CUN. CHEM. 40/1, 149-157 (1994)

CLINICAL CHEMISTRY, Vol.40, No. 1, 1994 149

A History of Blo-Science Laboratories

Bio-Science Laboratories (BSL) was started in Febru-ary 1948. In 1985, it was acquired by SmithKline Beck-

man, becoming part of its laboratory network that wasrenamed “SmithKiine Bio-Science Laboratories.” In1989, following the acquisition of SmithKline Beckmanby the Beecham organization, the network was againrenamed, “SmithKline Beecham Clinical Laboratories”(SKBCL), and the name “Bio-Science” disappeared from

public view except for scattered references in the SK-BCL Directory of Services. In 1948, the BSL staff con-sisted of its four founding partners, who had only a few

thousand dollars for initial capital. When the last of thefounders retired in 1981, BSL had >20 major US loca-tions and three foreign branches and affiliates; con-

ducted several hundred different tests, with sales inexcess of $85 000 000; and employed >1500 people inthe US alone. Change, sometimes quite severe, charac-terized its life; the one constant that penetrated allaspects of the organization, however, was the dedicationof its founders to professionalism, quality, and research.The following personal and reflective narrative is in-tended to present both a history of BSL and an accountof its contributions to the profession of clinical chemis-try and to the AACC.

In 1948 the practice of medicine in general, and oflaboratory medicine in particular, was far removed inscope and sophistication from what we see today. Forexample, the principal antibacterials were a few sulfo-nainidea and penicillin; psychopharmacology was virtu-

ally nonexistent; adrenal and thyroid hypofunctionwere treated with endocrine organ extracts; and plasmacholesterol had just appeared on the scene as beingsomehow related to atherosclerosis and coronary arterydisease. In the clinical laboratory, chemistry’s contribu-tion to the assessment of health and disease was minor

in comparison with the roles of bacteriology, hematol-ogy, and urinalysis. Thyroid status was assessedthrough determination of the basal metabolic rate. Thefew protein hormones that could be measured were bio-assayed by using frogs, rabbits, and mice. Enzyme as-says did not appear until 1954. Analytical precision wasencompassed in the concept of assaying duplicates. Theindependent clinical laboratory was definitely held inlow regard, a grudgingly accepted adjunct to the hospi-

tal laboratory, because of what was perceived to be“poor” quality of performance and a “commercial” taint.To round out the context, Medicare and the ClinicalLaboratory Improvement Act of 1967 were 20 years inthe future. Few states had any legislation pertaining tothe clinical laboratory. Not until December 1948 would

11 scientists get together in New York City to form theAmerican Association of Clinical Chemists.

The Start-Up

It was with this situation in mind that three Armyofficers and one Navy officer decided they were ready totake up the challenges of postwar civilian life. They hadserved during World War II in their professional capac-ities: one was a physician who had decided while inmedical school that he didn’t want to practice medicineon patients; the other three had doctorates in bacteriol-ogy. The four had met after the war at Camp Detrick,MD, and were doing research in biological warfare.Duty at Camp Detrick was fine, but it was still just partof the transition process in returning to civilian life. Ascivilians they wanted to continue with research andplanned to fund this ambition with a laboratory busi-ness doing mainly industrial analyses backed up by amedical clinical laboratory. Southern California seemedto be the right place; opportunities in the region wereexpected to grow and the climate was benevolent. Thefour men were Sam Berkman, PhD; Orville Golub, PhD;

Richard Henry, MD; and Milton Segalove, PhD (Fig. 1).The business was to be named Bio-Science Laboratories.

The quartet moved to Los Angeles with financial helpfrom friends and family that, when added to their per-sonal savings, amounted to $55 000. This was to supportthe four families and launch the enterprise. Each drewa salary of $5000 annually; the rest of the nest egg wasused to rent space, buy equipment and supplies, andprovide working capital.

In February 1948, BSL opened for business. Henryand Berkman manned the clinical laboratory in a smalloffice building in Beverly Hills, and Golub and Segaloveworked in a larger laboratory about five miles (-30 km)away, near Culver City. Duties included everythingfrom cleaning animal cages to venipuncture of patientsand doing tests to the usual battery of clerical tasks.Then there was constant selling, Henry visited physi-cians and Golub called on industrial firms. Sometimesthe skies were sunny as exemplified by the numerousspecimens that appeared on opening day. Sometimes theskies were dark, such as the next 6 weeks, when hardlya specimen arrived.

Growth was not remarkable, working capital some-times got perilously low, and disaster often seemedclose. Acceptance by the local medical community wasslow and sometimes resisted. For example, Henry hadjoined the laboratory director subsection of the countymedical society. A pathologist who owned and directedan independent laboratory objected to Henry’s presence

Fig. 1. The foundersof Bio-ScienceLaboratories.Left to right: Richard Henry, MD; Orville Golub, PhD; Milton Segalove, PhD;and Sam Berkman, PhD, In Februaiy, 1969, at the time of Dr. Segalove’sretirement

150 CUNICAL CHEMISTRY, Vol. 40, No. 1, 1994

and invoked a bylaw that prohibited laboratory direc-tors from being in business with “lay persons,” includingdoctoral scientists. He was given the alternatives of

dissociation from his partners or withdrawing from theAssociation; he chose the latter.

The encouragement of the original supporters, how-ever, kept the scales tipped in the direction of stayingopen. Despite the slow growth, fiscal policy remainedclear: the “business” came first and spare cash wasplowed back into it. An employee was hired to free thefour from some nontechnical duties, such as washinganimal cages and tending animals. When possible,newer and better equipment was bought. But businessgrowth was not comforting.

