Gastrointest Endoscopy Clin N Am

14 (2004) 1 – 9

History and development of

capsule endoscopy
Gavriel J. Iddan, DSc*, C. Paul Swain, MD
Given Imaging, Ltd., New Industrial Park, 13 HaYetzira St., POB 258, Yoqneam 20695, Israel

In 1981 I went on sabbatical from Rafael Ltd. in Israel where I specialized in

electro-optics and went to work for Elscint Ltd. in Boston, developing special
X-ray tubes and ultrasonic probes. During my stay in Boston I befriended my
neighbor, Prof. Eitan Scapa, an Israeli gastroenterologist, also on sabbatical, who
was working in one of the hospitals in the Boston area. During our many meet-
ings, we discussed our respective fields and in this way I learned first hand
about fiber optic endoscopes and colonoscopes, their operation, and their limita-
tions—especially the inaccessibility of the small intestine. Prof. Scapa challenged
me into finding a way to view the small intestine but at that time I had no idea
how to do it.
During my next sabbatical to the US in 1991, Prof. Scapa visited me and again
challenged me to find a solution to the problem of viewing the small intestine.
By this time (10 years later), small format charge-coupled devices (CCD) im-
age sensors had become available as a result of the ever-increasing desire to
build small video cameras. These CCDs were used by the leading endoscope
manufactures to introduce new generation of CCD-based endoscopes that pro-
jected video onto a monitor, replacing the uncomfortable and complicated fiber-
scope method.
At that time, I thought about the possibility of cutting the camera tip of the
endoscope and let it move naturally through the digestive tract, while maintaining
a thin umbilical cable to the endoscope. However, knowing that the length of the
small intestine can be as long as 5 m, I realized that this was not feasible. The next
idea was to cut the thin umbilical cable and replace it with a transmitter. To this
end, I purchased a miniature transmitter kit for future experiments.

This article gives an account on the development of capsule endoscopy beginning with the
seminal work done in Israel at Rafael Ltd. by Gavriel J. Iddan and the parallel efforts of C. Paul
Swain in the UK. Since 1998, these two groups combined their efforts to develop the wireless video
capsule endoscope.
* Corresponding author.
E-mail address: iddan@givenimaging.com (G.J. Iddan).

1052-5157/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.giec.2003.10.022
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In 1992, when I returned to my position as electro-optical engineer, I con-

tinued to develop the idea of a transmitter-equipped camera. Consulting with
numerous gastroenterologists, I realized that there were still many challenges.
Basic questions that needed to be answered were: How would the lens be kept
clean? Would the physician be available for the 8-hour passage time?
I consulted an expert on CCD cameras and he made it very clear that a
miniature battery-equipped CCD camera will operate for only 10 minutes before
exhausting the battery. This didn’t even take into account the energy required
by the transmitter and the illumination source.
At this point, the challenges seemed to be overwhelming and I was ready to
give up the whole project, but decided to forge forward and try to resolve the
obstacles one at a time.

Implementing the first optic solution

The first assumption was that ogive-shaped optics would allow the intestinal
wall to rub itself against the window thus cleaning it continuously while forming
direct contact imaging. An axicon optic window was fabricated. Using a minia-
ture CCD, these optics and a miniature incandescent light source, experiments
proved this solution yielded reasonable images (Fig. 1).

Fig. 1. The wireless capsule endoscope.

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A simplistic experiment was performed using a store-bought chicken to

determine the frequency and power required to transmit a video signal through
tissue whereby a transmitting antenna was placed inside the chicken and a re-
ceiving antenna outside the chicken. The resulting measurements indicated that
when the setup was tuned to the proper frequency, microwatt level power was
sufficient to transmit a clear video image. This result was very encouraging.

