“Systems Therapeutic for Physiological Renormalization,” A Paradigm Shift in Therapeutics

As Dr. Thomas Kuhn, a former physics professor at Harvard and Berkeley, taught in his book, The Structure of Scientific Revolutions, scientific fields undergo periodic “paradigm shifts” rather than progressing in a linear and continuous way, and that these paradigm shifts lead to new approaches in understanding what scientists would never have considered valid before. Such a paradigm shift is now underway for drugs and therapeutics, and has been described as “Systems Therapeutics for Physiological Renormalization.” Until now, the paradigm for drug and therapeutic development has been reductionistic, where a small molecules was developed to target one pathway in an attempt to remedy the diseases or condition. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, long believed to be the oracle for teaching pharmacology to physicians and other practitioners, taught that “the small molecule had to specifically hit its target, and only its one target.” That is, develop a drug that specifically hits one target, and only one target, and that is the best way for drug development. However, most diseases and conditions involve many perturbed pathways, and a drug that targets only one of these many pathways is a drug doomed to failure or suboptimal therapeutic effect. Such is the case for well over 50% of the FDA-approved drugs on the market today, they don’t work. The drugs that don’t work include many cancer drugs, that are toxic and only cause harm. While this problem has received media attention, the world’s largest lobby, the medical-industrial complex, drowns out these reports by saturating the media with drug propaganda. This problem only became worse when physicians, such as Francis Collins, ushered in genomic fashionistaism, teaching that the small molecules should not only hit just one target, but that the target should be at the level of the genome. As Dr. Stephen Rappaport, Ph.D. at Berkeley teaches us, over 90% of diseases are caused by our exposome and the genome is not the underlying cause. Yet, Collins in all of his ignorance, called for genetically sequencing everyone, carrying your genetic sequence on a card that can be read by physicians, such that the physician can then treat you based on the information contained on your “genomics card.” Another physician, Leroy Hood, was quoted as saying, ” your entire genome and medical history will be on a credit card. You just put it in there [a computer] and a physician will instantly know what he’s dealing with.” Besides irrational thought underlying Collin’s call for a “genome card,” fraud was in his calling to make such ignorant claims. When found out, Collins said, “the significance and the scope of the fabrication in this circumstance, of which I had not the slightest idea, began to be very apparent.” In other words, Collins had no idea what was going on in his lab, and was attaching his name to “scientific papers” of which he had nothing to do with. This is called “ghostwriting,” where physicians put their names on “scientific papers” yet have had nothing to do with the study. The practice is rampant for practitioners, i.e. physicians. Leading other physicians astray, who control over 95% of biological research spending in the US given that physicians control the National Institutes of Health, Collins would cause biological research in the USA to be highly biased towards looking for diseases in all the wrong places – the genome. This bias continues today and has been taken to such an absurd level that almost every gene studied has been linked to a disease. Further upsetting those who believe that mutations in the genome underlie disease, is that mutations in the genome don’t happen just by chance, but are driven by environmental influences. Basically, one’s health status is not only influenced by your current environment acting at the protein level of your body, but also by what your ancestors experienced in their environments acting on their genetics and epigenetics. So what you do in life, including your diet, directly effects your health and can cause most diseases, but also will have consequences to your children and their children. As such, when what one has experienced in life disrupts their physiology, mostly acting at the protein level of the body, the resulting disease can be treated by renormalizing the physiology. This means, renormalizing the protein (and other molecules such as lipids) content of the afflicted tissues. As an example of the therapeutic benefit of this “systems therapeutic for physiological renormalization” approach, our group has demonstrated its efficacy in the skin for a number of conditions, including radiation dermatitis in cancer patients. The approach was also shown by Maguire and colleagues to be effective in protecting the nervous system from neurodegenerative diseases in an experimental animal model. The safety of this technology has been demonstrated, and the mechanism of action partially described. The approach has also been discussed in an interview of Dr. Greg Maguire by Dr. Tom Kleyman of the Physiological Society. Dr. Maguire has also recently described in a journal publication, Human Vaccines and Immunotherapeutics, how the “systems therapeutics for physiological renormalization” approach may help to make safer and more efficacious vaccines, helping to better prevent the spread of the disease. Stay tuned, there is much more to come, including our approach in treating immune and autoimmune conditions as I began to describe in my 2021 paper.

California’s Emerging Lithium Valley at the Salton Sea: Will California Overtake Germany as the World’s Fourth Largest Economy?

California is the fifth largest economy and the innovation hub of the world. In 2020, California accounted for $84.3 billion in Venture Capital investment, while #2 New York had $17.8, Massachusetts $15.9, and lowly Texas just $4.4. With 3 of the 4 top tech hubs (#1 San Francisco Bay Area, #3 Los Angeles, and rapidly growing #4 San Diego; NYC area is #2), California is an industrial giant and the world’s leader in industries such as aerospace, green technology, and biotech (which far exceeds that of #2 New York). Number one San Francisco Bay Area includes Silicon Valley’s hub, the most inventive city on the planet, San Jose. Having previously started the semiconductor and computer industry, the internet, and biotech, California has created another industry. The electric vehicle revolution, powered by lithium ion batteries, has begun, with much thanks to the two engineers who founded Tesla, Marc Tarpenning and Martin Eberhard, working in Berkeley, and to government funding from the Obama and Biden administrations and the state of California. The state of California is booming as its policies and funding propels the EV revolution, and with a $97 Billion surplus this year and $75 Billion last year, California is investing in green technology, including major investment in the state’s grid to meet the anticipated electrical demand. Yes, government does most of the risk taking and funds most innovation. As Dr. Mariana Mazzucato, Ph.D., professor of economics, says, “Every major technological change in recent years traces most of its funding back to the state.” If you’re reading this on a computer or a mobile phone, almost all aspects of the technology allowing you to read this article was government funded. The US government and State of California funded the 2nd generation transistor (created at UC Berkeley) powering the chipset in your device. For example, relating to EVs, as we continuously watch the fire and explosion of Tesla automobiles because of a number of reasons, including spontaneous combustion, and phantom braking, faulty camera systems, broken suspension, or the autopilot system fails and crashes the car, leading to a battery explosion and long lasting fire, government funded companies, such as Safecore in Carlsbad, CA (this is a beautiful tech hub in North County San Diego), are focused to solve the problem that Elon Musk ignores., forcibly hides, and knowingly allowed to continue despite safety issues. Elon Musk’s “hubris” is leading to a huge downfall of Tesla. As Dan O’Dowd, a Caltech trained engineer and successful creator of safe software writes, we simply don’t know how dangerous the Tesla autos are because Tesla fails to release the necessary data to understand Tesla crashes. Although what Musk has done to harm Tesla diminishes the image of the EV industry in general, since the days of Jimmy Carter’s creation of the DOE and his promotion of the solar industry (including solar panels on the White House), many have understood the importance of moving away from fossil fuels to renewable energy sources. President Carter is a Naval Academy trained nuclear engineer, who was called in to lead the team to diffuse North America’s first nuclear reactor meltdown, so he has had a deep understanding of energy systems and understood early-on the importance of solar. However, when Reagan, a near-moron who dressed well, subsequently became president, he lacked this understanding and had the solar panels removed from the White House. Despite Republicans failing to understand the importance of solar, solar technology would continue to be developed as Germany, Japan, and China would take the US-developed technology and commercialize it. Obama would restore a national energy plan that Carter had started. Thus, the energy needed to recharge batteries will come from a number of sources, including solar panels that were invented at government funded Bell Labs, and the lithium ion batteries were invented by groups of scientists at the State University of New York and the DOE, after the whole field of lithium ion electrochemistry was started at Berkeley Lab in California in the 1950s. EVs need computers to manage their electrical system, and the transistor in computers was invented at government supported Bell Labs and later commercialized in California with support from CalTech professor Dr. Arnold Beckman, Ph.D. The next generation transistor, the 3D transistor, commercialized by Intel, was invented at UC Berkeley by Dr. Chenming Hu, Ph.D. an immigrant from Taiwan who was educated at Berkeley. Constructing circuit boards composed of many transistors was made possible by another technology invented at Berkeley, the SPICE program that allowed integrated circuits to be analyzed so that they could be properly constructed. Now, scientists at UC Merced and UC Santa Cruz have discovered that solar panel canopies over California’s massive canal system have multiple positive effects, including more efficient solar panels due to the cooling effects of the water on the panels and also that shading the water leads to much less evaporation and more available water. Working with the universities, the state of California, and the Trulock Irrigation District, the private company Solar AquaGrid in Marin County is spearheading this new project. Project Nexus as it is called, is innovative and will be widely deployed over the coming years and feed efficient solar energy into battery storage systems throughout the state of California. Monitoring and protecting the grid and all that is attached to it is a company called Siloxit in Concord. They’ve developed sensors and communication methods to monitor the integrity of the grid. If the Siloxit technology finds a problem, ALD Technical Solutions of San Diego (ranked the 2nd most inventive city in the world) can fix it with their new composite repair technology. Their technology was developed with the help of CalTestBed, a California funded program at UC campuses to support the development of green energy. California’s universities are not only educating the high-tech workers for these industries, but are instrumental in developing and deploying new technologies. Another innovation occurring in solar panels is the development of transparent solar panels originally invented at MIT and Michigan State University and being commercialized by Ubiquitous Energy in Redwood City. Under intense study, imagine the enormous amount of energy that could be generated by these organic solar panels if they covered the many “glass skyscrapers” in our cities. And solar tiles for roofing applications are now being made by GAF Energy in San Jose (the most innovative city in the world). This is actual roofing solar technology that works, not the fraudulent solar tiles that Elon Musk was selling, for which he was taking $1,000 deposits. An enormous amount of capital and talent is flowing into the EV revolution. While some people spend their days on Twitter pretending to have founded companies and created the company’s technology, many others are quietly doing that actual work. As examples, Blue Current in Hayward, California was founded by UC Berkeley professor Dr. Nitash Balsara, Ph.D. and Stanford professor Dr. Joseph DeSimone, Ph.D. with $30 million from Koch Strategic Platforms. They are pioneering a solid-state silicon technology for EV batteries, an alternative to the massive lithium ion battery industry. And in Berkeley, scientists from the Berkeley Lab founded a company, Poly Plus, making a new lithium solid state battery with a glass (thin and conducts ions) protected lithium anode that greatly increases charge density. SK Batteries, one of the largest battery producers, has partnered with Poly Plus to develop this new technology for their batteries. The world’s first technology incubator, Teknekron, was formed in Berkeley in 1968 by Harvey Wagner and Berkeley professor, Dr. George Turin. Their program of “guided entrepreneurship” led to the successful formation of many tech companies, and many young tech entrepreneurs who would go on to help build the “Silicon Valley,” the place that undergirds the EV revolution, which is anchored by Berkeley, whose graduates created Apple, Intel, Google Earth, Marvell Technologies (developed in-car WiFi connectivity), Tesla, and Lucid Motors, and Stanford, whose graduates created Google, Nividia and Hewlett-Packard.

