SE P 2 1 1993
`‘TEAL! n .DL.rLm\.r.o LIDHARY
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`Page 1 of 9
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`ILMN EXHIBIT 1020
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`

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`EB OURNAL
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`Editorial
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`Biocliversity—en lntemafionel Challenge. R. R. Cohtrefl .
`News 8 Features
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`BioBits
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`Special Feature:
`Biotechnology core facilities: trends and update. K. M. Jvanerich, R. L. Niece, M. Rohde, E. Fowler,
`endT.K.Heyes .
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`Serial Review
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`1107" K
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`Extracellular Matrix 3: Evolution of the extracellular matrix in invertebrates. R. Har-Hand M. L. Tanzer .
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`Reviews
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`Y. Henry, M. Lepoivre,
`EPFI characterization of molecular targets for N0 in mammalian cells and organelles.
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`J.-C. Drapier, C‘. Ducrocq, J.-L. Boucher, and A. Guissani .
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`Biology of free radicai scavengers: an evaluation of ascorbate. R. C. Rose and A. M. Bode .
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`POINT-COUNTEHPOINT
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`Selective brain cooling in humans: “fancy” or fact? M. Cebenec .
`Specialized brain coolingin humans? G. l..BrengeImann .
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`METHODOLOGY
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`Two-dimensional NMH investigations of the interactions of antibodies with peptide antigens.
`J. Anglisrer, T. Server)‘, 8. Jlber, R. Levy, A. 214?, R. Hiikr, and D. Feigelson .
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`Microcomputer-assisted kinetic modelin of mammalian gene expression.
`J. L. Harymve .
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`Research Communications
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`I. A. Paul, A. S. Basile,
`Sigma receptors modulate nicotinic receptor function in adrenal chromaffin cells.
`E. Rojas, M’. B. H. Youdfm, B. De Costa, P. Skalnick, H. B. Pollard, and G. A. J. Kuribers .
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`Retinoids: in vitro interaction with retinal-binding protein and influence on plasma retinol.
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`R. Berni, M. Clerici, G. Melpeai L. Cleric and F. Formelli .
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`HIV binding to its receptor creates specific epitopes for the CD4/gp120 complex.
`J. M. Gershoni,
`G. Demsava, D. Raviv, N. I. Smomdiosky, and D. Buyaner .
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`HYPOTHESIS
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`Cell cycle control, DNA repair, and initiation of carcinogenesis. W. K. Kaufmann and D. G. Kaufman .
`Erratum .
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`50 Years Ago
`Enzyme Nomenclature: A Personal Retrospective.
`Calendar
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`E. C. Webb .
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`1171
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`1179
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`1185
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`1188
`1191
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`1192
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`Employment Opportunities .
`New Products Er Literature .
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`The FASEB Jnurrul .-TSSN {B92-RS381 is pubfished 1'5 rirnos a year {monthly excepts issues in .f-‘ebruery and 2 issues in Anni‘! by FASEB. Q60 Fieckwiile Pike,
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`Page 2 of 9
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`

`
`NEWS & FEATURES
`
`SPECIAL FEATURE
`
`Biotechnology core facilities: trends and update
`rurrnnrn M. rvsnrrrcur - nomrn I... insert,‘ MICHAEL nounr:,1rr.1zAss'rn sown-:r:,5
`AND TIMOTHY K. HAYES
`
`‘Biomolecular Resource Center, University of California, San Francisco, California 94143-0541, USA; TUniversity of
`Wisconsin Biotechnology Center, Madison, Wisconsin 53705, USA; ‘Antigen Inc, Amgen Center, Thousand Oaks,
`California 91320, USA; ‘Autoimmune, 123 Spring St., Lexington, Massachusetts 02174, uss; and "Department of
`Entomology, Institute for Biosciences and Technology, 'Ii-atas Agricultural Experimental Station, 'Iv':xas A & M
`University, College Station, ‘Texas, 77343-2475, USA
`
`-
`
`A survey of 128 bio-
`ABSTRACT
`technology core facilities has provided
`data on the finances, services, space
`requirements, and
`nnel. An aver-
`age facility had four full-time person-
`nel and 7.5 major instrument systems,
`and occupied 969 sq. ft. Average total
`income was $244-,000fyear, but annual
`user fee income was only $125,000.
`Typically, facilities required substan-
`tial
`institutional support or grants.
