Charles Leblond
Encyclopedia
Charles Philippe Leblond, (February 5, 1910 – April 10, 2007) was a pioneer of cell biology
and stem cell
research and a former Canadian professor of anatomy. Leblond is notable for developing autoradiography and his work showing how cells continuously renew themselves, regardless of age.
on a histological section containing a radio element, the emulsion was eventually activated by the radio-element; and if thereafter routine photographic development and fixation
were applied to the emulsion-covered section, black silver grains appeared in the emulsion wherever it overlay sites containing a radio-element. This liquid emulsion approach has been used to develop a new High Resolution Autoradiography procedure characterized by close contact between emulsion and section. Such close contact makes it possible to localize the radio-elements in the section at high resolution
, so that radio-elements can be localized at high magnification in the light microscope.
This procedure has been utilized to examine some of the dynamic features of body components, with the main findings as follows:
His results threw doubt on the validity of three traditional concepts dear to biologists in the earlier part of the twentieth century: "stability" of the cell, in which the cell and its components are unchanging, permanent structures; "specificity" of cell function, in which each cell type has a distinct, unique function; and "activity-rest alternation" of cell function, in which each period of cellular activity is followed by a period during which the activity ceases.
He has proposed replacing cell "specificity" by "multipotentiality", "activity-rest alternation" by "continuity" and "stability" of cell components by "renewal". These various results have provided the foundation not only for modern stem cell research, but also for modern cell biology.
As Nobel laureate George Palade noted on the occasion of the 1992 Prix Marie-Victorin
to Leblond, Charles Leblond’s discoveries are so fundamental that they are taught in schools and colleges throughout the world.
, France
, in 1910, the son of a building contractor who died when Leblond was only 10 years old, leaving his mother to raise four boys on her own. A brilliant student, Leblond debated becoming a film producer, an architect or a scientist. In the end, he decided on science, and enrolled in Medicine at the University of Paris
. He was fascinated by his first course in histology
and decided to pursue this field as a career.
Leblond obtained his M.D. degree from the University of Paris
in 1934. His doctoral thesis described the histochemical localizion of ascorbic acid
, which he found to predominate in steroid-secreting cells. This study led him, with a Rockefeller postdoctoral fellowship
in hand, to the endocrinology
-orientated Department of Anatomy
at Yale University
in 1935, where he carried out studies on factors influencing maternal behavior. It was here that he met his wife Gertrude Sternschus, to whom he was married for 64 years.
In 1937, Leblond joined the Laboratoire de Synthese Atomique in Paris which was involved in preparing radioactive isotopes for use in investigating the fate of various molecules in biological processes. Under the guidance of Antoine Lacassagne, Leblond injected radioiodine-128
, into a rat
and found that the label promptly accumulated in the thyroid gland, presumably incorporated into the thyroid hormone precursor thyroglobulin
. To localize this label more precisely within the thyroid tissue, Leblond attempted to use the novel technique of autoradiography.
Unfortunately, Leblond’s first attempt to use autoradiography failed, the reason being that the radioiodine-128 isotope, with its extremely short half-life
(25 minutes), disintegrated so quickly that too little radioactivity remained to be detected by the photographic emulsion.
as a lecturer in histology, and quickly rose to assistant (1943), associate (1946), and then full professor of anatomy (1948). He served as the chair of the Department of Anatomy from 1957–1974.
At McGill, Leblond used the newly-available radioiodine-131
with a half-life of 8 days, to repeat his autoradiographic experiment on thyroid tissue. With this method, the resolving power was less than 100 µm, but nonetheless he was able to localize the radioactivity to specific thyroid [follicles].
Leblond’s early career at McGill was interrupted by World War II
, during which he served in the Free French Forces
. He was dispatched first to Rio de Janeiro
, then to London
, where he conducted medical exams of would-be soldiers.
"In 1946, after returning to Montreal from service with the Free French Forces, it was clear to me that the crude technique previously used for radioautography had to be improved". In collaboration with Leonard Bélanger, Leblond worked on increasing the resolution
of the autoradiographic technique. They were advised by physicist Pierre Demers to melt the emulsion from Eastman Kodak
lantern slides, paint it directly on the sections, and then develop the emulsion while it was still attached to the histologic sections. This resulted in a tenfold improvement in resolution. Subsequently, Leblond and his colleagues developed a technique in which the histologic slides were dipped directly into liquid emulsion. The use of thinner sections and emulsion coats led to further advances in resolution, and the introduction of tritium was a technical milestone.