The Breakthrough

In 1949, an event occurred that had important lastingconsequences, the result of a staff contact at the Los

Angeles County Hospital, a huge acute-care public in-stitution and the teaching hospital for the University ofSouthern California (USC) School of Medicine. DickHenry had been accepted to the USC teaching staff at itscounty facility. There he was introduced to Paul Starr, aphysician with a national reputation as a clinical andresearch thyroidologist. In 1951, physicians interestedin assessing thyroid status had to rely largely on mea-surement of the basal metabolic rate, a measurementthat was highly variable and nonspecific. Starr con-vinced Henry that thyroid status could be assessed rea-sonably well at the Hospital because Al Chaney, itsChief Clinical Chemist, had developed a reproduciblemethod for chemically measuring the protein-bound io-dine of serum (PBI), and inferentially the serum thyrox-ine concentration. The method was complex, quite labo-rious, and required the use of intricate customizedglassware-yet it worked. Because Chaney had a smallprivate laboratory business in Pasadena in addition tohis appointment at the Hospital, the benefits of thismeasurement were available to only a few practitioners

in the community and to the patients of the Hospital.

With Chaney’s generous loan of the special glasswareneeded, Henry and Golub went to work at BSL settingup the PBI method. The method involved serum proteinprecipitation and washing, wet digestion of the proteinpellet, distillation of released iodine into a receptacle,and measurement of that iodine by its catalysis of thereduction of ceric ion by arsenite. The digestion was anart; iodine in the air and on the premises was a contam-ination disaster; and little was known about specimenstability. It was a miserably difficult, one-specimen-at-a-time procedure but it could be made to perform. Sincethe four partners had to work all day to keep the busi-ness going, method development had to be done at nightand on weekends. It took Golub and Henry about 6weeks to learn how to control the test, assess its accu-racy and precision, and establish the conditions for spec-imen stability. The method remained tedious and labo-rious, but its improvement allowed the PBI to bemeasured reliably over a wide range of conditions andvalues. Once the improved test became available to theLos Angeles medical community, business growth atBSL accelerated markedly.

Repercussions of this development came to light whenLawson Wilkins, at the Johns Hopkins Medical Centerin Baltimore and a pioneer in pediatric endocrinology,became aware of BSL’s abffity to do the PBI. Apparentlyhis awareness came from one of his students, a BeverlyHills internist and a client of BSL. At Wilkins’s insti-gation, the Medical Center laboratory sent specimens to

BSL for analysis: “splits,” repeat splits, resubmissions,and “spikes”-all blind. The results were so good thatdaily shipments from Hopkins soon became routine.

When the dry ash method of Barker, Humphrey, andSoley was published in 1951, BSL quickly adapted it tomass production. I remember in 1966 that we were

analyzing well >1000 specimens a day, coming from allover the country and abroad, with exquisite precisionand a routine turnaround time of 24 h. Today I doubtthat the PBI is being done in the US at all.

The Learning Curve

The lessons from these experiences were fundamen-tal. First, recognition by the independent laboratorianof the present and future needs of the medical commu-

nity for new diagnostic aids could lead to significantgrowth. This was supported when the Johns HopkinsCenter soon began making requests for other tests, thekind that in the early 1950s were called “reference” or“specialized.” Accordingly, BSL’s attitude on new testdevelopment became increasingly aggressive, favoringsignificant risk taking. Indeed, BSL led the way in mak-ing specialty tests available to the national medicalcommunity. A few of these are shown in Table 1. Otherlaboratories, for various reasons, considered these teststo be only of research importance, but at BSL theyrepresented opportunity for growth. Today, many of

those are “old hat,” done routinely by using kits andautomated instrumentation.

Secondly, the basic commitment to quality becamestrongly reinforced. Henry, as director, was morally and

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Table. 1. SpecialIzed tests and year first offered to themedical community.

Test

Protein-boundiodineIn serumDirect determinationof eplnephrlneand norepinephrinein

urine and tissueAssay of 17-hydroxycortIcosterlodsin urineChemical assay of aldosterone In urinePaperchromatographicIdentificationof aminoacidsin urineRadiometricassay of uraniumand plutoniumin urineElectrophoreticmeasurementofthyroxine-bindingglobulin

in serumUltracentrifugal confirmation of hyperlipoproteinemiasLong-acting stimulatorof Graves disease in serumChromosomeanalysisDirect measurement of free thyroxinein serumLeclthln/sphingomyelin ratio in amnioticfluidEstradiol receptor assay in tissueParathyrold hormonein serumAngiotensin-convertingenzyme in serumHPLC measurement of propanotol In serum

Hemoglobin A1 measurementby isoelectricfocusing

professionally committed to patient care, as were hispartners. This attitude was concretely transferred to thefirst-level supervisors, giving them the authority to can-cel an analytical run if, in their opinion, the results weresuspect. Similarly, managers were required to requestdiscontinuance of testing if the procedure was not func-tioning properly. That such decisions sometimes en-tailed costs and reductions in revenue in the five and sixfigures range was irrelevant.

