Gideon Koren

Gideon Koren M.D., FACMT, FRCP(C) (Hebrew: גדעון קורן‎; born 1947 in Tel Aviv) is a Canadian pediatrician, clinical pharmacologist, and toxicologist. Koren is also a composer of Israeli popular music.

Biography

Early life and academic background

Born in 1947 in Tel Aviv in the British Mandate of Palestine, just prior to the establishment of the State of Israel, Gideon Koren was raised in the neighbouring little town of Kiryat Ono. His father was the chief engineer of Reading Power station of the Electricity Company in Tel Aviv. In his childhood he played French horn in the orchestra of the premilitary youth Gadna.

Koren received his Doctor of Medicine from the Sackler School of Medicine at Tel Aviv University in 1973. After a period of military service, he pursued postgraduate clinical studies in pediatrics and pediatric nephrology, and research training in pediatric toxicology and pharmacology and membrane biology at the Hospital for Sick Children and the University of Toronto. He joined the staff of the university and hospital and rose rapidly through the ranks to full professorship in pediatrics, pharmacology and medicine, won a Career Scientist Award from the Ontario Ministry of Health and established an international reputation as an expert in the field of clinical pharmacology and toxicology. He had a role in a controversial hospital dispute.[1][2] He was later awarded the endowed Ivey Chair in Molecular Toxicology at the Schulich School of Medicine at The University of Western Ontario. At UWO, he heads the establishment of a national program in human toxicology in parallel to his continuing work at the University of Toronto and the Hospital for Sick Children.[3]

Arts background

In parallel to his academic career, Gideon Koren is an established, award-winning composer and author. In 1971, while studying medicine at TAU, Gideon “Gidi” Koren founded the Israeli musical group, The Brothers & the Sisters (ha'achim veha'achayot). Koren’s songs and the group’s unique Israeli folk/country style put them at the top of the charts and of Israel’s popular annual song competitions for over a decade. The band performed many of Gideon Koren’s classic songs and musical plays for children.[4][5][6]

In 1974, in collaboration with Israeli superstar Shlomo Artzi, Koren composed a record album based on his grandmother Keri's story, A Journey to Noteland, introducing the world of music to children. A musical based on the book and CD of A Journey to Noteland had its stage debut in Israel in 2008 and continues to be performed for elementary school children throughout the country.[7]

In 1992 he founded the Bear Theatre at the Hospital for Sick Children in Toronto, the only such theatre worldwide where health professionals perform weekly for hospitalized children and their families. The musical "Tails" — script, songs, direction and children's book by Koren — has served as a model for other hospitals. In July 2007 the theatre celebrated 15 years and 750 shows.[8][9][10] At the hospital, Koren goes by the nickname "Gidi" and takes pride in wearing eccentric hats to the performances of "Tails."

In 2004, Koren's band, The Brothers and the Sisters, reunited by popular demand with the composer’s active support. In 2005, they toured North America following the publication of a commemorative Hebrew-English book of the beloved Israeli poet Natan Yonatan’s poetry accompanied by a CD of his songs set to music by Koren and performed by the band.[11][12] Since then The Brothers and the Sisters have continued to appear throughout Israel in programs featuring Koren’s hit songs, many of which were written to the words of Israel’s foremost poets, including Yehudah Amichai, Leah Goldberg, Rachel, Natan Yonatan, Amir Gilboa, and Ze’ev Jabotinsky. In 2008, NMC released a double CD and documentary booklet of 44 of the band’s favorites. 42 of these songs had music and/or lyrics and arrangements by Koren, as well as his participation as musician in early recorded accompaniments. Celebrating this collection and the band’s comeback, Israel’s Channel One dedicated a one-hour holiday TV special to The Brothers and the Sisters, who performed old favorites and new songs by Gidi Koren.

