Changing DNA from Atoms to Bits - Hoover Institute on Synthetic Biology and Governance Systems

I did a live stream this afternoon and someone mentioned this talk. Listening to it now.

Jason and I are planning to do a talk about tokenized governance. Crazy to contemplate that this tokenized gamification may extend to computational biology.

Hey @ldaven he references wanting to get Mark Cuban’s take around timestamp 12 minutes 20 seconds.

Interesting - near the end he says the only freestanding university program of genetic engineering in the world is in Estonia - the blockchain capital and home of Kratt law for AI.

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Drew Endy is a member of the bioengineering faculty at Stanford University and BioBricks Foundation president (biobricks.org). His research teams pioneered amplifying genetic logic, rewritable DNA data storage, reliably-reuseable standard biological parts, and genome refactoring. Drew helped launch the new undergraduate majors in bioengineering at both MIT and Stanford; he also co-founded the iGEM competition, a global genetic engineering “olympics” now engaging over 6,000 students annually (igem.org). In 2013 the White House recognized Drew for his work on open-source biotechnology and, more recently, he received an honorary doctorate from the Technische Universiteit Delft. Drew has served on the US National Science Advisory Board for Biosecurity and the Committee on Science, Technology, & Law; he currently serves on the World Health Organization’s Smallpox Advisory Committee. Drew lives in Menlo Park, California with Christina Smolke (Stanford colleague & Antheia, Inc., CEO), their two boys, and two cats. Drew was a co-founder of Gen9, Inc., a DNA construction company; he returned to serve as a director while Gen9 was successfully acquired. Drew worked briefly with the Rapid Evaluation team at Google [X] and also served on the building project team for the Shriram Center at Stanford. He is a founding co-director of the NIST/Stanford Joint Initiative for Metrology in Biology (jimb.stanford.edu). Esquire magazine recognized Drew as one of the 75 most influential people of the 21st century.

Education

PhD, Dartmouth, Biotechnology & Biochemical Engineering (1998)

MS, Lehigh, Environmental Engineering (1994)

BS, Lehigh, Civil Engineering (1992)


Professor Smolke’s research program focuses on developing modular genetic platforms for programming information processing and control functions in living systems, resulting in transformative technologies for engineering, manipulating, and probing biological systems. She has pioneered the design and application of a broad class of RNA molecules, called RNA devices, that process and transmit user-specified input signals to targeted protein outputs, thereby linking molecular computation to gene expression. This technology has been extended to efficiently construct multi-input devices exhibiting various higher-order information processing functions, demonstrating combinatorial assembly of many information processing, transduction, and control devices from a smaller number of components. Her laboratory is applying these technologies to addressing key challenges in cellular therapeutics, targeted molecular therapies, and green biosynthesis strategies.

Education

Postdoctorate, UC Berkeley, Cell Biology (2003)

Ph.D., UC Berkeley, Chemical Engineering (2001)

B.S., USC, Chemical Engineering (1997)

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The other comment that stood out for me was the guy who talked about de-globalizing through personal home-based 3-D printing of objects transmitted as “bits,” for efficiency and sustainability.

I’m thinking that will likely be connected to good behavior tokens @Jason_Bosch

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I meant to post this earlier today . . .

Engineering RNA Devices for Cellular Information Processing, Sensing, & Control

As examples of functional RNA molecules playing key roles in the behavior of natural biological systems have grown, there has been growing interest in the design and application of synthetic counterparts. Our laboratory is exploring the design of functional RNA molecules that couple ligand-binding activities to diverse regulatory activities to create programmable genetic sensors and controllers; thereby providing new tools for accessing and controlling information in biological systems. Our approach focuses on elucidating quantitative design principles and developing modular design platforms supporting a new input/output (I/O) technology for biological systems. By accessing a variety of gene-regulatory mechanisms, we are building tailored RNA control devices that function in a range of organisms, respond to small molecule and protein inputs, and interface with diverse systems. Our I/O technology can be coupled with other genetic devices to build more complex information processing capabilities into living systems, such as signal amplification, error detection, signal restoration, and differential sensing.

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The person my husband drinks beer with on Fridays is a former yeast researcher. After trying to have a conversation about the ethics of this I became disinvited from the gatherings.

That’s why I’ve said I stand with the yeast. First them, then us.