I remember in 1964 requesting suspension of our dou-ble-isotope derivative assay for urinary aldosterone be-cause of spurious counts in the quality-control assays.At that time, we were the only independent laboratoryoffering this assay and the volume was enormous, butthe department was shut down. Charles Sobel (he wasChief Chemist of BSL from 1950 until his retirement in1968) and I and the “aldo” staff formed a research teamthat worked 12-h days continually for several weeks tosolve the problem. Although we notified our clients ofthis state of affairs, the specimens continued to pour in,and we had to commandeer refrigerators and buy addi-tional units to store the specimens until the assay couldbe resumed. The problem was solved when we foundthat one of the radioactive reagents had an odd contam-inant. The cost of correcting this problem was consider-able, but the loss of revenue was probably minusculebecause, throughout this episode, our clientele did notslow down their submission of specimens.

Those were the days before modern automation waseven a concept. Automation then really meant mecha-nization. Nevertheless, business growth increasingly re-quired specimen processing in large batches. Specimensused exclusively for quality control constituted at least10% of those run in a batch, and they covered the fullrange of clinically expected values. In addition, severallayers of quality assurance schemes were put in place,ranging from on-site visual inspection of quality control

records through several in-house systems (such as mail-ing assayed specimens to ourselves) to services obtained

from governmental and professional agencies.1950 The FBI story had a third outcome. Service to Johns

Hopkins showed that the East Coast medical commu-

ig nity was only 24 h and a 6g postage stamp away. This1957 market potential was immediately appreciated and Orv1959 Golub was soon arranging to send announcements about1959 the PBI to physicians and laboratories all over the coun-1961 try. BSL became known, perhaps pejoratively, as “that

mail order lab out West.” The fact of the matter was that1961 tests of the quality that Johns Hopkins could get were1965 also made available to practitioners in such places as1962 International Falls, MN, and to a 99-bed hospital in the1968 Florida panhandle.1970 A final significance of the PBI story remains to be

told. The availability of this measurement nationally

1974 excited a great deal of interest. Many phone calls and1976 letters came requesting information about interpreta-1978 tion, interferences by drugs and diagnostic materials,1982 and what were then called “normal” ranges, and the

like. This prompted the production in 1951 of a leafletentitled “The FBI and Other Tests of Endocrine Dys-function.” It was a purely informational publication,detailed and referenced, and dedicated to better under-standing of the interpretation of such specialized tests.The leaflet has since disappeared; no copies exist that Iknow of. Its effects, however, were long lasting It wasfollowed by a much larger booklet addressing a widerange of specialized tests in chemistry, toxicology, mi-crobiology, and immunology. This booklet becameknown as “The Bio-Science Handbook” and was revisedwhenever a new group of tests had been put into oper-ation or when a need for updating was perceived. Thisoccurred almost annually: The laboratory scientists incharge of the various specialties were its authors. TheHandbook was used not only by the client laboratoriesbut also by hospital and academic programs because itsoriginal orientation was maintained: to provide infor-

mation important to the medical understanding andinterpretation of specialized laboratory tests.

The Growth Curve: Getting Bigger

The full effect of these events accelerated a change inthe nature of BSL. The volume of work in the clinicalpart grew sharply and steadily, while the industrial endlanguished. It became increasingly apparent that largemanufacturers of biological products referred their test-ing needs to in-house services, and there was a dearth ofsmaller organizations that could use the BSL analyticalcapabilities. The industrial laboratory of BSL did haveone solid client: the clinical part of BSL. With the startof the PBI assay, specimen processing was increasinglyreferred to the larger capacity of the Culver City branch.By 1952, the clinical operations so dominated the indus-trial operations that the partners had to recognize thattheir business really consisted of specialized laboratorytesting for the national medical community.

In the early years, through 1979, the owners madeother attempts to diversify, ranging from returning to

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industrial analytical chemistry, making science-based

educational toys, breeding research animals, and man-ufacturing laboratory instrumentation, to selling clini-cal chemistry test kits. Success with these ventures wasat best modest and, in spite of the efforts and resourcesdevoted, the outcomes were unimpressive.

Growth of BSL rushed forward. The original site nearCulver City was about 2000 sq. ft. In 1953 BSL moved toa facility of -6000 sq. ft. in an industrial area in WestLos Angeles. This open space between two preexistingbuildings was soon enclosed with a floor, a roof, and twoends put in place, and the interior became the labora-tory. By 1955, it was obvious this facility would be soonoutgrown. Land was bought on a main thoroughfarenearby and a first-class 16 000 sq. ft. building was con-structed and, occupied in 1957. By 1960, this area wasdoubled and, in 1964, land was again sought for a largerfacility. In 1966, BSL moved into its permanent home, a70000 sq. ft. laboratory located on 17 acres of land inthe San Fernando Valley. By 1970, this was increased to100 000 sq. ft. and to 125 000 sq. ft. in 1975. Whenseveral outbuildings were added, the physical size of thelaboratory stopped being of interest to anyone otherthan the plant engineer and the accountants.

The story of BSL, however, is not about the growth offacilities but of its professional staff. In 1950, CharlesSobel, who had been Chief Chemist for the Health De-partment of the City of Chicago, joined BSL. He wasbroadly experienced in ana1ytital chemistry, very in-ventive, and practical. He had learned clinical chemis-try during World War II as a field hospital laboratoryofficer in New Guinea. At BSL, his forte was devisingnew and better ways to do old jobs and to improveaccuracy and precision while maintaining efficiency. Asa troubleshooter, he was rarely led astray by superfici-alities. In 1955, 5. L. Jacobs, an organic chemist, joinedthe group; in 1956, Neil Chiamori, also an organicchemist, was recruited.

