Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 13
Inventing Medical Devices:
Five Inventors' Stories
Development of Technicon's Auto Analyzer
EDWIN C. WHITEHEAD
In 1950 Alan Moritz, chairman of the department of pathology at
Case Western Reserve University and an old friend of mine, wrote to
tell me about Leonard Skeggs, a young man in his department who
had developed an instrument that Technicon might be interested in. I
was out of my New York office on a prolonged trip, and my father,
cofounder with me of Technicon Corporation, opened the letter. He
wrote to Dr. Moritz saying that Technicon was always interested in
new developments and enclosed a four-page confidential disclosure
form. Not surprisingly, Dr. Moritz thought that Technicon was not
really interested in Skeggs's instrument, and my father dismissed the
matter as routine.
Three years later Ray Roesch, Technicon's only salesman at the
time, was visiting Joseph Kahn at the Cleveland Veterans Administra-
tion Hospital. Dr. Kahn asked Ray why Technicon had turned down
Skeggs's invention. Ray responded that he had never heard of it and
asked, "What invention?" Kahn replied, "A machine to automate
chemical analysis." When Ray called me and asked why I had turned
Skeggs's idea down, I said I had not heard of it either. When he told
me that Skeggs's idea was to automate clinical chemistry, my reaction
was, "Wow! Let's look at it and make sure Skeggs doesn't get away."
That weekend, Ray Roesch loaded some laboratory equipment in
his station wagon and drove Leonard Skeggs and his wife Jean to New
York. At Technicon, Skeggs set up a simple device consisting of a
peristaltic pump to draw the specimen sample and reagent streams
through the system, a continuous dialyzer to remove protein molecules
13
OCR for page 14
14
MEDICAL DEVICE INNOVATION AND HEALTH CARE
that might interfere with the specimen-reagent reaction, and a spec-
trophotometer equipped with a how cell to monitor the reaction. This
device demonstrated the validity of the idea, and we promptly entered
negotiations with Skeggs for a license to patent the Auto Analyzer.
We agreed on an initial payment of $6,000 and royalties of 3 percent
after a certain number of units had been sold.
After Technicon "turned-down" the project in 1950, Skeggs had
made arrangements first with the Heinecke Instrument Co. and then
the Harshaw Chemical Co. to sell his device. Both companies erro-
neously assumed that the instrument was a finished product. However,
neither company had been able to sell a single instrument from 1950
until 1953. This was not surprising, because Skeggs's original instru-
ment required an expensive development process to make it rugged
and reliable, and to modify the original, manual chemical assays.
Technicon spent 3 years refining the simple model developed by Skeggs
into a commercially viable continuous-flow analyzer.
A number of problems unique to the Auto Analyzer had to be
overcome. Because the analyzer pumps a continuous-flow stream of
reagents interrupted by specimen samples, one basic problem was the
interaction between specimen samples. This problem was alleviated
by introducing air bubbles as physical barriers between samples.
However, specimen carryover in continuous-flow analyzers remains
sensitive to the formation and size of bubbles, the inside diameter of
the tubing through which fluids flow, the pattern of peristaltic pumping
action, and other factors.
Development of the Auto Analyzer was financed internally at
Technicon. In 1953 Technicon had ongoing business of less than $10
million per year: automatic tissue processors and slide filing cabinets
for histology laboratories, automatic fraction collectors for chroma-
tography, and portable respirators for polio patients. Until it went
public in 1969, Technicon had neither borrowed money nor sold equity.
Thus, Technicon's patent on Skeggs's original invention was central
to the development of the Auto Analyzer. Without patent protection,
Technicon could never have afforded to pursue the expensive devel-
opment of this device.
Early in the instrument's development, I recognized that traditional
marketing techniques suitable for most laboratory instruments would
not work for something as revolutionary as the Auto Analyzer. At
that time, laboratory instruments were usually sold by catalog salesmen
or by mail from specification sheets listing instrument specifications,
price, and perhaps product benefits. In contrast, we decided that
OCR for page 15
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
15
Technicon had to market the Auto Analyzer as a complete system-
instrument, reagents, and instruction.
Technicon's marketing strategy has been to promote the Auto
Analyzer at professional meetings and through scientific papers and
journal articles. Technicon employs only direct salesmen. The company
has never used agents or distributors, except in countries where the
market is too small to support direct sales.
To introduce technology as radical as the Auto Analyzer into
conservative clinical laboratories, Technicon decided to perform clin-
ical evaluations. Although unusual at that time, such evaluations have
since become commonplace. An important condition of the clinical
evaluations was Technicon's insistence that the laboratory conducting
the evaluation call a meeting of its local professional society to announce
the results. Such meetings generally resulted in an enthusiastic en-
dorsement of the Auto Analyzer by the laboratory director. I believe
this technique had much to do with the rapid market acceptance of
the Auto Analyzer.
Other unusual marketing strategies employed by Technicon to
promote the Auto Analyzer included symposia and training courses.
Technicon sponsored about 25 symposia on techniques in automated
analytical chemistry. The symposia were generally 3-day affairs,
attracting between 1,000 and 4,500 scientists, and were held in most
of the major countries of the world including the United States.
Because we realized that market acceptance of the Auto Analyzer
could be irreparably damaged by incompetent users, Technicon set up
a broad-scale training program. We insisted that purchasers of Auto
Analyzers come to our training centers located around the world for
a 1-week course of instruction. I estimate that we have trained about
50,000 people to use Auto Analyzers.
Introduction of Technicon's continuous-flow Auto Analyzer in 1957
profoundly changed the character of the clinical laboratory, allowing
a hundredfold increase in the number of laboratory tests performed
over a 10-year period. When we began to develop the Auto Analyzer
in 1953, I estimated a potential market of 250 units. Currently, more
than 50,000 Auto Analyzer Channels are estimated to be in use around
the world.
