily, Bubba responded well to the treatment, and he became the first fish to survive chemotherapy – and cancer! 

After his treatments, he spent many happy years entertaining visitors and serving as an inspiration for human cancer survivors. The Shedd Aquarium reported receiving many calls from people affected by the disease, especially children, asking how Bubba was and gaining strength and courage from the knowledge that he had survived his own ordeal and that chemotherapy had extended his life. And beyond that, he was a personal favourite for many at the aquarium.

"Bubba overcame some incredible odds over the years, and that's what made him so special to us," said George Parsons, director of the Shedd's Fish department, to the Underwater Times. "Every once in a while for the last three years we have been getting phone calls from kids with cancer or from their parents, wondering how he is doing." 

After regaining his health, Bubba was moved to a new home in the 400,000-gallon main pool of the Shedd's new $43 million Wild Reef gallery, so his fans could properly appreciate his beauty. He even got a new 5-inch friend – a golden trevally fish, which swims around him and eats his scraps.

"He is such a character," said Rachel Wilborn, one of his keepers, to the Washington Post. "He is so curious, always coming around to see what you are doing. If you give him a food item that he doesn't like, he spits it right back at you, then looks you right in the eye, waiting to see what else you can come up with."

After many happy years in his new home, the magnificent fish passed away in August 2006 from age-related issues. A Shedd official said his autopsy shows only “evidence of multiple organ system failure consistent with [Bubba’s] age.”

"It's going to be tough now, if I have to tell people he's no longer with us," said Parsons.

But nevertheless, even though Bubba has passed, his story lives on as a testament to the compassion of his healthcare providers and all who loved him. His body was even donated to Chicago’s Field Museum across the street, where they will keep Bubba’s skeleton as a part of its enormous fish collection and cryogenically freeze his tissue samples, preserving them for study by future generations of scientists.

"If you want to know why we went to all this effort for a fish," Wilborn said, "all you have to do is look into his adorable face. We did it for Bubs because he is such a cool fish."

- More Here

Curbing Animal Testing

I hope this happens soon as in few months: 

Animal testing is a relic from a bygone era but still promoted fervently by interest groups and government agencies as the “gold standard” in experimental sciences for predicting response in people. That is even though — in drug development, for instance — animals are notoriously poor predictors of drug safety and efficacy in humans. To this end, exclusive reliance on animal testing translates into irrecuperable delays in the development of medicines, missed opportunities due to misguided regulatory principles, and exorbitant costs ultimately passed onto consumers.

A jarring 90-95% of experimental drugs fail in clinical trials after acceptable outcomes data in animals are used to justify their advancement for testing on humans. Moreover, scores of potentially life-saving drugs are prematurely abandoned once they confer no benefits to animals, exacerbating an already inefficient animal-centric drug discovery paradigm. Failed oncology trials alone are estimated to cost $50-$60 billion annually. Most new-generation therapies (e.g., cell therapy, immunotherapy) are by design human-specific, and testing on animals is a fool’s errand.

Through decisive actions, DOGE could in principle curb unreliable testing on animals in favor of prioritizing technology-driven, human-relevant alternatives. By doing so, it would — in a singular swoop — reduce waste across federal contracts and grants, promote modern drug development, lower healthcare and prescription drugs cost, bolster national competitiveness, improve environmental health and safety testing, and modernize practices within all health and regulatory agencies.

Francis S. Collins, the longest-serving former director of the National Institutes of Health, wrote in the journal Nature a decade ago that “preclinical research, especially work that uses animal models, seems to be the area that is currently most susceptible to reproducibility issues.” Consistently, 89% of preclinical studies, most of which involve animals, cannot be reproduced!

Reducing the dependency on the key variable (i.e., animal models) associated the most with irreproducibility (e.g., the failure to translate results from the laboratory to the clinic) is one sensible approach to limit fiscal waste in medical research and, more broadly, healthcare.

The cost of developing a single new drug is a stupefying $2 billion with an average development time of 10-15 years from target identification in the laboratory to market release, not factoring in withdrawals or recalls. Poor reliability of animal models in the drug discovery workflow compounds sky-high research and development costs to disincentivize investment in many disease domains. Case in point, 95% of the 7000-plus rare diseases that affect 25-30 million Americans have not a single FDA approved drug to treat them.

[---]

Yet to this day, inexplicable delays in implementing the FDA Modernization Act 2.0 (FDAMA 2.0) are causing significant regulatory confusion among drug sponsors. The failure to act on the part of the FDA, the regulatory agency chiefly responsible for implementing this policy mandate, is in turn a good example of government discordancy, if not malfeasance.

In 2023, a bipartisan group of Senators, led by Rand Paul, R-Ky., and Cory Booker, D-N.J., sent a letter to the FDA demanding an explanation for the stultification and an implementation timeline of the enacted law. When no progress materialized, alarmed lawmakers introduced in February of 2024 the FDA Modernization Act 3.0 (FDAMA 3.0) in the U.S. House of Representatives, H.R. 7248  (and later in the U.S. Senate, S. 5046) to assure FDAMA 2.0 implementation and accomplish further improvements.

Sleeping Beauties Of Science

Many scientific papers receive little attention initially but become highly cited years later. What groundbreaking discoveries might have already been made, and how can we uncover them faster?

