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Tweeting on the 10th Annual Personalized Medicine Conference at the Harvard Medical School, November 12-13, 2014

Posted in Academic Publishing, Conference Coverage with Social Media, Personalized and Precision Medicine & Genomic Research, Scientific & Biotech Conferences: Press Coverage on November 16, 2014| Leave a Comment »

Tweeting on the 10th Annual Personalized Medicine Conference at the Harvard Medical School, November 12-13, 2014

@HarvardPMConf, #PMConf, @SachsAssociates, @AVIVA1950, @pharma_BI 

@pharma_BI

LEADERS IN PHARMACEUTICAL BUSINESS INTELLIGENCE

@pharma_BI @Pharma_BI · 6m6 minutes ago

Content of the Presentations at the 10th Annual Personalized Medicine Conference at the… http://lnkd.in/dHC4Gsz 

@pharma_BI @Pharma_BI · 8m8 minutes ago

Presentations: Personalized Medicine Conference @HMS http://wp.me/p2kEDv-6Xb  @Pharma_BI,@HarvardPMConf,#PMConf,@SachsAssociates,@AVIVA1950

@pharma_BI @Pharma_BI · 15h15 hours ago

Researchers silence leading cancer-causing gene http://lnkd.in/d3CKYdh 

@pharma_BI @Pharma_BI · Nov 14

The hunt for “unexpected genetic heroes” http://lnkd.in/dSGTV7i 

@pharma_BI @Pharma_BI · Nov 14

Researchers test cancer treatments on patients’ own cells http://lnkd.in/dbXt8Jb e

@pharma_BI @Pharma_BI · Nov 13

2:15PM 11/13/2014 – Panel Discussion Reimbursement/Regulation @10th Annual Personalized… http://lnkd.in/dsJrBQm 

@pharma_BI @Pharma_BI · Nov 13

2:15PM 11/13/2014 – Panel Discussion Reimbursement/Regulation @10th Annual Personalized Medicine Conference at the… http://wp.me/p2kEDv-6Jt 

@pharma_BI @Pharma_BI · Nov 13

1:00PM 11/13/2014 – Panel Discussion Genomics in Prenatal and Childhood Disorders @10th Annual… http://lnkd.in/dciqQBe 

@pharma_BI @Pharma_BI · Nov 13

1:00PM 11/13/2014 – Panel Discussion Genomics in Prenatal and Childhood Disorders @10th Annual Personalized… http://wp.me/p2kEDv-6Jr 

@pharma_BI @Pharma_BI · Nov 13

11:30AM 11/13/2014 – Role of Genetics and Genomics in Pharmaceutical Development @10th Annual… http://lnkd.in/d7NSE4R 

@pharma_BI @Pharma_BI · Nov 13

11:30AM 11/13/2014 – Role of Genetics and Genomics in Pharmaceutical Development @10th Annual Personalized Medicine… http://wp.me/p2kEDv-6Jp 

@pharma_BI @Pharma_BI · Nov 13

10:15AM 11/13/2014 – Panel Discussion — IT/Big Data @10th Annual Personalized Medicine… http://lnkd.in/dJHZxzB 

@pharma_BI @Pharma_BI · Nov 13

10:15AM 11/13/2014 – Panel Discussion — IT/Big Data @10th Annual Personalized Medicine Conference at the Harvard… http://wp.me/p2kEDv-6Jn 

 

@pharma_BI @Pharma_BI · Nov 13

8:30AM 11/13/2014 – Harvard Business School Case Study: 23andMe @10th Annual Personalized… http://lnkd.in/d_D44HG 

@pharma_BI @Pharma_BI · Nov 13

8:30AM 11/13/2014 – Harvard Business School Case Study: 23andMe @10th Annual Personalized Medicine Conference at… http://wp.me/p2kEDv-6Jl 

@pharma_BI @Pharma_BI · Nov 13

8:00AM 11/13/2014 – Welcome from Gary Gottlieb, M.D., Partners HealthCare @10th Annual… http://lnkd.in/dBhznW7 