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@AMcD

What I wrote in February 2021:

3) RE: Digital to Biological Converter

Edling explained that this device is “currently in development.” However, Andrew Hessel, President of Humane Genomics, explained in his presentation at Exponential Medicine 2015 that he is already using his version of this device. It should be noted that Humane Genomics claims to develop synthetic viruses for animal and human health. In Hessel’s 2015 presentation, within his framework of designer bio-nanotechnology, he looks at biological cells in all living things as a type of computing and manufacturing hardware that self-assembles. He elaborated that it has a programming language — DNA. He said that he does nanotechnology digitally, and in a way that scales and then he can share the code. He emphasized that one has to consider programming living cells to do the work, and that he uses DNA to do this.

Around the 7:40 time stamp, Hessel described a nano printer he uses called the DNA synthesizer that has specialized bio-nano digital design software: “It is a printer that prints the DNA molecule . . . chemical bit by chemical bit by chemical bit, and strings it together to write code. It’s really the only printer that I’m interested in, for the most part, because it’s really the only chemical printer you can have sitting on a desk that can do so many different things because it can reprogram the cell — which is essentially a 3D printer for millions of chemicals all in one go.” Please note that at the 7:43 timestamp, he displayed a graphic showing a DNA printer that prints engineered viruses and engineered organisms, that he claimed is currently available and goes beyond the capabilities of 3D printing prosthetics, tissues, and organs for human bodies. At the conclusion of his talk, there was a brief Q&A, in which Hessel opined that “viruses are the apps for the body,” such that viruses are what allow “genetic code to move between species and through the world.”

Note: In Hessel’s 2015 talk, he refers to the work of Moderna at time stamps: 9:03 and 18:52, in the context of reprogramming cells with synthetic proteins, peptides, and polymerases which may be able to self-assemble and be electronically controlled to write DNA.

In June 2017, VICE Media published an article, “Craig Venter’s ‘Digital-to-Biological Converter’ Is Real.” The author, Jordan Pearson, described the tabletop device called the Digital-to-Biological Converter (DBC), that received digital representations of DNA over the Internet and then reconstructs them using adenine, cytosine, guanine, and thymine. Craig Venter, founder of Synthetic Genomics, explained that the precursor of his device was used to synthesize an avian flu vaccine in 2013. According to Venter, the current iteration can print DNA, RNA, viruses, vaccines and bacteriophages.

As stated by VICE author, Pearson, *“The idea, as Venter describes it, is for every major hospital, clinic, and corporation in the world to own a DBC. If a viral outbreak hits, the vaccine could be sent around the world in a digital file in minutes and produced locally, instead of being stockpiled and shipped out. *‘We could stop pandemics in their tracks,’ Venter said.


I think my post from September 2021 is also very relevant (speaks to the yeast as well):

Fan continued in her 2017 analysis, This isn’t the first time that scientists hijacked life’s algorithms to reprogram cells into nanocomputing systems . Previous work has already introduced to the world yeast cells that can make anti-malaria drugs from sugar or mammalian cells that can perform Boolean logic. Yet circuits with multiple inputs and outputs remain hard to program. The reason is this: synthetic biologists have traditionally focused on snipping, fusing, or otherwise arranging a cell’s DNA to produce the outcomes they want (my emphasis).”

Fan sounded a few warnings:

“But DNA is two steps removed from proteins, and tinkering with life’s code often leads to unexpected consequences . For one, the cell may not even accept and produce the extra bits of DNA code. For another, the added code, when transformed into proteins, may not act accordingly in the crowded and ever-changing environment of the cell (my emphasis).”

“What’s more, tinkering with one gene is often not enough to program an entirely new circuit. Scientists often need to amp up or shut down the activity of multiple genes, or multiple biological “modules” each made up of tens or hundreds of genes.”

“It’s like trying to fit new Lego pieces in a specific order into a room full of Lego constructions. Each new piece has the potential to wander off track and click onto something it’s not supposed to touch.”

“Getting every moving component to work in sync—as you might have guessed—is a giant headache.”

Fan expounded, “Because RNAs bind to others so predictably, we can now design massive libraries of gate and trigger units to mix-and-match into all types of nano-biocomputers.”

“Although the technology doesn’t have any immediate applications, the team has high hopes.”

“For the first time, it’s now possible to massively scale up the process of programming new circuits into living cells. We’ve expanded the library of available biocomponents that can be used to reprogram life’s basic code (my emphasis) . . .”

