Fastest Computer Finds Chemicals Against Coronavirus

CNN story at this link: https://www.cnn.com/2020/03/19/us/fastest-supercomputer-coronavirus-scn-trnd/?hpt=ob_blogfooterold

Mammal Brains Inspire AI Breakthroughs

Cornell University – March 16, 2020 -- When you smell an orange, the scent is most likely combined with several others: car exhaust, garbage, flowers, soap. Those smells bind simultaneously to the hundreds of receptors in your brain's olfactory bulb, obscuring one another, yet you can still recognize the smell of an orange, even when it's blended with a totally different pattern of other scents.


The precise mechanics of how mammals learn and identify smells have long eluded scientists. New Cornell research explains some of these functions through a computer algorithm inspired by the mammalian olfactory system. The algorithm both sheds light on how the brain works and, applied to a computer chip, rapidly and reliably learns patterns better than existing machine learning models.


"This is a result of over a decade of studying olfactory bulb circuitry in rodents and trying to figure out essentially how it works, with an eye towards things we know animals can do that our machines can't," said Thomas Cleland, professor of psychology and senior author of "Rapid Learning and Robust Recall in a Neuromorphic Olfactory Circuit," which published in Nature Machine Intelligence March 16.


"We now know enough to make this work. We've built this computational model based on this circuitry, guided heavily by things we know about the biological systems' connectivity and dynamics," Cleland said. "Then we say, if this were so, this would work. And the interesting part is that it does work."


Cleland and co-author Nabil Imam, Ph.D. '14, a researcher at Intel, applied the algorithm to an Intel computer chip. The research chip, known as Loihi, is neuromorphic -- meaning it's inspired by the way the brain functions, incorporating digital circuits that mimic the way neurons communicate and learn. For example, the Loihi research chip is based on many parallel cores which communicate via discrete spikes, and the effects delivered by each of these spikes can change based solely on local activity. This architecture requires fundamentally different strategies for algorithm design compared ]
with existing computer chips.


Using neuromorphic computer chips, machines could learn to identify patterns or perform certain tasks a thousand times faster than by using the computer's central or graphics processing units, as most programs do. Running certain algorithms on the Loihi research chip also uses about a thousand times less power than traditional methods, according to Intel.

]
The chip is the optimal platform for Cleland's algorithm, which can accept input patterns from an array of sensors, learn multiple patterns rapidly and sequentially, and then identify each of these meaningful patterns despite strong sensory interference. The algorithm can successfully identify odors even when their pattern is 80% different from the pattern the computer originally learned.

]
"The pattern of the signal has been substantially destroyed," Cleland said, "and yet the system is able to recover it."

]
The mammalian brain is stunningly adept at identifying and remembering smells, with hundreds or even thousands of olfactory receptors and complex neural networks rapidly analyzing the patterns associated with odors. Our brains also retain what we've learned even after we've acquired new knowledge -- something that's easy for mammals but difficult for artificial intelligence systems. ]
Particularly in deep learning approaches, everything must be presented to the network at the same time, because new information can distort or destroy what the system learned before.

The brain-inspired algorithm solves this problem, Cleland said.

]
"When you learn something, it permanently differentiates neurons," he said. "When you learn one odor, the interneurons are trained to respond to particular configurations, so you get that segregation at the level of interneurons. So on the machine side, we just enhance that and draw a firm line."

It also explains a previously misunderstood phenomenon: why the olfactory bulb of the brain is one of the few places where mammals can create new neurons after they've reached adulthood.


"The computational model turns into a biological hypothesis for why adult neurogenesis is important," Cleland said. "Because it does this thing that otherwise would make the system not work. So in that sense, the model is feeding back into biology. And in this other sense, it's the basis for a set of devices for artificial olfactory systems that can be constructed commercially."


The brain's complexity motivated Cleland to focus his neuroscience research around a theoretical approach guided by explicit computational models.


"When you start studying a biological process that becomes more intricate and complex than you can just simply intuit, you have to discipline your mind with a computer model," he said. "You can't fuzz your way through it. And that led us to a number of new experimental approaches and ideas that we wouldn't have come up with just by eyeballing it."


The study was partly funded by the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health.


                 https://www.sciencedaily.com/releases/2020/03/200316141517.htm

What Keeps Working Memory Going?

Yale University – March  19, 2020 -- Working memory, the ability to hold a thought in mind even through distraction, is the foundation of abstract reasoning and a defining characteristic of the human brain. It is also impaired in disorders such as schizophrenia and Alzheimer's disease.


Now Yale researchers have found a key molecule that helps neurons maintain information in working memory, which could lead to potential treatments for neurocognitive disorders, they report March 19 in the journal Neuron.


"Working memory arises from neuronal circuits in the prefrontal cortex," said senior author Min Wang, senior research scientist in neuroscience. "We have been learning that these circuits have special molecular maintenance requirements."


Neurons in the prefrontal cortex excite each other to keep information "in mind." These circuits act as a sort of mental sketch pad, allowing us to remember that caramelized onions are cooking in the frying pan while we search the next room for a pair of scissors.