@pharma_BI @Pharma_BI · Nov 13

8:00AM 11/13/2014 – Welcome from Gary Gottlieb, M.D., Partners HealthCare @10th Annual Personalized Medicine… http://wp.me/p2kEDv-6Jj 

11/12/2014

@pharma_BI @Pharma_BI · Nov 12

4:00PM 11/12/2014 – Panel Discussion Novel Approaches to Personalized Medicine @10th Annual… http://lnkd.in/daUaWmJ 

@pharma_BI @Pharma_BI · Nov 12

4:00PM 11/12/2014 – Panel Discussion Novel Approaches to Personalized Medicine @10th Annual Personalized Medicine… http://wp.me/p2kEDv-6Jh 

@pharma_BI @Pharma_BI · Nov 12

3:15PM 11/12/2014 – Discussion Complex Disorders @10th Annual Personalized Medicine Conference… http://lnkd.in/dFw8PFj 

@pharma_BI @Pharma_BI · Nov 12

3:15PM 11/12/2014 – Discussion Complex Disorders @10th Annual Personalized Medicine Conference at the Harvard… http://wp.me/p2kEDv-6Jf 

@pharma_BI @Pharma_BI · Nov 12

1:45PM 11/12/2014 – Panel Discussion – Oncology @10th Annual Personalized Medicine Conference… http://lnkd.in/dfuA33j 

@pharma_BI @Pharma_BI · Nov 12

1:45PM 11/12/2014 – Panel Discussion – Oncology @10th Annual Personalized Medicine Conference at the Harvard… http://wp.me/p2kEDv-6Jd 

@pharma_BI @Pharma_BI · Nov 12

1:15PM 11/12/2014 – Keynote Speaker – International Genetics Health and Disease @10th Annual… http://lnkd.in/dxGYNkd 

@pharma_BI @Pharma_BI · Nov 12

1:15PM 11/12/2014 – Keynote Speaker – International Genetics Health and Disease @10th Annual Personalized Medicine… http://wp.me/p2kEDv-6Jb 

@pharma_BI @Pharma_BI · Nov 12

11:30AM 11/12/2014 – Personalized Medicine Coalition Award & Award Recipient Speech @10th… http://lnkd.in/dj6kNbv 

@pharma_BI @Pharma_BI · Nov 12

11:30AM 11/12/2014 – Personalized Medicine Coalition Award & Award Recipient Speech @10th Annual Personalized… http://wp.me/p2kEDv-6J7 

@pharma_BI @Pharma_BI · Nov 12

11:00AM 11/12/2014 – Keynote Speaker – Past, Present and Future of Personalized Medicine @10th… http://lnkd.in/dwuk4Cn 

@pharma_BI @Pharma_BI · Nov 12

11:00AM 11/12/2014 – Keynote Speaker – Past, Present and Future of Personalized Medicine @10th Annual Personalized… http://wp.me/p2kEDv-6J5 

@pharma_BI @Pharma_BI · Nov 12

9:20AM 11/12/2014 – Panel Discussion – Genomic Technologies @10th Annual Personalized Medicine… http://lnkd.in/dWKdAqi 

@pharma_BI @Pharma_BI · Nov 12

9:20AM 11/12/2014 – Panel Discussion – Genomic Technologies @10th Annual Personalized Medicine Conference at the… http://wp.me/p2kEDv-6J3 

@pharma_BI @Pharma_BI · Nov 12

8:50AM 11/12/2014 – Keynote Speaker – CEO, American Medical Association @10th Annual… http://lnkd.in/ds72S6i 

@pharma_BI @Pharma_BI · Nov 12

8:50AM 11/12/2014 – Keynote Speaker – CEO, American Medical Association @10th Annual Personalized Medicine… http://wp.me/p2kEDv-6J1 

More

@pharma_BI @Pharma_BI · Nov 12

8:20AM 11/12/2014 – Special Guest Keynote Speaker – The Future of Personalized Medicine @10th… http://lnkd.in/dcEN4FJ 

@pharma_BI @Pharma_BI · Nov 12

8:20AM 11/12/2014 – Special Guest Keynote Speaker – The Future of Personalized Medicine @10th Annual Personalized… http://wp.me/p2kEDv-6IZ 

