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Noncanonical Amino Acids Inspire the Development of Novel Drugs

From Cambridge, U.K., to Cambridge, MA, and from creating better cytokines to aiding gene therapy, the development of new amino acids is likely to open…

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6 months ago

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By Julianna LeMieux, PhD

The first amino acid, discovered in 1806, had a disarmingly ordinary source: asparagus juice. Hence the name asparagine. The next amino acids to be discovered had sources that were, if anything, even more humble. By 1820, cystine had been isolated from urinary stones, glycine from gelatin, and leucine from muscle and wool. All of the common amino acids were discovered by 1935, when threonine emerged from studies of animal nutrition involving growth stimulation assays.

Although threonine was the last of the 20 common amino acids, it was not the last of the proteinogenic amino acids. There were two more: selenocysteine, which was discovered in 1986, and pyrrolysine, which was discovered in 2002. These more recently discovered (and less commonly found) amino acids opened questions about the adaptability and utility of amino acids. Are there others that remain undiscovered? Could new amino acids be engineered? If so, what applications could they enable?

These questions prompted researchers to venture beyond their textbooks and initiate the study of noncanonical amino acids (ncAAs). Indeed, ncAAs have been inspiring academic work for over two decades. They have also been the focus of commercial activity, albeit only in recent years.

Much of this activity occurs at startup companies. One such company is Constructive Bio, which was launched to apply research initiated by Jason Chin, PhD, at the MRC Laboratory of Molecular Biology (MRC-LMB). Another such company is GRO Biosciences (GRObio), which is commercializing research initiated by George Church, PhD, at Harvard Medical School. The academics may have pioneered the biology underlying ncAAs and how they can influence protein engineering. Now, it is the companies’ work to turn that research into a new class of improved drugs.

Starting from scratch

When describing the work going on at Constructive Bio, Ola Wlodek, PhD, the company’s CEO, refers to noncanonical amino acids, or ncAAs. Other scientists working in this space may refer to nonstandard amino acids, or nsAAs. This is a “to-may-to/to-mah-to” issue, she explains. Everyone is talking about the same thing: amino acids outside of the natural code of 20 (or 22).

Ola Wlodek, PhD
Contructive Bio

Constructive Bio, Wlodek continues, is interested in writing genomes from scratch to “open the chemical space of cells into many new possibilities.” Because the company relies on large-scale genome synthesis technology to write genomes from scratch, it can modify the existing alphabet of ncAAs. It can even create completely new blueprints.

According to Wlodek, Chin decided that Constructive Bio could write things better, “from de novo, from the get-go.” This is backed by decades of work and multiple papers from Chin’s academic group. His laboratory showed, in high-profile papers published in 2019 and 2021, that it is possible to write a genome from scratch with little redundancy in the genetic code.1,2 The lack of redundancy when it comes to genetic code (or, as they say, reimagining the genetic codes of the cells) allows the cells to produce designer biomolecules with novel functionalities.

Why do this? To build cellular biofactories, Wlodek answers. ncAAs allow the researchers at Constructive Bio to bring novel functionalities to peptides, proteins, and polymers. The goal is making biomolecules—designer proteins of the future—through cellular biofactories that will skip over many of the steps found in current bioprocessing technologies.

Wlodek points to the specific example of semaglutide, the active ingredient in Ozempic (approved for type 2 diabetes) and Wegovy (approved for weight loss). Semaglutide is a peptide that requires an ncAA at its N-terminus. To manufacture Ozempic, Novo Nordisk relies on solid-phase synthesis—a method that comes with certain supply chain challenges. The goal at Constructive Bio is to avoid such challenges. Specifically, the company aims to make ncAA-containing drugs (and endow them with designer properties) through bacterial synthesis, a common means of producing biologics.

