Covid-19 - Origins Of An Outbreak

 The way that we are using the planet as opposed living with the planet. 

Be An Epistemic Spoilsport

Well, it was learning; as I said, we know a lot; but the ratio between what any of us can know, and what we need to know in order to be competent in our knowledge, well, that’s like a big ratio, man, and not in our favor.

An alternative, and maybe one we can more ably manage, is to follow Herre Climacus and look instead for complications. I do not mean trolling. To troll is to raise unproductive difficulties for the vicious joy of making other people upset. That’s for losers. I’m talking about making productive difficulties for the virtuous joy of recalling ourselves and our friends to our own limitations; in short, being an epistemic spoilsport. What don’t we know? What don’t we understand? What doesn’t seem to fit? Why is it that we know more than ever, and yet, and yet?

Of course one can raise these questions as offensive maneuvers; we can play the part of skeptics to knock know-it-alls from their high and mighty thrones, or we can pretend not to understand one thing in the hopes of persuading someone to believe another thing instead. But I am recommending something more naive and genuine. Honest and reflective people might consider owning up to the fact that they really don’t understand what’s going on with this or that, and don’t have a sexy opinion to offer. And they can broadcast this expression of failing to others, who might at first seem surprised or bemused at such a flat refusal to play the trade opinions game, but after a few minutes they may recognize that good lord there is the possibility of a real conversation on offer here, and together we might express our befuddlements and share in our perplexities, and at the end of the night feel as if in our shared ignorance there is a shared humanity.

You don’t have to know everything in order to see that you understand very little, but a little bit of knowledge helps. And that’s all we are ever likely to have as individuals, even with 5G networks. This is why I am thinking we just might be able to pull this off. We can’t do full knowledge; that’s way too big. We can’t even reach a respectable level of knowledge. But a little knowledge, and some wonder, and some complications that we can meaningfully share with one another, that we can do. A little less confidence, if you please, and more honest talk. Tell me what you don’t know.

- More Here

Illusion of knowledge causes more pain and suffering than lack of knowledge. Instead, embrace epistemological modesty - it will change your mind and then heart. You will become a kinder human being who acts according to our impermanence, sees beauty in every living being on earth and mindful of every precious moment we have. 

The most difficult subjects can be explained to the most slow-witted man if he has not formed any idea of them already; but the simplest thing cannot be made clear to the most intelligent man if he is firmly persuaded that he knows already, without a shadow of doubt, what is laid before him.

- Mark Twain

Wise Words On LLM's & AI Ethics In General

It’s easier to build an artificial brain that interprets all of humanity’s words as accurate ones, composed in good faith, expressed with honorable intentions. It’s harder to build one that knows when to ignore us.

[---]

If large language models (LLM) are in our future, then the most urgent questions become: How do we train them to be good citizens? How do we make them ‘‘benefit humanity as a whole’’ when humanity itself can’t agree on basic facts, much less core ethics and civic values?

- Steven Johnson, A.I. Is Mastering Language. Should We Trust What It Says?

How can we expect an unbiased AI when it's trained using data generated by biased humans?

Sterilizing Immunity

The idea that vaccinating a certain percentage of the population would stop transmission of SARS-CoV-2 was a seductive but unhelpful description of herd immunity. This understanding comes from the so-called sterilizing immunity provided by infection or vaccination against diseases like measles. Sterilizing immunity means an individual can no longer be infected or infect others. Reach a certain percentage or “threshold” of this immunity in a population (around 95% for measles) and transmission comes to halt and the virus is eliminated.

This, however, is neither the exclusive nor even the most common understanding of herd immunity — and it is misleading for Covid-19. SARS-CoV-2 is not like the measles virus, but more like influenza, a virus that does not produce sterilizing immunity, returning every season like clockwork.

[---]

For SARS-CoV-2, herd immunity should not have been seen as an elimination threshold. Instead, it should have helped us understand that as immunity accumulated in the population, whether from infection or vaccination, the epidemic would recede before everyone was infected. Acknowledging that we couldn’t stop all infections, policy should have focused on minimizing the exposure of those already known to be at enormously increased risk of severe disease, while also limiting the harms caused by prolonged restrictions.

