The International Journal of Artificial Organs / Vol. 32 / no. 4, 2009 / pp. 191-196
Obituary
“Inventions can’t wait”: A tribute to Willem Johan Kolff
JÖrg VIENKEN1, HOrST KLINKMANN2, gErHArD rAKHOrST3
BioSciences, Fresenius Medical Care, Bad Homburg - Germany
Biocon Valley GmbH, Rostock - Germany
3
Department of Biomedical Engineering, University of Groningen, Groningen - the Netherlands
1
2
Prof. Dr. Willem (Pim) Johan Kolff, the Nestor of artificial organ technology passed away in his home in Newtown Square, Pennsylvania, USA on February 11, 2009 at
age 97. His friends, pupils and colleagues say farewell to
a true medical revolutionary with wholehearted admiration and gratitude. The medical device industry owes him
respect for his achievements which initiated a successful
worldwide business while keeping millions of sick patients
alive.
For decades medical engineers had been intrigued by
the possibilities of using spare parts for failing organs. The
first routinely applied device to save the lives of patients
was the artificial kidney. It was the logical forerunner of the
many artificial organs which were later realized or promoted
by the brilliant and creative Pim Kolff (Fig. 1). Creativity derives from an inner drive accompanied by genuine intuition
and is not always necessarily based on knowledge. In fact,
sometimes knowledge of accepted rules puts the brakes
on creative ideas because we know “that’s impossible!”
Fig. 1 - Dr. Willem Johan (Pim) Kolff (19112009).
During his entire life, Pim Kolff challenged such scholastic
assumptions by repeatedly turning the impossible into reality. His credo, as described by Paul Teschan in 1998, was
always “New ways of thinking!” (1). The father of artificial
organs used his ingenuity for artificial spare parts to make
that an actuality.
To summarize his lifetime achievements, Dr. Kolff received
13 honorary doctoral degrees as well as numerous prizes
and decorations, including the Japan Award in 1986, the
highly prestigious Albert Lasker Award for Clinical Medical
Research in 2002, and the National Award of Engineering
(NAE) in the United States in 2003. In 1990, Life magazine
listed him among the 100 most important Americans of
the 20th century. In his home country, the Netherlands, he
ranked 47 in the “List of the Greatest Dutchmen” published
in 2004. Since 1984, he has been represented in the “The
National Inventors Hall of Fame™” for his invention of the
“Soft Shell Mushroom Shaped Heart” (US Patent Number
3,641,591). The Hall of Fame honors the women and men
responsible for the great technological advances that make
human, social and economic progress possible.
An announcement for the NAE award published in March
2003 in Science magazine explained the advances that Dr.
Kolff stood for: “Today, thanks to Dr. Willem Kolff and his
artificial organs, more than a million patients around the
world go on living longer, fuller lives. Dr. Willem Kolff will
save 1.2 million lives before bedtime.”
Two books devoted to Dr. Kolff perfectly describe what
he was and what he did by using the term “life”: the first
book, entitled Inventor for life. The story of W.J. Kolff, father
of Artificial Organs is the only biography currently available on Dr. Kolff, written by Herman Broers (2); the second
was dedicated to him by his former co-worker Jacob van
Noordwijk (3) and is entitled Dialysing for Life, the Development of the Artificial Kidney.
© Wichtig Editore, 2009
0391-3988/191-06$25.00/0
A tribute to Willem Johan Kolff
Fig. 2 - Scheme of the rotating drum, as it was used in the first series
of dialyses. A cellophane tube is wound spirally around a large horizontal cylinder. The blood in the tube sinks to the lowest point. When
the tube rotates in the direction of the arrow, the blood will move
from left to right (from (6)).
Willem Johan Kolff was born on February 14, 1911 in Leiden, the Netherlands. When Pim Kolff reflected about his
youth, he stated: “I didn’t want to be a doctor when I was a
boy, because I didn’t think that I could bear to watch people
die, and I’m not so sure that I’m resigned to it yet. My father
was director of the Tuberculosis-Sanatorium at Beekbergen,
where I spent a good deal of my childhood, and I remember
very well how we would go back to the sanatorium in the
evening to check on a patient or chest film. We would walk
for hours in the pinewoods on the grounds unraveling some
particularly difficult problems. His example finally swayed
me from my original conviction that I was cut out to be a zoo
keeper!” (4). Fortunately for the sake of many patients and
their lives, Dr. Kolff did not follow his original dreams.
In the following, we would like to provide a brief summary of his achievements in the field of artificial organs. It
might explain to the interested reader why we call Dr. Kolff
the father of artificial organs today.