In reviewing the 35-year history of the Auto Analyzer, I have come
to the conclusion that several factors significantly influenced our
success. First, the Auto Analyzer allowed both an enormous improve-
ment in the quality of laboratory test results and an enormous reduction
in the cost of doing chemical analysis. Second, physicians began to
OCR for page 16
16
MEDICAL DEVICE INNOVATION kD HEALTH CAM
realize that accurate laboratory data are useful in diagnosis. Last
reimbursement policies increased the availability of health care.
Plasmapheresis
EDWIN C. WHITEHEAD
l
In the early 1940s, I read a provocative article by Arthur Wright,
professor of surgery at New York University. Dr. Wright observed
that by removing the plasma from a blood donation and then reinfusing
red blood cells in the donor, one could bleed the donor twice a week
instead of once every 7 weeks.
At the time, Technicon Corporation was doing some work with
William Aaronson, who was a pathologist at Morrisania Hospital in
New York and also had a private laboratory. He and I discussed
Wright's article and decided that the process would be practical only
if it were automated. Otherwise, taking a blood donation, separating
the cells from the plasma, and reinfusing the red blood cells in the
donor would be too laborious.
This was during World War II, and every newspaper and advertise-
ment called for donations of plasma, which was sorely needed by the
military. Dr. Aaronson and I reasoned that, since most of the soldiers
in the United States were young and healthy, bleeding soldiers twice
a week might be a better way of obtaining plasma than depending on
donations from the civilian population. If we could make a small,
portable, rugged, relatively inexpensive device to automate the process
described by Wright, the military and the Red Cross should have great
need for it.
Aaronson and I experimented to determine the most efficient way
to separate blood and plasma. The design we finally settled on was a
cone-shaped container with radially extending blades that divided the
container into separate compartments. Blood was drawn from the
donor through a needle and injected directly into the center of the
spinning container. Red cells were packed by centrifugal force at the
outer edges of the container and plasma formed a layer closer to the
center. We started removing plasma as soon as we had drawn 100 ml
of blood. By the time the 400-ml blood donation was drawn, the plasma
had been removed into a plastic bag. Saline solution was then added
to the donor's red blood cells and the cells were fed back to the donor
by gravity through the same needle used to draw the blood.
In 6 months we had developed an operating prototype. We decided
OCR for page 17
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
1
~7
to try it out by hiring a professional blood donor, bleeding the donor
twice a week, and doing weekly blood chemistry studies to see if the
donor experienced any ill effects. We managed to find a donor, but
when we explained what we intended to do, he looked first startled,
then frightened, and quickly picked up his hat and walked out.
Aaronson and I tried to enlist other paid donors with the same result
and finally decided to test our prototype by bleeding each other. I
would stop at Aaronson's laboratory on my way home from work each
Monday and Friday afternoon, and we would bleed each other. In
1944, after 6 months of observing no adverse effects, we decided that
it was time to market the device.
We made appointments with Red Cross, Army, and Navy offices in
Washington, D.C., to demonstrate the device. Aaronson and I boarded
the train from New York to Washington carrying a large box that
contained substantial quantities of donated whole blood packed in ice.
Feeling pleased with ourselves, we had reserved seats in the club car.
We plunked down our large box and took our seats. Near Philadelphia,
we noticed a thin, red stream of blood running from the box. Although
our fellow passengers were too polite to comment, we were so
embarrassed that we pretended the box did not belong to us until we
got to Washington. Fortunately, only one of the bottles had broken.
When Aaronson and I arrived in Washington, we were told by the
Red Cross, the Army, and the Navy that, despite public appeals, the
one thing the military had in abundance was blood plasma! In fact,
both the Navy and the Army made a point of telling us that the first
thing to be jettisoned in time of battle was blood plasma. Thus, our
"market" completely disappeared and we abandoned our project,
having spent a considerable amount of effort and receiving a patent
for our invention.
Pneumatic Extradural
Intracranial Pressure Monitor
ALAN R. KAHN
Intracranial pressure (ICP) is monitored to detect dangerous pressure
increases in patients with head or spinal trauma, craniotomies, Reye's
syndrome, and certain drug intoxications. Before the invention of the
pneumatic extradural ICP monitor in 1980, monitoring of ICE was
generally accomplished by means of fluid-filled catheters (or other
similar appliances) with one end in direct contact with the patient's
OCR for page 18
18
MEDICAL DEVICE INNOVATION AND HEALTH CARE
cerebrospinal fluid and the other end connected to a conventional
pressure transducer. A device that detects ICP from a site outside the
aura (the outermost and toughest membrane covering the brain) had
been on the market for several years, but the pressure sensor in that
device is very complicated and fragile, is slow to respond to changes,
and is limited in accuracy. Thus, although that device established the
usefulness of extradural ICP monitoring and has found application in
certain medical centers, its use has been limited because of the
complexity and inaccuracy of its sensing system.
In contrast, the pneumatic extradural ICP monitoring system makes
it possible to measure ICP simply, accurately, and at low cost. The
invention includes a disposable sensor that is accurate, rugged, and
inexpensive to construct. The invention also includes a pneumatic
system in a monitoring module that powers the sensor and provides
self-checking and failure detection. The system has been designed as
a sophisticated microprocessor-based instrument and has been intro-
duced to the market by Meadox Instruments, Inc.
THE INVENTION PROCESS
The invention of the ICP monitor was not the result of new
technological developments but was rather the application of a basic
physical principle that had been overlooked in the area of pressure
measurement. In recent years, advances in technology have been made
primarily in the field of electronics, and scientists and engineers tend
to ignore other physical modalities such as pneumatics. Most of my
inventions have been in the area of sensing and measurement and
make use of basic physics rather than new technological developments.
