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Keywords:

  • General hematology;
  • laboratory practice;
  • laboratory automation;
  • biography;
  • cellular analysis;
  • flow cytometry

Summary

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

2013 is the centenary of Wallace Coulter's birth. He was an engineer, inventor, entrepreneur and visionary. He transformed the practice of laboratory hematology with his invention of the Coulter Principle and its application to blood cell analysis, together with the company he founded to bring it and his subsequent inventions and innovations to the world. He was born in modest circumstances and he remained modest in his outlook on life, despite his magnificent achievements, his successes, his numerous prestigious awards and his wealth later in life. This article traces his early life, his career, his achievements and the immense benefits he brought to the people of this planet.


Early Life

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

Wallace Henry Coulter was born on February 17, 1913, in Little Rock, Arkansas, to Joseph R. Coulter and Minnie May Johnson Coulter. His father was a train dispatcher, and his mother was an elementary school teacher. He had one brother, named Joseph. At age three, he was already fascinated with numbers and gadgets. When Wallace was offered a bicycle for his eleventh birthday, he asked instead for his first radio kit. In 1924 and for many years thereafter that would have been a crystal radio kit. It would have consisted of a piece of galena crystal, a thin wire with a sharp end (a ‘cats-whisker’), a tuning coil, and electromagnetic headphones. To use it, one would try with the ‘cats-whisker’ to find a spot on the crystal that would pick up a radio station broadcasting at a particular frequency and then try to ‘fine-tune’ the station with the tuning coil. The user had to be very patient and persistent. These characteristics and his overall passion for science and technology pervaded his entire life.

Wallace Coulter spent his youth in McGehee, Arkansas, a small town near Little Rock, graduating from McGehee High School. He attended his first year of college at Westminster College in Fulton, Missouri; however, his interest in electronics led him to transfer to the Georgia Institute of Technology for his second and third years of study.

This was the early 1930s, and due to the Great Depression, he was unable to complete his education. Wallace's interest in electronics manifested itself in a variety of unconventional jobs. For example, he worked for the radio station WNDR in Memphis, Tennessee filling in as a radio announcer, maintaining the equipment, and conducting some of the earliest experiments on mobile communications.

In 1935, Wallace joined General Electric X-Ray as a sales and service engineer in the Chicago area servicing medical equipment. When an opportunity to cover the Far East became available, he seized the chance to live and work there, where he stayed for 24 months.

Wallace first went to the Philippines, where the local GE Office was manned by technicians from many countries. He admired the lush landscape and varied tropical fruits. In his free time, he visited the open air markets. This experience fostered his love of tropical fruits. Later in life, he maintained a tropical fruit farm with lychee, longan, carambola, and more than 20 varieties of mangoes.

After 6 months in Manila, Wallace was asked to make sales and service calls in the more remote regions of the GE territory. He traveled to Hong Kong, Macao, and Canton, finally settling in Shanghai for 6 months. He became fascinated with Chinese history, art, and culture. He admired jade carvings of all colors, shapes, and sizes, but mostly loved figurines of people and animals. He maintained this interest in Chinese art throughout his life. His jade collection filled his office in later years and he delighted in showing and describing it to every visitor who expressed interest.

Wallace transferred to Singapore where he remained until the Japanese threatened the city in late 1941. He tried to leave on one of the passenger ships leaving the country, but failed to obtain a ticket. As the Japanese began bombing the city, he found a small cargo boat bound for India and left under cover of darkness in December. After a few weeks in India, Wallace realized that returning to the United States through Europe was impossible. He made his way through Africa and South America taking nearly 12 months to eventually return to the United States at Christmas, 1942. Wallace's sojourn in the Far East and his long journey home traversing four continents were a transformational experience for a young man from small-town America. It forever influenced his values, both professionally and personally.

The Coulter Principle

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

After the War, Wallace worked for several electronics companies, including Raytheon and Mittleman Electronics in Chicago. He set up a laboratory in his garage at home to experiment in his spare time with different applications of optics and electronics on promising ideas and projects. His brother Joseph often worked together with him. One project was for the Department of Naval Research, where Wallace was trying to standardize the size of solid particles in the paint used on US battleships to improve its adherence to the hull. As part of his study of the paint's properties, he planned to run the paint through an aperture and count the particles using an electric current. Wallace said: ‘When we started we didn't have much money, so we made an aperture by making a small hole with a hot needle in a piece of cellophane from a cigarette package. It didn't hold up long, but we were able to count some particles’. Held onto the end of a glass tube by a rubber band, the punctured cellophane separated two electrodes connected to a source of electric current while particles suspended in ionic medium were passed through the aperture while the current was flowing.

