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Daily Archives: July 7, 2021
Get ready for the Sept. 14 recall election – San Bernardino County Sun
Posted: July 7, 2021 at 2:46 pm
Its happening. After several attempts to trigger a recall election against Gov. Gavin Newsom since 2019, Californians now have a set date for deciding whether to remove the governor from office. Last week, Lt. Gov. Eleni Kounalakis announced the recall election would be held on Sept. 14.
Will Gov. Newsom face the same fate as Gov. Gray Davis did in 2003?
Will a prominent Democrat enter the race?
Will Democratic voters rally to Newsoms defense?
Will Newsom benefit from a relatively early recall election?
For these questions and more, well find out soon enough.
As of this writing, the pro-recall campaign seems to face an uphill battle.
In May, the Public Policy Institute of California reported that nearly six in 10 likely California voters would vote to oppose the recall.
Likewise, the Institute of Governmental Studies based at UC Berkeley reported five months ago that 36% of Californians said they would vote to remove the governor.
Months later, recall support remained stagnant.
Perhaps these favorable figures for the governor are a function of polling. Perhaps there are many more Californians willing to back the recall than could be reflected in surveys. Again, time will tell.
Obviously, Californias Democratic establishment believes an earlier than anticipated election will benefit Newsom.
But there are risks.
Wildfires, power outages, the impacts of drought and any sudden return of lockdown policies could aid the efforts of recall supporters.
Either way, expect a lot of money to be raised and spent by special interests on both sides regardless of what successes and failures occur.
Then theres the matter of candidates.
In 2003, there were 135 candidates on the ballot. This time, along with some outliers, theres a whos-who of California Republican and Libertarian alternatives in the running.
From celebrities such as Caitlyn Jenner to former elected officials like Doug Ose and Kevin Faulconer to elected officials Republican Assemblyman Kevin Kiley and Libertarian Riverside County Supervisor Jeff Hewitt, there are plenty of significant names.
But will they be able to energize voters in the way Arnold Schwarzenegger? Will they need to? That all remains to be seen.
One thing is clear. The recall is a legitimate tool from the state constitution empowering the public to keep elected officials in check. Now that a large number of Californians worked to trigger a recall, its time to pay attention to the arguments for and against recalling Gov. Newsom.
Over the next two months ahead, thats what we intend to do.
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Leo Morris column: Indiana – an independent state it its own way – The Herald Bulletin
Posted: at 2:46 pm
Once again, the Internet comes through with another silly list that is fun to argue about precisely because it is pointless to do so.
Indiana, we are told by the website WalletHub, is the sixth-worst state in the union for the independence of its citizens, better only than the awful quintet of Louisiana, Kentucky, Mississippi, South Carolina and Alaska.
Using a set of metrics including the states dependence on federal money, individuals bad habits (such as opioid abuse and social media addiction) and the rates of bankruptcy and foreclosure, the site says we Hoosiers are just not a self-sufficient lot.
Utah, the same survey said, is the most self-sufficient state, which struck me as odd. Just this morning, that states governor was on TV, boasting to a smarmy news reader about how proud she was of the states COVID-19 rules compliance and long-range plan to fight climate change.
That sounds like sucking up both to Washington and the whole world at the same time.
Outraged on behalf of my beloved Hoosier state, I went looking for other rankings.
According to cheatsheet.com, which considers only the percentage of a states general revenue that comes from the federal government, North Dakota is the most independent state at 16.8%. Indiana doesnt do so well on that list, either, ranking 10th worst at 38%.
Perhaps Gov. Eric Holcomb will keep that in mind the next time hes inclined to gripe about federal interference. Strings, Governor, strings.
At thetopten.com, a different criterion is used: How would a state do if cut off from the rest of the country? Texas, with a robust economy, diverse and energetic population and a National Guard that could defeat many countries armies, came out on top, followed closely by California and New York.
Makes sense. Bigger is better, no matter how much their current politics might be screwed up.
Both intrigued and puzzled, I then sought the ranking of states on libertarianism.
The Cato Institute says the most libertarian state, based on the degree of personal and economic freedom its citizens enjoy, is Florida, followed by New Hampshire and hooray for us! Indiana. On the Mises Institute list, Florida and New Hampshire are first and second, but Indiana falls to 10th, still not bad.
How can Indiana be both one of the least independent states and one of the most libertarian?
Because, remember silly and pointless. Self-reliance is, by definition, something possessed by or lacking in individuals, not a quality that can easily be applied in the aggregate to a whole people.
And its a state of mind. Most of the things that give most of us a sense of independence are, ironically, things that also connect us to others, such as our cars and the ubiquitous smartphone.
Because my parents had to buy so much on credit, I feel naked without a certain amount of cash in my pocket, never mind that my debit card is almost universally accepted.
But what if we were suddenly cut off from everybody like, well, like Texas or California adrift from the union?
My brother has the right idea. He has several weeks worth of water and emergency food supplies laid in, and hed probably lose his mind if somebody spirited it away.
The Federal Emergency Management Agency recommends we all have at least a three-day disaster kit at home, including food and water and everything from a flashlight and battery-operated radio to a First-Aid kit and garbage bags.