The new study shows that these prefrontal cortical circuits depend upon the neurotransmitter acetylcholine stimulating muscarinic M1 receptors aligned on the surface of neurons of the prefrontal cortex. Blocking muscarinic M1 receptors reduced the firing of neurons involved in working memory, while activating the M1 receptors helped restore neuronal firing. Because acetylcholine actions at M1 receptors are reduced in schizophrenia and Alzheimer's disease, the M1 receptor may serve as a potential therapeutic target, the authors suggest.


Wang notes that a drug currently under development for the treatment of schizophrenia stimulates this M1 receptor and has shown promise in early clinical trials.


]Yale's Veronica Galvin is first author of the paper, which was primarily funded by the National Institutes of Health.

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https://www.sciencedaily.com/releases/2020/03/200319125228.htm

20 Films That Are True to History

   1.               12 Years a Slave

   2.               A Night to Remember

   3.                        Apollo 13

   4.               Black Robe   

   5.                        Come and See

   6.                        Das Boot

   7.                  Downfal8.     

   8.             Gettysburg

   9.                         The Assassination of Jesse James by the Coward Robert Ford

110.                        Lincoln (Steven Spielberg version)

111.                        Master and Commander: The Far Side of the World

112.                        Saving Private Ryan

113.                        Schindler’s List

114.                        Stalingrad

115.                        The Last Emperor

116.                        Tora! Tora! Tora!

117.                        The Lion in Winter

118.                        Fruitvale Station

119.                        All the President’s Men

120.                        Zodiac

                       http://standardnews.com/historical-films-true-history/1/

Four Timelines for Life Returning to Normal

The coronavirus outbreak may last for a year or two, but some elements of pre-pandemic life will likely be won back in the meantime.



“The new coronavirus has brought American life to a near standstill, closing businesses, canceling large gatherings, and keeping people at home. All of those people must surely be wondering: When will things return to normal?


“The answer is simple, if not exactly satisfying: when enough of the population—possibly 60 or 80 percent of people—is resistant to COVID-19 to stifle the disease’s spread from person to person. That is the end goal, although no one knows exactly how long it will take to get there.”


                    -- Joe Pinsker, writing in The Atlantic, March 26, 2020


Much more at: https://www.theatlantic.com/family/archive/2020/03/coronavirus-social-distancing-over-back-to-normal/608752/

Normal G7 Life Ist Kaput

Here it is, the best existing article on the coronavirus pandemic. You might want to go back and reread it in a day or two.  I didn’t copy and paste the entire article because the color graphs are vitally important.


Forget the nonsense from the Oval Office that things will get back to normal before Easter on April 12^th.


https://www.technologyreview.com/s/615370/coronavirus-pandemic-social-distancing-18-months/


The above linked article did not answer my own multi-trillion dollar question:  “Will this virus mutate?”

Wild Females Outlive Wild Males

Milner Centre scientists working as part of an international team found that, like humans, female wild animals tend to live significantly longer than males.


University of Bath, March 24, 2020 -- An international team of scientists studying lifespans of wild mammals have found that, just like humans, females tend to live significantly longer than their male counterparts.


The researchers looked at the lifespans of 101 different species, from sheep to elephants, and found that females lived an average of 18% longer than males for more than 60% of the species studies. In humans, females tend to live around 7.8% longer.


The study, led by scientists at University Lyon 1 and published in the prestigious journal, Proceedings of the National Academy of Sciences, found this was not due to the sexes aging at different rates but that females had an average lower risk of mortality in adulthood than males.

It was unclear from the data as to why females survive longer than males, however the authors suggest that it could be due to complex interactions between the local environmental conditions and sex-specific costs of reproduction.


Professor Tamás Székely, from the Milner Centre for Evolution at the University of Bath, was one of the authors of the study. He said: ‘We’ve known for a long time that women generally live longer than men, but were surprised to find that the differences in lifespan between the sexes was even more pronounced in wild mammals than in humans.


“This could be either because females are naturally able to live longer, or that female mortality drops compared with males.


“For example, lionesses live at least 50% longer in the wild than male lions. We previously thought this was mostly due to sexual selection – because males fight with each other to overtake a pride and thus have access to females, however our data do not support this. Therefore there must be other, more complex factors at play.


“Female lions live together in a pride, where sisters, mothers and daughters hunt together and look after each other, whereas adult male lions often live alone or with their brother and therefore don’t have the same support network.


“Another possible explanation for the sex difference is that female survival increases when males provide some or all of the parental care. This is also true in birds. Giving birth and caring for young becomes a significant health cost for females and so this cost is reduced if both parents work together to bring up their offspring.”


The researchers plan to compare the data on wild animals with that of captive zoo animals, which do not have to deal with predators or competition for food or mates. This will allow them to measure the extent to which biological differences between the sexes have an effect on life expectancy.


“By affecting males and females differently, harsh environmental conditions such as a high prevalence in pathogens, is likely to cause sex-differences in lifespan.