Professional contributions

In 1985, Koren founded the Toronto Hospital for Sick Children's Motherisk Program, which he continues to direct. Motherisk counsels women, their families and health professionals on the safety risks of drugs, chemicals, radiation and infections during pregnancy and lactation. Motherisk counselors talk to hundreds of women and their healthcare providers each day.[13]

Since 1986, Koren has trained physicians from over 30 countries, and over 80 graduate students in pharmacology, making his program the largest worldwide.[14]

Koren has been a Senior Scientist of the Canadian Institutes of Health Research (CIHR).[15] In 2004, Koren was appointed by the National Institutes of Health (NIH) of the United States Department of Health and Human Services as the inaugural chairperson of the Steering Committee for the newly created Obstetric-Fetal Pharmacology Research Unit Network.[16] Since 2005, Koren has been the Course Director of the Annual Summer Institute in Maternal-Fetal Pharmacology, a collaboration between the National Institutes of Health and Canadian Institutes of Health Research.[17][18]

Research

Koren's research in maternal–fetal and pediatric pharmacology and toxicology has focused on understanding the complex interactions between drugs, both illicit and medicinal, and the developing human being. These include the effects of drugs taken by the mother on her unborn baby, the role of the placenta in modulating fetal damage, and the way babies and children handle drugs. Koren and his colleagues use research approaches ranging from those of molecular and cell biology to whole-body pharmacokinetic or dynamic experiments and population studies. They collaborate with specialists in the field of psychology in order to measure the neurobehavioural effects of drugs on infants and children.[19]

Together with colleagues at the University of Western Ontario, Koren is studying ecological system toxicology with a focus on the health risks to aboriginal Canadians residing near oil refineries in Western Ontario.

FASD focus

Gideon Koren is the founder of the FACE (Fetal Alcohol Canadian Expertise) Network[20] and founding editor of the peer-reviewed Journal of FAS International (Fetal Alcohol Syndrome).[21] At the forefront of FASD (Fetal Alcohol Spectrum Disorder) research and the development of screening and diagnostic techniques,[22] he is also committed to outreach to medical professionals and community workers in the Northwest Territories and around the globe, both in person and through electronic media.[23][24]

Publications

Gideon Koren is a reviewer and editor for journals and has published over 1000 peer-reviewed articles[25] and 15 medical books,[26] among them:

Notable achievements

Preventing renal damage

Koren has found a way to prevent severe kidney damage caused by the cancer drug ifosfamide by using the antidote n-acetyl cysteine. The drug ifosfamide can save the lives of children with certain cancers, but often at the grim price of damaging the kidneys. Koren’s discovery may save the kidneys and have a major impact on the lives of these children.[27]

Codeine during breastfeeding

Koren described a breastfed infant who died from opioid toxicity following the use of codeine by his mother. This was the first described death of an infant by a drug in breastfeeding, secondary to the genetic predisposition of the mother to produce more morphine from codeine. Further research by his group has shown that this is not a rare phenomenon.[28]

FAEE

Using the baby’s first bowel movement (meconium), Koren’s group showed that, by measuring a by-product of alcohol (FAEE), they could detect objectively babies exposed to excessive maternal drinking in pregnancy.[29]

Folic acid

Koren’s group has shown that the fortification of flour with folic acid in Canada has resulted in a dramatic decrease in neuroblastoma, an early and very dangerous cancer in young children.[30]

Drugs in pregnancy

Through over 500 research papers on drugs in pregnancy, Koren has identified drugs and chemicals that are damaging to the fetus (e.g., organic solvents, corticosteroids, lithium, misoprostol), and those that are safe to take (e.g., paxil, calcium channel blockers, prozac).[31]

Nausea and vomiting in pregnancy (NVP)

Koren and coauthors analyzed the estimated cost and actual burden to society caused by nausea with and without vomiting among the pregnant woman associated with the Hospital for Sick Children's Motherisk program.[32] However, a later study of NVP conducted by the research group concluded that "NVP has an enhancing effect on later child outcome" but can be safely treated with diclectin.[33]

Long-term safety

Koren established the only group worldwide that systematically studies brain development in children exposed in utero to drugs. The group has tested IQ, language, attention and behavior in children exposed during pregnancy to antidepressants, cocaine, cyclosporine, antiepileptics, and many other drugs.[34]

Neonatal pain

Koren and his group documented in 1997, for the first time, that neonates remember the pain of circumcision 6 months later, as evidenced by enhanced response to vaccination. This has been marked as a breakthrough in the understanding of the long-term effects of early pain.[35]

Drugs that can kill toddlers

Koren established, for the first time, a list of drugs that can kill a toddler even with only one adult tablet. Dr. Koren suggests that this list needs to be acknowledged by physicians because toddlers often accidentally consume adult medication.[36]

Publication bias

Koren’s group claims to have pioneered the research into sources of misinformation and bias in information given to pregnant women.[37] This has led to major changes in the methods of counseling pregnant women.