Beyond the fact that CO2 in the Earth’s atmosphere continues to rise and has reached it’s highest level in history, not to mention death-causing pollution such as PM2.5 (small, 2.5 micron particles that traverse through the lungs), weaning ourselves from vehicles powered by petroleum and gas is especially important during times when murderous dictators, such as Putin and even the Texas oilmen, lawyers, and bankers who support Putin, control much of the world’s hydrocarbons. Texas is the leading emissions producer in the US, accounting for 15% of greenhouse gases in 2019. Elon Musk is trying to make pollution in Texas worse by drilling for gas in the state, and by destroying a nature preserve in Boca Chica in violation of an FAA agreement, and for no reason other than to watch failed spaceships explode in an inane stated goal to colonize Mars. And, while Texas discourages, even punishes, companies who are moving to more sustainable energy practices, California promotes the movement of a clean energy industry. Part of the regressive policies in Texas include their independent, deregulated power grid that frequently fails, not only killing people, but also shutting down businesses. Few electric cars are currently sold in Texas compared to California, but should Texans want to use EVs in the future, their grid will not support a significant move in that direction. Moving clean energy forward in the US has been, particularly in places like Texas that is hydrocarbon-centric, and continues to be difficult in the face of conservative politicians who receive dark money from these dirty corporations. For example, the FBI charged Larry Householder, Ohio’s Republican Speaker of the House, with a conspiracy to pass a $1.5 billion bailout in return for $61 million in dark money. The racketeering was allegedly orchestrated by Householder and the utility FirstEnergy to kill Ohio’s renewable energy law and prop up aging coal and nuclear power plants. Despite the piles of cash funneled to Republicans from dirty energy companies, legacy automakers are now racing to catch the company that two engineers, Martin Eberhard and Mark Tarpenning, founded in 2003, Tesla Motors (https://www.youtube.com/watch?v=eblPwXFb7TE). The two made a great combination given that Martin Eberhard had trained as a mechanical engineer at the Univ. Illinois, and Marc Tarpenning had trained as a computer scientist and electrical engineer at UC Berkeley (Berkeley fosters the 2nd highest number of entrepreneurs, 2nd only to Stanford in nearby Palo Alto). The combination of talents was perfect for developing an electric car. Working hard and quietly, not spending their days on Twitter, Eberhard and Tarpenning had the vision, created the company using their own money, developed the technologies that underly Tesla’s success (e.g. motors, electric battery packs, and gearing), and led the team that designed Tesla’s first two models. Martin and Marc had been influenced to build an electric car when they drove the iconic tzero built in San Dimas by AC Propulsion, an electric propulsion company led by a number of CalTech alumni. The work at CalTech on sustainability will grow exponentially in the coming years as the university’s new $750M Resnick Sustainability Center has broken ground. Had the erratic Elon Musk not been so wealthy and able to take control of Tesla, Eberhard and Tarpenning would have built a better car than what Tesla currently makes. As Sandy Munro has said, “If that car [Tesla] was made anywhere else, and Elon wasn’t part of the manufacturing process, they would make a lot of money.” According to Consumer Reports in 2021, Tesla ranked 27th out of the 28 auto brands for reliability. Sandy Munro, who takes apart and reverse-engineers cars to assess quality, issued a brutal appraisal of the Model 3 citing “flaws that we would see on a Kia in the ’90s.” He noted inconsistencies such as uneven gaps between exterior panels and paint job issues, saying “I can’t imagine how they released this.” One Tesla customer reported that his roof fell off. Others report the paint peeling off. The flaws in Tesla automobiles are even worse than stated by Sandy Munro. In Germany, all cars must be inspected by the TUV to make sure dangerous flaws don’t exist. Upon inspection by the TUV, Tesla cars are failing. One in ten Tesla cars inspected by the TUV are defective, the worst EV on the market. Structural problems have been found that may explain why Tesla cars can explode. One in 20 Tesla autos have had a serious no-start situation or a breakdown serious enough that it had to be taken off the road. Musk, in a hostile takeover, having stumbled into a PayPal fortune despite not working for and not being a founder of PayPal, gained control of Tesla and ruined what was once an innovative company making innovative cars. Musk would create a cult to hide the nonsense that he had orchestrated at Tesla. Now under Musk, Tesla “lacks a low carbon strategy” and “codes of business conduct,” along with racism and poor working conditions reported at Tesla’s factory in Fremont, California, led to the company being dropped from the S&P 500′s ESG index. Now that Musk has used government money from the US and California, taxpayer’s dollars, to monetize the company that others built, he doesn’t wish to share what we, the people, helped him to monetize. True to form, Musk moved Tesla from the land of innovation, California, to the land of where the technology was innovated elsewhere and monetized by Robber Barons, Texas. Texas is a place where Musk will be able pay employees wages so low that he later apologizes for his contempt of workers and continues his polluting of the environment without consequence. Pollution is rampant in Texas, and Tesla will fit well into the lax environmental laws of Texas. Perhaps Elon will find hydrocarbon deposits at the Round Rock factory and drill there. Having diesel powered back-ups is one of his tricks to fool his cult following. What Musk is doing matters, because he is using huge amounts of capital that could be otherwise used for sound and useful purposes. To better subvert free speech, and to self-promote and espouse libertarian values that enhance robber barons such as himself, Musk purchased Twitter and will take the company private. Once private and not a public company, the SEC no longer regulates the company and Musk can say and tweet robber baron proclamations without regulatory scrutiny. That’s a major sales and marketing tool for Musk, and a loss for intellectual discourse within a public forum. Controlling Twitter is also a great platform for creating the false narrative that he, Musk, founded Tesla and created its technology. Someone should give Musk a copy of Dr. Dacher Keltner’s, “The Power Paradox” so that he can learn how power and money creates what Musk has become. Professor Keltner explains, “My own research has found that people with power tend to behave like patients who have damaged their brain’s orbitofrontal lobes (the region of the frontal lobes right behind the eye sockets), a condition that seems to cause overly impulsive and insensitive behavior.” Thanks to his impulsivity, another problem Musk has brought to Tesla is his obsession with the self-driving system, a “disaster waiting to happen.” Musk refuses to talk with government officials about the problem, and gets away with it. Sandy Munro has judged the Tesla self driving system to be “crap.” More hype from Musk includes his promotion of the 4680 lithium ion battery being produced for Tesla by Panasonic. This is a bigger battery cell than what is currently used, and Musk says it’s revolutionary. But the release of the 4680, like much of what Musk promises, has not materialized and the design may have major flaws, such as electrochemical instability (teardown shows abnormal salts throughout the battery cell’s interior) and unsafe levels of heat and rapid degradation. Further, as written in the Verge about the supposed robot that Musk has promised his cult followers, with “Musk, it’s difficult to parse the reality from the smokescreen of bullshit he tends to throw out.” Musk is a man who opines on many things he clearly doesn’t understand, such as declaring the Covid-19 pandemic would be over in April 2020. Thanks to the hard work of two engineers who don’t pretend to know everything, Martin Eberhard and Marc Tarpenning, and despite Musk’s technical inabilities, but thanks to his con artist capabilities, a so-called “snake oil salesman” who builds a cult of followers using Twitter bots, last year, 2021, Tesla sold 936,000 vehicles, most of which were built in California. As Nobel Laureate, Dr. Daniel Kahnman, Ph.D. teaches us, “luck plays a large role in every story of success; it is almost always easy to identify a small change in the story that would have turned a remarkable achievement into a mediocre outcome.” Musk has been very lucky, starting with his birth into a wealthy family, followed by being associated with geniuses who have created technologies and companies from which he would prosper.

Solar energy the least expensive energy available today, will fuel this revolution by charging the batteries. Massive solar energy products are underway in California. For example, Clearway Energy Group in San Francisco is developing a project with 482 MW of solar power and 394 MW of energy storage capacity in San Bernadino. To put this value into perspective, 1 megawatt of solar power generates enough electricity to meet the needs of 164 U.S. homes (so the project powers close to 80,000 homes). In Oakland, California, a startup called Leap Photovoltaics is working on a redesigned solar cell that could cut the cost of manufacturing in half. As these solar panels age and need to be recycled, start-up SolarCycle in Oakland will bring these used panels into the circular economy. The power of solar to electrify our grids was recently demonstrated by California when 100% of the state’s energy was derived from clean energy, mostly solar, sources on April 30, 2022. In 1995, the US made about 40% of solar panels worldwide, but today it’s about 5%. Technologically advanced solar companies in the US, such as Solyndra in San Jose, would lose market share and go bankrupt as Republicans in the US Congress failed to support our companies when the Chinese dumped cheap, subsidized solar panels on the market. Once the Chinese force the US solar companies into bankruptcy, it’s the Chinese who then buy the companies to acquire their technology and expertise. The Chinese continue to drive US companies into bankruptcy as Republicans continue to believe in something that doesn’t exist, namely “free markets.” This continues to happen today. Also in San Jose, Auxin Solar, a manufacturer of solar panels, acting through a petition to the Dept. of Commerce, continues to fight unfair Chinese government supported solar panel manufacturers. Although the Obama, Trump, and Biden administrations have placed tariffs on Chinese solar panels, the Chinese skirt these tariffs by selling their panels in the US through shell companies located in non-tariff countries. An easy bolster to US manufacturing, including solar panels, would be the Build Back Better bill in Congress, which won’t be passed because of Republicans along with Senator Joe Manchin who continue to allow the Chinese to surpass the US in technological capabilities. As an example, the US government has solar powered vehicles on Mars, including a flying helicopter, remotely controlled from Earth, while billionaire-led space companies, subsidized by NASA technology and by diminution of the billionaire’s taxes, recreate what NASA did 60 years ago, putting men into suborbital space. The transfer of economic output of the US from government technology programs to billionaire technology programs, where billionaires take polluting joyrides into suborbital space occurs as the Chinese government, using the old US playbook where taxes drive new technologies, new companies, and new industries, means that the Chinese now have their own space station, a successful lunar lander, and a space ship orbiting Mars. More to the point, the Chinese government has positioned their country into a place of EV dominance by supporting its home industries and leveraging the continued weakness of US Republicans to understand how to build and support, for the long-term, US industries. As the US has embraced Reaganomics, China has embraced the successful economics that Eisenhower and Kennedy used to build the world’s most advanced country. Sadly, the US can no longer even build the most advanced semiconductor chipsets as Reagan failed to support the building of new advanced fabs in the US, while Japan did. The trend continued until President Biden announced government funding to the US semiconductor industry to regain our lead in semiconductor manufacturing and design. EVs, and many things electronic, don’t work without advanced semiconductor chipsets. For example, Tesla uses chips from Intel and AMD, both located in the Silicon Valley. The “government is not the solution, it is the problem,” and “I don’t want intellectuals in my government” mindset espoused by Reagan, and taken to heart by right-wing shibboleths, would allow the Japanese, Germans, and Chinese to overtake the US in most areas of high tech. Want the world’s most advanced semiconductors, go to Taiwan or South Korea. Want solar panels, go to China. Want lithium ion batteries, go to Japan (Panasonic makes the batteries for Tesla). And for innovation, as a country, Germany is the leader. The Reaganesque euphemism for allowing US high tech manufacturing to move overseas in quest of quick bucks would be, “we’re building a knowledge-based economy.” Dr. Andy Grove, Ph.D., the successor at Intel to Dr. Gordon Moore, Ph.D., Intel’s founder, both of whom were educated in chemistry at Berkeley, warned us many times about this “knowledge-based economy” nonsense. The importance of manufacturing was told to us back in 1987 when two Berkeley professors, Stephen S. Cohen and John Zysman, published their treatise on the subject, “Manufacturing Matters: The Myth of the Post-Industrial Economy.” Once a country loses its high-tech manufacturing base, it forgets how to do most things, and loses its ability to innovate and scale in a new marketplace. The spoils go to those who retain a competitive manufacturing base, and that is now overseas for many high tech industries. This is important to not only semiconductors for EVs, but also for EV batteries, where the US-invented lithium ion battery is now dominantly manufactured in Asia. US companies have focused on return-on-investment (not investing in capital intensive manufacturing) and the stock market for rapid gains, and lost sight of the long-term benefits to investing in manufacturing of what they design.

Bolstering the slouching US, is the state of California where the state had more than 222,000 business startups from January 2020 through March 2021 – more than Texas and Florida combined. During this period, California accounted for nearly 16% of the country’s new business starts.  If California were a country, the state would be the world’s greatest innovator, but the rest of the US drags down what could be. Why does California lead the nation in innovation? One important reason is the world’s greatest university system, the University of California, the world’s leader in new patents. Remember, government funding creates whole new industries, such as the biotech industry when the DOE funded Nobel Laureate Dr. Donald Glaser at UC Berkeley to create the world’s first biotech company, Cetus Corporation, in Berkeley CA. That was back in 1971 before Reagan’s anti-government mentality hit the US. From the company would arise not only PCR (invented at Cetus by UC Berkeley-trained chemist, Dr. Kerry Mullis, Ph.D., a Nobel Laureate), the technology underlying many scientific advances, and many of the Covid-19 diagnostic tests, but the whole biotech industry would emerge in California and then spread to Boston and the rapidly growing San Diego area (biotech and tech sectors), the fourth biggest startup hub in the US. In the third leading startup hub in the US, behind San Francisco and New York, Los Angeles, government funding would create the internet, beginning at the University of California, Los Angeles. That was 1969, before Reagan’s “government is the problem, not the solution” mentality hit US Republicans. Thanks to recent, beginning in the 80s under Reagan, deregulation, privatization, and a drastic reduction in taxation of corporations and the wealthy, great mansions would be built in the US, but building innovation would be transferred overseas as the wealthy monetize what taxpayers helped to build. For many more examples of what government has brought us, read Dr. Mazzucato.