Upon returning to the garage one cold, blustery evening in 1947, Wallace realized that he had forgotten to replace the lid on his paint sample. The liquid had become solid and therefore would not flow through the aperture. Not wanting to go back out in the cold to obtain another sample of paint, he asked himself, ‘What substance has a viscosity similar to paint and is readily available?’ Using his own blood, a needle and some cellophane, he discovered that cells passing through an aperture interrupted an electrical connection and emitted electrical pulses that could be measured. Thus, the principle of using electronic impedance to count and size microscopic particles including human blood cells suspended in a fluid was invented – the Coulter® principle.

Wallace's first attempts to patent his invention were turned away by more than one attorney who believed ‘you cannot patent a hole’. Persistent as always, he undertook a prolonged search for an attorney willing to prepare a patent application. Finally, in 1948, a patent attorney named Irving Silverman recognized the new method's significant potential, and in August 1949, a patent application was filed [1]. But the patent examiner also doubted that a hole could be patented. Fortunately, the patent examiner, whose name is not recorded on the patent, also surmised that if an application were to include more examples of how the Coulter principle would be applied, a patent might be obtained on the principle of sensing particles in a constricted current path. The seminal patent for the more broadly defined new Coulter principle was issued on October 20, 1953, with the preferred embodiment being a pinpoint aperture formed in the lower wall of a test tube. Diagrams for the patent are shown in Figures 1 and 2.

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Figure 1. Page 1 of diagrams for Coulter Principle Patent.

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Figure 2. Page 2 of diagrams for Coulter Principle Patent.

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Remembering his visits to hospitals while working for GE X-Ray, where he had observed laboratory workers hunched over microscopes manually and laboriously counting blood cells from diluted blood samples in hemocytometer counting chambers, Wallace focused the first application of his invention on counting red blood cells. He developed an analytical instrument that could be used to apply his principle to practical problems. This instrument became known as the Coulter® Counter™ (Beckman Coulter Inc., Miami, FL, USA). This device increased the number of cells counted per sample approximately 100 times greater than the usual microscope count by counting in excess of 6000 cells per second and reduced the statistical counting error by a factor of approximately 10 times. Additionally, it decreased the time it took to count the cells from 30 min to fifteen seconds.

This major improvement in counting accuracy required that the volume of cell suspension flowing through the aperture be accurately measured. Together, Wallace and his brother Joe invented an elegant solution that provided very accurate volumes based on a mercury manometer. Combined with a microscope focused on the aperture, this metering system formed the basis of a sample stand that would remain essentially unchanged for over 30 years. In 1952, the first two integrated instruments were built. They consisted of a single compact console incorporating the new sample stand, interface electronics, oscilloscope, and electric decade counters to count the voltage pulses as cells passed through the aperture. In 1953, these prototypes were sent to the National Institutes of Health (NIH) for evaluation. The NIH published its findings in two key papers published in 1956 [2] and 1957 [3], citing the improved accuracy of counting and the convenience of the Coulter method of counting blood cells. In May 1956, a patent application was filed on the manometer metering system [4].

Wallace publicly disclosed his invention on October 3, 1956, at the National Electronics Conference. This led to the publication in 1957 of his one and only technical paper entitled ‘High Speed Automatic Blood Cell Counter and Cell Size Analyzer’ [5]. The paper stated: ‘In the new counter individual cells are caused to move through a small constricted electric current path in the suspending fluid and detection is based upon differences in electrical conductivity between the cell and the suspending fluid. The constricted current path is analogous to a light beam of small dimensions in an optical system. In passing through the small current path in the fluid the individual blood cell changes the electrical resistance in the circuit, and causes a change in the voltage drop appearing across the current path. The electric current path of small dimensions and the flow of cell bearing fluid through the path is provided for with a very simple structure. The boundary of the current path is the bore of a submerged orifice of small dimensions in the wall of an insulated vessel’.

