The New York Times - 06.08.2019

D4 N THE NEW YORK TIMES, TUESDAY, AUGUST 6, 2019

the engines will fail’?” Dr. Weber said.

“Would you go in a car if the manufacturer

said, ‘There are airbags, but 5 percent of the

time they won’t deploy’?”

Dr. Jeff Shuren, the director of the F.D.A.’s

Center for Devices and Radiological Health,

suggested the agency may take additional

regulatory action. “Improvements are nec-

essary,” he said in a statement in April. No

action has yet been taken, however.

Hidden Defects

Duodenoscopes are long, flexible tubes

with a fiber-optic camera at one end. The

tube is inserted through the patient’s mouth

and stomach, then into the first part of the

small intestine, called the duodenum.

The procedure, called endoscopic ret-

rograde cholangiopancreatography, is used

to diagnose and treat diseases of the pan-

creas, bile duct and gallbladder, such as life-

threatening jaundice, tumors, blocked bile

ducts and stones. More than half a million

such procedures are performed each year

in the United States.

The alternative is open surgery, which

carries its own risks, said Dr. Bret Petersen,

a gastroenterologist at Mayo Clinic in Roch-

ester, Minn. “Taking a gallstone out surgi-

cally would be almost unheard-of today,” he

said.

But the inability to properly clean the in-

strument between patients has proved to be

its “Achilles heel,” he added. The devices

cannot be exposed to high heat to be steril-

ized, as many instruments are.

It is difficult to clean the narrow inner

tubing by hand, and duodenoscopes, unlike

other endoscopes, have a movable elevator-

like mechanism at the tip that can be manip-

ulated to adjust the position of surgical in-

struments.

The mechanism makes the scope more

versatile, but also more difficult to clean, as

it contains microscopic crevices where bod-

ily fluids and bacteria can lodge.

Olympus Medical Systems Corporation,

Pentax of America and Fujifilm Medical

Systems USA manufacture most of the duo-

denoscopes in use in the United States, with

the lion’s share made by Olympus. Until re-

cent hospital outbreaks, the F.D.A. had

never asked to review manufacturers’ data

about cleaning the complex instruments.

The agency allows many medical devices

onto the market without subjecting them to

the kind of safety and effectiveness testing

required for new drugs if the devices are

deemed “substantially equivalent” to a

medical device already on the market. It is

the manufacturer’s responsibility to make

sure the new device works properly — and

that it can be properly cleaned between

uses.

The manufacturers claim that as long as

health facilities clean and disinfect the de-

vices according to the instructions — a com-

plicated process that can involve more than

100 steps, including visual inspections to

check that no “soil or debris is visible” after

cleaning — duodenoscopes are safe.

The instructions also say devices should

be returned to the manufacturer once a

year for service and maintenance.

Since 2012, however, hundreds of patients

in the United States and Europe have been

infected in dozens of outbreaks linked to

contaminated duodenoscopes. Among the

infectious agents is carbapenem-resistant

Enterobacteriaceae, bacteria that do not re-

spond to a powerful class of antibiotics. The

infection has a 50 percent mortality rate.

More than 30 patients in Seattle were in-

fected with resistant strains of bacteria

such as C.R.E. by duodenoscopes between

2012 and 2014, and 11 died, though many

were already critically ill. Dozens of pa-

tients at a Park Ridge, Ill., hospital were in-

fected with C.R.E. in 2013.

In 2015, two patients died and five were

sickened after being infected with C.R.E.

during procedures involving duodeno-

scopes at the Ronald Reagan U.C.L.A. Medi-

cal Center in Los Angeles.

Recently, doctors in Boston reported the

first known transmission of a microorgan-

ism resistant to colistin, a last-resort antibi-

otic, through a duodenoscope that had been

cleaned according to the manufacturer’s

guidelines and F.D.A. recommendations.

When the scope was sent back to the

manufacturer and taken apart, an internal

defect was discovered that left the danger-

ous bacteria clinging to the instrument. The

manufacturer, Pentax, recalled the defec-

tive devices last year.

“There is really no way we could have

been able to pick up on these internal de-

fects — that’s one of the main takeaways of

this story,” said Dr. Erica S. Shenoy, the as-

sociate chief of infection control at Massa-

chusetts General Hospital.

An F.D.A. advisory panel called for steril-

ization of duodenoscopes four years ago,

when the outbreaks first came to light. To-

day, steam heat — the gold standard for

cleaning and sterilization — can still dam-

age the scopes, creating cracks where bac-

teria can lodge and necessitating more fre-

quent replacements.

In February 2015, the F.D.A. asked manu-

facturers to analyze the contamination

rates of their devices. But so far, manufac-

turers have only completed about 60 per-

cent of the required sampling. One of the

smaller companies has only completed 15

percent of the required tests.

Single-Use Scopes

The flurry of infection outbreaks puts pa-

tients, hospitals and health care providers

in a quandary.

Modern medicine relies extensively on

duodenoscopes and other flexible tubular

“scopes” with cameras at the tips — includ-

ing bronchoscopes to check the lungs, and

colonoscopes to screen for colon cancer —

to diagnose and treat diseases without

surgery.