As volume and capabilities grew, it became obviousthat the laboratory was tied to quality, and new testsand the issue of doctoral-level support became impor-tant. The question now became, how fast and in whatdirection? Jacobs and Chiamori were the first steps, butby 1959 the partners felt that more specialists wereneeded. In 1959, B. N. Horwitt (endocrinology), V. J.Pileggi (chemistry), and I (radioisotopes) were recruited.We were followed in 1960 by I. Olitzky (microbiology),in 1961 by G. Stevenson (toxicology), and in 1965 by G.Kessler (automation) and H. Goldenberg (research).

These were not the only doctoral recruits. A commoncorporate practice was to reorganize operations as con-ditions changed and challenges were perceived. As aresult, technical departments were subdivided into sec-tions, each having one or more doctoral scientists re-sponsible for its operation, and more doctoral managerswere recruited. Fig. 2 shows the rate at which the doc-toral staff grew. At its staffing peak in 1981, BSL had>49 doctoral personnel, covering the entire range ofmedically related scientists and including biostatisti-cians and computer specialists.

I I I I I I1950 1955 1960 1965 1970 1975 1980

Fig. 2. Growth ofdoctoralstaffat Bio-ScienceLaboratories,1949-1982.

Although BSL philosophy had focused strongly onprofessionalism, growth meant formalizing a variety ofpolicies to accommodate the changing character of itsscientific staff From the beginning, attendance at sci-entific meetings was encouraged and fully supported;giving a research presentation was not a necessary pre-condition. Participation in the affairs of professionalorganizations was also encouraged and supported. Manystaff members held significant elective and appointedoffices in the AACC as well as serving on a variety of itscommittees. Richard Henry was President of the AACCin 1963, and Ralph Thiers in 1973. Frank Ibbott was aDirector-at-Large from 1972 through 1974; Larry Ja-cobs served as Treasurer during 1982-1985. In addition,many of us headed and worked on committees at thenational and local section level and took on leadershipresponsibilities for putting together at least three mm-tional meetings sponsored by the Southern Californiasection: the Los Angeles meeting in 1962, the Las Vegasmeeting in 1974, and the Anaheim meeting in 1982.Furthermore, BSL support of staff participation was notnarrowly limited to scientific organizations but reachedinto public and civic affairs. Dick Henry was heavilyinvolved in drafting the original regulations imple-menting the Clinical Laboratory Improvement Act of1967, and others of us were involved in local civic func-tions, with the blessing and support of the laboratory.

Research

At the outset of the enterprise, research was a raisond’etre. The four founders, being quick learners, realizedthat research was not a reward but a necessity, albeit apleasant one, if the future was to be grasped. Accord-ingly, once the PBI story had been digested, researchbegan to be regarded in a different and evolving man-ner. Research was seen as the way to maintain andimprove quality as well as the way to increase efficiencyand productivity and to discover and exploit new oppor-tunities. Research was the way all methods and proce-dures were brought into the repertoire offered to themedical community. New methods could come only fromtwo sources: from re-researching the scientific literature

or from the concepts and efforts of the BSL staff. Accord-

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ingly, the newly recruited doctoral scientists were ex-pected to participate actively in the research life of thelaboratory. The following is an example.

Early in 1959, the founders recognized that no onethen at BSL was capable of exploiting the potential ofradioactive materials for clinical chemistry; that wasthe reason I was hired. When I arrived toward the end of1959, space was again tight; expansion of the West LosAngeles facility was in the planning phase. I was givena chair in the library as my office, a laboratory the sizeof a walk-in closet, and one technologist. I was to doresearch with radioactive materials. The charge givento me was literally that broad, and it characterized thecorporate attitude: research was important and neces-sary, from new methods, method improvement, and ad-aptation of methods used in research to routine service.It was up to me to discover useful avenues and to choosethe projects after consulting with others on staff. Short-term payoff was not decisive, and maintaining the lab-oratory’s reputation for innovation was a powerful mo-tivator in selecting a project. What pertained to meapplied to all the other doctoral scientists on the staff.

From the start of Bio-Science through most of 1965,research was done in an unstructured atmosphere: Eachof us did his own thing with no compelling central or-ganization. With the compartmenta]ization and growthof the laboratory, however, a difficult management prob-lem emerged. The department heads, such as the chiefsof Chemistry or Endocrinology, began to use their re-search technicians in production whenever crunches cc-curred. Various approaches, from admonitions to theassignment of a group of “floaters,” were tried to avoidsuch personnel diversions; none was satisfactory. Ac-cordingly, a formal research department was estab-lished in mid-1965, staffed with three doctoral-level sci-entists and several technical assistants. Policyencouraged department chiefs to continue with re-search, but support would last only so long as theirresearch staff was used for that purpose.

This organizational form, in contrast to the previous“laissez faire” form, persisted through the mid-1970s.During that time, the Research Department grew in sizeand capabilities. For example, toward the end of 1969,the Department had several doctoral researchers, in-cluding a biostatistician, each supported with technicalassistants; at its peak in 1982, there were seven full-time Ph.D. scientists in the Department, and its person-nel budget alone was >$800 000 annually.

By 1969, however, the direct role of the departmentchiefs began to diminish, until it was uncommon for oneto be doing “hands on” research. This came not fromcorporate policy nor from the knuckle-rapping of theloss of research technicians but from the evolving chal-lenge of the increasing complexity of production. Therole of the chiefs became consultative, operatingthrough involvement in specific projects of the ResearchDepartment and through participation in the progressreport seminars of that Department.