Artificial kidney
In October 1938, a patient named Jan Bruning died from
end-stage renal failure at the hospital in Groningen. Willem
Kolff saw him dying and started to search the literature for
methods to remove urea and other uremic toxins (5). He
went back over the first attempts to create an artificial kidney, published by Abel and colleagues in the USA, Georg
Haas in Germany and Heinrich Necheles in China. Kolff
then started his first experiments on blood washing with
cellophane tubes and heparin as an anticoagulant. Without
performing any prior animal trials, he applied his rotating
drum device for the first experimental hemodialysis on a
young uremic patient named Gustav Boele in winter 19421943, whereas the first “official” hemodialysis with this revolving drum was performed on a young woman on March
17, 1943 (3).
192
Kolff profited at that time from the support and cooperation of Robert Brinkman, a professor of Medical Biochemistry at the University of Groningen. Brinkman and Kolff
took a cellophane tube of about 45 cm, closed one end
with a knot and filled it partially with only 25 mL of an aqueous solution of urea, expelled the air from the remainder of
the tube and closed that end as well with a knot. They then
placed the flat sack on a board in a tank of water. An electric motor slowly moved the board up and down so that
the water in the tank was in constant motion. The urea in
the sack originally had a concentration of 4 g/L. After half
an hour of dialysis, they were unable to recover any urea
from the cellophane sack. Dr. Kolff attributed this success
to the favorable ratio between the surface, the volume of
the cellophane sack, as well as to the agitation of the sack
(6). Consequently, the hollow drum of his first artificial kidney had a fin inside to keep the water in constant motion
(3). Anticipating the need for safety conditions, Kolff put
specific emphasis on removing all traces of pyrogenic remnants of bacteria from rubber tubes and glassware.
Following the Nazi occupation of the Netherlands and
the appointment of a national socialist as a new head of
the Groningen clinic, Dr. Kolff left Groningen for the city of
Kampen in 1940. Here, he pursued his experiments on the
artificial kidney. Fortunately, he got in contact with Hendrik
Berk, the director of the local enamel factory, who advised
him to replace the formerly used vertical cylinder and wind
the cellophane tube around a horizontally arranged drum.
This meant that the blood would have to flow from a stationary tube into the rotating cellophane tube (Fig. 2, from
(6)). Dr. Kolff received his first rotating drum for clinical use
from Berk towards the end of 1942 (3) and performed a
hemodialysis treatment lasting 20 minutes. For the subsequent 15 patients, however, dialysis therapy lasted at least
six hours. Dr. Kolff was aware of osmotic forces to remove
water. Thus, he raised the glucose concentration in his
bath to diminish the patient’s edema (3).
It also became soon apparent that there had been insufficient control of sodium and potassium ion concentration.
The determination of these ions was time consuming and
not precise enough, that is, the presence of heparin often
interfered with the determination of potassium. However,
the experience gained in this way contributed markedly
to the successful treatment on September 11, 1945 of a
woman suffering from both cholecystitis and nephritis.
Dr. Kolff reported on this case in many interviews and
presented the clinical chemical behavior of this patient in
his doctoral thesis submitted to the University of Groningen on January 16, 1946 (Fig. 3): “Sophia Schafstadt was
the first patient where you can honestly say she would
Vienken et al
Fig. 3 - The first clinical picture of patient 17 (Sophia Schafstadt),
who owed her life to the artificial kidney. graph on top represents
the urea content of her blood before and after dialysis. The vertical
arrows indicate both the 80 liters of blood that flowed through the
artificial kidney, and the 60 g of urea removed. Open rectangles at
the bottom indicate the volume of urine passed by the patient, the
shaded ones the grams of urea the patient has excreted (from (6)).
Fig. 4 - Dr. Kolff explains a model of the rotating drum to two generations of pupils, Jörg Vienken (left) and Horst Klinkmann (middle)
in 1999.
have died had she not been treated with dialysis. And she
was in a prison right after the war, for collaborating with the
Germans and many of my fellow countrymen would have
liked to wring her neck. She was brought to us in renal
failure. My duty is not to wring her neck, but to treat her.
And, we treated her. She was comatose when she came
in. And after so many hours of treatment, I bent over her
and said, “Mrs. Schafstadt, can you hear me?” And she
slowly opened her eyes and said, I am going to divorce
my husband, and she did.” Following this successful treatment, Dr. Kolff aimed to make this therapy elsewhere available. The rotating drum was successfully used outside
the Netherlands, in the United Kingdom and in the United
States. Today, models of his rotating drum are on exhibit in
Kampen and in Germany (Fig. 4).