The scientific literature is vast. No individual human can fully know all the published research findings, even within a single field of science. Regardless of how much time a scientist spends reading the literature, there’ll always be what the information scientist Don Swanson called ‘undiscovered public knowledge’: knowledge that exists and is published somewhere, but still remains largely unknown.

Some scientific papers receive very little attention after their publication – some, indeed, receive no attention whatsoever. Others, though, can languish with few citations for years or decades, but are eventually rediscovered and become highly cited. These are the so-called ‘sleeping beauties’ of science.

The reasons for their hibernation vary. Sometimes it is because contemporaneous scientists lack the tools or practical technology to test the idea. Other times, the scientific community does not understand or appreciate what has been discovered, perhaps because of a lack of theory. Yet other times it’s a more sublunary reason: the paper is simply published somewhere obscure and it never makes its way to the right readers.

What can sleeping beauties tell us about how science works? How do we rediscover information the scientific body of knowledge already contains but that is not widely known? Is it possible that, if we could understand sleeping beauties in a more systematic way, we might be able to accelerate scientific progress? 

[---]

Indeed, one of the most famous physics papers, Albert Einstein, Boris Podolsky, and Nathan Rosen (EPR)’s ‘Can Quantum-Mechanical Description of Physical Reality Be Considered Complete?’ (1935) is a classic example of a sleeping beauty. It’s number 14 on one list that quantifies sleeping beauties by how long they slept and how many citations they suddenly accrued.

The EPR paper questioned whether quantum mechanics could truly describe physical reality. The stumbling block was the phenomenon of ‘quantum entanglement’, where two quantum particles have a history of previous interaction and remain connected in such a way that means any measurement of a property of one of them influences that property in the other, regardless of how far away from each other they are.

[---]

The first is Karl Pearson’s 1901 paper ‘On Lines and Planes of Closest Fit to Systems of Points in Space’. It looks like a classic case of a sleeping beauty: it was published in a primarily philosophical outlet with the rather unwieldy name of The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science, and seems to have slept soundly for a whole century, only being fully awakened in 2002 with a huge surge of citations.

It’s certainly true that the twenty-first century brought with it many more ways to use Pearson’s 1901 insights. What he had described was what eventually became the statistical workhorse known as principal components analysis (PCA) – which became particularly useful after the advent of digital ‘big data’ to discover patterns and summarize large, unwieldy datasets in a smaller number of variables. But even without those datasets, the technique of PCA itself was well used across the entire twenty-first century, from psychology to palaeontology.

It’s hard to say why the 1901 paper suddenly started being cited around 2002 – the explanation could be pure luck and social dynamics, with one study happening to cite it and others following suit – but it wasn’t because PCA, which by that point was taught in every basic statistics course, had been ‘rediscovered’.

- Lost Science

Evolutionary Foundations For Cancer Biology

Abstract

New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer.

Conclusion

The benefits of using evolutionary principles to understand cancer provide a specific example of the benefits of evolutionary medicine more generally. An evolutionary approach can help us understand why cancer exists and how it progresses (somatic evolution), how cancer cells interact with environments (ecological approaches), why it is not more common (natural selection for cancer suppression mechanisms), and why cancer suppression mechanisms can never be perfect (constraints, trade-offs, and other evolutionary reasons for vulnerability to disease). Evolution is essential for understanding cancer. It provides a framework for studying the evolutionary origins and progression of cancer that is parallel and complementary to the Hallmarks of Cancer framework for studying the mechanisms of cancer.

The importance of an evolutionary understanding cancer is not just an academic pursuit; it has great clinical utility that remains largely untapped. Evolutionary theory and methods have led to critical advances that promise to improve how we understand and treat cancer. For example, the finding that diversity in the premalignant biopsies predicts progression to cancer (Maley et al. 2006; Merlo et al. 2010) suggests methods for risk stratification, and a focus of clinical resources on those patients with the highest likelihood of cancer progression. Also, the development of novel therapeutic approaches, such as Gatenby's adaptive therapy algorithm (Gatenby et al. 2009), holds the promise of revolutionizing the way some cancers are treated—shifting the focus from eliminating every cancer cell, to controlling cancer by manipulating selection forces within the tumor. An evolutionary analysis of chemotherapy resistance suggests that taking another biopsy after a relapse may identify resistant mutations and guide targeted second line therapies. Finally, a clearer understanding of how large organisms suppress cancer (Caulin and Maley 2011), and the trade-offs inherent in cancer suppression, will inspire new strategies for risk assessment and cancer prevention. An example is provided by Hochberg et al.'s (this issue) discussion of new strategies to limit or eradicate incipient neoplasms by reducing microinflammation which may spur neoplastic progression, and by reducing the accumulation of DNA damage by administering poly ADP ribose polymerase inhibitors.

In retrospect, it is remarkable that the evolution of cells within tumors was not recognized until the 1970s with Nowell's (1976) paper ‘The clonal evolution of tumor cell populations.’ Despite subsequent wide acceptance of evolutionary explanations for cancer progression, applications of evolutionary thinking remain limited; for instance, evolutionary terms are used in only about 1% of the abstracts of papers on therapeutic resistance (Aktipis et al. 2011). While applications of evolutionary principles to the problems of cancer are in their infancy, they are growing fast, as illustrated by many recent conferences across the world, and the creation of two centers for the study of evolution and cancer, the Center for Evolution and Cancer at the University of California, San Francisco, and the Centre for Ecological and Evolutionary Cancer Research at University of Montpellier. We anticipate that evolutionary applications that advance cancer research and treatment will speed the growth of evolutionary medicine more generally, and that as more physicians have opportunities to learn the basic science of evolutionary biology, their insights will further advance our understanding of cancer, as well as the rest of medicine.