- More Here

This is another example of how politics and ideology rule's people's decisions even while facing death from a virus. 

Have no doubt, anti-vaccine parade started because one side was convinced it was panacea and they were convinced so because other side thought vaccine was a farce and they thought so because ... 

These ideologically driven bullshit amplifies continuously until any reminiscence of the truth vanishes from the brain. 

Non-Human Animal Menopause

An idea is like a virus. Resilient. Highly contagious. And even the smallest seed of an idea can grow. It can grow to define or destroy you.

- Cobb, Inception (The Movie)

It really doesn't matter if one is scientifically "savvy" or not. Ideologies block the head and make one a living example of Dunning–Kruger effect. In other words, one becomes a moron with no self awareness. Being a moron is destructive since it unleashes so much pain and sufferings. 

Here's another example of humans not accepting a simple fact about non-human animals while in the process causing so much pain and suffering on them. It just baffles me what they accomplish by living inside their head?

In 1981, Helene Marsh and her mentor discovered the truth about a basic biological process—but it took many researchers years to accept it.

Helene March stood in front of a hotel conference room filled with other marine mammal researchers. It was December 1981, and the Australian scientist had spent years working with her mentor, Toshio Kasuya of the University of Tokyo, studying reproduction in short-finned pilot whales: dark, round-headed animals about the length of a pickup truck. She had big news.

At the time, scientists thought that wild animals did not live beyond their reproductive years. But Marsh and Kasuya had been studying samples collected from some 300 short-finned pilot whales: Marsh had examined their ovaries, while Kasuya determined each animal’s age by counting growth rings visible in cross-sections of their teeth. When they combined their data, they found that female short-finned pilot whales stopped reproducing around the age of 36, but still lived for about 14 years more. For the first time ever, Marsh and Kasuya had discovered menopause in a non-human animal.

Despite the breakthrough finding, which challenged our understanding of a fundamental biological process, reaction to her talk was less than positive. “The mainly male audience was quite scathing,” Marsh says. “They couldn’t believe that there would be females in a population that had stopped breeding, because the reason they were there was to breed.”

More than 40 years later—with science now firmly on her side—Marsh remembers some of the comments in the wake of her talk, including: “‘This cannot be true. There would be no point in the females remaining alive if they weren’t reproducing.’”

“It was,” Marsh says calmly, “incredibly sexist.”

The reaction of Marsh’s audience was not surprising. After all, conventional thinking throughout science and the Western medical establishment at the time was that humans were the only species where the females lived beyond their reproductive years.

“We’ve been told that only through the grace of modern medicine—vaccines, surgery, antibiotics—are women are living long enough to experience menopause,” says gynecologist and obstetrician Jen Gunter, author of The Menopause Manifesto. “Nobody ever says that about men, that because of vaccines they are living long enough to have erectile dysfunction.”

“For so long, menopause has been viewed through this lens of failure, that there couldn’t be any medical use for it,” Gunter adds. “While most animals do die after their reproductive life is over, finding animals that keep living and thriving is more proof that this is a natural process, that they evolved to live past their reproductive function.”

[---]

Marsh and Kasuya’s finding, eventually published in an International Whaling Commission report rather than a science journal, never attracted media attention. But in 2012, University of Exeter researchers reported that orcas, or killer whales, also experience menopause. Their research was picked up by multiple outlets, including The New York Times and the BBC. Subsequent papers documented menopause in false killer whales, narwhals, and beluga whales.

University of Exeter’s Darren Croft, the senior scientist for the killer whale research, acknowledges the ground-breaking impact of Marsh and Kasuya’s discovery for his field. “This paper, published in the ’80s, showing that we have a wild population of pilot whales where the females live well beyond their reproductive years, was the first and only evidence of that until the data started to mature on the resident killer whale studies,” says Croft, adding that more recent research on menopause in toothed whales, including orcas, builds on Marsh and Kasuya’s findings in short-finned pilot whales. “The original discovery is fundamental,” Croft says.