How many of us do? How about an emergency kit for the car in case it breaks down in the middle of nowhere in the middle of winter?
Show me that list of who is emergency ready and who isnt and Ill tell you whether the state is independent or not, silly though it may be.
And remember, there is a fine line between self-reliant and self-defeating. In other words, if I may refer to an old Twilight Zone episode, if you dont have a fallout shelter, you really ought to be friends with a neighbor who does.
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Cryptocurrencies dream of escaping the global financial system is crumbling – The Guardian
Posted: at 2:46 pm
Since a mysterious figure named Satoshi Nakamoto first created bitcoin after the 2008 financial crash, cryptocurrencies have multiplied. There are now thousands of coins in circulation, with names that sound like jettisoned intergalactic missions: Libra, Ethereum, Stellar, Auroracoin. Though they differ in branding, almost all cryptocurrencies share a common fantasy: to remove the money supply from the hands of politicians and sidestep the financial institutions that govern the movement of cash across the Earth. But its recently become obvious that cryptocurrencies can escape neither of these things.
Indeed, the libertarian dream shared by their early proponents appears to be dying at the very moment cryptocurrencies have broken through to the mainstream. Stablecoins are pegged to the value of national currencies, while the US Federal Reserve is developing its own digital currency. Elsewhere the Bank for International Settlements recently lent its support to central bank digital currencies for the first time. These developments turn the original purpose of stateless money on its head. Even El Salvadors recognition of bitcoin as legal tender is being criticised by true believers for forcing consumers to accept the cryptocurrency, thus undermining the very principle of choice.
Despite cryptos futuristic branding, its intellectual origin story is more mundane. The idea of a stateless money supply first arose in debates over a common European currency. While the 1992 Maastricht treaty paved the way for the introduction of the euro in 1999, this wasnt the only currency model on the table at the time. A lesser-known idea, proposed by the German economist Herbert Giersch in 1975, imagined a parallel currency called the europa that would circulate alongside and compete with national currencies rather than replacing them. Along with fellow economist members of the neoliberal Mont Pelerin Society, Giersch thought what he called currency competition in the title of a 1978 book would gradually draw people away from their lira, francs and drachmas.
Gierschs student Roland Vaubel, who would help found the Alternative fr Deutschland (AfD) party nearly four decades later, was drafted by the European Commission to explore the idea. Meanwhile, in 1976, Friedrich Hayek, who was in regular contact with Giersch and Vaubel, published two pamphlets with the rightwing Institute of Economic Affairs. Hayeks essays one on choice in currency, the other on the denationalisation of money became touchstones for those who wanted to bring stateless money into existence.
But once it was clear that the euro had beaten out the europa, libertarians began to look elsewhere for places to experiment. By the second half of the 1990s, the internet seemed to offer a space that lay beyond national sovereignty and earthly territory. In 1996, the internet activist John Perry Barlow proclaimed that legal concepts of property, expression, identity, movement, and context do not apply online. Some libertarians went further than Barlow and pragmatically observed that the old laws of property might be more secure than ever in cyberspace, where users could escape the reach of national governments and taxes. In 1998, the runner-up for the Mont Pelerin Societys Hayek prize forecast that the internet would undermine the monopoly supply of money by governments and allow people to choose between different private money suppliers.
This vision of money without states was captured in a 1997 libertarian manifesto written by the investment adviser James Dale Davidson and former Times editor William Rees-Mogg (father of the Conservative MP Jacob Rees-Mogg). Disguised as an airport paperback, The Sovereign Individual: How to survive and thrive during the collapse of the welfare state predicted that the internet would denationalise money. People could forgo reliance on the legal tender approved by governments and instead use immaterial cybercash, which the authors imagined as encrypted sequences of multihundred-digit prime numbers. Cybercash, they argued, will bring Hayeks logic vividly to life.
Their book proved popular with a little-known venture capitalist in San Franciscos Bay Area. The young Peter Thiel was enthused by Davidson and Rees-Moggs vision for a nationless digital currency, and in 1999 he launched PayPal, bringing their prophecy closer to reality. Thiels company was just the beginning of what would later become a proliferation of different digital currencies. But in recent months, a less starry-eyed future for crypto has come into focus. The first flaw in the bitcoin model used by the majority of cryptocurrencies is, ironically, a consequence of its own success. Solving the equations to acquire new bitcoins (referred to as mining) requires large volumes of computer hardware that frequently overheats and is extremely energy intensive. Estimates put the annual energy usage of bitcoin mining between that of Sweden and Malaysia.
And as these mines multiply, their operations begin to stretch and even overwhelm national power grids. Iran banned bitcoin mining last month after it led to blackouts and possibly the shutdown of a nuclear reactor. Multiple provinces in China, one of the worlds biggest producers of bitcoin, banned mining too, leading to reports of miners relocating their hardware to sites of more traditional underground extraction in Canada, South Dakota and Texas.
Chinese crackdowns are extending to holdings in crypto too, sending the value of bitcoin tumbling. South Korea recently seized tens of millions of dollars of crypto assets from its wealthy citizens in a clampdown on tax avoidance precisely what the techno-libertarians hoped digital cash would make impossible. And earlier this month, the US Justice Department announced it had managed to track down and recover most of the ransom paid in bitcoin to hackers of the Colonial Pipeline. The traceless currency leaves a trail after all.