The necessary technical information can be found in any basic physics
textbook.
I first had the idea for the pressure management technique used in
this instrument in 1964 as a way to measure the elasticity of human
skin for a study on aging. At the time, I worked for a major corporation
that did not see a market for a device with that application, and no
product was ever developed.
In 1980, during a discussion on ICP monitoring, I realized that my
old idea could be modified for use in this new application. I offered
the company with which I was employed the opportunity to develop
this product under a royalty arrangement, but the company declined.
Subsequently, I left that company to join a research and development
consulting firm as an equal partner with the two existing partners, and
we invested our time and personal funds to develop a prototype ICP
OCR for page 19
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
19
monitoring system. It took 6 months to build and test the first prototype
in our laboratory and to perform preliminary tests in animals.
FINANCING AND MARKETING
Perhaps the most difficult step we encountered was in obtaining
funding for design and marketing of the product. This was complicated
by the fact that my partners and I were primarily interested in the
R&D process and did not wish to get involved in marketing. Negoti-
ations with venture capital firms and other conventional sources of
capital proved unsuccessful, because acceptance of the extradural
method of ICP monitoring was limited by the existing product, and it
was difficult to project just how an improved product would affect
market growth. Therefore, conservative sales projections were used
in the business plan. These projections made the venture less attractive
and affected our ability to obtain funding.
We finally established a joint venture with Meadox, a biomedical
company that had facilities for manufacturing the sensors and saw our
ICP monitoring device as an efficient way to enter the market for
electronic products. Each of the three partners in our R&D firm owned
9 percent of the new joint venture company and shared a royalty on
product sales. Our R&D company received a contract from the joint
venture company to develop the product and subsequently to manu-
facture the electronic portion of the system until such time as the
contractors learned more about the product and could take over all of
the manufacturing. Although sales of the ICP monitoring systems in
the United States proceeded as anticipated in our conservative pro-
jection, the monitoring device was foreign to the Meadox product line
and was subsequently discontinued.
Invention of an Electronic Retinoscope
ARAN SAFIR
Following a year at Cornell University as an engineering student, I
entered the U.S. Navy when I turned 18. On the basis of an aptitude
test, I was placed in a training program for electronic technicians. The
training lasted nearly a year and was rigorous and thorough. My Navy
training and World War II ended almost simultaneously, and I spent
another year in the Navy working on aircraft radio and radar systems.
/
OCR for page 20
20
MEDICAL DEVICE INNOVATION AND HEALTH CAME
During that year, I decided that a career in medicine might offer a
good combination of science, technology, and the social disciplines. I
entered New York University as a premedical student majoring in
English; later I entered medical school. Medical school was not much
fun—rote memorization is not my strongest skill. In retrospect, I can
see the early indications of some factors that would later assume great
importance in my life.
In high school, I had been seriously interested in photography-
both the technology and the art. I had neither time nor money for it
in medical school, but I turned to optics to help me learn pathology.
Each student was given hundreds of slides of pathology specimens to
be studied under the microscope so that the features of various diseases
could be memorized. While studying my slides, I discovered that I
could place my microscope on the floor underneath a small table that
had a ground glass top. When I darkened the room, I could see the
projected image of the microscope slide on the tabletop.
Thus, I set about making my microscope into a projector. I bought
the most powerful truck headlight bulb I could find, attached it to a
transformer through an adjustable resistor so that I could operate the
bulb well above its rated voltage, purchased some surplus lenses, and
soldered together various rectangular and cylindrical tin cans to form
a powerful substage lamp for my microscope. A small prism deflected
the beam onto a white poster board on the wall, giving an image about
2 feet in diameter. With this device, several friends and I often studied
our slides together and helped each other to learn.
Still, I thought of this as only a passing diversion, almost occupational
therapy, because I had always been a good mechanic and enjoyed
building things. About 2 years later, I had a brief exposure to
ophthalmology, which is all that most medical students get. But even
during that brief exposure, I realized that I had to make almost no
effort to memorize those parts of the textbook that dealt with the
formation of images by the eye. When we went to the ophthalmological
clinics and could look into the eyes of patients through widely dilated
pupils, I was thrilled by the magic of the eye as an optical instrument.
It was not until many months later, during my internship, that I had
any opportunity to try my hand at surgery. When I found that I was
good at surgery and enjoyed it, I began to think seriously of ophthal-
mology as a career. Still, it was my intention at the time to become a
practitioner of ophthalmology and to return to my hometown to
establish a private practice. I clearly recall that at my residency
interview at the New York Eye and Ear Infirmary, when the governing
board of six senior surgeons asked me whether I intended to do
OCR for page 21
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
~1
research, my reply was: "I don't know. I think I would like to try, to
see whether I'm any good at it."
I became a resident at the New York Eye and Ear Infirmary in 1956.
That institution was known mostly for the excellent opportunity it
gave the trainee to observe, learn, and participate in the practice of
ophthalmology, but offered little experience or opportunity in research.
There was a small scientific program, but residents were rarely
involved.
I reported for duty as a resident at the infirmary on July 1, 1956.
After being issued white uniforms, I was shown to the clinic. There I
was put in the care of a second-year resident who was clearly too
busy with his own clinical problems to spend much time with me. He
sat me down on a stool in a little booth where a patient sat next to a
box of ophthalmological trial lenses. This was to be my first experience
with refraction of the eye. Handing me a small instrument that
resembled a flashlight, which he told me was a retinoscope, the second-
year resident explained that I was to look through the little hole in the
mirror and direct the beam of light into the patient's pupil. When I
shined the light into the patient's eye, he explained, I would observe
the patient's pupil glowing with light reflected from inside the eye. By
tilting the mirror, I could make the reflected light move across the
pupil. I was to sit at arm's length from the patient and observe whether
the light coming back out of the pupil moved in the same direction as
the light I shined on the patient's face, or in the opposite direction. If
the light moved in the same direction, I was to take lenses from one
side of the box, while if the light moved in a contrary direction, I was
to take them from the other side of the box. I was to select lenses that
would make the light appear to stop moving. Wishing me good luck,
the resident went off to his own tasks.
