Flipping a switch inside the head: Radio-operated remote control of neuronal activity

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Source: Rockefeller University
URL: seek.rockefeller.edu/flipping-a-switch-inside-the-head/
Cf.: patents.google.com/patent/US10786570B2/en

Genetically engineered cells, nanoparticles and RF magnetic fields
Source: patents.google.com/patent/US10786570B2/en
In an embodiment of the invention, the cells to be targeted may be genetically engineered to express one or more genes encoding physiologically active proteins of interest, such as those proteins providing a therapeutic benefit. The cells are genetically engineered in such a way that expression of the protein(s) of interest is induced in the cell upon excitation of the nanoparticles which results in a localized temperature increase or an increase in nanoparticle motion. Alternatively, the cells to be targeted may be engineered to express a non-encoding nucleic acid molecule of interest such as an antisense or siRNA molecule. Additionally, the target cells maybe genetically engineered to express a temperature sensitive protein, such as a temperature sensitive ion channel, wherein an increase in temperature mediated by the excited nanoparticles results in a cellular response through activation of the ion channel.
In another embodiment of the invention, target cells may be engineered to intracellularly express a protein that is capable of acting as an activated nanoparticle upon exposure to a RF magnetic field. Such proteins include for example, the iron storage protein ferritin. Such proteins may be expressed in the cell as fusion proteins to target their location to a specific site within the cell, for example, in close proximity to a temperature sensitive channel.

With new technology, scientists are able to exert wireless control over brain cells of mice with just the push of a button. The first thing they did was make the mice hungry.
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Friedman and his colleagues have demonstrated a radio-operated remote control for the appetite and glucose metabolism of mice—a sophisticated technique to wirelessly alter neurons in the animals’ brains. At the flick of a switch, they are able to make mice hungry—or suppress their appetite—while the mice go about their lives normally. It’s a tool they are using to unravel the neurological basis of eating, and it is likely to have applications for studies of other hard-wired behaviors.

Friedman, Marilyn M. Simpson Professor, has been working on the technique for several years with Sarah Stanley, a former postdoc in his lab who now is assistant professor at the Icahn School of Medicine at Mount Sinai, and collaborators at Rensselaer Polytechnic Institute. Aware of the limitations of existing methods for triggering brain cells in living animals, the group set out to invent a new way. An ideal approach, they reasoned, would be as noninvasive and non-damaging as possible. And it should work quickly and repeatedly.

Although there are other ways to deliver signals to neurons, each has its limitations. In deep-brain stimulation, for example, scientists thread a wire through the brain to place an electrode next to the target cells. But the implant can damage nearby cells and tissues in ways that interfere with normal behavior. Optogenetics, which works similarly but uses fiber optics and a pulse of light rather than electricity, has the same issue. A third strategy—using drugs to activate genetically modified cells bred into mice—is less invasive, but drugs are slow to take effect and wear off.

The solution that Friedman’s group hit upon, referred to as radiogenetics or magnetogenetics, avoids these problems. With their method, published last year in Nature, biologists can turn neurons on or off in a live animal at will—quickly, repeatedly, and without implants—by engineering the cells to make them receptive to radio waves or a magnetic field.

“In effect, we created a perceptual illusion that the animal had a drop in blood sugar.”

“We’ve combined molecules already used in cells for other purposes in a manner that allows an invisible force to take control of an instinct as primal as hunger,” Friedman says.

The method links five very different biological tools, which can look whimsically convoluted, like a Rube Goldberg contraption on a molecular scale. It relies on a green fluorescent protein borrowed from jellyfish, a peculiar antibody derived from camels, squishy bags of iron particles, and the cellular equivalent of a door made from a membrane-piercing protein—all delivered and installed by a genetically engineered virus. The remote control for this contraption is a modified welding tool (though a store-bought magnet also works).