Chained to the Earth by cables and wire, crypto is more likely to live on as an extension of the nation state than as a means of escaping it. Like goldbugs before them, crypto fans may have to acclimatise to their hobby horse being, at best, a volatile new asset class for high-risk hedging rather than a truly alternative global currency (though even on this, opinions differ). Most travellers to the crypto craze since its initial spike in late 2017 seem to be drawn not by the possibility of bringing Hayeks vision to life, but by a willingness to take risks for speculative payoffs. Indeed, the future for crypto now looks less like a techno-utopian dream or libertarian fantasy, and more like subordination to the very thing it was designed to overthrow: the nation states monopoly over the money supply.
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Gov. DeSantis and the need for viewpoint diversity in higher education | Column – Tampa Bay Times
Posted: at 2:46 pm
Floridas Republican Gov. Ron DeSantis recently signed a bill to protect against indoctrination in the states colleges and universities. The new law, which went into effect on July 1, requires Floridas public colleges and universities to conduct an annual survey measuring intellectual freedom and viewpoint diversity on their campuses. The laws goal is to assess the extent to which competing ideas and perspectives are presented and how free students, faculty, and staff feel to express their beliefs and viewpoints.
The Florida law does not specify what will be done with the survey results, but Gov. DeSantis suggested that budget cuts could result if universities and colleges are found to be indoctrinating students. It used to be thought that a university campus was a place where youd be exposed to a lot of different ideas, DeSantis said. Unfortunately, now the norm is really these are more intellectually repressive environments.
DeSantis is currently a frontrunner for the 2024 Republican presidential nomination. Indeed, he edged former President Donald Trump in a recent straw poll taken at the Western Conservative Summit. The problem DeSantis has identified is not unique to Florida Indianas Republican governor signed a similar bill last month and it traces directly to the political biases of the processes by which faculty are hired. Many of the same colleges and universities that tout tenure as a way to encourage free thought censor it by not allowing conservative and libertarian faculty candidates who think freely to get in the door.
I once suggested on the ConLawProf group email list that law schools need to hire more conservative and libertarian candidates (with more meaning, at a minimum, at least one). The reaction? One law professor posted that I was nuts to suggest such a thing. Libertarian law professor Nicholas Quinn Rosenkranz quipped at a Federalist Society conference on intellectual diversity in the legal academy that his leftist colleagues at Georgetown felt that three conservatives on a law faculty of 120 was plenty and perhaps even one or two too many.
Anecdotes aside, Northwestern University law professor James Lindgren has published detailed statistical surveys that document that Republicans and Christians are the groups most under-represented in the law professoriate. If the small handful of right-leaning and Christian law schools is excluded from the dataset, the problem is actually worse. Additional studies demonstrate that lack of viewpoint diversity among faculty extends campus-wide. For example, according to research conducted last year by the National Association of Scholars, Democratic professors outnumber their Republican colleagues by a ratio of 8.5 to 1 on top college campuses.
Research since World War II has consistently found overwhelmingly left-oriented political attitudes and ideological self-identification among college and university faculty the report notes. The report also found that the most drastic differences in the ratio were among professors of English, at 26.8 to 1, sociology, at 27 to 1, and anthropology, 42.2 to 1. Less subjective majors such as mathematics (5.5 to 1), chemistry (4.6 to 1), and economics (3 to 1) were less politically biased.
Not surprisingly, DeSantis critics are throwing fits. Nikki Fried, the Florida agriculture commissioner who is challenging DeSantis for governor next year, compared the governors actions to what authoritarian regimes do. Charles P. Pierce wrote in Esquire that DeSantis is a wingnut who is as full of crap as the Christmas goose. Steven Benen toned it down a bit for MSNBC by merely opining that the new law is absurd.
What DeSantis critics fail to appreciate is that truth is most likely to emerge from the clash of ideas. U.S. Supreme Court Justice Oliver Wendell Holmes famously referred to it as the marketplace of ideas, while John Stuart Mill expressed this same view in his classic book On Liberty. The peculiar evil of silencing the expression of an opinion is that it is robbing the human race, Mill wrote. Posterity as well as the existing generation those who dissent from the opinion, still more those who hold it.
Gov. DeSantis received his undergraduate degree from Yale and his law degree from Harvard. He should be commended for recognizing that faculty need to start behaving like professors again.
Scott Douglas Gerber is a law professor at Ohio Northern University and an associated scholar at Brown Universitys Political Theory Project.
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Letter: Writer doesn’t know what the Tea Party was – INFORUM
Posted: at 2:46 pm
Leland Jenson recently wrote a letter insulting his political opponents and spewing leftist buzzwords. He jumps all over the place trying to connect unrelated topics from completely different political camps. For example, he said, Our national democratic institutions are being undermined by Tea Party extremists (Vanilla Isis), trying to lump the Tea Party movement in with the January 6th capital riot. To understand how stupid this is, one must first understand what the Tea Party movement was.
Despite what the media would have you believe, Republicans and Libertarians dont actually get along very well. The Tea Party movement was an attempt to form a coalition between Libertarians and Republicans to focus on one single issue: government spending. The movement did manage to get a few hardline fiscal hawks elected to Congress, but it failed to give Ron Paul (now retired) the presidency.