Hair analysis

Koren’s laboratory pioneered the use of neonatal hair to show exposure to drugs of abuse in pregnancy. Drugs such as cocaine,[38] methamphetamine, heroin, etc., accumulate in the neonatal hair during its growth and hence serve as a “memory” of what happened during fetal life. This method has revolutionized the diagnosis of in utero exposure to drugs. Koren's research in this area has also led to a new biological marker that can be used to help prevent heart attacks, measuring chronic stress over time.[39]

Koren, a clinical pharmacologist, was not qualified to be MDTL’s director, “Dr. Koren saw himself as an expert in the interpretation of [hair-testing] results,” though he “never had formal training in forensic toxicology or any experience in a forensic toxicology laboratory.” Moreover, “it is clear that [Koren] did not understand the basic elements of forensic toxicology that are necessary to provide interpretations of test results.” Koren also “was not trained to testify as an expert” in court, Lang writes. http://www.macleans.ca/society/health/explosive-judicial-review-puts-lens-on-gideon-koren-and-sickkids/

Deferiprone controversy

In 1996, a controversy erupted with regard to the safety and effectiveness of deferiprone. Koren believed the drug was effective for certain patients.[40] Olivieri of Toronto believed the drug was unsafe and ineffective.[41] Following the initial controversy surrounding this drug trial in Toronto, Koren sent five anonymous harassing letters to colleagues and later denied having done so.[42] Two independent inquiries by the CAUT and CPSO found that Koren had lied about sending the anonymous letters and only admitted guilt when confronted with DNA evidence against him.[43][44] Both also found academic misconduct with respect to the way in which he published the research article cited above on the safety and effectiveness of deferiprone. CAUT accepted "the parties’ submissions that this misconduct should not be represented as fraudulent" and further remarked that "It was the behaviour that preceded the research misconduct that the Committee found most unsettling."

A later study using more data than in the Olivieri study found no evidence of that long-term therapy with deferiprone caused progression of hepatic fibrosis.[45] Cumulative worldwide experience has confirmed Koren's position on deferiprone, indicating that deferiprone is safe and effective for some patients.[46] As a direct result of Olivieri’s public media campaign, approval for the medication was stalled,[47] meaning that North American children continued to be denied a medication which had since been approved around the world in dozens of countries[48] and could be the only hope for survival for some children.[1][49][50][51][52]

Awards and distinctions

Currently held positions

Selected list of currently held positions (2010):[55][56][57][58]