In 1958, Wallace and his brother, Joseph Coulter, Jr., founded Coulter Electronics to manufacture, market, and distribute their Coulter Counters. From the beginning, this was a family company, with Joseph, Sr., serving as secretary–treasurer. The Coulters' father had served as weekend secretary and accountant from the beginning of their venture, but now at age 68, he retired as a railroad telegrapher and began a second career working with his sons, only going into partial retirement in 1971 at the age of 81.

Wallace and Joe, Jr., built the early models, loaded them in their cars and personally sold each unit. In 1959, to protect the patent rights in Europe, subsidiaries in the United Kingdom and France were established. The Coulter brothers relocated their growing company to the Miami area in 1961, where they remained for the rest of their lives, exerting a powerful influence for good on the community around them.

Wallace was determined that his company should supply the customer with everything that was needed to perform the analyses: reagents, quality control materials, analyzer service, customer education, operator training, and full system support by immediate telephone service and on-site customer visits. Competitors would sometimes wistfully and somewhat enviously complain that the Coulter systems would break down just as often as theirs, but that Coulter's service was so good that the analyzer would be in full operation again before the laboratory director even knew that it had broken down!

Wallace continued to focus the resources of his company on advancing cellular analysis. Coulter Corporation was a pioneer in the development of monoclonal antibodies and flow cytometry, not only for analytical purposes, but also for innovative therapeutic uses. The B-1 antibody (anti-CD20) was developed under Wallace's guidance, and successful use for treatment of refractory non-Hodgkin's B-cell lymphoma by radioimmunotherapy was first reported in 1993 [6] and subsequent papers showed its long-term efficacy. Radioimmunotherapy is now regarded as a highly promising revolutionary therapy for many tumors. As a result of this continued expansion into new technologies, together with the growth of its existing business, Coulter Corporation was one of the largest privately owned diagnostic companies in the world by the 1990s. Under Wallace's leadership and drive, the company developed into the industry leader in blood cell analysis equipment, employing almost 6000 people, with over 80 000 instrument installations on six continents. The company developed entire families of instruments, reagents, and controls, not just in hematology, but also in flow cytometry, industrial fine particle counting, and other laboratory diagnostics.

In October 1997, Coulter Corporation was acquired by Beckman Instruments, Inc., and the combined company became Beckman Coulter, Inc., a New York stock exchange–listed global provider of diagnostic systems and consumables.

Wallace Coulter's Personal Characteristics

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

Wallace Coulter was tremendously successful as a businessman; yet, he did not fit the stereotype of a hard-driving Chief Executive Officer (CEO) of a large company. Unusual for a CEO, he spent much time visiting the company's research laboratories and remained very familiar with the details of research in his company. He was unassuming and modest. His trademark attire outside the office was a battered canvas fishing hat and he drove himself to and from his office in a small vehicle, rather than traveling in a large chauffeured limousine.

Wallace remained single his entire life; his company and its employees became his extended family. He was a compassionate man who loaned money to employees who were trying to buy a new home or facing serious family illness, and he did not expect to be repaid. He encouraged his employees in personal conversations to make the best of their own talents. He avoided the spotlight for himself, pointing out that all accomplishments were the result of team efforts. He did not live in luxury and directed the profits of his privately owned company back into development of the company, providing funding in particular for research and development.

Upon the sale of Coulter Corporation to Beckman Instruments Inc., he ensured that his family of employees was ‘taken care of’ by setting aside a total fund of $100 million to be paid to each and every employee around the world based on their years of service.

Impact of the Coulter Principle

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

The Coulter principle is responsible for much of the current practice of hematology laboratory medicine in hematology analyzers and flow cytometers. The complete blood count (CBC) is the most commonly ordered diagnostic test worldwide. More than ninety-five percent of CBCs are performed on instruments using the Coulter principle. In addition, the use of the Coulter principle modernized industry by establishing a method for quality control and standardization for particles in drug manufacture, cosmetics, beer, wine, food processing, rocket fuel, and, yes, paint manufacture. The impact of the Coulter principle on the medical, pharmaceutical, biotechnology, food, beverage, and consumer industries is immeasurable.