Those government funded solar panels aren’t the only way to collect solar energy. In Pasadena, Department of Energy-funded Heliogen is using AI-controlled mirrors to concentrate the solar energy to produce heat and other forms of power such as hydrogen. Also in Pasadena, a consortium of California universities, the Liquid Sunlight Alliance, led by CalTech is working on the molecular capture of solar energy in liquids. Stay tuned on this – even the conformational change of a molecule in liquid is a means to store energy for later use. Other new technologies, such as fusion power, will help make the energy to charge batteries like that being developed by TAE Technologies, spun-out of the University of California, Irvine, in Foothill Ranch, California and in close-by Irvine where Kronos Fusion Energy is located, and at the National Ignition Facility in Livermore, CA. Fusion reactors will create energy in the same way stars do, without toxic waste, and produce the electrical power in the coming years (about 2035 according to the Natl Academies of Sciences) needed to recharge the batteries of electrical vehicles. Some of the obstacles to be overcome in a commercially viable fusion reactor have been discussed, and include parasitic power consumption. General Atomics, in San Diego, has been doing fusion research since the 1950s, and makes many of the key components , including magnets, for the reactors. The infrastructure for these clean energy storage systems is now being built using 3D concrete printing techniques developed by RCAM Technologies in Los Angeles. Autonomous, electric construction equipment to finish the project is being made by Canvas in San Francisco. The physical layout of the construction site can now be made, more accurately and much faster, using an EV made by Dusty Robotics in Santa Clara. Other promising energy generating technologies include Low Energy Nuclear Reactions as explained by chemist Dr. Robert Tanzella (who trained at UC Berkeley Chemistry and was a scientist at SRI International in Menlo Park), currently being developed for commercialization at Brillouin Energy in Berkeley, CA. As I understand it, Brillouin Energy is using an electrolytic reaction that use hydrogen and palladium, and has been found to yield excess energy levels of between 30-400%. Another technology to store excess energy from solar and wind sources is carbon capture of thermal energy, being pioneered by Antora Energy in Sunnyvale. If you need to quantify the thermal conductance in your thermal energy storage device, look no further than Quantum Design in San Diego. Working to make solar panels more efficient by capturing and storing heat energy in the solar panels is Icarus RT in San Diego. In San Carlos, Swift Solar, founded by Drs. Joel Jean, Ph.D and Max Hoerantner, Ph.D., who trained in electrical engineering and physics, is developing perovskite solar cells instead of silicon solar cells for more efficient solar panels. And wind power is now benefitting from new vertical wind turbines by California Energy & Power in Ontario, California. Their wind turbines are more efficient than previous designs and can be easily and safely deployed close to the end user. Uprise Energy in San Diego is designing and manufacturing portable wind turbine-battery systems for mobile deployment. Among others, the US military is backing their technology. A long duration zinc bromine flow battery for the grid, called the EnergyPod, is being developed to store renewable energy by Primus Power in Hayward, CA. In San Jose, Lyten , a highly regarded battery manufacturer, is developing lithium-sulfur batteries for storage and mobility. And, of course, green hydrogen is another means by which energy will be produced and used to charge batteries. Verdagy in beautiful Moss Landing, New Hydrogen in Santa Clarita, and Bloom Energy in San Jose, founded by a NASA scientist who developed fuel cells for spacecraft, Dr. KR Sridhar who has a Ph.D in Nuclear Engineering, are using electrolyzer technology to split water into hydrogen and oxygen. Dr. Wilson Hago, a physical chemist, has created Hago Energetics, located in Thousand Oaks, to use carbon capture technology to make green hydrogen from biomass waste. In San Diego, Oberon Fuels is converting waste to low- and negative carbon fuels, including hydrogen. Mote Inc in Los Angeles is making hydrogen from wood waste, and injecting the CO2 waste into the deep layers of the geological formations that underlie Kern County’s oil fields. Calwave, a spin-out of UC Berkeley and Berkeley Lab and its Cyclotron Road incubator, is harnessing the constant power of ocean waves. All of these technologies, along with solar from companies such as Spectrolabs in Sylmar and NanoSolar in San Jose, likely have a place in generating clean energy for charging EV batteries. Companies such as 8 Minute Solar in Los Angeles implement the latest technologies into solar systems that include battery storage. While lithium ion batteries are dominant in the EV application, and new lithium ion battery technologies, such as a new mechanical wave technology from UCSD spinout, SonoCharge in San Diego, other battery technologies may also work well, and complement lithium ion. For example, Enzinc located at the UC Berkeley Richmond Station in Richmond CA, has developed a new 3D sponge technology that allows zinc to be safely and efficiently used as the battery’s ion. While lithium may have a greater energy density than does zinc, the zinc sponge battery has less energy loss than the lithium ion batteries. Enzinc is funded by the CalSEED program, which is The California Sustainable Energy Entrepreneur Development Initiative, a $24m grant program created to help early stage California clean energy startups bring their concepts and prototypes to market. CalSEED is administered by CalCEF Ventures, in Oakland, on behalf of the California Energy Commission. Sodium ion batteries have already been commercialized by Natron Energy in Santa Clara, and a sodium all solid-state battery system is being developed by Unigrid in San Diego. In San Francisco, NDB is developing self-charging batteries, the so-called Nano Diamond Battery, that is powered by recycled nuclear waste. CO2 is produced to some degree in most manufacturing processes, including green manufacture of solar panels. Other means to store solar energy include using compressed air, being developed by Kepler Energy Systems in Sacramento. To capture the CO2 that is generated during manufacturing of these technologies, Twelve, located in Berkeley, has a process that is capturing carbon from CO2 in the air for use in making industrial chemicals, part of the circular economy. And in nearby Pleasanton, Kiverdi, led by Dr. Lisa Dyson, a physicist at Berkeley Labs, is using carbon capture to make a number of commercial products, including food at its subsidiary, Air Protein. Carbon capturing algae is used to make a substitute for plastic, algae pellets, by Loliware in San Francisco. Green, synethetic fuel is being made by Prometheus Fuels in Santa Cruz using carbon capture, with a large investment from BMW and venture capital, while algae is being used for carbon capture to make synthetic fuel by Viridos in San Diego, with manufacturing plants at the Salton Sea. Spun out of UCLA is CarbonBuilt in Los Angeles, using carbon capture to make concrete. And in San Carlos, Ebb Carbon uses an electrochemical technique to draw carbon from the air and sink it into the ocean. Organic waste is converted to hydrogen by Kore in Los Angeles, and also in Los Angeles, stuff in the dump goes to the pump when Wasteful converts garbage to fuel. Electrolysis equipment for some of these carbon capture technologies is made by Aepnus in Oakland, founded by two Berkeley alum.

Many EV manufacturers call the state of California home, including the four different Tesla factories in the Fremont area, currently covering a floor area of almost 7,000,000 sq/ft (https://en.wikipedia.org/wiki/List_of_Tesla_factories) and plans to greatly expand even more in California. The electric motors themselves are becoming more efficient for many reasons, including additive manufacturing technologies that replace coil winding in the motors, produced by Elmworks in Berkeley. Energy management systems for these EVs is critical to their performance and has been developed for many of the cars, including Tesla, by AutoMotivePower in Los Angeles. Some of the other EV companies include Lucid in the Silicon Valley. The Lucid Air, with over 500 miles range on one charge, was awarded Motor Trend’s 2022 Car of the Year. Lucid uses a Nvidia, located in Santa Clara, chipset to implement its self-driving technology. Peter Rawlinson is the CEO of Lucid, having left Tesla, where he was VP of Vehicle Engineering before leaving because of Elon Musk’s bizarre behavior and huge ego. Mr. Musk creates competition for Tesla by bleeding talent. Parenthetically, Musk is not only not the founder of Tesla or PayPal as he claims, but also not the founder of reusable rockets. Masten Space Systems in Mojave, CA first developed reusable rockets, which captured the imagination of Musk (at 4 min into the video, the reusable rocket is shown). Masten is currently developing a lunar lander for NASA along with a GPS system for the moon. Faraday Forward in Los Angeles, who has their manufacturing plant in Hanford, CA, which is on the California High Speed Rail line, is expected to begin production Q3 2022. California’s high speed rail, will be all electric, and the cars will be built in Sacramento by Siemans Mobility, which builds hybrids and all electric trains. Faraday Forward is led by Dr. Carsten Breitfeld, a doctor of engineering and founder of Byton and former VP of engineering at BMW. As one might expect of a company led by a doctor of engineering from Germany with experience at BMW, the Farady Future is technologically advanced, more so than the Tesla vehicles, well engineered, and has been reviewed very favorably by industry technologists. Some of the other EV companies include Zoox in Foster City, Karma Motors with its design center and manufacturing in Moreno Valley, Rivian in Irvine with its highly rated truck (the aforementioned Sandy Munro loves this truck so much that he bought one) and another company in Irvine is Alpha with its much talked about Wolf, Fisker in Manhattan Beach, Mullen Automotive in Brea, Eli Electric Vehicles in Long Beach, Indie EV in Vernon, Edison Future in Anaheim, Seres in Santa Clara, truck makers XOS in Los Angeles, Motiv in Foster City, Battle Motors in Venice, Boulder Electric Vehicles in Chatsworth and Vantage Vehicle in Corona, Green Power Motor Company in Los Angeles building purpose specific trucks, such as school buses, Taylor-Dunn in Anaheim building electric utility vehicles. Phoenix Motorcars in Anaheim builds medium duty electric trucks and forklifts. Wrightspeed in Alameda, founded by Ian Wright, who helped to found Tesla, converts ICE trucks into EVs. In Harbor City, Balquon is building large drayage EVs, buses, and EVs for use at ports. Although Canoo was founded in Torrance, and still maintains engineering facilities there, the company moved to Arkansas (bad move given Arkansas is the 4th worst state to live) after it received funding from investors in that state. Making a successful auto company is difficult and capital intensive, and many will not succeed. Canoo is likely one that with fail. Aptera in San Diego and Humble Motors in Los Angeles both build solar/battery designed EVs. Aptera’s solar car uses a radical design, including a fuselage-like body to reduce aerodynamic drag, and 3 wheels with motors at the wheels to reduce mechanical friction. If you live in beautiful San Diego, where the Aptera is made, the sun shines almost everyday for at least some part of the day- meaning you’ll never need to plug-in your car because the solar panels do the charging. Ampere Motors of Santa Monica offers three-wheel electric vehicles. EV companies also include the bus makers BYD and Proterra in SoCal, electric tractor makers Soletrac in Santa Rosa, Monarch Tractor (a CNBC top 50 disruptor) in Livermore, and ZTractor in Palo Alto, small electric commercial vehicles made by Karrior Transelectric in Gardena and by Biliti Electric in Culver City, motorcycle makers Zero Motorcycles in Scotts Valley (Santa Cruz area), Onyx in El Segundo, and Lightning in San Jose, small last-mile delivery bikes made by URB-E in Los Angeles, VEO in Santa Monica, an e-scooter and e-bike-sharing startup, Razor making escooters in Cerritos, Boosted making electric skateboards and skooters in San Rafael, Electric Bike Co in Costa Mesa and Bird Bike in Santa Monica making electric bicycles, Eglide making electric skateboards in Santa Monica, and Siemans Mobility in Sacramento building electric trains in a solar powered factory. Parallel Systems in Culver City, CA, is working on electric trains that are fully automated. Need to deliver a package locally, but don’t have time to drive the package to its destination? Faction, in South San Francisco has a small driverless car that can do it for you. Nuro of Mountain View has also commercialized a robotic delivery vehicle, and the next time you order a pizza for home delivery, Nuro may be the carrier. In Los Angeles, Coco has developed a small battery powered delivery cart for local use, while Serve Robotics in Redwood City has a similar tehnology. Udelve in Burlingame has developed a fully autonomous EV for multiple deliveries, which is in operation in San Mateo. Cruise in San Francisco is building the Cruise Origen, a self-driving city automobile. The Cruise vehicle is now, as of June 2022, in commercial operation in its hometown of San Francisco. And, if you need a custom designed electric vehicle, including battery design and powertrain, Evolectric in Long Beach can do it for you. Slip on your Rothy’s of San Francisco driving shoes, made of recycled plastic water bottles or your Blueview shoes, created by UC San Diego professors, made from algae that are fully recyclable, for the next car. If an EV supercar, capable of well over 200 mph is what you need, Drako Motors in San Jose can build it for you. Meanwhile, in San Francisco, Open Motors is focusing on the MaaS market. Mobility as a Service, where cars are made for and sold to large fleet companies, such as Uber Technologies in San Francisco, and not at the retail level, is forecast to be a huge, perhaps, dominant market. Even legacy automakers, such as Mercedes-Benz , BMW, Volkswagon, and Ford have EV research centers in the Silicon Valley, as well as in San Diego County where Mercedes designed their Vision EQXX. While Apple’s Tim Cook has said an Apple Car is being developed, and rumors say it will be launched in 2024 or 2025, no details have been forthcoming. Google has also been working on its own car for over a decade, and Waymo, located in Moutain View, is now Google’s self-driving car company. They also have self-driving trucks through their program called Waymo Via. TuSimple in San Diego, led by Dr. Xiaodi Hou, awarded a Ph.D. from CalTech in Neural and Computer Systems, has developed self driving cargo trucks (Class 8) that currently operate between Dallas and Phoenix. With a 2021 IPO valued at over $8.5 billion and the only company operating self driving trucks carrying cargo, TuSimple is the leader in automated driving. Embark in San Francisco, Aurora in Mountain View, and Plus in Cupertino are also self-driving cargo truck companies. These commercial trucks are aerodynamically inefficient at highway speeds where 65% of energy expended is air friction. Aeromutable in Palo Alto, a spinout of Stanford Univeristy, has an add-on active flow control device capable of reducing the power required to overcome aerodynamic drag by over 16%. In San Francisco, Pronto is is making self-driving commercial hauling vehicles. Gatik, in Mountain View, makes self-driving trucks that are hauling wood pulp and paper for Georgia-Pacific. Another company in San Diego developing autonomous driving systems is the wireless communications giant, Qualcomm, who recently announced a collaboration with BMW. Also in San Diego is the Brain Corporation that produces small robotic, electric powered vehicles, such as industrial floor cleaning robots and delivery tugs, with over 16,000 of their robots deployed in businesses throughout the world. Electric motors and drivetrains for EVs are designed and made by AC Propulsion in San Dimas. Another type of EV is the Virgin Hyperloop, based in Los Angeles, and planned to allow passenger and cargo vehicles to travel at 1,000k/hr in a vacuum tube running between San Francisco and Los Angeles. The hyperloop was originally conceived and patented in 1945 by Dr. Robert Goddard, Ph.D., the famous physicists who is the originator of liquid fuel rockets. Perhaps in another 75 years someone will figure out how to make this work, but it will require someone other than a charlatan to make it happen.