How do you start to think about making proteins with new amino acids? With the end goal in mind, Wlodek answers. First, Constructive Bio identifies a problem with a biologic. For example, cytokine drugs are unstable. Indeed, they may be so vulnerable to the rigors of administration that their ability to carry out the functions of (structurally identical) natural cytokines is compromised. Second, the company develops a solution. For example, a redesign solution could enhance the stability of cytokine drugs so that they could be taken less frequently or in lower doses. (Redesigns typically involve chemical modifications that introduce novel and pharmacologically beneficial properties.) Third, the team at Constructive Bio links its solutions, on the ncAA level, with discoveries around tRNA synthase, the enzyme responsible for loading an ncAA onto a tRNA.

Constructive Bio focuses on using orthogonal elements—that is, elements that react with the novel ncAA and its codon but nothing else—to minimize cross-reactivity. Orthogonality can depend on choosing the right starting point. For example, in synthetase discovery, starting with pyrrolysyl-tRNA synthetase (PylRS) can be advantageous. Still, the enzymes must be evolved so that they start recognizing only the ncAA (and tRNA) of interest through their active sites. Then, the reaction is specific and has high fidelity.

Like other synthetic biology companies, Constructive Bio must face scaling challenges. It was launched last August, and it currently employs 15 people at a site in Cambridge, U.K. Soon, the company will move to a larger facility, also in Cambridge. Another move the company plans is one from small-scale to large-scale fermentation.

Constructive Bio maintains that its decision to use Escherichia coli may facilitate scaling. The company’s E. coli strain is not an average laboratory strain. It’s called Syn61 because it uses only 61 codons in its genome, not 64 like other bacteria. The three “excess” codons were replaced in every single coding sequence in the Syn61 genome, meaning that 18,000 codons across the genome were changed in one go. But even with its new genetic code, Syn61 behaves like standard E. coli.

Wlodek indicates that Constructive Bio is pragmatic. It looks at synthetic biology as a tool and not as a business model. It leaves fundamental research tasks, such as determining the degree to which the genetic code can be reduced, to the Chin laboratory. Indeed, the company is content to turn discoveries from the Chin laboratory into practical applications. In Wlodek’s words, the company is interested in the “fruit of the technology.”

The proteins that Constructive Bio is starting with are complex biologics with new functionalities. But Wlodek says that the company won’t stop at drugs. Instead, it will pursue the “completely programmable polymers of the future.”

Turning immunity around

Like Constructive Bio, Cambridge, MA-based GRObio develops ncAA-based technology that has academic roots. In GRObio’s case, the research started in the Church laboratory at Harvard Medical School.

When Dan Mandell, PhD, was a postdoctoral researcher in the laboratory, he fully recoded the UAG codon and repurposed it to incorporate an nsAA. One implication of this work was that other codons could be recoded. Another was that a one-codon reassignment could permit an nsAA to be installed, as Mandell says, “anywhere you want, as many times as you want.” Eventually, this work led to a genomically recoded organism (GRO).

The organism that GRObio is working on now, together with colleagues, will have seven codons reassigned. According to GRObio, it will be a “radically recoded organism.” The microbe cannot be made through genome editing, like the first one. Rather, it will be created through whole genome synthesis.

The goal is to get rid of the tRNA to truly repurpose selected codons so that no competition remains in the organism. Recoding seven codons will yield three tRNAs and one stop codon. In that case, four nsAAs can be different at the same time, in the same protein. But whether it’s one or seven, these bacteria are production organisms that make proteins with nsAAs. (The nsAAs are made somewhere else, and then fed to the organism like standard amino acids.)

GRObio’s ProGly nsAAs
GRObio’s ProGly nsAAs are designed to reprogram the immune system by inducing tolerance and blocking the induction of stimulatory T and B cells. The lynchpin in the process is the dendritic cell. Typically, an antigen induces an immunogenic state in a dendritic cell, setting off an immunogenic reaction. ProGly flips the switch. After recognizing a ProGly nsAA, the dendritic cell becomes tolerogenic and sets off a tolerogenic immune response. The technology, GRObio hopes, will lead to treatments for autoimmune disorders.

GRObio has two platform chemistries: DuraLogic and ProGly. DuraLogic creates proteins that are more stable. For example, it can extend the half-lives of proteins, enabling more convenient administration regimens—lower and less frequent doses—through the flattening of pharmacodynamic profiles. One can lose the peaks and troughs that come with having too much or too little of a drug.

