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Homage - Professor CLAUDE NICOLAU, a chemist who hopes to overcome diseases considered to be incurable

de Alexandru T. Balaban, Texas A&M University at Galveston, Texas, USA


Several years ago, the Roumanian Academy elected Professor Claude Nicolau as Honorary Member and on May 4, 2016 celebrated his 80th anniversary in a festive session with the following program:

- opening remarks (by Acad. Prof. Ionel Haiduc);

- supramolecular and adaptive chemistry. Bioorganic and drug discovery aspects - Recent advances (by Prof. Jean-Marie Lehn, University of Strasbourg);

- Prions - from crazy scientists to new therapeutic concepts for Alzheimer's disease (by Prof. Detlev Riesner, Heinrich Heine Universitat Düsseldorf);

- Claude Nicolau - Scientist and entrepreneur par excellence (by Prof. Irwin Rosenberg, Human Nutrition Research Center on Aging, Boston);

- Professor Claude Nicolau - a multivalent man (by Dr. Niculae Ionescu, Institute of Physical Chemistry Ilie Murgulescu, Bucharest;

- from the Center of Radiobiology to the Craiova University and then - over lands and oceans - back to Bucharest (by Acad. Victor Voicu);

- reply and closing remarks (by Prof. Claude Nicolau), followed by J. S. Bach's Cantata BWV211.

The 80th anniversary of Professor Claude Nicolau was a welcome opportunity for honoring a brilliant Roumanian scientist who is also a French citizen and permanent resident of the United States of America, where he lives at present.

He is a French citizen because he was born in 1936 Paris from parents who were French citizens.

His father, Stefan S. Nicolau, M. D. Ph.D., was a researcher at the Pasteur Institute where he worked between 1920 and 1939.

He had completed in 1920 his medical studies in Bucharest and Cluj. At the Paris University he obtained in 1925 a doctorate in sciences, after having worked during the First World War in the 2nd Hospital for Contagious Diseases in Moldova.

At the Pasteur Institute he was promoted from Assistant to Associate, then Head of Laboratory, and for four years between 1932 and 1936 the Pasteur Institute sent him as Head of Laboratory to the National Institute of Medical Research in London.

He accepted in 1939 the invitation to return to Roumania as Professor of Bacteriology at the Faculty of Medicine in Iasi, as successor of Dr. Alexandru Slatineanu, who had been an important mentor for him. In 1942 he obtained a transfer to the Faculty of Medicine in Bucharest as Professor, founding the Chair of Inframicrobiology that he led till his retirement in 1962.

He had a brilliant career being elected as corresponding member of the Roumanian Academy in 1946 and as titular member in 1948. He founded in 1949 the Institute of Inframicrobiology (at present the Institute of Virology Stefan S. Nicolau) and was its Director till his death in 1967. He was Claude's example for loving the research that improves human health.

As a student at the Chemistry Faculty of the Bucharest University, where he graduated in 1957, Claude had as a model the professor of Physical Chemistry, Ilie G. Murgulescu, who combined in his lectures elegance with mathematical rigor.
Claude, with his bright intelligence, and huge diligence, knew how to put to work the advantages fate had offered him.

For several months he worked at the Institute of Atomic Physics in Magurele, then during the next three years he obtained his doctorate degree in physical chemistry at the Humboldt University in Berlin.

After his return in Roumania, he was appointed between 1962 and 1970 as assistant professor and then as associate professor at the Chair of Physical Chemistry of the Institute of Petroleum, Gas, and Geology (IPGG) which then was located in Bucharest. He did post-doctoral work at the University of Liege (Belgium, 1964) and at the University of York (England, 1968).

I remember how Claude presented at the pubic sessions of the Roumanian Chemical Society his communications: with his fantastic memory, which is still intact at present, he recited bibliographic references with title, author and journal names, year and page, as if he was reading this information. Often, when I was visiting the Chairman of the Department of Organic Chemistry at IPGG, professor Valeriu Vantu, I found there Claude, and we had long philosophical or scientific discussions on varied topics.

Around that time, more precisely between years 1965 and 1968, Claude was Director of the Radiobiology Center of the Ministry for Public Health. He imported for this Center various modern instruments that were unique in Roumania.

Some of these could also be used by external researchers, including those from the Chair of Organic Chemistry of the Bucharest Polytechnic, where I was working. One of these instruments was the infrared spectrophotometer, operated skillfully by a friend of mine, the pharmacist Gheorghe Mateescu. He also established modern research programs, attracting a number of talented young researchers.