- Full paper here

Words Of Wisdom On Cancer

Remember, this is from a cancer research scientist! 

If it took so many years for a well trained person like her to get an "insight" that cancer is part of a complex system then there is no hope for common folks to understand ever. 

What you eat, where you live, how many chemicals you use in everyday life, outsourcing the food you eat, little choices you make every second - all matters plus zillion other things.The good news is you can control all this while you cannot control your race, your parents and such. 

But yet people prefer to believe "they" have "cure" for cancer, "war" on cancer and other stupid theories. 

I paid in the most painful way with Max's life with the choices I made and the beliefs of other people. 

So next time someone close to you is diagnosed with cancer - don't walk or run for cancer,  don't dwell in support groups to find closure (whatever that means) instead unpack their lifestyle - I mean everything, donate your data and  urge someone close to do so too. 

Let's get to the insights: 

One problem is the high level of variation, or heterogeneity, in tumours: variation between people, between tumours within the same person and even between regions within the same tumour.

By variation, I mean this: if you separated out the cancer cells within a tumour, they would not all be identical. You would find subpopulations of cells with diverse molecular characteristics. Some subpopulations will be larger than others, but this can change in time as the cancer progresses, and as it is challenged by different types of treatments.

This variation is not just the result of differences in the genetics of cells within a tumour. There are also differences in epigenetics (reversible changes to DNA that can impact how the genetic information is read), differences in the environment surrounding the tumour (e.g., oxygen levels, acidity levels), and differences in the interactions between the cancerous cells and other types of cells: cells that provide structure, cells that make up blood vessels, immune cells and even microbes.

Add to that the genetic and environmental differences between people, and differences in the ways cancer developed in each individual.

What you end up with is a highly complex picture in which tumours can exploit a potentially infinite pool of resources in order to continue to grow, spread and evade destruction.

[---]

We can view a tumour as a complex system, in which many components interact with and influence each other, with the purpose of keeping the tumour alive and thriving. Any changes within this system can impact, either positively, or negatively, the tumour’s ability to persist and thrive.

Therapeutic interventions aim to destabilise this complex system, in order to shrink and destroy the tumour. But as we saw earlier, these interventions are relatively homogenous, focusing on a small number of molecular alterations, whereas the tumour can leverage a much more diverse repertoire of changes.

Very Good Sentence On Cancer

Cancer continues to kill 10 million people around the world every year.  We need to acknowledge that we do not yet understand how cancer forms and why metastatic cancer continues to be incurable and lethal. Analogies, metaphors, and comparisons that anthropomorphize the disease take away from the serious fact that we still do not know how to cure metastatic cancer. There is much work to be done.   Let’s be uncomfortable.

- Cancer & Metaphor

Ant's Can Detect Cancer Soon!

Ants have such a refined sense of smell, in fact, that researchers are now training them to detect the scent of human cancer cells.

A study published this week in the journal Proceedings of the Royal Society B: Biological Sciences highlights a keen ant sense and underscores how someday we may use sharp-nosed animals — or, in the case of ants, sharp-antennaed — to detect tumors quickly and cheaply. That’s important because the sooner that cancer is found, the better the chances of recovery.

“The results are very promising,” said Baptiste Piqueret, a postdoctoral fellow at the Max Planck Institute for Chemical Ecology in Germany who studies animal behavior and co-wrote the paper. He added, however: “It’s important to know that we are far from using them as a daily way to detect cancer.”

[---]

For his study, Piqueret’s team grafted pieces of a human breast-cancer tumor onto mice and trained 35 ants to associate urine from the tumor-bearing rodents with sugar. Placed in a petri dish, the silky ants (Formica fusca) spent significantly more time near tubes with urine from the “sick” mice compared with urine from healthy ones.

“The study was well conceived and conducted,” said Federica Pirrone, an associate professor at the University of Milan who was not involved in the ant research but has conducted similar investigations into the smelling ability of dogs.

[---]

The way we diagnose cancer today — by drawing blood, taking biopsies and conducting colonoscopies — is often expensive and invasive. Animal behaviorists are imagining a world in which doctors one day tap species with keen senses to help spot tumors quickly and cheaply.

Dogs can sniff out the presence of cancer in body odor, past research has shown. Mice can be trained to discriminate between healthy and tumor-bearing compatriots. Nematodes are attracted to certain organic compounds associated with cancer. Even the neurons of fruit flies fire in the presence of certain cancerous cells.

But ants, Piqueret suggested, may have the edge over dogs and other animals that are time-consuming to train.

- More Here 

E.O. Wilson would have been delighted to hear this progress!

Dogs May Hold Key To Treating Cancer in Humans

I have been writing about this for years now - most of the future cancer treatments for humans will be coming from dogs. 

I wasn't just blinded by Max but it's a fact that dogs don't care about sharing data. Most humans would gladly fart in public rather than share their health data. 