`Cost recovery (user fee income divided
`by total income) averaged 49%. Dur-
`ing the last 5 years user fee income, to-
`tal income, and cost recovery have in-
`creased. ln-house charges for protein
`sequencing and peptide synthesis in-
`creased approximately 30%, while
`oligonucleotide synthesis charges
`decreased by 74%. The costs (charges
`corrected for subsidy from non-user fee
`income)
`for most services did not
`significantly change, except
`that
`oligonucleotide
`synthesis
`costs
`decreased by 25% in 1992. DNA syn-
`thesis had the highest throughput per
`month (116 samples),
`followed by
`amino acid analysis (86 samples) and
`DNA sequencing (67 samples). Other
`services averaged from 5 to 60 samples.
`DNA synthesis and purification were
`the services used by the greatest num-
`ber of principal investigators. A num-
`ber of services including DNA sequenc-
`ing, mass
`spectrometry, capillary
`electrophoresis, RNA synthesis, elec-
`troblotting, and carbohydrate analysis
`have been introduced in the last 3
`
`years. Although these services are
`characterized by high levels of methods
`development and non-user runs, they
`are offered by twice the percentage of
`facilities as in 1989, and are increas-
`ingly contributing to facility in-
`come.— lvanttich, K. M., Niece, R.
`L., Rohde, M., Fowler, E., Hayes, T. K.
`Biotechnology core
`trends and
`update. FASEBJ. 7: 1109-1114; 1993.
`
`biotechnology ' cm faa'Iity
`Key Hinds.‘
`' DNA ‘ protein
`
`OPTIMAL MANAGEMENT or STATE-OF"I‘HEr
`
`Artr biotechnology core facilities requires
`that
`the facility personnel, administra-
`tors, a.nd users have access to current
`data on the technologies, personnel, and
`finances of core faciliti. To meet this
`need, we have compiled the following
`survey of 128 protein and/or nucleic acid
`biotechnology core facilities. The data
`are compared to similar but less com-
`prehensive data from a survey of 40 fa-
`cilities in 1987 (1) and of 124- facilities in
`1991 (2, 3). Special attention is given to
`core facility data that have shown the
`greatest change over this period of time.
`In addition, information on several new
`technologies not covered in the previous
`surveys is presented.
`
`EXPERIMENTAL PROCEDURES
`
`The data presented are based on a sur-
`vey mailed in_]anuary 1992 to the 225
`members of
`the Association of Bi-
`omolecular Resource Facilitifi. Mailings
`and receipts of responses were handled
`by
`the Wisconsin Survey Research
`Laboratory. The identity of the respond-
`ing laboratories is not known to the
`authors.’
`Typically, data are reported as one or
`more of the following: mean, standantl
`deviation, range, median, and n values.
`Where calculations were made on data,
`the manipulations were performed sam-
`ple by sample, and mean, standard devi-
`ation, etc. were directly compiled on the
`new data set. In several data sets,
`the
`mean and median agree poorly, differ-
`ing by a factor of two or more. This
`reflects the wide ranges of these data. In
`approximately 15 data sets, there were
`single points differing from the nearest
`value by a factor of 10 or more. In these
`cases,
`the outlier was removed, with a
`note made in the text or table. In the
`
`data on personnel percent effort and
`highest degree, there were several high
`values, and in these cases the median
`was thought to better represent the data
`than the mean.
`
`Statistical analysis of the significance
`of dilferencm between means was per-
`fonned using Student’s if
`test for un-
`paired data. The standard deviations of
`the two populations to be compared
`were not assumed to be equal. A
`significant
`cliffercnce between means
`was taken to be P < 0.01, with P < 0.05
`as 8. probably significant difference.
`A copy of the survey and the sup-
`plemenral tables are available from the
`corresponding author.
`
`RESULTS AND DISCUSSION
`
`Responding biotechnology facilities
`
`A total of 128 completed questionnaires
`were returned within 16 wk, correspond-
`ing to an overall response rate of 57%.
`The respondents included 88 academic,
`15 research institutions, 20 industrial, 3
`government laboratories, and 2 uniden-
`tified. Unless otherwise indicated,
`the
`following report combines all of these
`categories.
`
`Technical capabilities of
`biotechnology facilities
`
`The percentages of 128 core facilities
`that offered various biotechnology serv-
`ices were compilcd. While each of the
`six most commonly available procedures
`(protein sequencing, amino acid analy-
`sis, peptide synthesis, DNA synthesis,
`HPLC peptide isolation, and fragmen-
`tation of proteins) was offered by 4-5% to
`86% of the core facilities, only 22 (17%)
`laboratories offered all six of these serv-
`ices. Approximately one-third (36%) of
`the facilities offered five of the six serv-
`
`1To whom correspondence should be ad-
`dressed.
`7A preliminary account of this study was
`presented at the Association of Biomolecular
`Resource Facilities Symposium at the Sixth
`Symposium of the Protein Society, San
`Diego, California, July 25-29, 1992.
`
`Vol. 7
`
`September 1993
`
`NEWS 8: FEATURES
`
`
`
`Page 3 of 9
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`

`
`NEWS 8- FEATURES
`
`TABLE 1. Throughput of biotechnology torcfacilitiu
`
`Service
`
`Mean
`
`Peptide synthesis‘
`Peptide purification
`DNA synthesis“
`DNA purification
`RNA synthesis
`Protein sequencing“
`DNA sequencing
`Elcctroblotting
`Fragmentationiprolein
`HPLC peptide isolation
`Amino acid analysis"
`Carbohydrate analysis
`Capillary electrophoresis
`Mass spectrometry
`Other analysis
`
`11
`7
`116
`59
`41-
`35
`6?
`6
`5
`12
`85
`3!
`51
`58
`41
`
`Samples!month
`
`SD
`
`13
`12
`119
`99
`3
`62
`58
`6
`5
`23
`156
`27
`59
`47
`83
`
`Range
`
`112-30
`016-70
`2-500
`03-500
`1-10
`1-450
`5-200
`1-20
`0.5—25
`05-150
`0.5- I 100
`2-80
`1-175
`1-150
`0.‘!--300
`
`N
`
`65
`4-2
`58
`27
`8
`98
`14
`31
`39
`53
`83
`7
`11
`12
`ll
`
`Median
`
`8
`3
`84
`25
`2
`20
`4-1
`-1
`4
`5
`25
`Mr
`25
`58
`10
`
`'1’ < 0.05 relative to 1939.
`P < 0.01 relative to
`‘All of the outliers shown in this table arose l'rom one facility, a laboratory with $3.2 million budget. 15 full-time employees: and Bi instruments.
`‘P < 0.01 relative to 19B'.I'.
`One additional outlier was 2500 for amino acid analysis.
`1939.
`'P < 0.05 relative to 198?.
`
`ices. The 1992 data on the percentage of
`facilities offeri.ng services are similar to
`that from previous surveys, except that
`the percentages of facilities offering mass
`spectrometry, capillary zone electropho-
`resis, or RNA synthesis increased from
`apprtzotirnately 7% in 1989 to approxi-
`mately 13% in 1992.
`facilities oflcring
`The number of
`amino acid analysis, oligonuclootide and
`peptide synthesis, and protein sequenc-
`ing strikingly increased from 1987 to
`1989, but has changed little since. This
`parallels the striking increase in number
`of facilities responding, from -1-0 in 1987
`to approximately 125 in 1989 and 1992.
`(supplementary Table 1).’
`The number of instruments per facil-
`ity was tracked h-om 1987 through 1992.
`No significant changes in numbers of
`amino acid analyzers, peptide syn-
`thesizers, and protein sequencers oc-
`curred during that
`time period. The
`number of oligonucleotidc synthesizers
`increased from 1987 to 1989 but not
`significantly further in 1992 (supplemen-
`tary Table 1).
`In Table 1 are shown the runs per
`month by service. There was considera-
`ble va.ria.tion in the number of samples
`that were processed per month in difl'er-
`ent facilities. For instance, the number
`of amino acid analyses, carbohydrate
`analyses, capillary electrophoresis runs,
`fragrnentations, and HPLC peptide iso-
`lations each varied from 3,000-
`to
`6,000-fold among different
`facilities.
`
`Ssupplernentary tables are available from
`the corresponding author.
`
`These broad ranges were in many cases
`due to a single outlier that varied from
`the next highest number by up to
`‘240-fold. We removed these outliers and
`
`they are noted in the table.
`The service with the highest through-
`put per month was DNA synthesis aver-
`aging ca. 115 samples per month. Next
`were amino acid analysis and DNA se-
`quencing at 86 and 67 samples per
`month. Between 35 and 60 samples per
`month were characteristic of several
`services, including synthetic oIigonucleo-
`tide purification, mass
`spectrometry.
`protein sequencing,
`template prepara-
`tion, amino acid and carbohydrate anal-
`ysis, and capillary electrophoresis. The
`lowest throughputs (3 to 11 samples per
`month) were for RNA synthesis, peptide
`synthesis and purification, electroblot-
`ting, fragmentation, and HPLC peptide
`isolation.
`
`Compared to previous surveys, pep-
`tide synthesis throughput per month in-
`creased significantly since 1987, but not
`since
`1989. Oligonucleotide synthesis
`throughput
`significantly increased in
`each survey and protein sequencing
`throughput
`increased relative to both
`earlier
`surveys. Amino acid analysis
`througltput was unchanged. Through-
`puts for other services were not available
`for either 198? or 1989.
`
`The numbers of runs per month per
`instrument showed the same rank as
`runs per month, except that the runs per
`month per instrument were highest for
`amino acid analysis (80)
`followed by
`DNA sequencing and oligonucleotide
`synthesis (60) (data not shown).
`Approximately 80% of the facilities
`offering peptide synthesis also offered
`
`synthetic peptide purification. In con-
`trast, only ca. 55% of the facilities ofl'er-
`ing oligonucleotide synthesis also offered
`oligo purification.
`Cycles per month were reported for
`only four services. These data were used
`to calculate the number of cycles per
`sample, which was 16 (SD, 6) for pep-
`tide and RNA synthesis and protein se-
`quencing, but
`31
`for oligonuclcotide
`synthesis (SD, 4-5) (data not shown).
`The quantities
`roduoed or required
`for the services 0 etecl by biotechnology
`facilities were surveyed. For protein se-
`quencing,
`fragmentation, and amino
`acid analysis,
`the amounts required
`were not
`significantly diiletent
`from
`1989. There was tremendous variation
`
`from facility to facility n:ga.rcling scales
`of syntheses or amounts of sample re-
`quired for each service. For 11 of 15 serv-
`ices the standard deviation exceeded the
`mean. It is not clear to what extent this
`reflects difierent purposes (i.e.,
`large-
`scale oligo syndtcsis vs. primer synthe-
`sis) or differences in instrumentation
`(supplementary Table 2).
`Regarding the turnaround times for
`services, all services were characterized
`by means of 2.9 to 8.7 days tumamund
`time,
`except peptide
`synthesis
`and
`purification, which had means of 20 and
`14 days,
`respectively. Relative to 1989,
`oligonuclootidc synthesis delivery times
`decreased slightly but significantly from
`4.3
`to
`3.5
`days. There were
`no
`significant changes in turnaround times
`for other services (supplementary Table
`2 .
`)The percentage of runs devoted to
`non-user runs plus methods develop-
`ment ranged from a low of 8% to more
`
`NEWS 8: FEATURES
`
`Vol. 7‘
`
`September I993
`
`
`
`Page 4 of 9
`
`

`
`than 45%. DNA synthesis had the
`lowest percentage, with peptide synthesis
`and purification, and template prepara-
`tion having percentages in the teens.
`Services with relatively high percentages
`of runs devoted to non-user runs plus
`methods development (from 30 to 35 %)
`were RNA synthesis, electroblotting,
`fragmentation, and carbohydrate analy-
`sis. Only mass spectrometry and capil-
`lary electrophoresis were more than
`40%. For each service, the percentage of
`runs devoted to non-user runs and the
`percentage of runs devoted to methods
`development individually were within a
`factor of two, except for RNA synthesis
`and electroblotting, where more than
`thnec-fourths of
`the
`total was
`for
`
`and carbohy-
`methods development,
`drate analysis where more than three-
`fourths of the total was from non-user
`runs (supplementary Table 3). These
`numbers may reflect
`the development
`stage of these technologies.
`Data were collected on the number of
`
`years that services have been offered and
`the number of principal invmtigators us-
`ing each service. No earlier data are
`available for comparison. All of the six
`major services have been oflered for ap-
`proximately ‘1- to 6 years. Recently in-
`troduced services, olfered for a median
`of 1 to 3 years, include RNA synthesis,
`DNA sequencing, carbohydrate analy-
`sis, and capillary electrophoresis (sup-
`plementary Table 4).
`The average number of principal in-
`vestigators using the major
`services
`ranged from a high of approximately 50
`for oligonucleotide synthesis and 4-0 for
`synthetic oligonucleotide purification to
`3 to 6 for carbohydrate analysis, capil-
`lary electrophoresis, RNA synthesis,
`HPLC, clccwoblotting, and fragmenta-
`
`including protein
`tion. Other services,
`and DNA sequencing, amino acid anal»
`ysis, and mass spectrometry are sup-
`ported by an intermediate number (10 to
`25) of principal
`investigators
`(sup-
`plementary Table 4).
`
`Personnel and space
`
`Based on the personnel data, the average
`core facility had approximately 4.1 staff.
`The total number of staff in 1992 in-
`creased by approximately 45% relative
`to 1987 and 1989. In an average facility,
`approximately 25% of the staff had a
`Ph.D., 20% a. M.S., 50% a B.S., and 5%
`or less had another degree (1989/1992
`only). This was essentially unchanged
`over the last 5 years.
`We compiled data on the percent
`effort devoted in total and by service by
`the director and all other personnel. The
`median effort for each service was less
`than 100%. This confirms that in most
`facilities an average individual perfonns
`more than one service. DNA sequencing
`and oligonucleotide synthesis received
`the most effort, with a median total
`effort of 80%. The median total effort
`for peptide synthesis and protein se-
`quencing was 50-60%. The least effort
`was spent on capillary electrophoresis
`with a median of 20% total effort in 23
`facilities. Except for administration,
`in
`which the director contributed a median
`of 20% effort relative to 18% for other
`personnel, and capillary electrophoresis
`the director contributed less than half of
`the effort of the other personnel in each
`service (data not shown).
`We calculated that each staff member
`was responsible for an average of 1.3 in-
`strument systems by dividing the 7.5 in-
`strument systems in an average core fa-
`
`TABLE 2. Space considerations in b:'am:fmn£agy facilities
`
`Space, sq. ft.
`
`Service
`
`Mean
`
`Peptide synthesis
`DNA synthesis
`Protein sequencing
`DNA sequencing
`HPLC
`Amino acid analysis
`Carbohydrate analysis
`Capillary electrophoresis
`Mass spectrometry
`Office
`Consultation
`
`160
`14-9
`176
`156
`152
`121
`115
`64
`156
`163
`93
`
`SD
`
`1+6
`14‘!-
`153
`116
`152
`103
`101
`64
`97
`134-
`77
`
`Range
`
`12-800
`10-612
`18-800
`15-400
`10-760
`6-600
`15-350
`6-300
`10-275
`
`1 5-800
`1 1-375
`
`Total
`‘P < 0.05 relative to 1989.
`
`20-4670
`888
`959
`'1’ < 0.01 relative to 1969.
`
`Vol. 7
`
`September 1993
`
`NEWS 64 FEATURES
`
`NEWS 8- FEATURES
`
`cility (Table 1) by the mean number of
`full-time personnel
`(4.1). This is
`the
`same as in 1989. This was consistent
`with the conclusion drawn from percent
`effort by service data that each person
`was responsible for more than one in-
`strument systemlservice.
`The space requirements of typical
`core facilities in total and by service are
`given in Table 2. On the average, these
`facilities used a total of 959 sq. ft., which
`includes laboratory, office, and consulta-
`tion space. Compared to 1939,
`there
`were no significant differences in space
`utilization for peptide or oligonucleotide
`synthesis, DNA sequencing or HPLC
`instrumentation, or office and consulta-
`tion space. However, the total space for
`amino acid analysis and for protein se-
`quencing decreased by approximately
`35%. The space (sq. ft.) allotted per in~
`strument also declined for amino acid
`analysis and protein sequencing. Protein
`sequencing, which in 1989 accounted for
`about 27% of the total available space in
`facilities that offered that service, uti-
`lized only 18% of total space in 1992. No
`significant
`increase in space allotment
`per instrument was observed for any
`purpose. No comparable data on space
`were available from 1987. It would ap-
`pear that in a typical facility instrument
`density has increased.
`For
`instrumentation not previously
`surveyed, the space requirement per in~
`strument was 60 sq. ft. for capillary elec-
`trophoresis and carbohydrate analysis
`and 160 sq. ft. for mass spectrometry.
`
`Biotechnology facilities: finances,
`charges, and costs
`
`An important measure of an institution's
`need for, use of, and support of a core
`facility is the size of the facilitfs annual
`operating
`budget. We
`report
`the
`finances of academic plus research insti-
`tutions because in only these Classes did
`a significant number of respondents pro-
`vide this information (Tlable 3). The
`average operating expenditure that in-
`cludes personnel, supplies, and instru-
`ment repair and maintenance, but not
`equipment purchases, was $250,000 for
`1992. That value compares to $197,000
`in 1989 and to $158,000 in 1987.
