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The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier & Jennifer A. Doudna

Reporters: Stephen J. Williams, Ph.D. and Aviva Lev-Ari, PhD, RN

 

UPDATED on 11/12/2020

Harvard’s Jack Szostak congratulates former advisee Jennifer Doudna

It was a toast from one Nobel laureate to another, sweetened by the pride of a mentor to a prized student.

When Jennifer Doudna Ph.D. ’89 was honored on Wednesday with the Nobel Prize in chemistry for her work on the CRISPR gene-editing technique, she became the second person to gain such an honor from the lab of Jack Szostak, a genetics professor at Harvard Medical School and Massachusetts General Hospital, and professor of chemistry and chemical biology at Harvard’s Faculty of Arts and Sciences.

Szostak, who won the Nobel Prize in physiology or medicine in 2009 for work on how telomere caps keep the body’s chromosomes from breaking down, advised Doudna’s doctoral work on RNA and on Wednesday raised a glass in honor of Doudna, now at the University of California, Berkeley. In a tweet, Szostak expressed his delight at seeing someone he once guided through her early scientific steps soar to science’s highest reaches:

Doudna received the prize together with Emmanuelle Charpentier, for their work discovering and developing CRISPR as a precise gene-editing tool. In just the eight years since the pair announced their discovery the use of the technique has rapidly spread to a host of fields, allowing researchers to alter the code of life and develop resistant crops, new medical therapies, and even anticipate curing inherited diseases.

 

UPDADTED on 11/2/2020

 

Announcement of the Nobel Prize in Chemistry 2020

Live webcast from the press conference where the Royal Swedish Academy of Sciences will announce the Nobel Prize in Chemistry 2020.

 

 

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2020 to

Emmanuelle Charpentier
Max Planck Unit for the Science of Pathogens, Berlin, Germany

Jennifer A. Doudna
University of California, Berkeley, USA

“for the development of a method for genome editing”

Genetic scissors: a tool for rewriting the code of life

Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.

Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.

“There is enormous power in this genetic tool, which affects us all. It has not only revolutionised basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.

As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.

In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.

Illustrations

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”

Illustration: Using the genetic scissors (pdf)
Illustration: Streptococcus’ natural immune system against viruses:CRISPR/Cas9 pdf)
Illustration: CRISPR/Cas9 genetic scissors (pdf)

Read more about this year’s prize

Popular information: Genetic scissors: a tool for rewriting the code of life (pdf)
Scientific Background: A tool for genome editing (pdf)

Emmanuelle Charpentier, born 1968 in Juvisy-sur-Orge, France. Ph.D. 1995 from Institut Pasteur, Paris, France. Director of the Max Planck Unit for the Science of Pathogens, Berlin, Germany.

Jennifer A. Doudna, born 1964 in Washington, D.C, USA. Ph.D. 1989 from Harvard Medical School, Boston, USA. Professor at the University of California, Berkeley, USA and Investigator, Howard Hughes Medical Institute.

SOURCE

https://www.nobelprize.org/prizes/chemistry/2020/press-release/

 

Nobel Prize in Chemistry awarded to scientists who discovered CRISPR gene editing tool for ‘rewriting the code of life’

(CNN)The Nobel Prize in Chemistry has been awarded to Emmanuelle Charpentier and Jennifer A. Doudna for the development of a method for genome editing.

They discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and micro-organisms with extremely high precision.
Before announcing the winners on Wednesday, Göran K. Hansson, secretary-general for the Royal Swedish Academy of Sciences, said that this year’s prize was about “rewriting the code of life.”
The American biochemist Jennifer A. Doudna (left) and French microbiologist Emmanuelle Charpentier, pictured together in 2016.
 
The CRISPR/Cas9 gene editing tools have revolutionized the molecular life sciences, brought new opportunities for plant breeding, are contributing to innovative cancer therapies and may make the dream of curing inherited diseases come true, according to a press release from the Nobel committee.
 
