It’s an all-too-familiar story. A laboratory somewhere announces that they have discovered a chemical formula that cures a previously intractable disease like cancer.
It works perfectly in Petri dishes, and in mice, and even in monkeys, and now the human trials begin.
Months later, we read that the formula not only didn’t work, but it made the patient sicker.
Why is pharmacology so difficult?
Biological evolution is nothing like human thinking. Biological evolution is much more like machine learning.
Adversarial examples are inputs to machine learning models that cause the model to make a mistake; they’re like optical illusions for machines.
To get an idea of what adversarial examples look like, consider this demonstration from Explaining and Harnessing Adversarial Examples: starting with an image of a panda, the attacker adds a small perturbation that has been calculated to make the image be recognized as a gibbon with high confidence.
An adversarial input, overlaid on a typical image, can cause a classifier to miscategorize a panda as a gibbon.
To the human eye, both panda pictures seem identical, but the machine “sees” them differently.
Pharmacology is difficult and machine-learning can be inscrutable, for essentially the same reasons. They do not follow the straight-line logic of human thought.
Consider this A to B puzzle.
To the human brain, the algorithm for traveling from A to B might be:
Begin at A
Travel along the dotted line to the airplane.
Pass through the airplane to B.
Stop.
Now consider this maze. What is your algorithm for going from one opening to the other?
Your algorithm might be:
Enter at either the top-left or bottom-right opening.
Take any route.
If that route gets you to the other opening, stop.
If that route doesn’t get you to the other opening, go to #5.
Enter at either the top-left or bottom-right opening, and take a different route from any route you ever have taken previously.
Go to #3.
That’s the way you, as a typical human, might operate.
But this is the way a machine might begin:
Erase half the lines.
If you come to a dead end, open it and continue.
Fold the paper in half so one opening touches the other.
Draw a new maze.
Write new rules.
Jump up and down on the maze.
Marry someone who owns a compass.
Ask for the solution.
In short, both evolution and machine learning defy human rules and logic. but after many, many moves, might take you from one opening to the other.
For instance, if you marry someone who owns a compass (#7), that person also mighthappento own a diagram that happensto show the solution to the maze. That’s how evolution operates.
The process may require millions of iterations, but computers work fast and evolution has plenty of time.
So those millions of iterations very well could provide a solution. It’s similar to the old story about the infinite number of monkeys pressing an infinite number of computer keys, and at some point (an infinite number of points, actually) they type all of Shakespeare’s plays.
Humans always are time-constrained. Biological evolution is not, which means that the paths to the survival of life can be mind-bendingly complex.
For decades, cancer researchers have wondered whether they could starve tumors into submission by choking off their blood supply and thus preventing their fast-growing cells from getting enough food and oxygen.
They developed a drug, Avastin, that blocks a molecular signal triggering blood vessel growth, or angiogenesis.
But, mysteriously, Avastin failed to improve survival unless patients received chemotherapy drugs at the same time — implying that Avastin was somehow helping the chemo to be more effective.
That piqued the interest of Rakesh Jain, a cancer researcher. “How can a drug that kills the blood supply help chemotherapy? You need the blood supply to get the drugs into the tumor.”
He started digging deeper, and what he found turned conventional wisdom on its head.
The blood vessels that deliver food and oxygen — and chemotherapy drugs — to a tumor tend to be highly abnormal.
Instead of the usual large, straight, simply branched vessels, the ones in and around a tumor are often unevenly distributed, misshapen, and tangled.
As a result, some parts of the tumor end up far from any blood vessels and thus have little exposure to chemo.
Those same regions become starved of oxygen, and this hypoxia suppresses the immune system and also acts as a signal for the tumor cells to metastasize, or disperse to new sites.
(The blood vessels that supply a tumor often become misshapen and tangled, preventing chemo drugs from reaching the tumor. Drugs that restore normal blood flow can help make chemo more effective.)
Moderate doses of Avastin don’t outright suppress formation of blood vessels around a tumor but can actually make them look more normal, so that they can deliver chemotherapy more efficiently and evenly.
Jain’s clinical collaborators found — surprisingly — that patients who responded with increased blood flow to the tumor lived longer than patients in whom the blood flow declined.