The researchers’ first challenge was to find something in a neuron that could serve as an antenna to detect the incoming radio signal or magnetic field. The logical choice was ferritin, a protein that stores iron in cells in balloon-like particles just a dozen nanometers wide. Iron is essential to cells but can also be toxic, so it is sequestered in ferritin particles until it is needed. Each ferritin particle carries within it thousands of grains of iron that wiggle around in response to a radio signal, and shift and align when immersed in a magnetic field. We all have these particles shimmying around inside our brain cells, but the motions normally have no effect on neurons.
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Friedman’s team realized that they could use a genetically engineered virus to create doorways into a neuron’s outer membrane. If they could then somehow attach each door to a ferritin particle, they reasoned, they might be able to wiggle the ferritin enough to jostle the door open. “The ‘door’ we chose is called TRPV1,” says Stanley. “Once TRPV1 is activated, calcium and sodium ions would next flow into the cell and trigger the neuron to fire.” The bits borrowed from camels and jellyfish provided what the scientists needed to connect the door to the ferritin (see How to outfit a brain sidebar, right).

Once the team had the new control mechanism working, they put it to the test. For Friedman and Stanley, whose goal is to unravel the biological causes of overeating and obesity, the first application was obvious: Try to identify specific neurons involved in appetite. The group modified glucose-sensing neurons—cells that are believed to monitor blood sugar levels in the brain and keep them within normal range—to put them under wireless control. To accomplish this, they inserted the TRPV1 and ferritin genes into a virus and—using yet another genetic trick—injected them into the glucose-sensing neurons. They could then fiddle with the cells to see whether they are involved, as suspected, in coordinating feeding and the release of hormones, such as insulin and glucagon, that keep blood glucose levels in check.

How to outfit a brain for radio control

Once the virus had enough time to infect and transform the target neurons, the researchers switched on a radio transmitter tuned to 465 kHz, a little below the band used for AM radio.

The neurons responded. They began to fire, signaling a shortage of glucose even though the animal’s blood sugar levels were normal. And other parts of the body responded just as they would to a real drop in blood sugar: insulin levels fell, the liver started pumping out more glucose, and the animals started eating more. “In effect,” Friedman says, “we created a perceptual illusion that the animal had low blood glucose even though the levels were normal.”

Inspired by these results, the researchers wondered if magnetism, like radio waves, might trigger ferritin to open the cellular doors. It did: When the team put the mice cages close to an MRI machine, or waved a rare-earth magnet over the animals, their glucose-sensing neurons were triggered.

Stimulating appetite is one thing. Could they also suppress it? The group tweaked the TRPV1 gene so it would pass chloride, which acts to inhibit neurons. Now when they inserted the modified TRPV1 into the neurons, the rush of chloride made the neurons behave as if the blood was overloaded with glucose. Insulin production surged in the animals, and they ate less. “This seems to indicate clearly that the brain as well as the pancreas is involved in glucose regulation,” Friedman says.

Friedman and Stanley hope that biologists will be able to use the remote-control system to tackle a range of neural processes other than appetite. And beyond being a basic research tool, the method could potentially lead to novel therapies for brain disorders.


www.rockefeller.edu/our-scientists/heads-of-laboratories/

Graphene biointerfaces for optical stimulation of cells

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Researchers have developed a technique that allows them to speed up or slow down human heart cells growing in a dish on command – simply by shining a light on them and varying its intensity. The cells are grown on a material called graphene, which converts light into electricity.

See video (University of California): www.eurekalert.org/multimedia/927967

Savchenko, A., Cherkas, V., Liu, C., Braun, G. B., Kleschevnikov, A., Miller, Y. I., & Molokanova, E.. (2018). Graphene biointerfaces for optical stimulation of cells. Science Advances

, 4(5)
Plain numerical DOI: 10.1126/sciadv.aat0351
DOI URL
directSciHub download

Matt, A., Liang, H., Fishman, M., Gracheva, E., Wang, F., Zhang, X., … Zhou, C.. (2023). Graphene-enabled optical cardiac control in Drosophila melanogaster. In J. A. Izatt & J. G. Fujimoto (Eds.), Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII

(p. 81). SPIE
Plain numerical DOI: 10.1117/12.2652964
DOI URL
directSciHub download

Immunization Via Mosquito Bite With Radiation-attenuated Sporozoites (IMRAS)

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clinicaltrials.gov/ct2/show/NCT01994525

Sponsor:
U.S. Army Medical Research and Development Command

Collaborators:
Seattle Children’s Research Institute (SCRI)
Bill & Melinda Gates Foundation
Principal Investigator:Nimfa Teneza-Mora, MD,Naval Medical Research Center
Information provided by (Responsible Party):
U.S. Army Medical Research and Development Command

