Bloomberg Businessweek - USA (2019-11-25)

◼ TECHNOLOGY

23

PHOTOGRAPH

BY

JOHN

FRANCIS

PETERS

FOR

BLOOMBERG

BUSINESSWEEK.

ILLUSTRATIONS

BY

BROWN

BIRD

DESIGN

①Increasingly,bacteria

thatcauseinfections

aremutatingtosurvive

bombardmentfrom

powerfulantibiotics

②Researchershave

programmedviruses

calledphagestotarget

a specificbacterium

causinganillness

whileleavingthe

body’shelpfulbacteria

unharmed

③Injectionsofbillions

ofphageshavebeen

usedtotreatabout

50 superbugpatients

in theU.S.

treatments, “and then when all the bacteria was

gone, it just went away.” A month later he got his

heart transplant.

Grimwood is one of about 50 patients who’ve

been treated in the U.S. with doctor-directed

infusions of billions of the arachnoid-looking

viruses known as phages. At the University of

California at San Diego and elsewhere around the

world, researchers and drugmakers are betting

that so-called phage therapy can help close the

growing gaps in medical treatment created by the

spread of antibiotic-resistant bacteria and other

superbugs. They say phages are the ultimate

biodegradable “smart bomb” because they can be

programmed to destroy a single harmful bacterium

without blowing up other, helpful strains that

occur naturally in a person’s body, as antibiotics

do. “It’s really important to keep the microbiome

intact to theextent possible,”says Steffanie

Strathdee,UCSD’sassociatedeanofglobalhealth

sciencesandco-director of a phage therapy center.

Pharmaceutical companies have taken notice.

BiomX Inc., which is using phages to treat patients

for strains of bacteria linked to ulcerative colitis and

other chronic diseases, has teamed with Johnson &

Johnson’s Janssen Pharmaceuticals unit to work on

therapies for inflammatory bowel diseases. Janssen

has also announced a licensing deal with Locus

Biosciences Inc. to genetically engineer phages that

can fight infections of the respiratory tract and other

organ systems. The U.S. National Institutes of Health

hassupporteda seriesofphageresearchprojects,

includinga three-phagecocktailthatsuccessfully

treatedthedrug-resistant abscesses in a gravely ill

teenager with cystic fibrosis.

Although most of these projects remain years

away from the open market, scientists and pharma

companies are optimistic that synthetic biology will

speed the discovery and development of medically

useful phages, as well as make them patentable

and thus far more profitable. “Once you get good

investments, you’ll be surprised where the field

goes,” says Anthony Fauci, director of the National

Institute of Allergy and Infectious Diseases.

The medical use of antibacterial viruses dates

backa century.It flourishedintheSovietUnion

underJosefStalinbutfelloutofuseintheWestwith

theadventofpenicillinandsubsequentantibiotics.

Now,however,bacteriaarerapidlyaccumulating

antibiotic-resistant genes in response to the use of

thesedrugsinhumanmedicineandagriculture.

Anantibiotic-resistantinfectionkillssomeonein

theU.S.roughlyevery 15 minutes,theCentersfor

DiseaseControlandPreventionreportedonNov.13.

So scientists are trying to take better advantage of

THE BOTTOM LINE Using viruses to target bacteria has been out

of fashion in the U.S. since the advent of penicillin, but overuse of

antibiotics is making phage therapy an attractive option again.

▲ Strathdee, a phage

researcher, got a very

personal demonstration

of their power

other phage properties, too, including some phages’

abilities to make bacteria less virulent and even

reverse drug resistance.

That was the case with Tom Patterson, a psy-

chiatry professor at UCSD who in 2016 fell criti-

cally ill and became the first U.S. patient treated

with this kind of therapy for a systemic superbug.

With a severe abdominal infection that resisted all

known antibiotics, he was soon comatose and close

to death. Strathdee, Patterson’s wife, suggested

phages in a final attempt to save him. “A couple of

days after we began intravenous phage therapy,” she

says, “he lifted his head off the pillow and kissed his

daughter’s hand.” While fending off the phage, the

bacterium inadvertently disrupted some of its own

antibiotic-evading abilities, rendering it susceptible

to a cheap pill often used to treat acne.

The pharma companies continue to tinker with

phages’ genetic codes, but it’s been a challenge

for scientists to find viruses that precisely match

their bacterial targets. Martha Clokie, who runs a

phage research lab and teaches at the University of

Leicester, about 100 miles north of London, spent

years hunting for the bane of the deadly diarrheal

bacterium Clostridioides difficile, or C. diff, which

kills about 13,000 Americans a year. She eventu-

ally found some promising samples in the smelly

estuarine soils of southeast England and is testing

them in hamsters. And she’s using another phage

to target salmonella. “In each new phage you find,”

Clokie says, “there are new things that you can never

dream of.” �Jason Gale, with John Lauerman

● How phage therapy

works: