Gideon Koren
Encyclopedia
Gideon Koren M.D.
, FACMT
, FRCP(C) (born 1947) is a Canadian
pediatrician, clinical pharmacologist, and toxicologist. Dr. Koren is also a noted composer
of Israel
i popular music
.
and the University of Western Ontario
. He is Professor of Pediatrics, Pharmacology, Pharmacy and Medical Genetics
at the University of Toronto
, and Professor of Medicine, Pediatrics, and Physiology-Pharmacology at the Schulich School of Medicine
of the University of Western Ontario
.
In 1985, Dr. Gideon 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.
Since 1986, Dr. Koren has trained physicians from over 30 countries, and over 80 graduate students in pharmacology, making his program the largest worldwide.
Gideon Koren has been a Senior Scientist of the Canadian Institutes of Health Research
(CIHR) . In 2004, Dr. 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 (OPRU) Network.
Since 2005, Dr. 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
.
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. Dr. 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.
Together with colleagues at the University of Western Ontario, Dr. Gideon Koren is studying Ecological System Toxicology with a focus on the health risks to aboriginal Canadians
residing near oil refineries in Western Ontario.
). At the forefront of FASD (Fetal Alcohol Spectrum Disorder
) research and the development of screening and diagnostic techniques, 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 the electronic media.
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 kidney and have a major impact on the lives of these children.
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.
), 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.
with folic acid
in Canada has resulted in a dramatic decrease in neuroblastoma
, an early and very dangerous cancer in young children.
(e.g., organic solvents, corticosteroids, lithium
, misoprostol
), and those that are safe to take (e.g., paxil, calcium channel blockers, prozac).
However, regarding safety of Paxil (paroxetine) use in pregnancy, research literature much more recent (2010) than Dr. Koren's own 1998 paper (above) - found a specific association between Paxil use and infant cardiovascular defects. A previously unknown and particularly strong association between Paxil and hypospadias (penile malformation) was also concluded in this study.
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.
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.
even with only one adult tablet. These drugs need to be acknowledged by physicians because toddlers often accidentally consume adult medication
.
to show exposure to drugs of abuse in pregnancy. Drugs such as cocaine, methamphetamine
, heroin, etc., accumulate in the neonatal hair during its growth and hence serve as a long term “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.
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. 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
.
, Gideon “Gidi” Koren founded the Israeli musical group, “The Brothers and 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.
In 1974, in collaboration with Israeli superstar Shlomo Artzi
, Dr. 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.
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 Dr. Koren — has served as a model for other hospitals. In July 2007 the theatre celebrated 15 years and 750 shows. 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. 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: Yehudah Amichai, Leah Goldberg
, Rachel
, Natan Yonatan
, Ze’ev Jabotinsky and others. 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.
, current president of the University and then Dean of the Faculty of Medicine and Vice Provost for Relations with Health Care Institutions, and others went on record regarding Olivieri's having "advanced 'demonstrably incorrect' allegations against others" and having used “hundreds of thousands of dollars of legal fees and services” from teachers' union funds, and then being “unable to admit she made a mistake....” Prof. Naylor also went on record citing the bias of CAUT and its Inquiry as having favored Olivieri and her Union and pointing to the lack of independence of both committees. While Olivieri was admired in some circles for defending academic freedom when news of the controversy first broke, others continue to question her publicity-seeking, concerned that Olivieri was wrongly placed on a pedestal during the deferiprone controversy and that her science was wrong. Cumulative worldwide experience has confirmed Dr. Koren's position on deferiprone, indicating that deferiprone is safe and effective for some patients. As a direct result of Nancy Olivieri’s public media campaign, approval for the medication was stalled, meaning that North American children continued to be denied a medication which had since been approved around the world in dozens of countries and could be the only hope for survival for some children.
The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients...."
On the contrary, the wisdom of the FDA's accelerated (Fast Track) approval of deferiprone, is severely scrutinized in Dr Sidney Wolfe’s (PUBLICCITIZEN) detailed letter (Oct. 12, 2011), to the FDA where he concludes. “…..given the lack of data from adequate and well-controlled clinical trials demonstrating the safety and efficacy of deferiprone, as well as serious questions raised by DSl's inspection of study LA01 regarding the integrity of clinical trial data presented to the FDA by the sponsor, we urge the FDA to reject approval of NDA #021825 for deferiprone…….FDA approval of deferiprone based on such inadequate data would indeed set a recklessly dangerous precedent for drugs reviewed under an accelerated approval process in the future”.
The FDA briefing notes associated with the decision reveal that the request for regular or normal approval for marketing of deferiprone was declined by the FDA following scientific review because the evidence presented in the Apotex New Drug Application failed to adequately demonstrate safety and efficacy. Also the FDA site inspection of Olivieri’s trials showed that Apotex had wrongly omitted or misrepresented 45% of the Olivieri data in its submission to FDA.