For those who dont know, Ron Paul can be thought of as the libertarian version of Bernie Sanders. His son, Sen. Rand Paul, R-Ky., is one of the last remaining remnants of the Tea Party. The movement that got Trump elected in 2016 was completely different and unrelated. That movement was all about national populism, not government spending.
The Tea Party movement was very short lived and it functionally died after the 2012 election. The modern Republican party today arguably does not care about the national debt and how much of the annual budget goes to simply paying interest.
Secondly, Im at a loss for words at Jenson calling the tea party vanilla isis. ISIS is a theocratic movement whose goal is to create a Sunni Islamic state. The Shia muslims were treated just as badly as non-muslims, sometimes worse; they could either convert or be killed. The Sunni muslims under ISIS control were forced to follow the strictest Islamic protocols (sharia law), such as men not shaving their beards and women being forced to cover themselves; thats putting it lightly. Failure to comply could result in barbaric thousand-year-old styles of executions such as crucifixions and stoning, including women and children.
Jenson is concerned about bigotry, misogyny and equality or whatever. When the Tea Party was active, the gay marriage debate was in full swing; the Supreme Court did not settle that discussion until 2015, long after the Tea Party ended. Libertarians are generally supportive of gay marriage, Republicans were not. The coalition required them to put their differences aside. Similarly, Libertarians are generally far less religious than Republicans; even the ones that are religious arent authoritarian about it. You wouldnt find the Tea Party pushing for prayer in schools or the Ten Commandments in front of courthouses. Comparing the Tea Party to ISIS doesnt even make sense, not even as a vanilla version. The Tea Party was less theocratic than Republicans in general at the time.
In conclusion, Jenson doesnt know what hes talking about. The Tea Party was not conservative republican extremism.
P. S. Trickle-down economics is not a real thing. The only time you hear those words are when Democrats are attacking a strawman. You wont find academic proponents of it.
William Smith lives in Fargo.
This letter does not necessarily reflect the opinion of The Forum's editorial board nor Forum ownership.
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With Capitalists Like These – Splice Today
Posted: at 2:46 pm
There are virtually no defenders of capitalism in the world, yours truly and a handful of others being the rare exceptions. Capitalism endures because it works and its basic principles accurately describe the physical universe, not because of any significant cultural pressure to believe in it. Nonetheless, you hear claims that market fundamentalists abound, as if the world is full of maniacs consistently bashing government and praising property rights.
Even I shouldnt properly be called a market fundamentalist, if that slur is meant to imply an allegiance to an overall pattern of market activity for its own sake regardless of the consequences for the human participants involveda position that may be held by no one. At a fundamental level, in fact, Im a utilitarian, wanting the greatest possible happiness for the greatest possible number over the lifetime of the universe. I dont really understand what else would or should morally motivate anyone. And I think the greatest happiness is made possible by secure property rights.
Unfortunately, as Lenin wisely predicted, most practicing capitalistsbusinesspeoplefeel so little loyalty to the principles underlying the system that created them that theyll sell us the rope with which we will hang them.
The billionaire investor vice chairman of Berkshire Hathaway, Charlie Munger, for example, praises the power and decisiveness of the Chinese Communist Party, currently the worlds most influential engine of non-capitalist central planning, and says he wishes the U.S. were as tough in crushing its business mavericks as China has been in slapping down Jack Mas ideas for more free-market-oriented banking options.
The commies arent capitalisms only adversaries these days, though, not by a long shot. This month brings a conference in Alexandria, Virginia that shows how useless the long arc of conservative thinking has proven to be in making the case for capitalism.
Populist-leaning figures including Sen. Marco Rubio (now de-emphasizing his long history of sugar industry subsidies), Senate candidate and author J.D. Vance (now rapidly deleting his old anti-Trump, pro-Evan McMullin tweets), and new National Review editor Ramesh Ponnuru, under the auspices of the Catholic-inclined Intercollegiate Studies Institute, will talk about topics such as capitalism being anti-family and the need for economic thought to be transformed in the wake of (largely imaginary) decades of social devastation wrought by global markets. This may at least help clarify some of the grievous miscommunications between libertarians and conservatives over the past decade.
Before people of any political stripe wish for the taming of purportedly heartless market institutions, its worth noting that those institutions are often at their worst when they are least market-like. It seems like only yesterdaythe 1990sthat increasingly customized, personalized services were the direction markets were headed. Our biggest complaints about them now seem to be generated by the handful of aberrant, still somewhat novel, large companies that presume to behave like governments.
Big Tech and the Trump Organization alike have their critics, but isnt each adjacent to government, and prone to behave like government, to a degree that few of the worlds millions of other companies are? more commercial and less governmentalless authoritarianbehavior is needed, even within the private sector. Do you really want either Big Tech or the Trump Organization becoming more entangled with the actual government, constantly mingling with regulators? Enforcing simple laws that ensure Big Tech and the like do not become Big Fraud would be enough to keep capitalism coloring inside the lines.