Angiogenesis inhibitors work, in other words, for exactly the opposite reason than scientists initially thought.
Because we are the result of evolution, and evolution uses counter-intuitive “thinking,” solutions to our physical problems can come from that same, counter-intuitive thinking.
Consider, for example, the “illogical” the use of stimulants to combat ADHD:
Most parents wouldn’t give a child with attention deficit hyperactivity disorder (ADHD) a caffeinated drink, for fear that their hyperactivity would only worsen.
Evolutionary “thinking” and machine learning are not straight-line. They both are the product of “random walk,” processes, in which each step is non-directed, but evaluated for success or failure.
Five eight-step random walks from a central point. Some paths appear shorter than eight steps where the route has doubled back on itself.
If a step has some immediate value, or at least is not fatally harmful, it is retained as the basis for a next step, even though that earlier step may not have seemed to bring one closer to an ultimate solution.
Human thinking seeks solutions. We don’t have the time or capacity to retain and use all the various steps that might have had immediate value or not been fatallly harmful.
There are many routes to “survival of the fittest” (or more accurately, “survival of the fit enough“). Within our lifetimes, we can’t try them all.
Machine-learning works fast, but it doesn’t display its individual steps. It can tell you where it is, but not how it got there.
In the “panda/gibbon” example, above, we do not see the steps that led to the misidentification. We do not see the “logic.”
Because our brains are made by natural selection, while logic is an artificial construct, we do not know the details of why the following illusion works:
The illustration seems to quiver. Move it and it will seem to flap like a butterfly.
Biological evolution and machine learning are similar in that they operate via the random walk, a seemingly illogical, unpredictable, and indirect process, alien to human thinking.
Unless, sometime in the distant future, we know, then program a computer with, the cause/effect of every atom and every linkage in the human body, while overcoming the limits of the Uncertainty Principle, we repeatedly will be amazed that when starting from A, B, C and reaching X, Y, Z, we did not pass through L, M, N.
And that is why pharmacology is so difficult, really almost impossible.
The most important problems in economics involve the excessive income/wealth/power Gaps between the richer and the poorer.
Wide Gaps negatively affect poverty, health and longevity, education, housing, law and crime, war, leadership, ownership, bigotry, supply and demand, taxation, GDP, international relations, scientific advancement, the environment, human motivation and well-being, and virtually every other issue in economics.
Implementation of The Ten Steps To Prosperity can narrow the Gaps:
Bernie Sanders has proposed a list of his Presidential aspirations, which is long on goals, though short on specific details.
The next time you hear me attacked as a socialist, remember this: I don’t believe that government should take over the grocery store down the street or control the means of production.
President Trump was elected with a much shorter list (eliminate Obamacare, build a wall, do the NRA’s and Vladimir Putin’s bidding, deny science, attack allies while sucking up to dictators), and blame others for his failures, so perhaps Bernie can be forgiven for his omission of specificity.
New York Times: 8/22/19
Sen. Bernie Sanders (I-Vt.) on Thursday unveiled an aggressive $16.3 trillion climatechange plan that calls for the U.S. to reach 100 percent renewable energy for electricity and transportation “no later than” 2030, as well as for “complete decarbonization” by 2050.
He refers to the plan itself, which would also declare climate change a national emergency, as a Green New Deal.
Reaching 100 percent renewable energy for electricity and transportation by no later than 2030 and complete decarbonization by 2050 at latest – consistent with the United Nations Intergovernmental Panel on Climate Change goals – by expanding the existing federal Power Marketing Administrations to build new solar, wind, and geothermal energy sources.
Ending unemployment by creating 20 million jobs needed to solve the climate crisis. These jobs will be good-paying, union jobs with strong benefits and safety standards in steel and auto manufacturing, construction, energy efficiency retrofitting, coding and server farms, and renewable power plants.
We will also create millions of jobs in sustainable agriculture, engineering, a reimagined and expanded Civilian Conservation Corp, and preserving our public lands.
Directly invest an historic $16.3 trillion public investment toward these efforts, in line with the mobilization of resources made during the New Deal and WWII, but with an explicit choice to include black, indigenous and other minority communities who were systematically excluded in the past.
A just transition for workers. This plan will prioritize the fossil fuel workers who have powered our economy for more than a century and who have too often been neglected by corporations and politicians.