 
There have also been some ethical concerns around the CRISPR technology, however.
Charpentier, a French microbiologist, and Doudna, an American biochemist, are the first women to jointly win the Nobel Prize in Chemistry, and the sixth and seventh women to win the chemistry prize.
close dialog

 

Jennifer Doudna wins 2020 Nobel Prize in chemistry

 

First Day in a Nobel Life: Jennifer Doudna

12,365 views
Oct 7, 2020
 
Scenes from day that UC Berkeley Professor Jennifer Doudna won the Nobel Prize For the full story, visit: https://news.berkeley.edu/2020/10/07/… University of California, Berkeley, biochemist Jennifer Doudna today won the 2020 Nobel Prize in Chemistry, sharing it with colleague Emmanuelle Charpentier for the co-development of CRISPR-Cas9, a genome editing breakthrough that has revolutionized biomedicine. CRISPR-Cas9 allows scientists to rewrite DNA — the code of life — in any organism, including human cells, with unprecedented efficiency and precision. The groundbreaking power and versatility of CRISPR-Cas9 has opened up new and wide-ranging possibilities across biology, agriculture and medicine, including the treatment of thousands of intractable diseases. Doudna and Charpentier, director of the Max Planck Institute for Infection Biology, will share the 10 million Swedish krona (more than $1 million) prize. “This great honor recognizes the history of CRISPR and the collaborative story of harnessing it into a profoundly powerful engineering technology that gives new hope and possibility to our society,” said Doudna. “What started as a curiosity‐driven, fundamental discovery project has now become the breakthrough strategy used by countless researchers working to help improve the human condition. I encourage continued support of fundamental science as well as public discourse about the ethical uses and responsible regulation of CRISPR technology.” Video by Clare Major & Roxanne Makasdjian
SOURCE

 

Jennifer Doudna wins 2020 Nobel Prize in chemistry

 

Jennifer Doudna in the PBS Movie CRISPR

Our critically-acclaimed documentary HUMAN NATURE is now streaming on NETFLIX. #HumanNatureFilm. Find out more about the film on our website.

 

Other Articles on the Nobel Prize in this Open Access Journal Include:

2020 Nobel Prize for Physiology and Medicine for Hepatitis C Discovery goes to British scientist Michael Houghton and US researchers Harvey Alter and Charles Rice

CONTAGIOUS – About Viruses, Pandemics and Nobel Prizes at the Nobel Prize Museum, Stockholm, Sweden 

AACR Congratulates Dr. William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Dr. Gregg L. Semenza on 2019 Nobel Prize in Physiology or Medicine

2018 Nobel Prize in Physiology or Medicine for contributions to Cancer Immunotherapy to James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University Institute, Japan

2017 Nobel prize in chemistry given to Jacques Dubochet, Joachim Frank, and Richard Henderson  for developing cryo-electron microscopy

2016 Nobel Prize in Chemistry awarded for development of molecular machines, the world’s smallest mechanical devices, the winners: Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard L. Feringa

Correspondence on Leadership in Genomics and other Gene Curations: Dr. Williams with Dr. Lev-Ari

Programming life: An interview with Jennifer Doudna by Michael Chui, a partner of the McKinsey Global Institute

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via Special COVID-19 Christopher Magazine

Special COVID-19 Christopher Magazine

Christopher-coverAntonio Giordano, MD, PhD. explains what COVID is and how to contain the infection, pointing also to what will require attention next.

Please see this special release at http://online.fliphtml5.com/qlnw/zgau/#p=1

 

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via Dr. Giordano Featured in Forbes Article on COVID-19 Antibody Tests in Italy and USA

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My Memories Tell a Story to Share

Author: Larry Howard Bernstein, MD, FCAP 

Contact: 413-727-8523

 

Updated on 6/2/2020

In preparation for a PODCAST with Dr. Larry, we prepared the following content:

For many years, he was the Chief Scientific Officer and Member of the Board of Leaders in Pharmaceutical Business Intelligence (LPBI) Group, a Pharmaceutical Media Venture with several Cloud Based products: (1) an Open Access Online Scientific Journal

PharmaceuticalIntelligence.com, (2) a BioMed e-Series of 16 volumes in Medicine (3) A Real Time Press Coverage of Biotech and Medical Conferences (4) a Podcast Library of Interviews with Key Opinion Leaders (4) A Platform with Composition of Methods and (5) a Team of Experts, Authors, Writers.