At some point in the mid-1970s, research took anotherstep in the direction of structure. A Research Committee

was formed, charged with the selection of researchprojects to be undertaken. The Committee included acorporate executive, the Medical Director of the VanNuys facility, the head of the Marketing Department,the corporate coordinator of research, the head of theResearch Department, and, I think, one or two others.Except for the marketing head, all were scientific per-sonnel. Marketings function was to give us an insightinto the outside world’s interests but the preponderantdeterminant in selecting projects continued to be theprofessional judgment of the scientific people. Thisstructure continued through 1982; I am unaware ofwhat happened after that.

Table 2 helps provide an overview of research andresearch publications at BSL; the actual number ofmethods researched and the number of papers publishedare significantly larger (present in-house records are notcomplete). Many were quite simply new tests, some-times for newly reported constituents of clinical inter-est. The areas covered every specialty of the clinicallaboratory, from the most routine clinical chemistrythrough toxicology, immunology, and endocrinology tocytogenetics and receptor assays. A large proportion ofthe publications, >10% involving various laboratoryspecialties, were methodological, ranging from quality-control procedures and statistical criteria through ref-erence range refinements.

Publishable research was certainly encouraged, butthe mission of the Research Department went well be-yond this. Studies on specimen stability, improvements

Table 2. BSL research publications, 1951-1982.Subject area Number

ChemistiyEnzymesProteinsand aminoacidsUpidsand lipoproteinsDrugsand drugsof abuseUver functionInorganic materialsMisc. (vitamins,porphyrins,etc.)

EndocrinologyThyroidstatusProteinhormonesAdrenocorticalfunctionAdrenomedullaryfunctionAndrogensand estrogensMisc. (cyclicAMP, prostaglandins,receptors,etc.)

BiostatisticsAccuracy and precisionNormal values and referencerangesQualitycontroland controlchartsMisc. (stability,methodcomparisons,etc.)

Microbiologyand immunologyTechnology

InstrumentsContinuous-flowanalysisMisc. (kit evaluations, etc.)

Publicpolicy and educationChromosomestudies

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in accuracy and precision, method simplification, pro-cess computerization, phasing new tests into routineoperations, adaptation of research procedures for rou-tine use, and troubleshooting method breakdowns:These activities were also on our plate. On several cc-casions, teams from the Research Department were dis-patched to various of the sifihiRtes, both in the US andabroad, to assist in introducing the methods developedand in operation at the Central Laboratory. It was com-monplace to have healthcare institutions of all stripesengage BSL in the design and execution of research

programs of variable duration and complexity, in whichthe specimen analysis would be done by BSL. Several ofthese arrangements involved developing and installingnew methods. For example, the National Institute ofArthritis and Metabolic Diseases instituted a broadlipid research project concerning the role of cholesterolin coronary artery disease. This program, which lastedfrom 1973 through 1984, involved the repeated periodic

analyses for several blood constituents in >3800 sub-jects. This was an international project, and BSL wasinvolved from the early planning stages throughoutthe entire execution of the study. Similar projects wereengaged with various individual investigators and sev-eral pharmaceutical organizations. Hence, Bio-Sci-ence’s activity in research was much broader than ap-parent from its armamentarium of exotic tests and itspublications list. Research was a basic element in thecorporate culture, reflecting itself in staffing, budget-ing, and all aspects of planning, making BSL an excit-ing workplace.

Research and the Niche

Bio-Science’s contribution to the practice of laboratorymedicine was the creation/discovery of a niche in the econ-omy: a national market characterized by an appetite fornew, specialized tests. This was particularly envisioned asapplying to methods devised for particular research inter-ests and usually coming from some academic institution,then modified for use in the specialty laboratory, far re-moved in time and space from the patient.

Throughout its life, BSL was committed to researchand its fruits. After institution of the Chancy PBImethod in 1951, there was a continual string of publi-cations on that method and its refinements. Followingthese papers came reports on methods of other markersof thyroid function: the “F3” uptake (1960), measure-ment of the thyroxine-binding globulin in serum (1961),a column chromatographic method for thyroxine (1962),the detection of the Long-Acting Thyroid Stimulator ofGraves Disease (LATS) (1962), the direct measurementof “free” thyroxine in serum (1971), and the measure-ment of thyroxine by competitive protein-binding(1972). These lines of research development are justexamples of numerous similar programs, mainly in en-docrinology, in which methods were adapted from theresearch laboratory to application in a high-volume ser-vice laboratory. An example was a series of refinementsof the analysis for aldosterone in urine, ranging fromNowacznski’s chemical method (1958) through the Kli-

man and Peterson double-isotope derivative assay(1962) to a radioimmunoassay (1976).

A dramatic example of jumping on the research band-wagon was the estradiol receptor assay. The ResearchCommittee had kept the need for such an assay on itsshort list for some time but lacked a suitable opportu-nity. Early in 1974 a group of European research work-ers published an assay for estrogen and androgen recep-tors in the British Medical Journal. We promptlyarranged with J. P. Persijn, one of the coauthors, to setup the method at BSL. The assay used surgically re-moved breast tumor tissue and was valuable in thetherapeutic strategy for metastatic breast cancer. Per-sun brought several hundred patients’ specimens withhim, and a BSL research crew was quickly assembled.Within weeks, the method,, including a number of sig-nificant improvements, was in place and, by the end of1974, was running routinely. Although this was early inthe understanding of the applicability of the assay, itwas quickly seized upon and increasingly used.