`The operational expenses of facilities
`at academic and research institutions is
`
`given in Table 3. The major expenditure
`was for staff, followed by supplies and
`reagents. Three- to fivefold lower levels
`of expenditure were for service contracts
`plus repairs or for depreciation. More
`than 80 facilities reported expenditures
`for the first
`three categories, whereas
`only 15 facilities reported depreciation of
`equipment as an expense. The dollar
`
`
`
`Page 5 of 9
`
`

`
`NEWS 8' FEATURES
`
`TABLE 3. Optmnbnai expauer and income sources all research and amdzmit biotecfinolagy facilities
`
`Expense
`
`Service contractsfrepairs
`Personnel
`Equipment depreciation
`Suppliesheagents
`Total
`
`Income source
`
`User fees
`Howard Hughes Med. Inst.
`Federal grants/contracts
`Other grantslcontracts
`Institutional support
`Total
`
`Mean
`
`$24,000
`$123,000
`$34,000
`$96,000
`$250,000
`
`$125,000
`$112,000
`$129,000
`$30,000
`$90,000
`$244,000
`
`SD
`
`$21,000
`$94,000
`$22,600
`$110,000
`$200.000
`
`$129,000
`$145,000
`$171,000
`$171,000
`$73,000
`$198,000
`
`N
`
`84
`81
`15
`85
`77
`
`Median
`
`$13,000
`$115,000
`$27,000
`$56,000
`$210,000
`
`$92,000
`$110,000
`$74,000
`$21,000
`$50,000
`$203,000
`
`Range
`
`$1,000—$l00,000
`-$13,000—$590,000
`$9,000-$100,000
`$5,000-$510,000
`I4-7,000—$958,000
`
`$3,000—$750,000
`$5.000-$334,000
`$5,000-$350,000
`$5,000—$665,000
`$2,000-$350,000
`$23,000—$920.000
`
`amounts per category and die percen-
`tages of expenditure per category were
`not
`significantly diflctent
`from 1989
`figures, mtcept for a 36% increase in the
`service
`contracts/repair
`category
`for
`1992 (P < 0.05). The total operating
`expenditure
`of
`$250,000 was
`not
`significantly different from the total in-
`come (Table 3).
`For a typical facility, the total funding
`and expenditure for capital equipment
`for 1992 was approximately $70,000.
`Surprisingly, capital equipment carpen-
`ditures decreased twofold from 1989 to
`1992 (P < 0.01). The most frequent (31
`of 4-3 facilities) source of capital equip-
`ment funds was the home institution,
`followed by federal or other grants and
`the Howard Hughes Medical Institute.
`The dollar amounts for funding for cap-
`ital equipment from these sources did
`not significantly difler from each other
`(data not shown).
`The total income from all sources for
`research plus academic facilities in 1992
`was $244,000 (SD, $l98,000, N = 79).
`
`This was not significantly difierent from
`the $194,000 income reported in 1989.
`User
`fees were the most consistent
`source of income for academic and
`research institutions. These fees con-
`
`tributed to the income of 70% (62 of 30)
`facilities that reported full financial de-
`tail. On average, user fees paid for 49%
`of facility operational expenses (Table 3).
`The percentage of cost recovery from
`user fees has increased from 41-7% in
`1989 and from 41% in 1987.
`Several diflerent funding sources were
`tapped to help facilities deal with budget
`deficits. By far the most common source
`of extra funds was the home institution
`(43 of 64 facilities). Aside from institu-
`tional support, one to live respondents
`reported the following methods of cover-
`ing deficits:
`I) funds from research
`grants, 2) contributions from dependent
`research PIOJOCIS, 3) Howard Hughes
`Medical Institute, 4) private grants or
`endowments, and 5) rollover deficit to
`the next year’s budget. ‘This was essen-
`tially unchanged from 1989.
`
`These increasing budgets and in-
`comes of biotechnology facilities did not
`reflect
`increased
`sulxidy
`from any
`source, but would appear to reflect,
`among other possibilities: I) increased
`cost
`recovery (see above), and 2) in-
`creased income from services. Calcu-
`lated income (calculated from through-
`put and charges) for the three services
`that provided the most income, namely,
`peptide synthesis, DNA synthesis, and
`protein sequencing, increased by 24 to
`90% or
`increased
`by
`$30,000
`to
`$100,000 per a.nnum over the last 5
`years. Income for amino acid analysis
`(the only other service tracked over the
`last 5 year period) decreased by ca. 50%
`or by $23,000 from 1989. In addition,
`user fee income from numerous newer
`services offered only for the last
`1
`to 3
`years added to the increased income.