Instead, each political faction in its own way seems lately to flee from entrepreneurs and into the arms of regulators. The right now wants God or populist government to smash chaotic markets. The left always disliked capitalism. The liberals want every inch of it regulated and its participants guilt-tripped any time they interact with each other (and then liberals want to be rewarded for their vandalism with praise for their tolerance and compassion). Even many libertarians, though pro-capitalist in principle, find economics confusing or embarrassing and would rather talk about something ostensibly separate and more popular: sex, radar scanners, constitutional law, medicinal marijuana, you name it, anything that keeps them from sounding like stock-trading fuddy-duddies.
Give capitalism a chance, thoughnot just in the world but within your own perceptions. Even when you see some ostensibly non-governmental civil society institutions screw up, note the high frequency with which the screw-up ensued from a brush with government or mimicry of government. Its sad the Boy Scouts just had to pay $1 billion in settlements for overlooking child molestation incidents, but before you try pinning that one on predatory capitalism, notice the Boy Scouts, always a bit paramilitary in tone, have in recent decades had both a past CIA director and a future Secretary of State as their president. Maybe if Boy Scouts spent more time buying and selling and less time following leaders orders in darkened woods like good soldiers, theyd be a billion richer right now.
A libertarian architect friend of minealso a solid family man and pillar of his community, rest assuredpoints out to me the release this week of Anthony Fontenots book Non-Design: Architecture, Liberalism, and the Market, an argument that the best things in architecture and urban design in recent decades have happened when planners were held at bay and the spontaneous order of the marketplace was allowed to play out. Such observations were growing more common back in the 1990s, in the wake of Communisms catastrophic failure and the reduced perceived necessity for the U.S.s own military-industrial complex, not to mention the welfare state.
Lets rekindle the playful courage to see what markets can do, and this time lets be more explicit about it. Non-libertarian political thinkers constantly claim they have the courage to do whats necessaryalways meaning the courage to use force against their various enemies (or at least recommend someone else use force on their behalf). We should respond by summoning the courage to teach economics and argue openly for defending individual rights. No more hiding behind the latest popular environmental, military, anti-racist, electoral, or aesthetic cause and pretending that Us too! is a powerful enough slogan to carry the day for liberty.
Have the guts to tell the next market-basher and property-rights-violator you encounter hes wrong, whether hes conservative, communist, corporate CEO, or even craven libertarian thinktank staffer.
Todd Seavey is the author of Libertarianism for Beginners and is on Twitter at @ToddSeavey
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Improving the response to cancer immunotherapy by reactivating the ‘guardian of the genome’ – FierceBiotech
Posted: at 2:45 pm
The p53 protein earned the nickname guardian of the genome because it plays a key role in DNA damage response by preventing cells with faulty DNA from dividing. Mutations or malfunctions in p53 have been implicated in many types of human cancers.
In some tumors, normal p53 function is blocked by high levels of another protein called MDM2. Now, scientists from the Karolinska Institutet in Sweden and U.S. biotech Aileron Therapeutics have early evidence that reactivating p53 by inhibiting MDM2 with a drug developed by the company could boost the immune response against tumors. They reported their findings in the journal Cancer Discovery.
Based on positive results in mice and patient tissue samples, the researchers suggested that the MDM2 inhibitor could be used alongside checkpoint inhibitors to help more cancer patients benefit from immuno-oncology agents.
The p53 protein protects against genomic changes in part by blocking repetitive DNA elements that could alter the human genome. These include sequences known as endogenous retroviruses, which were incorporated into the human genome from ancestral infections.
The Karolinska-led team was surprised to discover that p53 could induce the expression of endogenous retrovirus sequences in different cancer cell lines from breast cancer, osteosarcoma, colon cancer and melanoma.
RELATED:Unleashing the cancer-fighting gene TP53 in leukemia with a novel combination treatment
The researchers went on to explore reactivating p53 with MDM2 inhibitors in lab dishes. When we blocked the suppressor MDM2, p53 activated endogenous retroviruses which induced antiviral response and boosted the production of immune-activating interferons, Galina Selivanova, the studys senior author, explainedin a statement.
Interferons are inflammatory molecules needed for effective immune responses. They're also major regulators of tumor-infiltrating immune cells, the researchers noted. In addition to affectinginterferons and related genes, p53 activation enhanced antigen presentation and processing, which could prime cancer cells for targeting by the immune system, the team showed.
Based on thosefindings, the scientists figured the method might work well with PD-1 inhibition, which lifts the brakes that tumors impose on the immune system.
In another mouse model of colon cancer, treatment with Ailerons ALRN-6924, an advanced analog of thedrug, promoted the recruitment of tumor-infiltrating immune cells, especially CD8+ killer T cells, as well as an increase of tumor-suppressing M1 macrophages, the team reported. Combining the drug with a PD-1 inhibitor also produced a complementary anti-tumor effect.
RELATED:New approaches to treating cancer with off-the-shelf immune-stimulating bispecific antibodies
ALRN-6924 is in a phase 1b trial to prevent adverse bone marrow effects in patients undergoingchemotherapy. The Karolinska-led team analyzed biopsy samples from two melanoma patients in the trial before and after treatment. They found p53 was activated in tumors and that the interferon pathway and activity of other genes related to the anti-tumor immune response were enhanced.