High Resolution Autoradiography procedure continues to be used today by molecular biologists to detect RNA
molecules in situ, and to study the localization of genes
and DNA
sequences.
To maintain the population of spermatogonia, the seminiferous epithelium was shown to contain a population of stem cells which divided to produce differentiated cells as well as to maintain their own number. As noted in a seminal publication by Leblond, "the reappearance at each cycle of a new dormant cell which acts as the stem cell of spermatocyte
s is described as the 'Stem Cell Renewal Theory'" . This article is the first one in which nests of cells dividing in an adult organ are designated as “stem cells”.
Leblond and his colleagues also found evidence for the presence of occasional adult stem cells even in tissues which are composed almost entirely of non-dividing cells. In skeletal muscle
, the muscle fibers had been shown to exhibit an age-related increase in the number of nuclei
. His studies showed that muscle satellite cells could be considered to be adult stem cells in muscle fibers.
From the studies of Leblond and his colleagues, it was concluded that the body has three types of cell populations:
To mark his 65th birthday in 1975, Leblond was honored at an international symposium on the existence of stem cells in adult tissues; the resulting book, Stem Cells of Renewing Cell Populations, was the first formal, comprehensive account on the subject.
It is of interest that autoradiographic studies by Leblond during this period also settled a controversy regarding the cellular site of synthesis of ribonucleic acid. Using radiolabeled cytidine in some forty cell types, he and his colleagues were the first to demonstrate decisively that RNA is continuously synthesized in the nucleus and then migrates to the cytoplasm.
region in most cell types was dramatically stained by the periodic acid-Schiff staining technique, which is specially directed to carbohydrate-rich proteins carrying 1,2 glycols. In the electron microscope, using the periodic acid silver technique, there was a gradient of staining intensity from the cis
to the trans
side of the Golgi apparatus, suggesting that carbohydrate residues were added to proteins at this site.
To test this hypothesis, light and then EM autoradiographic studies were carried out by Leblond and Neutra in 1966 after injecting rats with 3H-glucose or 3H-galactose. Within ten minutes, the label was dramatically localized to the Golgi apparatus of intestinal goblet cells, indicating that this was the cellular site of addition of sugar residues in the synthesis of the carbohydrate side chains of mucous glycoproteins.
This discovery had a tremendous impact on the scientific community, being the first evidence for a functional role of the Golgi apparatus in the synthetic process.
. This launched a twenty-year molecular exploration culminating in the concept of the basement membrane as an integrated polymer
, rather than as layers of separated macromolecules initially favored by others.
Leblond continued to attend all weekly departmental seminars well into his 90’s and continued to publish in peer-reviewed journals into the new millennium. He learned to use a computer at age 90, starting a presentation at an international conference back in 2004, by noting: "A month ago, I thought Power Point was a tool for sharpening pencils."
His total contributions resulted in the publication of 430 scientific papers, many of them still frequently cited. In late September 2006, he published his final article—about detecting the MMP9
cysteine
activation switch for the first time in remodeling cartilage
.
Leblond was preceded in death by his wife of 64 years, Gertrude Sternschuss, who died in 2000. After Gertrude died, Leblond married a childhood friend, Odette Lengrand, in 2001; they were both 91. Odette died in 2004.
-magenta
coloring of carbohydrate 1-2-glycol groups20,21 inspired Leblond’s Golgi and cell coat discoveries also elegantly inspired the Leblond wardrobe, automobile and even home interior and country home name – Val Mauve.
One of Leblond’s continuing interest was his endeavour to ensure the usage of the correct name for the technique which he had spent a lifetime developing. In a review chapter written in 1987, entitled: “Radioautography: The role played by anatomists in the development and application of the technique.”, he writes: The reasons why the term “radioautography” is preferred to “autoradiography” for the detection of radioactive elements by photographic emulsion are as follows. The term “autoradiography” is a compound word including the term “radiography”. This term is defined as a picture produced by an x-ray beam that has passed through an object. Since this object, for instance a bone examined after a fracture, is located between the source of radiation and the emulsion, it appears white in the emulsion; that is, it is seen as a negative image. In contrast, when radioactive elements are seen in sections, the object under study is itself the source of the radiation that influences the emulsion. The black image thus produced is a photographic positive. It may be referred to as an autograph, that is “the reproduction of form or outline of anything by an impression from the thing itself” (Oxford English Dictionary, 1975). Hence, the author called it initially a “radioactive autograph”. Later, on the advice of an editor, he condensed these two words into “radioautograph”. The procedure is often called “autoradiography” but “radioautography” is the correct term.