***
Study Type : Interventional (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase 1 Trial With Challenge to Assess the Safety and Biomarkers of Protection in Malaria-naïve Adults of Immunization Via Mosquito Bite With Radiation-Attenuated Plasmodium Falciparum Sporozoites (IMRAS)
Actual Study Start Date : January 24, 2014
Actual Primary Completion Date : December 20, 2016
Actual Study Completion Date : February 2017
***

This is a Phase 1 open-labeled study. In addition to safety and tolerability of Plasmodium falciparum Sporozoites (PfRAS), this study is a comprehensive, systems biology-based effort to identify and validate biomarkers of protection with PfRAS immunization, comparing sterility protected to nonprotected study subjects. The goal of the trial design is to achieve approximately 50% sterile protection in order to facilitate the identification of biomarkers and correlates of protection.

Following true-immunization or mock-immunization, study subjects and nonimmunized infectivity controls will receive a challenge via the bites of 5 An stephensi mosquitoes carrying infectious P falciparum sporozoites within a controlled clinical environment (controlled human malaria infection, CHMI) to determine the level of sterile protection.

Architects & Engineers for 9/11 Truth

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15 years later: on the physics of high-rise building collapses.
Europhysics News, 47 4 (2016) 21-26
DOI: dx.doi.org/10.1051/epn/2016402
© European Physical Society, EDP Sciences, 2016
1Steven Jones
2Robert Korol
3Anthony Szamboti
4Ted Walter
1Brigham Young University
2McMaster University (emeritus)
3Mechanical design engineer in the aerospace industry
4Architects & Engineers for 9/11 Truth

Conclusion
“It bears repeating that fires have never caused the total collapse of a steel-framed high-rise before or since 9/11. Did we witness an unprecedented event three separate times on September 11, 2001? The NIST reports, which attempted to support that unlikely conclusion, fail to persuade a growing number of architects, engineers, and scientists. Instead, the evidence points overwhelmingly to the conclusion that all three buildings were destroyed by controlled demolition. Given the far-reaching implications, it is morally imperative that this hypothesis be the subject of a truly scientific and impartial investigation by responsible authorities.”

epn2016474p21

Herman Kahn’s escalation ladder

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Echevarria II, A. (2021). Herman Kahn and Escalation. In War’s Logic: Strategic Thought and the American Way of War (Cambridge Military Histories, pp. 93-110). Cambridge: Cambridge University Press. doi:10.1017/9781316135730.008

Summary

Chapter 5 analyzes the thinking of Herman Kahn, who dared to think the unthinkable. It describes his “America,” which again was that of the golden age of the middle class, but which also overlapped with the sense of malaise that plagued the 1970s. Like the limited war theorists, Kahn agreed military instincts needed to be curbed, and he attempted to counter uncertainty by arguing, largely in vain, that escalation itself was also a bargaining process with systematic waystations or steps embedded along its path. This chapter discusses his model of war’s nature, which, like those of Brodie, Osgood, and Schelling, priviledged war’s political dimension, though he gave policy more agency than did they.

www.cambridge.org/core/books/abs/wars-logic/herman-kahn-and-escalation/19C080FABFE3FCD66358C5AF1366486A


Outside physics and statistics, works written by Kahn include:

