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How an Overnight COVID-19 Test Took 35 Years to Invent
By Shlomo Maital
Dr. Fang Zhang
As Darwin observed, when he was praised for his breakthrough: Scientists stand on the shoulders of giants. Now, a new genetic test for COVID-19 may be as quick, simple and cheap as a self-administered pregnancy test, with two lines on a slip of paper.
Here is the story. Let’s begin by noting that the hero is ethnic Chinese, Fang Zhang, a researcher at MIT’s Broad Institute. With massive anti-Asian and anti-Semitic hatred filling the Internet, it is fitting the hero should be named Zheng.
Chapter One. Some 35 years ago, a biologist named Kary Mullis invented PCR. Polymerase chain reaction (PCR) is a method used in molecular biology to rapidly make millions to billions of copies of a specific DNA sample. This allows scientists to take a very small sample of DNA and amplify it to a large enough amount to study in detail. For example, suppose you are looking for the presence of the genetic material of a virus. You take a swab, use PCR, make millions of copies of the stuff, and then it becomes easy to detect it in a test tube. Mullis won the Nobel Prize for this discovery, in 1993.
Chapter Two. CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats. (A palindrome is a word or phrase that reads the same forwards and backwards, e.g. a man a plan acanal panama. ) The discovery of clustered DNA repeats occurred independently in three parts of the world. The first description of what would later be called CRISPR is from Osaka University researcher Yoshizumi Ishino and his colleagues in 1987.
Say you want to modify a specific gene – snip it out, replace it, test it, etc. First, you ‘tag’ it with a molecule (like putting a big road sign, “HERE I AM!”, on it). Second, you attach an enzyme to the tag. The enzyme cuts the CAN right at that spot! You can then replace the faulty or offending gene with a different improved one.
Chapter Three. MIT. Dr. Zhang and other researchers have retooled CRISP-R. They use it not to snip out a gene, but to give a signal that the enzyme has reached its target – a piece of genetic material that is unique to COVID-19. When this happens, a screaming signal is emitted, say, figuratively, a bright Day-Glo sign saying, Yikes, it’s the novel coronavirus!
Chapter Four. Translate the complex lab procedure to a simple cheap test. Take samples from a person’s throat and nose. Put it into a test tube with chemicals that tear open viruses. Use an eye dropper to put some of the liquid into a second test tube containing CRISPR. Put the test tube in hot water, at 140 degrees F. (80 C.). Stick a piece of paper into the tube. If two lines appear: COVID-19 is present.
The test worked on 12 patients, and can be simplified greatly and produced at $6 per test. This may enable massive population-wide testing, that can help open societies and economies without a massive second-wave of plague.
Classic scientific breakthrough: 35 years, and an overnight breakthrough!
Why COVID-19 Will Hurt the Global Economy
By Shlomo Maital
COVID-19 Map
The ‘new coronavirus’ dubbed boringly COVID-19 has brought to mind an insight of Charles Darwin:
It is not the species best adapted to their environments, that thrive and prosper, but rather, those who learn fastest to adapt to changes in their environment.
The reason? Environments are constantly changing. Living species have to adapt, and some do it far better than others.
Viruses are an example. Keep in mind- viruses are not actually living things, as cells are. A virus is a small infectious agent that reproduces only inside the living cells of an organism. It inserts its ribonucleic acid (RNA) into the DNA of the cell, reproduces, kills the cell, bursts out and continues with its marauding raid on the human body, like Genghis Khan’s pony-mounted fighters.
Viruses can infect all types of life forms. And they have learned, through evolution and mutation, to defeat the human body’s antibodies – soldier cells that attack and kill foreign invaders, or antigens. Viruses learn and adapt fast.
And we humans?
The damage to the global economy from the COVID-19 virus will be greater than we expect. World capital markets, down 10% and more, are now waking up to this fact. But why?
Most economic downturns occur on the demand side of the supply-demand nexus. Some shock occurs, people cut back, spend less, invest less, governments slash spending, exports fall – and the fall in demand slows the economy. This is standard, and it describes every single economic downturn.
When President Reagan implemented huge tax cuts in 1981 and then again in 1984, he ascribed them to ‘suppy side economics’ – desire to boost the supply of saving and capital, by putting more income in the hands of the wealthy. It worked – but not in the way Reagan thought. The rich spent the money, there was a huge demand boom, and America had a decade-long demand-side stimulus boom.
COVID-19 is unique, because it is the first major supply-side disaster, since the global economy’s architecture was redesigned and rebuilt at Bretton Woods, NH, in July 1944, 76 years ago. China produces a great many of the world’s manufactured goods and parts. Most of its factories have slowed or closed. This is a huge disruption to the intricate system of global supply chains.
What can be done? Very little, because we have neglected supply side policies, and have underestimated how fragile and delicate the global supply chain system is.
Central banks can slash interest rates, but interest rates are already rock bottom. Governments can spend money, but they already are running big deficits.
And anyway, these are demand-side policies. Yes, they can help soften the demand problems arising from the supply shocks – tourism is collapsing, airlines are in trouble, etc. But these are secondary symptoms.
How to restore the global supply chain? That’s the key issue. It requires a meeting of the world’s leading countries; meanwhile global companies like Apple are scrambling to find quick temporary fixes, and there are few good ones.
Darwin was right. Our environment changed, when a tiny virus originating in Wuhan, China, set out to spread itself. How fast we learn to adapt will determine how costly that little virus will be to the world.
The Creativity of Nature:
How One Creative Scientist Harnessed It
By Shlomo Maital
Prof. Frances Arnold, Caltech
Frances Arnold is a professor of chemical engineering at California Institute of Technology, in Pasadena, CA. She won the 2018 Nobel Prize for chemistry, along with two others. She is only the fifth woman in history to win the Chemistry Nobel.
Prof. Arnold has had numerous personal tragedies. She has overcome all the grief – and not a small amount of gender discrimination. UK border police interrogated her for over two hours, when she told them she was “coming to meet the Queen” (she was – but a lot of nutty people say that, apparently).
Prof. Arnold won the Nobel for finding a creative way to leverage the powerful creative force of evolution. Instead of designing new chemicals from scratch, to fight crop-eating pests, remove laundry stains or clean up oil spills, Arnold figured out how to get Nature to do it.
“You start with a protein that already has some features you’re interested in”, she said, “ and use standard lab techniques to randomly mutate the gene that encodes the protein. Then you look for slight improvement in the resulting protein, in the direction you seek. You mutate the improved version again and again and screen the output. You do this with a bacterial workhorse, like E. coli….. you encourage the microbes to rise to the challenge, adapt, survive.”
In Dr. Arnold’s lab, organisms have been ‘mutated’ to stitch together carbon and silicon, or carbon and boron. “We’re discovering that nature can do chemistry, in the lab, we never dreamed was possible”, Dr. Arnold said. Arnold has invented the new field of evolutionary chemistry – using Nature’s incredibly creative system known as evolution and ‘survival of the fittest’, to create random mutations, select the ones that work, perfect them – and change the world. Nature is creative, in much the same way that humans are – try things, fail, try again, find something that does work and run with it. That is how we humans were created – and according to Darwin, all the millions of species on earth.
Arnold has launched a number of startups, including one that synthesizes insect pheromones and fends off agricultural pests by simply driving them crazy and confusing them.
Much of Dr. Arnold’s pioneering research was done while she fought breast cancer that had spread to her lymph nodes. She underwent surgery, radiation and chemo, all while raising three young boys and working day and night in her lab. And in 2010 her husband Andrew Lange killed himself; her middle son William, 20, died in an accident in 2016.
“Why would I give up?” said Arnold. “First you learn you have no control. Then you straighten up, fetch your invitation and go to meet the Queen.”