60 mins had a wonderful segment on the same last Sunday: 

Dogs live in our world. They get all the same diseases we do. They eat our food. They're exposed to the same environmental pollutants. But they also have all the same genes that we do. And they have mutations in those genes that make them susceptible to everything you and I get - whether it's diabetes or cancer or neuromuscular diseases. Everything humans get, dogs get.

 

The Breakthrough Science of mRNA Medicine

Like proteins, messenger RNAs are long chainlike molecules composed of building blocks. The four building blocks that make up messenger RNAs form what is known as the genetic code. As their name implies, messenger RNAs carry messages: messages that are translated by your body in order to create proteins. Thus messenger RNAs are the language of life. And the human body has a lot to say.

[---]

mRNA's are transient. The amount of protein produced is dependent on how much of that mRNA is present. And they can be induced over and over again to produce the same effect. So wow, it seems so simple. If we could treat a disease, if there's a protein that's missing to treat a disease, then we could simply give a few copies of an mRNA to the body for it to produce that protein. If that protein's only needed once, then maybe a single dose would suffice. If a protein is needed multiple times, then we can dose mRNA over and over again. And that's exactly what's happening. So when I went on clinicaltrials.gov this morning, it turns out that there are over 175 clinical trials now open using mRNA-based medicines that are recruiting patients. Another 54 clinical trials are waiting in the [wings], ready to be opened. So there is a coming tsunami of mRNA medicines.

[---]

And for cancer patients, we're creating personalized cancer vaccines. These vaccines are meant to train their bodies, their immune systems, to attack their cancers. These are truly personalized medicines, one vaccine for one person.

[---]

Now for personalized cancer vaccines to be the most effective, we need to get them made and back to the patient as quickly as possible. We aim for a turnaround time of 45 days. By January of 2020, we had already manufactured, quality-controlled and delivered to several dozen patients personalized cancer vaccines. So we had the know-how and the capacity to manufacture vaccines quickly. Thus, when the sequence of the SARS-CoV-2 virus was posted to a public web server on January 10, 2020, we got immediately to work. Within two days, we had agreed with our collaborators at NIH on exactly which form of the spike protein to put in our vaccine. Because we had done so so many times before, it then took our mRNA design team just one hour to design the mRNA that we immediately put on to our manufacturing equipment. We were then able to make that RNA, get it quality-controlled, fill-finished and shipped off to NIH for the clinical trial in 45 days. 

What I find truly remarkable is that that mRNA sequence that took us one hour to design is the same mRNA sequence that went into your arms, that ended up in Spikevax, our now fully approved vaccine. One hour to design a medicine that has saved countless lives.   

[---]

Having learned to speak the language of mRNA, the language of life, we can now use it to create medicines that are just for one person, like a personalized cancer vaccine, or can be rapidly produced and distributed to entire populations, like the COVID-19 vaccines. And the best part? The best part is we're simply tapping into your body's own ability to make its own medicines. 

- Melissa J. Moore, RNA researcher

I was upset about the insanity of anti-vaccination but yet I prefer to live in a world where diversity of compliance (amongst other things as long as it doesn't cause pain and suffering) thrives. Otherwise, this blue planet will be one big North Korea. People should not follow trends blindly and learn to pause and question everything to distill the truth. 

Diversity instigates randomness which feeds the complex systems and in turn helps with evolution albeit we don't know if that evolution would be good for humans or not.  

The main issue is here is not polarization of vaccination compliance but its the skin in the game. 

1. If you don't "believe" (whatever crap that means) in vaccine because you don't like to follow orders other than self or for the love of your tribe then you should write it in your will and promise yourself that you will never take mRNA vaccine for cancer or any other disease you would (not might) encounter as you grown old. 
2. If you "believe" (whatever crap that means) in vaccine because of your love for your tribe and with no understanding nor appreciation of science and dedicated humans behind it and you do so to prove that other side is wrong and in the end you do it for virtue signaling then you should start donating your medical data to help with cancer and other research since "other" side doesn't do that. 

The above two cases are the quintessential poster child portrayed in Jonathan Haidt's The Righteous Mind: Why Good People Are Divided by Politics and Religion. 

And the third kind:

• If you have gratitude that we live in a place and time where innovation in medicine thrives and helps to reduce pain and suffering then I salute you. Understand, these innovations means that we don't have to test on animals for medicine. Please, speak up against animal testing (FDA, your senator etc.) because it not only causes immense sufferings on animals but it is a barricade for future innovation in medicine. You or your loved will be a victim of it sooner or later. 

It is extremely sad that a virus and a break through in medicine has also become a victim of political  polarization. As much as it makes me sad, I understand this is part of evolution unfolding in front of our eyes and I am grateful we haven't become North Korea. 

I will try to explain in simplistic terms for people not driven by ideology nevertheless got caught in the fear mongering:

• With vaccination, you are training your immunity (by inducing the corresponding protein if you have it or propagating the protein if you don't have it) to prepare for the defense when covid comes home. 
• If you don't take the vaccine and prefer the natural immunity to open up the defense when covid comes home then you are skipping the training the immunity and going into war with no training. It might work. "Might" is the word. But it will not work if you don't have the protein. This is the key difference.And also understand the difference between sterilizing immunity and non-sterilizing immunity of vaccines based on different virus (think small pox and covid, former is sterilizing while the later is not). 