I worked very hard at this first refraction and was quite upset by it.
Like other young physicians, I had spent years learning to be competent
in difficult matters. To be thrust suddenly back into complete incom-
petence and at the same time to have responsibility for patient care
was disturbing to me. I recall going to lunch that day and sitting across
the table from that same second-year resident. I told him, "If I can
see those lights moving in the pupil, I'll bet I can make a photoelectric
device that will see them better and faster." That was the conception
of my idea of an automatic retinoscope.
The retinoscope is basically a small lamp that shines light on a
mirror with a hole in its center. Light reflected from the mirror enters
the patient's pupil and illuminates the retina at the back of the eye.
Nearly all the light is then absorbed, but a small fraction is reflected
OCR for page 22
22
MEDICAL DEVICE INNOVATION AND HEALTH CARE:
back, passes through the pupil, and leaves the patient's eye. The light
that is reflected by the retina goes through the optical system of the
patient's eye and acquires characteristics of that system.
The light rays leaving the eye can be either convergent, parallel, or
divergent. If a patient's eye has excessive converging power, as it
does in myopia (nearsightedness), the light rays leaving the eye will
converge to a point in space at some distance in front of the eye. The
distance from the patient's eye to that point is a measure of the amount
of myopia (the closer the point to the eye, the greater the degree of
myopia). An eye with no refractive error sends out parallel rays, and
a farsighted eye sends out divergent rays.
The retinoscopist sits in front of the patient, looks through the sight
hole in the center of the mirror, and decides whether the emerging
light rays have reached a convergent point between him and the patient
or have not yet converged by the time they get to his eye. The patient,
merely has to hold fairly still and gaze at a distant target. The examiner
puts lenses in front of the patient's eye to bring the convergent point
to a standard place, at the examiner's eye. The lenses needed to
accomplish this are a measure of the eye's refractive state.
With this objective measurement, the examiner can go to the next
phase of the examination, in which the patient's subjective responses
to various lenses are elicited. There is usually good agreement between
retinoscopic measurements and the patient's subjective responses.
Because retinoscopy depends on the examiner's skill, which varies
considerably among practitioners, and the patient's subjective re-
sponses, are affected by the patient's personality, the final judgment
of the patient's visual status often requires complex decision making.
Shortly after beginning my work in the clinic, I drew up plans for
the construction of an electronic retinoscope and presented my ideas
to the research committee of the New York Eye and Ear Infirmary. I
asked them for sufficient laboratory space and a budget for some
equipment so that I might try out my idea. They gave me about 6 feet
of bench space in someone else's laboratory, allowed me to borrow a
double-beam oscilloscope, and gave me a drawing account of about
$500. I set to work building an instrument.
The hospital had a lathe and a drill press that were gathering dust
for want of a machine shop, so I was asked to build one for them.
With the aid of one of the hospital's engineering staff, I constructed a
machine shop to which I was subsequently given free access.
The chief administrator of the hospital recommended that I obtain
a patent on my invention and suggested that I go to a former West
Point classmate of his who had become a senior partner in a well-
OCR for page 23
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
~3
known New York patent firm. I did this, and the senior patent attorney
assigned my case to a young patent attorney who had just joined the
firm. That was when I found out that patent attorneys have degrees
both in law and in a scientific discipline. In the young attorney's case,
it was electrical engineering.
The New York Eye and Ear Infirmary gave me a key to the library
and research building and, over the course of about a year and with
the aid of my attorney friend, I built a working model of the electronic
retinoscope. The instrument was crude—the photocells were housed
in the film carrier of an old view camera, the image of the subject eye
was formed by a telescope made from the mailing tube that had held
my diploma from medical school, and many of the parts were surplus
that I had purchased at the outdoor hardware stalls on Canal Street in
New York. But 18 months after I started, I had a working model that
demonstrated the feasibility of the method and was able to measure
the refractive state of schematic eyes, which are metal and glass
simulations of human eyes and are commercially available to students
of refraction who are learning retinoscopy.
An important scene stands out in my memory of those times. As
soon as the retinoscope was operating satisfactorily, I invited a few
close friends to come and see it. Rather late one evening we gathered
in the lab: my patent attorney, my girlfriend, and three or four
ophthalmological buddies. I explained the device and what to look for
on the oscilloscope, dimmed the room lights, and put the instrument
through its paces. The outputs of the photocells could be easily seen
on the oscilloscope. As the schematic eye was changed from nearsighted
to farsighted, the oscilloscope tracing showed the change and clearly
identified the crucial neutral point when the convergent point of the
rays emerging from the eye was brought to precisely the correct
distance, exactly as in clinical retinoscopy.
The instrument had a rotating light beam deflector for creating the
scan of light across the eye. There were mirrors and lenses that cast
moving patterns of light, not only on the schematic eye, but on the
walls of the lab as well. The oscilloscope face flickered with green
evanescent tracings. In the darkened lab, it was dramatic.
