H
Henry Young
Guest
Differences of opinion - Part II
I would like to apologize to Kaci?s Mom and others in this forum for my sarcastic posting from yesterday. While I stand behind everything I said I could have been more diplomatic in my approach. And for that I apologize. I get a bit testy when I am not feeling well, which is occurring right at the moment. I am in the worst lupus crisis I have ever had. Instead of one or two systems being affected ? all my organ systems are being affected. I took morphine for the pain several weeks ago, 100 mg every four hours, but it makes me ?loopy? and my lucidity goes out the window. Moreover, the side effects are not very nice, especially at such a high dose. I am off morphine now because of the side effects, and now I am in constant pain. Every thread of my body is screaming to me that it hurts and wants me to make it stop and I choose not to.
Let me give you a little history of my scientific background so you know where I am coming from. I am considered by many in my field as one of the original pioneers of non-hematopoietic adult stem cells.
I began my research on non-hematopoietic adult stem cells at a time (1970?s) when these particular cells were thought not to exist. The only cell types that were published at the time were progenitor cells, the immediate precursor cells to adult differentiated tissues. Progenitor cells have a defined biological clock before they are pre-programmed to senesce and die. Moreover, they form only a few, if not just a single cell type. Unfortunately, precursor cells were designated in the literature as ?stem cells?, and some of my peers have perpetuated this in their publications even to this day.
My first exposure to biological research was working in a lab that was attempting to transplant adult differentiated tissues into animals. There were one of either two end results to the experiments? 1) the animal would flat out reject the tissue as foreign and get rid of it (tissue rejection), or 2) the animal would wall off the transplant with scar tissue and sequester it. The body did not know what to do with the foreign tissue.
During this time I had identified a cell or groups of (quiescent) cells, unrecognized previously, that were sequestered in the connective tissues surrounding bone, cartilage, and within the connective tissues of skeletal muscle, dermis of the skin, adipose tissue, and surrounding blood vessels. These particular cells would become activated upon wounding the animal with the result that you could see a change in the material immediately surrounding the cells. The cells would then release themselves from their organ connective tissue compartments and home to the sites of injury. There they would completely replace the missing tissues. I stared publishing that work in the late 1970?s.
I next ventured to a laboratory where I could identify the unknown material histochemically (biochemical identification using histological tissue sections). I discovered that the material was composed of sugar residues called glycoproteins, glycosaminoglycans, and proteoglycans. I could identify each subtype of these materials by their particular staining patters. In addition, that there were other glycoproteins that appeared to stimulate these strange cells to act to repair the tissue.
I next ventured to a laboratory where I could learn to isolate and indentify the particular material I had seen histochemically. I accomplished this feat as well as learning how to culture different types of cells and how the cells would react under various culture conditions.
From there I went to a laboratory that cultured human cancer cells, i.e., osteosarcomas (bone cancers) and chondrosarcomas (cartilage cancers). I learned to use antibodies to recognize various components of the cells, both inside the cells and outside the cells. Moreover, we could pick out a single cancer cell from a group of cells based on its own particular staining pattern.
I then matriculated to where I am today. I set up a research laboratory to identify both the unknown cells and the particular factors that acted on these unknown cells. It took me three years to understand how to isolate the cells, grow the cells outside the body in cell culture, how to freeze the cells without killing them, how to clone the cells from single cells using medium conditioned by factors released from the cells themselves, etc. I then submitted a grant to the National Institutes of Health (NIH) proposing to do the process we had just completed. Their response was ?adult stem cells do not exist, therefore your ideas are flawed and we will not support your research?. One reviewer even called me ?lunatic fringe? and that my ideas were in the realm of science fiction. I turned around and published the data in a peer reviewed scientific journal.
We cloned another set of these cells from a different species of adult animal, performed the same work following our previous protocols and isolated a similar population of cells with the same functions. I again applied to NIH for funding and was turned down, because ?adult stem cells do not exist; only progenitor cells exist?. We published that data as well.