But here’s the kicker (as expressed by neuroscientist Fan) . . . and the punchline to this entire mRNA programming story:

“Because we’re using RNA, a universal molecule of life, we know these interactions can also work in other cells, so our method provides a general strategy that could be ported to other organisms . . . Ultimately, the hope is to program neural network-like capabilities into the body’s other cells. Imagine cells endowed with circuits capable of performing the kinds of computation the brain does . . . Perhaps one day, synthetic biology will transform our own cells into fully programmable entities, turning us all into biological cyborgs from the inside. How wild would that be? (my emphasis)”


Also from my post in September 2021:

It is my opinion that this injectable nano-biologic is a literal ticket into becoming a mechanized, mineable, and programmable commodity amidst bio-digital slavery, and the adjoining QR-coded geofencing passport is simply the window dressing. We are staring down the barrel of a loaded gun, and the ammo is the transhumanist cocktail leading in only one direction — toward imperialistic-steered extinction of currently-defined humans (a soft genocide, if you will).

Make no mistake, this presumably nanotoxin-laced, genetic-altering serum may be a novel baptism vehicle into a not-so-holy cult of transhumanism. The emerging technology platform may be poised to replace the sacred structured water that sustains us and our DNA — which seems to reflect the true science and source of life.

While I stated that I did not wish to be redundant in this essay, I feel compelled to return to one self-proclaimed professional biohacker, in particular, (whom I previously featured in Part 3). As Chairman and Co-founder of Genome Project-write (GP-write), Andrew Hessel is not only prominent and influential in the field of synthetic biology, he is a strong voice within the Singularity movement as well. He openly admits to desiring to rewire and reprogram organisms “to do jobs they can’t do in their natural state.” Hessel aims to merge human with machine via nanotechnology and programmable software (AKA synthetic messenger RNA). We should keep in mind that programmable RNA (of which mRNA is one form) is a living computational nano-device.

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Thanks for pulling that information out. It’s so overwhelming.

CONNECTING ATOMS TO BITS – WHY IT MAY NOT BE ENOUGH ?

IOT IS A DESIGN METAPHOR for DIGITAL TRANSFORMATION X.0

Shoumen Palit Austin Datta

In the illustration below (Fig 2), I have included my projections (circa 2000), to highlight the progression from the physical world of atoms, to the transformation, in terms of the digital economy, where information about atoms may be represented by bits (Digital Twins) or bits, per se, may be information or data from decisions, processes and things, referring to the internet of things or IoT and industrial IoT. A few projections11 did not materialize12 but exceptions may prove the rule, albeit, partially. Other models by Poire (see Figure 24) suggests that the 2020’s may witness transformative changes.

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Andrew Hessel at Singularity U in 2017 “Biology is Nanotechnology”

minute 9: “we’re able to take a drop of blood and get a full genome”

minute11: [The company] “Health Nucleus is starting to build avatars, a digital health representation of the human being… that gets deep into your personal health…[at] the core of your story.”

—Health Nucleus was founded in San Diego by J. Craig Venter Craig Venter's Health Nucleus tries to reshape medicine

August 2020-- Andrew Hessel, interviewed by Josh Wolff :

Wolff: Can you tell me more about the process of developing the viruses?

[A.H.] “We begin with small molecule drugs. We sort of throw away those because while you can computationally predict those, you have no idea how they are going to end up in the body – and what kind of reaction will ensue. So, we began with biologics, and we tried to remove this hard-to-predict problem.

“Cells, viruses – they’re all machines, in a way. So we began by making a synthetic virus totally from scratch. It’s not as difficult as it may seem. You see, it’s just that no one is doing it. There has been paltry development in the field over the past 20 to 30 years. If you look at the number of viruses that have been sequenced, there may be around 8300. If you look at the number of viruses that have been synthesized, there may have been 30. This field is ripe for growth…” https://www.ssbprobe.com/articles/2020/7/11/an-interview-with-andrew-hessel-founder-of-humane-genomics


Dr. Charles Morgan, PTSD specialist, speaks at the Modern War College June 2018

Morgan talks about DREADDs, a yeast platform developed by Venter

…“Related to [medicine and individualized drugs] is DREADDs; Designer Receptors that can be remotely controlled – You can design a [cell] receptor, create a cell, put it somewhere in the body and you can remotely activate it when the brain is exposed to the right signal. Using this technology, people have been able to transfer memories from one fruit fly to another by signaling through a light stimulus into the retina. Right now [2018], in most animals it’s done by putting a substance into the body that will actually activate the neurons in the way that you want it. So [with DREADDs] you have the capacity to create any [biologically synthesized] product as long as you know the DNA sequence and insert it into a living system and you can remotely control it.”