@pharma_BI @Pharma_BI · Nov 12

8:00AM 11/12/2014 – Welcome & Opening Remarks @10th Annual Personalized Medicine Conference at… http://lnkd.in/d_td-SS 

@pharma_BI @Pharma_BI · Nov 12

8:00AM 11/12/2014 – Welcome & Opening Remarks @10th Annual Personalized Medicine Conference at the Harvard Medical… http://wp.me/p2kEDv-6IX 

@pharma_BI @Pharma_BI · Nov 11

Hashtags and Twitter Handles for 10th Annual Personalized Medicine at Harvard Medical School, 11/12 – 11/13/2014 http://wp.me/p2kEDv-6V9 

@AVIVA1950

Aviva Lev-Ari ‏@AVIVA1950  Nov 13

11:30AM 11/13/2014 – Genetics/Genomics in Pharmaceutical Development @10th Annual Perso… http://wp.me/p2kEDv-6Jp  via @Pharma_BI, @AVIVA1950

• Aviva Lev-Ari ‏@AVIVA1950  Nov 13

  8:30AM 11/13/2014 – HBS Case Study: 23andMe @10th Annual Personalized Medicine … http://wp.me/p2kEDv-6Jl  via @Pharma_BI, @AVIVA1950

• Aviva Lev-Ari ‏@AVIVA1950  Nov 13

  8:00AM 11/13/2014 – Gary Gottlieb, M.D., Partners HealthCare @10th Annual Personalize… http://wp.me/p2kEDv-6Jj  via @Pharma_BI,@AVIVA1950

• In reply to Aviva Lev-Ari

  Stephen J Williams ‏@StephenJWillia2  Nov 12Philadelphia, PA

  @AVIVA1950 I have all done including 11:00 Mirella talk tweeted to @Pharma_BI and to conference tags and handles

• Stephen J Williams ‏@StephenJWillia2  Nov 12

  @AVIVA1950 @Pharma_BI @HarvardPMConf meeting notes form #PMConf up on http://www.pharmaceuticalintelligence.com  @FierceBiotech @PharmaNews

  View conversation

1. Aviva Lev-Ari ‏@AVIVA1950  Nov 13

   2:15PM 11/13/2014 – Reimbursement/Regulation@10th Annual Personalized Medicine http://wp.me/p2kEDv-6Jt  via @Pharma_BI,@HarvardPMConf, #PMConf

    

   Aviva Lev-Ari ‏@AVIVA1950  Nov 12

   11:30AM 11/12/2014 – PM Coalition Award & Recipient Speech @10th Annual P… http://wp.me/p2kEDv-6J7  via @Pharma_BI @HarvardPMConf #PMConf

Results for @HarvardPMConf

1. @pharma_BI ‏@Pharma_BI  49m49 minutes ago

   Presentations: Personalized Medicine Conference @HMS http://wp.me/p2kEDv-6Xb  @Pharma_BI,@HarvardPMConf,#PMConf,@SachsAssociates,@AVIVA1950

2. Stephen J Williams ‏@StephenJWillia2  Nov 13

   Panel Discussion #Genomics in Prenatal & #Childhood #Disorders @HarvardPMConf http://wp.me/p2kEDv-6Jr  via @Pharma_BI #PMConf @MedscapePeds

3. Stephen J Williams ‏@StephenJWillia2  Nov 13

   Great #personalizedmedicine #conference @HarvardPMConf ! Great #Socialmedia Kudos to all #PMConf! Annotated notes @Pharma_BI & our site

   1. 