There is slight probability that you will die of choking every time you eat but yet you eat everyday. Most food made by corporations fucks with your immunity and factory farm dead bodies of animals who went through hell on earth will certainly fuck with your immunity. 

Like everything else in life there is a probability that mRNA vaccine might kill you or fuck with your immunity but its much lesser than the probability of covid fucking with your immunity or killing you.

This is one of my favorite scenes from the movie Zero Dark Thirty and how Maya's character struggles to explain the difference between certainty and probability. 

[In a CIA Conference room with CIA Director, his deputies and Maya]

CIA Director: I'm about to go look the President in the eye, and what I'd like to know, no fucking bullshit, is where everyone stands on this thing. Now, very simply, is he there, or is he not fucking there?

Deputy Director: We all come at this through the filter of our own past experiences. I remember "Iraq WMD" very clearly, I fronted that, and I can tell you the case for that was much stronger than this case.

CIA Director: A fuckin' yes or a no.

Deputy Director: We don't deal in certainty, we deal in probability. I'd say there's a sixty percent probability he's there.

The Wolf: I concur. Sixty percent.

George: I'm at eighty percent. Their OPSEC is what convinces me.

CIA Director: You guys ever agree on anything?

Dan: Well, I agree with sixty, we're basing this mostly on detainee reporting and I spent a bunch of time in those rooms. Who knows? I'd say it's a soft sixty, sir. I'm virtually certain there's some high value target there, I'm just not sure it's bin Laden.

CIA Director: This is a cluster-fuck, isn't it?

Jeremy: I'd like to know what Maya thinks...

Deputy Director: We're all incorporating her assessment into ours...

Maya: A hundred percent he's (Osama bi Laden) there. Okay, fine, ninety-five percent because I know how certainty freaks you guys out, but it's a hundred.

Can Cancer Be Treated by Changing Its Cells?

After 18 years of studying the secret lives of cells and their RNAs, Spector’s team had zeroed-in on one culprit enabling breast cancer to spread: a long non-coding RNA called MALAT1. When healthy epithelial cells lining the surface of the milk ducts in the breast develop an excess of this molecule, they go bonkers. In biology, proper balance is key to health, so when some RNAs are overexpressed (meaning too many) or under-expressed (meaning too few), diseases can develop.

The overexpression of this RNA makes breast epithelial cells lose their biological sense of self and start proliferating and spreading. “They’ve lost control,” explains Robert MacLeod, chief scientific officer at Flamingo Therapeutics, a company that is collaborating with Spector. “Normal epithelial breast cells know what they have to do, such as produce milk proteins when needed. But cancer cells think they need to grow and survive and look for a new home and metastasize to new organs.” It is as if the rogue RNAs act like the cells’ molecular murder accomplices, enabling them to sneak around. “We showed that the MALAT1 RNA is involved in cells’ migration and metastases,” Spector says.

The next step was to see what happens if the amount of that RNA was reduced by a drug. To accomplish this Spector’s team and collaborators at Ionis Pharmaceuticals, a company that licensed the MALAT1 program to Flamingo Therapeutics, devised a clever molecular trick. They built a compound able to bind to the RNA akin to how two sides of a zipper or Velcro straps stick together. Called an antisense oligonucleotide, the compound consists of 16 nucleotides that are complementary to a specific region on the MALAT1 RNA so that when the two encounter each other in a cellular soup, they cling together. That marks the rogue RNAs for execution, molecular style. It sends a signal to a voracious team of enzymes that slice up the RNAs like miniature scissors. “When this oligonucleotide finds MALAT1 in the cells, it binds to it and stimulates the recognition by enzymes that will degrade the RNA,” Spector explains.

But the most surprising thing happens after that, says MacLeod. With the decreased amount of MALAT1 RNA in them, the cells recover some of their biological identity. “This drug seems to reprogram the cells and they suddenly remember who they are,” MacLeod says. “Oh, I am a breast epithelial cell, and I don’t need to metastasize and go someplace. Instead, I should do some things here at my home, such as supporting the mammary gland function.”

Spector’s team named their prospective therapeutic MALAT1 RX. They found that it stopped the cancer’s progression in mice and in organoids—the mini-tumors grown from the chunks donated by Kostroff’s patients. The next step would be trying it in living people in a clinical trial, which Spector hopes will happen within a year or two. “We are starting the conversation with the FDA,” MacLeod says.

For a typical drug development timeline, MALAT1 RX is moving fast. Even though Kostroff’s patients who so altruistically donated their tissues to Spector’s research may not benefit from this future drug, those a few years down the road may be luckier. “We started with no inclination that this may ever get to the clinic,” Spector says. “So the fact that we’re hoping to go to a clinical trial in about a year or two is extremely exciting. It would be a very significant triumph of fundamental research that we hope will really make a difference.” 

- More Here

The most important take away is that to even have small progress to find good treatments (I am avoiding the word "cure" for obvious reasons), people have to sacrifice and donate data. 

Your data is more precious than dollars if we want to make progress n healthcare!!

What Max went through shouldn't happen to any living being. Neo, Fluffy and Garph are living a healthy life from the lessons learned from Max's suffering. I donate their data and mine where ever it's needed. You should do so too. 

