Scientists Are Retooling Bacteria to

Cure Disease
By manipulating DNA, researchers are trying to create
microbes that, once ingested, work to treat a rare
genetic condition — a milestone in synthetic biology.

A newborn is tested for PKU, a rare inherited blood

disorder, at a hospital in California. CreditSpencer
Grant/Science Source

In a study carried out over the summer, a group of

volunteers drank a white, peppermint-is concoction laced with billions of bacteria.

The microbes had been engineered to break down a naturally occurring toxin in the
blood.

Most of us can do this without any help. But for those who cannot, these microbes
may someday become a living medicine.

The trial marks an important milestone in a promising scientific field known as

synthetic biology. Two decades ago, researchers started to tinker with living things
the way engineers tinker with electronics.

They took advantage of the fact that genes typically don’t work in isolation. Instead,
many genes work together, activating and deactivating one another. Synthetic
biologists manipulated these communications, creating cells that respond to new
signals or respond in new ways.

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Until now, the biggest impact has been industrial. Companies are using engineered
bacteria as miniature factories, assembling complex molecules like antibiotics or
compounds used to make clothing.

In recent years, though, a number of research teams have turned their attention
inward. They want to use synthetic biology to fashion microbes that enter our
bodies and treat us from the inside.

The bacterial concoction that volunteers drank this summer — tested by the
company Synlogic — may become the first synthetic biology-based medical
treatment to gain approval by the Food and Drug Administration.

The bacteria are designed to treat a rare inherited disease called phenylketonuria,
or PKU. People with the condition must avoid dietary protein in foods such as meat
and cheese, because their bodies cannot break down a byproduct, an amino acid
called phenylalanine.

As phenylalanine builds up in the blood, it can damage neurons in the brain,

leading to delayed development, intellectual disability and psychiatric disorders.
The traditional treatment for PKU is a strict low-protein diet, accompanied by
shakes loaded with nutritional supplements.

But in experiments on mice and monkeys, Synlogic’s bacteria showed promise as

an alternative treatment. On Tuesday, company investigators announced positive
results in a clinical trial with healthy volunteers.

The researchers are now going forward with a trial on people with PKU and expect
to report initial results next year.

Tal Danino, a synthetic biologist at Columbia University, said that a number of

other researchers are working on similar projects, but no one has moved forward
as fast as Synlogic. “They’re leading the charge,” he said.

One of Synlogic’s co-founders, James J. Collins, a synthetic biologist at M.I.T.,

published one of synthetic biology’s first proofs of principle in 2000.

He and his colleagues endowed E. coli bacteria with a way to turn a gene on and
off when they were exposed to certain chemicals — “like a light switch for genes,”
Dr. Collins said in an interview.
“I think anywhere there are bacteria in the body is an opportunity to engineer them
to do something else.”

At first, the scientists envisioned using rewired bacteria as environmental sensors

— perhaps detecting airborne biological weapons and producing a chemical signal
in response.

But then came the microbiome.

In the mid-2000s, microbiologists began charting our inner menagerie of microbes,

the vast diversity of organisms that live inside healthy people. The microbiome is
continually carrying out complex biochemistry, some of which helps shield us from
diseases, scientists found.
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Synthetic biologists soon began wondering whether they could add engineered
bacteria to the mix — perhaps as internal sensors for signs of disease, or even as
gut-based factories that make drugs the body needs.

“You can’t overestimate the impact of the microbiome work,” said Jeff Hasty, a
former student of Dr. Collins who now runs his own lab at the University of
California, San Diego. “That, in a nutshell, changed everything.”

Dr. Collins and Timothy K. Lu, another synthetic biologist at M.I.T., co-founded
Synlogic in 2013, and the company began looking for diseases to take on. One of
their picks was PKU, which affects 16,500 people in the United States.

Drugs have recently become available that can drive down levels of phenylalanine.
But they only work in a fraction of patients, and they come with side effects of their
own.

“The current tools that we have available are not good enough,” said Christine S.
Brown, the executive director of the National PKU Alliance.

For years, researchers have explored treating PKU with gene therapy, hoping to
insert working versions of the defective gene, called PAH, into a patient’s own
cells. But so far the approach has not moved beyond studies in mice.
A transmission electron microscopy image of Synlogic’s newly engineered
bacteria.CreditW.M.Keck Biological Imaging Facility, The Whitehead Institute.

