Her Husband Was Dying From A Superbug. She Turned To Sewer Viruses Collected By The Navy.


Scientists have long dismissed “phage therapy” as a fringe idea
pushed by eccentrics who enjoy fishing in sewage. But now the
Navy is betting on it.

Originally posted on May 06, 2017, 13:17 GMT

Updated on May 06, 2017, 14:52 GMT

Courtesy of Strathdee and Patterson

Steffanie Strathdee and Tom Patterson visiting Egyptian
pyramids

Two days after walking through the pyramids, Tom
Patterson got very sick. The psychiatry professor was in
Egypt with his wife on one of their many adventurous
vacations away from life in California. One minute he was
fine, hamming it up in a touristy horse-and-buggy ride across
the desert. The next, he couldn’t stop sweating and vomiting.

The 300-pound 68-year-old was airlifted from a clinic in
Cairo to one in Frankfurt and then finally back to San Diego,
where doctors confirmed a severe infection in his abdomen.

The culprit was a bacteria called Acinetobacter
baumannii
, the notorious “Iraqibacter” that emerged in
military medical facilities during the Iraq War. It now tops
the
international list of dangerous superbugs that don’t
respond to most antibiotics. Some Iraqibacter cases improve
with a very old, last-resort antibiotic called colistin. But
it didn’t work on Tom.

The infection soon spread to Tom’s blood and lungs. For
months he was in a San Diego ICU bed in excruciating pain,
often hallucinating, falling in and out of a coma. By late
February of 2016, his doctors said they were out of options.

Tom’s wife, Steffanie Strathdee, is the director of UC San
Diego’s Global Health Institute, and one of the world’s
experts on how HIV spreads across the world. She deeply
understood how superbugs, left unchecked, would kill millions
of people — including, suddenly, her husband.

Sitting in the hospital room, she turned to Tom. “Honey, the
antibiotics aren’t working,” she recalled saying. “I need to
know from you if you want to keep fighting, because I don’t
want to keep you alive just for me. Squeeze my hand if you
want me to push ahead.” He squeezed.

Over the next seven months, Steffanie went on a remarkable
medical quest, and one that might not have been possible if
not for her unique position in the upper echelon of academic
science. She gained access to a century-old treatment —
“phage therapy” — in which a patient gets custom-made viruses
to kill their festering infection. And she and her colleagues
found these viruses, called phages, in a surprising place: a
heavily guarded Maryland lab run by the US Navy.

U.S. Navy Photo / Katie Berland

Theron Hamilton, head of genomics and bioinformatics at
the Biological Defense Research Directorate of the Naval
Medical Research Center

This is strange, not least because mainstream scientists have
long dismissed phage therapy as a fringe idea pushed by
eccentrics who enjoy fishing in sewage (where many phages
live). But over the past 15 years, as more and more bacteria
have evolved ways to evade our antibiotic arsenal, Navy
scientists have turned to phages as a last line of defense. A
run-of-the-mill freezer in the Maryland lab holds what’s one
of the world’s largest phage libraries: more than 300
viruses, collected on ship-based laboratories all over the
world. None of the phages had ever been tested in an infected
person — until Tom.

This has never been done anywhere in the country
until this case,” said Lieutenant Commander Theron Hamilton,
head of genomics and bioinformatics at the Biological Defense
Research Directorate of the Naval Medical Research Center.
Last week, his team presented Tom’s case at a phage conference at
the Institute Pasteur in Paris.

But while the scientists in Paris celebrated the 100-year
anniversary of the discovery of phages, these biological
weapons are nearly impossible to get to patients in the US.
Using nature’s own viruses to treat infections doesn’t jive
with the FDA’s process for approving new pharmaceuticals, nor
Big Pharma’s motive to sell one-size-fits-all pills for the
masses.

“Everybody — the FDA and the medical community in general —
has been slow to take the risk that would be required to
really engage fully with a phage therapeutics program,”
Hamilton said. “I don’t want to sound too cavalier, but I
don’t think anybody is anywhere close to where the Navy is on
this.”

MIT / Wikipedia

Phages attacking a bacterium

The day after her dying husband squeezed her hand,
Steffanie talked to a colleague whose friend had contracted a
similar antibiotic-resistant infection. In a desperate search
for a treatment, this friend of a friend had flown all the
way to the Eastern European country of Georgia to try phage
therapy. It had worked.

Steffanie, who has a degree in microbiology, knew what phages
were but had never heard about using them on people. After
digging through the papers in English on the treatment, she
found just a handful
of
case reports of patients trying phages in US hospitals,
or who had found a way
to order them from Georgia. But these were extraordinary
cases.

