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Bacteria: The Good, The Bad, and The Designer

By WallStreetDaily.com Bacteria: The Good, The Bad, and The Designer

Synlogic, a spinout from MIT, is about to test a pill that contains 100 billion genetically engineered microbes that will help fight a rare disorder. It may be the first of many “synthetic biotics.”


I start just about every day with a banana and a bowl of Grape-Nuts mixed with yogurt — Fage, to be sure — and I like just about every flavor, but my favorites are “Honey” and “Key Lime.”

So that’s how I get my Lactobacillus bulgaricus and my Streptococcus thermophilus, the live and active cultures that define yogurt.

These probiotics also help prevent gastrointestinal infections, boost the body’s immune system, fight certain types of cancer, and prevent osteoporosis.

They’re “good” bacteria.

We know all about the other kind, the “superbugs,” or “antibiotic-resistant bacteria,” that threaten all sorts of bad outcomes for humankind.

Indeed, an April 2016 case described in the American Society for Microbiology’s journal Antimicrobial Agents and Chemotherapy“sounded alarm bells among scientists over fears that common infections will soon be untreatable.”

“Common infections will soon be untreatable.”

That’s how Scientific American describes the implications of a Pennsylvania woman who “developed a urinary tract infection (UTI) with bacteria that fought off an antibiotic of last resort called colistin, and had  15 genes for resistance to other antibiotics.”

A year ago, Chinese and British researchers published a paper detailing “the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.”

In short, plasmid (“a small, circular, double-stranded DNA molecule that is distinct from a cell’s chromosomal DNA”) facilitates sharing of the colistin-resistance gene. And that means it can spread far, wide, and fast when bacteria come into contact.

“Common infections will soon be untreatable.”

Colistin is widely used in food-animal production in China.

As Dr. James Johnson, a professor of medicine and senior associate director of the Infectious Diseases Fellowship Program and the VA Molecular Epidemiology Unit at the University of Minnesota, put it to Scientific American, “The emergence of mcr-1 likely occurred because of extensive use of colistin in food animal production — which is yet another example of how injudicious use of antimicrobials comes back to hurt us.”

But there’s much more to the bacteria story — which is a long one, perhaps about 3.5 billion years, according to research presented by scientists from Old Dominion University at the 2012 meeting of the Geological Society of America.

The story includes all sorts of good outcomes for humankind.

Did you know that there are as many bacteria and “resident microbes” in our bodies as there are human cells?

Bacteria also help us “make vitamins, break down some garbage, and even maintain our atmosphere,” according to MicrobeWorld.

And researchers are getting closer and closer to “designer” bacteria that will actually help us treat disease.

On November 10, 2016, Cambridge, Massachusetts-based synthetic biology startup Synlogic announced that it had secured a composition-of-matter patent covering “a live engineered bacterium modified to assimilate ammonia for the potential treatment of hyperammonemia-based diseases such as urea cycle disorders (UCDs) and hepatic encephalopathy.”

Synlogic’s No. 1 drug candidate, SYNB1020, is basically a patented form of the probiotic bacterium E. coli Nissle engineered to jump-start the body’s ability to process nitrogen and ammonia. The pill form will contain 100 billion engineered bacteria.

Did you know that there are as many bacteria and “resident microbes” in our bodies as there are human cells?

Nitrogen and ammonia are byproducts of the body’s normal breakdown of proteins.

Under normal circumstances, six enzymes in the urea cycle help process nitrogen into ammonia and remove it from the bloodstream. The liver turns ammonia into urea, which then leaves the body as urine.

Ammonia is a highly toxic substance. Treating UCDs — genetic disorders caused by a mutation — is critical to preventing “hyperammonemia,” or elevated blood ammonia. If ammonia reaches the brain through the blood, it can cause irreversible brain damage, coma, and/or death.

SYNB1020 is in the preclinical development stage. The company plans to file an application with the Food and Drug Administration for the first treatment of patients during the first quarter of 2017.

As MIT Technology Review notes, this is a novel concept.

“The idea of swallowing genetically modified bacteria might seem odd,” writes Antonio Regalado. “But purpose-built germs could be a new way to take over physiological functions that people’s own bodies can’t perform if they are sick, and a substitute for pills or injections.”

There are — in light of evidence indicating bacteria are quite able to mutate into indestructible forces — concerns that this particular engineered strain, SYNB1020, could “share” its DNA with yet another strain and create entirely new organisms.

Uncontrolled, injudicious use of antibiotics created the “antimicrobial resistance” monster. We don’t need any more of that.

Synlogic notes that SYNB1020 will have a short life span — too short to share DNA. And they’ll only operate in a low-oxygen environment, such as the gut. That it relies on the nutrient thymidine, which isn’t found in the digestive tract, also ensures it “will divide only once before dying.”

We have to get a firm grip on the waste consequences, too. Synlogic is just one company working on “designer” bacteria. There are others out there, and we’re essentially going to be pissing this stuff away — which may indeed include living microbes — into the waste management system.

Uncontrolled, injudicious use of antibiotics created the “antimicrobial resistance” monster. We don’t need any more of that.

But where there’s great risk, there’s great reward.

We’re talking about potential anti-cancer drugs based on salmonella, which causes food poisoning, yes, but also concentrates in tumors.

And there are applications for one of the yogurt bacteria, Lactobacillus, that would enable folks to safely consume nuts, milk, and other stuff some people simply can’t digest.

As Sveta McShane of SingularityHub notes, “We have entered a fascinating new phase of human development where we can deliberately control our own biology and that of the organisms living in our bodies.”


NBNBC

Synlogic — “we have reimagined the potential of probiotics” — was co-founded by James Collins, the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT.

The company has raised about $70 million, with backers including founding investors Atlas Venture and New Enterprise Associates (NEA) as well as OrbiMed HealthCare Fund Management, Deerfield Management Co., and the Bill & Melinda Gates Foundation.

Synlogic’s most recent round, of $40 million in Series B funding was led by OrbiMed and included Deerfield, Atlas, and NEA. It closed in February 2016.

That money will help Synlogic answer the question of whether we can program “genetic switches” into microbes and help them help us fight diseases both rare and common.

Smart Investing,

David Dittman
Editorial Director, Wall Street Daily

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About Louie Lewis

Louie Lewis
Successful forex trading starts with you first. Then comes the actual strategies and techniques. I have been involved with forex and forex trading for a few years now. It is a wonderful way to build wealth. The learning never stops and I want to help others along their journey into this wonderful market of opportunity.

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