“When you create a cell and put it in somebody’s body, you have to figure out where you want it [to go]—what if you want it in their brain, right? And…you don’t want to do surgery to plant it in their brain to affect the way [they] think and act [then the] route to that is through stem cells… They call them God cells –they can turn into anything…unlike other cells in your body to become anything you want them to become and they can go find their home in the body and park there and do the work that you’d ike them to do. [ Power point shown “Mesenchymal stem cells: Infused peripherally can access brain tissue” Linan Liu et. al. 2013] So once you know the technology is [here] to edit, splice and program the cell and the technology currently exists to administer it… you can have things activated in other peoples’ brains. You can have the timed release of information on demand.

“DNA encryption –and it’s quite important– …I’ll just say the short story on this [is] people have figured out how to hide imagery in the DNA of bacteria and when you phosphoresce the bacteria you can discover the information or you can have the information reproduced in string form, the form of a protein. Dr. [George] Church up at Harvard has shown quite well that you can store a lot of information in one gram of DNA… at room temperature…for a very long time. So between CRISPR [developed by Church], storage capacity and programming cells, the new way to hide information is going to be in DNA… Why would you have a digital system when you can have a DNA system to store all the information you’ll ever need –photos, records, everything… You can hide information in bacteria and when the bacteria multiply they can go into spore form and last for a very long time. No one can scan you and find a bacteria. We don’t have anything that can detect that, so if you want to encode information… [in] DNA, and you don’t want it in your own body…[you get it back if] you scrape it [off], put it in a dish and unpack the information. This is all available now. This isn’t science fiction. [min33-37]

“What Are DREADDs? Designer Receptors Activated Only by Designer Drugs" (DREADDs) belong to a class of proteins called chemogenetic proteins. These engineered proteins allow scientists to control nerve cell activity in ambulatory animals.

“DREADDs allow G-protein-coupled receptors to respond to synthetic ligands and not their natural ligand, acetylcholine. They are activated by a molecule called clozapine-N-oxide (CNO) which is biologically inert.

“G-proteins are important cell signaling molecules, and researchers can investigate cell function in living organisms by modulating this signaling in time and space. The greatest use of DREADDs is in neuroscience because CNO can easily cross the blood-brain barrier.

“…DREADDs are mutant muscarinic receptors…” What are DREADDs?.

The Use of DREADDs to Deconstruct Behavior

2016—“A central goal in understanding brain function is to link specific cell populations to behavioral outputs…. This technique allows for the control of molecularly defined subsets of cells through engineered G protein-coupled receptors (GPCRs), which have the ability to activate or silence neuronal firing… DREADDs are used ubiquitously to modulate GPCR activity in vivo and have been widely applied in the basic sciences, particularly in the field of behavioral neuroscience. Here, we focus on the impact and utility of DREADD technology in dissecting the neural circuitry of various behaviors including memory, cognition, reward, feeding, anxiety and pain. By using DREADDs to monitor the electrophysiological, biochemical, and behavioral outputs of specific neuronal types, researchers can better understand the links between brain activity and behavior. Additionally, DREADDs are useful in studying the pathogenesis of disease and may ultimately have therapeutic potential.” The Use of DREADDs to Deconstruct Behavior - PMC

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Mad scientists. I’ve seen the term DREADs, but didn’t really get what they were. Thanks.

““Optogenetics is very good if you want millisecond control,” he notes. Chemogenetics, on the other hand, is easier to use, and more practical for activating larger populations of neurons. Instead of implanting light fibers all over the brain, “you can put the drug in the drinking water,” Dr. Roth explains, and simultaneously activate all the cells containing your DREADD, wherever they are located.”

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Seriously spooky article, Alison. I’m going to dig into it.

@AMcD @jenlake Note: I inserted engineered nanotech myself each time I saw “virus” or “viruses” or “virus particles” or “viral vectors” . . .

Mikhail G. Shapiro, Ph.D., assistant professor of chemical engineering at the California Institute of Technology, turned to ultrasound to develop a noninvasive technique for getting viruses (engineered nanotech) into specific brain regions. First, micrometer-size bubbles are sent into the bloodstream, then focused ultrasound is applied to the area of interest, with millimeter precision.

“Wherever we’re applying the ultrasound, these bubbles expand and contract with the ultrasound wave,” Dr. Shapiro says. As the bubbles bump against the blood–brain barrier, he explains, they create an opening that allows virus particles (engineered nanotech) to enter the brain, just in that location.

“This allows us to specify, based on where we’re applying the ultrasound, what spatial part of the brain we want to modulate,” Dr. Shapiro continues. The blood–brain barrier stays open about two hours, and during that time viral vectors (engineered nanotech) containing chemogenetic elements can be injected in the bloodstream.