Phages are the most diverse and numerous life forms on earth
— millions of them coat our skin, live inside our guts, and
flow through our faucets. They’re completely harmless to us,
but deadly to bacteria. And unlike antibiotics — which wipe
out broad swaths of bacteria, even species that are
beneficial to us — phages have specific targets. A phage
injects its DNA into its prey, which then replicates rapidly
before rupturing and killing the cell, releasing even more
viruses to repeat the attack.

“It’s the only medicine that grows.”

“It’s the only medicine that grows,” Ryland Young, head of
the Center for Phage Technology at Texas A&M University,
told BuzzFeed News.

Phage therapy blossomed in Eastern Europe after World War II,
largely because researchers there were blocked from
developing the mass-produced antibiotics sweeping the West.

“If you went to major scientific meeting in the US in the
1950s and talked about phage therapy, you’d be laughed out of
the room,” Young said. “The Eastern Europeans kept it alive
in some ways, because in the West we were actually running
away from it.”

To this day, clinics in Georgia offer phage therapy
“cocktails” alongside antibiotics as a standard treatment for
fighting against bacterial infections.

Meanwhile, the 130 different antibiotics prescribed every day
in the US are slowly but surely losing the war against
bacteria. Six superbugs in particular, known as the “ESKAPE”
pathogens, have emerged as the biggest threats to human
health, infecting at least 2 million Americans every year,
and killing at least 23,000.

Tom’s bacteria, Acinetobacter baumannii, is the “A” in
“ESKAPE.” But Steffanie was determined not to let her husband
become one of those statistics.

Courtesy Steffanie Strathdee

Her first call was to the head of the infectious
disease unit at UC San Diego, Chip Schooley. “I said, ‘Hey
Chip, I think we’re running out of options. What about phage
therapy? I know it sounds a little woo-woo, but I think it
may be our only shot,’” she recalled.

“It was a radical approach,” said Schooley, a virologist
whose own research involves finding ways to kill HIV,
hepatitis C, and herpes. “I try to get rid of viruses, not
use them to try to treat patients.”

But he was quickly convinced that phages were probably Tom’s
only option. He agreed to call the FDA and see whether the
agency would allow him to give Tom phages as a “compassionate
use,” meaning an experimental treatment that does not have to
abide by normal drug regulations. But first, Steffanie needed
to find someone who had phages that matched Tom’s specific
infection.

She found Ry Young at Texas A&M, one of the few
biologists in the US who’s trying to understand how phages
work. Steffanie sent him a long email about Tom’s story, with
a photo of Tom in his hospital bed. Young gets these sorts of
desperate emails a lot, and typically gives an apologetic
canned response. But when he heard from Steffanie, he decided
that she was knowledgeable and connected enough that phage
therapy could actually save her husband. They ended up
talking on the phone for two hours, and Young agreed to help.

Steffanie sent Young a sample of Tom’s superbug, and Young
immediately began testing it against the small library of
phages his Texas team had amassed. None worked.

“So I did two things: I emailed and phoned everybody that I
knew in the world that had research programs with
baumannii phages,” Young said. He called researchers
in India, Australia, and Europe, and at a small company in
San Diego. Within a couple weeks, he received roughly 45
phages from around the world.

Then he went on what he calls a “good old-fashioned phage
hunt” — collecting samples from sewage plants in Texas and
isolating nearly 100 other phages that might work for Tom.

The FDA, meanwhile, got back to Schooley. They told him
they’d be willing to let Tom undergo phage therapy, as long
as the final product was totally purified. They also gave him
a new contact they thought might be helpful: the country’s
largest phage collection, at the Navy lab.

U.S. Navy Photo / Katie Berland

For years, the Navy had only tested its phages in mice. When
Hamilton came on as the director in 2015, he was encouraged
to shut down the phage research arm, which he was told was a
“financial hole.” Instead, he decided to finally test their
phages in people.

Tom was the perfect first case. “Someone’s life was hanging
in the balance here,” Hamilton said. “I saw no reason not to
try.”

On March 15 of last year, Schooley received a FedEx package
containing styrofoam coolers of purified phage cocktails from
Young’s lab, marked with a “biohazard” sticker. That same
day, the FDA officially signed off on the experimental
treatment. There was no time to lose: Tom’s kidneys were
failing and Steffanie had just signed his dialysis
papers.

“The day the first batch of phages came to Tom’s bedside, the
lead pharmacist brought them as if he was the ringbearer at
the wedding ceremony,” Steffanie said. “It was surreal
looking at this — a royal procession of some kind.”