Leblond had 4 children for which, in a true Cartesian manner, he chose names starting with the letter "P": Philippe, Paul, Pierre and (Marie)-Pascale. He also had 7 grandchildren.
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
and stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
research and a former Canadian professor of anatomy. Leblond is notable for developing autoradiography and his work showing how cells continuously renew themselves, regardless of age.
Main research interests
In 1946, Leblond found that, when he poured liquid photographic emulsionPhotographic emulsion
Photographic emulsion is a light-sensitive colloid, such as gelatin, coated onto a substrate. In silver-gelatin photography, the emulsion consists of silver halide crystals suspended in gelatin, and the substrate may be glass, plastic film, paper or fabric....
on a histological section containing a radio element, the emulsion was eventually activated by the radio-element; and if thereafter routine photographic development and fixation
Fixation (histology)
In the fields of histology, pathology, and cell biology, fixation is a chemical process by which biological tissues are preserved from decay, thereby preventing autolysis or putrefaction...
were applied to the emulsion-covered section, black silver grains appeared in the emulsion wherever it overlay sites containing a radio-element. This liquid emulsion approach has been used to develop a new High Resolution Autoradiography procedure characterized by close contact between emulsion and section. Such close contact makes it possible to localize the radio-elements in the section at high resolution
Image resolution
Image resolution is an umbrella term that describes the detail an image holds. The term applies to raster digital images, film images, and other types of images. Higher resolution means more image detail....
, so that radio-elements can be localized at high magnification in the light microscope.
This procedure has been utilized to examine some of the dynamic features of body components, with the main findings as follows:
- The existence of stem cells in adult organs, as shown by autoradiography with labeled thymidineThymidineThymidine is a chemical compound, more precisely a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine in double-stranded DNA...
. - The continuity of protein synthesisProtein biosynthesisProtein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
in living cells, as shown by autoradiography with labeled amino acids. - The key role of the Golgi apparatusGolgi apparatusThe Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
in protein glycosylationGlycosylationGlycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
, as shown by autoradiography with labeled hexoseHexoseIn organic chemistry, a hexose is a monosaccharide with six carbon atoms, having the chemical formula C6H12O6. Hexoses are classified by functional group, with aldohexoses having an aldehyde at position 1, and ketohexoses having a ketone at position 2....
s.
His results threw doubt on the validity of three traditional concepts dear to biologists in the earlier part of the twentieth century: "stability" of the cell, in which the cell and its components are unchanging, permanent structures; "specificity" of cell function, in which each cell type has a distinct, unique function; and "activity-rest alternation" of cell function, in which each period of cellular activity is followed by a period during which the activity ceases.
He has proposed replacing cell "specificity" by "multipotentiality", "activity-rest alternation" by "continuity" and "stability" of cell components by "renewal". These various results have provided the foundation not only for modern stem cell research, but also for modern cell biology.
As Nobel laureate George Palade noted on the occasion of the 1992 Prix Marie-Victorin
Prix Marie-Victorin
The Prix Marie-Victorin is an award by the Government of Quebec that is part of the Prix du Québec, which "goes to researchers in the pure and applied sciences whose work lies in fields outside biomedicine. These fields include the natural and physical sciences, engineering, and technology, and the...
to Leblond, Charles Leblond’s discoveries are so fundamental that they are taught in schools and colleges throughout the world.
Early days
CP Leblond was born in LilleLille
Lille is a city in northern France . It is the principal city of the Lille Métropole, the fourth-largest metropolitan area in the country behind those of Paris, Lyon and Marseille. Lille is situated on the Deûle River, near France's border with Belgium...
, France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
, in 1910, the son of a building contractor who died when Leblond was only 10 years old, leaving his mother to raise four boys on her own. A brilliant student, Leblond debated becoming a film producer, an architect or a scientist. In the end, he decided on science, and enrolled in Medicine at the University of Paris
University of Paris
The University of Paris was a university located in Paris, France and one of the earliest to be established in Europe. It was founded in the mid 12th century, and officially recognized as a university probably between 1160 and 1250...