Dr. Bernstein had contributed 1,400 curated articles to LPBI’s Journal, mentioned above and served as Editor and Content Consultant to each of the 16 volumes in LPBI’s BioMed e-Series.

Examples of the TOP articles in the Journal by e-Readers Views shows the cardinal positioning of Dr. Bernstein’s publications.

 

Top Posts for all days ending 2020-06-02 (Summarized)      
       
All Time      
Title Views Author Name Type of Article
Home page / Archives 676,690 Internet Access Tabulation
Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View? 17,117 Larry H. Bernstein, MD, FACP Investigator Initiated Research
Recent comprehensive review on the role of ultrasound in breast cancer management 14,242 Dr. D. Nir Commission by Aviva Lev-Ari, PhD, RN
Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) and PRADAXA (dabigatran) 13,839 Dr. Pearlman, MD, PhD, FACC & Aviva Lev-Ari, PhD, RN Commission by Aviva Lev-Ari, PhD, RN
Paclitaxel vs Abraxane (albumin-bound paclitaxel) 13,709 Tilda Barliya, PhD Investigator Initiated Research
Apixaban (Eliquis): Mechanism of Action, Drug Comparison and Additional Indications 8,230 Aviva Lev-Ari, PhD, RN Investigator Initiated Research
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care 7,903 Dr. Pearlman, MD, PhD, FACC & Aviva Lev-Ari, PhD, RN Investigator Initiated Research
Mesothelin: An early detection biomarker for cancer (By Jack Andraka) 6,540 Tilda Barliya, PhD Investigator Initiated Research
Our TEAM 6,505 Internet Access Tabulation
Biochemistry of the Coagulation Cascade and Platelet Aggregation: Nitric Oxide: Platelets, Circulatory Disorders, and Coagulation Effects 5,221 Larry H. Bernstein, MD, FACP Investigator Initiated Research
Interaction of enzymes and hormones 4,901 Larry H. Bernstein, MD, FACP Commission by Aviva Lev-Ari, PhD, RN
Akt inhibition for cancer treatment, where do we stand today? 4,852 Ziv Raviv, PhD Investigator Initiated Research
AstraZeneca’s WEE1 protein inhibitor AZD1775 Shows Success Against Tumors with a SETD2 mutation 4,535 Stephen J. Williams, PhD Investigator Initiated Research
The History and Creators of Total Parenteral Nutrition 4,511 Larry H. Bernstein, MD, FACP Commission by Aviva Lev-Ari, PhD, RN
Newer Treatments for Depression: Monoamine, Neurotrophic Factor & Pharmacokinetic Hypotheses 4,365 Zohi Sternberg, PhD Investigator Initiated Research
FDA Guidelines For Developmental and Reproductive Toxicology (DART) Studies for Small Molecules 4,188 Stephen J. Williams, PhD Investigator Initiated Research
The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets 4,038 Dr. Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD, FACP & Aviva Lev-Ari, PhD, RN Commission by Aviva Lev-Ari, PhD, RN
Founder 3,895 Aviva Lev-Ari, PhD, RN Investigator Initiated Research

 

That small sample from a universe of 1,400 articles reflects just a glimpse of the topics that he had covered in his writing.

In addition, in 2020 the Journal ontology has 700 Categories of Research, more than 50% were create by Dr. Bernstein for allowing a precise classification of the wide range of topics his life body of research had covered, chiefly: Cancer, Genomics, Pathology, Coagulation, Cardiovascular, Nutrition, Cell Biology and Biochemistry Processes, at large.

Dr. Bernstein served on the Board of Director of NAACLS and the American Library Association Commission on Accreditation and he is listed in the America’s Top Physicians.

He has three patents:

1. Measuring Lactate Dehydrogenase Isoenzymes by differential inhibition of heart and muscle enzymes using the inhibition by a triplex formed by pyruvate – NAD+ and LDH.