Schooley pumped those phages through tubes in Tom’s stomach,
aimed at the original site of his infection. Two days later,
the Navy’s more potent phages arrived. For these, the doctors
used a more extreme approach, injecting the viruses straight
into Tom’s bloodstream — a method that, to their knowledge,
had never been done in the US.

The next day, Tom went into septic shock. “Everybody thought
we’d killed him,” Steffanie said, and they quickly turned off
the phage infusions. But as it turned out, the shock was
caused by a different kind of bacteria. So, two days later,
they resumed the phage therapy. “It was just a roller
coaster,” she said.

Not long after that, Tom opened his eyes for the first time
in weeks, and recognized his daughter standing by the
hospital bed.

A month later, Tom went outside for the first time, in a
wheelchair. He had stopped using a ventilator, began talking,
and played gin rummy with his daughter.

But the battle wasn’t over. Around the same time, the
Iraqibacter became resistant to the phages, and Tom’s health
began to sharply decline, yet again.

Schooley sent a sample of the mutated bacteria back to the
Navy. Hamilton’s team screened their phage library again, and
sent back a new, tailor-made cocktail to attack the new phase
of Tom’s infection.

It all happened within a few days, which Hamilton sees as one
of phage therapy’s many advantages over traditional
pharmaceuticals. “There’s absolutely no comparison,” Hamilton
said. “It could be years to develop a new drug.”

In August, nine months after Tom left Egypt, he finally left
the hospital and went home.

“In my mind, I was the biggest guinea pig on earth,” Tom told
BuzzFeed News. He’s still 100 pounds lighter than when he was
first hospitalized, but is finally getting back to normal
life and to his psychology research at UCSD. “The bureaucracy
that was overcome, the number of scientists that came to my
aid — they made my survival possible.”

Tom’s case is spurring action in the Navy’s
financially stagnant program for phage therapy. Hamilton’s
team has funding to genetically sequence each of the 300
phages in their library, the first step towards getting the
FDA to approve a formal clinical trial. Once the researchers
screen the phages to make sure they don’t contain genes for
toxins or antibiotic resistance, they will start big clinical
trials in people.

Hamilton hopes the trials, which they’re planning to do this
summer in collaboration with a private company called
Adaptive Phage Therapeutics, will produce enough data to take
the phages to market. Although the treatments will initially
be for the US military, the company could commercialize them.

Hamilton hopes that the FDA will allow it to bypass one of
the main hurdles now facing phage therapy in the US: Each
custom-made phage cocktail would need to be approved as its
own drug, a stringent process that would make phage therapy
all but impossible, Hamilton said. If the FDA instead
approved the whole library, then researchers could make
personalized cocktails for each patient without requiring
approval each time.

“If every phage is considered a new drug, there will never be
a phage therapy industry.” 

“If every phage is considered a new drug, there will never be
a phage therapy industry,” Young said.

But, Hamilton acknowledges, making this change would be a
“paradigm shift” for the FDA, and it has yet to publicly
signal that it’s something it would even consider. The agency
declined to comment for this story.

Money, too, stands in the way of bringing phage therapy to
the masses. Because phages, like antibiotics, are only taken
for short periods of time and will never be blockbusters like
Viagra or Lipitor, few pharmaceutical companies would make
the investment to bring them to market. And, since phages can
be found in nature, patenting would also be difficult. “If a
company invests money in phages, there’s nothing to keep
somebody from isolating another phage that’s close to it and
doing the same thing,” Young said. “That’s a problem.”

The barriers mean that phage therapy is almost certainly not
going to be the solution to the growing antibiotics crisis.
But with no
new antibiotics in the pipeline, this unusual treatment
is one of the only things that might actually help. “I doubt
that we’re going to turn away from antibiotics any time in
the near future,” David Weiss, director of the Antibiotic
Resistance Center at Emory University School of Medicine,
told BuzzFeed News. But, he added, “traditional antibiotic
therapy and phages might in theory be used together.”

Steffanie will be a coauthor, along with Hamilton, Schooley,
and Young, on a forthcoming scientific paper about Tom’s
phage therapy experience, and she and Tom are working on a
book.

“Phage therapy as a field kind of collided with our lives in
this miraculously surreal way,” she said. “Every time I look
at him now I just think that every day is a gift.” ●

Azeen Ghorayshi is a science reporter for BuzzFeed News and
is based in New York. Her PGP Fingerprint is 9739 9DAE 607E
A66A 3683 AC20 E34B D2A0 8899 74C4

Contact Azeen Ghorayshi at Azeen.Ghorayshi@buzzfeed.com.


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