Our area of the southeast received a hurricane-generated flood that lasted for a long time. Our research labs were without power for two weeks and I lost everything - all my clonal cell lines, conditioned medium, etc. Afterwards, I began anew and isolated and cloned, from single cells, another set of these particular cells from yet a different species of adult animal (adult rat). I had a collaborator in France label the clones with a genomic marker (a gene sequence for an insect beta-galatosidase, something that is never found in mammalian tissues). Because it is a gene sequence embedded in the DNA of these cloned stem cells, each time the cells divide the resultant cells have the same amount of beta-Gal as the original cell. Since beta-Gal is an insect sequence, antibodies can be easily generated against it and now we have a label that can track the cells, both in culture and when they were transplanted into the animal.
This was about the time that Dr. Thompson and Dr. Gearhart published on the existence of human embryonic stem cells with the ?plasticity? to form any cell in the body and essentially having ?immortality?, Suddenly, I was not quite the lunatic that mainstream scientists (from Harvard, Stanford, Johns Hopkins, etc.) thought I had been. Maybe adult stem cells did exist, but certainly, they did not have the plasticity of embryonic stem cells.
Since their publications came out in 1998 and 1999, we have published on adult-derived germ layer lineage mesodermal stem cells (also called mesenchymal stem cells), adult-derived pluripotent epiblast-like stem cells, and adult-derived totipotent stem cells. We have cloned them from single cells, had them labeled with a genomic marker, characterized them using a wide array of protocols, and tested these cells in various animal models of disease, i.e., type-I diabetes, myocardial infarctions, bone marrow transplants, vascular ischemia, infertility, and Parkinson?s disease, just to name a few of our ongoing projects.
What separates me from most of my peers is that I am a ?splitter rather than a lumper?. In other words, I want to know everything I can about individual cell types within a population that is giving a desired effect, rather than accepting the desired effect without questioning what individual cells are doing to achieve the desired effect.
If I have offended you, I am sorry and want to apologize to you. I just want to help and get information out there for ?users? of the technology to ask their respective caregivers. That is all. Dr. Young
I would like to apologize to Kaci?s Mom and others in this forum for my sarcastic posting from yesterday. While I stand behind everything I said I could have been more diplomatic in my approach. And for that I apologize. I get a bit testy when I am not feeling well, which is occurring right at the moment. I am in the worst lupus crisis I have ever had. Instead of one or two systems being affected ? all my organ systems are being affected. I took morphine for the pain several weeks ago, 100 mg every four hours, but it makes me ?loopy? and my lucidity goes out the window. Moreover, the side effects are not very nice, especially at such a high dose. I am off morphine now because of the side effects, and now I am in constant pain. Every thread of my body is screaming to me that it hurts and wants me to make it stop and I choose not to.
Let me give you a little history of my scientific background so you know where I am coming from. I am considered by many in my field as one of the original pioneers of non-hematopoietic adult stem cells.
I began my research on non-hematopoietic adult stem cells at a time (1970?s) when these particular cells were thought not to exist. The only cell types that were published at the time were progenitor cells, the immediate precursor cells to adult differentiated tissues. Progenitor cells have a defined biological clock before they are pre-programmed to senesce and die. Moreover, they form only a few, if not just a single cell type. Unfortunately, precursor cells were designated in the literature as ?stem cells?, and some of my peers have perpetuated this in their publications even to this day.
My first exposure to biological research was working in a lab that was attempting to transplant adult differentiated tissues into animals. There were one of either two end results to the experiments? 1) the animal would flat out reject the tissue as foreign and get rid of it (tissue rejection), or 2) the animal would wall off the transplant with scar tissue and sequester it. The body did not know what to do with the foreign tissue.
During this time I had identified a cell or groups of (quiescent) cells, unrecognized previously, that were sequestered in the connective tissues surrounding bone, cartilage, and within the connective tissues of skeletal muscle, dermis of the skin, adipose tissue, and surrounding blood vessels. These particular cells would become activated upon wounding the animal with the result that you could see a change in the material immediately surrounding the cells. The cells would then release themselves from their organ connective tissue compartments and home to the sites of injury. There they would completely replace the missing tissues. I stared publishing that work in the late 1970?s.