ProGly (programmable glycosylation) uses preglycosylated nsAAs to direct how an immune system responds to a protein. Mandell refers to this as antigen-specific tolerization, which could be useful as a treatment for autoimmune disease.

Using ProGly, GRObio modifies a known antigen, creating a version that has tolerogenic and glycosylated amino acids. When the ProGly version is administered to patients, it can tolerize them. The ProGly version is the same protein that the person would be reacting to, but with a tolerogenic glycan signature.

A ProGly drug, GRObio asserts, can induce antigen-specific T regulatory cells to reeducate the immune system and, in doing so, alter the autoimmune disease progression. Key to this process are the dendritic cells, which the ProGly drug changes from stimulatory to tolerogenic. When the dendritic cells present the antigen in a tolerogenic context, naïve T cells become T regulatory cells rather than T helper or T effector cells.

GRObio’s first program is for the auto-immune disorder myasthenia gravis. A ProGly drug, the company hopes, will tolerize patients to the acetylcholine receptor, which is what 85% of myasthenia gravis patients react to. Mandell reports that GRObio has promising preclinical data using the myasthenia gravis rat model.

GRObio can also use this platform to tolerize a patient to a protein from an outside source, such as a protein therapy causing an antibody response, which will lead to a decrease in the drug’s activity over time. By making a ProGly version of the marketed enzyme replacement therapy, GRObio can create a version that will not induce antibodies in the patient. The enzyme will not be blocked or cleared, and the glycans will not interfere with its activity.

Because GRObio has developed a system that can tamp down immune responses, the company is pushing into the gene therapy space. The Achilles’ heel of gene therapy is the inability to control the body’s immune response to the delivery vehicle—most notably adeno-associated virus (AAV). A mechanism to control the immune response would allow therapies for people who have previously seroconverted to AAV (and have thus become ineligible for additional AAV-based treatments). It would also make gene therapy safer, given that many adverse events are due to an immune response to the AAV vector carrying the genetic payload.

When a similar strategy is used to treat autoimmune disease, it may be possible, GRObio asserts, to tolerize humans to key proteins in the AAV capsule by using a ProGly version of the empty virus-like particle. GRObio says that it aims to partner with gene therapy companies in order to tolerize patients to its capsid.

From Cambridge, U.K., to Cambridge, MA, and from creating better cytokines to aiding gene therapy, the development of new amino acids is likely to open up a world of possibilities in drug development and in many other applications. As Wlodek declares, now that the chemical alphabet of bacteria can be expanded, “The sky is the limit.”

 

References
1. Fredens J, Wang K, de la Torre D, et al. Total synthesis of Escherichia coli with a recoded genome. Nature. 2019; 569(7757): 514–518.
2. Robertson WE, Funke LFH, de la Torre D, et al. Sense codon reassignment enables viral resistance and encoded polymer synthesis. Science. 2021; 372(6546): 1057–1062.

The post Noncanonical Amino Acids Inspire the Development of Novel Drugs appeared first on GEN - Genetic Engineering and Biotechnology News.

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Mortgage rates fall as labor market normalizes

Jobless claims show an expanding economy. We will only be in a recession once jobless claims exceed 323,000 on a four-week moving average.

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10 hours ago

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March 8, 2024

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Everyone was waiting to see if this week’s jobs report would send mortgage rates higher, which is what happened last month. Instead, the 10-year yield had a muted response after the headline number beat estimates, but we have negative job revisions from previous months. The Federal Reserve’s fear of wage growth spiraling out of control hasn’t materialized for over two years now and the unemployment rate ticked up to 3.9%. For now, we can say the labor market isn’t tight anymore, but it’s also not breaking.

The key labor data line in this expansion is the weekly jobless claims report. Jobless claims show an expanding economy that has not lost jobs yet. We will only be in a recession once jobless claims exceed 323,000 on a four-week moving average.