Another assay is an example of the bizarre. In 1958,J. M. McKenzie published an assay for the bioassay onthyrotropin (TSH) in serum. It was not very good at lowlevels but did demonstrate the presence of a humoralfactor that showed a long-acting stimulator effect on thethyroid (LATS), unlike TSH. No one really understoodthe LATS part of the assay and it more reflected anacademic interest than a medical concern, at least atthat time. Nevertheless, we felt that we had to set it upbecause of our commitment to leadership in specialtytesting. It was an unbelievably complex procedure, re-quiring dozens of mice and loads of and was fright-fully expensive. With the assistance of W. Vanderlan ofthe Scripps Research Foundation and D. Solomon of theUCLA Medical School, assay development was startedin early 1962 and in operation by mid-1962. At first, wewould get about one specimen a month, a vexing situa-tion. I think it was at least 5 years before the volume ofsamples allowed us to break even on costs. It was atriumph of principle over business sense that turned outfavorably. By the time the assay was supplanted by asimpler methodology, the medical community was usingit heavily and we were showing profits.

Finally, the ultracentrifuge story. Around 1948, Gof-

man and coworkers showed a link between serum cho-lesterol concentrations, atherosclerosis, and coronaryartery disease. Bear in mind that this was in the pre-Fredrickson era, which began in 1969. Again, the com-mitment to leadership was evident. Around 1964-65, webought two ultracentrifuges, a Beckman Model L pre-paratory and a Model E analytical, for the determina-tion of low-density and very-low-density lipoproteins.The medical community, academic and otherwise, wasaware of this capability but used it sparingly. This wasanother example of principle triumphing over businesssense; I doubt whether we recovered even the electricitycosts for running the assays.

Many other examples, both successful and foolish,could be provided. Nevertheless, adventures such as theabove secured the preeminence of Bio-Science, and for

CUNICAL CHEMISTRY, Vol. 40, No. 1, 1994 155

about 20 years BSL occupied this niche almost exclu-sively. Our preeminence and exclusivity was challengedfirst by the Nichol Laboratory and then later when thelaboratory business began to consolidate into largechains, where specialization was felt to be affordable interms of assets and staff.

Management

The developments of the first decade of its life pro-pelled changes in the future organization and operatingphilosophy of BSL. The business had gotten too big tohave a loosely structured organization and still afforddirect control of operations; a more formal and sophisti-cated system was required. Beginning in 1959, the earlystaffing strategy of generalists was changed to one ofspecialists, and the four partners began to move out oftechnical operations, becoming managers of those whomanaged. By 1965, the necessities of the future hadbecome clear: the four had become managers of thosewho managed research and the earlier dream of person-ally doing research was gone.

Accordingly, two patterns of activity emerged. First,starting about 1965, the four partners, and later thenext level of managers, undertook various formal andstructured educational programs in management prin-ciples and technics. This impulse was maintainedthroughout the rest of Bio-Science’s life and was ex-tended to all levels of management and supervision.Second, changes in business and technical organizationbecame commonplace. These ranged from dividing tech-nical operations into 4 broadly defined units to morethan 10 narrowly defined units, from single departmen-tal leadership to shared leadership-and back again.

Various factors underlay these changes, such as theneed to increase efficiency, to sharpen technical control,to respond to the emergence of new specialties and tech-nology and so forth. Throughout these fluctuations wasthe growth of the clinical scientists from managers oftechnology to operations managers, whose duties in-creasingly embraced production, research, finance,staffing, and corporate planning.

I believe that this state of affairs and its philosophicalimplications had a unique though subtle and indirect ef-fect on our profession and Association. What had evolvedwas an increasing broadening and independence of theclinical chemist from that of a manager of specializedtechnology to the operation of independent profit centersand participant in the overall management and develop-ment of the Company. To give this some perspective, re-member that in those days, the late 1960s through theearly 1970s, the clinical chemist was largely regarded as ascientific resource person and an adjunct to the patholo-

gist; real professional independence and control were un-common. By the mid-1970s, the AACC was just beginningto think of educational programs in technical manage-ment. So Bio-Science had an impact on our profession byproviding a model of the clinical scientist as an indepen-dent leader of a technical enterprise, with broad capabili-ties and responsibilities.

The GrowthCurve: Getting Different

In 1966, an event that determined the nature of Bio-Science’s future took place: a minority interest in theownership of the laboratory was purchased by the DowChemical Co. This action was the first step in a process

that resulted in complete ownership by Dow by 1973.The consequences of the Dow association were manybut, for the purposes of this story, their main inipor-tance lay in two areas. First, the Dow relationship pro-

vided a sense of financial stability that stimulated BSLto embark on a broadly conceived program of growth byacquisition, association, and branch development. Sec-ond, the professionalizing of the clinical scientist asbusiness managers achieved greater importance nowthat Dow offered a model and advancement opportuni-ties that had not previously existed. As far as Dow wasconcerned, the BSL acquisition was a step in the pene-tration of the medical and biological sciences fields,which Dow perceived as areas of rapid growth and op-portunity.

In the 14 years of my acquaintance with Dow, it in noway inserted itself into the professional operations ofBSL. We continued with what we had always been do-ing, and with the same constraints and hopes. The con-cerns for quality and research exactly suited Dow’s phi-losophy, and laboratory safety was greatly stimulated atBSL by Dow’s highly developed safety programs. Whatwas necessary was the assurance of the continuity oftechnical leadership. In 1967, James Winkelman, MD,was brought in as Assistant Director. Winkelman was awell-trained clinical pathologist, bright, energetic, andaggressive, with a natural bent for the borderland worldwhere technology and business meet. He pursued tech-nical and professional interests at the corporate level.This was the first step in changing the corporate orga-nization to prepare for growth.

