CRISPR and Disease Control

 Nature published a brief summary of the recent CRISPR treatment in vivo for a rare disease. They note:

Intellia encased RNA molecules coding the guide RNA and the Cas9 protein in nanoparticles made of biomolecules called lipids, which can be taken up by the liver. The guide RNA sends Cas9 to snip the TTR gene; the cell’s DNA-repair processes then mend the break, but often make mistakes that can disable the gene and halt production of the TTR protein. A month after treatment, TTR production was reduced in all participants. In one person who received the higher of the two tested doses, it fell by 96% — a result that Gillmore, who was an investigator on the trial, finds particularly exciting. Current treatments can reduce TTR by as much as 80%. But he says that a therapy that knocks TTR production down further would increase the chance that his patients’ symptoms would stop getting worse — and might even lead to improvement.

Sound familiar, it is mRNA in a lipid carrier. just like the COVID vaccine. But now it targets certain cells producing the missing protein.

We recently published a paper on how this can be used with prostate cancer targeting the PSMA surface protein of the malignant cells and using CRISPR to enter the cell and stop its proliferation through a forced apoptosis. Just a thought piece but wait a year or two.

A Day Not to Repeat

 We hit 100F, that global warming thing I guess. But then the power went out. As usual. Seems the local power grid, if one can call it that, is a classic tree and branch allowing for single points of failure. Seems power folks never heard of ring networks or low failure rates. That is why I moved my company from New Jersey to Prague, reliable power. The Czechs know how to do things right. In NJ, not so much.

So power is back, happily I have a generator, but then I download a Dell update and the brand new system crashes. Dead! Call Dell, three hours on the phone, glad I bought the premium support package, and manage a patch, and am told I need to do a complete OS load and buy all new apps! So I gave it one last try to reboot with a Restore Point, looks like it was working and then power outage again, this time from 4PM to 2 AM. Fortunately I had the generator yet the temp closed in on 100F in computer room! 

Success, I think, Restore Point seems to have worked. Temps are to hit 103F today and 90% humidity. Bangkok was much better. Nicer people.

That is why NJ is a third world country, no offense to third world countries, perhaps it is a fourth world country. High taxes, bloated Government, failing infrastructure, high prices etc. Hope that tunnel across the Hudson does not collapse! Love the Goldman folks who are our rulers. 

It is worth noting that power utilities are stuck in the 19th century. Their networks are single points of failure, they spend a minimum amount on maintenance, betting on repairs being cheaper, their top management in my opinion focus on the bottom line and are generally ignorant of the key technologies. This is a key issue with Infrastructure. We really do not need more of the same. Telecom has evolved again and again. Not so for power, water, sewer. The Romans had a better network.

Also BTW, social distancing is very easy at 103F and 90% humidity.

Marx and Tree Cutting

 The classic debate is one on value. Marxians state that the value of a product or equally a service is based on the labor content. In contrast the value could equally be determined in the eye of the buyer.

Let me examine a small example, tree removal. Now we have a bunch of white ash all infected and to be removed by the town because they are on town property. We also have lots of other trees on private property needing removal for a variety of reasons. 

Town trees are removed by the town by town employees who are union and paid by the hour. Non town trees are removed by competing companies with workers usually being Central or South Americans. The result:

1. Town trees take 2-3 days to remove one tree. Why work any harder. There are plenty of trees.

2. Non Town trees get 3 to six per day per crew. They get paid by the number of trees removed not by the hour.

Now what would Marx say a fair price for tree removal should be? The union labor town employee slow worker price of an inflated wage or the competitive price of private business? Same result just that it costs 6-20 times more for the town to remove a tree than if one gets a local company to do so.

So much for Marx.

What If?

 Science Magazine published an interview with the current head of the WHO. The following Q and A is most telling:

Q:Operation Warp Speed wasn't designed to vaccinate the world. It was designed to deliver vaccines for the American people and protect the country. What if there had been a different administration that had a more global vision?

A:The problem of just focusing on one country is we will not use the full potential of the whole world. I would turn to the G7 first, and [then] I would take G20, which controls 80% of the [global economy]. They can influence the whole world. What we have been saying from the start—solidarity, everybody contributes to the basket. That [conversation] should happen, and that's what we have been pushing for. This is not just the responsibility of the U.S., but of all the major countries that have capacity for financial [help] or even production capacity.