  • 1960. On Thermonuclear War. Princeton University Press. ISBN 0-313-20060-2
  • 1962. Thinking about the unthinkable. Horizon Press.
  • 1965. On escalation: metaphors and scenarios. Praeger. ISBN 1-41283004-4
  • 1967. The Year 2000: a framework for speculation on the next thirty-three years. MacMillan. ISBN 0-02-560440-6. With Anthony Wiener.
  • 1968. Can we win in Viet Nam? Praeger. Kahn with four other authors: Gastil, Raymond D.; Pfaff, William; Stillman, Edmund; Armbruster, Frank E.
  • 1970. The emerging Japanese Superstate: challenge and response. Prentice Hall. ISBN 0-13-274670-0
  • 1971. The Japanese challenge: The success and failure of economic success. Morrow; Andre Deutsch. ISBN 0-688-08710-8
  • 1972. Things to come: thinking about the seventies and eighties. MacMillan. ISBN 0-02-560470-8. With B. Bruce-Briggs.
  • 1973. Herman Kahnsciousness: the megaton ideas of the one-man think tank. New American Library. Selected and edited by Jerome Agel.
  • 1974. The future of the corporation. Mason & Lipscomb. ISBN 0-88405-009-2
  • 1976. The next 200 years: a scenario for America and the world. Morrow. ISBN 0-688-08029-4
  • 1979. World economic development: 1979 and beyond. William Morrow; Croom Helm. ISBN 0-688-03479-9. With Hollender, Jeffrey, and Hollender, John A.
  • 1981. Will she be right? The future of Australia. University of Queensland Press. ISBN 0-7022-1569-4. With Thomas Pepper.
  • 1983. The Coming Boom: economic, political, and social. Simon & Schuster; Hutchinson. ISBN 0-671-49265-9
  • 1984 Thinking about the unthinkable in the 1980s. New York: Simon and Schuster. ISBN 0-671-47544-4
  • The nature and feasibility of war, deterrence, and arms control (Central nuclear war monograph series), (Hudson Institute)
  • A slightly optimistic world context for 1975–2000 (Hudson Institute)
  • Social limits to growth: “creeping stagnation” vs. “natural and inevitable” (HPS paper)
  • A new kind of class struggle in the United States? (Corporate Environment Program. Research memorandum)

Einstein’s opposition against Operation Paperclip

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Under Operation Paperclip, which began in May 1945, the scientists who had helped the Third Reich wage war continued their weapons engineering work for the US government, developing missiles, chemical and biological weapons, aerospace medicine (to enhance the performance of military pilots and astronauts) and many other armaments at a feverish and paranoid pace that marked the Cold War. The age of weapons of mass destruction had dawned, and with it came the treacherous concept of “brinkmanship” – the art of pursuing a dangerous policy to the limits of safety before stopping.
The atrocities that followed Hitler’s Final Solution were unfathomable to the rest of the world. Nazi technicians had decided to melt down the gold teeth in their prisoners’ fillings, but thought it easier to kill the victims first for easy access to the jaw.

Ice baths were filled with ice-cold water and a prisoner placed naked in them to find out how long an air force pilot could withstand ice-cold water in a crash. In the notes on this experiment, the Nazi doctors used the term “adult pig” in reference to a human test subject.

The doctors routinely subjected the prisoners to operations without anaesthesia. One man had part of his liver removed in this way, and a young woman had her shin bones removed.

In other experiments, limbs were severed and sewn back on at a different angle.
The US military intelligence knew all of this, yet carefully manoeuvred their Paperclip Doctors out of prosecution at Nuremberg and into America to begin work. This caused some outrage in the international media. Albert Einstein denounced Operation Paperclip in a letter to President Truman.

We hold these individuals to be potentially dangerour. Their former eminence as Nazi Party members and supporters raised the issue of their fitness to become American citizens and hold key positions in American industrial, scientific, and educational institutions.



Thomas Paine: Common Sense (1776)

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“A long habit of not thinking a thing wrong, gives it a superficial appearance of being right, and raises at first a formidable outcry in defense of custom. But the tumult soon subsides. Time makes more converts than reason.”
~Thomas Paine, Common Sense

“Society is produced by our wants, and government by wickedness; the former promotes our happiness positively by uniting our affections, the latter negatively by restraining our vices. The one encourages intercourse, the other creates distinctions. The first is a patron, the last a punisher.”
~Thomas Paine, Common Sense

“Government, like dress, is the badge of lost innocence; the palaces of kings are built on the ruins of the bowers of paradise.”
~Thomas Paine, Common Sense

EU Vaccines Strategy

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commission.europa.eu/strategy-and-policy/coronavirus-response/public-health/eu-vaccines-strategy_en

Legislative documents

Communication: “A united front to beat COVID-19”
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Commission decision on implementing Advance Purchase Agreements on COVID-19 vaccines
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Communication on preparedness for COVID-19 vaccination strategies and vaccine deployment
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Coronavirus: Towards a common vaccination strategy
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Commission’s centralised approach on procuring Covid-19 vaccines on behalf of the Member States
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(247.41 KB – PDF)

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Annex to the Decision of the European Commission on approving the agreement with Member States on procuring Covid-19 vaccines on behalf of the Member States and related procedures
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(326.73 KB – PDF)

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Communication on the EU Strategy for COVID-19 vaccines
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