      Aviva Lev-Ari ‏@AVIVA1950  Nov 13

      2:15PM 11/13/2014 – Reimbursement/Regulation @10th Annual Personalized Medicine http://wp.me/p2kEDv-6Jt  via @Pharma_BI,@HarvardPMConf,#PMConf

   2. Aviva Lev-Ari ‏@AVIVA1950  Nov 13

      2:15PM 11/13/2014 – Reimbursement/Regulation@10th Annual Personalized Medicine http://wp.me/p2kEDv-6Jt  via @Pharma_BI,@HarvardPMConf, #PMConf

      1. Stephen J Williams ‏@StephenJWillia2  Nov 13

         For Annotated @HarvardPMConf meeting notes please see http://pharmaceuticalintelligence.com/  from @Pharma_BI #PMConf

         1. Stephen J Williams ‏@StephenJWillia2  Nov 13

            How #pharma uses #genomics: @LillyHealth on #Alzheimers & #oncology @HarvardPMConf http://wp.me/p2kEDv-6Jp  via @Pharma_BI #PMConf @PharmaNews

         1. Aviva Lev-Ari ‏@AVIVA1950  Nov 13

            1:00PM 11/13/2014 – Genomics: Prenatal/Childhood Disorders @10th Annual Per http://wp.me/p2kEDv-6Jr  via @Pharma_BI,@HarvardPMConf, #PMConf

         1. Stephen J Williams ‏@StephenJWillia2  Nov 13

            Notes @HarvardPMConf Prof Hammermesh @HarvardHBS reviews @23andMe, #innovation & #HealthPolicy http://wp.me/p2kEDv-6Jl  via @Pharma_BI #PMConf

         2. Aviva Lev-Ari ‏@AVIVA1950  Nov 13

            11:30AM 11/13/2014 – Genomics in Pharmaceutical Development@10th Annual Perso… http://wp.me/p2kEDv-6Jp  via @Pharma_BI, @HarvardPMConf,#PMConf

            1. Aviva Lev-Ari ‏@AVIVA1950  Nov 13

               10:15AM 11/13/2014 – IT/Big Data 10th Annual Personalized Medicine Conferenc http://wp.me/p2kEDv-6Jn  via @Pharma_BI, @HarvardPMConf, #PMConf

            1. Stephen J Williams ‏@StephenJWillia2  Nov 12

               Panel Discussion by #genomics #startups – #venturecapital on rise! http://wp.me/p2kEDv-6Jh  via @Pharma_BI #PMConf @HarvardPMConf #investment

            2. Stephen J Williams ‏@StephenJWillia2  Nov 12

               #Cancer experts discuss their concerns of #personalizedmedicine @HarvardPMConf to #endcancer http://wp.me/p2kEDv-6Jd  via @Pharma_BI #PMConf

            1. Stephen J Williams ‏@StephenJWillia2  Nov 12

               What’s the #genomics strategy for Complex #psychriatic Disorders? @HarvardPMConf http://wp.me/p2kEDv-6Jf  via @Pharma_BI #PMConf #merck

               1. Aviva Lev-Ari ‏@AVIVA1950  Nov 12

                  4:00PM 11/12/2014 – Novel Approaches to Personalized Medicine @10th Persona… http://wp.me/p2kEDv-6Jh  via @Pharma_BI @HarvardPMConf #PMConf

               1. Aviva Lev-Ari ‏@AVIVA1950  Nov 12

                  3:15PM 11/12/2014 – Complex Disorders @10th Annual Personalized Medicine http://wp.me/p2kEDv-6Jf  via @Pharma_BI @HarvardPMConf #PMConf

               Aviva Lev-Ari ‏@AVIVA1950  Nov 12

               1:45PM 11/12/2014 – Panel Oncology @10th Annual Personalized Medicine http://wp.me/p2kEDv-6Jd  via @Pharma_BI @HarvardPMConf #PMConf

               1. Aviva Lev-Ari ‏@AVIVA1950  Nov 12

                  1:15PM 11/12/2014 – International Genetics Health&Disease @10th Annual Person… http://wp.me/p2kEDv-6Jb  via @Pharma_BI @HarvardPMConf #PMConf

                  Stephen J Williams ‏@StephenJWillia2  Nov 12

                  To Follow Meeting Notes of #personalizedmedicine @HarvardPMConf see http://wp.me/p2kEDv-6V9  via @pharma_BI #PMConf

                  

               1. Stephen J Williams ‏@StephenJWillia2  Nov 11

                  Follow the 10th Annual #personalizedmedicine Conference Live @harvardmed use @HarvardPMConf or #PMConf http://wp.me/p2kEDv-6V9  via @Pharma_BI