`This would appear to indicate that the
`facilities are becoming more cost effec-
`tive as their throughput increases and
`they provide additional
`services. Of
`course, some of the t effectiveness
`
`TABLE 4-. In-house charge: for szrriices in itialeclznaiagy fuiiriier
`
`Set-up charges
`
`Per cycle charges
`
`Service
`
`Peptide synthesis
`Peptide purification
`DNA synthesis
`DNA purification
`RNA synthesis
`Protein sequencing
`DNA sequencing
`Template preparation
`Electroblotting
`Fragmentationlprotein
`HPLC peptide isolation
`Amino acid analysis
`Carbohydrate analysis
`Mass spectrometry
`‘outlier of 100.
`
`S1‘)
`
`$155
`$139
`$13
`$40
`$61
`$79
`$32
`$2
`$53
`$74
`$74
`$19
`$14
`148
`
`Range
`
`$10—750
`$10-525
`$4-70
`$1-175
`$l0—200
`38-350
`$l5—l25
`$5-10'
`$l5—200
`$10—250
`$l0—250
`$8—116
`$5—40
`325-133
`
`SD
`
`$12
`
`$1
`
`$4
`$10
`
`Range
`
`$6-60
`
`$2—5
`
`$2-17
`$3-50
`
`NEWS & FEATURES
`
`Vol. 7
`
`September 1993
`
`
`
`Page 6 of 9
`
`

`
`Service provided
`
`Cost‘
`mean (SD)
`
`Charge
`mean (SD)
`
`N
`
`$978(353)‘
`25 mer peptide synthesized
`31956006)”
`3186051)‘
`25 mer oligo synthesized
`s93(3o)“
`5140935)
`15 mer RNA synthesized
`$2s5(173)
`Amino acid analysis
`s35(19)'
`s7o(3s)‘
`Protein sequence (25 cycles)
`3371514)‘
`3-l27(252)‘
`DNA sequence
`H1(32)
`sszrss)
`‘Cost
`is defined as charge corrected for % cost recovery from user
`‘P -C 0.05 relative to
`fees of 41-9%.
`“P < 0.01 relative to 198?.
`‘P < 0.05 relative to I939.
`193?.
`‘P C 0.01 relative 10 I939.
`
`60
`55
`1 ‘2
`6+
`66
`8
`
` :%—— NEWS & FEATURES
`may also reflect lowered reagent costs
`TABLE 5. Carl and charge: for selected sewices at biotechraalog}-facilities
`being passed onto users.
`It is clear that few biotechnology facil-
`ities survive on user fees alone. Only
`four facilities reported user fees as their
`sole source of income, and only two fa-
`cilities collected enough fees to cover
`their annual expenses. The two facilities
`that supported themselves solely on user
`fees had incomes of $310,000 and
`$780,000. The services offered and the
`charges of these two facilities are consi-
`dered below.
`Of particular concern to users of cone
`facilities are the charges for services (Ta-
`ble 4-). Among those facilities of all types
`that operated on a fee-for-service basis,
`there was a large range in the percentage
`of total operating expenses that were
`recovered from user fees (see above),
`which at least in part explains the 2- to
`175-fold range in service charges shown
`in Table 4. In this series of surveys, this
`is
`the first
`time that we have distin-
`
`the increased percentage of cost recovery
`over the last 5 years (from 41% to 49%)
`indicate that core facility's
`increased
`efliciency
`or
`economy
`decreased
`charges,
`the latter perhaps related to
`both ecomonies and decreased reagent
`costs.
`
`The charges for a given service do not
`reflect the total costs for that service, as
`most facilities do not exist on user fee in-
`come alone. Therefore we have calcu-
`lated the cost of each service. This is
`defined as the charge corrected for the
`cost recovery from user fees. The cost of
`protein sequencing and peptide synthe-
`sis in 1992 did not significantly differ
`from that in 1987 or 1939. Amino acid
`
`while
`fluctuated,
`costs
`analysis
`oligonucleotide synthesis cost declined
`by 25% in 1992, after no significant
`change between 1989 and 1937.
`Of the most commonly provided serv-
`ices,
`the most expensive service for
`charges and costs remained peptide syn-
`thesis,
`followed by protein sequencing,
`RNA synthesis, oligonucleotide synthe-
`sis; then amino acid analysis and DNA
`sequencing.