2. Measuring the mitochondrial Malate Dehydrogenase using the inhibition of mMDH by a triplex formed by OAA – NAD+ – and mMDH in the laboratory of Nathan Oren Kaplan (NAS).

3. Measuring a cancer modified MDH by loss of mMDH inhibition with Prof. Johannes Everse. In addition, only a provisional patent was filed for Converting Hematology Based Data into an Inferential Interpretation under the direction of Prof. Ronald Raphael Coifman (NAS). No patent was filed for the statistical determination of myocardial infarct using two assays for creatine kinase MB. No patent was filed for the diagnosis of myaocardial infarct using a neural network under the supervision of Izaak Mayzlin, eminent mathematician from former Soviet Union;
No patent was filed for the determination of myocardial infarct using Kullback Entropy.

My lab was the only one to get down to reliable measurements of transthyretin of 20 mg/L. I co-chaired the First International Transthyretin Congress in Strasbourg, at the invitation of Yves Ingenbleek, MD, PhD, Professor of Pharmacology, University Louis Pasteur, Strasbourg.

I chaired the 14th and was an invited participant in the 17th Ross Roundtable on Nutrition, Organized and Chaired the Beckman Roundtable on Pre-albumin in Los Angeles, was responsible for the AACC first document of Standards of Clinical Laboratory Practice with Lawrence Kaplan, and was recipient of the Labbe/Garry award of the Nutrition Division of AACC).

Other projects in normalizing the NT-proBNP for age and estimated glomerular filtration rate (eGFR), were successful, but widespread implementation is even more gradual than was TTR.

  • Could you tell us about the research project that had the most significance in your career?

You worked with two noted researchers – Gil David and Yale University’s Chairman of the Mathematics Department Ronald Coifman – to develop a software system which is today’s equivalent of electronic health records that gathers medical information, generates metrics and analyzes data in real-time, providing a health diagnosis for an individual’s medical condition.

 

4/19/2020

The Schwartz and Auslander Families

I was born a triplet to David and Lillian Bernstein on December 28, 1941, the first set of triplets born in Highland Park Hospital in some 20 years, but on graduation from Mumford High School, Detroit, Michigan in 1960, we were one of three sets of triplets. We were Larry, Leslie and Linda, who were preceded by Sharon, a sister two years older, also a December baby. Our parents were middle class and our father was a dental technician, so a family with four children was not easy to bring up. We always lived in a household of two families, with my uncle Irving and aunt Elsie Bernstein, living in the lower level, having two children, Barbara, who was our age, and Richard, who was the older brother. When we were born, under the circumstance of my grandmother, Bobby Mulvin (Mulvina in Hungarian), three calls were made in successive days to inform the family in Cleveland, Ohio, of our birth. My mother’s father and mother were Julius and Mulvina Schwartz, from the Hungarian edge of Austria on the Raba River, who moved the family to Cleveland as the intentions of Hitler became clear. My mother had two older brothers and a younger sister, David, Herman and Bernice. David had already been a United States citizen when the Schwartz family moved to the United States in 1931, and Herman was a third year medical student in Budapest after completing a year in Vienna, having been valedictorian of his high school class after special arrangement of his local catholic priest. But Herman had to move from Hungary months prior to graduation because immigration would close. Lillian was 18 years age when she brought her 11 year old sister to America. Julius and David worked in the dry cleaning business in Cleveland. There was also a Mulvina cousin, Biederman, who was a jeweler in Vienna who moved to Cleveland, but his father did not escape the Nazis. Their children were Alan and Marvin, Lois, Robert and Barbara (Liss), Lucille and Janice. Another two generations have passed. Robert was a merit scholar in upstate New York, became a reporter on the Miami Herald, and had three children. He died too young of leukemia. Barbara married and had 3 Wolfe children, two boys and a girl.