As others got interested in the apparatus and began to operate it
themselves, I stepped back to the far side of the room and watched
them. A new feeling swept over me and I verbalized it internally:
"Look at what I have done. What started as an idea in my head has
created a new machine and has gathered these people here and captured
their interest." I had a feeling of power and wonder, a very good
feeling, and though I have experienced it again since then, it has never
been so poignant. Surely, there are many reasons for people to
OCR for page 24
24
MEDICAL DEVICE INNOVATION AND HEALTH CARE;
experience such feelings, but invention is one that I have known, and
I suspect that those who do not invent do not often appreciate the
emotional importance of the act.
The young patent attorney was rather excited about this project
because his review of the patents in existence had led him to conclude
that we were opening up an entirely new field. The idea of dynamic
scanning to measure an optical system had not been patented before.
After about 2 years of effort, we filed a patent application in 1958.
The patent was not granted until 1964, after several rejections and a
hearing. The entire 6-year proceeding, which cost me a great deal of
money and effort, seemed to be designed to test my persistence rather
than my inventiveness.
In 1964 I received a letter from Bausch & Lomb asking me if I was
interested in licensing my patent to them. A contractual agreement
was arranged between the Bausch & Lomb Company and me. It was
8 years from the time we signed the contract until Bausch & Lomb
offered an instrument for sale. In that time, another company came
out with an automatic refracting machine, and the Bausch & Lomb
retinoscope never achieved a significant share of the market. Now
there are several automatic refracting machines on the market. Most
of them are made in Japan, and one of them made by a major Japanese
company uses the principle that I patented. For this, the company
paid me royalties during the last year of the life of my patent.
I made very little money from this invention. If I were to reckon
my income from it in dollars earned per hours spent, I would have
been far better off to have spent my time practicing ophthalmology.
The First Successful
Implantable Cardiac Pacemaker
WILSON GREATBATCH
On April 7, 1958 Dr. William C. Chardack, Dr. Andrew Gage, and
I implanted the first self-powered implantable cardiac pacemaker in
an experimental animal. In October of that year, Dr. Ake Senning in
Stockholm attempted the first human implant. That device worked for
only 3 hours and then failed. A replacement device worked for 8 days,
after which the patient survived unstimulated for 3 years. Two years
later, in 1960, Dr. Chardack, Dr. Gage, and I implanted the first
successful cardiac pacemaker in a human.
OCR for page 25
INtJENTl~G MEDICAL DEVICES: FIVE INVENTORS' STORIES
~5
At the time, we predicted an annual use of perhaps 10,000 pacemakers
per year. Soon thereafter, however, the implantable pacemaker became
the treatment of choice for complete heart block (impairment of
conduction in heart excitation) with Stokes-Adams syndrome (a con-
dition caused by heart block and characterized by sudden attacks of
unconsciousness). Today nearly 30 years later—pacemakers have
assumed forms and functions that we never dreamed of, and the world
pacemaker market is approaching 300,000 units per year.
When World War II was over in 1945, I decided to register at the
School of Electrical Engineering at Cornell University in Ithaca, New
York. As an undergraduate at Cornell, I got my first exposure to
medical electronics. To feed my family, I occasionally worked as an
electronics technician, building intermediate-frequency amplifiers for
what was later to become the Arecibo, Puerto Rico, radiotelescope.
One day, in an adjacent lab, I saw Cornell graduate student Frank
Noble measuring blood pressure in a rat by recording the change in
tail size as a pulse of blood traversed it. Frank's electronic plethys-
mograph belonged to the psychology department's Animal Behavior
Farm at Varna, New York, near Ithaca. Research at the Animal
Behavior Farm dealt with conditioned reflex under neurosis, and Frank
was responsible for measuring heart rate and blood pressure in some
100 sheep and goats there. I became very interested in this work, and
when Frank left to become head of an electronics laboratory at the
National Institutes of Health, I inherited his job.
During the summer of 1951, two New England brain surgeons spent
their summer sabbatical at the farm performing experimental brain
surgery on the hypothalamus of goats. At lunchtime we would sit on
the grass in the bright Ithaca sun and talk shop. I learned much
practical physiology during our discussions. One day, the subject of
heart block came up. When the surgeons described it, I knew I could
fix it but not with the vacuum tubes and storage batteries then
available.
By the time the first commercial silicon transistors became available
(at $90 each) in 1956, I had become an assistant professor of electrical
engineering at the University of Buffalo, I was also spending time with
Dr. Simon Rodbard and Dr. Robert Cohn at the Chronic Disease
Research Institute in Buffalo.
Sy Rodbard was interested in fast heart sounds, which we recorded
with an oscilloscope and a movie camera. I wanted a 1-kilohertz
marker oscillator and built one out of a single transistor and a United
Transformer Company model DOT-1 (UTC DOT-1) transformer. My
marker oscillator used a 10-kilohm base-bias resistor. One day, I
OCR for page 26
26
MEDICAL DEVICE INNOVATION AND HEALTH CARE;
reached into my resistor box to get a 10-kilohm resistor but misread
the color codes, and instead of getting the brown-black-orange resistor,
I got a brown-black-green (1 megohm) resistor. The circuit started to
squeg (oscillate in bursts) with a 1.8-millisecond pulse followed by a
1-second quiescent interval. During the quiescent interval, the transis-
tor was cut off and drew practically no current. I stared at the thing
in disbelief and then realized that this was exactly what was needed
to drive a heart. I built a few more. For the next 5 years, most of the
world's pacemakers were to use a blocking oscillator with a UTC
DOT-1 transformer just because I grabbed the wrong resistor!
I found little enthusiasm locally for an implantable cardiac pace-
maker. Each medical group I approached said, "Fine idea, but most
of these patients die in a year or so. Why don't you work on my
project?"