I next ventured to a laboratory where I could identify the unknown material histochemically (biochemical identification using histological tissue sections). I discovered that the material was composed of sugar residues called glycoproteins, glycosaminoglycans, and proteoglycans. I could identify each subtype of these materials by their particular staining patters. In addition, that there were other glycoproteins that appeared to stimulate these strange cells to act to repair the tissue.
I next ventured to a laboratory where I could learn to isolate and indentify the particular material I had seen histochemically. I accomplished this feat as well as learning how to culture different types of cells and how the cells would react under various culture conditions.
From there I went to a laboratory that cultured human cancer cells, i.e., osteosarcomas (bone cancers) and chondrosarcomas (cartilage cancers). I learned to use antibodies to recognize various components of the cells, both inside the cells and outside the cells. Moreover, we could pick out a single cancer cell from a group of cells based on its own particular staining pattern.
I then matriculated to where I am today. I set up a research laboratory to identify both the unknown cells and the particular factors that acted on these unknown cells. It took me three years to understand how to isolate the cells, grow the cells outside the body in cell culture, how to freeze the cells without killing them, how to clone the cells from single cells using medium conditioned by factors released from the cells themselves, etc. I then submitted a grant to the National Institutes of Health (NIH) proposing to do the process we had just completed. Their response was ?adult stem cells do not exist, therefore your ideas are flawed and we will not support your research?. One reviewer even called me ?lunatic fringe? and that my ideas were in the realm of science fiction. I turned around and published the data in a peer reviewed scientific journal.
We cloned another set of these cells from a different species of adult animal, performed the same work following our previous protocols and isolated a similar population of cells with the same functions. I again applied to NIH for funding and was turned down, because ?adult stem cells do not exist; only progenitor cells exist?. We published that data as well.
Our area of the southeast received a hurricane-generated flood that lasted for a long time. Our research labs were without power for two weeks and I lost everything - all my clonal cell lines, conditioned medium, etc. Afterwards, I began anew and isolated and cloned, from single cells, another set of these particular cells from yet a different species of adult animal (adult rat). I had a collaborator in France label the clones with a genomic marker (a gene sequence for an insect beta-galatosidase, something that is never found in mammalian tissues). Because it is a gene sequence embedded in the DNA of these cloned stem cells, each time the cells divide the resultant cells have the same amount of beta-Gal as the original cell. Since beta-Gal is an insect sequence, antibodies can be easily generated against it and now we have a label that can track the cells, both in culture and when they were transplanted into the animal.
This was about the time that Dr. Thompson and Dr. Gearhart published on the existence of human embryonic stem cells with the ?plasticity? to form any cell in the body and essentially having ?immortality?, Suddenly, I was not quite the lunatic that mainstream scientists (from Harvard, Stanford, Johns Hopkins, etc.) thought I had been. Maybe adult stem cells did exist, but certainly, they did not have the plasticity of embryonic stem cells.
Since their publications came out in 1998 and 1999, we have published on adult-derived germ layer lineage mesodermal stem cells (also called mesenchymal stem cells), adult-derived pluripotent epiblast-like stem cells, and adult-derived totipotent stem cells. We have cloned them from single cells, had them labeled with a genomic marker, characterized them using a wide array of protocols, and tested these cells in various animal models of disease, i.e., type-I diabetes, myocardial infarctions, bone marrow transplants, vascular ischemia, infertility, and Parkinson?s disease, just to name a few of our ongoing projects.
What separates me from most of my peers is that I am a ?splitter rather than a lumper?. In other words, I want to know everything I can about individual cell types within a population that is giving a desired effect, rather than accepting the desired effect without questioning what individual cells are doing to achieve the desired effect.
If I have offended you, I am sorry and want to apologize to you. I just want to help and get information out there for ?users? of the technology to ask their respective caregivers. That is all. Dr. Young