Throughout the 1960s, BSL dominated the national

market for specialty testing, with the majority of thelarger hospitals, clinics, and healthcare institutions inthe US as clients. However, the profits and growth pos-sibifities of the clinical laboratory business were attract-ing the attention of large companies such as W. R. Grace,Abbott Laboratories, Revlon, and Bristol-Meyers, who,like Dow, began to acquire or build chains of medicallaboratories. For Bio-Science a 6g stamp and 24-h servicecould no longer be enough: A local presence distributedthroughout the marketplace was required. The first stepin implementing this concept was the acquisition of theSamson Laboratories in 1968.

BSL was strongly managed and its leaders recognized

that growth by accretion would be a new experience;hence, a testing of that challenge was necessary. Sam-son was a modest laboratory with a good reputation butnot much in the way of specialty testing. Its value lay ingiving BSL the chance to learn how to manage a labo-ratory from a distance, where central managementcould not be so strongly applied. This turned out to be areal learning experience.

Samson Laboratories presented a multitude of prob-

156 CUNICAL CHEMISTRY, Vol. 40, No. 1, 1994

lems, ranging from top-level interpersonal relationshipsthrough communications to technical operations. BSL’ssystem and attitudes in plRnning, control, and systemsorientation increasingly came into conflict with the highlypersonal and informal style of a smaller business. It wasdifficult for the manager of a small organization to acceptthe idea that the concerns of the parent entities, such asDow and BSL, could sometimes be at stake. The mix of apast owner and his staff staying in place and management

from afar was fraught with difficulty and could, on occa-sion, be dangerous. The lesson learned was that futurebranches would have to be mini-BSLs, built from theground up, using official BSL methods, BSL systems, andBSL-tested equipment and led by BSL people.

Accordingly, in 1970 a Directors Training Programwas established at the Van Nuys facility, its purposebeing to train doctoral personnel for directorship ofbranch laboratories. Because the Branch Directorswould have little of the support available at Van Nuys,the programs covered all facets of the laboratory busi-ness: technical operations, office operations, personneladministration, government regulation, finance, and soforth. This program produced a stream of Directors forabout the 10 years the branch movement was underway.

At the same time as branches were being established,other forms of expansion were under way. BSL hadcontracted for the total management of the laboratoriesof several small hospitals. The clash with the hospitalculture was an alien experience; this form of expansion-ism stayed small and lasted only a few years. Moresuccessful were the “total equity” acquisitions with theoriginal ownership and management being kept inplace, as in the Dow-BSL model. One was in Canada,another in Brazil, a third in Hawaii, a fourth in Boston,and several in southern California. There were also twojoint start-up ventures involving foreign chemical com-panies: C. H. Boehringer in Germany (1971) and Te*jinin Japan (1977). With BSL providing technology andtraining, laboratories were set up in these countries,and the successful businesses established are still oper-ating to this day.

Thus, the growth phase that started in 1968 with theacquisition of the Samson Laboratories resulted 14years later in a network of >25 branches and affiliates,with the main laboratory in Van Nuys at its center.During those 14 years, sales quadrupled, profits dou-bled, the staff grew to >1500, and the “system” contin-ued to constantly reorganize itself. A systemwide spec-imen pickup service was instituted in early 1974, and anational network of sales representatives was in placeby early 1976. By 1978, almost all locations were com-puter-linked with each other and the main laboratory,with the linkup serving not only technical and analyti-cal operations but also administrative and financialfunctions. The branches used the same analytical meth-ods and quality-control and assurance systems so that,except for the local service, clients everywhere werereceiving the product of a single laboratory: BSL. That

had been the main professional principle governing thegrowth movement and it had been achieved.

The Beginning of the End

In 1982, after the founders had all retired, Dow soldBSL to the American Hospital Supply Corp. Because, toall appearances, the relationship had been nothing butmutually beneficial, I can only provide personal specu-lations as to Dow’s motive in this action. The chemicalindustry as a whole is cyclical in nature; its peaks andvalleys in profits arise from a variety of causes in theworld marketplace. Dow has prided itself; and still does,in never having missed or reduced a dividend paymentto its stockholders. The late 1970s were not good yearsand threatened this commitment. Because operationswere not sufficiently profitable, liquidation of assets wasthe route taken: ergo, the sale of BSL. For AIlS, Bio-Science was very tempting It was expected to meldbeautifully into the AIlS hospital supply and communi-cations networks. The purchase was accomplished inrecord time, a matter of a few months.

AIlS, however, did not keep BSL very long. The ven-ture went the way of many in the late 1960s. The clin-ical laboratory business looked promising, but learningto deal with its particular nature required a goodlyamount of stamina and expertise. Also, in my opinion,there was an inadequate understanding of the differencebetween a case of test tubes and a clinical laboratoryreport. It took only two annual business cycles for AHSto learn that it didn’t want to pay the price. Duringthose 2 years, many of the doctoral-level managers leftBSL and the Research Department was reduced signif-icantly. BSL was again sold, this time to the thenSmithKline Beckman, an organization that knew thebusiness and was willing and able to allocate the re-sources necessary for growth.