“Comparing the sex gap in lifespan and aging across several populations of the same species is definitely full of promises,” said Jean-François Lemaître from the National Centre for Scientific Research (University Lyon 1, France) and coordinator of this study.


https://www.bath.ac.uk/announcements/scientists-investigate-why-females-live-longer-than-males/

Edge of the Milky Way Found

“Astronomers have long known that the brightest part of the Milky Way, the pancake-shaped disk of stars that houses the sun, is some 120,000 light-years across (Science News: 8/1/19). Beyond this stellar disk is a disk of gas. A vast halo of dark matter, presumably full of invisible particles, engulfs both disks and stretches far beyond them (Science News: 10/25/16). But because the dark halo emits no light, its diameter is hard to measure.


“Now, Alis Deason, an astrophysicist at Durham University in England, and her colleagues have used nearby galaxies to locate the Milky Way’s edge. The precise diameter is 1.9 million light-years, give or take 0.4 million light-years, the team reports February 21 in a paper posted at arXiv.org.”


                             —Ken Croswell writing in Science News, March 23, 2020


More at https://www.sciencenews.org/article/astronomers-have-found-edge-milky-way-size

Ancestor of All Animals Identified in Australian Fossils

A wormlike creature that lived more than 555 million years ago is the earliest known bilaterian


University of California Riverside – March 23, 2020 -- A team led by UC Riverside geologists has discovered the first ancestor on the family tree that contains most familiar animals today, including humans.


The tiny, wormlike creature, named Ikaria wariootia, is the earliest bilaterian, or organism with a 
front and back, two symmetrical sides, and openings at either end connected by a gut. The paper is published today in Proceedings of the National Academy of Sciences.


The earliest multicellular organisms, such as sponges and algal mats, had variable shapes. 

Collectively known as the Ediacaran Biota, this group contains the oldest fossils of complex, multicellular organisms. However, most of these are not directly related to animals around today, including lily pad-shaped creatures known as Dickinsonia that lack basic features of most animals, such as a mouth or gut.


The development of bilateral symmetry was a critical step in the evolution of animal life, giving organisms the ability to move purposefully and a common, yet successful way to organize their bodies. A multitude of animals, from worms to insects to dinosaurs to humans, are organized around this same basic bilaterian body plan.


Evolutionary biologists studying the genetics of modern animals predicted the oldest ancestor of all bilaterians would have been simple and small, with rudimentary sensory organs. Preserving and identifying the fossilized remains of such an animal was thought to be difficult, if not impossible.


For 15 years, scientists agreed that fossilized burrows found in 555 million-year-old Ediacaran Period deposits in Nilpena, South Australia, were made by bilaterians. But there was no sign of the creature that made the burrows, leaving scientists with nothing but speculation.


Scott Evans, a recent doctoral graduate from UC Riverside; and Mary Droser, a professor of geology, noticed miniscule, oval impressions near some of these burrows. With funding from a NASA exobiology grant, they used a three-dimensional laser scanner that revealed the regular, consistent shape of a cylindrical body with a distinct head and tail and faintly grooved musculature. The animal ranged between 2-7 millimeters long and about 1-2.5 millimeters wide, with the largest the size and shape of a grain of rice -- just the right size to have made the burrows.


"We thought these animals should have existed during this interval, but always understood they would be difficult to recognize," Evans said. "Once we had the 3D scans, we knew that we had made an important discovery."


The researchers, who include Ian Hughes of UC San Diego and James Gehling of the South Australia Museum, describe Ikaria wariootia, named to acknowledge the original custodians of the land. The genus name comes from Ikara, which means "meeting place" in the Adnyamathanha language. It's the Adnyamathanha name for a grouping of mountains known in English as Wilpena Pound. The species name comes from Warioota Creek, which runs from the Flinders Ranges to Nilpena Station.


"Burrows of Ikaria occur lower than anything else. It's the oldest fossil we get with this type of complexity," Droser said. "Dickinsonia and other big things were probably evolutionary dead ends. We knew that we also had lots of little things and thought these might have been the early bilaterians that we were looking for."


In spite of its relatively simple shape, Ikaria was complex compared to other fossils from this period. It burrowed in thin layers of well-oxygenated sand on the ocean floor in search of organic matter, indicating rudimentary sensory abilities. The depth and curvature of Ikaria represent clearly distinct front and rear ends, supporting the directed movement found in the burrows.


The burrows also preserve crosswise, "V"-shaped ridges, suggesting Ikaria moved by contracting muscles across its body like a worm, known as peristaltic locomotion. Evidence of sediment displacement in the burrows and signs the organism fed on buried organic matter reveal Ikaria probably had a mouth, anus, and gut.


"This is what evolutionary biologists predicted," Droser said. "It's really exciting that what we have found lines up so neatly with their prediction."

                        https://www.sciencedaily.com/releases/2020/03/200323152108.htm

Blocking Sugar Structures on Viruses and Tumor Cells

Artificial sugar-binding protein may inhibit cell growth

Technical University of Munich – March 17, 2020 -- During a viral infection, viruses enter the body and multiply in its cells. Viruses often specifically attach themselves to the sugar structures of the host cells, or present characteristic sugar structures on their surface themselves. Researchers have developed a new type of protein reagent for identifying biological sugar structures, which may block the spread of an illness in the body if used for blocking the sugar structures of a cell or a pathogen.  


