At the end of the year 2014, Van Noorden et al. published an interesting analysis in the journal Nature entitled “The top 100 papers”, in which the 100 most cited research of all time were described [1]. Most of the readers of Clinical Chemistry and Laboratory Medicine would now argue that this has probably little to do with our education, expertise and daily activities, at least until exploring the full list of papers. Despite the fact that the vast majority of these articles deal with topics of biology and medicine, eight papers in the “top 10” describe laboratory methods or applications (Table 1). Most of these articles should be regarded as milestones, providing essential contributions to development and evolution of modern laboratory science. Indeed, the eldest of us can recall using the Lowry and Bradford techniques for measuring protein extracts for both routine and research applications, transferring proteins from polyacrylamide gels to nitrocellulose sheets according to the procedure of Towbin et al., or even analyzing genetic material with techniques based on the original method described by Sanger and Chomczynski. Even the Laemmli buffer, described in the second most cited paper, has represented a vital refinement of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for separating proteins according to their relative electrophoretic mobility.
Mostly cited scientific papers of all time (up to the year 2014), according to Van Noorden et al. [1].
| 1. | Lowry OH, et al. Protein measurement with the folin phenol reagent. J Biol Chem, 1951. |
| 2. | Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970. |
| 3. | Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 1976. |
| 4. | Sanger F, et al. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA, 1977. |
| 5. | Chomczynski P. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem, 1987. |
| 6. | Towbin H, et al. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA, 1979. |
| 7. | Lee C, et al. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B, 1988. |
| 8. | Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys, 1993. |
| 9. | Folch J, et al. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem, 1957. |
| 10. | Thompson JD, et al. Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res, 1994. |
Articles dealing with laboratory techniques are in bold.
Although it is unlikely that anybody will be ever able to truthfully appraise the contribution of diagnostic testing to the clinical reasoning and the therapeutic management, it is now undeniable that laboratory medicine provides a kind of information that increasingly supports (and occasionally replaces) the clinical judgment. The remarkable progress in genetics, genomics and other “omics” experienced in the last decades have enabled a paradigmatic change in the role of laboratory medicine, leading the way to enhanced personalized health care and disease prevention based on the identification of risk factors and more effective biomarkers [2, 3]. Crossing the boundaries from research to clinical application requires standardization and harmonization of pre-, intra- and post-analytical issues, and laboratory professionals must play an active role in this enterprise [4–6]. In spite of this bright future, the daily scenario is actually dramatic. Squeezed between an unprecedented economic crisis and shortage of vocations around the globe, the ecosystem of laboratory medicine is increasingly seen as a commodity by most stakeholders [7]. Indeed, clinical laboratories are categorized among the healthcare services, and in particular among the 10 health care services that produce tangible health benefices [8]. However, what is seemingly unclear to certain clinicians, hospital administrators, policymakers and even to some colleagues, is that the laboratory is “at service”, but not “a servant”. The valuable analysis published by Van Noorden and colleagues provides – maybe unconsciously – a clear support to this concept, wherein no major advance in science and medicine has been (and will likely be) possible without the use of laboratory techniques (Table 1). It is also understandable that some wicked politics of closure or irrational consolidation of clinical laboratories would not be effective to generate favorable revenues for a bankrupt health care, especially when economic analyses are the main drivers for reorganization or networking. This is clearly true if one considers that the expenditure for in vitro diagnostic testing represents <2% (at best) of the total budget of the healthcare systems worldwide [9, 10].