Electric airplanes, space ships, drones, and helicopters are part of the California EV revolution too, such as Wright Electric in Los Angeles, Surf Air in Hawthorne, Joby Aviation in Santa Cruz, Kitty Hawk in Palo Alto, Archer Aviation in Palo Alto, Wisk Aero in Mountain View, and Ampaire in Los Angeles (currently flying commercial flights in Hawaii). The City of Los Angeles is actively fostering this movement. Robinson Helicopter in Torrance, for the past six years, has been working with Tier 1 Engineering of Santa Ana, CA, flight-testing and refining an electric-powered version of the Robinson R44 — the world’s best-selling general aviation helicopter for the past 22 years — with more than 7,200 delivered. M4 Aerospace Engineering in Long Beach, working with UC San Diego, the #3 rated public university and 15th overall, has been funded by NASA to develop an electric powered air taxis. San Diego County not only has 3 top tier public universities, but for a variety of reasons, is rated one of the best places to start a tech comapny. Commercial drones are made by Hitec in San Diego, Inovadrone in San Diego, and Skydio in Redwood City, and commercial heavy-lift hybrid drones by Parallel Flight Technologies in Santa Cruz. Autonomous, electric air and sea vehicles for defense are made by Anduril in Irvine. Software for autonomous flight of the drones is made by Auterion in Moorpark. Another clean technology for aircraft is hydrogen power, such as that being developed by Universal Hydrogen in Los Angeles. Leaving the surface of the Earth for space can now be accomplished with electric pump rocket engines pioneered by Rocket Labs in Long Beach, CA and New Zealand. Rocket Lab’s Rutherford Engine uses a lithium ion battery to power the engine’s pump, a first in the industry and a game changer. In nearby El Segundo, part of the world’s largest space hub in the Los Angeles area, Impulse Space, founded by the co-founder of SpaceX (in Hawthorne, CA), Tom Mueller, who developed most of the propulsion systems for SpaceX, including the Merlin rocket engine, is developing new propulsion systems for ships that are already in space. Battery and solar will be part of the mix. In support of the aerospace industry, additive manufacturing (3D printing of components) is done by Morp3D in El Segundo and Relativity Space in Los Angeles. Once you arrived to your destination, the moon perhaps, get onboard the battery-solar operated FLEX vehicle from Venturi Astrolab in Hawthorne. Currently flying through the skies fighting murderous Russians in Ukraine is the battery powered Switchblade drone made by AeroVironment in Simi Valley. A more secret EV drone, called the Phoenix Ghost, deployed in the Ukraine comes from Aevex Aerospace in beautiful Solana Beach, part of North County San Diego. Analysts speculate that the Phoenix Ghost is a comparatively small weapon that could be hard to see against the cloud cover that shrouds much of Ukraine in late April and in May. Medical supplies are being delivered to remote areas by drones manufactured by Zipline in South San Francisco, and Wing in Palo Alto is delivering food and medicine throughout the world. If you need to travel on the water or under the water, EVs are available. Bedrock in Richmond, CA, is developing electric submarines and Lear Boats in Garden Grove and Arc in Los Angeles can make for an electrifying experience on the surface. SeaSatellites in San Diego makes small sea-going solar-EVs for data collection. Also in San Diego, a spin-out of the Scripps Institution of Oceanography at UCSD, Marine Robotic Vehicles makes electronic vehicles for capturing data in the oceans. Of course, electric boats for use in the harbor have been available for years from Duffy in Newport Beach. Bigger electric boats, including ferries, are being built in Alameda by Switch Maritime. Impossible Mining in Pasadena makes electric mining vehicles that travel the ocean floor collecting precious metals for use in battery production. Last year, electric vehicles became California’s No. 1 export. When you order yours, don’t forget to look for the vegan leather option for the interior. Companies such as Mycoworks and Bolt Threads, both of which are located in Emeryville have pioneered making leather from mushrooms (certain mushrooms form much collagen, the same material that forms the dermis of the skin and composes animal leather), an eco-friendly, renewable source of leather.

Batteries play an important role at EV charging stations too. As an example, for rapid charging and to better keep charging stations off of the grid, companies such as Freewire in Oakland, ChargePoint in the Silicon Valley, Volta in San Francisco, Noodoe in Irvine, EV Connect in El Segundo, EV Safe Charge in Los Angeles, Sema Connect in Santa Barbara, KIGT eChargers in Ontario, Webasto in Monrovia, Amply in Mountain View, Envoy Technologies and Chargie in Culver City, and EVgo in Los Angeles use batteries, including recycled EV batteries, to generate the energy needed to recharge your EV. EV Safe Charge in Los Angeles now has a charging bot, called Ziggy, that is, itself, an autonomous EV used to charge other EVs. Rapid charging and discharge used for rapid power delivery is implemented by using super capacitors made by Maxwell Technologies in San Diego and Licap Technologies in Sacramento. Qmerit in Irvine sets-up integrated charging stations, and has partnered with Lucid. Recycled EV batteries are being repurposed by RePurpose Energy in Fairfield. New battery technologies have emerged in California too, including the solid-state lithium battery makers, QuantumScape, Sparkz, and Sakuu. Sparkz has developed a lithium-phosphate battery that it hopes will challenge the Chinese dominated manufacturing of these batteries, and is building a new manufacturing plant in Livermore. A number of new lithium ion battery technologies are being developed, for example, by Sienza in Pasadena, CA. They use a technology originating from CalTech, where the architecture of the battery increases the area of charge and decreases the distance of charge movement. Battery Streak in Thousand Oaks is developing lithium batteries based on a new technology developed at UCLA, the #2 public university in the US, by materials scientists Dr. Bruce Dunn and Dr. Sarah Tolbert, that enables fast charging times. They’ve been funded by the National Science Foundation. Battery Streak uses Niobia that charges more like a capacitor than a chemical battery where the battery charges without chemical phase change. This new material yields faster charge times, less generation of heat during charging, and extended battery life. In San Leandro, at Coreshell Technologies, a group of scientists and engineers who trained at UC Berkeley, the highest ranked university in the US, have developed a new thin-layer electrode technology for lithium ion batteries. Coreshell’s new technology looks so promising in the short term that Tesla cofounder, Mark Tarpenning has invested. Ensurge in San Jose develops microbatteries using precise semiconductor manufacturing technologies. In Santa Clara, Gridtential is making batteries with a new silicon wafer technology. A 3d battery technology has been developed by Enovix in Freemont, and a 3d printing technology was developed by Sakuu for its sold-state battery production, a manufacturing process that saves about 30% in weight and space and makes the batteries more efficient (https://3dprintingindustry.com/news/sakuu-corporation-starts-work-on-new-pilot-facility-for-3d-printed-solid-state-batteries-194778/). New materials for batteries are developed and tested in San Diego at Wildcat Discovery Technologies. Imprint Energy in Alameda is making ultrathin, flexible, printed batteries for IoT (internet of things) devices, sensors, wearables. One of the companies making the 3D printers to manufacture these parts is Carbon in Redwood City. Safer and more efficient lithium metal batteries are being developed by Cuberg in San Leandro. In San Diego, UCSD-spinout, South 8 Technologies, has developed a new Liquified Gas Lithium Electrolyte technology that provides stability of the lithium electrolyte. They’ve been funded by the US government, State of California, and a number of private companies. To enhance battery design, AI is used by Chemix, located in Mountain View. Mitra Chem in Mountain View is developing new cathode technologies for batteries. Rapid, robotic battery swapping in EVs is being developed by companies such as Ample in San Francisco. This allows you to pull into a battery station, much the same as “paleoliths” did with their ICE vehicles at gasoline stations, and rapidly change your battery and then drive-on. Once installed, batteries are typically difficult to diagnose for remaining battery life and wear. Rejoule in San Diego makes battery diagnostics easier and is developing the means to revitalize operating batteries. Even the iconic German microscopy company, Zeiss, has an innovation center in California (Dublin) for optoelectronic innovations in battery technologies. To better distribute energy during times of great demand, energy can be stored in EV batteries during low demand periods from sustainable sources, and then, using a technology from Nuvve in San Diego, send the energy from the vehicle to the grid, so-called vehicle-to-grid technology.

Co-locating the lithium supply with battery and battery pack manufacturers such as Amprius in Fremont (they have been battery specialists for California’s huge aerospace industry of 760 companies), Sila Nanotechnologies (silicon anode technology) in Alameda, Evolectric in Long Beach, Octillion in Richmond, Romeo Power in Los Angeles, Ampcera in the Silicon Valley, OneCharge in Irvine, Totex in Torrance, SimpliPhi Power in Oxnard, Zeronox in Porterville, Enevate in Irvine, Trojan Battery Co in Sante Fe Springs, Zelos Energy in San Leandro, TerraWatt in Santa Clara, Totex in Torrance, and Flux Power in San Diego County, and EV manufacturing in a single area is a terrific opportunity for developing an environmentally friendly supply chain and removing 20 or more inefficient links from that chain. To this end, California-based Statevolt plans to build a $4 Billion EV battery gigafactory with 54 GWh output planned at Salton Sea area, supplying 650,000 electric vehicles annually. This is a new company, so how well it performs remains to be seen. Implementing these batteries into the EV is complicated, and the battery packs for EVs are a big part of the complication. CelLink in San Carlos, makes high-conductance circuits that integrate busing, fusing, voltage monitoring, and temperature monitoring wiring systems into a single circuit. This circuitry saves space and weight over traditional wiring systems. Meanwhile in Santa Clara, AyarLabs has developed a new optical input-output (I/O) technology to integrate different circuits. By forgetting wires, connectors have more speed and bandwidth, and are lighter. The company was part of UC Berkeley’s Citrus Incubator, and has garnered $130M in Series C funding and established a number of significant partnerships. Solar-battery systems are made by YouSolar in Santa Clara. Working to make existing lithium ion batteries more efficient, using a simple drop-in additive is Sili-Ion, also funded by CalSEED, in Riverside.