This shows that there are synergies that should be exploited between substances that block MDM2 and modern immunotherapies, Selivanova said in a statement. A combination of these can be particularly important for patients who dont respond to immunotherapy.
Aileron recentlylaunched another phase 1b trial in patients with p53-mutated non-small cell lung cancer. The trial is testing ALRN-6924 as a protective agent for patients undergoing chemotherapy with or without immune checkpoint inhibitors.
Many other companies have MDM2 inhibitors in their arsenals. These include Roches idasanutlin, which failed a phase 3 acute myeloid leukemia (AML) trial last year. Through a licensing deal last year, Rain Therapeutics gained rights to Daiichi Sankyos milademetan (DS-3032). And Novartis is developing siremadlin (HDM201), while Amgen has AMG 232.
Selivanova is a co-founder of Boston biotech Aprea Therapeutics. The company is developing a p53 reactivator dubbed eprenetapopt (APR-246). The drug, used in tandem with AbbVie and Roches Venclexta and Celgenes Vidaza, just reporteda win from a phase 1/2 trial in TP53-mutant AML.
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Improving the response to cancer immunotherapy by reactivating the 'guardian of the genome' - FierceBiotech
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Role of Genomic Testing in HR Positive Breast Cancer – Cancer Network
Posted: at 2:45 pm
Lee Schwartzberg, MD, FACP, of West Cancer Center & Research Institute, discusses the role of genomic testing in hormone receptor-positive breast cancer and compares information provided by various assays approved for use.
Kristie Kahl: So Dr. Schwartzberg, what are the genomic assays and what is their role in early breast cancer?
Lee Schwartzberg, MD, FACP: The third aspect of looking at factors that will help us determine prognosis and predict a value in adjuvant therapy for breast cancer are the newer genomic assays. Newer in the sense that theyve now been around for about 15 years and are used quite broadly. These assays look at an expression panel of genes in the tumor. This is not germane, of course. This is looking at the tumor and the expression panel. They were originally done with arrays of mRNA, or messenger RNA, which shows the expression of each of those genes. And either using a panel type of technology or using PCR [polymerase chain reaction] technology for the specific genes that would determine we can get a score of whether a particular tumor is low-, intermediate-, or high-risk for recurrence. Now, we have several different types of genomic assays or commercial assays that are available. Interestingly, they all use a different gene set to come to these decisions. All of them are validated. They are very good at prognosis in terms of telling whether a patients tumor and typically combined with the clinical features that I mentioned already, will be low-risk, intermediate-risk, or high-risk for recurrence of disease. Initially, these assays were established for node-negative patients.
Recently, we have had prospective studies looking in the node-negative or in the node-positive setting how well these assays predict for a recurrence of disease or not. These assays are also important to help us make a decision about chemotherapy up front. The 21-gene assay and the 70-gene assay have been looked at prospectively and give us information about the benefit of chemotherapy in those people that have low-, intermediate-, or high-risk scores. What we find is those with high scores benefit from chemotherapy in that setting whether they are node-negative or node-positive. So, that has become the standard for helping make the decision about chemotherapy in many patients with early-stage breast cancer. As I mentioned before, we do not use genomic expression profiles to make a decision about adjuvant endocrine therapy because we essentially offer that to any patient who is hormone receptor-positive.
Transcript edited for clarity.
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Role of Genomic Testing in HR Positive Breast Cancer - Cancer Network
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View from India: Genome labs initiated to study virus mutations – E&T Magazine
Posted: at 2:45 pm
Delta Plus, a sub lineage of Delta, a variant of Covid-19, has spread across many nations. It has also affected people in Indian states.
On the one side, the national vaccination programme is in full swing. The jab appears to be reassuring. In fact, the Centre has invited bids for drone-led vaccine delivery in remote areas and challenging locations. A standard protocol for vaccine delivery through Unmanned Aerial Vehicles (UAV) has been developed by the Indian Council of Medical Research (ICMR) in collaboration with the Indian Institute of Technology (IIT), Kanpur.
That doesnt mean to say that everyone is safe. No, far from that, theres a murky dimension to it. Delta itself has boosted the second wave of the infection in India. The World Health Organisation (WHO) has described Delta as a Variant of Concern (VoC). The second wave is not yet over, though the case trajectory is coming down. Being highly infectious, Delta has now mutated into Delta Plus, also known as AY.1.
What makes Delta Plus more dangerous than Delta is that it contains an additional mutation called K417N first found in the Beta variant of South Africa. This is in addition to the Delta variant (B.1.617.2), which drove India's deadly second wave of the pandemic. Delta Plus is very resistant to medication, treatment and vaccination, quite apart from being highly transmittable. Alarmingly, it affects the lung cells and is less responsive to the monoclonal antibodies therapy. That means those who have been vaccinated are likely to be affected by Delta Plus and it can even lead to clinical illness.
All these characteristics have been identified by INSACOG (Indian SARS-CoV-2 Genomic Consortia), a consortium of 28 laboratories of Ministry of Health and Family Welfare, Department of Biotechnology, Indian Council of Medical Research (ICMR) and Council of Scientific and Industrial Research (CSIR) for whole genome sequencing in the context of Covid-19. INSACOG also offers timely inputs on appropriate public health response measures to be adopted by states and union territories.