From charge-coupled device to complementary metal oxide semiconductor

During 1993, our attention was called to an article published by E. Fossum
from the Jet Propulsion Laboratory in Pasadena, California, describing a new
generation of video imagers requiring a fraction of the power consumed by the
existing miniature CCD imagers [1]. The article also described how the new
device incorporated all necessary camera circuits onto one small silicon wafer.
This important development brought the capsule closer to reality. Another
conceptual breakthrough was separation of the device into three subsystems,
imager/transmitter (capsule), receiver/recorder, and workstation. This separation
eliminated the need for the patient and the physician to be in proximity for the
length of the 8-hour examination.
A multiple antenna array system was incorporated to guarantee proper radio
reception from the capsule as it moved throughout the entire gastrointestinal
tract. It was later observed that this could be the basis of a triangulation local-
ization system.
The initial patent application was filed on January 1994.

Professor C. Paul Swain’s research in the United Kingdom

In September 1994, and totally unbeknownst to Dr. Iddan, halfway across
the world in the United States, Dr. C. Paul Swain, a gastroenterologist from
London, England, presented the possibility of wireless endoscopy during the Los
Angeles World Congress of Gastroenterology, in an invited talk entitled Micro-
waves in Gastroenterology.

C. Paul Swain relates

Since 1981, I have been working with a brilliant researcher—a physicist and a
bioengineer—Tim Mills at University College, London. We first worked together
on lasers and radio frequency for the treatment of bleeding. Together we have
developed a number of novel endoscopic devices and were the first to describe
sewing methods for use at flexible endoscopy and have some claim to have first
developed methods at flexible endoscopy for stapling, band ligation, anastomosis,
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knot tying, endoscopic mucosal resection, thread cutting, full thickness resection,
and gastroplasty for obesity. In the course of our development of endoscopic
sewing devices, we developed methods for attaching radiotelemetry capsules to
the wall of the esophagus and stomach for long-term measurements of pH. One
of us had a wireless pH capsule sewn to the wall of his stomach, which continued
to transmit measurements of intragastric pH for more than 3 months before it
was removed at flexible endoscopy by cutting the thread. Our group had been
using this technology clinically and experimentally for several years.
In the early 1990s, both video cameras and wireless transmitters were
becoming smaller. We decided to explore this technology for experimental en-
doscopy. For this purpose, we acquired the smallest video cameras and trans-
mitters available. The problem was to find components and devices, which were
small enough to swallow.
In 1993 we appointed Feng Gong to work with us. He was to do a PhD at
University College on the development of sewing machines and related technol-
ogy (which he subsequently completed in 1999). We had a grant for his project
from Science and Engineering Research Council (SERC)—which is a govern-
ment body that funds scientific research (sparingly) in the UK.
With his help, we began to search Japanese trade journals for the smallest new
video cameras and processors. With a limited budget, we started to buy the
smallest cameras and processors available to initiate bench and animal testing.
We also contacted technical firms who worked with the British Broadcasting
Corporation (BBC) and became aware that low light level TV transmission had
revolutionized battlefield television journalism, and that cameras could be con-
cealed in tie-pins or handbags for covert journalism. We visited some of the so-
called spy shops in London, which supply transmitters and small video cameras
for installation in bedrooms by private detectives or other users. Most of these
oddly transmit on illegal frequencies but are sold openly and we acquired a
couple of these. Some could tune through a variety of frequencies. For the
security and surveillance market, some small video cameras were becoming
available at surprisingly low cost. We also contacted a specialist firm, which had
developed sports video equipment. They had buried a video camera in a cricket
stump using a prism so that the trajectory of the ball could be followed as it
approached the batsman. A cricket stump was less than 3-cm wide so we know it
would be almost possible to pass a device like this through the esophagus. We
acquired our first microwave transmitter and receiver from them and began to
test them.
Tim Mills thought that doing a PhD on endoscopic sewing devices was too
practical to allow the award of this as a degree in medical Physics and so Feng
was asked to do a feasibility study on remote robotic endoscopy and to do power
calculations to see how long we could run simple experimental devices on bat-
teries that could transmit images through the anterior abdominal wall.
I was invited to talk on the uses of microwaves in gastroenterology at a world
congress in Los Angeles in 1994. We had developed a microwave device for
treating gastrointestinal bleeding and cancer but chose also to talk on the pos-
 G.J. Iddan, C.P. Swain / Gastrointest Endoscopy Clin N Am 14 (2004) 1–9 5