Marsh went on to have an exemplary career in scientific research, education, and conservation. She is an award-winning, internationally recognized expert in dugongs and marine conservation and, in 2021, was recognized as an Officer of the Order of Australia, one of the nation’s highest civilian honors. But in all the praise heaped on her work, there isn’t a word about short-finned pilot whales.

“I think I did other stuff that was more important from a conservation and policy point of view,” says Marsh, who still teaches and has a hand in science-based conservation work. “From a theoretical biology point of view, the pilot whale post-reproductive work was the most interesting thing I ever did.”

I have personally read so many research papers and even books "claiming" that human females live beyond their reproductive years to groom their offsprings (think - grand mother's wisdom). I have also read, elephants with missing older matriarch find it hard to survive during drought times and don't know to avoid lion territories because they lack the wisdom of their older matriarch. If it's not obvious, the experience of older human animal and non-human animals brings in a wisdom for survival during tough times. 

My Life As A Mentalist

Mentalism forces people to consider that things they previously thought to be impossible are, in fact, possible. My father was a philosophy professor at New York University for more than 50 years. Mentalism, like philosophy, involves the quest to figure out the unknown; there’s a strong metaphysical aspect to it. And, like stand-up comedy, mentalism asks its practitioners to observe the human condition, find the things we have in common, and make a connection with the audience. Both are all about understanding patterns.

After that demonstration at the Waldorf, I wanted to understand how it worked, and to learn how to read thoughts myself. I probably acquired close to a thousand books on mentalism, and several hundred videos. I found a couple mentors, too. I started practicing whenever I could, doing simple demonstrations everywhere I went. I worked up one demonstration where someone drew a picture and I duplicated it without ever seeing it, standing in a far-off location. I perfected another where I asked a person to think of a loved one, and then I guessed their loved one’s name. After blowing people away, everywhere from dinners out to the checkout line, I started doing my mind-reading act at parties, and eventually I took a shot at going pro. Over the past 10 years I’ve traveled around the world several times, performing in hotels, comedy clubs, cruise ships, and theaters.

The longer I do this work, the less I believe in the supernatural and the more I believe in intuition. So much of what I do is based on psychology, observing human behavior, and recognizing patterns of thought and body language. It’s also about knowing how to control someone’s choices through linguistics or “verbal judo,” as mentalist Andy Nyman calls it. I can get a volunteer to make the choices I want them to make without them, or the audience, ever getting a sense of my process.

- More Here

What we don't know, immediately becomes magic. That is the essence of bullshit manufacturing factory inside humans. Humans lack the innate sense of humility and gratitude - hence, it's hard for them to accept known and unknown facts they cannot comprehend. 

 

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

The Last Tourism

The less we are convinced of our exceptionalism, the greater ability we have to understand and contribute to our environment, the less blindly driven we are by our own needs, the more clearly we can appreciate the needs of those around us, the more we can appreciate the larger ecosystem of which we are a part. 

Peace is when we realize that victory and defeat are almost identical spots on one long spectrum. 

Peace is what allows us to take joy in the success of others and to let them take joy in our own. 

Peace is what motivates a person to be good, to treat every other living thing well, because they understand that it is a way to treat themselves well. 

We are one big collective organism engaged in one endless project together. We are one. 

We are the same. 

Still, too often we forget it, and we forget ourselves in the process.

- Ryan Holiday, Stillness is the Key

I stopped traveling because I couldn't spend a day without Max. So we never flew except spending occasional days in the wilderness alone with Max and serenity - which lead having our own Walden in the wilderness which Max would have adored! 

My despise for travel has now, turned into hatred. In the past 2 decades "travel" has become a fad. It has risen to moronic levels that people work 80 hours a weeks to save dollars  to spend few mind numbing days taking selfies for the sole reason of signaling.  They are not screwing themselves but screwing the entire ecology and cause animal suffering (think bullfighting in Spain). 

A new documentary, aptly titled The Last Tourist  came a decade too late but still never too late. 

This film is a wake-up call.

We need to dramatically rethink the way we travel.

In 1950, there were 25 million international tourist arrivals. In 2020, that number was expected to be 1.6 billion. That means more people traveling than at any other point in history.