In Buffalo we had the first local chapter in the world of the Institute
of Radio Engineers, Professional Group in Medical Electronics (the
IRE/PGME, now the Biomedical Engineering Society of the Institute
of Electrical and Electronics Engineers). Every month, 25 to 75 doctors
and engineers met for a technical program. Our chapter had a standing
offer to send an engineering team to assist any doctor who had an
instrumentation problem. One day in the spring of 1958, I went with
such a team to visit Dr. William Chardack on a problem dealing with
a blood oximeter. Dr. Chardack was Chief of Surgery at the Veterans
Administration Hospital in Buffalo. Imagine my surprise at finding that
his assistant was one of my old high school classmates, Andy Gage
(later chief of staff at the hospital)! Our visiting team could not help
Dr. Chardack much with his blood oximeter problem, but when I
broached my pacemaker idea to him, he walked up and down the lab
a couple of times, looked at me strangely, and said, "If you can do
that, you can save 10,000 lives a year." Three weeks later in April
1958, Dr. Chardack, Dr. Gage, and I had our first model cardiac
pacemaker implanted in a dog.
Our experimental work was done on dogs that had been put into
complete heart block by occluding the atrioventricular (AV) bundle
with a tied suture. We had no heart-lung machine. The operating team
stood poised like runners waiting for the starting gun. Upon a "go"
signal, the team occluded the large vessels, opened the heart, occluded
the AV bundle with the tied suture, closed the heart, and released the
large vessels, all in 90 seconds!
We were naive about early pacemaker designs. We initially thought
that wrapping the module in electric tape would seal it. We soon
OCR for page 27
I¢ENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
27
found, however, that any void beneath the tape would fill with fluid,
so we began to case our electronics in a solid epoxy block. Within a
year, we had worked our animal survival time up from 4 hours to 4
months and felt ready to start looking for a suitable patient.
Building pacemaker units began taking more of my time than my
job would allow, so I quit my job to work full time on the pacemaker
in 1960. I had $2,000 in cash and enough to feed my family for 2 years.
I took the $2,000 and went up into my wood-heated barn workshop.
In 2 years I had made 50 pacemakers, 40 of which went into animals
and 10 into patients.
The 10 patients had their pacemakers implanted by Dr. Chardack
and his associates. Most of the patients were older people in their
sixties, seventies, and eighties, typical of the usual heart-block patient.
However, two of the patients were children and one was a young man
with a wife and two children. The young man, I remember, had worked
in a local rubber factory until he collapsed on the job one day. Soon
thereafter, he had another severe attack in which his mother-in-law
applied resuscitation and brought him back. Before implantation of
the pacemaker, the young man's prognosis was grim. After recovery,
he retrained as a hairdresser, worked full time, and joined a bowling
team. This man was still alive and well in late 1987. Another patient I
remember well, also in complete heart block with Stokes-Adams
syndrome, was a woman in her sixties. She was our seventh patient.
A few years ago, when our local engineering society named me
"Engineer of the Year," she came to my award dinner. The news
media called her the "Pacemaker Queen." She died not too long ago,
in her eighties, after having been paced for over 20 years.
In early 1961, Jim Anderson and Palmer Hermundslie of the Med-
tronic Company, which manufactured external, hand-held pacemakers,
hew into Buffalo from Minneapolis. At a luncheon table in the Airways
Hotel at the Buffalo airport, we worked out a license agreement for
the implantable cardiac pacemaker. The next day we had it notarized
at a local bank. This agreement was the beginning of the Medtronic
Chardack-Greatbatch Implantable Cardiac Pacemaker, which domi-
nated the field for the next decade.
The license agreement was a very tight one. I assumed design control
for all Medtronic implantable pacemakers. I signed every drawing,
every change, and had to approve every procurement source. The
device had to be called a "Chardack-Greatbatch Implantable Cardiac
Pacemaker" in all company brochures, advertising, and communica-
tions, both within the company and without. The quality control
program reported directly to me for 10 years. I sat on the board of
directors and had a major (and noisy) input to all company affairs,
OCR for page 28
28
MEDICAL DEVICE INNOVATION ED HEALTH CAM
pushing pacemakers and dropping unprofitable product lines like
cardiac monitors and defibrillatory. Within 2 years Medtronic had
become number one in pacemakers. Today, over two decades later,
Medtronic is still number one, and has a sales volume of nearly $300
million a year.
Dr. Chardack was just as active as I, but in an unofficial, behind-
the-scenes way. His papers, his case reports, his spring-coil electrodes,
and his personal recommendations really "sold" the Medtronic device
to the profession. Dr. Chardack's professional stature and reputation
in the field were unparalleled. He was Medtronic's most effective and
most credible "salesman" in those critical early days.
We soon found that the highest grade military components were not
good enough for the "zero defect" requirements of pacemakers. The
warm, moist environment of the human body proved to be a far more
hostile environment than outer space or the bottom of the sea. We
had predicted a 5-year pacemaker in our first 1959 paper, but even by
1970 we were getting only 2 years.
The miniature DOT-1 transformers that we initially used were wound
with exceptionally fine wire and proved troublesome. We continued
to experience failures until we finally went to a transformerless design.
The Medtronic 5862 (my last design for Medtronic) used a three-
transistor, transformerless, complementary multivibrator circuit (after
Roger Russell's patent) which could not "hang up." With diode-
isolated, dual-battery packs and voltage-doubler output, it was probably
the most reliable of the mercury-powered pacemakers of the 1960s.
Early transistors were inconsistent. We identified several failure
modes due to contamination and leaky seals. We adopted the policy
of segregating the transistors into beta (current gain) classes and then
heat-soaking them for 500 hours at 125°C; they were transferred to
dry ice five times during this period. Any transistor that developed
leakage or drifted more than one beta class was discarded. This was
followed by a shock test. We lost about 15 percent of the GE 2N335
transistors in this program, but never lost one subsequently in a
pacemaker. (The Minuteman space program later adopted much the
same approach for high-reliability missile components after we pub-
lished our procedures.)