Alternatives to scoping are limited and

include substitute medical tests and pro-

cedures, like stool tests that screen for colon

cancer in lieu of colonoscopies. (Scopes

used for colon cancer screening are consid-

ered much less risky, however, since they

are used in a part of the body already teem-

ing with bacteria.)

New low-temperature sterilization tech-

nologies may make it possible to disinfect

scopes more effectively. And it is possible to

manufacture disposable scopes that could

be discarded after a single use.

Single-use bronchoscopes are already

making their way to market, although they

are not expected to replace reusable scopes.

But there is no disposable duodenoscope.

The rising prevalence of superbugs —

life-threatening germs that are resistant to

powerful antibiotics — has heightened the

sense of urgency.

“As long as organisms were susceptible

to antibiotics, there really wasn’t a problem,

because even if the scopes were transmit-

ting bacteria, you give patients antibiotics

prophylactically before and after pro-

cedures, and you take care of it,” said Larry

Muscarella, a health care consultant who

scours medical device reports submitted to

the F.D.A. and has often been the first to

identify infection risks.

But prophylactic antibiotics no longer

guarantee protection. A rise in antibiotic-re-

sistant infections worldwide is nearing a

crisis point: The persistent misuse and

overuse of antibiotics in people, plants and

farm animals has led to the proliferation of

bacteria that resist treatment to most avail-

able antibiotics.

The World Health Organization has

called the growth in antibiotic-resistant dis-

ease one of the most significant threats to

global health. The design of duodenoscopes

makes them particularly susceptible to har-

boring these and other bacteria.

But the risk to any given patient is small,

and duodenoscopes are not significant fac-

tors in the rise of drug-resistant bacteria,

said Dr. Alexander J. Kallen, an epidemiolo-

gist at the Centers for Disease Control and

Prevention.

“It’s more of a public health concern than

a concern for the individual patient,” he

said. “The majority of people who get ex-

posed to a scope contaminated with bacte-

ria don’t suffer an adverse consequence.”

“For most patients, it’s a risk they should

absolutely be aware of,” Dr. Kallen added.

“But in most situations the benefits of the

procedure probably outweigh the risks of

an adverse event.”

The controversy has raised concerns

about the safety of other reusable, flexible

“scopes,” all of which have long, closed

channels that are difficult to clean, let alone

sterilize.

The F.D.A. warned health care providers

in 2015 that bronchoscopes, which are used

to examine the lungs, had been linked to

more than 100 infections and might remain

contaminated even after proper cleaning.

Late last year, researchers inspected two

dozen bronchoscopes that had been cleaned

and disinfected at three medical centers,

and found that all retained “residual con-

tamination” after the cleaning process, in-

cluding pathogens like mold and E. coli.

All 24 bronchoscopes had irregularities

apparent to the naked eye, including resi-

dues, retained fluid, scratches and other

damage. An accompanying editorial said

that the results were alarming, and that the

pulmonology community had “buried its

head in the sand regarding this issue.”

In January, researchers at the University

of Pittsburgh reported on a cluster of inten-

sive care unit patients whose drug-resistant

infections were all traced back to a single

bronchoscope.

Ambu, a Danish company, is already mar-

keting a disposable bronchoscope, officials

said. The company is also testing a dispos-

able colonoscope. It anticipates having ad-

ditional endoscopes — including a dispos-

able duodenoscope — on the market in the

United States by 2020.

Though many hospitals in the United

States have purchased single-use broncho-

scopes, Ambu’s former chief executive,

Lars Mercher, said the company encoun-

tered resistance to disposables when the

product was launched.

“It was hard to even get acceptance for

the idea that there was contamination in the

hospital,” he said.

Devices That Are Hard to Sterilize

SCIENCE SOURCE

FOOD AND DRUG ADMINISTRATION/ASSOCIATED PRESS

C.D.C., VIA REUTERS

DAMIAN DOVARGANES/ASSOCIATED PRESS

CONTINUED FROM PAGE D1

Top, a duodenoscope during a procedure.

Above, Dr. David Feinberg, right, president

of the U.C.L.A. Health System. Near left,

Enterobacteriaceae, bacteria that have been

transmitted by duodenoscopes in hospitals.

Far left, the tool’s tip is hard to sterilize.

As corporate giants like Ford,
General Motors and Waymo
struggle to get their self-driving
cars on the road, a team of re-
searchers in China is rethinking
autonomous transportation using
a souped-up bicycle.

This bike can roll over a bump
on its own, staying perfectly
upright. When the man walking
just behind it says “left,” it turns
left, angling back in the direction
it came.

It also has eyes: It can follow
someone jogging several yards
ahead, turning each time the
person turns. And if it encounters
an obstacle, it can swerve to the
side, keeping its balance and

continuing its pursuit.
It is not the first-ever autono-
mous bicycle (Cornell University
has a project underway) or, prob-
ably, the future of transportation,

although it could find a niche in a
future world swarming with
package-delivery vehicles, drones
and robots. Nonetheless, the
Chinese researchers who built the
bike believe it demonstrates the
future of computer hardware. It
navigates the world with help

from what is called a neuromor-
phic chip, modeled after the hu-
man brain.
In a paper published last week
in Nature, the researchers de-

scribed how such a chip could
help machines respond to voice
commands, recognize the sur-
rounding world, avoid obstacles
and maintain balance. The re-
searchers also provided a video
showing these skills at work on a
motorized bicycle.