The laboratory directed by Arne Skerra, Professor of Biological Chemistry, has its focus on designing artificial binding proteins for therapeutic applications. The laboratory's current research findings are paving the way for the development of new types of binding proteins for biological sugar structures, which play a significant role in cancer as well as infectious diseases.


Recognizing biological sugar structures


"The recognition of specific sugar molecules, or so-called carbohydrates, is of vital importance in many biological processes," Prof. Skerra explains. Most cells carry a marker consisting of sugar chains which are attached to the outside of the cell membrane or to the membrane proteins, thus enabling the body to identify where these cells belong or whether certain cells are alien. Pathogens also have sugar structures of their own, or they can bind to these.


Proteins, which perform a wide range of functions within cells, generally have only low affinity to sugars. Thus, their molecular recognition poses a challenge. The reason: water molecules look similar to the sugar molecules, meaning that they are basically hidden in the aqueous environment of the cells. Prof. Skerra's research group therefore set out to design an artificial binding protein with a peculiar chemical composition which makes it easier to bind to biological sugar structures.


A boric acid group implemented into a protein as amino acid


Amino acids are the building blocks of proteins. As a rule, nature only uses 20 amino acids in all living organisms. "Using the possibilities opened up by synthetic biology, we have employed an additional artificial amino acid," reports researcher Carina A. Sommer.


"We have succeeded in incorporating a boric acid group, which exerts intrinsic affinity to sugar molecules, into the amino acid chain of a protein. In doing this, we have created an entirely new class of binding protein for sugar molecules," Sommer explains. This artificial sugar-binding function is superior to natural binding proteins (so-called lectins) both in strength and with regard to possible sugar specificities.


"The sugar-binding activity of boric acid and its derivatives has been known for nearly a century," says Prof. Skerra. "The chemical element boron is common on earth and has low toxicity, but so far has largely remained unexplored by organisms."


"By using X-ray crystallography, we have succeeded in unraveling the crystal structure of a model complex of this artificial protein, which allowed us to validate our biomolecular concept," explains scientist Dr. Andreas Eichinger.


The next step: towards medical application


Following approximately five years of fundamental scientific research, the findings from Prof. Skerra's laboratory can now be applied to practical medical needs. Prof. Skerra points out: "Our results should not only be used to support the future development of new carbohydrate ligands in biological chemistry, but should also pave the way for creating high-affinity agents for controlling or blocking medically-relevant sugar structures on cell surfaces."

Such a "blocking agent" could be used for conditions in which strong cell growth is evident or when pathogens are attaching themselves to cells, for example in oncology and virology. If we are successful in blocking the sugar-binding function and in slowing down the progress of a disease, this would give the patient's immune system sufficient time to mobilize the body's natural defense.

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                                  https://www.sciencedaily.com/releases/2020/03/200317103817.htm

Microbial DNA in Blood May Indicate Cancer

From a simple blood draw, microbial DNA may reveal who has cancer and which type, even at early stages

By Heather Buschman, PhD


UC San Diego  -- March 20, 2020 -- When Gregory Poore was a freshman in college, his otherwise
healthy grandmother was shocked to learn that she had late-stage pancreatic cancer. The condition was diagnosed in late December. She died in January.


“She had virtually no warning signs or symptoms,” Poore said. “No one could say why her cancer wasn’t detected earlier or why it was resistant to the treatment they tried.”


As Poore came to learn through his college studies, cancer has traditionally been considered a disease of the human genome — mutations in our genes allow cells to avoid death, proliferate and form tumors.


But when Poore saw a 2017 study in Science that showed how microbes invaded a majority of pancreatic cancers and were able to break down the main chemotherapy drug given to these patients, he was intrigued by the idea that bacteria and viruses might play a bigger role in cancer than anyone had previously considered.


Poore is currently an MD/PhD student at University of California San Diego School of Medicine, where he’s conducting his graduate thesis work in the lab of Rob Knight, PhD, professor and director of the Center for Microbiome Innovation.


Together with an interdisciplinary group of collaborators, Poore and Knight have developed a novel method to identify who has cancer, and often which type, by simply analyzing patterns of microbial DNA — bacterial and viral — present in their blood.

The study, published March 11, 2020 in Nature, may change how cancer is viewed, and diagnosed.


“Almost all previous cancer research efforts have assumed tumors are sterile environments, and ignored the complex interplay human cancer cells may have with the bacteria, viruses and other microbes that live in and on our bodies,” Knight said.


“The number of microbial genes in our bodies vastly outnumbers the number of human genes, so it shouldn’t be surprising that they give us important clues to our health.”


Cancer-associated microbial patterns


The researchers first looked at microbial data available from The Cancer Genome Atlas, a database of the National Cancer Institute containing genomic and other information from thousands of patient tumors. To the team’s knowledge, it was the largest effort ever undertaken to identify microbial DNA in human sequencing data.


From 18,116 tumor samples, representing 10,481 patients with 33 different cancer types, emerged distinct microbial signatures, or patterns, associated with specific cancer types. Some were expected, such as the association between human papillomavirus (HPV) and cervical, head and neck cancers, and the association between Fusobacterium species and gastrointestinal cancers. But the team also identified previously unknown microbial signatures that strongly discriminated between cancer types. 
For example, the presence of Faecalibacterium species distinguished colon cancer from other cancers.