. He was fascinated by his first course in histology
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
and decided to pursue this field as a career.
Leblond obtained his M.D. degree from the University of Paris
University of Paris
The University of Paris was a university located in Paris, France and one of the earliest to be established in Europe. It was founded in the mid 12th century, and officially recognized as a university probably between 1160 and 1250...
in 1934. His doctoral thesis described the histochemical localizion of ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
, which he found to predominate in steroid-secreting cells. This study led him, with a Rockefeller postdoctoral fellowship
Rockefeller Foundation
The Rockefeller Foundation is a prominent philanthropic organization and private foundation based at 420 Fifth Avenue, New York City. The preeminent institution established by the six-generation Rockefeller family, it was founded by John D. Rockefeller , along with his son John D. Rockefeller, Jr...
in hand, to the endocrinology
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
-orientated Department of Anatomy
Anatomy
Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...
at Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
in 1935, where he carried out studies on factors influencing maternal behavior. It was here that he met his wife Gertrude Sternschus, to whom he was married for 64 years.
In 1937, Leblond joined the Laboratoire de Synthese Atomique in Paris which was involved in preparing radioactive isotopes for use in investigating the fate of various molecules in biological processes. Under the guidance of Antoine Lacassagne, Leblond injected radioiodine-128
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
, into a rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
and found that the label promptly accumulated in the thyroid gland, presumably incorporated into the thyroid hormone precursor thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
. To localize this label more precisely within the thyroid tissue, Leblond attempted to use the novel technique of autoradiography.
Unfortunately, Leblond’s first attempt to use autoradiography failed, the reason being that the radioiodine-128 isotope, with its extremely short half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
(25 minutes), disintegrated so quickly that too little radioactivity remained to be detected by the photographic emulsion.
Development of autoradiography
In 1941, Leblond moved to McGill UniversityMcGill University
Mohammed Fathy is a public research university located in Montreal, Quebec, Canada. The university bears the name of James McGill, a prominent Montreal merchant from Glasgow, Scotland, whose bequest formed the beginning of the university...
as a lecturer in histology, and quickly rose to assistant (1943), associate (1946), and then full professor of anatomy (1948). He served as the chair of the Department of Anatomy from 1957–1974.
At McGill, Leblond used the newly-available radioiodine-131
Iodine-131
Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical...
with a half-life of 8 days, to repeat his autoradiographic experiment on thyroid tissue. With this method, the resolving power was less than 100 µm, but nonetheless he was able to localize the radioactivity to specific thyroid [follicles].
Leblond’s early career at McGill was interrupted by World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, during which he served in the Free French Forces
Free French Forces
The Free French Forces were French partisans in World War II who decided to continue fighting against the forces of the Axis powers after the surrender of France and subsequent German occupation and, in the case of Vichy France, collaboration with the Germans.-Definition:In many sources, Free...
. He was dispatched first to Rio de Janeiro
Rio de Janeiro
Rio de Janeiro , commonly referred to simply as Rio, is the capital city of the State of Rio de Janeiro, the second largest city of Brazil, and the third largest metropolitan area and agglomeration in South America, boasting approximately 6.3 million people within the city proper, making it the 6th...
, then to London
London
London is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
, where he conducted medical exams of would-be soldiers.
"In 1946, after returning to Montreal from service with the Free French Forces, it was clear to me that the crude technique previously used for radioautography had to be improved". In collaboration with Leonard Bélanger, Leblond worked on increasing the resolution
Optical resolution
Optical resolution describes the ability of an imaging system to resolve detail in the object that is being imaged.An imaging system may have many individual components including a lens and recording and display components...
of the autoradiographic technique. They were advised by physicist Pierre Demers to melt the emulsion from Eastman Kodak
Eastman Kodak
Eastman Kodak Company is a multinational imaging and photographic equipment, materials and services company headquarted in Rochester, New York, United States. It was founded by George Eastman in 1892....
lantern slides, paint it directly on the sections, and then develop the emulsion while it was still attached to the histologic sections. This resulted in a tenfold improvement in resolution. Subsequently, Leblond and his colleagues developed a technique in which the histologic slides were dipped directly into liquid emulsion. The use of thinner sections and emulsion coats led to further advances in resolution, and the introduction of tritium was a technical milestone.
High Resolution Autoradiography procedure continues to be used today by molecular biologists to detect RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
molecules in situ, and to study the localization of genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequences.
