Hello troll pup. How are you doing tonight?
I can see that you are full of holiday spirit.
I am here now and your viral infection is active.
I have a few comments:
1972-B.Ekblum,et al. Response to Exercise after Blood Loss and Reinfusion.Journal of Applied Physiology.1972 Aug;33(2):175-80. publishes about hemoglobin changes and exercise performance changes after blood transfusions. In the same year, Lasse Viren wins the 5k and 10k gold at the Olympics, and repeats both wins in the 1976 Olympics. There were suspicions of blood transfusions by the Finns, but we will never know for sure.
1976-Waldemar Cierpinski cheats to win gold medal for East Germany over Frank Shorter.
1980-Cierpinski again wins marathon. Kaarlo Maaninka of Finland wins silver in 10k and bronze in 5k, and is found to have done blood transfusions.
1982-Francesco Conconi of Italy publishes journal articles about the anaerobic threshold, with variations on the CONCONI test being done to this day on runners and cyclists.
1984-Allberto Cova of Italy wins 10k Olympic gold and did blood transfusions. Marti Vainio of Finland wins silver in the 10k, but is caught with the anabolic steroid metenolone, which was possibly in his old stored blood which he transfused before the race, but forgot he was on metenolone when the blood was withdrawn for storage. He was not a very smart doper. It is also discovered that one third of the US Cycling team at the 1984 Olympics, which won 9 medals, were doing blood transfusions.
1985-blood transfusions are declared illegal and banned, but there is no test for detection.
1987-New England Journal of Medicine publishes trial of recombinant EPO called Epogen, made by the biotech firm Amgen. Amgen ironically goes on to be a major sponsor of the cycling Tour of California, where many of the riders are using its EPO product.
1987 - 5 Dutch cyclists die.
1988- 2 Dutch cyclists die. 1 Belgian cyclist dies.
http://www.nytimes.com/1991/05/19/us/stamina-building-drug-linked-to-athletes-deaths.html
1988- Dr. Francesco Conconi publishes a study on serum EPO levels in cross-country skiers:
https://www.ncbi.nlm.nih.gov/pubmed/3384528
https://en.wikipedia.org/wiki/Francesco_Conconi
1988-Salvatore Antibo from Italy wins Olympic silver in 10k and Gelindo Bordin wins the gold medal in the marathon. Bordin also wins Boston in 1990.
1989-Epogen approved by FDA for use in US.
1989-EPO moves into cycling in a big way. 5 more Dutch cyclists die.
1990- 2 more Dutch cyclists die and 3 more Belgian cyclists die.
1990- IOC bans EPO, but there is no test for detection of EPO.
1990-1991- track has 3 to 5 sub 13:10 5k perfomers and/or performances per year.
1991- Dr. Gabriele Rosa arrives in Kenya and sets up his first training camp.
1992- Dr. Eufemiano Fuentes of Spain (of later Operation Puerto fame) is a doctor in Spain as Fermin Cacho wins the 1500m at the Barcelona Olympics. Dieter Baumann wins the 5k and Khalid Skah wins the 10k.
1993-14 men break 13:10 a total of 21 times, while the Chinese women go on a rampage with Wang Junxia 29:31.78 10k WR, 8:06.11 3k WR, that still stand to this day. (New 29:17.45 by Alamaz Ayana in 2016 Update to come at the end of 2016.)
1993-2000-rampant EPO use with no test for detection and records are smashed, with huge depth of fast times by many people in track and cycling. Cyclists like Pantani and Riis pushing their hematocrits up to dangerous levels of 60 or 65%. Cycling finally institutes a hematocrit cutoff limit of a max hematocrit of 50% or you can't race and cyclists respond by all of them then having hematocrits of 48-49.5%, which is just a coincidence that they are all just below the limit...right?