Thanks to the analysis of Van Noorden et al., we can strengthen the concept that the contribution of laboratory medicine is virtually unreplaceable in science (and medicine)… yet many (inside and outside the laboratory) seem to ignore it.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Van Noorden R, Maher B, Nuzzo R. The top 100 papers. Nature 2014;514:550–3.10.1038/514550aSearch in Google Scholar PubMed
2. Pasche B, Absher D. Whole-genome sequencing: a step closer to personalized medicine. J Am Med Assoc 2011;305:1596–7.10.1001/jama.2011.484Search in Google Scholar PubMed
3. Khoury MJ, Gwinn M, Yoon PW, Dowling N, Moore CA, Bradley L. The continuum of translation research in genomic medicine: how can we accelerate the appropriate integration of human genome discoveries into health care and disease prevention? Genet Med 2007;9:665–74.10.1097/GIM.0b013e31815699d0Search in Google Scholar PubMed
4. Plebani M. Evaluating laboratory diagnostic tests and translational research. Clin Chem Lab Med 2010;48:983–8.10.1515/CCLM.2010.188Search in Google Scholar PubMed
5. Plebani M, Marincola FM. Research translation: a new frontier for clinical laboratories. Clin Chem Lab Med 2006;44:1303–12.10.1515/CCLM.2006.238Search in Google Scholar PubMed
6. Plebani M, Laposata M. Translational research involving new biomarkers of disease: a leading role for pathologists. Am J Clin Pathol 2006;126:169–71.10.1309/5GHY0VCWBUY58EFXSearch in Google Scholar
7. Plebani M. Clinical laboratories: production industry or medical services? Clin Chem Lab Med 2015;53:995–1004.10.1515/cclm-2014-1007Search in Google Scholar PubMed
8. Institute of Medicine Committee on defining and Revising Essential Health Benefits Package for Qualified Health Plans. Report on essential health benefits: balancing coverage and costs, Washington DC, October 2011 Available from: http://iom.edu/~/media/Files/Report%20Files/2011/Essential-Health-Benefits-Balancing-Coverage-and-Cost/Essential%20Health%20Benefits%20RB_FINAL.pdf. Accessed 26 July, 2015.Search in Google Scholar
9. Barletta G, Zaninotto M, Faggian D, Plebani M. Shop for quality or quantity? Volumes and costs in clinical laboratories. Clin Chem Lab Med 2013;51:295–301.10.1515/cclm-2012-0415Search in Google Scholar PubMed
10. Lippi G, Mattiuzzi C. Testing volume is not synonymous of cost, value and efficacy in laboratory diagnostics. Clin Chem Lab Med 2013;51:243–5.10.1515/cclm-2012-0502Search in Google Scholar PubMed
©2015 by De Gruyter
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- Atypical hemolytic uremic syndrome: from diagnosis to treatment
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- Congress Abstracts
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- 47th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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Articles in the same Issue
- Frontmatter
- Editorials
- Laboratory medicine does matter in science (and medicine)… yet many seem to ignore it
- The standardization of the urine albumin assays: no longer deferrable
- Reviews
- The role of telomeres and vitamin D in cellular aging and age-related diseases
- Atypical hemolytic uremic syndrome: from diagnosis to treatment
- Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease
- EFLM Opinion Paper
- How to assess the quality of your analytical method?
- Genetics and Molecular Diagnostics
- Validation of CFTR intronic variants identified during cystic fibrosis population screening by a minigene splicing assay
- General Clinical Chemistry and Laboratory Medicine
- Uncertainty in measurement for 43 biochemistry, immunoassay, and hemostasis routine analytes evaluated by a method using only external quality assessment data
- A study examining the bias of albumin and albumin/creatinine ratio measurements in urine
- National survey on appropriateness of clinical biochemistry reporting in China
- Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine
- Determination of 21-hydroxylase autoantibodies: inter-laboratory concordance in the Euradrenal International Serum Exchange Program
- Value of a commercial kit for detecting anti-C1q autoantibodies and correlation with immunological and clinical activity of lupus nephritis
- Comparison of the bead-based simultaneous analysis of specific platelet antibodies assay (SASPA) and Pak Lx Luminex technology with the monoclonal antibody immobilization of platelet antigens assay (MAIPA) to detect platelet alloantibodies
- Measurement of the inflammatory response in the early postoperative period after hip and knee arthroplasty
- Whole blood thromboelastometry profiles in women with preeclampsia
- Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis
- Reference Values and Biological Variations
- Reference ranges of serum bile acids in children and adolescents
- Infectious Diseases
- Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection
- Cardiovascular Diseases
- Head-to-head comparison of 10 natriuretic peptide assays
- Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors
- Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death
- Identification of molecular species of oxidized triglyceride in plasma and its distribution in lipoproteins
- A new formula for estimation of low-density lipoprotein cholesterol in an ethnic Chinese population
- Letter to the Editors
- Laboratory medicine: let’s say it is the mirror of science (and medicine)
- The economic burden of hemolysis
- Acute effects of conventional and extended hemodialysis and hemodiafiltration on high-sensitivity cardiac troponins
- Cuvette carryover with the gentamicin assay on the Beckman AU480 analyser
- Comparison study of two commercially available methods for the determination of golimumab and anti-golimumab antibody levels in patients with rheumatic diseases
- Automated alkaline-pH electrophoresis followed by densitometry does not correlate with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins
- Progression from light chain myeloma to secondary plasma cell leukemia accompanied by peripheral blood eosinophilia
- Harmonization of results has not been fully achieved for serum immunoglobulin measurements
- The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
- Comparison of nucleated red blood cell count with four commercial hematological analyzers
- Reply to: The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
- Congress Abstracts
- Congress of Clinical Chemistry and Laboratory Medicine
- 47th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
- 15th EFLM Continuous Postgraduate Course in Clinical Chemistry and Laboratory Medicine