References

  1. 1 2
  2. ↑
  3. ↑ "The Ivey Chair in Molecular Toxicology - Schulich School of Medicine & Dentistry". Schulich.uwo.ca. Retrieved 13 November 2014.
  4. ↑ "Gidi Koren". Israel-music.com. Retrieved 13 November 2014.
  5. ↑ "The Tales of Shubi Dubi". Israel-music.com. Retrieved 13 November 2014.
  6. ↑
  7. ↑ "-". City Mouse. Retrieved 13 November 2014.
  8. ↑ "Reassuring message helps young patients". thestar.com. Retrieved 13 November 2014.
  9. ↑
  10. ↑ http://www.sickkids.ca/tails
  11. ↑ "Songs Carved Into Cliffs". Bros-and-sis.com. Retrieved 13 November 2014.
  12. ↑
  13. ↑ "The Hospital for Sick Children - Motherisk". Motherisk.org. Retrieved 13 November 2014.
  14. ↑ Koren G, Macleod SM: The state of pediatric clinical pharmacology;an international survey of training programs, Clin. Pharm Ther 1989;46:489-93.
  15. ↑
  16. ↑ Archived October 1, 2006 at the Wayback Machine
  17. ↑
  18. ↑
  19. ↑ The Hospital for Sick Children Research Institute, Annual Report 2002.
  20. ↑
  21. ↑ "The Hospital for Sick Children - Motherisk". Motherisk.org. Retrieved 13 November 2014.
  22. ↑ Gareri J, Chan D, Klein J, Koren G (January 2005). "Screening for fetal alcohol spectrum disorder". Canadian Family Physician 51 (1): 33–4. PMC 1479571. PMID 15732218.
  23. ↑ Archived September 26, 2007 at the Wayback Machine
  24. ↑ Koren G, Nulman I, Chudley AE, Loocke C (November 2003). "Fetal alcohol spectrum disorder". CMAJ 169 (11): 1181–5. PMC 264960. PMID 14638655.
  25. ↑
  26. ↑ "The Hospital for Sick Children - Motherisk". Motherisk.org. Retrieved 13 November 2014.
  27. ↑ Chen N, Aleksa K, Woodland C, Rieder M, Koren G (April 2008). "N-Acetylcysteine prevents ifosfamide-induced nephrotoxicity in rats". British Journal of Pharmacology 153 (7): 1364–72. doi:10.1038/bjp.2008.15. PMC 2437918. PMID 18278066.
  28. ↑ Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (August 2006). "Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother". Lancet 368 (9536): 704. doi:10.1016/S0140-6736(06)69255-6. PMID 16920476.
  29. ↑ Chan D, Knie B, Boskovic R, Koren G (July 2004). "Placental handling of fatty acid ethyl esters: perfusion and subcellular studies". The Journal of Pharmacology and Experimental Therapeutics 310 (1): 75–82. doi:10.1124/jpet.104.066597. PMID 15004219.
  30. ↑ French AE, Grant R, Weitzman S, et al. (September 2003). "Folic acid food fortification is associated with a decline in neuroblastoma". Clinical Pharmacology and Therapeutics 74 (3): 288–94. doi:10.1016/S0009-9236(03)00200-5. PMID 12966372.
  31. ↑ Koren G, Pastuszak A, Ito S (April 1998). "Drugs in pregnancy". The New England Journal of Medicine 338 (16): 1128–37. doi:10.1056/NEJM199804163381607. PMID 9545362.
  32. ↑ Piwko C, Ungar WJ, Einarson TR, Wolpin J, Koren G (April 2007). "The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program". Current Medical Research and Opinion 23 (4): 833–40. doi:10.1185/030079907X178739. PMID 17407640.
  33. ↑ Nulman I, Rovet J, Barrera M, Knittel-Keren D, Feldman BM, Koren G (July 2009). "Long-term neurodevelopment of children exposed to maternal nausea and vomiting of pregnancy and diclectin". The Journal of Pediatrics 155 (1): 45–50, 50.e1–2. doi:10.1016/j.jpeds.2009.02.005. PMID 19394042. Lay summary – Toronto Sun (April 23, 2009).
  34. ↑ Nulman I, Rovet J, Stewart DE, et al. (January 1997). "Neurodevelopment of children exposed in utero to antidepressant drugs". The New England Journal of Medicine 336 (4): 258–62. doi:10.1056/NEJM199701233360404. PMID 8995088.
  35. ↑ Taddio A, Katz J, Ilersich AL, Koren G (March 1997). "Effect of neonatal circumcision on pain response during subsequent routine vaccination". Lancet 349 (9052): 599–603. doi:10.1016/S0140-6736(96)10316-0. PMID 9057731.
  36. ↑ Koren G (1993). "Medications which can kill a toddler with one tablet or teaspoonful". Journal of Toxicology. Clinical Toxicology 31 (3): 407–13. doi:10.3109/15563659309000409. PMID 8355317.