The technique, which Shapiro calls “acoustically targeted chemogenetics,” or ATAC, eliminates certain downsides to setting up a chemogenetic system in animals with larger brains. For instance, the study of a larger region of the brain, or multiple different regions, typically involves dozens of injections of virus (engineered nanotech) and repeated piercings of the brain. With ATAC, the ultrasound beam can easily be shifted around to target the desired areas. “From the point of view of both convenience, and also, how much are you perturbing the brain through the surgical approach, I think this noninvasive technique has some advantage,” asserts Dr. Shapiro.


This stuff is DREADDful.

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[July 2021] Mikhail Shapiro, PhD, is a new type of scientist, one who combines the physical interactions of ultrasound with synthetic biology—the field of science that redesigns organisms for useful purposes by engineering them to have new abilities. Besides being a Professor of Chemical Engineering, a Heritage Medical Research Institute Principal Investigator, and the Director of the Center for Molecular and Cellular Medicine at the California Institute of Technology (Caltech), Dr. Shapiro has a 28-person research laboratory dedicated to ultrasound imaging and focused ultrasound. We interviewed him to learn about his incredible work creating bidirectional communication with cells by engineering them to express gas vesicles, making them sensitive to temperature changes, and modulating their activity through acoustically targeted receptors.

When and how did you get interested in focused ultrasound?
“Ultrasound imaging was my starting point, but over time our lab has developed several major efforts in focused ultrasound perturbation of cells. The first time that I noticed focused ultrasound was when I was in graduate school at the Massachusetts Institute of Technology (MIT). I was working on MRI imaging agents. Kullervo Hynynen was still in Boston at that time, and I heard him or one of his colleagues talk about using ultrasound to open the blood-brain barrier. I thought that it sounded totally crazy and wanted to learn more. After I saw his beautiful results, I was completely hooked, but I couldn’t add it to my research until I started my lab at Caltech in 2014. But then we started working on focused ultrasound right away.

How do you see the cells that you are perturbing?
We take advantage of the same genetic engineering that makes cell-based therapies possible. Most of these cells, such as CAR-T cells in cancer immunotherapy, have been genetically modified to have receptors that recognize tumors. Similarly, we developed a method to genetically modify cells so that they can be imaged and controlled by ultrasound. For this purpose, we adapted some very unusual air-filled proteins, called gas vesicles, which originally evolved as flotation devices in aquatic photosynthetic microbes, as imaging agents for ultrasound. The gas vesicles are genetically encoded, so we can put these specific genes into bacterial or mammalian cells. Based on the gene circuit we implement, the cells will produce gas vesicles when they encounter a certain signal in their environment. We can then use ultrasound imaging to see the gas vesicles that the cells are producing and see that the cells have been activated. And more recently we discovered that we could use focused ultrasound to “blow up” those gas vesicles and cause local effects like drug release or localized mechanical damage by seeding cavitation. It is like local production of a warhead that can be remotely triggered.

I am excited about our work in acoustically targeted chemogenetics. Our 2018 paper in Nature Biomedical Engineering showed how we can use ultrasound to open the BBB to allow systemically administered viral vectors to introduce chemogenetic receptors into neurons in the brain. After they are expressed, these chemogenetic receptors make the neurons at the ultrasound-targeted site become excited or inhibited when we administer a simple pill. Instead of responding to neurotransmitters like normal receptors, the chemogenetic receptors respond to otherwise inert small molecule drugs that are ingested and are permeable across the BBB (no additional BBB opening is required).

…After waiting a few weeks for the expression of the receptors, a pill is administered whenever we want to turn the functionality of the targeted brain circuit up or down. This is a type of selective pharmacology. While this might seem futuristic, it is based on well-established components. BBB opening and chemogenetics have been around for some time, and the type of viral vector that we used in the 2018 Nature Biomedical Engineering paper has been approved by the FDA for certain indications.

The 2018 study in mice focused on the hippocampus; we were able to prevent mice from forming memories on demand—or turn off memory formation. Based on that work, our laboratory received a grant from the NIH BRAIN Initiative to scale this technology to nonhuman primates. We are also improving each aspect of the technology, including the viral vectors. For example, we are modifying the amino acid sequence of the viral capsid to improve its entry into the brain across the BBB.

…We have a collaboration with Richard Anderson, PhD, a scientist who works on brain-machine interfaces here at Caltech, to use the functional ultrasound readouts from the brain as a brain-machine interface. The results of this work, just published in Neuron, have amazed me because they showed that the information content ultrasound can extract from the brain are sufficient to predict intended movements before they happen. We have been doing those experiments in non-human primates and have recently started a study in humans.