Regrettably, after the 1968 events in Czechoslovakia when the Prague Spring was crushed, Claude's Center was taken over by the Roumanian army, and Claude's directorship was terminated. Scientific collaborations with other researchers were discontinued, and the precious instruments imported by Claude were no longer used efficiently.

Claude's privileged situation allowed him to travel abroad for scientific meetings or stages to Israel, West Germany, and the United States, forming and tightening bonds that would prove to be very useful in the forthcoming years.

In 1970 Claude Nicolau accepted to become professor and chairman of the Chair-Laboratory of Biology-Genetics at the newly founded Faculty of Medicine in the University of Craiova. This move is similar in many respects to his father's move from Paris to Iasi, but the similarity ends here.

Claude invested all his energy for the progress of his new position, earning appreciation from the scientific and political environment in Craiova.

He commuted regularly between Bucharest and Craiova and directed his efforts towards raising the level of research and didactic activities. However, again dark political clouds descended on Roumania after Nicolae and Elena Ceausescu returned from their travels to China and North Korea. Funding for scientific research that did not produce immediate benefits was drastically cut, contacts with colleagues in the West were discouraged and restrained. In this atmosphere, Claude's isolated efforts could not bring the progress that he had hoped.

As a consequence, in 1973 he decided not to return to Roumania from a travel to West Germany. Professor Oskar E. Polansky, the Director of the Max Planck Institute for Radiation Chemistry in Mülhim/Ruhr offered him the position of Associate Professor and Head of Laboratory at his institute, where he worked for almost eight years till 1981.

From Germany, Claude continued his West-oriented inclinations, and became Professor (Directeur de Recherches Scientifiques I) at the National Center for Scientific Research, Center for Molecular Biophysics in Orléans. For three years (1983-1986) he was the Director of this Center.

In 1986 he received an invitation from the Medical College pf Texas A&M University (TAMU) in College Station, Texas to become Visiting Professor at this University. Based on his previous achievements, he obtained a substantial industrial grant, and bought to College Station his whole team from Orléans.

The research results that he published during the four years at TAMU were of such value that in 1990 he was appointed Visiting Professor at the most prestigious university in the USA, Harvard Medical School in Boston, Massachusetts. He was the Director of the Research and Development Department of the Center for Blood Research Laboratory, affiliated to Harvard Medical School.

Claude invited me there for two months to his Laboratory at Harvard Medical School with my wife, Nelly, and we were often guests at his house with Christa, his wife.
Boston is a city similar to European cities, in which there is no Cartesian grid of streets and avenues, so that on driving occasionally his Mercedes car I had to rely on Nelly's reading the map quickly and giving me directions.

Claude's bibliography includes 11 books as author or editor (a selected list ordered chronologically is included in the bibliography <1-6>), over 200 published papers, and 16 chapters in books edited by other scientists.

Even more important are his patents (over 50) that assure his paternity over his inventions, as well as the companies that he co-founded so that his discoveries can become new tools against diseases that plague humanity.

My son, who teaches chemistry at Marseille University, was one of Claude's coworkers in the team that attempted to overcome the Alzheimer Disease. He is a co-author of a paper describing a liposome-based therapeutic vaccine for mice having β-amyloid plaques <7>; later work by Professor Nicolau and his coworkers, using monoclonal human antibodies, led to an effective immuno-therapy of early Alzheimer Disease, now in a Phase III Clinical Trial.

Gene transfer using liposomes is another of Claude's discoveries and may be used for medical purposes in the future <8, 9>.

One of Claude's most significant discoveries in a collaboration with Jean-Marie Lehn, (one of the three 1987 Chemistry Nobel Prize laureates) involves myo-inositol trispyrophosphate (ITPP), a novel allosteric effector of hemoglobin, which shows, in several animal models a significant anti-cancer activity <10, 19>. A treatment of different hepato-billiary diseases using ITPP is in a phase II clinical trial.

I cannot enumerate all Claude's contributions to biochemical and medical sciences.. However, I will declare that his discoveries attempting to cure diseases that are now considered to be incurable have assured him a prominent place in the history of biochemistry, biology, and medicine.'