Armed with the microbiome profiles of thousands of cancer samples, the researchers then trained and tested hundreds of machine learning models to associate certain microbial patterns with the presence of specific cancers. The machine learning models were able to identify a patient’s cancer type using only the microbial data from his or her blood.


The researchers then removed high-grade (stage III and IV) cancers from the dataset and found that many cancer types were still distinguishable at earlier stages when relying solely on blood-derived microbial data. The results held up even when the team performed the most stringent bioinformatics decontamination on the samples, which removed more than 90 percent of the microbial data.


Applying the microbial DNA test


To determine if these microbial patterns could be useful in the real world, Knight, Poore and team analyzed blood-derived plasma samples from 59 consenting patients with prostate cancer, 25 with lung cancer and 16 with melanoma, provided by collaborators at Moores Cancer Center at UC San Diego Health. Employing new tools they developed to minimize contamination, the researchers developed a readout of microbial signatures for each cancer patient sample and compared them to each other and to plasma samples from 69 healthy, HIV-negative volunteers, provided by the HIV Neurobehavioral Research Center at UC San Diego School of Medicine.


The team’s machine learning models were able to distinguish most people with cancer from those without. For example, the models could correctly identify a person with lung cancer with 86 percent sensitivity and a person without lung disease with 100 percent specificity. They could often tell which participants had which of the three cancer types. For example, the models could correctly distinguish between a person with prostate cancer and a person with lung cancer with 81 percent sensitivity.


“The ability, in a single tube of blood, to have a comprehensive profile of the tumor’s DNA (nature) as well as the DNA of the patient’s microbiota (nurture), so to speak, is an important step forward in better understanding host-environment interactions in cancer,” said co-author Sandip Pravin Patel, MD, a medical oncologist and co-leader of experimental therapeutics at Moores Cancer Center at UC San Diego Health.


“With this approach, there is the potential to monitor these changes over time, not only as a diagnostic, but for long-term therapeutic monitoring. This could have major implications for the care of cancer patients, and in the early detection of cancer, if these results continue to hold up in further testing.”


Comparison to current cancer diagnostics


According to Patel, diagnosis of most cancers currently requires surgical biopsy or removal of a sample from the suspected cancer site and analysis of the sample by experts who look for molecular markers associated with certain cancers. This approach can be invasive, time-consuming and costly.


Several companies are now developing “liquid biopsies”— methods to quickly diagnose specific cancers using a simple blood draw and technologies that allow them to detect cancer-specific human gene mutations in circulating DNA shed by tumors. This approach can already be used to monitor progression of tumors for some types of already-diagnosed cancers, but is not yet approved by the U.S. Food and Drug Administration (FDA) for diagnostic use.


“While there has been amazing progress in the area of liquid biopsy and early cancer detection, current liquid biopsies aren’t yet able to reliably distinguish normal genetic variation from true early cancer, and they can’t pick up cancers where human genomic alterations aren’t known or aren’t detectable,” said Patel, who also serves as the deputy director of the San Diego Center for Precision Immunotherapy.


That’s why there’s often a risk that current liquid biopsies will return false-negative results in the setting of low disease burden. “It’s hard to find one very rare human gene mutation in a rare cell shed from a tumor,” Patel said. “They’re easy to overlook and you might be told you don’t have cancer, when you really do.”


According to the researchers, one advantage of cancer detection based on microbial DNA, compared to circulating human tumor DNA, is its diversity among different body sites. Human DNA, in contrast, is essentially the same throughout the body. By not relying on rare human DNA changes, the study suggests that blood-based microbial DNA readouts may be able to accurately detect the presence and type of cancers at earlier stages than current liquid biopsy tests, as well as for cancers that lack genetic mutations detectable by those platforms.


Limitations and cautions


The researchers are quick to point out that there’s still the possibility blood-based microbial DNA readouts could miss signs of cancer and return a false-negative result. But they expect their new approach will become more accurate as they refine their machine learning models with more data.


And while false negatives may be less common with the microbial DNA approach, false positives — hearing you have cancer when you don’t — are still a risk.


Patel said that just because a cancer is detected early, it doesn’t mean it always requires immediate treatment. Some DNA changes are non-cancerous, changes related to aging, harmless or self-resolve. 

You would never know about them without the test. That’s why more screening and more cancer diagnoses might not always be a good thing, Patel said, and should be determined by expert clinicians.


The team also cautioned that even if a microbial readout indicates cancer, the patient would likely require additional tests to confirm the diagnosis, determine the stage of the tumor and identify its exact location.


Looking ahead


Knight said many challenges still lay ahead as his team further develops these initial observations into an FDA-approved diagnostic test for cancer. Most of all, they need to validate their findings in a much larger and more diverse patient population, an expensive undertaking. They need to define what a “healthy” blood-based microbial readout might look like among many, diverse people. They’d also like to determine whether the microbial signatures they can detect in human blood are coming from live microbes, dead microbes or dead microbes that have burst open, dispersing their contents — an insight that might help them refine and improve their approach.


In the future, blood-based microbial DNA readouts might be used to detect a variety of different cancers.