For molecular imaging of brain activity, we are trying to engineer our gas vesicles to produce an ultrasound signal that depends on molecular events in neurons, such as changes in gene expression or the activity of certain proteins such as enzymes. This is similar to what other scientists are doing with fluorescent biosensors, which are well established but are limited by the depth of the neurons relative to how far light can penetrate. Therefore, if we can express our gas vesicle-based sensors in the brain, we can look at the signals with ultrasound instead of light. This technology could answer basic neuroscience questions, such as, “How does emotion work? Or how do we recognize faces?”

…Many postdoctoral researchers who come to work in my lab are ultrasound experts who want to work on cellular function. We are building a good track record of turning ultrasound engineers into people who are able to also work on synthetic biology. Now several of them are starting their own labs.

Are you creating a new field between ultrasound and cellular biology?
I hope so.

[see the list of funders and collaborators]

**

[Wikipedia]

Gas vesicles, also known as gas vacuoles, are nanocompartments in certain prokaryotic organisms, which help in buoyancy.[1] Gas vesicles are composed entirely of protein; no lipids or carbohydrates have been detected…

Role in vaccine development

Gas vesicle gene gvpC from Halobacterium sp. is used as delivery system for vaccine studies.

Several characteristics of the protein encoded by the gas vesicle gene gvpC allow it to be used as carrier and adjuvant for antigens: it is stable, resistant to biological degradation, tolerates relatively high temperatures (up to 50 °C), and non-pathogenic to humans.[15] Several antigens from various human pathogens have been recombined into the gvpC gene to create subunit vaccines with long-lasting immunologic responses.[16]

Different genomic segments encoding for several Chlamydia trachomatis pathogen’s proteins, including MOMP, OmcB, and PompD, are joined to the gvpC gene of Halobacteria. In vitro assessments of cells show expression of the Chlamydia genes on cell surfaces through imaging techniques and show characteristic immunologic responses such as TLRs activities and pro-inflammatory cytokines production.[17] Gas vesicle gene can be exploited as a delivery vehicle to generate a potential vaccine for Chlamydia. Limitations of this method include the need to minimize the damage of the GvpC protein itself while including as much of the vaccine target gene into the gvpC gene segment.[17]

A similar experiment uses the same gas vesicle gene and Salmonella enterica pathogen’s secreted inosine phosphate effector protein SopB4 and SopB5 to generate a potential vaccine vector. Immunized mice secrete pro-inflammatory cytokines IFN-γ, IL-2, and IL-9. Antibody IgG is also detected. After an infection challenge, none or significantly less amount of bacteria were found in the harvested organs such as the spleen and the liver. Potential vaccines using gas vesicle as an antigen display can be given via the mucosal route as an alternative administration pathway, increasing its accessibility to more people and eliciting a wider range of immune responses within the body.

Role as contrast agents and reporter genes

Gas vesicles have several physical properties that make them visible on various medical imaging modalities.[18] The ability of gas vesicle to scatter light has been used for decades for estimating their concentration and measuring their collapse pressure . The optical contrast of gas vesicles also enables them to serve as contrast agents in optical coherence tomography, with applications in ophthalmology.[19] The difference in acoustic impedance between the gas in their cores and the surrounding fluid gives gas vesicles robust acoustic contrast.[20] Moreover, the ability of some gas vesicle shells to buckle generates harmonic ultrasound echoes that improves the contrast to tissue ratio.[21] Finally, gas vesicles can be used as contrast agents for magnetic resonance imaging (MRI), relying on the difference between the magnetic susceptibility of air and water.[22] The ability to non-invasively collapse gas vesicles using pressure waves provides a mechanism for erasing their signal and improving their contrast. Subtracting the images before and after acoustic collapse can eliminate background signals enhancing the detection of gas vesicles.

Heterologous expression of gas vesicles in bacterial[23] and mammalian[24] cells enabled their use as the first family of acoustic reporter genes.[25] While fluorescent reporter genes like green fluorescent protein (GFP) had widespread use in biology, their in vivo applications are limited by the penetration depth of light in tissue, typically a few mm. Luminescence can be detected deeper within the tissue, but have a low spatial resolution. Acoustic reporter genes provide sub-millimeter spatial resolution and a penetration depth of several centimeters, enabling the in vivo study of biological processes deep within the tissue.

