My take on cancer: diplomacy

APOTHEOSIS by Vasily  Vereshchagin

War or diplomacy 

What is easier: to start a war or to avoid it through diplomacy? What do you prefer? An uncertain ending with millions of lives lost or a diplomatic path of logic, perseverance, and compromise that saves millions of lives?




Wars start with pointing fingers

After a somewhat-preventable disaster strikes, the pointing of fingers starts. However, trying to identify the culprits does not reverse the consequences of any disaster. In the past 40 years, “pointing fingers”, followed by an announcement of a WAR ON CANCER, has been our  strategy against the dreaded disease. 

The prevalent notion has been that we can deal with cancer by identifying the mutations that contribute to the abnormal cell development. This great eureka moment goes like this:

“AH, IT IS THE MUTATION IN THE GENES X, Y, and/or Z that causes cancer.”

This realization is followed by the design of drugs against the mutant gene products X, Y or Z. Does it work? To be fair, the strategy works, sometimes... In most cases, however, the strategy is beneficial (profitable) for the drug company, but not for the patient. Why?

1. The approach is (frequently) this of management of the disease, but not cure.

2. Each cancer patient has a unique combination of gene mutations; therefore, we need to determine the precise mutation profile of each patient. Even if we do so, we may not have the targeted drugs to "attack" patient's unique mutation profile.

3. With time, cancer changes its mutation landscape. If at the start of the treatment, the identified mutations are X, Y, and Z, by the end of the treatment, there could be an abundance of cancer cells with mutations Z, W, and D. The outcome? The treatment regimen fails, the patient dies, the pharmaceutical company offering the treatment profits. Hopefully, the patient’s family is not financially broke.
 
What is wrong with our strategy of pointing fingers? First and foremost, TIMING.

Before any disaster strikes, and before we reach the stage of pointing fingers, there is a period, during which the potential for a disaster could be evaluated, and if high, could be addressed. 

Evaluating, addressing and preventing a disaster is the path of diplomacy:

prevention = diplomacy  

Cancer is not different from other disasters, including wars. There are risk factors that we can eliminate, and signals that we can detect BEFORE CANCER STRIKES. 

The same way WARS could be prevented by smart diplomats, CANCER can be prevented by smart leaders of the nation.  The researchers have already contributed to deciphering what causes CANCER, it is time for our leaders to implement the knowledge and prevent most of the cancer cases.

Although both WARS and CANCER have taken and will take millions of lives, they can also make some people filthy rich. Is this why we go for a war with CANCER, rather than employ some diplomacy with CANCER (i.e., with the well known sources of risk factors: the tobacco, food, agricultural industries and even our educational system that reinforces sedentary lifestyle)? 

Motivation

This weekend I was going through the archives of J L Collins, and found his post on motivation. Here is a snippet from the post, in which a successful salesperson was asked what motivated him. The answer was:

“The most motivating thing any manager ever did for me was to say that the best thing he could do was to stay the hell out of my way and let me do my job. And then he did just that. I made him and our company a lot of money during those years, and loved every minute of it.”

For more on "aspiration management" look at Ken Georgie Mathew's diagram:

 

The hierarchy of needs and its relation to aspiration management by Ken Georgie Mathew 

 If you are interested in the topic, you can find a great discussion on the five sources of motivation at the website of Quintus Curtius.

Pulse: the rapid and transient change from a baseline

The sensory deprivation of winter

As a scientist, I have noticed that cyclicity (the quality of something to recur at regular intervals) or periodicity (the quality or character of being periodic; the tendency to recur at intervals) is the rule for living organisms.

At the level of a single cell, signaling pathways have to “pulse” in order to support the proliferation of the cell. Once the pulsatile characteristics disappear, life ends. A stable increase or decrease of a signaling pathway is a sign of approaching demise.

Cyclicity/periodicity is also required at the level of the organism. Our higher functions and biological needs are normal only if they obey to cyclicity. Interruptions in cyclicity results in health problems. Of course, we have buffers (our biological range of resilience) to withstand deviations from the pattern of cyclicity, but eventually these “buffers” are depleted.

