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This remarkable volume is a testament to the evolution of calcium research within living cells and the profound impact it has had on the field of science. It chronicles the journey from the earliest days of studying calcium within the cell, well before the groundbreaking work of a celebrated Nobel laureate in chemistry, to the creation of innovative “modern fluorescence calcium indicators” that have become indispensable tools in contemporary research and drug screening. These modern indicators primarily utilize UV and green fluorescence, providing a non-invasive window into the world of cellular calcium.
I was happy when Dr. Taylor agreed to write the Foreword for the book in memory of Roger because when he started his fluorescence journey in 1982, Dr. Lansing, then a professor at Carnegie Mellon University was leading a novel program for developing fluorescence-based biosensors of cellular physiology and light microscope imaging and had just recruited Alan Waggoner and that was the main fluorescence base in the country. Therefore Dr. Taylor and Dr. Waggoner were his first colleagues in the field.
I am happy he remembered Dr. Waggoner and the late Dr. Haugland for their contribution to fluorescence applications in the country.
The introduction starts with the definition of the title of the book and the author, and then proceeds to tell the story of ACR-2.
The story includes the development of ACR-2 as an improvement from its predecessor ACR-1 by structure and properties and its commercialization to ICR.
After that, the first four chapters are introduced with short summaries of their chemistries and the final short chapter, which is the biography of the author is added to conclude the introduction.
1.Asante Calcium Red-2 (ACR-2) is the name of the first true red-emitting fluorescent CYTOSOLIC calcium indicator with ideal physical properties for cells.
It was made in response to a need for a good red-emitting fluorescent calcium indicator since modern fluorescent calcium indicators were invented and introduced in 1982 by the late Roger Tsien, 2008 Nobel Prize Laureate, Akwasi Minta and Grzegorz Grynkiewicz, following a comprehensive review article on red fluorescent calcium indicators by authors the below.
(Dr Akwasi Minta-ACR-2)1
Currently all useful CYTOSOLIC fluorescent calcium indicators are either green-emitting or ratiometric Ultraviolet-emitting and the article reviewed all the red-emitting calcium indicators from1982 to the time of the review (2014), their physical, biophysical properties and some of their applications to date.
Their conclusion and the reason for my making ACR-2 is summed up in the paragraph below.
(The paragraph here)2
2.Dedication to the memory of Roger Tsien,2008 Nobel Laurate in Chemistry
Roger was awarded the Nobel prize for his discovery and development of the green fluorescent protein, but his fluorescence career started with the invention of a synthetic fluorescent indicator, ‘Quin-2’, for measuring calcium in cells specifically in the CYTOSOL. The beauty of this invention is that he studied Physics and Chemistry as an undergraduate and earned a PhD in Physiology, but he learned organic synthesis during his graduate studies to design, synthesize and work on how to use it in measuring calcium in cells. He learned organic synthesis in the department of Organic Chemistry in Lensfield Road, Cambridge UK. I was a graduate student in organic chemistry at the same time and saw him attending our seminars and coming to the laboratory after hours. I was surprised when I saw his landmark paper on the design and synthesis of Quin 2, because the chemistry was extensive and elegant for a part-time chemist. He chose fluorescence, the most sensitive form of detection of compounds in the cell, for his invention, and so Greg and I had to advance his invention as synthetic organic chemists to create fluorophores, Fura, Fluo, Indo, etc. I am dedicating ACR-2 to his memory but I have taken advantage of it to describe how he started and how we developed this new and current way of studying calcium in cells.
I have emphasized CYTOSOL because he never liked seeing our dyes in organelles. In fact, most of the red dyes made before ACR-2 either go into the mitochondria because they have a positive charge on a nitrogen or go into membranes because of hydrophobicity.
Roger passed away on August 24, 2016, at a young age of 64 and is missed by many including Dr. Lansing Taylor who wrote a foreword to this book.
3.The book has been divided into five Chapters to include my biography (chapter 5); the design, synthesis and applications of ACR-2,(chapter 4); Red-emitting fluorescent calcium indicators, their importance in biology, the case presented by the authors of the review article, and the flaws in all the red fluorescent calcium indicators they presented and red indicators before ACR-2, (Chapter 3); the story of modern fluorescent calcium indicators since 1982 to 2022, (Chapter 2); the measurement of calcium in cells before 1982, (Chapter1). Introduction to the book and all the chapters begins the chapters. I have only one figure for the appendix, and it is very important for the design of ACR.