Selected bibliography

1. C. NICOLAU and Z. SIMON. Biofizica Moleculara. Editura Stiintifica, Bucuresti, 1968.
2. C. NICOLAU. Editor: Experimental Methods in Biophysical Chemistry. Wiley, London, 1973)
3. C. NICOLAU (author and editor). Virus-Transformed Cell Membranes. Academic Press, New York, 1978.
4. C. NICOLAU (editor). O2 Transport in Red Blood Cells, Pergamon Press, Oxford, 1986.
5. C. ROPARS, M. CHASSAIGNE and C. NICOLAU, eds. Red Blood Cells as Carriers for Drugs. Potential Therapeutic Application. Advances in the
Biosciences, vol. 67; Pergamon Press, Oxford, 1987.
6. C. NICOLAU and D. CHAPMANN (editors). Horizons in Membrane Biotechnology, Wiley-Liss Inc., New York,1990.
7. C. NICOLAU, R. GREFERATH, T. S. BALABAN, J. E. LAZARTE, and R.J. HOPKINS, A liposome-based therapeutic vaccine against beta -amyloid
plaques on the pancreas of transgenic NORBA mice. Proc. Natl. Acad. Sci. USA., 2002, 99, : 2332-2337.
8. C.NICOLAU, A. LEPAPE,P.SORIANO, F.FARGETTE, M.-F.JUHEL In vivo expression of rat insulin after i.v. administration of the liposomeentrapped
gene for rat preproinsulin I. Proc. Natl. Acad Sci. USA, 1983, 80, 1068-1072.
9. C. NICOLAU and A. CUDD.,Liposomes as Carriers of DNA. Critical Rev. in Therap. Drug Carrier Syst. 1989, 673, 239-271.
10. B.P. TEISSEIRE,C.ROPARS, M.O.VALLEZ, R.A. HERIGAULT and C.NICOLAU, Physiological effects of high-P50 erythrocyte transfusion in
piglets, J.Appl. Physiol. 1985, 58,1810-1817.
11. K. C. FYLAKTAKIDOU, J.-M. LEHN, R. GREFERATH, C. NICOLAU Inositol tripyrophosphate: a new membrane permeant allosteric effector of
haemoglobin, Bioorg Med Chem Lett. 2002, 15, 1605-1608.
12. C. KIEDA , R. GREFERATH, C. CROLA DA SILVA, K.C. FYLAKTAKIDOU, J.-M. LEHN, C. NICOLAU, Suppression of hypoxia-induced HIF-1alpha
and of angiogenesis in endothelial cells by myo-inositol trispyrophosphate-treated erythrocytes. Proc Natl Acad Sci USA 2006, 103, 15576-1581.
C. NICOLAU AND W. S. COLUCCI, Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin,
myo-inositol trispyrophosphate. Proc. Natl. Acad. Sci. USA, 2009, 106, 1926-1929.
14. C. D. DUARTE, R. GREFERATH, C. NICOLAU AND J.-M. LEHN, myo-Inositol trispyrophosphate: a novel allosteric effector of hemoglobin with
high permeation selectivity across the red blood cell plasma membrane. ChemBioChem, 2010, 11, 2543-2548.
15. K. C. FYLAKTAKIDOU, C. D. DUARTE, A. KOUMBIS, C. NICOLAU AND J.-M. LEHN (2011); Polyphosphates and pyrophoshates of hexapyranoses
as allosteric effectors of human hemoglobin: synthesis, molecular recognition and oxygen release. ChemMedChem, 2011, 6, 153-168.
normalization with PO2 increase and endothelial PTEN activation by inositol tris-pyrophosphate brings novel tumor treatment. J. Mol. Med.
2013, 91, 883 - 899
NICOLAU; Enhanced oxygen release by Red Blood Cells to tumors leads to HIF-1 suppression and eradication of early hepatoma in rats.
ChemBioChem 2011, 12, 777-783.
18. C.NICOLAU, Conformation specific therapeutic vaccines against protein misfolding diseases. Rev. Roum. Chim. 2011, 56, 317-323
19. Z. RAYKOV, S. P. GRIKOVA, G. BOUR, J.-M. LEHN, N. A. GIESE, C. NICOLAU, AND M. APRAHAMIAN, myo-Inositol trispyrophosphate-mediated
hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficaly, Int. J. Cancer, 2014, 34, 2572-2582.

Alexandru T. Balaban
Texas A&M University at Galveston, Texas 77553, USA

Revista de Chimie, vol. 67 , no. 8, 2016
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