sibility of using microwaves for transmission of images from a robotic capsular

camera in public for the first time there. The first abstract on this topic was also
published in Gut in 1994 entitled an ‘‘Endorobot for flexible endoscopy, a
feasibility study’’ [2]. It was presented as a poster at the British Society of
Gastroenterology and did not attract much attention.
We started to develop crude devices to see if we could transmit moving images
with some of these small cameras and transmitters. Microwave frequencies were
used for most of the transmissions because the bandwidth was not a problem as
it might be with some low radio frequencies. We looked at calculations of
absorption of microwaves in tissue. Tim had worked extensively on light ab-
sorption in tissue and we knew that some microwave frequencies were not
absorbed much by water and fat.
By 1996, we started to wrap our video camera and wireless transmitter devices
in tissue to test transmission through the stomach wall [3]. We studied batte-
ries and available light sources. Our first device used a miniature bulb as a light
source. The principle of transmitting video images through the human body was
tested by placing the device in a box through which microwaves could not
penetrate and pressing a window, cut in the box, against the abdomen. Color video
images were obtained by placing a receiver behind the body of the volunteer.
At this time, our first in vivo experiment occurred when we surgically inserted
into a live pig stomach a large prototype device that used a video camera,
microwave transmitter and light source with batteries. The device used a dome
shaped wire cage to keep the tissue away from the lens, because of the airless
nature of this endoscopy and the whole device was placed in a transparent plastic
bag. The stomach and abdomen were closed surgically. The device worked and
we could see the pylorus open and close. At this stage we were acquiring images
at 30 frames a second and could run this device for about 20 minutes [3].
Although the cheapest available CCD chip cameras were now small enough to
be swallowed and some had low power requirements, the processor boards were
larger, flat and square, or rectangular and the smallest we could purchase was
25-mm square, which was still a bit too large to swallow. We knew that we could
get all the components into a device that could be swallowed but that we would
have to get it made for us, and we asked the electronics section of the Medical
Physics department to do this for us. They agreed to do this for £7,000, which
was a lot of money for us at that time.
At this point, our team was still unaware of Given Imaging’s existence and the
progress Gavriel Iddan had already made.

The two groups meet

In 1995 Iddan first presented the idea of a wireless endoscopic capsule to
Gavriel Meron, who at that time was the CEO of Applitec Ltd., specializing in
small endoscopic cameras for fiberscopes. In 1997 the initial patent was published
[4] and RDC Ltd. (a private incubator company), agreed to establish a new start-up
6 G.J. Iddan, C.P. Swain / Gastrointest Endoscopy Clin N Am 14 (2004) 1–9

headed by Gavriel Meron with Iddan as his advisor. In 1997 they became
acquainted with the independent work on wireless endoscopy performed by Prof.
C. Paul Swain.
In the fall of 1997, Gavriel Meron first met Paul Swain and Alexander (Sandy)
Mosse at the UEGW meeting in Birmingham, England. It was at this time that Mr.
Meron presented his plans for establishing a Company that would focus on a
swallowable capsule platform for gastrointestinal diagnostics. It was believed that
progress would be much faster if the two groups joined forces. Although Paul
Swain’s group had concentrated on the human physiology and the challenge of
transmitting from within the body, Gavriel Iddan’s group knew about develop-
ments in complementary metal oxide semiconductor (CMOS) imaging, which
meant that good quality images could be acquired using substantially less power
than with CCD technology. This development, which Swain’s group was not aware
of at the time, was crucial to the manufacture of a practical capsule endoscope.
In 1998 Gavriel Meron met Prof. Swain again in Rome. The meeting almost
did not take place—the first attempt at a meeting failed when Paul Swain’s plane
was struck by lightening and was forced to land in Geneva. However, following
this meeting, Professor Paul Swain agreed to collaborate with Given Imaging in
the development of the wireless capsule endoscope.