 

Results for #PMConf

 

@pharma_BI ‏@Pharma_BI  1h1 hour ago

Presentations: Personalized Medicine Conference @HMS http://wp.me/p2kEDv-6Xb  @Pharma_BI,@HarvardPMConf,#PMConf,@SachsAssociates,@AVIVA1950

Stephen J Williams ‏@StephenJWillia2  Nov 13

Importance of #healthinsurance #healthpolicy & #ACA for #personalizedmedicine? http://wp.me/p2kEDv-6Jt  via @Pharma_BI #PMConf #patientchat

• Stephen J Williams ‏@StephenJWillia2  Nov 13

  Panel Discussion #Genomics in Prenatal & #Childhood #Disorders @HarvardPMConf http://wp.me/p2kEDv-6Jr  via @Pharma_BI #PMConf @MedscapePeds

• Stephen J Williams ‏@StephenJWillia2  Nov 13

  Great #personalizedmedicine #conference @HarvardPMConf ! Great #Socialmedia Kudos to all #PMConf! Annotated notes @Pharma_BI & our site

Aviva Lev-Ari ‏@AVIVA1950  Nov 13

2:15PM 11/13/2014 – Reimbursement/Regulation @10th Annual Personalized Medicine http://wp.me/p2kEDv-6Jt  via @Pharma_BI,@HarvardPMConf,#PMConf

1. Stephen J Williams ‏@StephenJWillia2  Nov 13

   For Annotated @HarvardPMConf meeting notes please see http://pharmaceuticalintelligence.com/  from @Pharma_BI #PMConf

1. Stephen J Williams ‏@StephenJWillia2  Nov 13

   How #pharma uses #genomics: @LillyHealth on #Alzheimers & #oncology @HarvardPMConf http://wp.me/p2kEDv-6Jp  via @Pharma_BI #PMConf @PharmaNews

Aviva Lev-Ari ‏@AVIVA1950  Nov 13

1:00PM 11/13/2014 – Genomics: Prenatal/Childhood Disorders @10th Annual Per http://wp.me/p2kEDv-6Jr  via @Pharma_BI,@HarvardPMConf, #PMConf

2. Stephen J Williams ‏@StephenJWillia2  Nov 13

   Notes: #BigData #health #technology in #cancer #bioinformatics #genetictesting @HarvardPMConfhttp://wp.me/p2kEDv-6Jn via @Pharma_BI #PMConf

   1. Aviva Lev-Ari ‏@AVIVA1950  Nov 13

   2. 8:30AM 11/13/2014 – HBS Case Study: 23andMe @10th Annual Personalized Medicine … http://wp.me/p2kEDv-6Jl  via@Pharma_BI,@HarvardPMConf,#PMConf

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Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

Posted in Diagnostic Immunology, Disease Biology on November 16, 2014| Leave a Comment »

Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

Author and Curator: Larry H Bernstein, MD, FCAP

Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present

http://pharmaceuticalintelligence.com/2014/11/16/diagnostics-industry-and-drug-development-in-the-genomics-era-mid-80s-to-present/

Emergence of an IVD Clinical Automated Diagnostics Industry

Why tests are ordered

1. Screening
2. Diagnosis
3. Monitoring

Historical Perspective

Part 1: The early 20th Century

Case in point 1: Arterial Blood Gases.  Van Slyke. National Academy of Sciences.

The test is used to determine the pH of the blood, the partial pressure of carbon dioxide and oxygen, and the bicarbonate level. Many blood gas analyzers will also report concentrations of lactate, hemoglobin, several electrolytes, oxyhemoglobin, carboxyhemoglobin and methemoglobin. ABG testing is mainly used in pulmonology and critical care medicine to determine gas exchange which reflect gas exchange across the alveolar-capillary membrane.