We will guarantee five years of a worker’s current salary, housing assistance, job training, health care, pension support, and priority job placement for any displaced worker, as well as early retirement support for those who choose it or can no longer work.
Declaring climate change a national emergency. We must take action to ensure a habitable planet for ourselves, for our children, and for our grandchildren. We will do whatever it takes to defeat the threat of climate change.
Saving American families money by weatherizing homesand lowering energy bills, building affordable and high-quality, modern public transportation, providing grants and trade-in programs for families and small businesses to purchase high-efficiency electric vehicles, and rebuilding our inefficient and crumbling infrastructure, including deploying universal, affordable high-speed internet.
Supporting small family farms by investing in ecologically regenerative and sustainable agriculture. This plan will transform our agricultural system to fight climate change, provide sustainable, local foods, and break the corporate stranglehold on farmers and ranchers.
Justice for frontline communities – especially under-resourced groups, communities of color, Native Americans, people with disabilities, children and the elderly – to recover from, and prepare for, the climate impacts, including through a $40 billion Climate Justice Resiliency Fund.
Commit to reducing emissions throughout the world, including providing $200 billion to the Green Climate Fund, rejoining the Paris Agreement, and reasserting the United States’ leadership in the global fight against climate change.
Meeting and exceeding our fair share of global emissions reductions. We will reduce domestic emissions by at least 71 percent by 2030 and reduce emissions among less industrialized nations by 36 percent by 2030 — the total equivalent of reducing our domestic emissions by 161 percent.
Making massive investments in research and development.We will invest in public research to drastically reduce the cost of energy storage, electric vehicles, and make our plastic more sustainable through advanced chemistry.
Expanding the climate justice movement. We will do this by coming together in a truly inclusive movement that prioritizes young people, workers, indigenous peoples, communities of color, and other historically marginalized groups to take on the fossil fuel industry and other polluters to push this over the finish line and lead the globe in solving the climate crisis.
Investing in conservation and public lands to heal our soils, forests, and prairie lands. We will reauthorize and expand the Civilian Conservation Corps and fully fund the Land and Water Conservation Corps to provide good-paying jobs building green infrastructure.
One may disagree with some aspects of this list, but if one truly wishes to “make America great, again,” the list overall is a much better starting place than caging children and deny the poor of medical insurance.
There is, however, one aspect of the list that demonstrates abject cowardice and ignorance:
“This plan will pay for itself over 15 years“, Bernie claims.
“We will pay for the massive investment we need to reverse the climate crisis by:
Making the fossil fuel industry pay for their pollution, through litigation, fees, and taxes, and eliminating federal fossil fuel subsidies.
Generating revenue from the wholesale of energy produced by the regional Power Marketing Authorities. Revenues will be collected from 2023-2035, and after 2035 electricity will be virtually free, aside from operations and maintenance costs.
Scaling back military spending on maintaining global oil dependence.
Collecting new income tax revenue from the 20 million new jobs created by the plan.
Reduced need for federal and state safety net spending due to the creation of millions of good-paying, unionized jobs.
Making the wealthy and large corporations pay their fair share.
Sanders says his proposal would “pay for itself” in 15 years and create 20 million jobs. It would impose new taxes on the fossil fuel industry and eliminate subsidies, which he says would account for $3.1 trillion and be a way of making the industry “pay for their pollution.”
No, the plan will not pay for itself. Nor will federal taxpayers fund the plan. Federal taxes pay for nothing.
The plan, as proposed, will be funded by federal deficit spending, which will pump $16 trillion growth dollars into the economy. The federal government, being Monetarily Sovereign, never can run short of its own sovereign currency, the U.S. dollar.
It’s our little secret. Don’t tell the people we don’t use their tax dollars.
Ben Bernanke: “The U.S. government has a technology, called a printing press (or, today, its electronic equivalent), that allows it to produce as many U.S. dollars as it wishes at essentially no cost.”
Alan Greenspan: “Central banks can issue currency, a non-interest-bearing claim on the government, effectively without limit. A government cannot become insolvent with respect to obligations in its own currency.”
St. Louis Federal Reserve: “As the sole manufacturer of dollars, whose debt is denominated in dollars, the U.S. government can never become insolvent, i.e.,unable to pay its bills. In this sense, the government is not dependent on credit markets to remain operational.