The real problem was the gross fumbling in the EU in developing and distributing the vaccine and the problem in Wuhan with the release and exposure of the world population. The initial US program was a classic example of US entrepreneurial efforts, try as many as possible and let the individuals work with the best available researchers. Regrettably if the current administration were in charge we would be still selecting the "appropriate" staff mix and lives were being lost. 

"Turn to the G7 first" would get us nowhere. Turn to the entities who had the competence. Much of mRNA was initially targets at cancer immunotherapy across a large entrepreneurial base. Keeping NIH and CDC out of the process was a sign of brilliance. The result speaks for itself. 

If we followed the WHO we may very well have collapsed the G7 economically and destroyed half the population.

NJ 2021 06 26

 We will be entering July this week. Frankly since we have almost 70% of the State vaccinated or infected, thus immune, the remaining infections should be multiplied by 3 to compare and if so we still have a high infection rate. 

Let us start with state new infections. Low but remember the three times factor!

County thus shows an increase rate given the lower base! Where are any competent Public Health officials? This is a possible fifth wave...

Mortality is leveling but we had 14 LTC deaths this week! How can that be?

Mortality rates are low but present...

State prevalence is flat but again the adjustment for the smaller base. So much for herd immunity. Damn the facts can be annoying...

County shows ever worse...

Town doubling time is up again

Incidence of town and county low..

Town prevalence seems to be dropping...

Normalized incidence is flat. This is a cluster effect with poor Public Health...

This is the driver....low vaccinate rates...

Little Things Count

Details are important. Ask any surgeon. Now the CDC has a web site which allegedly posts daily data on vaccines, infections and the like. I have been following it for a few months now and it has become a nightmare. Updates fail on weekends, posting times are totally erratic, and data is highly questionable. Public facing presentation should be perfect. Details count. Trust in the CDC has totally evaporated.

Pope and President

 In 601, Gregory, the Bishop of Rome, there was no singular "Pope" back then and would not be for another 100 years, deferred to the Emperor in Constantinople. In addition for the previous 500 plus years decisions were made by Councils, including Bishops, no Cardinals for again another 400 years. It was a Councillor Church. However there was always tension between Emperor and Bishops. From Constantine, to Justinian and beyond, the Emperors dictated much Church doctrine. Nicaea is an example as is the Arian controversy. The Bishop of Rome, senior amongst Bishops but equal as well, was elected by the people of Rome. Thus we see a Church making decisions based on councils of learned Bishops, often with vicious infighting, and Bishops being elected in a democratic manner.

Then by 1348 the now Pope was in Avignon, a captive of the French King, Rome was a mess and Ockham declared the Pope a heretic. He may have had a point. But I leave that for another day.

The in 1870 at the First Vatican Council, Pius IX squeezes through the "doctrine" of infallibility. Namely the "Pope" can never be wrong in faith or morals. One wonders when that really started and why it took two millennia.

Now as The Hill reports:

Catholic bishops who voted to advance an effort that could deny President Biden Communion over his stance on abortion are being accused of hypocrisy by critics of the decision. Biden, just the second Catholic U.S. president in history, regularly goes to church and touts his faith as a deeply personal aspect of his life. Yet the U.S. Conference of Catholic Bishops (USCCB) voted last week to proceed with drafting a formal statement on the meaning of Communion, which will include whether pro-choice politicians such as Biden should be denied it. The decision runs counter to the wishes of Pope Francis and has put the church at the center of a roiling debate over Biden, abortion and Catholicism. It has also invited comparisons to former President Trump, with critics of the vote pointing in outrage to examples where Trump was not aligned with the church.

Now the Church has rules and Councils of Bishops have precedence. Break the rules and you are out of the club. One can say, "Remember Avignon".  Perhaps that may concern the current Bishop of Rome.

NJ 2021 06 19

 Another week and still a slow simmer. It would help to know the demographics of the newly infected. First the new infected for the state. Lower than last year and it should be.

The county has an almost constant 10 a day. If we had a competent epidemiologist then this would be driven to zero. I have never seen such inadequacy, but after all they are Government workers.

Deaths seem to be dropping. LTC are still about 1 a day. It shold be zero. Also the mortality rate for those now infected is 6%!

State prevalence is low

County shows that standard 10 per day times 12 days. Flat! Why?