I have described the Cleveland side of the family. My mother worked making ties in Cleveland for a friend of my father’s family. She helped bring him to Detroit and married my mother. My father came from Czeckoslovakia, his father having a tree farm on the Carpathian mountains, near the border with Poland. He became a Schochet (kosher chicken). He had a sister, Rivka. Rivka married a cantor after her husband died. My grandmother was in the Auslander family. Auslander means out of the land. A rabbi brought his family out of Spain and changed the family name to Auslander. My grandfather was Meyer and grandmother was Rachel (Bobby Rochel). They lived two streets from the elementary school, so we had lunch at the grandparents house. My grandmother had sisters Esther, Edna, Katie, Jeanette. We go to a next generation rich in talent. This family lived in the city of Detroit, which has an interesting history.

 

The Jewish Community

Grandfather Meyer was very orthodox, but he shaved, and attended the Gelitzioner Shul, but our mother objected to her children going to an orthodox yeshiva school that was too rigid. Our mother read a lot to become knowledgable and also fluent in the English language. Our father read the Detroit Free Press and the business section daily. Some of our family went to the reform synagogue, Temple Israel, that did not use rigorous Hebrew in prayer. We attended the Bnai Moshe synagogue, which had Rabbi Moses Lehrman, whose daughter became an English teacher at our school. There was a cantor, and there was a superb reader of the Torah (Baal Koreh). The president of the Bnai Moshe was the founder of a salami that was the equal to that in New York.

 

Detroit

Detroit was a city on the Detroit River that was once known as Fort Ponchartrain at the time of the Revolutionary War with the British. There were Indians at the edge of the Upper Peninsula. The Upper Peninsula was obtained by Governor Lewis Cass from Wisconsin an a trade that made Toledo a part of Ohio. Detroit and the Detroit River became a crossing point for Negroes at the time of flight from the Southern states during the Civil War. Windsor, Ontario was a point of transfer of liquor from Winsor, Ontario. Detroit became important when Henry Ford brought automation into auto manufacturing, and it was followed by Dodge/Crysler and General Motors. Neighboring Dearborn, Michigan became a city where there was later a Ford Museum, and it was known to be only for whites and non-jews. There was also before my arrival an anti-Semitic priest, Father Coughlin. In addition, Henry Ford was known to disseminate “The Elders of Zion. So the city was somewhat divided, as perhaps other cities – like New York. Philadelphia, Chicago, and Los Angeles – that had distinctly jewish and black neighborhoods that one might consider ghettos. The city of Highland Park, within Detroit, was Polish. The jewish neighborhood migrated from Chicago Boulevard toward Livernois, and beyond to beyond Seven Mile Road, and eventually beyond Eight Mile Road, the Detroit border.

My early childhood was on Sturtevant, between Linwood and Dexter. Linwood extended to middle Detroit, where there was an automobile convention center. There was a theater at the corner of Linwood and Livernois. There was an upper middle class neighborhood adjacent to Oak Park, and a zoo on Woodward Avenue. The synagogue my family attended was on Dexter, and there was a butcher shop, a bakery, and the Dexter Davison Market. My aunt Edna had an ice cream parlor a short distance from the synagogue on Dexter. She had two sons and one became a doctor and the other a professor.
The McCullough elementary school and across the street a United Hebrew School were walking distance from where my family lived, with many children on our street. Milk was delivered to a milkbox, and an alternative way of entering the home was through the milkbox. The next door neighbor had a dog named Blackie. He was child friendly. There were many children in the neighborhood. My best friend in elementary school was an Armenian boy, Michael Michalian.

 

High School and College

We moved from the old neighborhood at the time were to attend High School. My brother and I joined the chess club and learned from Peter Wolf, who excelled at it. Mumford High School chess club won the city championship over Redford High School, taking the cup four years in succession. I also found a friend in high school a grade ahead, Fred Baskin, who was extremely bright and very social. The triplets graduated from high school and entered WSU in 1960. When we finished high school we all went to Wayne State University (WSU), where I majored in chemistry, and was a premedical student. Fred had a Merit Scholarship. I prepared myself sufficiently so that if I were not to qualify for medical school, I could follow a suitable career. My older sister, Sharon, was a very fine pianist and she entered WSU with a General Motors Scholarship three years earlier. She excelled in mathematics. She has taught piano for years and still does so at 80 years age. Fred went on to graduate school in biochemistry at University of California, Berkeley and I went on to medical school at Wayne State University upon graduation. My sister Linda did graduate work and obtained a Master degree in biology at Wayne State, married a psychiatry graduate, and they moved to California and raised two boys. I shared the same room as Leslie, but I did not see changes in him that lead to attempted suicide and admittance to the hospital. The three of us spent a summer at the NIH in a study of Schizophrenia. Leslie went to San Diego to be near Linda.