The first prototype is manufactured and swallowed

Paul Swain continues

In 1998, our group visited the FDA in Bethesda. The outline of an animal
study was proposed, which was to be performed on pigs in the United Kingdom.
We were going to inject colored inks into the small intestine to mark areas at
endoscopy and then see how many of these could be recognized at wireless
capsule and push enteroscopy. It turned out that all anesthetic agents which we
used completely abolished peristalsis in pigs that gastric emptying times were
about 12 hours and that push enteroscopy as a means of delivering capsules into
the duodenum was much more difficult than I had imagined.
In the meantime we found that using thread and sewing small beads at various
sites in the small intestine was a better way to go, and we felt that we had developed
the model we needed to test the capsule. We elected to do the study in dogs in
Israel. We found that the anesthetic agents usually did not abolish peristalsis in
these animals and developed a hydraulic device like the cup of an acorn on a
catheter for delivering capsules through the pylorus into the duodenum in dogs.
Successfully overcoming the enormous obstacles of size, transmission strength,
battery power, image resolution, among many others, working prototypes were
produced in January 1999 by the Given Imaging Research & Development group
headed by Dr. Arkady Glukhovsky. I visited Given Imaging offices and work-
shop in Yoqneam in Israel and together we experimented around with wired de-
vices in excised pig small intestine.
 G.J. Iddan, C.P. Swain / Gastrointest Endoscopy Clin N Am 14 (2004) 1–9 7

The ethics committee at the Royal London Hospital approved my request to

conduct the initial testing of the wireless capsule endoscope in myself in August
1999. They were amused and curious about some of the paradoxes of approving a
protocol for volunteer self-experimentation. I had to designate a surgeon who
could remove the device if it got stuck.
In October 1999, in the clinic of Dr Eitan Scapa near Tel Aviv, Israel, I
swallowed the first capsule and on the next day, I swallowed the second one. At
this stage the capsule was 11  33 mm in diameter and only had two light emitting
diodes (LEDs). The aerial reception was a single dipole arranged in a ring and
was hand-held over the abdomen, which had to follow capsule movement to
optimize reception. Because we had had substantial difficulty with delayed gastric
emptying in early animal studies, we were worried that the device would not leave
the stomach. Our first acquired images had poor quality real-time viewing. Several
images were low quality because it took some practice to hold the aerial in the
best position. To encourage transition through the pylorus and into the small
intestine, I tried lying flat on my left side. During this initial experience, the bat-
teries ran out after about 2 hours.
An endoscopy was performed to determine that the capsule had left the stomach.
We were not absolutely sure that the capsule had passed the pylorus, because the
real-time images were suboptimal; we found that they were substantially better
after processing. Once we saw that the capsule had left the stomach, we knew we
had acquired small intestinal images. I was able to compare the completely painless
swallowing of the capsule with the experience of a conventional gastroscopy.
Arkady Glukhovsky (head of R&D at Given Imaging at the time) suggested I
undergo an radiograph to show the position of the capsule. The radiograph
showed that the capsule had reached the cecum. The next morning I swallowed
the second capsule in my hotel room. The Given Imaging team brought all the
electronic equipment necessary to the room. On this occasion all the technical
aspects operated successfully. We were now practiced at optimizing the reception
and I enjoyed watching the lovely sea view during this capsule endoscopy exami-
nation. The second capsule transmitted for more than 6 hours. The Given Imag-
ing engineers processed the images before I flew back to the United Kingdom the
next day and the quality was good. We had a substantial length of small intestinal
imaging with a lot of artifact on the first run. The second was much better and the
capsule reached the cecum. I had to pass through the fairly rigorous Israeli airport
security with the second capsule still possibly transmitting inside me. Their
detectors did not find it. I retrieved this capsule in the toilet at my hospital in
London the next morning.
I had several subsequent visits to Given Imaging to help with the animal study
that the Food and Drug Administration had wanted and to continue to help on the
further development. The animal study turned out to be demanding using a push
enteroscope and our hydraulic delivery system to deliver the capsules through the
pylorus of the dogs. The trick was to identify the pylorus and press the capsule
against it, then wait for the pylorus to open and push the catheter forward when a
wave of antral contraction opened the pylorus.
8 G.J. Iddan, C.P. Swain / Gastrointest Endoscopy Clin N Am 14 (2004) 1–9