Another breakthrough in the development of the artificial kidney was the construction of the first disposable coil
dialyzer in cooperation with Dr. Bruno Watschinger from
Vienna, Austria. In the early days of dialysis, the Travenol company marketed what was later to become one of
the most commercially successful artificial kidneys at the
onset of dialysis therapy.
When he submitted his doctoral thesis to the University
of Groningen in 1946 (6), Dr. Kolff quite rightly thanked his
nurses in his introductory presentation and repeated this
sentiment many times during his lifetime. As an example,
in 2005 he proposed a festival to honor dialysis nurses and
proposed to organize such a meeting regularly in Kampen.
He wrote in a letter to Jörg Vienken: “Sister M. ter Welle
was my first head nurse when I came to Kampen. Nobody
taught me more than sister ter Welle. She had been assisting the surgeon and could instruct me in some surgery. I
came fresh from the University. Sister ter Welle had enormous experience. She had marvelous understanding of
the patients. She helped me to see what was wrong. She
advised, she supported, she consoled. Recognition of the
importance of the dialysis nurses is long overdue!”
Artificial lung
During his first experiments with the artificial kidney, Dr.
Kolff observed that there was blood which turned dark
red to light red after passing through his dialysis machine.
He believed that such a device could be the basis for a
heart-lung machine and worked on it. He performed animal experiments on a pump-oxygenator at the hospital in
Kampen supported by the PhD student Cornelius Dubbelman (7), who published his results and experiences in his
thesis in 1953.
After moving to the United States in 1950, Kolff became
a US citizen in 1956. He continued his work on a heart lung
apparatus as a member of the research staff of the Cleveland Clinic Foundation. Later in 1957, this device became
the first clinically-applied membrane oxygenator.
Dr. Kolff reported later. “I began to make blood oxygenators to be used in heart-lung machines, but the hospital in
Kampen was too small for open heart surgery. One of the
reasons I left for the United States was that I had to be in
a hospital large enough to have a cardiac surgical department. When I came to Cleveland I brought three excellent
193
A tribute to Willem Johan Kolff
Fig. 5 - Dr. Kolff wearing an artificial kidney for holiday dialysis.
Fig. 6 - Outline for the testing of an artificial lung provided on June
17, 2002.
heart-lung machines, but nobody in the United States was
interested. I had to wait five years before the heart surgeon began to realize that he could not do all the surgery
blindly.”
William Dobelle (1941-2004) fitted a Brooklyn man with the
world’s first artificial eye.
Wearable devices
In 1967, Dr. Kolff moved to the University of Utah and
served as Professor of Surgery in the School of Medicine,
later as Director of the local Institute for Biomedical Engineering. Here, he created the largest medical engineering
program for artificial organs at that time worldwide.
For the first time, he introduced a wearable artificial kidney for his home dialysis patients (Fig. 5). Horst Klinkmann,
at that time head of the hemodialysis program in Salt Lake
City, successfully performed a series of holiday dialyses
in the Utah desert on patients with this wearable device.
Similar to the wearable device in use today, Kolff´s wearable dialysis system applied a combination of adsorbers
and filters.
Wearable oxygenators were of paramount interest for Dr.
Kolff in his later years. He proposed a wearable artificial
lung together with Dr. Sony Jacob in 2002 and provided an
outline to test such a device (Fig. 6).
Kolff also carried out research which showed that the
electrical stimulation of certain parts of the brains of blind
people could produce the sensation of seeing points of
light. His research bore fruit when in 1999 his collaborator
194
Artificial heart
The artificial heart was another focus of Kolff´s clinical
and engineering interests. It became his focus in the second half of his scientific life (Fig. 7). Dr. Robert Jarvik and
Dr. Don Olson, who joined him for his Artificial Heart program in Utah, became his main co-workers in this project.
In 1981, a calf survived for more than 260 days, and subsequently, Kolff submitted a proposal to the FDA for clinical application. On December 2, 1982, Dr. Kolff’s 35 years
of dedication culminated in the first implant of his artificial
heart into dentist Barney Clark by the surgeon Dr. William
De Vries. Clark, who was hours from death prior to the surgery, lived for 112 days.
Today, there have been more than 780 implants, accounting for more than 150 patient years of life on the
artificial heart. Originally designed as a permanent replacement heart, the CardioWest artificial heart is currently approved as a bridge to human heart transplant for
patients dying from end- stage biventricular failure. Kolff
enlisted 247 co-workers who helped him to develop the
permanent artificial heart (8), many of them coming from
abroad. He gave them the opportunity to participate in all
kinds of artificial organ research and work on new ideas.