Many nations are weighed down by Delta Plus, but Indias burgeoning population makes the situation much more serious than many parts of the world. Its understandable that ICU beds are being filled up as mortality rates are increasing. This has already hit the headlines as many people have succumbed to it. Wherever the transmission of Delta Plus has happened, the Centre has said that the states should take up immediate containment measures. The emphasis is on enhanced testing, tracking and vaccination in districts and clusters where Delta Plus has spread.
Given its pace of spread, the Centre has initiated genome sequencing labs at the Lok Nayak Jai Prakash Narayan Hospital and the Institute of Liver and Biliary Sciences (ILBS) Hospital. These Delhi-based labs are gearing up for what could be a third wave of the pandemic by studying the mutating coronavirus. R&D professionals will work towards building scientific data on the strain. After detecting Delta Plus variants, Haryana and Rajasthan have become home to genome sequencing facilities. Scientists can monitor the changing variants of Covid-19.
Even as Delta Plus is making news, biopharmaceutical company AstraZeneca has partnered with healthcare startup Docon Technologies to digitise 1,000 clinics across the country. The clinics will be provided with electronic medical record (EMR) systems to manage patient history and administer treatment accordingly.
All this is happening as the country is inching closer towardsa third wave of Covid. ICMR has informed the media that its too early to say if the Delta variant would contribute to the third wave. It definitely remains a matter of concern, as Delta Plus continues to spread rapidly.
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View from India: Genome labs initiated to study virus mutations - E&T Magazine
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Could editing the genomes of bats prevent future pandemics? – STAT – STAT
Posted: at 2:45 pm
Amid the devastating Covid-19 pandemic, two researchers are proposing a drastic way to stop future pandemics: using a technology called a gene drive to rewrite the DNA of bats to prevent them from becoming infected with coronaviruses.
The scientists aim to block spillover events, in which viruses jump from infected bats to humans one suspected source of the coronavirus that causes Covid. Spillover events are thought to have sparked other coronavirus outbreaks as well, including SARS-1 in the early 2000s and Middle East respiratory syndrome (MERS).
This appears to be the first time that scientists have proposed using the still-nascent gene drive technology to stop outbreaks by rendering bats immune to coronaviruses, though other teams are investigating its use to stop mosquitoes and mice from spreading malaria and Lyme disease.
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The scientists behind the proposal realize they face enormous technical, societal, and political obstacles, but want to spark a fresh conversation about additional ways to control diseases that are emerging with growing frequency.
With a very high probability, we are going to see this over and over again, argues entrepreneur and computational geneticist Yaniv Erlich of the Interdisciplinary Center Herzliya in Israel, who is one of two authors of the proposal, titled Preventing COVID-59.
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Maybe our kids will not benefit, maybe our grandchildren will benefit, but if this approach works, we could deploy the same strategy against many types of viruses, Erlich told STAT.
As the Covid-19 pandemic has killed more than 3.9 million people and triggered $16 trillion in economic losses, scientists, public health officials, ecologists, and many others have called for deeper investments in longstanding pandemic prevention measures.
Such measures include boosting global health funding, reducing poverty and health inequity, strengthening disease surveillance networks and community education, preventing deforestation, controlling the wildlife trade, and beefing up investments in infectious disease diagnostics, treatments, and vaccines.
Erlich and his co-author, immunologist Daniel Douek at the U.S. National Institute of Allergy and Infectious Diseases, now propose an additional measure: creating a gene drive to render wild horseshoe bats immune to the types of coronavirus infections that are thought to have triggered the SARS, MERS, and Covid-19 pandemics. They shared the proposal Wednesday on the Github publishing and code-sharing platform.
Though there is heated debate about whether the Covid-19 virus originated in a lab, most scientists say the virus is most likely to have originated in wild animals. There is strong evidence, for instance, that horseshoe bats carry the coronavirus that caused the SARS outbreak.
A gene drive is a technique for turbocharging evolution and spreading new traits throughout a species faster than they would spread through natural selection. It involves using a gene editing technology such as CRISPR to modify an organisms genome so that it passes a new trait to its offspring and throughout the species.
The idea of making a gene drive in bats faces such enormous scientific, technical, social, and economic obstacles that scientists interviewed by STAT called it folly, far-fetched, and concerning. Among other objections, they worried about unintended consequences with so radically tampering with nature.
We have other ways of preventing future Covid-19 outbreaks, argued Natalie Kofler, a trained molecular biologist and bioethicist and founder of Editing Nature, a group focused on inclusive decision-making about genetic technologies.
We need to be thinking about changing the unhealthy relationship of humans and nature, not to gene drive a wild animal so that we can continue our irresponsible and unsustainable behavior that is going to come back to bite us in the ass in the future.
Coming from anyone else, the idea might be laughed off.
But Erlich has a reputation as a visionary. In 2014, for instance, he and another scientist predicted that genetic genealogy databases might one day be used to reveal peoples identities. Four years later, that happened, when law enforcement officials used the method to identify a former California police officer as the notorious Golden State Killer. Erlich has since become chief scientific officer of the genetic genealogy company MyHeritage and he is also founder of a biotech startup, Eleven Therapeutics.