From the Fed: In the week ended March 2, initial claims for unemployment insurance benefits were flat, at 217,000. The four-week moving average declined slightly by 750, to 212,250


Below is an explanation of how we got here with the labor market, which all started during COVID-19.

1. I wrote the COVID-19 recovery model on April 7, 2020, and retired it on Dec. 9, 2020. By that time, the upfront recovery phase was done, and I needed to model out when we would get the jobs lost back.

2. Early in the labor market recovery, when we saw weaker job reports, I doubled and tripled down on my assertion that job openings would get to 10 million in this recovery. Job openings rose as high as to 12 million and are currently over 9 million. Even with the massive miss on a job report in May 2021, I didn’t waver.

Currently, the jobs openings, quit percentage and hires data are below pre-COVID-19 levels, which means the labor market isn’t as tight as it once was, and this is why the employment cost index has been slowing data to move along the quits percentage.  

2-US_Job_Quits_Rate-1-2

3. I wrote that we should get back all the jobs lost to COVID-19 by September of 2022. At the time this would be a speedy labor market recovery, and it happened on schedule, too

Total employment data

4. This is the key one for right now: If COVID-19 hadn’t happened, we would have between 157 million and 159 million jobs today, which would have been in line with the job growth rate in February 2020. Today, we are at 157,808,000. This is important because job growth should be cooling down now. We are more in line with where the labor market should be when averaging 140K-165K monthly. So for now, the fact that we aren’t trending between 140K-165K means we still have a bit more recovery kick left before we get down to those levels. 




From BLS: Total nonfarm payroll employment rose by 275,000 in February, and the unemployment rate increased to 3.9 percent, the U.S. Bureau of Labor Statistics reported today. Job gains occurred in health care, in government, in food services and drinking places, in social assistance, and in transportation and warehousing.

Here are the jobs that were created and lost in the previous month:

IMG_5092

In this jobs report, the unemployment rate for education levels looks like this:

  • Less than a high school diploma: 6.1%
  • High school graduate and no college: 4.2%
  • Some college or associate degree: 3.1%
  • Bachelor’s degree or higher: 2.2%
IMG_5093_320f22

Today’s report has continued the trend of the labor data beating my expectations, only because I am looking for the jobs data to slow down to a level of 140K-165K, which hasn’t happened yet. I wouldn’t categorize the labor market as being tight anymore because of the quits ratio and the hires data in the job openings report. This also shows itself in the employment cost index as well. These are key data lines for the Fed and the reason we are going to see three rate cuts this year.

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Inside The Most Ridiculous Jobs Report In History: Record 1.2 Million Immigrant Jobs Added In One Month

Inside The Most Ridiculous Jobs Report In History: Record 1.2 Million Immigrant Jobs Added In One Month

Last month we though that the January…

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10 hours ago

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March 8, 2024

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Inside The Most Ridiculous Jobs Report In History: Record 1.2 Million Immigrant Jobs Added In One Month

Last month we though that the January jobs report was the "most ridiculous in recent history" but, boy, were we wrong because this morning the Biden department of goalseeked propaganda (aka BLS) published the February jobs report, and holy crap was that something else. Even Goebbels would blush. 

What happened? Let's take a closer look.

On the surface, it was (almost) another blockbuster jobs report, certainly one which nobody expected, or rather just one bank out of 76 expected. Starting at the top, the BLS reported that in February the US unexpectedly added 275K jobs, with just one research analyst (from Dai-Ichi Research) expecting a higher number.

Some context: after last month's record 4-sigma beat, today's print was "only" 3 sigma higher than estimates. Needless to say, two multiple sigma beats in a row used to only happen in the USSR... and now in the US, apparently.

Before we go any further, a quick note on what last month we said was "the most ridiculous jobs report in recent history": it appears the BLS read our comments and decided to stop beclowing itself. It did that by slashing last month's ridiculous print by over a third, and revising what was originally reported as a massive 353K beat to just 229K,  a 124K revision, which was the biggest one-month negative revision in two years!

Of course, that does not mean that this month's jobs print won't be revised lower: it will be, and not just that month but every other month until the November election because that's the only tool left in the Biden admin's box: pretend the economic and jobs are strong, then revise them sharply lower the next month, something we pointed out first last summer and which has not failed to disappoint once.