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@jenlake ABSOLUTELY HORRENDOUS. Thank you for this elaboration. Unbelievable. Despicable, truly. This is dual-use (even if they do not admit as such)! Makes me wonder about the “gas bubbles” that some researchers have purportedly found in the COVID jabs.

Mikhail G. Shapiro, PhD, is an assistant professor of chemical engineering and a Heritage Principal Investigator at the California Institute of Technology. Previously, he was a Miller Research Fellow in Bioengineering and Molecular & Cell Biology at the University of California at Berkeley. His research is focused on the development of biomolecular technologies for non-invasive imaging and control of cellular function in the body using ultrasound and magnetic fields. Dr. Shapiro received his PhD in biological engineering as a Hertz and Soros fellow at the Massachusetts Institute of Technology with co-advisers Robert Langer and Alan Jasanoff and his BSc in neuroscience from Brown University. He conducted post-doctoral research in biophysics at the University of Chicago with Francisco Bezanilla.

Among his research accomplishments, Dr. Shapiro developed the first genetically engineered functional sensors for magnetic resonance imaging of the brain, discovered fundamental mechanisms by which infrared light stimulates neurons, and introduced the first genetically encoded molecular imaging agents for ultrasound. In addition to his research, Dr. Shapiro has been a co-founder of several life science start-up companies and served as a venture principal at Third Rock Ventures.

Dr. Shapiro was awarded a Hertz Foundation Thesis prize in 2009. He has received the Burroughs Wellcome Career Award at the Scientific Interface, the DARPA Young Faculty Award and Director’s Fellowship, the Pew Scholars Award, the Sontag Foundation Distinguished Scientist Award, the Packard Fellowship for Science and Engineering and the Technology Review TR35 award for top innovators under age 35.

More information about the Shapiro Lab can be found at shapirolab.caltech.edu.

Graduate Studies

Massachusetts Institute of Technology

Field of Study: Bioengineering

Thesis: Genetically Engineered Sensors for Non-Invasive Molecular Imaging using MRI

Awards

2020, Science News 10: Scientists to Watch, Science News Magazine
2019, Vilcek Prize for Creative Promise in Biomedical Science, Vilcek Foundation
2016, Packard Fellow, David & Lucile Packard Foundation
2010, TR35, MIT Technology Review
2009, Hertz Thesis Prize, Fannie & John Hertz Foundation
2004, Soros Fellow, Paul and Daisy Soros Fellowship for New Americans

Related News

01/08/21 Manipulating Proteins to Create Cellular Ultrasound

https://orcid.org/0000-0002-0291-4215

https://cce.caltech.edu/people/mikhail-g-shapiro

Research Summary

Molecular and cellular engineering; Non-invasive imaging and control of biological function; Cell and gene therapy; Neuroscience; Cancer; Nanotechnology; Synthetic biology

https://shapirolab.caltech.edu

https://authors.library.caltech.edu/114997/

Shapiro’s doctoral advisor:

RE: Manhattan Project

Qian Xuesen , or Hsue-Shen Tsien (Chinese: 钱学森; 11 December 1911 – 31 October 2009), was a Chinese mathematician, cyberneticist, aerospace engineer, and physicist who made significant contributions to the field of aerodynamics and established engineering cybernetics. Recruited from MIT, he joined Theodore von Kármán’s group at Caltech.[1]

he helped lead the Chinese nuclear weapons program.[6] This effort ultimately led to China’s first successful atomic bomb test and hydrogen bomb test, making China the fifth nuclear weapons state, and achieving the fastest fission-to-fusion development in history. Additionally, Qian’s work led to the development of the Dongfeng ballistic missile and the Chinese space program. For his contributions, he became known as the “Father of Chinese Rocketry”, nicknamed the “King of Rocketry”.[7][8] He is recognized as one of the founding fathers of Two Bombs, One Satellite.[9]

While at Caltech, Qian had secretly attended meetings with J. Robert Oppenheimer’s brother Frank Oppenheimer, Jack Parsons, and Frank Malina that were organized by the Russian-born Jewish chemist Sidney Weinbaum and called Professional Unit 122 of the Pasadena Communist Party.

Qian wrote Engineering Cybernetics, which was published by McGraw Hill in 1954. The book deals with the practice of stabilizing servomechanisms. In its 18 chapters, it considers non-interacting controls of many-variable systems, control design by perturbation theory, and von Neumann’s theory of error control (chapter 18). Ezra Krendel reviewed[38] the book, stating that it is “difficult to overstate the value of Qian’s book to those interested in the overall theory of complex control systems.”