The theme of cyclicity continues throughout our lives. We cannot appreciate something, if we have not experienced the opposite of this something (e.g, we appreciate the day after the night).

Spring is appreciated after the sensory deprivation of winter.

Financial independence is enjoyed after frugality and avoidance of “gratifications”.

Love is appreciated after emotional deprivation.

Satiety feels good only after starvation.
 
Satiety (emotional, material, financial, or physiological) has never resulted in anything great or creative. The best works of art have been the result of cyclicity. I have previously written about intermittent fasting and its amazing restoring and healing benefits. However, the other types of “starvation” can also kick-start life and creativity.

Learning how to live through periods of deprivation and discomfort allows us to fully appreciate life.

Best appreciated after a long and cold winter

Cleaning Out The Cellular Clutter

Some interesting work suggests that clearing the body of senescent cells can increase lifespan and enhance health:

Mice were much healthier and lived about 25 percent longer when scientists killed off a certain kind of cell that accumulates in the body with age.

What's more, the mice didn't seem to suffer any ill effects from losing their so-called senescent cells.

These are cells that have stopped dividing, though not necessarily because the cells themselves are old. "It's a normal cell that experienced an unusual amount of stress, and it decided to stop dividing," says Jan van Deursen, who studies senescent cells at the Mayo Clinic College of Medicine in Rochester, Minn.

Older creatures have a lot more of these cells than young 'uns. And even though the cells aren't dividing, they do keep busy — they secrete a mixture of chemicals that can trigger inflammation, which seems to be involved in just about every major age-related disease.

So van Deursen and his colleagues wanted to know: What would happen if you simply got rid of senescent cells? That's tough to do in humans, but possible in mice.

The researchers created mice that were genetically altered so that giving them a drug would trigger senescent cells to kill themselves. Then they waited until the mice reached middle age, and gave some of them the drug.

At first, wiping out the senescent cells didn't seem to make much difference. But as the mice got older, the research team could see that the treated mice looked healthier.

"And then when we started to record the life span of the animals, we saw that there was about a 25 percent extension in life span of animals that had their senescent cells removed from 1 year of age on," says van Deursen.

What's more, the treated mice had fewer cataracts, hearts with better stress tolerance, and improved kidney function. And losing the cells didn't seem to cause them any problems, the researchers report Wednesday in the journal Nature.

The bottom line, says van Deursen, is that "it seems like we're accumulating a cell type that we really don't need for anything and that makes us more unhealthy and reduces the length of our healthy lives."

Needless to say, the hunt is already on for drugs that could eliminate these cells in people. That's not going to happen tomorrow, of course, and useful drugs might never materialize. But the findings in mice provide researchers with a new place to look.

Van Deursen himself is working with a new company, Unity Biotechnology in San Francisco, that has some promising candidates.

A scientist named Judith Campisi, who studies senescent cells at the independent Buck Institute for Research on Aging, also works with Unity. She thinks the findings of the latest study are significant. "The impressive thing is those mice not only lived longer but they lived healthier," says Campisi.

But she cautions that removing these cells isn't going to be a magic bullet against aging.

"Obviously, even in the Nature paper, those mice got old and died," she points out.

And some research shows that these cells may have a useful role to play in our bodies. For example, there's evidence that senescent cells aid wound healing and that cellular senescence helps protect against cancer.

"One needs to move forward with care about trying to just kill off senescent cells with the anticipation that things will be wholly beneficial," says Dominic Withers, a researcher at the MRC Clinical Sciences Centre, Imperial College London.

He says it looks like these cells do contribute to aging, but it's too soon to say what to do with them.

"I think it's early days at the moment," Withers says. "There's still quite a lot to learn about whether you would want to try and kill senescent cells or do something to the senescent cells that exist, such as stop them secreting this cocktail of potentially bad molecules.