In 1964 Barough Berkovits (also a member of our chapter of the
Professional Group in Medical Electronics when the American Optical
Company Medical Electronics Division was in Buffalo) published a
series of papers on a new pacemaker concept in which the pacemaker
"listened" to the heart and worked only when the heart did not. A
"demand pacemaker" seemed like quite a good idea, and we began
working on an implantable version. My laboratory notebook says that
OCR for page 29
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
~9
we completed our first successful prototype on January 10, 1965. This
design went on to become the Medtronic model 5841, which was the
first implantable, inhibited-demand pacemaker to become commercially
available.
We gradually improved pacemaker reliability to the point that battery
quality became the limiting factor. It was increasingly apparent that
we would never achieve our objective of a "lifetime pacemaker" with
the zinc-mercury battery. I terminated my license with Medtronic
under friendly circumstances and established my own battery manu-
facturing company, Wilson Greatbatch Ltd. Battery manufacturing,
by the way, was another field about which I knew nothing.
By 1972, after looking into several types of batteries, we had settled
on a battery with a lithium anode, an iodine cathode, and a solid-state,
self-healing, crystalline electrolyte invented originally by Catalyst
Research Corporation in Baltimore. The development of the lithium
battery eventually removed the battery as the limiting factor in
pacemaker longevity. Today, nearly every pacemaker uses a lithium
battery of some sort, and nearly every surgical intervention for a
pacemaker problem is electrode-related rather than battery-related.
Wheelchairs for the Third World
RALF HOTCHKISS
For the past 20 years I have been involved in wheelchair design and
innovation. I became a paraplegic in 1966 and began by modifying my
first chair. I now work full time on wheelchair design. For the past 12
years, I have been involved in making stair-climbing wheelchairs,
stand/squat models, and high-speed sports chairs. My current focus is
the design of lightweight folding wheelchairs for manufacture in
developing countries.
NICARAGUA WHEELCHAIR PROJECT
In 1980 I was contacted by Bruce Curtis, a disabled man involved
with the independent living movement. He had just returned from a
trip to Caribbean and Central American countries, including Nicaragua.
He was most enthusiastic about a group of disabled people he had met
at a rehabilitation center in Managua, many of whom had become
disabled during the revolution of 1979. These disabled Nicaraguans
OCR for page 30
30
MEDICAL DEVICE INNOVATION AND HEALTH CARE:
needed assistance with wheelchair repairs and wanted to learn to drive
automobiles with hand controls. More important, they were very
interested in the concept of independent living, which had given birth
to numerous independent living centers in the United States.
On my first trip to Nicaragua in 1980, I met many disabled people
and began to assess their problems in obtaining and maintaining
affordable wheelchairs that would meet their needs. I found that the
disabled Nicaraguans who had managed to get wheelchairs used two
types of chairs. The vast majority of people had second- or third-hand
hospital-type chairs, which had hard tires and nonremovable armrests
and footrests, and which gave the users little flexibility of use or
mobility. Such wheelchairs had frequent breakdowns and were not
very useful outdoors. The second type of chair was a U.S. prescription
model, which few people had because it was very expensive by
Nicaraguan standards. This type of chair was easier to use but had
many of the same problems as the others. It was heavy, and the seat
widths of the standard imported models tended to be far too wide for
Nicaraguans. Many common replacement parts were impossible to get
because American wheelchairs are not made from generic, inter-
changeable parts.
During my 1980 trip, I also worked with disabled people from the
United States to provide information to disabled Nicaraguans about
independent living. This visit set into motion the formation of an
independent living center organized and run by disabled Nicaraguans
from the rehabilitation center. The Nicaraguan government gave the
group a house in Managua to use as an office. One of the group's top
priorities was to set up a wheelchair repair shop and to obtain new
wheelchairs that Nicaraguans could afford. The group also began to
plan for the eventual economic self-sufficiency of the independent
living center.
After returning to the United States, I submitted a proposal to a
Washington, D.C.-based group, Appropriate Technology International,
which would allow me to provide technical assistance to the Managua
independent living center for the establishment of a wheelchair repair
and manufacturing shop. This proposal was funded for 1 year. During
that year, I developed a prototype of a Third World-appropriate
wheelchair at my shop in Oakland, California, and made eight trips to
Nicaragua to help the independent living center organize its shop,
purchase its tools and equipment, develop wheelchair repair and
modification techniques, and begin making wheelchairs. Under a
second contract with Appropriate Technology International, we com-
pleted the Nicaragua project and began to spread the wheelchair design
OCR for page 31
INVENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
31
and its technology to disabled people and their organizations in the
Caribbean and Central and South America.
EVOLUTION OF THE DESIGN
The first prototype design for a Third World-appropriate wheelchair
was based on features that wheelchair riders in the Western world
often have learned to specify as modifications to the standard light-
weight folding wheelchair to enable it to be used over rough terrain.
When wheelchairs are used to climb curbs or follow rocky trails, for
example, they bend and break if they are not properly reinforced.
When they are propelled over rough ground, they lose traction and
become impossible to push if they do not have pneumatic tires.
Moreover, if they are any wider than necessary, they will not fit
through many doorways; if they are too heavy, they will be hard to
push and lift; if they do not fold, they will not fit in the aisle of a bus.
With rare exceptions, full-time users needing a single vehicle for
both indoor and outdoor use have found nothing better than four-
wheeled, rear-drive wheelchairs with the following features:
· Width: 24 inches maximum for a 16-inch or greater seat width.
· Length: 42 inches.
· Weight: 45 pounds for a fully equipped chair with armrest/fenders,
brakes, footrests, handrims. Lightweight aluminum folding chairs,
weighing as little as 30 pounds fully equipped, are now available at
high cost.