I worked very hard in my first two years of medical school. I engaged in a graduate study in embryology under Harry Maisel in the Anatomy Department, studying the evolution of the proteins of the lens of the eye (crystallins) under Prof. Harry Maisel, but I also studied the changes in the isoenzymes of lactate dehydrogenase (LD). He was an inspiring scientist, but I also had the opportunity to learn electron microscopy under Maurice Bernstein in the same department. When I finished the Master degree I returned to finish the last two years of medical school. This was a valuable experience under two inspiring mentors. In the study of the evolution of the LD isoenzymes I became extremely interested in the work of Nathan Kaplan at the Graduate University of Biochemistry in Boston, and the work of one of his graduate students who looked at the changes in the wings of avians, depending on flight characterics. I chose to go to the University of Kansas Medical School for residency and PhD in pathology. When I arrived in 1968, the pathologist whose work interested me had left to carry on the chairmanship elsewhere, but I was fortunate to meet Masahiro Chiga, who had left an Acting Chairman of Biochemistry to return to pathology. He was an inspiration. I finished less than a year when he recommended that I go to the University of California, San Diego to work with Nathan Kaplan. He modestly said that he had worked with the muscle enzyme of adenylate kinase (myokinase) that is different than the liver enzyme, but he hadn’t had the insight that Kaplan had. I stayed in touch with him until his death. My mother developed gastric cancer, quite rare then, and I visited her several times before she died. I also dated an old Mumford schoolmate, Audrey Mellon, who I married before going to San Diego.

 

 

University of Calfornia, San Diego

I found myself in a completely different environment in San Diego. One part of it was the enormous scientific environment, not only with Kaplan’s laboratory his two competent two assistants, and his several postdoctoral students, but also my engagement with several staff biochemists. There were presentations in the hallway next to Prof. Kaplan’s office, and some were from outside research institutions. It was amazing how when the medical school was opened, it had drawn talents from all of the best institutions. An unintended benefit was the beautiful ocean, the nearby La Jolla, and nearby other research centers. Dr. Kaplan was the Editor, and he cofounded Methods in Enzymology with Sidney Colowick, who had worked with Carl and Gerty Cori (Nobel Laureates) in St. Louis. They had both worked with Fritz Lippman in the discovery of Coenzyme A , the cofactor that acts as an acyl carrier, and either activates the acyl group for group transfer or electrophilic attack, or increases the acidity of the protons adjacent to the carbonyl group. He shared the Nobel Prize in Physiology in 1945 with Hans Krebs, who elucidated the Krebs cycle. Kaplan’s role in the discovery was significant. Interestingly, Hans Krebs work was related to work carried out in the laboratory of Otto Warburg (Nobel Laureate, 1937)), whose work pioneered the study of mitochondrial impairment if cancer.

My own work was not with lactate dehydrogenase, but with Malate dehydrogenase, a critical enzyme linked to mitochondrial function. While LDH catalyze the conversion of pyruvate to lactate with NADH as cofactor and the transfer of a proton, the reverse reaction was inhibited by a ternary complex formed by LDH-NAD- and lactate, but this reaction was weak with the muscle type LDH compared to the heart type LDH. In a similar manner the malate dehydrogenase had a mitochondrial and cytoplasmic isoenzyme, the mitochondrial MDH forming a ternary complex, but not the cytoplasmic enzyme. I spent many months purifying the mitochondrial enzyme from 50 lb of chicken hearts with first an ammonium sulfate precipitation, then a column separation, and dialysis. A study of the mitochondrial malate dehydrogenase was followed by stopped flow analysis and that showed the inhibition by transfer of the hydrogen to form a ternary complex.