On Cancer Vaccine

The idea is to deliver into the body bits of proteins, or antigens, from cancer cells to stimulate the immune system to attack any incipient tumors. The concept isn’t new, and it has faced skepticism. A decade ago, a Nature editorial dismissed a prominent breast cancer advocacy group’s goal of developing a preventive vaccine by 2020 as “misguided,” in part because of the genetic complexity of tumors. The editorial called the goal an “objective that science cannot yet deliver.” But now, a few teams—including one funded by the same advocacy group, the National Breast Cancer Coalition (NBCC)—are poised to test preventive vaccines, in some cases in healthy people at high genetic risk for breast and other cancers. Their efforts have been propelled by new insights into the genetic changes in early cancers, along with the recognition that because even nascent tumors can suppress the immune system, the vaccines should work best in healthy people who have never had cancer.

Researchers are trying out several vaccine strategies. Some use so-called tumor antigens, molecular markers that are scarce on healthy cells but plentiful on cancer cells. The Lynch vaccine instead targets “neoantigens,” a potent type of antigen only found on tumor cells. Some deploy just a single antigen whereas others use a large number, in a bid to broadly shield against cancer. The best approach is unclear, and developers also face the difficult challenge of measuring success without waiting decades for healthy people to develop cancers.

Early trials are yielding glimmers of promise. If the idea works to prevent one or a few cancers, it could be extended to meet an ambitious goal suggested by President Joe Biden: developing a vaccine that could prevent many types of cancer, modeled on the messenger RNA (mRNA) vaccines that have helped fight the COVID-19 pandemic. “We are a long way from a general vaccine” to prevent cancer, says medical oncologist Shizuko Sei of the National Cancer Institute’s Division of Cancer Prevention. “But it could be in the distant future. It’s a stepwise approach.”

[---]

As some teams are trying to broaden the immune response triggered by cancer vaccines, others want to make it safer and more precise by targeting neoantigens, only found on cancer cells. Those efforts have accelerated over the past decade thanks to a surge in tumor genome sequencing, which has revealed a flood of neoantigens. Some drive cancer growth, whereas others have no apparent function. Most are unique to an individual cancer—an obstacle for developing preventive vaccines, which have to target markers that can be predicted in advance.

Some neoantigens reliably appear on many people’s tumors, however. For instance, pancreatic cancer is almost always triggered by mutations in a growth protein called KRAS, which give rise to a predictable set of neoantigens. This spring, Johns Hopkins University immunologist Elizabeth Jaffee and colleague Neeha Zaidi will begin to safety test a vaccine containing mutated KRAS peptides in 25 men and women who haven’t had cancer but are at high risk because of an inherited mutation or family history. KRAS is like pancreatic cancer’s Achilles’ heel, Jaffee says: It’s the first of several genes to get mutated. As a result, the team hopes early tumor cells won’t be able to evade the vaccine by ditching KRAS and finding another way to grow.

Lynch syndrome cancers also sport a predictable set of neoantigens. That’s because patients’ DNA repair problem leads to “frameshift” mutations, which shift how a cell’s proteinmaking machinery reads a gene, scrambling the resulting protein in a consistent way. A peptide vaccine containing a few of these neoantigens, which was developed by a German team, caused no serious side effects when tested in people with cancer. A similar vaccine designed for mice with Lynch syndrome reduced tumor growth, researchers reported in July 2021 in Gastroenterology.

The vaccine Vilar-Sanchez’s team will test is more ambitious: It consists of viruses modified to carry DNA for a whopping 209 frameshift neoantigens found in Lynch tumors. People’s immune systems vary in how they respond to specific neoantigens, and different individuals’ tumors won’t all make the same set. “Therefore, the best [approach] is to have many,” says Elisa Scarselli, chief scientific officer of Nouscom, an Italian company developing the vaccine.

- More Here

Bioelectrical Approaches To Cancer As A Problem Of The Scaling Of The Cellular Self

Abstract

One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological disorder, not necessarily due to problems with the genetically-specified protein hardware. One aspect of morphogenetic coordination is bioelectric signaling, and indeed an abnormal bioelectric signature non-invasively reveals the site of incipient tumors in amphibian models. Functionally, a disruption of resting potential states triggers metastatic melanoma phenotypes in embryos with no genetic defects or carcinogen exposure. Conversely, optogenetic or molecular-biological modulation of bioelectric states can override powerful oncogenic mutations and prevent or normalize tumors. The bioelectrically-mediated information flows that harness cells toward body-level anatomical outcomes represent a very attractive and tractable endogenous control system, which is being targeted by emerging approaches to cancer.

- Full paper here

Facts About Bones

Over the past couple of decades, scientists have discovered that bones are participants in complex chemical conversations with other parts of the body, including the kidneys and the brain; fat and muscle tissue; and even the microbes in our bellies.

It’s as if you suddenly found out that the studs and rafters in your house were communicating with your toaster.

Scientists are still deciphering all the ways that bone cells can signal other organs, and how they interpret and respond to molecular messages coming from elsewhere. Already, physician-scientists are starting to consider how they might take advantage of these cellular conversations to develop new treatments to protect or strengthen bone.

- More Here

CAR-T Cell Cancer Therapies To Political Cancer Moonshot to End Cancer To Neo's Poop

Almost 50 years ago, Richard Nixon "declared" war on cancer. It was a futile effort which indirectly ended in Max dying of cancer and might kill me one of these days too. 