Legend of Tsien’s family[edit]

H.C. and H.S. Tsien[edit]

Tsien’s cousin, the famous aerospace scientist and engineer Tsien Hsue-shen (H.S.), also played important roles both in the United States and China (however, quite opposite to Hsue-Chu Tsien’s first-ROC-then-USA, H.S. first served the United States and later the PRC). H.S. was a co-founding father of the Caltech Jet Propulsion Laboratory (later acquired by NASA). The two cousins had totally different destinies. After 1949, Hsue-Chu Tsien decided to stay and work in the United States; however H.S., widely regarded as a victim of the McCarthyism during the 1950s, was deported to the communist China in 1956. H.S. became the prominent leader of China’s rocket and missile programs. In 1979, H.S. was awarded the prestigious Distinguished Alumni Award of Caltech, which he received in 2001.[4] H.S., a senior academician of both the Chinese Academy of Sciences and Chinese Academy of Engineering, died in Beijing on October 31, 2009, at age 97.

Hsue-Chu Tsien and H.S. not only shared the same paternal grandfather, but also were schoolmates. They matriculated at the same university (Jiaotong University) and had the same major. H.S. was one year senior.

Both Tsiens won the Boxer Indemnity Scholarship and went to study in the United States in the 1930s, with H.S. went to USA in August 1934, and Hsue-Chu Tsien followed after one year (in August 1935). They became school mates again in the United States, both studied at MIT, but H.S. later transferred to Caltech.

During World War II, H.C. was given the military rank of Air Force Colonel by the Republic of China when he served as the Deputy Chief Engineer at the Dading Airplane Factory (大定飛機製造廠) in Dading, Guizhou Province. Approximately at the same time, H.S., the cousin of H.C., was also temporarily given the military rank as colonel, but by the United States Army Air Forces.[5] In 1956 during the Sino-Soviet negotiation, H.S. was again temporarily granted military rank but as the Lieutenant General of the People’s Liberation Army; it was nominated by Zhou Enlai and approved by Chairman Mao Zedong.[6]

The science and engineering dynasty[edit]

Hsue-Chu Tsien married Yi-Ying Tsien (Née: Li; 李懿颖), her brothers were also MIT alumni and engineering professors at MIT. Two of Yi-Ying Tsien’s brothers S. Y. Lee and Y. T. Li are members of the National Academy of Engineering. Y. T. Li’s wife, T.D. Lin (林同端), is the sister of Tung-Yen Lin who was also a member of the National Academy of Engineering and received the National Medal of Science in 1986 from President Ronald Reagan. Tung-Yen Lin’s cousin Tung Hua Lin was also a member of the National Academy of Engineering and received the Theodore von Karman Medal in 1988. Tung Hua Lin’s son Robert Lin is a member of National Academy of Sciences.

Hsue-Chu Tsien had three sons, the oldest Richard W. Tsien is a famous neurobiologist at Stanford who’s also member of both the United States National Academy of Sciences and Institute of Medicine; the youngest - Roger Y. Tsien was a cell biologist who was the 2008 Nobel Chemistry Prize Laureate.[7]

"A big biowork studio like what Jason and this team has, it feels like a movie production lot and they’ve got to ship bio code that’s content that works reliably whatever the local context is. We are, on average very far from that technically because of our fundamental ignorance underlying our knowledge of of how cells operate. There is no natural cell on earth that’s completely understood. Even the best studied cells still have about 20 percent of their essential genes and nobody knows what they do. So what that leads to is very interesting practice and metaphor. So for example if we get a cell to do something useful the word we have is oh I hijacked the machinery of this cell. Solve the problem. Hijack the cell? So what does that mean? It’s like fancy bio engineering professors, We’re training hijackers. Cellular hijackers. I don’t want to do that. We’d much rather train Captains of cells."

They are playing around with life, which they admittedly don’t understand and are hijacking it. Yes, hijacking is the correct word. Not training Captains. These people are unbelievable!

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Remember when Tomicah Tillemann praised Estonia for “getting digital identity right” in response to your question at the Mormon Transhumanist Conference?

@AMcD you’ve talk about Estonia before. They are clearly a major test bed. First digital nation.

Ukraine is also very significant.

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Interesting how Jason Kelly From Ginko Bioworks suggests starting a “space race” to build a cell while throwing out marketing ideas for getting funding. It has to be in competition with China he says. Reminds me of the race to the moon narrative. In competition with Russia. And the “Cold War” narrative that led to massive build up of arms. It’s comforting to know he doesn’t think there’s “an appetite” for that.