A transmission electron microscopy image of Synlogic’s newly engineered

bacteria.CreditW.M.Keck Biological Imaging Facility, The Whitehead Institute
To Synlogic, PKU looked like a ripe opportunity to use synthetic biology to create a
treatment that might gain government approval.

Company researchers selected a harmless strain of E. coli that’s been studied for

more than a century. “Most people have healthy, good E. coli in their intestinal
tracts,” said Paul Miller, the chief scientific officer of Synlogic.

The researchers inserted genes into the bacteria’s DNA so that once they arrived
in the gut, they could break down phenylalanine like our own cells do.

One of the new genes encodes a pump that the bacteria use to suck up
phenylalanine around them. A second gene encodes an enzyme that breaks down
the phenylalanine into fragments. The bacteria then release the fragments, which
get washed out in urine.

The Synlogic team wanted the microbes to break down phenylalanine only in the
right place and at the right time in the human body. So they engineered the
bacteria to keep their phenylalanine genes shut down if they sensed high levels of
oxygen around them.

Only when they arrived in a place with little oxygen — the gut — did they turn on
their engineered genes.

To test the bacteria, the researchers created mice with the mutation that causes
PKU. When the mice received a dose of the bacteria, the phenylalanine in their
blood dropped by 38 percent, compared with mice without the microbes.

The researchers also tried out the bacteria on healthy monkeys. When monkeys
without the microbes ate a high-protein diet, they experienced a spike of
phenylalanine in their blood. The monkeys with engineered bacteria in their guts
experienced only a gentle bump.

For their human trial, Synlogic recruited healthy people to swallow the bacteria.
Some took a single dose, while others drank increasingly large ones over the
course of a week. After ingesting the bacteria, the volunteers drank a shake or ate
solid food high in protein.

On Tuesday, Synlogic announced that the trial had demonstrated people could
safely tolerate the bacteria. In addition, the more bacteria they ingested, the more
bits of phenylalanine wound up in their urine — a sign the bacteria were doing their
job.

The next step will be to see if the microbes can lower phenylalanine levels in
people with PKU.
“I’m amazed at how fast we got to where we are,” said Dr. Collins, who was not
involved in Synlogic’s PKU research.

In July, Dr. Danino and his colleagues published a review in the journal Cell
Systems, cataloging a number of other disorders that researchers are designing
synthetic microbes to treat, including inflammation and infections.

Dr. Danino and Dr. Hasty are currently collaborating on another project: how to use
synthetic biology against cancer.

One huge challenge in developing drugs for cancer is that they often fail to
penetrate tumors. But microbiome researchers have discovered that natural
bacteria regularly infiltrate tumors and grow inside them.

Now scientists are engineering bacteria that can also make their way into tumors.
Once there, they will unload molecules that attract immune cells, which the
researchers hope will kill the cancer.

“I think anywhere there are bacteria in the body is an opportunity to engineer them
to do something else,” said Dr. Danino.
 Sept. 3, 2018, 

Summary
In short, some scientists are manipulating the DNA to test the newborns in the
hospital in California, this summer some students gave the test to perform an
experiment, not all were accepted, drank a mixture of white mint with billions of
bacteria. The microbes had been designed to break down a natural toxin in the
blood.
they should follow an exorbitant diet without cheese or meat since it can damage
the neurons of the brain.
The investigators are practically playing with living beings, some companies do the
same for the creation of clothes.
Some doctors like dr. Collins or such a dancer got their point of view.

Why it is important?
It is important because in this new we learn about some new themes that we study
in class an in a more specific way, so in this article tell a current news in the united
states, specific in California’s hospital and in some companies experiments about
an interesting theme that this can help in future and give us more knowledge. This
help to know more and you can tell this to your friends.
 How does it relate to class?
It relates to bacterium class, that we expose in class and the teacher explain like
the form and their diseases this news talk about some new bacterium that are
specific to prevent diseases, this is a new experiment that you must drink a liquid
with some new bacteria’s and the people that can do this experiment have to use a
diet like without cheese and meet and food from animals.

Citation:
 https://www.nytimes.com/2018/09/04/health/
synthetic-biology-pku.html
 A version of this article appears in print on Sept. 3, 2018, on Page D1 of the New York edition with the
headline: Retooling Bacteria to Cure Disease. Order Reprints | Today’s Paper