Bernie demonstrates courage by proposing such far-reaching plans, but he demonstrates cowardice by failing to tell the voters the truth, namely:
Our Monetarily Sovereign federal government never can run short of its own sovereign currency, the U.S. dollar. It can afford anything, and it does not need to collect dollars from domestic or foreign taxpayers.
The federal deficit and debt are not a burden on the federal government or on federal taxpayers, nor do the deficit and debt limit any future federal spending.
The federal deficit and debt do not lead to inflation, which actually is caused by shortages of goods, not by excess dollars.
By hiding the facts, Sanders is reduced to proposing complex, economy-crushing tax-collection schemes supposedly to “pay for” the federal spending that the federal government easily pays for without taxes.
Thus Sanders must defend not only his spending proposals, but his tax-collection proposals, making passage of his plans far more difficult.
The most important problems in economics involve the excessive income/wealth/power Gaps between the richer and the poorer.
Wide Gaps negatively affect poverty, health and longevity, education, housing, law and crime, war, leadership, ownership, bigotry, supply and demand, taxation, GDP, international relations, scientific advancement, the environment, human motivation and well-being, and virtually every other issue in economics.
Implementation of The Ten Steps To Prosperity can narrow the Gaps:
With his slogan, “Make America Great, Again,” Trump implied that America was not great. And, historically speaking, he was right that America has not always been great.
There were, in fact, many times when we Americans disgraced ourselves.
We Americans disgraced ourselves during the years we enslaved, tortured and killed black people.
We Americans disgraced ourselves when we imprisoned Japanese Americans during WWII.
We Americans disgraced ourselves when we turned away the SS St. Louis, loaded with Jews trying to escape Hitler.
We Americans disgraced ourselves during the years we refused voting rights for women and blacks.
We Americans disgraced ourselves during the years of anti-Irish sentiment.
We Americans disgraced ourselves when we killed native Americans, and broke our treaties with them.
We Americans disgraced ourselves when we prosecuted the Vietnam war, unnecessarily killing millions of innocent Vietnamese and Americans.
We Americans still disgrace ourselves by jailing, per capita, more people than any other nation on earth, and then compounding the problem by giving guns — high-powered guns — to any fool who wants one.
We Americans still disgrace ourselves by denying millions of people affordable health care, while “lesser” countries offer it.
Millions of Americans disgrace themselves by supporting an absurd, immoral, ill-prepared, unqualified President.
Though America has been great in many, many ways, and still is, it is being led far, far from its previous glories.
(I have second thoughts about everything.” [At G7, 8/24/2019]
Newsweek DAILY BRIEFING – 08.21.2019 TRUMP ADMIN TO DETAIN CHILDREN INDEFINITELY
The Trump administration has issued a rule change that would end limits on migrant minors’ time in detentionand limit safeguards against cruel and unsanitary conditions.
California Senator Kamala Harris asked on Twitter Wednesday, “how does detaining families longer make our border secure or stop transnational gangs — things the DHS should actually be spending their time doing?”
Senator Elizabeth Warren: “The Flores agreement mandates that migrant children cannot be held in detention for more than 20 days. Today, the Trump administration announced its plans to roll back Flores—putting thousands of children in danger.
Inspectors found soiled, emotionally distraught children who were unable to brush their teeth or shower. The administration tried to justify not providing kids with soap and toothbrushes.
The new rule would remove a 20-day limit on detaining families in jails. Families will now be sent to “family residential centers” where they will remain until their immigration case is heard.
It takes an average of 713 days for a judge to hear a case.
“The detention of children can lead to trauma, suicidal feelings, and exposure to dangerously inadequate medical care,” said Clara Long, acting deputy Washington director at Human Rights Watch. “No amount of time in detention is safe for children and prolonged detention is particularly harmful.”
The torturing of innocent men, women, and children is not the badge of a great nation.
The Trump administration, rather than making America great again, instead has chosen to repeat the worst, immoral, cruel excesses of previously disgraced administrations.