Lithium is a key component of the lithium-ion batteries that power electric vehicles and is currently in short supply with shortages to become worse as the world moves to electric vehicles. While other battery technologies show promise, such as trivalent Aluminum ion batteries with a large and readily available supply of aluminum, after 30 years of development they are still not commercially viable and have many disadvantages compared to lithium ion batteries that must be overcome. Lithium demand is estimated to grow 8-10X by 2030. As Dr. Ned Mamalu, Ph.D., a former geologist at the US Geological Survey, teaches us, the USA has all the minerals it needs for battery (and other) technologies, but we don’t extract those minerals for many reasons. The US government and the State of California have enabled the mining of critical minerals necessary for EV production through a number of means, including funding and tax incentives, but as Dr. Mamalu argues, more must be done to better survey what minerals are present in our lands and laws and regulations must be carefully implemented to allow extraction of those minerals. Mining those minerals on US soil is more eco-friendly than having those minerals mined in parts of the world where regulations are lax that allow massive pollution to occur. Because the US has a number of volcanic, magmatic, plate tectonic, and other geological formations, all minerals are here in the US in abundance. One of these active volcanic fields is at the Salton Sea in Southern California, and has the potential to meet 40% of the future global lithium demand (https://www.energy.ca.gov/data-reports/california-power-generation-and-power-sources/geothermal-energy/lithium-valley). The lithium brine 7,000 ft below the Salton Sea has significant advantages over mining lithium from rock sources- namely, the lithium is already in a brine, whereas when mined from Pegmatite rock, much energy is required to put the lithium in a brine. Every 20,000 tonnes of lithium carbonate per year that can be produced through a small well at the Salton Sea represents an entire open pit that does not need to be quarried and eliminates the environmental impacts of pits. (https://www.jadecove.com/research/dlecambrianexplosion). Due to the thermodynamic characteristics of producing lithium chemicals from solid rock compared to brine, millions of tonnes of CO2 emissions can potentially be avoided by unlocking more brine resources that were previously considered uneconomic because not enough people understood that there were mechanisms to produce lithium chemicals from that brine (see jadecove.com). Thus, the lithium brine in the Salton Sea allows for a difficult, energy intensive and expensive step to be skipped, and makes for a “greener” source. And, speaking of green, having the source close to the factories that use lithium-ion batteries is another step in making the process greener. Now, in a project sponsored by the Dept. of Energy, scientists from Berkeley Lab, UC Riverside, and the Geologica Geothermal Group, Inc. in San Francisco, are quantifying and characterizing the lithium in the hypersaline geothermal reservoir at the Salton Sea. Companies currently extracting lithium from the Lithium Valley include Controlled Thermal Resources, in Imperial, using technology developed by Lilac Solutions in Oakland, Berkshire Hathaway Energy and San Diego-based EnergySource Minerals. Another important “green” factor is that lithium ion batteries can be recycled, and using the recycled materials to produce new batteries works well. Companies, such as KBI in Anaheim and Repurpose Energy in Fairfield, have been recycling batteries for years and are working on new methodologies for better lithium ion battery recycling. In Carlsbad (San Diego County), Smartville is developing end-to-end, distributed solutions for EV battery reuse and recycling. The Imperial County Board of Supervisors has recognized the revolution that is occurring in the county, and has established an extensive plan to foster their natural resource. Tax incentives for businesses to build extraction plants, battery production, and battery recycling facilities are included in the plan, along with the establishment of a new Cal Poly Imperial County university to provide the educational needs, such as engineers and chemists, for the emerging energy sector in the Salton Sea area. San Diego State University is developing a campus in the area to serve the needs of the new tech hub. California’s Lithium Valley Commission is in the process of developing the world’s first Clean Energy Campus at the Salton Sea

California is the innovation hub of the world, receiving about 50% of all venture funding – that’s as much as all of the other states combined. Despite the right-wing shibboleths who will tell us that low wages, no regulations, no taxes, giving cash to companies (part of the Texas strategy), and anti-union policies are what makes a business-friendly environment, California booms by doing the opposite and does not impose regressive laws, like Texas does, that include limiting the freedom and reproductive rights of women. As the fifth largest economy on the planet, and in a major growth phase, California is a leader in new housing starts (Trump slanted the 2020 census to diminish California’s population count for political purposes, leading to a massive undercount of non-whites), new business starts, and the Golden State has no peers among developed economies for expanding GDP, creating jobs, raising household income, manufacturing growth, investment in innovation, producing clean energy and unprecedented wealth through its stocks and bonds (Winkler, 2021, Bloomberg). By adding 1.3 million people to its non-farm payrolls between April 2020 and June 2021 — equal to the entire workforce of Nevada — California easily surpassed also-rans Texas and New York. California accounts for 63% of startup Unicorns (startups with a market cap of $1B or more) in the US, with a total market cap of 79% of that for Unicorns in the US. Further, California household income increased $164 billion, nearly as much as Texas, Florida and Pennsylvania combined, according to data compiled by Bloomberg (Winkler, 2021, Bloomberg). Between January 2018 through June 2021, California created or had 133,503 companies move to the state, by far the most in the US. Of the 6,924 corporate locations in California, 18% are research and development facilities, a ratio that easily beats the U.S. overall (11%), China (15%), U.K. (14%) and Japan (10%). Only Germany, at 19%, has a higher rate, according to data compiled by Bloomberg (https://www.bloomberg.com/opinion/articles/2021-06-14/california-defies-doom-with-no-1-u-s-economy). And, let’s not count out Germany. As erratic and poor decisions are made by Musk at Tesla, Mercedes is about to launch it’s new EV that has over 620 miles of range on one charge. The engineering on the new EQXX , designed in San Diego, is excellent and the car is beautiful. As Volkswagon sells more EVs in Europe than any other manufacturer, Sono in Munich has a new solar car coming, along with BMW moving fast on new EVs. Munich is Germany’s Silicon Valley, indeed many California companies are investing there. The world’s fourth and fifth largest economies are the world’s two great innovators.

While California is home to 12% of the U.S. population, the state attracted 47% of the most sought-after investment dollars deployed nationwide last year, according to National Venture Capital Association data. The investment in California is not big simply because the state is big, because California received nearly four times its share per capita of all such investments in the USA. Add in the emerging Lithium Valley at the Salton Sea, and all that will follow in the coming green revolution that depends on Lithium, California may be poised to overtake fourth place Germany in terms of GDP. To push forward the Lithium Valley, and the EV infrastructure in general, Governor Newsom has called for reform of The California Environmental Quality Act (CEQA), a California statute passed in 1970 and signed in to law by then-Governor Ronald Reagan, that slows down building important, green infrastructure. Indeed, the Democratic led legislature has made reforms and Newsom has signed them, but more reform is needed. A big thank you to Martin Eberhard and Mark Tarpenning whose vision and hard work at Tesla for many years began this revolution, along with the state of California’s help, including many laws supported and signed by then Governor Jerry Brown, and the US government under the direction of President Obama and VP Joe Biden who, through the Advanced Technology Vehicle Manufacturing loan program, provided Tesla with $465 million during a pivotal time in 2010. Two engineers, Martin Eberhard and Marc Tarpenning, working in Berkeley, CA, using their own money along with the help of private funding from Elon Musk, who would later become CEO and diminish the quality of the cars, and funding from the State of California and the US government began this revolution, which has now expanded to the beautiful, stark, mountain rimmed desert lands of the Salton Sea.

Coronavirus Covid-19: Some Questions and Answers

Many people have been asking questions about the Coronavirus outbreak. First, if you’re scared, you should be. This pandemic is not a hoax as expressed by people like Trump and Hannity, and the USA is woefully unprepared to diagnose, prevent, contain, mitigate, and treat this exponentially spreading and deadly disease. Understand, even if you don’t die from the disease, if you are severely infected with the disease you may suffer permanent scaring in you pulmonary system, potentially resulting in lifelong  respiratory problems. Be concerned, take action, and don’t panic. Follow good public health practices such as social distancing, cleansing your hands, and not touching your eyes, mouth, or nose unless you have cleansed your hands. To best set your immune system to fight the infection and quell the inflammation induced by your immune system response to the SARS-CoV-2 virus that causes Covid-19, eat right, exercise, don’t smoke, limit or stop alcohol consumption, and sleep well. In my book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts,” I detail much of what you can do to become healthier and improve your innate and adaptive immune systems. Eat vegetables, with soluble and insoluble fiber, limit salt and sugar intake, no processed oils, including olive oil, especially coconut oil and even MCTs. I’ll now answer some of the questions I’ve been asked about Covid-19.

Why is it called the novel “coronavirus”?

Novel because we’ve never seen this virus in the human population previously. This virus probably originated in bats and then spread to other animals with whom humans interact, including those animals in our food supply. The virus is called a coronavirus because of the 3 dimensional shape of the virus; named for the crown-like spikes on the virus’ surface.

What does this mean and what is known about how the virus compares to
others in the same family?

Human coronaviruses were first identified in the mid-1960s. There are seven coronaviruses that can infect people. These types of viruses are typically responsible for common colds more than serious diseases. However, coronaviruses are also behind some more severe outbreaks, including Covid-19, SARS, and MERS. These viruses mutate in time and new strains emerge. When the virus mutates, chemical and structural changes can result that may change the viruses’ spread and infection patterns. The dangerous new strain called SARS-CoV-2 started circulating, causing the disease COVID-19 in 2018, but seriously emerged in 2019. Scientists discovered and had warned that this disease would spread in 2018, but the Trump administration had dismantled the “Predict” program begun by President GW Bush and expanded by President Obama. Trump ignored warning after warning that an outbreak was imminent. We were caught totally unprepared for this pandemic because of Trump and his lack of scientists (Ph.D.) in key positions. Scientists, such as Prof. Dr. Wayne Getz, Ph.D. at UC Berkeley have published very recently the specific needs in order to understand, predict, and contain future outbreaks, especially due to zoonotic disease, borne from animal transmission.

I’ve heard that the novel coronavirus may be spread by droplets. Can you explain what this means and what is known thus far about the spread of the virus / how long these droplets may spread the virus between humans/on surfaces?

Yes, SARS-CoV-2 virus spreads most readily in droplets originating from our upper respiratory system and transmitted to others when we cough, sneeze, and even during talking. If you’ve ever smelled onion or garlic on someone’s breath, then you’re inhaling some form of droplets from that person, including any viruses contained in their breath. While the CDC recommends distancing yourself 3-6 ft from someone who is coughing or sneezing, a study from scientists at MIT found evidence that these droplets can travel much farther. Scientists have also found that these droplets that have landed on surfaces can remain active, potentially for hours. If you touch a surface with viral droplets, and then put your hand in your eyes, nose, or mouth, transmission may occur. This is known as fomite transmission. Viruses are not alive, but we refer to them as active or inactive. If you wash your hands with soapy water or 60-90% alcohol, you’ll inactivate the virus. The virus has a lipoprotein (Fat-protein) structure that covers the genetic material to protect the fragile RNA. Also expressed on the outer surface are proteins with specific amino acid sequences that impart a number of functions to the virus, including whether it can bind to proteins in lungs or cardiovascular systems. Washing your hands or applying alcohol can disrupt the lipoprotein coat and inactivate the RNA rendering the coronavirus harmless. This is similar to what is done to inactivated viruses for the development of an inactive vaccine.

Is our healthcare system prepared for this outbreak?

No. We still have few people being tested and have no idea of the spread, rate of infection, and morbidity and death rates from this disease. People who were originally diagnosed with influenza and died have now been found to have died of Covid-19. Our hospitals and clinics are likely to be overwhelmed with severe cases of Covid-19 within a few weeks. In Germany, for many reasons, including the country is run by a scientist (Dr. Merkel is a PhD level physical chemist), has medical care for all, and their physicians who earn an M.D. degree in addition to medical training have scientific training unlike here in the USA, has responded much better to the pandemic than has the USA. Science and evidence based decision making, with scientists who are trained and experienced at solving problems, leads to better outcomes. Unfortunately in the USA our response team is run by physicians, not scientists. Fauci and the rest have done a poor job at protecting the people of the USA. Our healthcare system is a mess in general, and this becomes becomes especially transparent during these times of crisis.