To be fair, not every aspect of the jobs report was stellar (after all, the BLS had to give it some vague credibility). Take the unemployment rate, after flatlining between 3.4% and 3.8% for two years - and thus denying expectations from Sahm's Rule that a recession may have already started - in February the unemployment rate unexpectedly jumped to 3.9%, the highest since February 2022 (with Black unemployment spiking by 0.3% to 5.6%, an indicator which the Biden admin will quickly slam as widespread economic racism or something).

And then there were average hourly earnings, which after surging 0.6% MoM in January (since revised to 0.5%) and spooking markets that wage growth is so hot, the Fed will have no choice but to delay cuts, in February the number tumbled to just 0.1%, the lowest in two years...

... for one simple reason: last month's average wage surge had nothing to do with actual wages, and everything to do with the BLS estimate of hours worked (which is the denominator in the average wage calculation) which last month tumbled to just 34.1 (we were led to believe) the lowest since the covid pandemic...

... but has since been revised higher while the February print rose even more, to 34.3, hence why the latest average wage data was once again a product not of wages going up, but of how long Americans worked in any weekly period, in this case higher from 34.1 to 34.3, an increase which has a major impact on the average calculation.

While the above data points were examples of some latent weakness in the latest report, perhaps meant to give it a sheen of veracity, it was everything else in the report that was a problem starting with the BLS's latest choice of seasonal adjustments (after last month's wholesale revision), which have gone from merely laughable to full clownshow, as the following comparison between the monthly change in BLS and ADP payrolls shows. The trend is clear: the Biden admin numbers are now clearly rising even as the impartial ADP (which directly logs employment numbers at the company level and is far more accurate), shows an accelerating slowdown.

But it's more than just the Biden admin hanging its "success" on seasonal adjustments: when one digs deeper inside the jobs report, all sorts of ugly things emerge... such as the growing unprecedented divergence between the Establishment (payrolls) survey and much more accurate Household (actual employment) survey. To wit, while in January the BLS claims 275K payrolls were added, the Household survey found that the number of actually employed workers dropped for the third straight month (and 4 in the past 5), this time by 184K (from 161.152K to 160.968K).

This means that while the Payrolls series hits new all time highs every month since December 2020 (when according to the BLS the US had its last month of payrolls losses), the level of Employment has not budged in the past year. Worse, as shown in the chart below, such a gaping divergence has opened between the two series in the past 4 years, that the number of Employed workers would need to soar by 9 million (!) to catch up to what Payrolls claims is the employment situation.

There's more: shifting from a quantitative to a qualitative assessment, reveals just how ugly the composition of "new jobs" has been. Consider this: the BLS reports that in February 2024, the US had 132.9 million full-time jobs and 27.9 million part-time jobs. Well, that's great... until you look back one year and find that in February 2023 the US had 133.2 million full-time jobs, or more than it does one year later! And yes, all the job growth since then has been in part-time jobs, which have increased by 921K since February 2023 (from 27.020 million to 27.941 million).

Here is a summary of the labor composition in the past year: all the new jobs have been part-time jobs!

But wait there's even more, because now that the primary season is over and we enter the heart of election season and political talking points will be thrown around left and right, especially in the context of the immigration crisis created intentionally by the Biden administration which is hoping to import millions of new Democratic voters (maybe the US can hold the presidential election in Honduras or Guatemala, after all it is their citizens that will be illegally casting the key votes in November), what we find is that in February, the number of native-born workers tumbled again, sliding by a massive 560K to just 129.807 million. Add to this the December data, and we get a near-record 2.4 million plunge in native-born workers in just the past 3 months (only the covid crash was worse)!

The offset? A record 1.2 million foreign-born (read immigrants, both legal and illegal but mostly illegal) workers added in February!

Said otherwise, not only has all job creation in the past 6 years has been exclusively for foreign-born workers...

Source: St Louis Fed FRED Native Born and Foreign Born

... but there has been zero job-creation for native born workers since June 2018!