Studies on the turnover of cells
Leblond used autoradiography to introduce radioactive precursors of DNA, and then examine the renewal and fate of cells of several basic tissue types. He demonstrated for the first time that most cells and tissues in the adult body undergo continued renewal. Using mathematical models and modern methods of quantitation, Leblond and his colleagues estimated with remarkable accuracy the turnover and mitotic rates of numerous cell types. He and his colleagues made fascinating discoveries that resulted in the introduction of "time dimension" to cells and tissues, opening the doors to the understanding of the cell cycle and to the identification of stem cells.Identification of Stem Cells in Adult Organs
In the male seminiferous epithelium, studies by Leblond and Yves Clermont in the early 1950’s had deciphered how spermatogonia gave rise to spermatocytes, which then differentiated into mature sperm cells in a specific cycle.To maintain the population of spermatogonia, the seminiferous epithelium was shown to contain a population of stem cells which divided to produce differentiated cells as well as to maintain their own number. As noted in a seminal publication by Leblond, "the reappearance at each cycle of a new dormant cell which acts as the stem cell of spermatocyte
Spermatocyte
A spermatocyte is a male gametocyte, derived from a spermatogonium, which is in the developmental stage of spermatogenesis during which meiosis occurs. It is located in the seminiferous tubules of the testis.-Spermatogenesis:...
s is described as the 'Stem Cell Renewal Theory'" . This article is the first one in which nests of cells dividing in an adult organ are designated as “stem cells”.
Leblond and his colleagues also found evidence for the presence of occasional adult stem cells even in tissues which are composed almost entirely of non-dividing cells. In skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
, the muscle fibers had been shown to exhibit an age-related increase in the number of nuclei
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
. His studies showed that muscle satellite cells could be considered to be adult stem cells in muscle fibers.
From the studies of Leblond and his colleagues, it was concluded that the body has three types of cell populations:
- "Static cell populations", which are composed of non-dividing cells and include no adult stem cells. These populations have the "stability" formerly attributed to all cells
- "Expanding cell populations" in which small numbers of adult stem cellAdult stem cellAdult stem cells are undifferentiated cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissues...
s exist, and give rise to skeletal fiber nuclei or glial cells of the brain - "Renewing cell populations" in which adult stem cells are an essential feature
To mark his 65th birthday in 1975, Leblond was honored at an international symposium on the existence of stem cells in adult tissues; the resulting book, Stem Cells of Renewing Cell Populations, was the first formal, comprehensive account on the subject.
Continuous Protein Synthesis in living Cells
When Leblond and his colleagues used 14C-bicarbonate, and then 35S-labeled amino acids to investigate protein synthesis, they were astonished to find that virtually all cells in the body incorporated label. This led them to the conclusion, considered heretical at the time, that all cells continually synthesized proteins. This was among the first evidence to replace the Specificity concept with the idea that most cells are multipotential in their functions.It is of interest that autoradiographic studies by Leblond during this period also settled a controversy regarding the cellular site of synthesis of ribonucleic acid. Using radiolabeled cytidine in some forty cell types, he and his colleagues were the first to demonstrate decisively that RNA is continuously synthesized in the nucleus and then migrates to the cytoplasm.
Role of the Golgi Apparatus in Protein Glycosylation
A majority of body proteins is glycosylated, although the proportion of carbohydrates in proteins is quite variable. Leblond had shown in earlier studies that the golgi apparatusGolgi
Golgi may refer to:*Camillo Golgi , Italian physician and scientist after which the following terms are named:**Golgi apparatus , an organelle in the eukaryotic cell...
region in most cell types was dramatically stained by the periodic acid-Schiff staining technique, which is specially directed to carbohydrate-rich proteins carrying 1,2 glycols. In the electron microscope, using the periodic acid silver technique, there was a gradient of staining intensity from the cis
Cis
Cis may have the following meanings:* "Cis-" as a prefix of Latin origin, meaning "on the same side [as]" or "on this side [of]", with several derived usages:** In chemistry, cis- refers to cis-trans isomerism...
to the trans
Trans
Trans is a Latin noun or prefix, meaning "across", "beyond" or "on the opposite side".Trans may refer to:- Science and technology :* Cis-trans isomerism, in chemistry, a form of stereoisomerism...
side of the Golgi apparatus, suggesting that carbohydrate residues were added to proteins at this site.