DONALD DEXTER VAN SLYKE died on May 4, 1971, after a long and productive career that spanned three generations of biochemists and physicians. He left behind not only a bibliography of 317 journal publications and 5 books, but also more than 100 persons who had worked with him and distinguished themselves in biochemistry and academic medicine. His doctoral thesis, with Gomberg at University of Michigan was published in the Journal of the American Chemical Society in 1907.  Van Slyke received an invitation from Dr. Simon Flexner, Director of the Rockefeller Institute, to come to New York for an interview. In 1911 he spent a year in Berlin with Emil Fischer, who was then the leading chemist of the scientific world. He was particularly impressed by Fischer’s performing all laboratory operations quantitatively —a procedure Van followed throughout his life. Prior to going to Berlin, he published the  classic nitrous acid method for the quantitative determination of primary aliphatic amino groups,  the first of the many gasometric procedures devised by Van Slyke, and made possible the determination of amino acids. It was the primary method used to study amino acid composition of proteins for years before chromatography. Thus, his first seven postdoctoral years were centered around the development of better methodology for protein composition and amino acid metabolism.

With his colleague G. M. Meyer, he first demonstrated that amino acids, liberated during digestion in the intestine, are absorbed into the bloodstream, that they are removed by the tissues, and that the liver alone possesses the ability to convert the amino acid nitrogen into urea.  From the study of the kinetics of urease action, Van Slyke and Cullen developed equations that depended upon two reactions: (1) the combination of enzyme and substrate in stoichiometric proportions and (2) the reaction of the combination into the end products. Published in 1914, this formulation, involving two velocity constants, was similar to that arrived at contemporaneously by Michaelis and Menten in Germany in 1913.

He transferred to the Rockefeller Institute’s Hospital in 2013, under Dr. Rufus Cole, where “Men who were studying disease clinically had the right to go as deeply into its fundamental nature as their training allowed, and in the Rockefeller Institute’s Hospital every man who was caring for patients should also be engaged in more fundamental study”.  The study of diabetes was already under way by Dr. F. M. Allen, but patients inevitably died of acidosis.  Van Slyke reasoned that if incomplete oxidation of fatty acids in the body led to the accumulation of acetoacetic and beta-hydroxybutyric acids in the blood, then a reaction would result between these acids and the bicarbonate ions that would lead to a lower than-normal bicarbonate concentration in blood plasma. The problem thus became one of devising an analytical method that would permit the quantitative determination of bicarbonate concentration in small amounts of blood plasma.  He ingeniously devised a volumetric glass apparatus that was easy to use and required less than ten minutes for the determination of the total carbon dioxide in one cubic centimeter of plasma.  It also was soon found to be an excellent apparatus by which to determine blood oxygen concentrations, thus leading to measurements of the percentage saturation of blood hemoglobin with oxygen. This found extensive application in the study of respiratory diseases, such as pneumonia and tuberculosis. It also led to the quantitative study of cyanosis and a monograph on the subject by C. Lundsgaard and Van Slyke.

In all, Van Slyke and his colleagues published twenty-one papers under the general title “Studies of Acidosis,” beginning in 1917 and ending in 1934. They included not only chemical manifestations of acidosis, but Van Slyke, in No. 17 of the series (1921), elaborated and expanded the subject to describe in chemical terms the normal and abnormal variations in the acid-base balance of the blood. This was a landmark in understanding acid-base balance pathology.  Within seven years after Van moved to the Hospital, he had published a total of fifty-three papers, thirty-three of them coauthored with clinical colleagues.

In 1920, Van Slyke and his colleagues undertook a comprehensive investigation of gas and electrolyte equilibria in blood. McLean and Henderson at Harvard had made preliminary studies of blood as a physico-chemical system, but realized that Van Slyke and his colleagues at the Rockefeller Hospital had superior techniques and the facilities necessary for such an undertaking. A collaboration thereupon began between the two laboratories, which resulted in rapid progress toward an exact physico-chemical description of the role of hemoglobin in the transport of oxygen and carbon dioxide, of the distribution of diffusible ions and water between erythrocytes and plasma,
and of factors such as degree of oxygenation of hemoglobin and hydrogen ion concentration that modified these distributions. In this Van Slyke revised his volumetric gas analysis apparatus into a manometric method.  The manometric apparatus proved to give results that were from five to ten times more accurate.