I returned to residency in pathology at UCSD under an NIH fellowship with Averill Liebow in the next year. Liebow was an internationally known expert in pulmonary pathology. He was also very amazing. A resident from Yale referred to Liebow noticing him sleeping in the back row and the professor called his name, the son of so and so, you can’t sleep in my class. His car was the first in the lot, until I came. Then when I went to the VA Hospital and parked on the other side, he noted that I parked around the corner. The chief of chemistry at the VA was an outstanding teacher and biochemist who subsequently took a position at Beckman-Coulter. I set up an assay in a study of swimming rats with Liebow. My first daughter was born during my residency and it was fascinating watching her learn to stand up. I took her to the San Diego zoo on weekends and she would stand up in her crib and say zoo, zoo. It was at this time that I collected urine specimens for a study of adenylate kinase with Percy Russell, and also took serum specimens from a study of creatine kinase MB in myocardial infarction that was done by the cardiologist Burton Sobel for my own study that was published.

 

At the end of my residency I had to give two years for my time deferred from the Vietnam War. Liebow called the Armed Forces Institute of Pathology in Washington to give me the best placement. I then spent the next two years working in orthopedic pathology with Lent C. Johnson, who was quite a genius. He determined the normal ratio of bone forming to bone removing cells, and did pioneering work in bone cancer. Liebow wanted me to return after the two years, but he had a stroke. At the end of two years I took a pathology position at the University of South Florida, Tampa, under Herschel Sidransky.

Herschel was an outstanding researcher from University of Pittsburg Medical School. He had several outstanding researchers in his department. I returned to my studies of malate dehydrogenase and in particular, the mitochondrial malate dehydrogenase in hepatic cancer from Herschel Sidransky’s animals. I had a grant from the Cancer Society. I also had the support in statistics from a mathematician.

Herschel became the Chairman of Pathology at George Washington University, Washington, DC. Several faculty went with him, but I received a substantial salary increase and a supportive offer from the University of South Alabama, Mobile, with a very enthusiastic pathology chairman. Just prior to leaving Florida, Naomi was born. I took on a role with the Medical Technology Program, and I also participated in program reviews, and some time later was on the National Committee for Clinical Laboratory Standards. The Chairman was a capable and enthusiastic neuropathologist who intended to build a good department, but it was not long after that the Chair of Medicine, also the Dean, set up a clinical laboratory for his own interest, without merit. I submitted a cancer grant proposal that was approvingly reviewed by the Chairman of Physiology. It was approved by the NIH without funding, with suggestions to consider. That was a point that I chose to move, and after two years, I moved the family to Des Moines, Iowa to work at the Iowa Methodist Medical Center, the second largest after University Hospital. The President of the hospital sent me a high school student and we completed a project on fetal lung maturity that we published. However, the move was not a good match, as the Chairman’s main concern was outside laboratory work and there was also a laboratory manager who was manipulative.

After two years we moved to Binghamton, New York to a position with Gustavo Reynoso, who came from Rochester, New York and was a very respected pathologist. There was a consolidation of hospitals that led to Dr. Reynoso taking the chairmanship of pathology at Norwalk Hospital, in Norwalk, Connecticut, and he procured a position for me at Bridgeport Hospital, in Bridgeport, CT. The move was very good with an excellent staff in pathology, and I was the director of chemistry and blood bank. This time I stayed for 20 years, and developed a very good relationship with the medical staff, the Chairman of Pathology, Dr. Marguerite Pinto, and particularly with my supervisors in Blood Bank and Chemistry. My Blood Bank supervisor married and moved to Greece and eventually was in charge of the Athens Blood Program.