Where did Nixon and others go wrong? 

No amount of money can end cancer, period. 

For starters, we need rudimentary data from cancer patients and non-cancer patients to even think about ending cancer. Without relevant data - all efforts to end cancer is futile. All fancy talks are sheer nonsense. 

So if you are donating money for some organization to support cancer then understand giving your data is more precious than money. 

Yes, Max and I have donated our genes to microbiomes in the past 15 years to support research on healthcare. What is the point of living my life if I cannot do this continuously before I kick the bucket? 

Some good news; CAR-T cell therapies for leukemia showed great results. But understand - this inference is based on 2 patients. Yes, 2 data points (one can now understand how deprived the world is of healthcare data) and we have no idea of CAR-T cell actually cured it or it was just small factor in a complex system. 

A few weeks after receiving an experimental cancer therapy that turns immune cells into tumour-killing hunters, Doug Olson’s doctor sat him down to give him news of his progress. “He said, ‘Doug, we cannot find a single cancer cell in your body,’” Olson recalls. “I was pretty convinced that I was done with cancer.”

Olson’s doctors, however, weren’t so sure. The year was 2010, and Olson was one of the first people with chronic lymphocytic leukaemia to receive the treatment, called CAR-T cell therapy. When his doctors — including Carl June and David Porter at the University of Pennsylvania in Philadelphia — wrote the protocol for the clinical trial that Olson was involved in, they hoped that the genetically engineered cells might survive for a month in his body. They knew that cancer research could be heartbreaking; they didn’t dare to expect a cure.

But more than ten years later, the immune cells continue to patrol Olson’s blood and he remains in remission. June is finally ready to admit what Olson suspected all along. “We can now conclude that CAR T cells can actually cure patients with leukaemia,” June told reporters at a press briefing describing results that were published in Nature on 2 February.

White House announced a more sensible approach to reduce cancer death (remember, they are still focusing on prevention more than actual cure): 

Taken together, these actions will drive us toward ending cancer as we know it today.

There’s so much that can be done.

• To diagnose cancer sooner — Today, we know cancer as a disease we often diagnose too late. We must increase access to existing ways to screen for cancer, and support patients through the process of diagnosis. We can also greatly expand the cancers we can screen for. Five years ago, detecting many cancers at once through blood tests was a dream. Now new technologies and rigorous clinical trials could put this within our reach. Detecting and diagnosing cancers earlier means there may be more effective treatment options. 
• To prevent cancer — Today, we know cancer as a disease we have few good ways to prevent. But now, scientists are asking if mRNA technology, used in the safe and effective COVID-19 vaccines to teach your body to fight off the virus, could be used to stop cancer cells when they first appear. And we know we can address environmental exposures to cancer, including by cleaning up polluted sites and delivering clean water to American homes, for example, through the Bipartisan Infrastructure Law.
• To address inequities — Today, we know cancer as a disease for which there are stark inequities in access to cancer screening, diagnostics and treatment across race, gender, region, and resources. We can ensure that every community in America – rural, urban, Tribal, and everywhere else – has access to cutting-edge cancer diagnostics, therapeutics, and clinical trials.
• To target the right treatments to the right patients — Today, we know cancer as a disease for which we understand too little about why treatments work for some patients, but not for others. We are learning more about how to use information about genetics, immune responses, and other factors to tell which combinations of treatments are likely to work best in an individual patient.
• To speed progress against the most deadly and rare cancers, including childhood cancers — Today, we know cancer as a disease for which we lack good strategies for developing treatments against many of the more than 200 distinct types. We can invest in a robust pipeline for new treatments, and the COVID-19 pandemic response has demonstrated we can accelerate clinical trials without compromising safety and effectiveness. 
• To support patients, caregivers, and survivors — Today, we know cancer as a disease in which we do not do enough to help people and families navigate cancer and its aftermath. We can help people overcome the medical, financial, and emotional burdens that cancer brings by providing support to navigate cancer diagnosis, treatment, and survivorship.
• To learn from all patients — Today, we know cancer as a disease in which we don’t learn from the experiences of most patients. We can turn our cancer care system into a learning system. When asked, most people with cancer are glad to make their data available for research to help future patients, if it can be done easily while respecting their privacy. Additionally, the diverse personal experiences of patients and their families make their input essential in developing approaches to end cancer as we know it.

I always said some of the big leaps in cancer research is going to come from dogs. Because dogs don't care about sharing their data. The company AnimalBiome is doing research to understand relationship between the microbiome and cancer: 

In the last decade, research on the microbiome has exploded in human medicine, primarily due to advances in technology that allowed scientists to take a closer look at this enormous group of organisms. Veterinary scientists were quick to adopt the new technology to look at the microbiome of animals.

AnimalBiome co-founder and Chief Science Officer Dr. Holly Ganz recognized the potential of the microbiome both from a diagnostic standpoint and also as a therapeutic target. Fecal samples have been collected from Study dogs each year they have participated in the Study. We also have information about the dogs’ health history, medications taken and diet. The combination of data and specimens provides a unique opportunity for Dr. Ganz’s team to learn more about links between the types and abundance of certain gut organisms and disease.