Wallace Coulter's Accomplishments and Awards

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

Wallace Coulter was a very private person who sought no public acclaim, yet his accomplishments and awards are numerous. He received 82 patents, many of which were issued to him for discoveries made late in his life. In 1960, he was awarded the highly prestigious John Scott Award for Scientific Achievement. This award, established in 1816 for ‘ingenious men and women’, is given to inventors whose innovations have had a revolutionary effect on mankind. Others who received this award include Thomas Edison, Marie Curie, Jonas Salk, and Guglielmo Marconi (his childhood hero, no doubt). Considering that this award was given to him rather soon after his invention became known and well before the Coulter principle had exerted its major impact on the world, one must admire the foresight of the Award Committee.

Wallace continued to receive many other awards from industry and academia. He received honorary doctorates from Westminster College, Clarkson College, the University of Miami, and Barry University. Although he was not a physician or hematologist, Wallace is the only person to receive the American Society of Hematology Distinguished Service Award for his enormous contributions to the practice of hematology. He was the recipient of the Association of Clinical Scientist's Gold Headed Cane Award and a Fellow of the American Institute of Medical and Biological Engineering (AIMBE). In 1998, he was inducted into the National Academy of Engineering. In 2004, he was posthumously inducted into the National Inventor's Hall of Fame.

Joseph Coulter, Jr., died in 1985. Wallace Coulter passed away on August 7, 1998, at the age of 85, after a long illness. In the last years of his life, he established the Wallace H. Coulter Foundation to improve health care through medical research, engineering, and education. Upon his death, he willed his wealth to the Foundation. In the years since his death, the Wallace Coulter Foundation has provided numerous multimillion dollar grants to Universities to establish and fund Departments of Biomedical Engineering, Research Institutes, and educational scholarships. The Berend Houwen Travel Awards for participation by laboratory hematology scientists from developing countries in ISLH meetings is funded by a generous grant from the Wallace H. Coulter Foundation, for which ISLH is extremely grateful.

As a pioneer of the diagnostic industry, Wallace Coulter leaves behind a legacy of his achievements, including critical advancements in diagnosis and treatment of disease, a dynamic corporation that will surely continue to innovate in health care, and a Foundation that generously funds improvements in health care for the population of the globe. His legacy also consists of colleagues, associates, friends, and family who were inspired by his influence. This author is humbly proud to consider himself one of those people.

Acknowledgements

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References

The author is deeply indebted to the following publications for much of the material in this article. It would be distracting for the reader to repetitively reference each of these publications for specific phrases that have been used. Instead, full acknowledgement with thanks to the authors of these publications is made here. Wallace H. Coulter - Engineer, Inventor, Entrepreneur, Visionary. Wallace H. Coulter Foundation. http://www.whcf.org/about/wallace-h-coulter. Accessed 11/17/2012. Graham, MD. The Coulter Principle: Foundation of an Industry. Journal of Laboratory Automation 8: 72–83. 2003. Clarkson University: About Wallace Coulter: A Legacy of Spirit & Vision. http://www.clarkson.edu/coulter/wallace_coulter.html. Accessed 11/22/2012.

References

  1. Top of page
  2. Summary
  3. Early Life
  4. The Coulter Principle
  5. Wallace Coulter's Personal Characteristics
  6. Impact of the Coulter Principle
  7. Wallace Coulter's Accomplishments and Awards
  8. Acknowledgements
  9. References
  • 1
    Coulter WH. Means for counting particles suspended in a fluid. U.S. Patent 2656508, filed August 27, 1949 and issued October 20, 1953.
  • 2
    Brecher G, Schneiderman M, Williams GZ. Evaluation of electronic red blood cell counter. Am J Clin Pathol 1956;26:143949.
  • 3
    Mattern CFT, Brackett FS, Olson BJ. Determination of number and size of particles by electrical gating: blood cells. J Appl Physiol 1957;10:5670.
  • 4
    Coulter WH, Coulter JR Jr. Fluid metering apparatus. U.S. Patent 2869078, filed May 9, 1956 and issued January 13, 1959.
  • 5
    Coulter WH. High Speed Automatic Blood Cell Counter and Cell Size Analyzer. Proc Natl Electron Conf 1957;12:103442.
  • 6
    Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD, Crawford SM, Burgess JM, Petry NA, Butchko GM, Glenn SD, Wahl RL. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med 1993;329:45965.