Now, Erlich says, its worth thinking about how a gene drive could work in bats.
Erlich proposes to modify bat genomes so that they would block coronavirus infections. He would create a genetic element, called a shRNA, that targets and destroys coronaviruses. He would then use CRISPR to insert this element into the bat genome. The insertion would also contain a component that pushes bats to preferentially pass the shRNA to their offspring, so that entire bat populations would soon resist coronavirus infection.
Its almost like creating a self-propagating vaccine in these bats, Erlich said.
The idea is intriguing, said geneticist and molecular engineer George Church of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Most of the proposals Ive heard involving gene drives have seemed quite attractive, and this is probably the most attractive, he said.
Creating a gene drive in bats would be enormously difficult, and perhaps impossible, other scientists say. Researchers have created gene drives in mosquitoes and mice in the lab, but none has been released in the wild. The most advanced gene drive projects intended for field use involve modifying mosquitoes to prevent the spread of malaria and attempting to engineer mice to stop them from causing ecological damage.
But its been difficult to engineer effective gene drives in mammals. Developmental geneticist Kim Cooper and her team at the University of California, San Diego, engineered a gene drive that spread a genetic variant through 72% of mouse offspring in her lab. That isnt efficient enough to quickly spread the desired trait in the wild.
Whats more, creating a gene drive in bats would be much harder than it is in mice, because bat researchers lack the genetic tools available in mice, said Paul Thomas, a developmental geneticist at the University of Adelaide in Australia, who is trying to engineer mouse gene drives.
And unlike mice, which can breed at 6 to 8 weeks of age, bats take two years to reach sexual maturity, so it would take much longer for a trait to spread throughout wild bat populations than in lab mouse populations.
They say the proposal is not an easy feat from a technical standpoint, and I think that underplays how hard it might be, Cooper said.
Biologists also say that Erlichs proposal is unlikely to work in the wild even if researchers get bat gene drives to work in a lab because bats are incredibly diverse.
There are 1,432 bat species, including multiple horseshoe bat species that carry coronaviruses and pass them among each other.
Wild viruses similar to the human Covid-19 virus have been found in bats across Asia, and in pangolins. And in June, Weifeng Shi of the Shandong First Medical University & Shandong Academy of Medical Sciences in Taian, China, found 24 coronavirus genomes in bat samples taken from in and around a botanical garden in Yunnan province, in southern China.
Engineering one gene drive in just one bat species would not solve the problem, biologists say.
Youd have to develop systems for entire bat communities, said evolutionary biologist Liliana Dvalos of Stony Brook University. Its the job of visionaries to come up with creative ideas, but this is a giant blind spot in their thinking.
Biologists are also concerned about focusing on bats themselves, because they may not be the most important source of human epidemics. No one has found the exact bat analog to the human Covid-19 virus, or definitively proven that spillover from bats did start the pandemic. Coronaviruses have also been found in other species, including palm civets, pangolins, and camels.
Further, nobody knows how eliminating coronaviruses might affect bats.
We dont know the implications of wiping out coronaviruses in bat populations, because we dont know how bats have evolved to coexist with these viruses, said virologist Arinjay Banerjee of the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon, Canada.
Some scientists, though, welcomed Erlichs proposal, hoping that it will focus attention on what it would take to create successful mammalian gene drive systems.
Royden Saah, for instance, coordinates the Genetic Biocontrol of Invasive Rodents (GBIRd) program, which is trying to engineer gene drives in mice to prevent island bird extinctions. He wants to see more funding to help scientists solve the technical obstacles to such projects, and involve more communities in discussions about these ideas.
I would be concerned if this proposal detracted from the need to fund public health infrastructure, said Saah. But with that caveat, he added, I think this proposal could make people think, OK, if we were to use this technology in this animal in this system, what would we need to do? There would need to be a foundation of ethical development, of clear understanding, of social systems and trust, and technology built in a stepwise manner.
Virologist Jason Kindrachuk of the University of Manitoba said that there are numerous technical and political challenges to a bat gene drive project, and that preventing future outbreaks should mainly involve tackling the challenges that drive spillover events, such as underfunded public health systems, poverty, food insecurity and climate-change-driven ecological disruption. But, he said, given the enormous economic and human toll of Covid-19 and other recent outbreaks, scientists and public health officials might also need to consider new approaches.
In the past, maybe we were blinded a little bit by our belief that we would just be able to increase surveillance and identify these pathogens prior to them spilling over, Kindrachuk said. We now realize that this is going to take a lot of different efforts, so theres an aspect from a research standpoint where we continue to look at things like this, and say, what are the top 5 to 10 things we should invest in.
Erlich acknowledges the obstacles to his proposal, but thinks they arent insurmountable. He thinks the project would require an international investment involving a multidisciplinary consortium.
While we totally agree about the technical complexities, technology advances at exponential rates, Erlich said. Things that are nearly impossible now can be totally reachable within a decade or so.
He also thinks a gene drive could be a better alternative than culling bats, which has been tried (unsuccessfully) in communities around the world, and that scientists could monitor for negative impacts on bat populations.
Lets discuss the idea and think about what we can do to identify a very rigorous and cautious way to test this approach, Erlich said. We dont like to mess with nature, but the current situation is not sustainable.
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