If a package is handled by an infected delivery person and they coughor sneeze on the package, could you theoretically become infected by touching it?

Yes, this would be an example of fomite transmission. A number of variables would contribute to whether you become infected in this way, including the level of infection of the person sneezing, how long the droplets sat on the surface, the volume of the droplet material on the surface of the package, and how much of the droplet you transmitted to your eyes, mouth, or nose. The fomite transmission won’t occur through the skin. A number of studies found evidence that fomite transmisssion is less probable than transmission by breathing-in aerosoled droplets from a cough or sneeze that contain the virus. Be careful, because the SARS-CoV-2 virus remains stable in the air and remain active for hours, perhaps even days, on some surfaces.

How does Covid-19 kill people?

Basically they die of suffocation, even when on a respirator. This virus, SARS-CoV-2 attaches itself to a number of sites in the body using the ACE2 receptor, including in our alveoli in the lungs. This virus also seems to bind to integrins that are expressed throughout the body. This possible pathway of entry is just beginning to be studied. The virus attaches to epithelial cells in the lungs, including in alveoli, where gas exchange occurs (Oxygen comes in, CO2 goes out) and sets up of a dramatic immune response to kill the virus. Along with cells dying from the virus, in the process of our killing the infection, collateral damage occurs where our own cells are damaged or killed. The damaged cells build up in the alveoli. Also liquid begins to seep into the alveoli because the matrix that normally prevents liquid flow has been damaged. Gas exchange stops occurring in the alveoli because of debris and liquid. No matter how much oxygen you pump-in, not enough enters the blood to sustain cellular respiration. If the patient is saved using a respirator, the damaged alveoli will likely suffer from scarring, called fibrosis, with possible ensuing respiratory problems. Scientist and physicians in China report that the those affected by Covid-19 respond well to steroids. Prophylactic and therapeutic low dose steroid oral tablets/inhalers at the earlier stage of COVID-19 and high dose steroid treatment according to the severity of the disease can play important roles in decreasing the fatality and pulmonary fibrosis.

I’ll answer more in an upcoming post.

 

 

Coronavirus Covid-19: What is it, and what can be done to mitigate the spread and effects of this virus?

The Trump adminstration is ill-prepared to respond to the current Covid-19 pandemic and is spreading disinformation about the virus (Thielking, 2020). As of Feb. 23, the CDC had tested just 479 people, not including those who were evacuated from other countries. Testing kits sent out by the CDC nationwide turned out to be faulty, meaning that just 12 labs across the country can currently run tests outside of the CDC. And the CDC didn’t allow the State of California and UC Berkeley to begin testing for Covid-19, even though UC Berkeley trained the scientists who developed the technology (PCR – Dr. Kary Mullis, Ph.D.) underlying the diagnostic tests, for over a week after having set-up a testing center. And the Trump administration allowed untrained, non-garbed federal workers to be directly exposed to known Covid-19 carriers in the Davis, California area. As a result, one patient was likely exposed to one of these workers and wasn’t tested as requested by physicians at UC Davis Medical Center, and now the patient is on a ventilator fighting for her life. Trump appointed morons, such as Chad Wolf, acting secretary of the Department of Homeland Security, said, in a wildly innaccurate statement, the fatality rate is ‘similar to seasonal flu.’ Therefore it is up to you to take good care of yourself during this pandemic, because Trump doesn’t care and Pence is incapable.

Unlike their common-cold-causing viral cousins, the emergent coronavirus Covid-19 can induce a viral-induced inflammatory, immune response throughout many of the patient’s organs. COVID-19 binds angiotensin-converting enzyme 2(ACE2). ACE2 is a receptor, an entranceway for Covid-19 to the airways and alveoli, where O2 – CO2 gas exchange occurs, and blood vessel linings. Death due to massive alveolar damage and progressive respiratory failure can occur.  This is why the Covid-19 epidemic has killed nearly 3,000 people, surpassing the SARS death toll in just weeks. While the death rate for Covid-19 (about 2%) appears to be a fifth of SARS, the novel coronavirus has spread faster (spread factor may be 3-5), although the data for Covid-19 are not yet clear.

For most patients, COVID-19 primarily stays in their lungs, because like the flu, coronaviruses are primarily respiratory diseases – most of the receptors they attach to in our bodies are located in the respiratory system. The virus spreads typically when an infected person coughs or sneezes, spraying droplets that can transmit the virus to anyone in close contact. Best to avoid being near people expressing such symptoms. Coronaviruses typically cause flu-like symptoms, where patients start out with a fever and cough that can progresses to pneumonia or even respiratory failure. Based on early data from China, 80% of the Covid-19 cases are mild and don’t require hospitalization (Zhang et al, 2020).

Initial infection of the Covid-19 coronavirus rapidly invades the two major classes of human lung cells; cells that make mucus and cells with hair-like protrusions called cilia. Mucus, part of the immune system, helps protect lung tissue from pathogens and make sure your breathing organ doesn’t dry out. The cilia cells move the mucus, clearing out foreign agents like pollen or viruses. The physical movement of the cilia may also induce mechanical autophagy (Kim et al, 2017), another means to clear pathogens from our cells. Activated by the presence of a viral invader, our bodies step up to fight the disease by recruiting immune cells to the lungs, including adult stem cells that also have immune cell properties (Maguire, 2020), to clear away the damage and repair the lung tissue. Holes are created in the lung tissue by the immune system’s hyperactive response that also creates scaring that both protect and stiffen the lungs. At this point patients often require ventilators to assist their breathing. The robust inflammatory response also makes the membranes between the aveoli and blood vessels more permeable, that can fill the lungs with fluid, reducing gas exchange and affecting the aveoli’s ability to oxygenate blood. Because the receptor recognition of Covid-19 virus is similar to that of SARS, which affects receptors in the gut, and because a number of patients have reported stomach problems during Covid-19 infection, Covid-19 is likely to present in the small intestine as does SARS when it infects humans (Wan et al, 2020).

So what can be done to avoid and mitigate the effects of coronavirus Covid-19? First, make sure to follow the advice of public health officials, not Donald Trump or his political appointees. These people are numbskulls (Levin, 2019). Second, avoid people with respiratory symptoms such as sneezing, coughing, and labored breathing. Wash your hands frequently, and avoid touching your eyes, nose, or mouth without having washed your hands. Don’t be led to believe that a surgical mask protects you from the virus- it doesn’t. Only a N-95 mask works well (about 95% filtration of virus particle) if properly fitted to the face. Respiratory viruses transmit mostly through droplet spread — which is coughing or sneezing on somebody — or in some cases by fomite transmission, which means you contaminate a surface which another person then immediately touches, and then touches their mouth, nose, or eyes. Viruses can maintain themselves in active state for hours, even days on surfaces, but Covid-19 is reportedly easily inactivated by alcohol.

To mitigate the effects of a virus infection, including Coronavirus Covid-19, you should be eating a mostly plant-based diet that includes significant amounts of insoluble and soluble fiber. I explain this in my book, Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts, but briefly, without you having to read my book which is a tome, here’s why. Soluble fiber is fermented and regulates the innate and adaptive immune systems to better fight viral infection and to better resolve the inflammation induced by the activation of the immune system (e.g. Trompette et al, 2018). And insoluble fiber will upregulate the immune system in a number of ways, including to induce mechanical autophagy that helps to clear infectious agents (Kim et al, 2017). Also, eating a plant based diet rich in many types of antioxidants sets-up an antioxidant cascade (Villanueva and Kross, 2012) that also helps to fight viral infection (e.g. Beck, 2001; Crump et al, 2013). My video update on Covid-19 is here. Let’s all do our part to mitigate the spread and ill-effects of this dangerous virus so that all may be healthy.

 

References

Beck MA (2001) Antioxidants and viral infections: host immune response and viral pathogenicity. J Am Coll Nutr. 20(5 Suppl):384S-388S.

Crump KE et al (2013) Antioxidant Treatment Regulates the Humoral Immune Response during Acute Viral Infection. J. Virology, DOI: 10.1128/JVI.02714-12.

Kim SW et al (2017) Shear stress induces noncanonical autophagy in intestinal epithelial monolayers. Mol Biol Cell. 28(22): 3043–3056.

Levin B (2019) JANET YELLEN: TRUMP IS AN EVEN BIGGER IDIOT THAN HE LOOKS. Vanity Fair, Feb 25, 2019.

Maguire G (2020) Stem Cells, Part of the Innate and Adaptive Immune Systems, as an Antimicrobial for Coronavirus Covid-19. Stem cells, health, technology, Feb 23, 2020.

Thielking M (2020) Trump’s no stranger to misinformation. But with the coronavirus, experts say that’s dangerous. STAT, Feb 26, 2020.

Trompette A et al (2018) Dietary Fiber Confers Protection against Flu by Shaping Ly6c Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism. Immunity. 2018 May 15;48(5):992-1005.e8

Villanueva C and Kross RD (2012) Antioxidant-Induced Stress. Int J Mol Sci. 2012; 13(2): 2091–2109.

Wan Y et al (2020) Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J. Virology, DOI: 10.1128/JVI.00127-20

Zhang et al (2020) Vital Surveillances: The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020. China CDC. http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51

 

 

Stem Cells, Part of the Innate and Adaptive Immune Systems, as an Antimicrobial for Coronavirus Covid-19.

China is in a state of emergency, with 76,936 infections and 2,442 deaths from Covid-19. China’s leader, Mr. Xi has said, coronavirus Covid-19 is the “the fastest spread, the widest scope of infections and the greatest degree of difficulty in controlling infections” of any public health emergency since the founding of the People’s Republic of China in 1949. With 600 cases in S. Korea, parts of Northern Italia now on lockdown because of an outbreak there with 132 new cases, 7 deaths in Iran with Pakistan and Turkey having closed their borders with Iran – people are scarred (NY Times, Coronavirus update, 2020-02-23).

So how do we best fight this spreading, deadly disease? Public health measures are our first line of and most important means of defense in this newly emerging epidemic. The development of new antimicrobials is another means of potentially fighting this infectious agent. And stem cells, and the molecules that stem cells release may be an important new means of developing such antimicrobial therapeutics. Although premature, stem cell treatments in clinical trials for Covid-19 infections are currently underway in China. Why would anyone think that stem cells can fight a viral infection such as Coronavirus Covid-19? Let’s have a quick look why. But first, a quick why  not. Stem cell transplants cause the tissue in the host to age; specifically, the very cells needed to fight the infection, the T-cells, have been found to express markers for advanced aging following bone marrow stem cell transplants (Wood et al, 2016). Therefore the immune system that is needed to fight the Coronavirus infection may be compromised by the stem cell transplant. This doesn’t happen when the molecules from the stem cells are used instead of the stem cells themselves (Maguire, 2019).

Now for the rationale. First, as part of the innate immune system, stem cells release peptides, known as antimicrobial peptides (AMPS) (Esfandiyari et al, 2019) that have been found to fight viral infections (Hsieh and Hartshorn, 2016). Stem cells are activated by viral infections to release these AMPs, and, interestingly, the stem cells themselves are protected from the viral infection and remain normally active cells even when infection affects the tissue compartment in which the stem cell resides (Wu et al, 2018).

Now, here’s some new and very powerful research suggesting that stem cells are part of the adaptive immune system. Drs. Shruti Naik, Ph.D. at NYU and Elaine Fuchs, Ph.D. at Rockefeller University found that if patches of skin in mice were wounded, causing inflammation, then allowed to heal, subsequent wounds in the same patch of skin would heal about 2.5 times more quickly than adjacent, previously unwounded skin. The effect in previously wounded skin could last up to six months given the conditions of the experiment. This functional adaptation was attributed to epithelial stem cells (EpSCs) and did not require a canonical immune response because skin-resident macrophages and T cells were not involved. What the study found was that EpSCs maintain chromosomal accessibility, where the DNA is less tightly packed and open to signals from the damaged tissue, at key stress response genes, activated by the inflammatory stimulus. This epigenetic change in the chromatin allowed, during a secondary inflammatory challenge to the same skin patch, genes in that patch of skin to be transcribed rapidly. While the secretome of skin stem cells has previously been shown to be altered by wounding, the exact nature of changes in the secretome was not reported in this study. However, underlying the memory of the stem cells in this study is Aim2, a portion of DNA that encodes an activator of the inflammasome, a conglomerate of proteins that contributes to the skin’s defense against bacteria and viruses. An emerging area of research is quickly expanding as scientists continue to explore stem cell memory, and the field of immune-stem cell interactions, and stem cells as a part of the immune system. The stem cell functions described here also means that your health is not just genetic. What you do, including wounding yourself or having an infection may have long term consequences to your health. And optimizing your health, including through diet, will minimize the negative consequences of these wounding events or infectious events, including viral infections (Maguire, 2020).