Travel is in an unfortunate state – and that’s even before COVID-19 brought it to a temporary standstill. Overtourism magnified the increasing impact on the environment, wildlife, and vulnerable populations around the world. Unintentionally, tourists have been destroying the very things they have come to see. Tourism reached a tipping point.

Yet, travel is also an opportunity. It can be leveraged as a force for good – to promote conservation, alleviate poverty, and positively transform the lives of people living in host communities, while fostering cultural connection and understanding between people from all walks of life. Tourism can spread peace and be the greatest form of wealth distribution the world has ever seen. This forced pause has presented us with the opportunity to reshape the travel industry as we know it.

This poignant film explores our ability to harness tourism’s power in a way that creates shared value for all – travellers and host communities alike – while preserving the places and natural resources we treasure most.

Change starts with us.

The one thing you can't escape in your life is yourself.

A plan ticket or a pill or some plant medicine is a treadmill, not a shortcut. What you seek will come if you sit and do work, if you probe yourself with real self-awareness and patience.

The next time we feel the urge to flee, to hit the road or bury ourselves in work or activity, we need to catch ourselves. Don't book a cross-country flight - go for a walk instead. Don't get high - get some solitude, find some quiet. There are far easier, far more accessible, and ultimately far more sustainable strategies for accessing the stillness we were born with. Travel inside your heart and your mind, and let the body stay put. 

- Ryan Holiday, Stillness is the Key

Fish Can Learn Basic Arithmetic

This is an anthropomorphic comparison and fish succeeded. But there are zillion more fish emotions and intelligence we cannot comprehend plus to top it off - human arrogance doesn't allow to comprehend . 

It is sheer stupidity and barbaric to slaughter billions of fish everyday for gastro intestinal pleasures (a.k.a your taste buds, tradition, culture, and nostalgia - whatever those crap means)

The rules were simple: If the shapes in the original image were blue, head for the door with one extra shape; if they were yellow, go for the door with one fewer. Choosing the correct door earned the fish a food reward: pellets for cichlids, and earthworms, shrimp, or mussels for stingrays.

Only six of the eight cichlids and four of the eight stingrays successfully completed their training. But those that made it through testing performed well above chance, the researchers report today in Scientific Reports.

When shown three blue shapes, for example, the animals correctly chose the door with four blue shapes, instead of two, with over 96% and 82% accuracy for stingrays and cichlids, respectively. Both species found subtraction slightly more difficult than addition on all the tests—a feeling likely shared by most toddlers.

To make sure the animals weren’t just memorizing patterns, the researchers mixed in new tests varying the size and number of the shapes. In one trial, fish presented with three blue shapes were asked to choose between doors with four or five shapes—a choice of “plus one” or “plus two” instead of the usual “plus one” or “minus one.” Rather than simply selecting the larger number, the animals consistently followed the “plus one” directive—indicating they truly understood the desired association.

The results aren’t all that surprising, given that fish have been shown to distinguish between relative quantities before. But this new study shows fish have a different strategy for dealing with small numbers that allows them to memorize and manipulate specific values—without the help of fingers to count, says zoologist Vera Schluessel, who led the study. And because cichlids and cartilaginous stingrays last shared an ancestor more than 400 million years ago, the study suggests this talent arose early in fish evolution.

“It certainly didn’t blow my mind that they’re capable of doing it,” says Culum Brown, a behavioral ecologist at Macquarie University who was not involved in the study. “But the fact that they could separate these two strategies out was really cool.”

Other animals, including parrots and bees, have demonstrated a similar aptitude for working with numbers. Despite not having the brain structures humans rely on for cognition, they manage to match our basic arithmetic skills, Schluessel notes.

“Many people think that they’re really stupid—fish in general,” Schluessel says. “They actually do have personalities … and they also can learn quite complex tasks.”

People often use the presumed ignorance of fish to excuse “awful” commercial fishing practices and callous pet maintenance, she adds. She hopes her work will encourage humans to see fish as sentient creatures like us that deserve to be treated with more respect.

“That’s the trend, you know—we’re basically chipping away at human arrogance,” Brown says. “We think that we’re the pinnacle of evolution, but we’re not.”