To advance blood-based microbial DNA readouts through the next steps toward regulatory approval, commercialization and clinical application of a diagnostic test, Knight and Poore have filed patent applications and they founded a spinout company called Micronoma, with co-author Sandrine Miller-Montgomery, PhD, professor of practice in the Jacobs School of Engineering and executive director of the Center for Microbiome Innovation at UC San Diego.


The latest study may prompt important shifts in the field of cancer biology, Poore said.


“For example, it’s common practice for microbiologists to use many contamination controls in their experiments, but these have historically been rarely used in cancer studies,” he said. “We hope this study will encourage future cancer researchers to be ‘microbially conscious.’”

The researchers also suggest cancer diagnostics may only be the beginning for the newly discovered cancer-associated blood microbiome.


“This new understanding of the way microbial populations shift with cancer could open a completely new therapeutic avenue,” Miller-Montgomery said. “We now know the microbes are there, but what are they doing? And could we manipulate or mimic these microbes to treat cancer?”


Additional co-authors include: Qiyun Zhu, Carolina Carpenter, Serena Fraraccio, Stephen Wandro, Tomasz Kosciolek, Stefan Janssen, Se Jin Song, Jad Kanbar, Robert Heaton, Rana McKay, Austin D. Swafford, UC San Diego; Evguenia Kopylova, formerly of UC San Diego, now at Clarity Genomics; and Jessica Metcalf, formerly of UC San Diego, now at Colorado State University, Fort Collins.


https://ucsdnews.ucsd.edu/pressrelease/microbial-dna-in-patient-blood-may-be-tell-tale-sign-of-cancer

31 Q&A About COVID-19

My thoughts on what to do now and other topics.

By Bill Gates, March 19, 2020


Yesterday I did a Reddit Ask Me Anything session on COVID-19. As usual, Redditors asked a lot of smart questions, and it was a great opportunity to have a fact-based discussion about this pandemic and what we can do to prevent the next one. (And as I mentioned in this exchange, it’s nice to have so many positive interactions in such an uncertain time.)

Below is a transcript of all the questions I could get to (lightly edited for length), along with my answers. I’ll be sharing more about COVID-19 here on the Gates Notes and on my social channels. In the meantime, stay healthy and keep washing your hands!


Redditor’s question: What about the current crisis worries you the most? What gives you the most hope?

My answer: The current phase has a lot of the cases in rich countries. With the right actions including the testing and social distancing (which I call “shut down”) within 2-3 months the rich countries should have avoided high levels of infection. I worry about all the economic damage but even worse will be how this will affect the developing countries who cannot do the social distancing the same way as rich countries and whose hospital capacity is much lower.

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Can you explain briefly what most Americans can do to help other Americans in this moment of crisis?

A big thing is to go along with the “shut down” approach in your community so that the infection rate drops dramatically to let us go back to normal as soon as possible. Some people like health care workers will be doing heroic work and we need to support them. We do need to stay calm even though this is an unprecedented situation.

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Is there any chance that the 18 month timeline for development of a vaccine can be shortened, and by how much?

This is a great question. There are over 6 different efforts going on to make a vaccine. Some use a new approach called RNA which is unproven. We will have to build lots of manufacturing for the different approaches knowing that some of them will not work. We will need literally billions of vaccines to protect the world. Vaccines require testing to make sure they are safe and effective. Some vaccines like the flu don’t for the elderly.

The first vaccines we get will go to health care workers and critical workers. This could happen before 18 months if everything goes well but we and Dr. Fauci and others are being careful not to promise this when we are not sure. The work is going at full speed.

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I’d also like to ask the same thing, but with regards to the timeline for an effective treatment.

A therapeutic could be available well before a vaccine. Ideally this would reduce the number of people who need intensive care including respirators. The Foundation has organized a Therapeutics Accelerator to look at all the most promising ideas and bring all the capabilities of industry into play. So I am hopeful something will come out of this. It could be an anti-viral or antibodies or something else.

One idea that is being explored is using the blood (plasma) from people who are recovered. This may have antibodies to protect people. If it works it would be the fastest way to protect health care workers and patients who have severe disease.

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As an educator, what is something I can do for my students, especially for my low-income students who don’t have access to technology during this time? I have tried to send reassuring emails (including cat pictures), but I worry about the educational impact, as well as the long-term impact to my students’ well being.

It is a huge problem that schools will likely be shut down for the next few months. I am impressed by the creative approaches that many teachers are coming up with to teach remotely. (If you are a teacher reading this, thank you for the work you’re doing.) But I know that not everyone is set up to teach remotely. There are a lot of good online resources out there, including Khan Academy, CommonLit, Illustrative Mathematics, Zearn, and Scholastic. Comcast and other internet connectivity providers are doing special programs to help with access. Microsoft and others are working on getting machines out but the supply chain is quite constrained. Unfortunately low-income students will be hurt more by the situation than others so we need to help any way we can.

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What do you think about China’s response to the outbreak? How would you rate their response on a scale 1-10?

After January 23 when they realized how serious it was they did strong social isolation which made a huge difference. Of course that isolation created a lot of difficulties for the people involved but they were able to stop the case spread. Other countries will do it somewhat differently but a combination of testing and social isolation clearly works and that is all we have until we get a vaccine.