[This is based on an excellent New York Times article, by Natalie Angier, who writes for the Science Times].
Evolution at its Strangest: The Glow-worm Cave
By Shlomo Maital
Those strange luminous ‘fishing lines’ in the picture are actually — strange luminous fishing lines. They are created by glow-worms, weird creatures that live clinging to the roof of the Waitomo Cave, here in New Zealand. Evolution has taught these creatures to attract their food – bugs and mosquitos that breed in the river below, that runs through the cave — by fluorescent luminosity. When the lights are turned out in the cave, there is a spectacular sight – the entire ceiling glows, with a thousand points of light, just like the heavens on a clear starry night. And the older the glow-worm, the more luminous it is. The ‘butterfly’ form lives only a day or two, and has no mouth (because it has no need to feed, its only job is to mate, reproduce, and die), but the worms live quite long. And it dangles those strange strings down, to trap its food.
Evolution has created creatures that are superbly adapted to every possible environment – deep under the sea, in steam vents, and here, in deep dark caves. Give Nature enough time, and it will solve any problem.
I think we can learn from these tiny glow-worms. They emerged because Nature tried experiments. By accident, one weird glow-worm was luminescent. His friends all laughed at him/her. Hey, look at Wormie there, he glows. Let’s sing him a song– Glow little glow-worm, glimmer, glimmer…. But Wormie caught loads and loads of bugs, enough to reproduce successfully. And then Wormie’s kids, too, glowed…and down the generations.
This too is how humanity can crack its toughest problems. Have enough creative people running around trying weird things, trying to ‘glow’, with bright ideas – and some of them may work. Some of them may one day light up the world.
Creativity & Innovation in Remote New Zealand
By Shlomo Maital
My wife Sharona and I are in New Zealand, on the very last leg of a world tour that has taken us around the world, from Brazil, to Boston, France, Singapore, Vietnam, Guangzhou and Shantou China, Hong Kong and now Auckland. It’s been a great adventure – we combined touring with lecturing, teaching, research and meeting the local Jewish communities on the Sabbath.
Here, I visited GridAKL, a local incubator located near Auckland Harbor, in the Wynyard Quarter, and designed to foster technological entrepreneurship. I met with Eva Perrone, whose title is “activation manager” and she showed me the facility. The first floor is an open ‘events’ area, where companies outside and inside the incubator can stage workshops, meetings, etc. The second floor is the incubator, designed as open space, with quiet areas, kitchens, and lots and lots of light.
Some of the entrepreneurs in GridAKL are from Aukland University of Technology (AUT), a fine university with entrepreneurial spirit.
Despite New Zealand’s remoteness from the world, it is super-connected, with fast broadband. Many of the startups in GridAKL are IT and software startups. New Zealand itself makes a living from tourism and dairy and food exports, but is eager to expand its portfolio and build a startup culture.
In our travels, from Brazil to Vietnam, to China, Hong Kong, and now New Zealand, we have seen young people eager to start businesses and change the world. This is an extremely positive trend. It is also one that should accelerate the heartbeat of an entrepreneur and pump a few grams of adrenaline. Today if you have a great idea, chances are so does someone else, who could be anywhere in the world, including places you might not think of.
Here in New Zealand, we saw an amazing site – the glow-worm cave (see my next blog), where Nature and Darwinian evolution has created incredible worms that glow in the dark inside the cave ceiling, and actually create tiny long ‘fishing lines’ that they use to catch their food (mosquitos and bugs). The ‘glow’ attracts the bugs. Evolution has produced amazing things, as species compete to survive. Entrepreneurship can do the same. The fierce competition among ideas and resources can generate truly wonderful new creative things that create value for the world and literally, produce something from nothing. And all it takes is a few young people (or young in spirit), some open spaces, accessible food (this is the key to a great incubator, Eva Perrone assured me, and I told her about Google’s executive restaurants in their Mountainview, CA campus), strong networking and a great university.
TIMnovate 