They all became part of a worldwide network of enthusi-
Vienken et al
Fig. 7 - 1967: Dr Kolff checks his first total artificial heart together
with his coworker Clifford Kwan-gett (Picture by courtesy of the J.
Willard Marriot Library, Salt Lake City, USA).
astic students and well-established researchers, a web
that Kolff established and which influenced many of their
careers in their later life.
Pim Kolff and the public
Kolff received a lot of publicity for his achievement and
added his own fuel to the fire (2). In an interview published
by the monthly journal Equinox in 1982, he stated: “Eventually artificial organs may be more powerful than human
organs. By 1998, a man might win the marathon because
he has an artificial heart. Of course, he may be disqualified
because of it!”
In order to characterize Pim Kolff´s life philosophy in
more detail, we should not forget one of his main social
attitudes. He was convinced that all patients around the
world should have access to artificial organs regardless
of their religious, political or socio-economic background.
Furthermore, he never accepted the politically based division of the world. As a personal milestone, he accepted to
simultaneously work as a fellow of the Humboldt Foundation in Munich and as a Professor at the University of Rostock. It is noteworthy that Munich and Rostock were located in the two different parts of Germany divided by the
Iron Curtain. In Rostock, he cofounded the Department for
Artificial Organs, which was most renowned in both East
and West Germany at that time.
In order to combine all international efforts in the field of
Artificial Organs and bring together engineering and medical sciences into one professional organization, he was
instrumental in founding the two most prestigious societies for artificial organs, the American Society for Internal
Artificial Organs (ASAIO) and the International Society for
Artificial Organs (ISAO). In cooperation with the European
Society for Artificial Organs (ESAO), he served until his
death as an Honorary Editor of The International Journal of
Artificial Organs.
Dr. Kolff also used his publicity to make statements in the
political arena. His oral presentations always ended with
two comments on a serious note. He opted against nuclear
wars, promoted the liberalization of drugs while promoting
a better control of drug abuse in order to avoid the early
criminalization of youngsters.
Without any question, Dr. Willem Kolff was the father of
Artificial Organ research and application in the 20th century. It was his vision that only an intense interdisciplinary
cooperation between engineers, physicians and natural
scientists can achieve the best results for the wellbeing of
patients.
His precise medical understanding of physiological and
clinical mechanisms, his engineering skills combined with
his unconventional thinking, made him one of the century’s
heroes of innovation in medical device technology. In the
future, the international scientific community, and we as
his pupils, will miss his unlimited vision, his scientific guidance, and his deep personal humanity.
Jörg Vienken
Horst Klinkmann
Gerhard Rakhorst
for the ESAO Board of Trustees and the Society
Address for correspondence:
Prof. Dr. Jörg Vienken
BioSciences, Fresenius Medical Care
Else Kroener Strasse 1
D-61342 Bad Homburg, Germany
e-mail: [email protected]
Prof. Dr. Horst Klinkmann
Schliemannstrasse 7
D-18059 Rostock, Germany
e-mail: [email protected]
Prof. Dr. Gerhard Rakhorst
Department of Biomedical Engineering
University of Groningen
Antonius Deusinglaan 1, P.O. Box 196
NL-9700 AD Groningen, the Netherlands
e-mail: [email protected]
195
A tribute to Willem Johan Kolff
REFERENCES
1.
2.
3.
4.
196
Teschan P. Kolff´s credo: new ways of thinking. Artif Organs
1998; 22: 934-7.
Broers H. Inventor for life, the story of W. J. Kolff, father of
Artificial Organs. Kampen, Netherlands: B&Vmedia Publishers; 2006.
Van Noordwijk J. Dialysing for Life: the development of the
Artificial Kidney. Dordrecht, Boston, London: Kluwer Academic Publishers; 2001.
Zenker W. Die Entwicklungsgeschichte der extrakorporalen
Hämodialyse von den Anfängen bis zur Routinetherapie
5.
6.
7.
8.
der Inneren Medizin. Munich: Verlag Volker Keller; 1994.
Thorwald J. Die Nierenleute. In: Die Patienten. Zürich: Droemer Knaur, Verlag Scholler; 1971. p 113-38.
Kolff W. De kunstmatige nier [The Artificial Kidney]. Dissertation. Kampen, Netherlands: J. H. Kok; 1946.
Dubbelman CP. Attemps to design an artificial lung apparatus for human adult. Amsterdam: Noord-Hollandsche Uitg
Maatschappij; 1953.
Kolff WJ. Artificial Organs – Forty years and beyond. Trans
Am Soc Artif Intern Organs 1983; 29: 6-24.