This is a huge issue - especially at a time of an illegal alien flood at the southwest border...

... and is about to become a huge political scandal, because once the inevitable recession finally hits, there will be millions of furious unemployed Americans demanding a more accurate explanation for what happened - i.e., the illegal immigration floodgates that were opened by the Biden admin.

Which is also why Biden's handlers will do everything in their power to insure there is no official recession before November... and why after the election is over, all economic hell will finally break loose. Until then, however, expect the jobs numbers to get even more ridiculous.

Tyler Durden Fri, 03/08/2024 - 13:30

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Economic Earthquake Ahead? The Cracks Are Spreading Fast

Economic Earthquake Ahead? The Cracks Are Spreading Fast

Authored by Brandon Smith via Alt-Market.us,

One of my favorite false narratives…

Published

13 hours ago

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March 8, 2024

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Economic Earthquake Ahead? The Cracks Are Spreading Fast

Authored by Brandon Smith via Alt-Market.us,

One of my favorite false narratives floating around corporate media platforms has been the argument that the American people “just don’t seem to understand how good the economy really is right now.” If only they would look at the stats, they would realize that we are in the middle of a financial renaissance, right? It must be that people have been brainwashed by negative press from conservative sources…

I have to laugh at this notion because it’s a very common one throughout history – it’s an assertion made by almost every single political regime right before a major collapse. These people always say the same things, and when you study economics as long as I have you can’t help but throw up your hands and marvel at their dedication to the propaganda.

One example that comes to mind immediately is the delusional optimism of the “roaring” 1920s and the lead up to the Great Depression. At the time around 60% of the U.S. population was living in poverty conditions (according to the metrics of the decade) earning less than $2000 a year. However, in the years after WWI ravaged Europe, America’s economic power was considered unrivaled.

The 1920s was an era of mass production and rampant consumerism but it was all fueled by easy access to debt, a condition which had not really existed before in America. It was this illusion of prosperity created by the unchecked application of credit that eventually led to the massive stock market bubble and the crash of 1929. This implosion, along with the Federal Reserve’s policy of raising interest rates into economic weakness, created a black hole in the U.S. financial system for over a decade.

There are two primary tools that various failing regimes will often use to distort the true conditions of the economy: Debt and inflation. In the case of America today, we are experiencing BOTH problems simultaneously and this has made certain economic indicators appear healthy when they are, in fact, highly unstable. The average American knows this is the case because they see the effects everyday. They see the damage to their wallets, to their buying power, in the jobs market and in their quality of life. This is why public faith in the economy has been stuck in the dregs since 2021.

The establishment can flash out-of-context stats in people’s faces, but they can’t force the populace to see a recovery that simply does not exist. Let’s go through a short list of the most faulty indicators and the real reasons why the fiscal picture is not a rosy as the media would like us to believe…

The “miracle” labor market recovery

In the case of the U.S. labor market, we have a clear example of distortion through inflation. The $8 trillion+ dropped on the economy in the first 18 months of the pandemic response sent the system over the edge into stagflation land. Helicopter money has a habit of doing two things very well: Blowing up a bubble in stock markets and blowing up a bubble in retail. Hence, the massive rush by Americans to go out and buy, followed by the sudden labor shortage and the race to hire (mostly for low wage part-time jobs).

The problem with this “miracle” is that inflation leads to price explosions, which we have already experienced. The average American is spending around 30% more for goods, services and housing compared to what they were spending in 2020. This is what happens when you have too much money chasing too few goods and limited production.

The jobs market looks great on paper, but the majority of jobs generated in the past few years are jobs that returned after the covid lockdowns ended. The rest are jobs created through monetary stimulus and the artificial retail rush. Part time low wage service sector jobs are not going to keep the country rolling for very long in a stagflation environment. The question is, what happens now that the stimulus punch bowl has been removed?

Just as we witnessed in the 1920s, Americans have turned to debt to make up for higher prices and stagnant wages by maxing out their credit cards. With the central bank keeping interest rates high, the credit safety net will soon falter. This condition also goes for businesses; the same businesses that will jump headlong into mass layoffs when they realize the party is over. It happened during the Great Depression and it will happen again today.