A series of papers on the CO2 titration curves of oxy- and deoxyhemoglobin, of oxygenated and reduced whole blood, and of blood subjected to different degrees of oxygenation and on the distribution of diffusible ions in blood resulted.  These developed equations that predicted the change in distribution of water and diffusible ions between blood plasma and blood cells when there was a change in pH of the oxygenated blood. A significant contribution of Van Slyke and his colleagues was the application of the Gibbs-Donnan Law to the blood—regarded as a two-phase system, in which one phase (the erythrocytes) contained a high concentration of nondiffusible negative ions, i.e., those associated with hemoglobin, and cations, which were not freely exchaThe importance of Vanngeable between cells and plasma. By changing the pH through varying the CO2 tension, the concentration of negative hemoglobin charges changed in a predictable amount. This, in turn, changed the distribution of diffusible anions such as Cl” and HCO3″ in order to restore the Gibbs-Donnan equilibrium. Redistribution of water occurred to restore osmotic equilibrium. The experimental results confirmed the predictions of the equations.

As a spin-off from the physico-chemical study of the blood, Van undertook, in 1922, to put the concept of buffer value of weak electrolytes on a mathematically exact basis.
This proved to be useful in determining buffer values of mixed, polyvalent, and amphoteric electrolytes, and put the understanding of buffering on a quantitative basis. A
monograph in Medicine entitled “Observation on the Courses of Different Types of Bright’s Disease, and on the Resultant Changes in Renal Anatomy,” was a landmark that related the changes occurring at different stages of renal deterioration to the quantitative changes taking place in kidney function. During this period, Van Slyke and R. M. Archibald identified glutamine as the source of urinary ammonia. During World War II, Van and his colleagues documented the effect of shock on renal function and, with R. A. Phillips, developed a simple method, based on specific gravity, suitable for use in the field.

Over 100 of Van’s 300 publications were devoted to methodology. The importance of Van Slyke’s contribution to clinical chemical methodology cannot be overestimated.
These included the blood organic constituents (carbohydrates, fats, proteins, amino acids, urea, nonprotein nitrogen, and phospholipids) and the inorganic constituents (total cations, calcium, chlorides, phosphate, and the gases carbon dioxide, carbon monoxide, and nitrogen). It was said that a Van Slyke manometric apparatus was almost all the special equipment needed to perform most of the clinical chemical analyses customarily performed prior to the introduction of photocolorimeters and spectrophotometers for such determinations.

The progress made in the medical sciences in genetics, immunology, endocrinology, and antibiotics during the second half of the twentieth century obscures at times the progress that was made in basic and necessary biochemical knowledge during the first half. Methods capable of giving accurate quantitative chemical information on biological material had to be painstakingly devised; basic questions on chemical behavior and metabolism had to be answered; and, finally, those factors that adversely modified the normal chemical reactions in the body so that abnormal conditions arise that we characterize as disease states had to be identified.

Viewed in retrospect, he combined in one scientific lifetime (1) basic contributions to the chemistry of body constituents and their chemical behavior in the body, (2) a chemical understanding of physiological functions of certain organ systems (notably the respiratory and renal), and (3) how such information could be exploited in the
understanding and treatment of disease. That outstanding additions to knowledge in all three categories were possible was in large measure due to his sound and broadly based chemical preparation, his ingenuity in devising means of accurate measurements of chemical constituents, and the opportunity given him at the Hospital of the Rockefeller Institute to study disease in company with physicians.

In addition, he found time to work collaboratively with Dr. John P. Peters of Yale on the classic, two-volume Quantitative Clinical Chemistry. In 1922, John P. Peters, who had just gone to Yale from Van Slyke’s laboratory as an Associate Professor of Medicine, was asked by a publisher to write a modest handbook for clinicians describing useful chemical methods and discussing their application to clinical problems. It was originally to be called “Quantitative Chemistry in Clinical Medicine.” He soon found that it was going to be a bigger job than he could handle alone and asked Van Slyke to join him in writing it. Van agreed, and the two men proceeded to draw up an outline and divide up the writing of the first drafts of the chapters between them. They also agreed to exchange each chapter until it met the satisfaction of both.At the time it was published in 1931, it contained practically all that could be stated with confidence about those aspects of disease that could be and had been studied by chemical means. It was widely accepted throughout the medical world as the “Bible” of quantitative clinical chemistry, and to this day some of the chapters have not become outdated.