The Ties that Bind

In a sense, Bio-Science, as I knew it, was a uniqueenterprise. The four partners were distinct personali-ties, varying greatly in their drive, self-assurance, so-ciability, political bent, intellectual interests, and otherattributes. They were alike, however, in their competi-tiveness, ranging from “very” to “totally.” One wouldthink that it was a situation ripe for conflict. Onlookersoften wondered how the association could have lastedand how this four-headed organism could produce such asuccessful enterprise. What helped smooth the interre-lationships among the four founders, particularly afterthe first 10 years, when the size and complexity of thedeveloping enterprise began to emerge, was the gradualseparation of some of their main responsibffities withinthe organization. This process was an evolution basedon exclusively pragmatic considerations that respectedindividual strengths and tolerated individual weak-nesses. Berkman was the business manager; he laterbecame busy with acquisitions and was the principalcontact with Dow. Henry maintained his interest inresearch and general laboratory management. Golubbecame the marketing specialist and set up the branch

CUNICAL CHEMISTRY, Vol. 40, No. 1, 1994 157

expansion and the sales force. Segalove took over theI day-to-day administration and personnel management

until he retired in 1969.I believe that two things were, paradoxically, the glue

and the lubricant that kept the organism intact andfunctioning smoothly. One was their early recognitionthat they had a successful enterprise under way and itneeded to be cared for. The business was not looked uponas a “cash cow” to be milked for immediate gain. Theopposite was the case; capital was plowed back to im-prove instrumentation, an uncommonly large propor-tion of professionals was employed, better and moresecure quarters were obtained, risks were supportedfinancially, and preparation for the future was foremost.For example, when they understood in 1951 that thePBI would make the business more secure, they re-warded themselves with a raise of $500 annually.Knowing the four, this kind of decision could only havecome from business judgment, not lack of enthusiasmfor the future.

The second tie was their philosophical unanimity. Thepartners thought as one in matters of professionalism,goals, ethios, and principles. This unmlimity determinedsafety practices, quality control and research productivity,service to public and professional organizations, publicimage, and service to the patient. Although the philosoph-ical character of BSL arose from the personalities of thefour, it was also firmly grounded in the belief that if youbuild abetter mousetrap, the world will beat a golden pathto your door-which, of course, it did.

Don’t think this is entirely an encomiuin. Thefounders were not easy taskmasters, nor did they con-duct their interrelationship in Olympian harmony.High standards of professionalism and quality meanthigh standards of performance. Executive frustrationwas easily aroused, and patience was not to be taken forgranted. The four argued often on matters of procedureand overlapping areas of authority. They could be crit-ical of each other’s performance as well as that of therest of the staff. Mutual respect, professionalism, and adedication to the common interest, however, took theedge off, made the working environment productive, andkept the staff morale high.

It is said that human organizations, be they univer-sity departments, governmental agencies, or industrialenterprises, are reflections of the personalities of theirleaders. From the perspective of the clinical chemist, theirreplaceable personality molding Bio-Science Labora-tories was that of Dick Henry. He was the legal andactual director of the laboratory, and his influence waslargely confined to technical operations. I believe Dickfully believed that nobody could do anything as well ashe. And he was often right. He was fast thinking andimpatient, and had great energy. If he couldn’t do some-thing very much better than most, he wouldn’t do it atall. His mind was truly an organ of pleasure. He wascontinuously competitive and could be so outspoken asto make compromise impossible. He could tell you flat

out when you were wrong and be astonished that you

would be disturbed by his statement; for him, right wasright and wrong was wrong. He had a gene for fairnessand another for integrity; his dedication to quality ofperformance and to the welfare of the patient was evi-dent to all. He commpnded great respect because of hisintellectual prowess and his honesty. Because of thesetraits, his abrasiveness was usually accepted and com-monly thought of as understandable if not justifiable.

The following anecdote may provide some flavor andinsight. In 1965, I became Dick’s assistant and “enforc-er.” On those occasions when I would come to him forguidance, invariably his impatient reaction would be,“Well, do the right thing!” He meant it quite literallyand without qualification but was not unaware or insen-sitive to the repercussions of that kind of answer. Thisattitude could have severe consequences. For example,his contract with Harper and Row to publish ClinicalChemistry: Principles and Technics required periodicupdates. The first edition, which he had written entirelyby himself, had been an extremely arduous task; hence,he turned the 1974 edition into a collaborative effortinvolving the entire doctoral staff of the laboratory. An-other similar effort was slated for the late 1970s, and allthe manuscripts were completed on schedule except one,the chapter on statistics. Dick felt that without thischapter the book would be second-rate and thereforeunacceptable: Thus, the third edition was cancelled. Heunderstood the cost of this action in all regards, both tothose who contributed as well as to the laboratory andthe profession; indeed, his dedication to the second edi-tion had been, “To the families of men who write books.”As severe as this decision was, however, all of us as wellas Dick’s partners accepted and supported it. I think thepublishers may have a third edition underway, entitledHeni’/s Clinical Chemistry. I am sure that it will bereceived with nostalgia by many besides me.

Endpiece

I close with another nostalgic indulgence. ClinicalChemistry News in 1992 reported the induction ofAACC’s 10 000th member. Quite properly, this eventwas recognized and celebrated as symbolic of the growthand development of our Association and our profession.Bio-Science was born at the same time as our Associa.tion, and its growth and development paralleled andinfluenced that of the AACC. However, BSL has nowvirtually disappeared except for such personal and re-flective accounts as this.

I thank the management of the Van Nuys, CA, facility of theSmithKline BeechamClinical Laboratories for making their filesand records available to me. My special thanks go to CarolineEhnan, Information SpecialistlLibrarian of that organization, forher gracious and generous help. My thanks go also to Orville J.Golub, one of the four founders, for keeping me from making errorsof fact. Lastly, I thank the Executive Committee of the AACCHistory Division for stimulating me to write this article and fortheir invaluable efforts in pre-editing it.

4624 La Subida P1.Tarzana, CA 91356

Norman D. Lee