My relationship with the residents in medicine and cardiology was very collaborative. When I was in the hospital recovering from a femoral fracture, I received a call from I.J. Good, Chairman and Editor of a mathematics journal to whom I had sent cardiac enzyme data some years before. He had finished and validated a program “Diagnosis of acute myocardial infarction from two measurements of creatine kinase isoenzyme MB with use of nonparametric probability estimation”, and they successfully ran the data. We published the paper in Clinical Chemistry. The President of the College of American Pathologist complimented the work at a national meeting. I also met another pathologist, Rosser Rudolph, at a pathology meeting and he had developed a powerful mathematical program that determined the entropy of diagnostic data. We collaborated for many years. In addition, I was really privileged to work with the father of my daughter’s classmate, Isaac Mayzlin, who was an important mathematician at Moscow University. We developed an neural network algorithm for myocardial infarction.

I had a very long, satisfying role in collaboration with Dr. Walter Pleban, who was the surgeon in charge of the only burn unit in Connecticut. I had been engaged in the nutritional support program with Dr. Pleban for some years because of my work on transthyretin. Unfortunately, the criteria using decrease in serum albumin that was in use was very inadequate for early recognition. Transthyretin is a plasma protein that binds to vitamin A and declines very early in protein malnutrition. A decline in transthyretin results in impairment of methionine metabolism. I also had a longstanding relationship with Prof. Yves Ingenbleek at University Louis Pasteur, Strasbourg, in this work. When Stanley Dudrick became the Chairman of Surgery, it was a fortunate circumstance. Stanley was the pioneer in developing intravenous nutrition and was nominated for the Nobel Prize for his work.

A year after Yale University took charge of the Bridgeport Pathology Department, I took a position as Chief of Clinical Chemistry and Blood Bank at the Methodist Hospital of Brooklyn. I had a very good relationship with surgery and medicine, and had superb projects with the residents, but also had excellent high school and college students work on projects. I was 65 years old five years later, and returned to work at Norwalk Hospital in charge of the Blood Bank while the position was recruited. After finishing my work there, I went to Yale University and developed a project with Ronald R. Coifman, the retired Chairman of Mathematics and his graduate student. It lead to the development of a powerful algorithm for interpreting the hemogram that we published. There is a substantial body of research being published of a similar nature, but it is not at all clear whether or how this will be incorporated into the electronic medical record. It reminds me of the support I had at Bridgeport Hospital using a laboratory system designed by Dr. Perry Seamonds that eliminated nonessential examination of peripheral smears by rules criteria. This laboratory system also alleviated the volume of laboratory testing to relieve the burden on the physicians. A different problem I later noticed was that the Hospital Systems that were later introduced had the laboratory, but did not include the Blood Bank! However, as the electronic medical record has evolved it has taken an enormous physician, nursing, and provider time that does not justify a reduction in staff.

After I had been done with my Yale project, I developed a visual problem and stopped driving. I had problems I would later realize. I had had two incidents in a few years that I drove my car off the road because of sleep apnea. I was walking in my neighborhood and had to stop and hold on to a tree for balance. In the case of sleep apnea, it was diagnosed earlier in a sleep apnea study in Brooklyn. I had a study at Yale that brought to my realization that I had thyroid cancer, for which I had thyroidectomy. However, I had diplopia after surgery which disappeared some time later. We moved to Northampton, Massachusetts when our daughter, Naomi and her husband Daniel with grandson Joseph moved, Naomi taking a teaching position at Holyoke Community College, and Daniel working as a neurologist at the VA hospital.

Prior to moving I was contacted by Aviva Lev-Ari, PhD, RN who was building an online medical forum known as Leaders in Pharmaceutical Business Intelligence (LPBI) Group, and I became the Chief Scientific Officer (CSO).  Over the decade I wrote many articles (1,390) in the Open Access Online Scientific Journal http://pharmaceuticalintelligence.com that were included in 16 organized e-Books in Medicine. Dr. Lev-Ari’s accomplishment is quite impressive. The e-Books are all available on Amazon.com

https://lnkd.in/ekWGNqA

I stopped contributing two years ago, but a graduate student had read my work and wanted my academic guidance (in Canada). She finished her thesis and graduated a year ago. It was a privilege to work with her. Since moving to Northampton, we has been in a very good community at Lathrup.

 

 

 

 

 

 

 

 

 

 

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