To test this hypothesis, light and then EM autoradiographic studies were carried out by Leblond and Neutra in 1966 after injecting rats with 3H-glucose or 3H-galactose. Within ten minutes, the label was dramatically localized to the Golgi apparatus of intestinal goblet cells, indicating that this was the cellular site of addition of sugar residues in the synthesis of the carbohydrate side chains of mucous glycoproteins.
This discovery had a tremendous impact on the scientific community, being the first evidence for a functional role of the Golgi apparatus in the synthetic process.
Other studies
Other classics include: identification of how skeletal bones grow through osteoblast deposition and osteoclast remodeling, early discovery of the biogenesis and metabolism of thyroxine and detection of triiodothyronine, early prediction of DNA semiconservative replication published days after the Watson and Crick Nature article, the discovery of axonal transport, the Warshawsky et al. finding that nascent proteins are processed from the rough endoplasmic reticulum through the Golgi apparatus into pancreatic zymogen granules (made in hot competition with the Palade lab at Rockefeller University), the first realization that the Golgi apparatus is the site of terminal glycosylation, the discovery of the cell coat, the cellular biogenesis of collagen, and new insights into the ultrastructure of basement membrane."Retirement" and later days
At 65, instead of retiring, Leblond continued his research with an NIH Fogarty Scholarship at the National Institute of Dental Research, where he learned about immunohistochemistryImmunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
. This launched a twenty-year molecular exploration culminating in the concept of the basement membrane as an integrated polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
, rather than as layers of separated macromolecules initially favored by others.
Leblond continued to attend all weekly departmental seminars well into his 90’s and continued to publish in peer-reviewed journals into the new millennium. He learned to use a computer at age 90, starting a presentation at an international conference back in 2004, by noting: "A month ago, I thought Power Point was a tool for sharpening pencils."
His total contributions resulted in the publication of 430 scientific papers, many of them still frequently cited. In late September 2006, he published his final article—about detecting the MMP9
MMP9
Matrix metallopeptidase 9 , also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B , is an enzyme that in humans is encoded by the MMP9 gene.- Function :...
cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
activation switch for the first time in remodeling cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
.
Leblond was preceded in death by his wife of 64 years, Gertrude Sternschuss, who died in 2000. After Gertrude died, Leblond married a childhood friend, Odette Lengrand, in 2001; they were both 91. Odette died in 2004.
Honorary Degrees of Doctor of Sciences
- Acadia UniversityAcadia UniversityAcadia University is a predominantly undergraduate university located in Wolfville, Nova Scotia, Canada with some graduate programs at the master's level and one at the doctoral level...
, 1972 - McGill University, 1982
- University of Montreal, 1985
- York UniversityYork UniversityYork University is a public research university in Toronto, Ontario, Canada. It is Canada's third-largest university, Ontario's second-largest graduate school, and Canada's leading interdisciplinary university....
, 1986 - Sherbrooke University, 1988
Prizes
- Prix Saintour, French Academy, 1935
- Gairdner Foundation International AwardGairdner Foundation International AwardThe Gairdner Foundation International Award is given annually at a special dinner to three to six people for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a precursor to winning the Nobel Prize in Medicine; as of 2007, 69 Nobel...
, 1965 - Isaac Schour Award, International Association for Dental ResearchInternational Association for Dental ResearchThe International Association for Dental Research is a professional association that focuses on research in the field of dentistry. The aim of this association by constitution is to promote research in all fields of oral and related sciences, to encourage improvements in methods for the prevention...
, 1974 - Henry Grey Award, American Association of Anatomists, 1978
- J.C.B. Grant Award, Canadian Association of Anatomists, 1979
- E-B Wilson Award, American Society for Cell Biology, 1982
- Duncan Graham Award, Royal College of Physicians and Surgeons of Canada, 1986
- Centennial Award, American Association of Anatomists, 1979
- Prix Marie-VictorinPrix Marie-VictorinThe Prix Marie-Victorin is an award by the Government of Quebec that is part of the Prix du Québec, which "goes to researchers in the pure and applied sciences whose work lies in fields outside biomedicine. These fields include the natural and physical sciences, engineering, and technology, and the...
, QuebecQuebecQuebec or is a province in east-central Canada. It is the only Canadian province with a predominantly French-speaking population and the only one whose sole official language is French at the provincial level....