Cracks in the foundation

We saw cracks in the narrative of the financial structure in 2023 with the banking crisis, and without the Federal Reserve backstop policy many more small and medium banks would have dropped dead. The weakness of U.S. banks is offset by the relative strength of the U.S. dollar, which lures in foreign investors hoping to protect their wealth using dollar denominated assets.

But something is amiss. Gold and bitcoin have rocketed higher along with economically sensitive assets and the dollar. This is the opposite of what’s supposed to happen. Gold and BTC are supposed to be hedges against a weak dollar and a weak economy, right? If global faith in the dollar and in the U.S. economy is so high, why are investors diving into protective assets like gold?

Again, as noted above, inflation distorts everything.

Tens of trillions of extra dollars printed by the Fed are floating around and it’s no surprise that much of that cash is flooding into the economy which simply pushes higher right along with prices on the shelf. But, gold and bitcoin are telling us a more honest story about what’s really happening.

Right now, the U.S. government is adding around $600 billion per month to the national debt as the Fed holds rates higher to fight inflation. This debt is going to crush America’s financial standing for global investors who will eventually ask HOW the U.S. is going to handle that growing millstone? As I predicted years ago, the Fed has created a perfect Catch-22 scenario in which the U.S. must either return to rampant inflation, or, face a debt crisis. In either case, U.S. dollar-denominated assets will lose their appeal and their prices will plummet.

“Healthy” GDP is a complete farce

GDP is the most common out-of-context stat used by governments to convince the citizenry that all is well. It is yet another stat that is entirely manipulated by inflation. It is also manipulated by the way in which modern governments define “economic activity.”

GDP is primarily driven by spending. Meaning, the higher inflation goes, the higher prices go, and the higher GDP climbs (to a point). Eventually prices go too high, credit cards tap out and spending ceases. But, for a short time inflation makes GDP (as well as retail sales) look good.

Another factor that creates a bubble is the fact that government spending is actually included in the calculation of GDP. That’s right, every dollar of your tax money that the government wastes helps the establishment by propping up GDP numbers. This is why government spending increases will never stop – It’s too valuable for them to spend as a way to make the economy appear healthier than it is.

The REAL economy is eclipsing the fake economy

The bottom line is that Americans used to be able to ignore the warning signs because their bank accounts were not being directly affected. This is over. Now, every person in the country is dealing with a massive decline in buying power and higher prices across the board on everything – from food and fuel to housing and financial assets alike. Even the wealthy are seeing a compression to their profit and many are struggling to keep their businesses in the black.

The unfortunate truth is that the elections of 2024 will probably be the turning point at which the whole edifice comes tumbling down. Even if the public votes for change, the system is already broken and cannot be repaired without a complete overhaul.

We have consistently avoided taking our medicine and our disease has gotten worse and worse.

People have lost faith in the economy because they have not faced this kind of uncertainty since the 1930s. Even the stagflation crisis of the 1970s will likely pale in comparison to what is about to happen. On the bright side, at least a large number of Americans are aware of the threat, as opposed to the 1920s when the vast majority of people were utterly conned by the government, the banks and the media into thinking all was well. Knowing is the first step to preparing.

The second step is securing your own financial future – that’s where physical precious metals can play a role. Diversifying your savings with inflation-resistant, uninflatable assets whose intrinsic value doesn’t rely on a counterparty’s promise to pay adds resilience to your savings. That’s the main reason physical gold and silver have been the safe haven store-of-value assets of choice for centuries (among both the elite and the everyday citizen).

*  *  *

As the world moves away from dollars and toward Central Bank Digital Currencies (CBDCs), is your 401(k) or IRA really safe? A smart and conservative move is to diversify into a physical gold IRA. That way your savings will be in something solid and enduring. Get your FREE info kit on Gold IRAs from Birch Gold Group. No strings attached, just peace of mind. Click here to secure your future today.

Tyler Durden Fri, 03/08/2024 - 17:00

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