· Traction and Maneuverability: A skilled rider of a four-wheeled,
rear-drive chair can easily shift all of his or her weight to the drive
wheels, giving full traction over rough terrain. When combined with
pneumatic tires and a flexible frame, the four-wheeled, rear-drive chair
gives excellent propellability and better stability than a three-wheeled
chair of comparable width.
· Ease of Assistance: The rear-wheel drive chair can be tipped back
on the rear wheels by an assistant and pushed or pulled over curbs
and rough terrain.
· Folds: To a width of 12 inches or less. Easy disassembly of the
chair by the rider has also been demanded by some users.
· Accessibility: The chair must not interfere with pulling close to a
worktable or, for users who cannot stand, making lateral transfers into
and out of the chair.
· Durability: The chair must stand up to the shock of ramming
curbs and chuckholes and withstand rough treatment in all types of
OCR for page 32
32
MEDICAL DEVICE INNOVATION AND HEALTH CARE
transit. It must not be prone to breakdowns, which can strand the
rider far from service facilities, and must perform with a minimum of
routine maintenance. Commercial chairs vary widely in this regard.
These criteria—important for active wheelchair riders in the Western
world—are particularly important for riders in Third World countries
where doors are narrower, turning spaces are smaller, roads are
rougher, curbs and steps are higher and less uniform, assistance in
getting over obstacles is needed more often, wheelchairs must be lifted
more often, and access to repairs is far more restricted.
Thus, my goal has been to design a wheelchair for manufacture and
use in developing countries. It was to be at least as good as the best
Western model but less expensive, made out of locally available
materials, and built in workshops set up with a minimum of capital.
During the first year, I did most of the work on designing and
revising prototypes for a Third World-appropriate wheelchair. After
that, one of the disabled Nicaraguans, Omar Talavera, made significant
contributions to the design. A visit in 1981 to Tahanan Walang
Hagdanan (house with no stairs) in the Philippines, where 20 wheelchair
riders had built more than 1,000 low-cost chairs, led to more significant
changes in our design.
The major problems in developing a workable prototype stemmed
from lack of materials and poor understanding of wheelchair use in
Nicaragua. The economic situation in Nicaragua made it difficult, and
sometimes impossible, for the wheelchair shop to purchase custom-
made wheelchair parts from outside the country. We were forced to
find ways to make wheelchair components out of standard Nicaraguan
hardware, and the unavailability of materials in Nicaragua quickly
began to dictate the design of our wheelchair. I had already decided
to use zinc-plated electrical conduit instead of inch-sized seamed metal
tubing, because the standard sizes of electrical conduit were more
available in Nicaragua. The prototype design changed as I discovered
what else was not available: hardened bolts, concentric tubing sizes,
suitable ready-made hubs, and more. We are still trying to figure out
how to make a high-resiliency, low-cost front wheel, but everything
else is now made out of locally available materials.
My naivete about the life-style of disabled Nicaraguans caused one
major change in the prototype. My original design called for a wooden
folding seat, which allowed me to use a simpler and stronger folding
mechanism than that in the average U.S. chair. That design had to be
scrapped, however, because I had not taken into consideration the
fact that, unlike wheelchair riders in the United States, most Nicaraguan
OCR for page 33
I^ENTING MEDICAL DEVICES: FIVE INVENTORS' STORIES
33
wheelchair riders do not sit on cushions. A wooden seat would cause
decubitus ulcers for people with spinal cord injuries. During the first
year, I bought some cushions and tried to convince the group to use
them. As the cushions wore out and needed replacement, I finally
realized why most Nicaraguans would never use cushions—they cannot
afford new ones.
I had also overlooked the need in Nicaragua for a folding wheelchair
that allows the rider to fold the chair partially without getting out of
it. The Nicaraguans partially fold their chairs to squeeze through the
narrow doorways that are common in that country. We now have
enough barrier-free buildings in the United States that this is not
considered an essential feature.
As a result of these economic and practical problems, the current
wheelchair design is almost completely original and is closely attuned
to the needs of disabled people who live in rural areas and cannot
afford anything but the cheapest wheelchairs.
THE FUTURE
The ability of the independent living center in Managua to proceed
beyond prototype development into marketing of wheelchairs has been
hampered by the problems the country has had in maintaining a general
inventory of basic materials. Another problem is that the disabled
people who run the independent living center and who grew up in
poverty are not used to the concept of purchasing in bulk. Instead,
they are used to buying today what they need today as a result, they
sometimes lose opportunities to buy needed materials when they are
available.
The potential market for wheelchairs in Managua is great if measured
by need. However, not many disabled Nicaraguans can afford to buy
their own wheelchairs, even though the Managua-made wheelchair is
much less costly than imported chairs. At present, materials for one
wheelchair cost about U.S.$80, and =5 person-days are needed to
complete each chair. The sales price is about U.S.$170. So far, 50
wheelchairs have been sold to private individuals in Nicaragua.
Durability and ruggedness have been major characteristics built into
our wheelchair's design, and it is hoped that the wheelchairs can be
maintained indefinitely.
We have begun to spread what we have learned. Under the spon-
sorship of Appropriate Technology International, we held workshops
in Jamaica, Peru, Costa Rica, Honduras, and California. Each mechanic
OCR for page 34
34
MEDICAL DEVICE INNOVATION AND HEALTH CARE
completed a wheelchair and took it home to use as a model for
production. A 150-page production manual, Independence Through
Mobility, is now available from Appropriate Technology International.
A new project, Appropriate Technology for Independent Living, has
begun in California to carry on the development and dissemination of
our wheelchair design worldwide.
Representative terms from entire chapter:
medical device