Province, 1992
Medals
- Flavelle MedalFlavelle MedalThe Flavelle Medal is an award of the Royal Society of Canada "for an outstanding contribution to biological science during the preceding ten years or for significant additions to a previous outstanding contribution to biological science". It is named in honour of Joseph Wesley Flavelle and is...
, Royal Society of CanadaRoyal Society of CanadaThe Royal Society of Canada , may also operate under the more descriptive name RSC: The Academies of Arts, Humanities and Sciences of Canada , is the oldest association of scientists and scholars in Canada...
, 1961 - Medal Léo-Pariseau, «Assoc. Canadienne Française pour l’Avancement des Sciences», 1962
- McLaughlin Medal, Royal Society of Canada, 1983
- George Gomori Medal, Histochemical Society, 1988
Other honours
- 1951 – Fellow of the Royal Society of CanadaRoyal Society of CanadaThe Royal Society of Canada , may also operate under the more descriptive name RSC: The Academies of Arts, Humanities and Sciences of Canada , is the oldest association of scientists and scholars in Canada...
- 1965 – Fellow of the Royal SocietyRoyal SocietyThe Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
, London, UK - 1970 - American Academy of Arts and SciencesAmerican Academy of Arts and SciencesThe American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
- 1988 - Royal Microscopical Society, UK, 1988
- 1995 – Canadian Medical Hall of FameCanadian Medical Hall of FameThe Canadian Medical Hall of Fame is a Canadian charitable organization, founded in 1994, that honours Canadians who have contributed to the understanding of disease and improving the health of people. It has a museum in London, Ontario, and has an annual induction ceremony.-2012:*Terry Fox*John...
- 2000 – Companion, Order of CanadaOrder of CanadaThe Order of Canada is a Canadian national order, admission into which is, within the system of orders, decorations, and medals of Canada, the second highest honour for merit...
- 2001 – Grand Officer, National Order of QuebecNational Order of QuebecThe National Order of Quebec, termed officially in French as l'Ordre national du Québec, and in English abbreviation as the Order of Quebec, is a civilian honour for merit in the Canadian province of Quebec...
Trivia
Periodic acid Schiff stain whose lively purplePurple
Purple is a range of hues of color occurring between red and blue, and is classified as a secondary color as the colors are required to create the shade....
-magenta
Magenta
Magenta is a color evoked by light stronger in blue and red wavelengths than in yellowish-green wavelengths . In light experiments, magenta can be produced by removing the lime-green wavelengths from white light...
coloring of carbohydrate 1-2-glycol groups20,21 inspired Leblond’s Golgi and cell coat discoveries also elegantly inspired the Leblond wardrobe, automobile and even home interior and country home name – Val Mauve.
One of Leblond’s continuing interest was his endeavour to ensure the usage of the correct name for the technique which he had spent a lifetime developing. In a review chapter written in 1987, entitled: “Radioautography: The role played by anatomists in the development and application of the technique.”, he writes: The reasons why the term “radioautography” is preferred to “autoradiography” for the detection of radioactive elements by photographic emulsion are as follows. The term “autoradiography” is a compound word including the term “radiography”. This term is defined as a picture produced by an x-ray beam that has passed through an object. Since this object, for instance a bone examined after a fracture, is located between the source of radiation and the emulsion, it appears white in the emulsion; that is, it is seen as a negative image. In contrast, when radioactive elements are seen in sections, the object under study is itself the source of the radiation that influences the emulsion. The black image thus produced is a photographic positive. It may be referred to as an autograph, that is “the reproduction of form or outline of anything by an impression from the thing itself” (Oxford English Dictionary, 1975). Hence, the author called it initially a “radioactive autograph”. Later, on the advice of an editor, he condensed these two words into “radioautograph”. The procedure is often called “autoradiography” but “radioautography” is the correct term.
Leblond had 4 children for which, in a true Cartesian manner, he chose names starting with the letter "P": Philippe, Paul, Pierre and (Marie)-Pascale. He also had 7 grandchildren.
External links
- Charles Philippe Leblond at The Canadian EncyclopediaThe Canadian EncyclopediaThe Canadian Encyclopedia is a source of information on Canada. It is available online, at no cost. The Canadian Encyclopedia is available in both English and French and includes some 14,000 articles in each language on a wide variety of subjects including history, popular culture, events, people,...
- Charles Philippe Leblond at The Canadian Medical Hall of Fame
- Prix Marie-Victorin Ceremony (in French)
- National Order of Quebec (in French)