`Of the two biotechnology facilities
`that were self supporting on user fees
`alone,
`one
`facility
`offered
`only
`oligonucleotide synthesis and purifica-
`tion and RNA synthesis. The remaining
`facility offered all of the services listed in
`Table 4-, except amino acid or carbohy-
`drate analysis, capillary electrophoresis,
`or mass spectrometry. The charges for
`services at the self-supporting facilities
`for the services listed in Table 5 were
`
`greater than the charges for the cor-
`responding service at an average facility,
`except for DNA sequencing. Because
`these two facilities are self-supporting,
`their charges equal
`their cost. Their
`costs were lower than the cost of cor-
`
`responding services at the average facil-
`ity for every service, except peptide syn-
`thesis and RNA synthesis. This suggests
`that they are self—supporting on user fees
`through eflicicncy and may support low
`levels of research and development.
`
`Service charges given in Table 4- and
`Table 5 were for users from within the
`host institution. Eighty-eight percent of
`the academic plus
`research facilities
`responded that
`they do accept users
`from outside their institution. Service
`
`charges were generally higher for users
`from “outside” institutions. Hence, 87
`respondents reported that
`they charge
`an outside user at an educational or
`
`institution 172% (140 SD) of
`nonprofit
`the in-house rate. The rate charged to
`commercial, outside users was 259%
`(221 SD). Both of these percentages are
`significantly
`higher
`than
`i.n
`1939,
`although the percentage of facilities ac-
`cepting orders outside of their institution
`is unchanged.
`
`CONCLUSIONS
`
`The data compiled from a. survey of 128
`core facilities provide a basis for estimat-
`ing the resources that might be needed
`to establish such a facility, the financial
`support that is likely to be required to
`keep it operating, and the technical
`capabilities that it might be expected to
`achieve.
`'
`
`As for technical capabilities, an aver-
`age facility might be expected to ofi'er at
`least five of the following six services:
`protei.n sequencing, amino acid analysis,
`peptide synthesis and isolation,
`frag-
`mentation of proteins, and DNA syn-
`thesis. Less than 25% of the core facili-
`ties
`that participated in this
`survey
`offered DNA sequencing, mass spec-
`trometry, capillary zone electrophoresis,
`or RNA synthesis, but the importance
`of
`these services
`is
`increasing. The
`monthly output of an average facility
`corresponds to 116 oligonucleotide syn-
`theses, 86 amino acid analyses, 67 DNA
`sequences, 35 protein sequencing runs,
`and 11 peptide syntheses. Turnaround
`times were 3 to 9 days for all services,
`except for peptide synthtsis and pl1l'l_fi(:n':l-
`tion, which had turnaround times of 14
`to 20 days.
`
`guished services for which a flat rate fee
`is charged from services for which the
`majority of the facilities levied a set-up
`charge plus a charge per cycle.
`The highest flat rate charge was for
`the purification of a synthetic peptide at
`approximately
`$200. The
`flat
`rate
`charges for mass spectrometry, HPLC
`peptide isolation, protein fragmenta-
`tionfisolation, and electroblotting cen-
`tered around $l00 per run. Carbohy-
`drate analysis was less expensive, but
`template preparation was the cheapest
`service offered at $8 per preparation.
`The services for which the majority of
`the facilities
`surveyed levy a set-up
`charge plus a charge per cycle include
`oligonucleotide, oligoribonuclcotide and
`peptide synthesis, and protein sequenc-
`ing (Table 4). Both the set-up charges
`and per cycle charges decreased in the
`following order: peptide synthesis, pro-
`tein sequencing, RNA synthesis, and
`oligonucleotide synthesis.
`Table 5 presents the charges for syn-
`thesis of 25 mer oligonuclcotide and
`peptide,
`for
`synthesis of a [5 mer
`oligoribonucleotide, and for 25 cycles of
`protein sequencing. These data are
`compared with available data from the
`1989 and 1987 surveys. The charge for
`synthesis of a 25 mer peptide and for 25
`cycles
`of protein
`sequencing have
`declined by 36% and 28%, respectively,
`since 1987. Amino acid analysis charges
`have fluctuated slightly over the last 5
`years. Oligonucleotide synthesis charges
`have
`strikingly declined, with 1992
`charges being 47% and 74% of 1987
`and 1989 charges, respectively. No data
`for DNA sequencing charges are availa-
`ble from earlier