Clinical Chemistry in Mid 20th Century

Case in Point 2:  Outstanding Contributions in Clinical Chemistry. 1991. Arthur Karmen.

Dr. Karmen was born in New York City in 1930. He graduated from the Bronx High School of Science in 1946 and earned an A.B. and M.D. in 1950 and 1954, respectively, from New York University. In 1952, while a medical student working on a summer project at Memorial-Sloan Kettering, he used paper chromatography of amino acids to demonstrate the presence of glutamic-oxaloacetic and glutaniic-pyruvic ransaminases (aspartate and alanine aminotransferases) in serum and blood. In 1954, he devised the spectrophotometric method for measuring aspartate aminotransferase in serum, which, with minor modifications, is still used for diagnostic testing today. When developing this assay, he studied the reaction of NADH with serum and demonstrated the presence of lactate and malate dehydrogenases, both of which were also later used in diagnosis. Using the spectrophotometric method, he found that aspartate aminotransferase increased in the period immediately after an acute myocardial infarction and did the pilot studies that showed its diagnostic utility in heart and liver diseases.  This became as important as the EKG. It was replaced in cardiology usage by the MB isoenzyme of creatine kinase, which was driven by Burton Sobel’s work on infarct size, and later by the troponins.

Case in Point 3. History of Laboratory Medicine at Yale University.

The roots of the Department of Laboratory Medicine at Yale can be traced back to John Peters, the head of what he called the “Chemical Division” of the Department of Internal Medicine, subsequently known as the Section of Metabolism, who co-authored with Donald Van Slyke the landmark 1931 textbook Quantitative Clinical Chemistry (2.3); and to Pauline Hald, research collaborator of Dr. Peters who subsequently served as Director of Clinical Chemistry at Yale-New Haven Hospital for many years. In 1947, Miss Hald reported the very first flame photometric measurements of sodium and potassium in serum (4). This study helped to lay the foundation for modern studies of metabolism and their application to clinical care.

The Laboratory Medicine program at Yale had its inception in 1958 as a section of Internal Medicine under the leadership of David Seligson. In 1965, Laboratory Medicine achieved autonomous section status and in 1971, became a full-fledged academic department. Dr. Seligson, who served as the first Chair, pioneered modern automation and computerized data processing in the clinical laboratory. In particular, he demonstrated the feasibility of discrete sample handling for automation that is now the basis of virtually all automated chemistry analyzers. In addition, Seligson and Zetner demonstrated the first clinical use of atomic absorption spectrophotometry. He was one of the founding members of the major Laboratory Medicine academic society, the Academy of Clinical Laboratory Physicians and Scientists.

Case in Point 4.  Nathan Gochman.  Developer of Automated Chemistries.

Nathan Gochman, PhD, has over 40 years of experience in the clinical diagnostics industry. This includes academic teaching and research, and 30 years in the pharmaceutical and in vitro diagnostics industry. He has managed R & D, technical marketing and technical support departments. As a leader in the industry he was President of the American Association for Clinical Chemistry (AACC) and the National Committee for Clinical Laboratory Standards (NCCLS, now CLSI). He is currently a Consultant to investment firms and IVD companies.

Nathan Gochman

The clinical laboratory has become so productive, particularly in chemistry and immunology, and the labor, instrument and reagent costs are well determined, that today a physician’s medical decisions are 80% determined by the clinical laboratory.  Medical information systems have lagged far behind.  Why is that?  Because the decision for a MIS has historical been based on billing capture.  Moreover, the historical use of chemical profiles were quite good at validating healthy status in an outpatient population, but the profiles became restricted under Diagnostic Related Groups.    Thus, it came to be that the diagnostics was considered a “commodity”.  In order to be competitive, a laboratory had to provide “high complexity” tests that were drawn in by a large volume of “moderate complexity”tests.

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