  37. ↑ Koren G, Graham K, Shear H, Einarson T (December 1989). "Bias against the null hypothesis: the reproductive hazards of cocaine". Lancet 2 (8677): 1440–2. doi:10.1016/S0140-6736(89)92044-8. PMID 2574369.
  38. ↑ Graham K, Koren G, Klein J, Schneiderman J, Greenwald M (December 1989). "Determination of gestational cocaine exposure by hair analysis". JAMA 262 (23): 3328–30. doi:10.1001/jama.262.23.3328. PMID 2585678.
  39. ↑ Shamah, David (October 2010). "Hair reveals stress levels and heart attack risks". Israel 21c Innovation News Service. Retrieved 13 November 2014.
  40. ↑ Diav-Citrin O, Atanackovic G, Koren G (February 1999). "An investigation into variability in the therapeutic response to deferiprone in patients with thalassemia major". Therapeutic Drug Monitoring 21 (1): 74–81. doi:10.1097/00007691-199902000-00011. PMID 10051057.
  41. ↑ Olivieri NF, Brittenham GM, McLaren CE, et al. (August 1998). "Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major". The New England Journal of Medicine 339 (7): 417–23. doi:10.1056/NEJM199808133390701. PMID 9700174.
  42. ↑ Report by the CPSO Discipline Committee, p.3
  43. ↑ Bonetta, Laura (2000). "Hate-mail author trapped by DNA.". Nature Medicine 6 (4): 364. doi:10.1038/74596. PMID 10742127.
  44. ↑ Birmingham, Karen (2000). "No dismissal for hate-mail author.". Nature Medicine 6 (6): 609–10. doi:10.1038/76146. PMID 10835652.
  45. ↑ Wanless IR, Sweeney G, Dhillon AP, et al. (September 2002). "Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia". Blood 100 (5): 1566–9. doi:10.1182/blood-2002-01-0306. PMID 12176871.
  46. ↑ Rund D, Rachmilewitz E (September 2005). "Beta-thalassemia". The New England Journal of Medicine 353 (11): 1135–46. doi:10.1056/NEJMra050436. PMID 16162884.
  47. ↑ Constantinou G, Melides S, Modell B (February 2003). "The Olivieri case". The New England Journal of Medicine 348 (9): 860–3; author reply 860–3. doi:10.1056/NEJM200302273480919. PMID 12606746.
  48. ↑ Victorhoffbrand, A (2005). "Deferiprone therapy for transfusional iron overload". Best Practice & Research Clinical Haematology 18 (2): 299–317. doi:10.1016/j.beha.2004.08.026. PMID 15737892.
  49. ↑ Tanner MA, Galanello R, Dessi C, et al. (April 2007). "A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance". Circulation 115 (14): 1876–84. doi:10.1161/CIRCULATIONAHA.106.648790. PMID 17372174.
  50. ↑ Miriam Shuchman (2005). The drug trial: Nancy Olivieri and the scandal that rocked the Hospital for Sick Children. Toronto: Random House Canada. ISBN 978-0-679-31084-6.
  51. ↑ "UB Professor Authors Page-Turner on Toronto Medical Scandal". Buffalo.edu. 13 June 2005. Retrieved 13 November 2014.
  52. ↑ Kollata, Gina (June 14, 2005). "In Drama Pitting Scientist vs. Drug Maker, All Are Punished". The New York Times. Retrieved 13 November 2014.
  53. ↑ Gideon Koren. "Essay for the 2011 CIHR/CMAJ award: Motherisk — caring for mothers, protecting the unborn". Cmaj.ca. Retrieved 13 November 2014.
  54. ↑ "Backgrounder – 2011 CIHR-CMAJ Top Achievements in Health Research Awards". Cihr-irsc.gc.ca. Retrieved 13 November 2014.
  55. ↑ "The Hospital for Sick Children - Motherisk". Motherisk.org. Retrieved 13 November 2014.
  56. ↑ "The Ivey Chair in Molecular Toxicology - Schulich School of Medicine & Dentistry". Schulich.uwo.ca. Retrieved 13 November 2014.
  57. ↑ "Gideon Koren, M.D., F.R.C.P.(C), F.A.C.M.T.". Pharmtox.utoronto.ca. Retrieved 13 November 2014.
  58. ↑ "About us". Clinpharmtox.uontario.ca. Retrieved 13 November 2014.
  59. ↑
  60. ↑ "Study offers new hope for kids with fetal alcohol syndrome". Canada.com. Retrieved 13 November 2014.
  61. ↑ "Therapeutic Drug Monitoring". Drug-monitoring.com. Retrieved 13 November 2014.
  62. ↑ "Fetal Alcohol Research". Motherisk.org. Retrieved 13 November 2014.
  63. ↑ "Canadian Foundation on Fetal Alcohol Research (CFFAR)". Fasdfoundation.ca. Retrieved 13 November 2014.
  64. ↑ Gideon Koren. "History of Tails at SickKids Telling Tails: Children's Literature Goes to the Hospital". Sickkids.ca. Retrieved 13 October 2014.

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