Trump’s method for “making America great, again,” includes insulting our allies:
Trump scolds Denmark, calls prime minister ‘nasty’
By Jan M. Olsen and Laurie Kellman Associated Press
Trump said Wednesday he scrapped his trip to Denmark because the prime minister made a “nasty” statement when she rejected his idea to buy Greenland as an absurdity.
“You don’t talk to the United States that way, at least under me,” Trump told reporters in Washington. “I thought it was not a nice statement, the way she blew me off.”
Danish Prime Minister Mette Frederiksen called the whole thing “an absurd discussion” and said she was “disappointed and surprised” that Trump had canceled his visit.
Trump’s cancellation was “deeply insulting to the people of Greenland and Denmark,” former Prime Minister Helle Thorning-Schmidt wrote on Twitter.
Claus Oxfeldt, chairman of Denmark’s main police union, told Danish media that “It has created great frustrations to have spent so much time preparing for a visit that is canceled,” Oxfeldt was quoted as saying.
No, Mr. Trump, you are not America, and America was not insulted. You, however, are known internationally as an absurd boor, and that, unfortunately, reflects poorly on us Americans.
In short, every day, it is you Mr. Trump, who insults America.
Trump doubles down on charge that Jews who vote Democrat are ‘disloyal’ [The New York Times]
President Trump on Wednesday repeated his allegation that Jews who vote for Democrats are “being very disloyal to Jewish people and very disloyal to Israel.”
Trump also thanked conservative radio host Wayne Allyn Root (an evangelical Christian) for saying Jews in Israel love Trump “like he’s the King of Israel” and “the second coming of God.”
Jonathan Greenblatt, the head of the Anti-Defamation League, said Trump was trying to make himself out to be a savior. “Literally, it’s hard to think of something less kosher than telling the Jewish people you’re the king of Israel, and therefore, we should have some fidelity to you.”
Trump’s comment that Jews are, or should be, loyal to Israel, is part of the bigot’s old trope that Jews are not loyal to the country in which they live.
It was the excuse Hitler gave for murdering them. That slur, together with Trump’s love for dictators, has him re-emerging as the next Hitler “wannabe.”
And as for showing loyalty to a bigot like Trump, the vast majority of Jews have learned from Hitler, the cost of bigotry. When any group is maltreated by a bigot, eventually the maltreatment falls on the Jews. It’s always the Jews.
With Trump as its leader, America cannot claim greatness, nor can those who continue to back Trump.
Trump says he’s ‘Chosen One’ to take on China over trade
From CNBC
President Trump on Wednesday framed his trade war with China in religious terms, saying he was “the Chosen One” to confront Beijing over economic policies he considers unfair to the U.S.
“This isn’t my trade war, this is a trade war that should have taken place a long time ago. Somebody had to do it,” Trump said. He then looked up and pointed to the heavens, saying, “I am the Chosen One.”
Historically, dictators have portrayed themselves as God, or one chosen by God.
From the Pharaohs to Rafael Trujillo (“God in Heaven, Trujillo on Earth”) to Francisco Macias Nguema (“There is no other God than Macias Nguema”) to Trump’s pal, Kim Jong-Il (“Creator of the Universe“).
Will Americans, one day, refer to Donald Trump as “the chosen one”?
Every day, Trump disgraces America and each of us. Fortunately, every four years, we are given the ability to reverse our past errors of judgment or immorality.
The most important problems in economics involve the excessive income/wealth/power Gaps between the richer and the poorer.
Wide Gaps negatively affect poverty, health and longevity, education, housing, law and crime, war, leadership, ownership, bigotry, supply and demand, taxation, GDP, international relations, scientific advancement, the environment, human motivation and well-being, and virtually every other issue in economics.
Implementation of The Ten Steps To Prosperity can narrow the Gaps:
The most important problems in economics involve the excessive income/wealth/power Gaps between the richer and the poorer.
Wide Gaps negatively affect poverty, health and longevity, education, housing, law and crime, war, leadership, ownership, bigotry, supply and demand, taxation, GDP, international relations, scientific advancement, the environment, human motivation and well-being, and virtually every other issue in economics.
Implementation of The Ten Steps To Prosperity can narrow the Gaps:
(The blood vessels that supply a tumor often become misshapen and tangled, preventing chemo drugs from reaching the tumor. Drugs that restore normal blood flow can help make chemo more effective.)
