Timing and Cancer therapy

I just heard the 10.00 p.m. news on CNN- about a testimonial success treatment of giving cancer therapy when your normal body cells are dormant (sleeping) and cancer cells are active and dividing. Dr. Gypta gave the commentary.
I don't know why people should consider this such a unique technique. When I was director of the Winnipeg Clinic Research Institute Laboratory and was invited by the Horner drug company to give a talk at a symposium in Montreal in 1967 during Expo I spoke of the importance of "Analysis of stages of the cell cycle in Chemotherapy"
Analysis of stages means determining in a tumor as well as normal body tissue the proportion of cells in different stages of the cell cycle, i.e G1, S (DNA synthetic ) stage, G2 or post DNA synthetic, M or mitotic when the cells are undergoing cell division which can be visualized with an ordinary microscope and G0 or the stage of differentiation . With most cancer very few - if any cells enter the G0 stage, instead after cell division (M stage) they renter G1 and proceed through the S,G2 and M stages.
I had devised a method to do this analysis based on the combined techniques of DNA cytophotometry and cellular autoradiography using tritiated thymidine.
So you see Anderson Cooper the technique is not that new. Unfortunately in biology and other sciences, advances may sit undiscovered for years- like Mendel and Genetics. In my case I could not promote the technique because within a year after I gave the presentation the Board of Directors headed by Dr. P.H. Thorlakson dissolved the private research lab which was associated with the Winnipeg Clinic. In order to survive financially I had to abandon research and go into medical practice. The technique was published in the Can. Med. Assoc. J.

Gene dosage and Disease

I shall zero in on 3 areas. Mongolism, Sex chromosomes and Huntingtons

Human karyotype consists of 46 chromosomes.There are 22 pairs of autosomes or body chromosomes and 1 pair of sex chromosomes- XX for females and XY for males
Mongolism is present in individuals who either have an entire extra chromosome 21 -or part of this autosomal chromosome. Therefore in Mongolism genes whose loci are on chromosome 21 are therefore present in triplet. To my knowledge there is no specific gene mutation which occurs in mongolism , rather symptoms are a manifestation of this gene dosage. The "Rag doll effect" is an overload of the gene for protein metabolism specifically involving the incorporation of lysine into the protein molecule , while the gene for the enzyme Superoxide Dismutase (SOD) upsets the balance of the chain of enzymes scavanging free radicals- SOD converts free radicals to the free radical hydrogen peroxide which catalase converts H2O2 to water and free oxygen. But catalase cannot handle this excess load of hydrogen peroxide produced by the excess SOD enzyme resulting in an excess of hydrogen peroxide in the body. This ROTS (reactive Oxygen Toxic Species ) is responsible for premature aging and the brain damage associated with mongolism. There are other effects of gene dosage effect. It is not surprising that clinicians now prefer using the clinical description Down's syndrome. Again let me repeat that there is no specific gene and/or mutation for mongolism but rather just the presence of an imbalance of 3 copies of the genes rather than two copies.

Genetic load is also well known for the sex chromosomes. In males recessive genes on the X chromosome will show symptoms like hemophilia and not in females (cf. Queen Victoria's geneolgy) unless of course the recessive gene is present in the homozygous state (i.e. on both X,s)- In Turner's- females with XO karyotype have unusual female diseases and could also manifest any diseases regardless of whether a gene is dominant or recessive. Kleinfelter's syndrome in males (XXY) because of the presence of 2 X's have many female features including poorly developed external genitalia and a low sperm count.

Huntington's chorea-The so called "gene" is located on chromosome #4. Here the scientists examine the genetic code itself- the triplets which code for specific amino acids. They find that while in normal subjects the number of repetitions of the triplet does not exceed 32, affected patients may have as many as 60,with age of onset and severity related to repition number (Werner's)

I recall when I got my PH.D. in Cytogenetics in Toronto in 1955, Watson and Crick had just deciphered the genetic code and mechanism of replication and translation. At the time I was employed with the Canadian Dept of Agriculture in Edmonton. In Plant Cytogenetics trisomy was the rage and cytogeneticists were incorporating whole chromosomes into wheat and other species to improve yield and other qualities of their crops. Lejeune had not yet demonstrated that mongolism was due to the presence of an extra chromosome- indeed clinical cytogenetics was in its infancy. since prior to 1956 most biologists believed that the human karyotype consisted of 48 and not 46 chromosomes. Now rather than introducing whole chromosomes we have the techniques to incorporate single genes into the human genome.