We became excited when we were able to see moving Ascaris in these

animals, which could not be seen on push enteroscopy. This was the first time I
saw pathology using wireless capsule endoscopy, which could not be seen by
other means. The engineers had become so slick that we could retrieve capsules
with the LEDs still flashing and replace the batteries and reuse the capsules again
within an hour.
By this time we had also been granted ethics approval for a human volunteer
study with larger numbers and also had ethics approval for the first patient studies
at the Royal London Hospital. In the meantime we wrote and submitted in
December 1999 the abstract for presentation of our work to be presented at
Digestive Disease Week in San Diego in 2000. In April we performed the first
patient trials with the wireless capsule in four patients with obscure recurrent
gastrointestinal bleeding. A small intestinal bleeding source was found in three of
these. We also wrote the work up for publication and thought that we would try
Nature because the first article on flexible endoscopy by Hopkins had been
published in that journal in 1954. The editors of Nature were quick to point out
that there had been no subsequent papers in Nature on endoscopic topics but
agreed to get referee’s comments and consider it and then agreed to publish it.
Nature insists that there is no disclosure or publicity before publication. We had a
period of anxiety when they lost our illustrations and the publication was delayed
by a week, which by chance caused the publication in Nature and the DDW
presentation to occur on the same day. The editors of Nature had added as a
header to our article ‘‘The discomfort on internal endoscopy may soon be a thing
of the past’’ and had released the article to the press with a moratorium on
publication until the article in Nature [5] was published.
Gastrointestinal Endoscopy published the account of our efforts in London
to develop this technology a few days after the publication of the Nature article
[6]. Gastroenterology published our experimental animal study in December
1999, the New England Journal report of our first four patients was published a
month later [7]. The device received a CE mark and Food and Drug Adminis-
tration approval in August 2000.

Acknowledgments
Paul Swain’s acknowledgments
I would like to acknowledge my debt to the Medical Physics Department at
University College, London and especially to Dr. Tim Mills, principal physicist
and my long-term colleague and friend. I thank Dr. Feng Gong who wrote his
PhD in part on this development, Dr. Sandy Mosse who wrote his PhD in part on
electrostimulation for moving the capsule remotely. I also thank my medical
colleagues, especially Dr. Mark Appleyard for his help with the demanding ani-
mal studies, the earliest clinical studies, and his important contributions to the
early publications on this method. Some of this work was included in his MD
thesis. I would like to thank Dr. Maria Mylonaki and Priv-Doz Dr. Annette
 G.J. Iddan, C.P. Swain / Gastrointest Endoscopy Clin N Am 14 (2004) 1–9 9

Fischer-Ravens for continuing the clinical studies and development and testing of
new devices at the Royal London Hospital.
Gavriel Iddan’s acknowledgments
I acknowledge the important contributions of Dr. Doron Sturlesi, who de-
signed the axicon optics, to Dov Avni who was instrumental in defining the
optimal imager, Dr. Eitan Scapa for providing me with the inspiration, Dr. Harold
Jacob for his continual guidance, and Gavriel Meron who made our dream into
a reality.

References
[1] Fossum ER. Active image sensors: are CCDs Dinosaurs? International Society for Optical En-
gineering (SPIE) 1993;1900:2 – 14.
[2] US Patent No. 5,604,531.
[3] Gong F, Swain CP, Mills TN. An endorobot for gastrointestinal endoscopy. Gut 1994;35:S52.
[4] Swain CP, Gong F, Mills TN. Wireless transmission of a colour television moving image from
the stomach using a miniature CCD camera, light source and microwave transmitter. Gut 1996;
39:A26.
[5] Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 2000;405:417.
[6] Gong F, Mills TN, Swain CP. Wireless endoscopy. Gastrointest Endosc 2000;51:725 – 9.
[7] Appleyard M, Glukhovsky A, Swain P. Wireless capsule diagnostic endoscopy for recurrent
small-bowel bleeding. N Engl J Med 2001;34:232 – 3.