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In your opinion, after this pandemic comes to a close, however long that may be, what should be the first step we as a global community take so that we are better prepared for the next pandemic?

The TED talk I did in 2015 talked about this. We need to have the ability to scale up diagnostics, drugs and vaccines very rapidly. The technologies exist to do this well if the right investments are made. Countries can work together on this. We did create CEPI = Coalition for Epidemic Preparedness Innovation which did some work on vaccines but that needs to be funded at higher level to have the standby manufacturing capacity for the world.

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Why do you think most world governments weren’t prepared if you and other experts warned of such events such as this?

No one could predict what the chance of a new virus emerging was. However we did know it would happen at some point either with a flu or some other respiratory virus. There was almost no funding. The creation of CEPI which was funded by our foundation, Wellcome, Norway, Japan, Germany, and the UK was a step but tiny compared to what should have happened. We prepare for possible wars and fires and now we have to have preparation for epidemics treated with the same seriousness. The good news is that our biological tools including new ways to make diagnostics, therapeutics and vaccines make it possible to have a strong response system for naturally caused epidemics.

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I live in Seattle, like you, and it feels like our testing has not increased. Our number of confirmed cases are starting to lag behind other states. What do you think gives? Effective social distancing or lack of testing?

The testing in the US is not organized yet. In the next few weeks I hope the Government fixes this by having a website you can go to to find out about home testing and kiosks. Things are a bit confused on this right now. In Seattle the U of W is providing thousands of tests per day but no one is connected to a national tracking system.

Whenever there is a positive test it should be seen to understand where the disease is and whether we need to strengthen the social distancing. South Korea did a great job on this including digital contact tracing.

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I read the Imperial College COVID-19 Response Team report as well as this explanation in a historical context. Essentially, it says that by doing nothing, 4 million Americans die. Through the mitigation strategy—i.e. social distancing and “flattening the curve”— it says that 1.1-2 million Americans will die. However, it also says that the suppression strategy, or “shutting everything down for 18 months”—will lead to only a few thousand people dying.

Do you agree with these numbers, and if so, is there any excuse for not immediately issuing a shelter in place order for the entire country?

Fortunately it appears the parameters used in that model were too negative. The experience in China is the most critical data we have. They did their “shut down” and were able to reduce the number of cases. They are testing widely so they see rebounds immediately and so far there have not been a lot. They avoided widespread infection. The Imperial model does not match this experience. Models are only as good as the assumptions put into them. People are working on models that match what we are seeing more closely and they will become a key tool. A group called Institute for Disease Modeling that I fund is one of the groups working with others on this.

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Covid-19 testing standards seem grossly unfair in favor of the rich and famous. Testing is happening for people like professional sports players, even those without any symptoms at all. I’m not talking about health care workers or people in essential jobs- I’m talking about actors, actresses, sports players and so on. On the flip side, the guidance from Kaiser in WA is that you must have a fever of 101.5 and either serious shortness of breath or a bad cough, and even then testing results take 5 days or more.

How is it that even with something like covid-19 testing, which the government is supposed to manage, the rich and famous are getting special treatment? Is there a big stash of tests that are reserved for “people that matter”? Isn’t it hypocritical for everyone else to be told they need to look out for the common good and avoid demanding too much of the health care system, meanwhile the rich and famous get whatever they want, when they want it?

We need to democratize and scale the testing system by having a CDC website that people go to and enter their situation. Priority situations should get tested within 24 hours. This is very possible since many countries have done it. Health care workers for example should have priority. Elderly people should have priority. We will be able to catch up on the testing demand within a few weeks of getting the system in place. Without the system we don't know what is missing—swabs, reagents etc..

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What do you think of the current approach the Netherlands is currently taking to combat this virus? They are not going to a full lockdown but rather try to spread it controllably in order to work towards “herd immunity”.

The only model that is known to work is a serious social distancing effort (“shut down”). If you don’t do this then the disease will spread to a high percentage of the population and your hospitals will be overloaded with cases. So this should be avoided despite the problems caused by the “shut down”. If a country doesn't control its cases then other countries will prevent anyone going into or coming out of that country. I think the Netherlands will end up doing what other countries are doing.

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Thoughts on chloroquine/hydroxychloroquine?

There are a lot of therapeutic drugs being examined. This is one of many but it is not proven. If it works we will need to make sure the finite supplies are held for the patients who need it most. We have a study going on to figure this out. We also have a screening effort to look at all the ideas for Therapeutics because the number being proposed is very large and only the most promising should be tried in patients. China was testing some things but now they have so few cases that that testing needs to move to other locations.

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How is your foundation helping the current pandemic? Are you donating money, producing products for health workers?

Our foundation is working with all the groups who make diagnostics, therapeutics and vaccines to make sure the right efforts are prioritized. We want to make sure all countries get access to these tools. We donated $100M in February for a variety of things and we will be doing more. One priority is to make sure that there is enough manufacturing capacity for therapeutics and vaccines. We have other efforts like our education group working to make sure the online resources for students are as helpful as they can be.