Over the next two years, AnimalBiome will analyze 2,100 stool samples from the Study to better understand the relationship between dog microbiomes and cancer, as well as other health outcomes.

How do they do it? Because they get data from Neo, Fluffy and Garph. There is no magic bullet. 

Neo, Fluffy, Garph and millions of other data from other pets will indeed help us make a small leap in understanding cancer. One data point from Neo is important than empty rhetoric and dollars. 

Check out the one and only healthcare dataset of 270 million plus Americans that exists even after 4 decades!

 

Words Of Wisdom (Against Trendy Tech & Too Much Cancer Screening)

You can’t test yourself to health. The things that really promote your health are not very sexy.  

Real food, regular movement, and finding purpose aren’t high-tech, but they are the true foundations of a long and healthy life.

- The Hidden Problems of Early Cancer Detection

Cancer Is Not Caused By Mutations

This quote is from... 1974 but yet most people rather "believe" in bullshit than understand the complexity and complex systems. 

We find ourselves at the present time in the era of molecular biology, and we are perhaps unduly influenced by the genetic code as the dominant principle in biology. Perhaps, in a decade or two from now, the dominant principle may shift to another plane, which in turn will influence our speculations about tumor causation.

- Biochemist Isaac Berenblum, 1974

Once again, I am learning all this after Max...

Similarly, instead of simply targeting the cancer, altering the microenvironment to disfavor its proliferation may provide a more viable long-term strategy, as the former immediately selects for resistance, accounting for the difficulty in keeping a patient in remission. Highlighting the importance of the microenvironment in regulating development, homeostasis, and cancer, biologist Mina Bissell writes,

“The sequence of our genes are like the keys on the piano; it is the context that makes the music.”

Cancer depends on context, as should our approach to treatment.

Of particular interest is the discrepancy between cancer frequencies at different sites. For example, colorectal cancer is very common while small intestinal cancer is 100 times less common despite the fact that the small intestine is five times longer (30 feet versus 6 feet for the colon) and characterized by nearly identical rates of mutation as the colon. The microenvironments are strikingly different, however, with the colon being host to more diverse and numerous microbiota. In addition, colorectal cancer almost exclusively occurs in the distal colon rather than the proximal colon where fermentation is greatest and short-chain fatty acid (SCFA) concentrations are typically higher. Lack of sufficient dietary resistant starch may prevent production of a short-chain fatty acid called butyrate, which lowers colonic pH, prevents pathogen invasion, and appears to preclude carcinogenesis, lending further evidence to the role of the colonic ecosystem in preventing or promoting cancer. To further illustrate the importance of the tissue microenvironment, Bissell expounds,

“Indeed, how else would one explain the tissue specificity of heritable cancers, for example, BRCA1 and breast cancer, where, despite mutations in all of more than 10 trillion cells, the tumors are not only tissue specific but also formed from just one or a few cells of those tissues?”

 

Miyabeacin - Found In The Balk Of The Willow Tree Has Potential In Cancer Therapy

Abstract

Willow (Salix spp.) is well known as a source of medicinal compounds, the most famous being salicin, the progenitor of aspirin. Here we describe the isolation, structure determination, and anti-cancer activity of a cyclodimeric salicinoid (miyabeacin) from S. miyabeana and S. dasyclados. We also show that the capability to produce such dimers is a heritable trait and how variation in structures of natural miyabeacin analogues is derived via cross-over Diels-Alder reactions from pools of ortho-quinol precursors. These transient ortho-quinols have a role in the, as yet uncharacterised, biosynthetic pathways around salicortin, the major salicinoid of many willow genotypes.

- Full paper here

How Whales Resist Cancer

However, given that cell division may lead to errors, larger animals should get more cancer. After all, bigger body, more cells/cell divisions, more possible mutations. Enter a paradox.

[---]

If we look within species, there seems to be a positive correlation between cancer risk and body size. Larger individuals → increased risk. But, when we look across species, this correlation breaks down. An elephant does not get more cancer than a mouse. This apparent resistance of larger-sized species to cancer is known as Peto’s paradox, named after English statistician Richard Peto who first observed it in 1977.

[---]

Evolution, it seems, has gifted the larger species some extra protection.

A new study now exposes some of those gifts by looking at the largest of animal groups: cetaceans. The whales.

The researchers went looking for clues in the genetic data of 7 species of cetacean (bottlenose dolphin, orca, beluga, Yangtze river dolphin, the sperm whale, common minke whale, and the bowhead whale). They also looked at 8 other species to have good points of comparison (cow, pig, dog, horse, microbat, human, mouse, and the African elephant).

They started with data on known tumor suppressor genes and then scoured the cetacean DNA for traces of those.

The scientist found evidence of positive selection for seven of the tumor-suppressing genes in whales: CXCR2 in all cetaceans and DAB2, ADAMTS8, DSC3, EPHA2, TMPRSS11A, ANXA1 specifically in baleen whales (which happen to be the largest of all whales). These genes are known to be involved (in humans) in cancers such as lung neoplasm, leukemia, teratocarcinoma, as well as in immune system disorders.

Another interesting finding was that cetaceans genes had a higher turnover rate, aka more gene loss and gain. This makes sense because the researchers also found more gene duplications. Extra gene copies give evolution more material to play with. (This turnover signal was strongest in the baleen whales as well.)

Evolution is cleverer than we are…

- More Here