A protege of the Italian Dr. Conconi, mentioned previously, went on to become much more famous. His name was Dr. Michele Ferrari, and he was the doctor to the stars of pro cycling. He was doctor to Lance Armstrong, who is the prototype for a pharmaceutical experiment gone mad disguised as an athlete. They did everything including EPO, autologous blood transfusions, the anabolic steroid testosterone, and Human Growth Hormone. What a name! You can't make this stuff up. The mad genius Dr. Ferrari really did turn his riders into Ferraris, with extra horsepower. He also did a great job making sure that 1) he kept Lance alive and didn't kill him and 2) that he somehow passed his drug tests. It was probably Ferrari that pioneered taking EPO by intravenous instead of subcutaneous injection, so that the EPO could be cleared faster, and the window for a positive epo test was then very small. Michele Ferrari is a very smart guy who is presently in trouble with tax authorities for hiding large amounts of money in secret bank accounts (that are not secret now) and he is also banned for life from cycling.
2000-first urine test for EPO detection is developed and used at the Olympics. The test improved around 2005. The new test for EPO leads athletes back to the old method of blood transfusions, to avoid detection.
2004-Italian Stefano Baldini wins gold medal in marathon. American Tyler Hamilton is caught doing a heterologous blood tranfusion of someone else's blood at the Olympics, where he won the gold medal. His B test at the Olympics had problems and he kept the medal on a technicality, but finally returned the medal in 2011. His lawyers used the famous "Tyler is a human chimera with a vanishing twin" defense to explain why he had blood from two different people in his bloodstream...which wins the comedy prize for funniest doping excuse ever.
2006- Operation Puerto with Dr. Fuentes and 200 bags of blood, steroids.
2008-CERA (Continuous Erythropoietin Receptor Activator), a new longer acting agent, with a much longer half-life 20x longer than EPO, is appoved for use in Jan, 2008 under the name Mircera. Rashid Ramzi tests positive for CERA at the 2008 Olympics, and loses his gold medal.
2009- Athlete Biological Passport (ABP) is started.
2009-2015-development of EPO mimetic peptides such as peginesatide.
There has also been recent development of orally active Hypoxia-Inducible Factor (HIF) stabilizers. You can take a pill which works like EPO. The company Fibrinogen has compounds FG-2216, FG-4592, and FG-4497, which stabilize HIF by inhibiting the enzyme prolyl-hydroxylase, which is involved in the breakdown of HIF-1alpha by the ubiquitin proteosome pathway. HIF is a transcription factor which increases the gene expression of about 200 different genes, including the gene for EPO. Increased levels of HIF-1 alpha signals cells in the kidney to increase transcription of erythropoietin (EPO), which travels to the bone marrow, binds to progenitor cells, and increases erythropoiesis, which is the production of new red blood cells. This is the mechanism of action of HIF stabilizers.
https://www.ncbi.nlm.nih.gov/pubmed/22362605
https://www.ncbi.nlm.nih.gov/pubmed/26808067
https://www.ncbi.nlm.nih.gov/pubmed/27346747
Another compound involved with HIF is cobalt chloride, which also acts as an HIF stabilizer, is orally active, but is not recommended, as it is toxic to the gastrointestinal system, thyroid, heart, liver and kidney. It may also cause cancer. There is now a blood test to test for cobalt levels.
Other recent research is looking at inhalation of the noble gases Xenon, and Krypton, as HIF activators of erythropoiesis. They have been used by Russian athletes. The compounds have recently been banned and there is now a test for them. The cheaters are always finding new ways to cheat and the testers are always trying to find new ways to catch the cheaters.
https://www.ncbi.nlm.nih.gov/pubmed/26939898
https://www.ncbi.nlm.nih.gov/pubmed/24861600
https://www.ncbi.nlm.nih.gov/pubmed/27001214
For further reading, check out: Simon Beuck, et al. Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis stimulating agents in current and preventive doping analysis. Drug Testing and Analysis 2012 Nov;4(11):830-45., which is from their special issue on Sports Drug Testing for Erythropoiesis-Stimulating Agents and Autologous Blood Transfusion. There are many interesting articles in this issue.
For more reading on the physiology and mechanism of action:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874847/