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Is there anything you can do to assist with ventilator production?

There are a lot of efforts to do this. If we do social distancing (“shut down”) properly then the surge of cases won’t be as overwhelming. Our foundation’s expertise is in diagnostics, therapeutics and vaccines so we are not involved in the ventilator efforts but it could make a contribution to have more especially as the disease gets into developing countries including Africa.

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Should there be a national shelter in place order? Why or why not?

Most people can shelter in their home but for people who that doesn’t work for there should be a place for them to go. We are working on seeing if we can send test kits to people at home so they don't have to go out and so the tests get to the people who are the priority. The US still is not organized on testing.

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What changes are we going to have to make to how businesses operate to maintain our economy while providing social distancing?

The question of which businesses should keep going is tricky. Certainly food supply and the health system. We still need water, electricity and the internet. Supply chains for critical things need to be maintained. Countries are still figuring out what to keep running.

Eventually we will have some digital certificates to show who has recovered or been tested recently or when we have a vaccine who has received it.

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When will this all end?

To bring it to small numbers globally we need a vaccine. Many rich countries will be able to keep the number of cases small (including the US) if they do the right things but developing countries will find it very difficult to stop the spread so a vaccine is critical. A group called GAVI helps buy vaccines for developing countries and they will play a key role once we have a vaccine being made in volume.

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How long will this go on?

This will vary a lot by country. China is seeing very few cases now because their testing and “shut down” was very effective. If a country does a good job with testing and “shut down” then within 6-10 weeks they should see very few cases and be able to open back up.

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Won’t a rebound happen after the shutdown ends?

It depends on how you deal with people coming in from other countries and how strong the testing effort was. So far in China the amount of rebound being seen is very low. They are controlling people coming into the country very tightly. Hong Kong, Taiwan and Singapore have all done a good job on this. If we do it right the rebounds should be fairly small in numbers. 

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What is the projected amount of positive cases in 1 month? 3 months? 6 months?

Any thoughts or theories as to what will happen in China when the lockdown is lifted?

Is it possible that a 2nd wave could come out?

China is not reporting much rebound. The number of cases in South Korea is going in the right direction. If people who test positive isolate themselves then the spread can be very low. The sooner people know they are infected the sooner they can isolate.

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Can you provide any estimates for how much of the world's population might become infected?

This will vary a lot by country. Taiwan, Hong Kong and Singapore acted quickly and will have very few cases. Even China will stay at a low level of their population (less than .01%) so far. Thailand is another exemplar. Unfortunately in poorer countries doing social distancing is much harder. People live in close proximity and need to work to get their food so there could be countries where the virus will spread broadly.

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Given the economic impact of COVID-related social distancing, isolation, and quarantine, is your foundation committed to anything beyond direct medical intervention? For example, increasing funding to food banks, politically supporting bills that provide income/sick leave for workers, etc.?

The Foundation is focused on its area of expertise which is diagnostics, therapeutics and vaccines. There will be lots of opportunity to give to social service organizations including food banks and I am sure people will be generous about this. Once we know who tests positive we can figure out how to support them so they can stay isolated and still get the food and medicine they need.

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I have friend who is an NHS doctor. Since yesterday he is working without masks as they have run out. Who is hogging all the masks?

I am sorry to hear this. This is an example of why we need the social distancing to minimize the number of cases and why we need the national testing network and database to get running as soon as possible.

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What about the NY Times report that just came leaking a government document saying this will be 18 months with “multiple waves”?

There are many models to look at what will happen. That article is based on a set of assumptions derived from Influenza and it doesn’t match what has happened in China or even South Korea. So we need to be humble about what we know but it does appear that social distancing with testing can get the cases down to low levels.

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But when they open back up is not like starting over? The total number of cured vs those who can still be infected is still small.

The goal is to keep the number infected to a small percentage. In China less than .01% of the population was infected because of the measures they took. Most rich countries should be able to achieve a low level of infections. Some developing countries will not be able to do that.

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Do you believe the news coming out of China though? It’s hard to at this point.

China is doing a lot of testing. South Korea is also doing a good job of testing. Once China got serious in January they have been quite open about their cases so yes the good news is they are seeing very few infections at this point. The US needs to get its testing system organized so we see what is going on.

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What precautions should I take when delivering things such as groceries to my grandparents to limit my exposure to them?

Hand washing is key. Keeping a distance. Having someone else do it if you have a fever or are coughing.

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Why are we not on a lockdown yet?

We are going into lockdown but as usual in retrospect we should have done it sooner. The sooner it is done the easier it is to get the cases down to small numbers.

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How is the economy likely to recover after all of this in your opinion?

Yes eventually. The economic impact of the “shut down” will be large but if it is done well (including the testing piece which I keep mentioning) eventually we can open back up.

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What do you see as the long-term strategy for fighting this pandemic and do you feel like it will adequately prepare us for the next?

I think that after this is under control that Governments and others will invest heavily in being ready for the next one. This will take global cooperation particularly to help the developing countries who will be hurt the most. A good example is the need to test therapeutics wherever the disease is to help the whole world. The Virus doesn't respect national boundaries.

                                https://www.gatesnotes.com/Health/A-coronavirus-AMA