The short video did not show
the limitations of the bicycle
(which presumably tips over
occasionally), and even the re-
searchers who built the bike

admitted in an email to The New
York Times that the skills on
display could be duplicated with
existing computer hardware. But
in handling all these skills with a
neuromorphic processor, the
project highlighted the wider
effort to achieve new levels of

artificial intelligence with novel
kinds of chips.
This effort spans myriad start-
up companies and academic labs,
as well as big-name tech compa-

nies like Google, Intel and IBM.
And as the Nature paper demon-
strates, the movement is gaining
significant momentum in China, a
country with little experience
designing its own computer pro-
cessors, but which has invested
heavily in the idea of an “A.I.

chip.”
The hope is that such chips will
eventually allow machines to
navigate the world with an auton-
omy not possible today. Existing

robots can learn to open a door or
toss a Ping-Pong ball into a plas-
tic bin, but the training takes
hours to days of trial and error.
Even then, the skills are viable
only in very particular situations.
With help from neuromorphic
chips and other new processors,

machines could learn more com-
plex tasks more efficiently, and be
more adaptable in executing
them.
“That is where we see the big
promise,” said Mike Davies, who
oversees Intel’s efforts to build

neuromorphic chips.
Over the past decade, the de-
velopment of artificial intelligence
has accelerated thanks to what
are called neural networks: com-
plex mathematical systems that
can learn tasks by analyzing vast
amounts of data. By metabolizing
thousands of cat photos, for in-
stance, a neural network can

learn to recognize a cat.
This is the technology that
recognizes faces in the photos you
post to Facebook, identifies the
commands you bark into your
smartphone and translates be-

tween languages on internet

services like Microsoft Skype. It

is also hastening the advance of

autonomous robots, including

self-driving cars. But it faces

significant limitations.

A neural network doesn’t really

learn on the fly. Engineers train a

neural network for a particular

task before sending it out into the

real world, and it can’t learn

without enormous numbers of

examples. OpenAI, a San Fran-

cisco artificial intelligence lab,

recently built a system that could

beat the world’s best players at a

complex video game called Dota

2. But the system first spent
   months playing the game against
   itself, burning through millions of
   dollars in computing power.
   Researchers aim to build sys-
   tems that can learn skills in a
   manner similar to the way people
   do. And that could require new
   kinds of computer hardware.
   Dozens of companies and aca-
   demic labs are now developing
   chips specifically for training and
   operating A.I. systems. The most
   ambitious projects are the neuro-
   morphic processors, including the
   Tianjic chip under development at
   Tsinghua University in China.
   Such chips are designed to
   imitate the network of neurons in
   the brain, not unlike a neural
   network but with even greater
   fidelity, at least in theory.
   Neuromorphic chips typically
   include hundreds of thousands of
   faux neurons, and rather than just
   processing 1s and 0s, these neu-
   rons operate by trading tiny
   bursts of electrical signals, “fir-
   ing” or “spiking” only when input
   signals reach critical thresholds,
   as biological neurons do.
   “This is about trying to bridge
   and unify computer science and
   neuroscience,” said Gordon Wil-
   son, the chief executive of Rain
   Neuromorphics, a start-up com-
   pany that is developing a neuro-
   morphic chip.
   Neuromorphic chips are by no
   means a re-creation of the brain.
   In so many respects, the work-
   ings of the brain remain a mys-
   tery. But the hope for such chips
   is that, by operating a bit more
   like the brain, they can help A.I.
   systems learn skills and execute
   tasks more efficiently.
   Because each faux neuron fires
   only on demand rather than
   continuously, neuromorphic chips
   consume less energy than tradi-
   tional processors. And because
   they are designed to process
   information in short bursts, some
   researchers believe they could
   lead to systems that learn on the
   fly, from much smaller amounts of
   data.
   In the video, the bicycle is not
   learning; it is merely executing
   software that had been trained to
   handle specific tasks, including
   recognizing spoken words and
   avoiding obstacles. But it is exe-
   cuting the software in an efficient
   way, which is important to vehi-
   cles that run on battery power.
   Researchers believe they can

eventually merge the training

process and the in-the-moment

execution, so that a bicycle could

learn as it goes, from just a few

moments of experience.

The rub is that building the

right hardware may require at

least several more years of re-

search. “We are still in the trial

and error stage,” said Georgios

Dimou, who previously worked on

Intel’s neuromorphic project.

The Chinese researchers be-

lieve that time will bring far more

than just autonomous bicycles.

Their paper paints the Tianjic

chip as a step toward “artificial

general intelligence,” a machine

that can do anything you and

your brain can do. But that is

merely the promise du jour. May-

be start with helping it learn to

ride a bike.

Self-Driving Bike Glides

Toward the Future of A.I.

PEI ET AL., NATURE
A frame taken from a video by researchers in China shows a self-driving bicycle.

By CADE METZ