New per day county and town. Look better

Doubling is up

Prevalence is still high, and again here we should be able to pinpoint the problem. Just about 100% of 65+ are vaccinated so who are these characters!

Normalized increases nationally still low

Vaccinations low but rising.

Europe, Russia and China

These three areas present somewhat uniquely different problems. For example:

1. Europe presents the complexity of the EU and its overly bureaucratic governances as well as its dependence on a US supported NATO system. Ironically Poland has one of the strongest military institutions. Poland is adjacent to Belarus which is in a sense a captive state of Russia and a buffer zone that Russia feels comfortable with. NATO was formed to address the Soviet threat coming from a Stalinist regime.  It is an amalgam of European forces, often poorly trained and organized, and underpinned by massive US forces, technology and dollars. One should really examine the need for NATO, especially a US backed and facilitated one. NATO was formed before the EU was created. The EU now has a larger population than the US and perhaps they should consider their own defense, perhaps allied with the US, but not led by the US. The current EU is all too often a sinecure for military and politicians as a transit to post political life in some lucrative manner.

 2. Russia is a vast territory whose economy is dominated by arms and extraction. It provides oil and gas, minerals, and other related resources and is a major seller of arms to a wide collection of buyers. Russia has ocean ports only on the eastern side on the Pacific and on the west, it has precarious access via the Baltic and the Black Sea. Russia views its adversaries to the west. Perhaps its eastward adversaries are neglected due to its massive loss in the war with Japan a century ago. In contrast to China, Russia does not hold claim to the Pacific. The Pacific is a protection for Russia from the west. Russia has no substantial consumer goods. It is not akin to China, where massive manufacturing of consumer products prevails. Russia also has an ongoing mentality of being threatened by remote neighbors. Thus, Russia seeks to have buffers between its territories and its putative adversaries. In a sense Belarus serves the purpose. Ukraine is a threat, especially if it were joining NATO. Ukraine can become a major flashpoint, dragging the US into a conflict of which it truly has no interest. A neutral Ukraine is a stable point. A NATO Ukraine is a stick in the eye of the Bear.

 3. China is a global threat. It has taken a while for many US politicians to recognize this. They are a threat because they want global hegemony via economic power. The economic power starts with manufacturing but moves on to bio technology. Yes, China can manufacture cheaply, just go to Walmart. No Russia products but tons of Chinese. Yet that is but a start. The true mover is the massive progress and advances China has and is making in biotech. One need just read the scientific literature and it shouts dominance. Yet this dominance is a double-edged sword. China can produce advanced therapeutics but it lacks the basic quality controls we demand in the west. Shar practices is de regur for all Chinese producers. The US now imports well over seventy percent of its over the counter drugs from China. One has no ideas as to their quality of safety. If China wanted to assert itself it could do so via ibuprofen and acetaminophen.  The recent pandemic is a clear example of all of the above. Millions dead, economies smashed, and politics distorted. China does not fear neighbors. The neighbors fear them.

 Overall, these three issues should be re-examined. NATO should become an EU force, allied with but not supported by the US. Russia must be understood by its basic fear of intrusion and thus needing safe buffers. China must be seen as a threat not due to nuclear weapons but due to its ever-expanding biotech expertise and global reach. China, lacking the checks and balances insuring safe and quality biotech products, presents the most significant flash point in the decades to come.

 

Gain of Function

 It is worth looking at the 2015 Gain of Function report by the NAS. They note:

On October 17, 2014, spurred by incidents at U.S. government laboratories that raised serious biosafety concerns, the U.S. government launched a 1-year deliberative process to address the continuing controversy surrounding so-called “gain-of-function” (GoF) research on respiratory pathogens with pandemic potential (White House, 2014a).1 GoF research is the latest example of U.S. efforts to develop oversight mechanisms for dual use research in the life sciences that can “reliably identify, and where necessary, mitigate risks while protecting scientific autonomy, discovery and innovation, public health, national security, and other critical interests”  The GoF controversy began in late 2011 with the question of whether to publish the results of two experiments involving H5N1 avian influenza and continued to focus on certain research with highly pathogenic avian influenza over the next 3 years.3 The new U.S. policy expanded the scope to include experiments with the coronaviruses that cause Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The heart of the U.S. process is an evaluation of the potential risks and benefits of certain types of GoF experiments with influenza, SARS, and MERS viruses that would “inform the development and adoption of a new U.S. Government policy governing the funding and conduct of gain-of-function research” (White House, 2014a:3). As part of the process, the government also instituted a pause in both new and current
funding for some GoF research projects while the evaluation was carried out.

 New USG funding will not be released for gain-of-function research projects that may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route. The research funding pause would not apply to characterization or testing of naturally occurring influenza, MERS, and SARS viruses, unless the tests are reasonably anticipated to increase transmissibility and/or pathogenicity. In parallel, we will encourage the currently-funded USG and non-USG funded research community to join in adopting a voluntary pause on research that meets the stated definition. (White House, 2014a:2)

 Initially, 18 research projects funded by the National Institutes of Health (NIH) were halted, although several involving the effort to develop an animal model for studying MERS were later exempted 

 

NJ 2021 06 12

 Another week with good news and bad news. First county prevalence. It is flat. Namely we have a small but continuing group of infected just swapping the infection.

Statewide it does appear good.

Death rates are low but much of this is another artifact of the State's grossly incompetent measuring system.

County incidence is low but steady

State incidence is low

Vaccinations nationally are horrible, well below the minimal 1 million a day target. There is a lot of fake news out there.

However the incidence normalized keeps decreasing showing a dying out of the pandemic.

Tow incidence still shows the hot spots.

New per day in county is low but the town has its classic "strong man" characters.

This is shown by an increasing prevalence, the Soprano Complex.

Gambling with Armageddon

Sherwin has written an interesting review of the events surrounding the Cuban Missile Crisis. It is in a sense a minute-by-minute summary of what occurred over the period with commentary on previous recollections and written reports. In a sense the author is attempting to set the record straight based upon new information and first-hand reports.

 The book is exhaustive in its coverage of the period but does preface it with the work leading to Hiroshima and the Eisenhower period of dealing with Soviet nuclear expansion.

 Overall, the book is expansive and details the interaction of the key players who make both assumptions and policy, often devoid of reality.

 In a sense the book is pro-Kennedy, with the exception of the slight interruptions of his “assistants”, Fiddle and Faddle, who seem to play some unstated role. One sees Kennedy dealing with the conflicting advice from his multiple advisors as well as having to deal with the generally pro-war military.

 For the most part the story has been told many times but there are several issues which it raises. First is the generally gross incompetence of the Intelligence community, the CIA, who after the Bay of Pigs fiasco seem to have just dug a deeper whole for themselves. The CIA seems to have continued its fumbling over an extensive period of time. Second is the Military Officers in command whose blatant dislike of the civilian leadership. Neither seemed to have served the American people well.

 The book does raise some serious issues:

 1.  Did the Executive and the Military have the faintest idea what damage could be brought by MT nuclear devices? No where in the discussion is there anyone telling Kennedy what may happen. These estimates were well known and circulated in DoD and the Executive. Millions of deaths would result in just a few seconds. These weapons would be 1,000 or more greater that Hiroshima (15KT),

 2. Why was there no psychological profiles of Khrushchev and other Soviet leaders so that one could have some understanding on how to deal with them and moreover why they did what they did? Despite the alleged attempt by Kennedy to try to understand Khrushchev there did not seem to have been any detailed profiling of the individuals nor any attempt to understand why they were doing what they were. This was another defect at the CIA then and I suspect now.

 3. Why did no one in the US side even realize that if they tried to neutralize the nuclear sites there would always be one or more unseen which would then be launched? This I have called the “cancer surgeon metaphor”.  Namely the surgeon can remove what the surgeon sees, yet unseen malignant cells result in terminal metastasis. The author recalls the Rumsfeld comment of “Known knowns” etc. The author clearly indicates that Rumsfeld “folly” was his matrix of perception vs reality had four entries, and it was missing fourth the bit him.

 4. The “loose cannon” problem. This is the problem of having some low-level office in charge of deploying a nuclear weapon doing so on their own initiative. In Ellsberg recent book he details a multiplicity of these occasions. Namely launch authority could be accomplished well below the Executive.

 The author does and exceptionally good job in detailing the facts as are know and it is done in a highly logical and accessible manner. Very well worth the read.

Moreover, when one thinks of risks to humanity, nuclear weapons are number one. It is regrettable that politicians in general seem clueless as to the massive destruction of all life from just a few of these mega weapons.