Wu and colleagues discovered that stem cells are hardwired to express antiviral interferon-stimulated genes (ISGs), which help them fight viral infections. Further, β-glucan, a bacterial and fungal cell wall component induced IL-1β release, which was capable of training both hematopoietic stem cell (HSCs) and myeloid progenitors. These conditioned HSCs and myeloid progenitors were able to more efficiently ward off inflammatory challenges when compared to naïve HSCs. Further, IL-1β-trained HSCs exhibited dramatic changes in their energy metabolism, displaying augmented glycolysis and cholesterol biosynthesis, adjustments that turned out to be critical for conferring downstream functional changes in β-glucan-dependent HSC training (Mitroulis et al., 2018). Combine this stem cell training with conditioning of the canonical adaptive immune cells, T-cells, through a high fiber diet that induces a allostatic state (Sterling, 2020) and is pro-resolving for viral infections (Trompette et al, 2018). What I’m describing here is a “systems therapeutic” for “physiological renormalization” (Maguire, 2019) so that the body can better fight the viral infection and more quickly and efficiently resolve the ensuing inflammation that induces much of the damage to the body.

So what can you do now why scientists are working on new antimicrobial therapeutics to fight Coronavirus Covid-19? First, follow public health measures as instructed by your local health authorities. Second, eat well, including a predominantly whole food plant based diet that includes soluble and insoluble fiber that will set the immune system in a state to better fight the infection and resolve the inflammation (Trompette et al, 2018; Maguire, 2020) and may induce mechanical autophagy in the gut to help clear infection (King, 2012). Like stem cells that release a rich variety of antioxidant types (Hong et al, 2019), eating predominantly plants will also provide a rich variety of antioxidants to setup the antioxidant cascade (Villanueva and Kross, 2012) to help quell the viral infection (Beck, 2001; Crump et al, 2013). More on this subject can be found in my book, Thinking and Eating for Two (Maguire, 2020).

References

Beck MA (2001) Antioxidants and viral infections: host immune response and viral pathogenicity. J Am Coll Nutr. 20(5 Suppl):384S-388S.

Crump KE et al (2013) Antioxidant Treatment Regulates the Humoral Immune Response during Acute Viral Infection. J. Virology, DOI: 10.1128/JVI.02714-12.

Esfandiyari R et al (2019) Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells. Heliyon. 2019 Oct; 5(10): e02652.

Hong HE et al (2019) Antioxidant action of hypoxic conditioned media from adipose-derived stem cells in the hepatic injury of expressing higher reactive oxygen species. Annals of Surgical Treatment and Research 97(4):159.

Hsieh IN and Kevan L. Hartshorn KL (2016) The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy. Pharmaceuticals (Basel). 2016 Sep; 9(3): 53.

King JS (2012) Mechanical stress meets autophagy: potential implications for physiology and pathology. Trends in Molecular Medicine, DOI:https://doi.org/10.1016/j.molmed.2012.08.002

Maguire G (2020) Physiological renormalization using systems therapeutics. Future Sci OA. 2020 Jan; 6(1): FSO428

Maguire G (2019) Transplanted stem cells survive a long time: do they make you sick? J Roy Soc Medicine, https://doi.org/10.1177/0141076819851657.

Maguire G (2020) Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Mitroulis I et al. (2018). Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell 172, 147–161.e12.

Naik S et al (2017). Inflammatory memory sensitizes skin epithelial stem cells to tissue damage. Nature 550, 475–480.

Sterling P (2020) What Is Health?: Allostasis and the Evolution of Human Design. MIT Press, Cambridge, MA.

Trompette A,  Gollwitzer ES, Pattaroni C et al. (2018) Dietary fiber confers protection against flu by shaping Ly6c − patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity 48(5), 992–1005.

Villanueva C and Kross RD (2012) Antioxidant-Induced Stress. Int J Mol Sci. 2012; 13(2): 2091–2109.

Wood WA et al (2016) Chemotherapy and Stem Cell Transplantation Increase p16INK4a Expression, a Biomarker of T-cell Aging. EBioMedicine. 2016 Sep; 11: 227–238.

Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann H-H, Wang Y, Silva LAV, Sarbanes S, Sun T, et al. (2018). Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell 172, 423–438.e425.

More Evidence That A Low-Fat, Plant Based Diet Extends Healthspan and Lifespan: Low Concentration MUFAs Activate SIRT1

Studies that have looked at whether consuming a diet rich in monounsaturated fatty acids (MUFAs) leads to reduced risk of heart disease have shown mixed results. The confusion arose because it makes a difference whether the MUFAs come from plant or animal products. In the first study to separately examine types of MUFA sources in relation to heart disease, researchers found that while MUFAs from plant-based foods such as olive oil and nuts do indeed lower risk, MUFAs from animal products such as red meats and dairy do not provide benefits. The studies were of calorie matched consumption of the different fat types and did not compare low fat versus high fat consumption (Zong et al, 2018). Much evidence has accumulated that low-fat, plant based diets have numerous positive effects in the human body, including shifting the innate and adaptive immune systems to a less inflammatory state, and one that resolves the inflammation more efficiently (Maguire, 2020). In other words, the low-fat, plant based diet allows one to regain allostais through physiological renormalization, where the body is healthy and in a state of optimal responsiveness (Sterling, 2020).

SIRT1, acting through PPAR-α/PGC-1α to upregulate mitochondrial biogenesis, has a wide-range of biological functions including chromatin structure maintenance, cell cycle control, metabolism, and the regulation of healthspan. Regulation of these pathways is partially dependent upon fatty acids, specifically monounsaturated fatty acids (MUFA) .

One study has found that MUFAs do not modulate SIRT1 activity (Feldman et al., 2013). However, this study employed a fixed concentration of 18:1 (100 μM) and used the H3 peptide as a substrate. As Najt et al (2020) have found, MUFAs do not activate SIRT1 at concentrations above 1 μM and do not enhance SIRT1 activity toward the H3 peptide pathway. Thus low-fat, i.e. low concentrations of MUFAs activate the SIRT1 pathway toward the H3 peptide and provide significant metabolic enahncement. These new mechanistic data translate into a recommended regimen of eating plants that are naturally high in MUFAs, and low in other fats, such as saturated fats. Given that low concentrations of MUFAs activate SIRT1, but high concentrations do not, eating refined oils, even if high in MUFAs, should be avoided.

References

Feldman JL et al  (2012) Sirtuin catalysis and regulation. J. Biol. Chem.2012; 287: 42419-42427

Maguire G (2020) Thinking and Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Najt et al (2020) Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1, Molecular Cell (2019). DOI: 10.1016/j.molcel.2019.12.003

Sterling P (2020) What Is Health?: Allostasis and the Evolution of Human Design. MIT Press, Cambridge, MA.

Zong G et al (2018) Monounsaturated fats from plant and animal sources in relation to risk of coronary heart disease among US men and women. The American Journal of Clinical Nutrition, Volume 107, Issue 3, March 2018, Pages 445–453

True Food Kitchen – An Inflammatory Nightmare

The ever expanding True Food Kitchen (TFK) purports to be “a restaurant inspired by the philosophy that food should make you feel better, not worse.” The TFK corporation is located in Phoenix, Arizona and has about 30 locations across America, all of which are owned by the corporation and are not franchised. According to Forbes, this a rapidly growing chain and its revenue grew 46% in 2017 from the previous year (Stern, 2019). The menu at TFK offers dishes such as kale guacamole, edamame dumplings, Mediterranean quinoa, turkey burgers, and grass-fed burgers. Entrées include a poke bowl, grilled salmon and grilled fish tacos, and charred cauliflower and creamy tomato soup. To some who bobble their heads to the corporate marketing scheme, this all sounds healthy. But let’s have a look beyond the marketing hype, and delve into the nutritional value of some of the TFK menu items.

Say you start your meal with a bowl of Cream Tomato Soup. That bowl of soup will contain 18 grams of fat, 9 of which are saturated fats, and you’ll ingest 1500 mg of sodium. The recommended daily allowance for sodium is 2,300 mg. That one bowl is 65% of your daily allowance of sodium. Now if you order the chicken sausage pizza to go along with that soup, you’ll ingest 32 grams of fat, 12 of which are saturated, and 1610 mg of sodium. That just brought the amount of sodium in your meal to a total of 3,110 mg, well beyond the recommended allowance. You’ve also just ingested 50 grams of fat, of which 21 grams are saturated. The American Heart Association recommends no more than 13 grams of saturated fat per day.  Eating all this fat, including too much saturated fat, will clog your arteries and induce vascular inflammation. The nutritional chart lists coconut as one of the ingredients in the soup, such that some unknown quantity of medium chain triglycerides  (MCTs) will also be present in the soup. All of these fats, including MCTs (Haghikia et al, 2015) can have both acute as well as chronic effects on host inflammatory responses in both the innate and adaptive immune systems (Maguire 2020).  Likewise, the intake of sodium increases inflammation in the innate and adapative immune systems, and induces dysbiosis in the gut (Maguire, 2020).

Maybe you can have the vegetable crudites instead of the soup. If so, you’ve just ingested 63 grams of fat, 7 of which are saturated, and 1500 mg of sodium. This is no better than the soup, and maybe worse given the 63 grams of fat, about twice as much as in the soup. If you’ve eaten the soup and the pizza, 95 grams of fat was consumed in one meal. Eating that one meal has just exceeded the amount of fat one should eat in the entire day.

Well, you say, this meal is better than going to Burger King for a Whooper and fries. Let’s see: a Whopper has 40 grams of fat, 12 of which are saturated, and 980 mg of sodium. The fries have 10 grams of fat, 1.5 of which are saturated, and 330 mg of sodium. So the Burger King meal of a Whopper and Fries has 50 grams of fat, 13.5 of which are saturated, and 1,330 mg of sodium. The TFK meal of vegetable crudites and pizza has 95 grams of fat, 19 of which are saturated, and 3,110 mg of sodium. Thus, the TFK meal has 45 more grams of fat, 5.5 more grams of saturated fat, and 1,780 mg more of sodium than does the Burger King meal.

The point here is that neither of these meals is healthy, and the meal from Burger King is, in some ways, healthier than the meal from True Food Kitchen, a purported “health-driven seasonal restaurant.” TFK is the penultimate marketing scheme brought to you by a corporation that delivers empty words and poor nutrition, with a measure of inflammation, dysbiosis, and clogged arteries full of foamy macrophages .

References

Haghikia A et al (2015) Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity 43: 817-829.

Maguire G (2020) Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Stern G (2019) True Food Kitchen: A Growing Restaurant Chain On A Mission. Forbes, Jan. 25, 2019.

 

Immune Therapy for Cancer: Enabling and Engineering T-Cells

T cell therapies are revolutionizing cancer treatment by achieving long-lasting remission in cancers, such as melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, and leukemia and lymphoma. An important function of the immune system is its ability to discern between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells, including cancer cells, while leaving the normal cells alone. To do this, it uses “checkpoints.” Immune checkpoints are molecules on certain immune cells that need to be activated (or inactivated) to start an immune response. Cancer cells sometimes develop the means to use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints have much promise as cancer treatments. These drugs are called checkpoint inhibitors, and first originated from the work of Prof. Dr. James Allison, Ph.D. at UC Berkeley. Dr. Allison would later be awarded the Nobel Prize in Physiology or Medicine for this work.

Importantly, checkpoint inhibition is a new paradigm in treating cancer, allowing the immune system to operate normally where T-cells can once again attack the cancer cells because of the drug therapy. Unlike previous methods, checkpoint inhibitors don’t work directly on the tumor or over boost the immune system. The checkpoint inhibitors simply institute “physiological renormalization” (Maguire, 2019), restoring normal T-cell physiology. The checkpoint inhibitor works by using a monoclonal antibody, a protein, that blocks the cancer cell signaling to the T-cell’s checkpoint mechanism. Normally the cancer cell is sending a signal to the T-cell that “fools the T-cell into thinking” that the cancer cell is a normal cell and one that should not be attacked by the T-cell. Important to the T-cells acting to kill the cancer cells, even when the patient is taking checkpoint inhibitors, is a plant based diet rich in fiber. The T-cell activity on the cancer cells is facilitated by fiber consumption, allowing the checkpoint inhibitor to work better to destroy the cancer cells (Worcester, 2019). I write about this in my new book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts.”

While Dr. Allison’s work on T-cells began in 1985 at Berkeley, the same year I came to Berkeley and joined the same department, Molecular and Cell Biology, Prof. Dr. Jennifer Doudna, Ph.D. at UC Berkeley would begin work in about 2010 on a technology as revolutionary as that of Dr. Allison. As co-inventor of CRISPR-cas9 technology, along with Prof. Dr. Emmanuelle Charpentier, Ph.D of the Max Planck Institute in Germany, Dr. Doudna invented a technology that would allow cells to be engineered by editing their DNA. Using this methodology, T-cells can now be made to inherently avoid the cancer cell’s evasion mechanisms using their ability to activate the checkpoint in T-cells to stop the T-cell from attacking the cancer. Using the CRISPR-cas9 methodology, the T cell receptor (TCR) complex located on the surface of T cells, which is central for initiating successful anti-tumor responses by recognizing foreign antigens/peptides bound to MHC-molecules, the patient’s own T cells are genetically engineered to express a synthetic (transgenic) TCR that can specifically detect and kill tumor cells. CRISPR-cas9 engineered T cell therapies are just beginning to revolutionize cancer treatment by achieving long-lasting remission in blood-related cancers, such as leukemia and lymphoma. These therapies involve removal of patient T cells, “reprogramming” them to attack cancer cells, and then transferring them back into the patient. Targeted gene inactivation (knockout) using CRISPR-Cas9 can enhance T cell activity and has the potential to expand cell therapy applications (Hamilton and Doudna, 2020).

Until the study of Stadtmauer et al (2020), whether CRISPR-Cas9–edited T cells would be tolerated and thrive once reinfused into a human was unknown. Stadtmauer et al (2020) present data from a phase 1 clinical trial (designed to test safety and feasibility, but not efficacy) on the first three cancer patients treated with CRISPR-Cas9–modified T cells. Given one infusion of the engineered T-cells, the three patients did not experience the feared “cytokine storm” that patients have previously experienced in clinical trials using genetically altered cells. The authors found a high-level engraftment and long-term persistence of the infused CRISPR-Cas9 engineered T cells in one of the patients who was carefully analyzed 4 months after infusion. The procedure uses lymphodepleting chemotherapy, and therefore the negative side-effects associated with this procedure were observed.  Although only three patients were treated, these findings represent an important advance in the therapeutic application of gene editing and highlight the potential to accelerate development of cell-based therapies, however experience with more patients given infusions of CRISPR-engineered T cells with higher editing efficiencies, and longer observation after infusion, will be required to fully assess the safety of this approach.

References

Hamilton and Doudna (2020) Knocking out barriers to engineered cell activity. Science, DOI: 10.1126/science.aba9844.

Maguire G (2019) Physiological renormalization using systems therapeutics. Future Sci OA. 2020 Jan; 6(1): FSO428.

Sanders R (2018) UC Berkeley research led to Nobel Prize-winning immunotherapy. Berkeley News, Oct.1, 2018.

Staudtmauer EA et al (2020) CRISPR-engineered T cells in patients with refractory cancer. Science, DOI: 10.1126/science.aba7365

Worcester (2019) Diet appears to play an important role in response to anti-PD-1 cancer immunotherapy. MD Edge, March 1, 2019.

Why Are So Many People Leaving Texas – And Why Are Most of Them Coming to California

Texas ranked third in the United States for the number of residents moving out of state (467,338) in 2017. The most popular out-of-state relocation destination for Texans was California (40,999). Let’s put this exodus from Texas into perspective vis-a-vis California.

Texas had a population in 2017 of 28.32 million. On a per capita basis then, the percent of people leaving Texas was 0.016. California lost just over 661,000 people to domestic migration in the 12 months ended in July 2017. Given California’s population in 2017 of 39.4 million, the per capita basis of people leaving California was 0.016, approximately the same rate as in Texas.

The reasons people leave California have received considerable national attention, and the cost of living coupled with our progressive environment are two key reasons why low income, conservative people without college degrees are moving to Texas. On the other hand, high income, educated Texans move to California where they will enjoy the opportunity to prosper in the fastest growing economy in the USA, where most innovation in the US occurs, and where culture and beauty abound.

Simple cost of living averages do not address the quality of life, and the quality of the goods or services available, and Texas does not offer anything close to what California offers. Consider, the average lifespan in TX- 78.5; average income in TX – $59,206; 18.5 percent of Texas residents, aged over 25 years, held a Bachelor’s degree; and the suicide rate was 13.0 per 100,000 in Texas. Whereas in California, average lifespan in CA – 80.9; average income in CA – $71,805; 21.3 percent of Californian residents, aged over 25 years, held a Bachelor’s degree; and the suicide rate was 11.1 per 100,000 in California. Moreover, California is the world’s fifth largest economy, surpassing many countries with much larger populations. Texas has the 10th largest economy in the world. Whereas California leads innovation in the world, economically and socially, Texas is known for oil and finance, stultifying old industries, and is socially regressive led by Republican politicians like Rafael Cruz. California per-capita GDP was $58,619 in 2016, whereas per capita income for Texas was $29,525 in 2017. But those are numbers, and we must also consider quality from a cognitive point of view.

Drive through Houston, TX, the state’s largest city, and you’ll be aghast by the foul smells in the air, tacky neighborhoods where strip clubs stand next to churches, the lack of city planning, an overabundance of superfund clean-up sites, and the general ugliness of the area. Many other cities are worse, and once beautiful Austin now suffers from a lack of strong zoning rules that means tall, ugly skyscrapers now tower over the University of Texas campus. Drive through the state, and most of what you see is dull and banal, and often ugly.

Now drive through California. That drive can include sights of the world’s tallest trees, Redwoods, the largest alpine lake in all of North America, Lake Tahoe, and the world’s most innovative university, UC Berkeley, that is surrounded by mountains and trees, and not skyscrapers, except of course the university’s beautiful Campanile. The drive can continue across the Golden Gate Bridge, into the most beautiful large city in the US, San Francisco, and then onto the largest trees in world, the giant Sequoias in the beautiful Sierra Nevada Mountains close to the highest mountain in the continental USA, Mt. Whitney. Head down south along the dramatic Big Sur coastline to Santa Barbara and enjoy California wine in America’s Riviera, and then continue south to Los Angeles, where the world’s best symphony performs in the world’s best concert hall. A drive into the mountains surrounding Los Angeles brings us upon Mt Wilson where anyone can peer though the giant 100 inch telescope where Nobel Laureate, Dr. James Hubble, Ph.D., discovered the expanding universe. Finish the trip in San Diego for relaxation, surfing, and fish tacos in a beautiful city nestled on the Pacific with the best weather in the USA and a history that dates back to 1769.

These are just a few of the reasons why Texans are fleeing their state and moving to California. All are welcome in California.

NAD Supplements : More Reductionist Quackery for Profit

NAD (nicotinamide adenine dinucleotide) is a molecule that supports basic cellular function and metabolism in a number of important ways, including protecting our DNA (Sambeat et al, 2019), converting food into usable energy and regulating our sleep-wake cycles. NAD decreases as we age, and low levels of NAD are associated with increased risk of heart disease, Type 2 diabetes, Alzheimer’s disease, and accelerated aging. Decreased NAD levels in our bodies can result from 1. the body making less NAD as we age, 2. more NAD being used in the body as we age because of aged related stress and damage, including oxidative damage, and 3. poor diet, including increased alcohol consumption as we age. Some excellent work has found that SIRT, a molecule dependent on NAD to be synthesized in our bodies, is involved in preventing stem cell aging that even prevents a pro-inflammatory state of the macrophages in our innate immune system (Luo et al, 2019), and also prevents aging-associated inflammation and insulin resistance (He et al, 2020).

There are two forms of vitamin B3, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), receiving attention for their ability to increase NAD levels. In mice studies, NR and NMN increase NAD levels, while some newer, small studies suggest the same is found in humans. Sounds great, right? NAD is important to a number of normal cellular functions and keeps some of our cell types young, so taking “NAD supplements” must be healthy and will slow the aging process. Where can I buy this stuff?

If you’ve read my book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts,” you’ll know to ask a few important questions before running off to the store to buy this supplement. And, after having asked those few questions, you’ll know the NAD supplement offered at your local store or online is a waste of money and potentially dangerous.

First, assuming that what you buy is actually the NAD supplement, and that is a big “if” given the supplement industry is rife with fraud, the increase in the concentration of NAD in blood cells shows that NR works to raise the concentration of NAD, but it is not evidence that having more NAD will increase life span or health span in humans, or even improve cellular function of any particular group of cells. We also don’t know how much NAD was getting into and affecting muscles or other organs, and that is difficult to measure. One study, sponsored by one of the NAD supplement companies,  found no correlation between the age of subjects and the level of NAD in their muscle and brain tissue (Elhassan et al, 2019). Therefore blood may not be an indicator for NAD throughout the body; not serving as a biomarker for the therapeutic effects in other tissues. The same study by Elhassen et al found that the supplement didn’t help improve the subject’s grip strength, muscle blood flow and metabolism, but concerningly increased a protein thought to be increased in type 2 diabetes and insulin resistance.

We also need to understand what levels of NAD are healthy. Is too much NDA dangerous? Some studies found that it is.  Deterioration of metabolic health, and dysfunction in fat cells along with an induction of glucose intolerance were found in those mice fed a large quantity of NAD supplements (Shi et al, 2019). Other studies in mice report similar results (Kourtzidis et al, 2018). Pools of increased NAD may also be a risk factor for cancer (Hong et al, 2019). And all NAD supplements are not the same in their actions, and supplements don’t act the same way as do the natural, endogenous precursors to NAD (Sambeat et al, 2019).

Again, if you’ve read my book, you know to ask the question, “compared to what?” If you go to Clinicaltrials.gov to see the basic study design of the trials testing NAD supplements, you’ll discover a level of stupidity in trial design that boggles the imagination. What is the NAD supplement being compared to? In none of the studies is diet being controlled for. And we know diet is very important for the levels of NAD in the body. For example, vegetables such as broccoli and cabbage contain 0.25–1.12 and 0.0–0.90 mg NMN/100 gm, fruits like avocado, tomato contain 0.36–1.60 and 0.26–0.30 mg NMN/100 gm, whereas raw beef has 0.06–0.42 mg NMN/100 gm. So if people are eating a poor diet, like most Americans, their natural supplementation of NMN will be low and easily raised by a NAD supplement. Further, without controlling diet in the NAD supplement group versus placebo group, especially in trials with small numbers of subjects, diet can easily confound the data. Moreover, in at least some of the studies, the placebo group was taking a sugar pill. Sugar has numerous deleterious effects within our different organs and microbiome, all of which can impact the clinical trials. The important clinical trial would be to compare the NAD supplement group with a group eating a whole food plant based diet. But given you can’t patent a whole food plant based diet, the monetary incentives are not in place to perform such a study. The mentality of all such gimmicks is to find that one “magic pill” to make me healthy and young, a reductionist strategy appealing to the lazy consumer, and to companies and providers who make a lot of money selling quackery. I have more to say about NAD and other supplements in my book. Hope springs eternal, but so do stupidity and greed.

References

Elhassan YS et al (2019) Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial. BioRxiv, doi: https://doi.org/10.1101/680462

He M et al (2020) An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance. Cell Metabolism, DOI:https://doi.org/10.1016/j.cmet.2020.01.009.

Hong SM et al (2019) Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level. Cancer Sci. 2019 Feb; 110(2): 629–638

Kourtzidis I.A., Dolopikou C.F., Tsiftsis A.N., Margaritelis N.V., Theodorou A.A., Zervos I.A., Tsantarliotou M.P., Veskoukis A.S., Vrabas I.S., Paschalis V., et al.  (2018) Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance. Exp. Physiol. 103:1357–1366. doi: 10.1113/EP086964.

Luo H et al (2019) Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging. Cell Rep. 26(4):945-954.e4.

Sambeat A et al (2019) Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage. Nature Communications volume 10, Article number: 4291

Shi W et al (2019) High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet.  Nutrients. 11(10).