FDA then informed Apotex that additional satisfactory randomized controlled evidence and a full, detailed audit of the Olivieri trials were required if Apotex was to pursue regular approval. The company declined and instead pursued 'accelerated' approval (known as conditional approval in Canada and other jurisdictions), which requires the lowest level of evidence.
Conditional or accelerated approval usually occurs BEFORE there has been time for conclusive clinical trials to be completed on promising new drugs, not AFTER a 20 year drug development program has generated randomized, controlled evidence which fails to demonstrate safety and efficacy.
In the end, the US FDA "accelerated approval" for last resort treatment with deferiprone was based on a single arm, non-controlled, non-randomized retrospective re-analysis of 264 patients selected from 746 patients in pooled data from studies previously conducted, showing a 20% reduction in serum ferritin in 52% of patients, the clinical significance of which is uncertain. There was "a lack of data to verify absence of a mortality disadvantage when deferiprone is used over a long period of time". The further studies to which the company must commit as part of accelerated approval are not yet described.
Doctor of Medicine
Doctor of Medicine is a doctoral degree for physicians. The degree is granted by medical schools...
, FACMT
American College of Medical Toxicology
The American College of Medical Toxicology , founded in 1993, is the largest organization of medical toxicologists in the United States and the world....
, FRCP(C) (born 1947) is a Canadian
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
pediatrician, clinical pharmacologist, and toxicologist. Dr. Koren is also a noted composer
Composer
A composer is a person who creates music, either by musical notation or oral tradition, for interpretation and performance, or through direct manipulation of sonic material through electronic media...
of Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
i popular music
Popular music
Popular music belongs to any of a number of musical genres "having wide appeal" and is typically distributed to large audiences through the music industry. It stands in contrast to both art music and traditional music, which are typically disseminated academically or orally to smaller, local...
.
Professional contributions
Gideon Koren is a pediatrician, pharmacologist and toxicologist at the University of TorontoUniversity of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
and the University of Western Ontario
University of Western Ontario
The University of Western Ontario is a public research university located in London, Ontario, Canada. The university's main campus covers of land, with the Thames River cutting through the eastern portion of the main campus. Western administers its programs through 12 different faculties and...
. He is Professor of Pediatrics, Pharmacology, Pharmacy and Medical Genetics
Medical genetics
Medical genetics is the specialty of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from Human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, but medical genetics refers to the...
at the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
, and Professor of Medicine, Pediatrics, and Physiology-Pharmacology at the Schulich School of Medicine
Schulich School of Medicine & Dentistry
The Schulich School of Medicine & Dentistry is the medical school of the University of Western Ontario, and is one of 17 medical schools in Canada and one of six in Ontario....
of the University of Western Ontario
University of Western Ontario
The University of Western Ontario is a public research university located in London, Ontario, Canada. The university's main campus covers of land, with the Thames River cutting through the eastern portion of the main campus. Western administers its programs through 12 different faculties and...
.
In 1985, Dr. Gideon Koren founded the Toronto
Toronto
Toronto is the provincial capital of Ontario and the largest city in Canada. It is located in Southern Ontario on the northwestern shore of Lake Ontario. A relatively modern city, Toronto's history dates back to the late-18th century, when its land was first purchased by the British monarchy from...
Hospital for Sick Children
Hospital for Sick Children
The Hospital for Sick Children – is a major paediatric centre for the Greater Toronto Area, serving patients up to age 18. Located on University Avenue in Downtown Toronto, SickKids is part of the city’s Discovery District, a critical mass of scientists and entrepreneurs who are focused on...
's Motherisk
Motherisk
Motherisk, created in 1985, is a clinical research and teaching program at The Hospital for Sick Children in Toronto, Ontario, Canada that provides information and guidance to pregnant or lactating women and to health care professionals regarding risks to the fetus from exposure to drugs,...
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
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
and lactation
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
. Motherisk counselors talk to hundreds of women and their healthcare providers each day.
Since 1986, Dr. Koren has trained physicians from over 30 countries, and over 80 graduate students in pharmacology, making his program the largest worldwide.
Gideon Koren has been a Senior Scientist of the Canadian Institutes of Health Research
Canadian Institutes of Health Research
Canadian Institutes of Health Research is the major federal agency responsible for funding health research in Canada. It is the successor to the Medical Research Council of Canada. It aims to create new health knowledge, and to translate that knowledge from the research setting into real world...
(CIHR) . In 2004, Dr. Koren was appointed by the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH) of the United States Department of Health and Human Services
United States Department of Health and Human Services
The United States Department of Health and Human Services is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. Its motto is "Improving the health, safety, and well-being of America"...
as the inaugural chairperson of the Steering Committee for the newly created Obstetric-Fetal Pharmacology Research Unit (OPRU) Network.
Since 2005, Dr. Koren has been the Course Director of the Annual Summer Institute in Maternal-Fetal Pharmacology, a collaboration between the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
and Canadian Institutes of Health Research
Canadian Institutes of Health Research
Canadian Institutes of Health Research is the major federal agency responsible for funding health research in Canada. It is the successor to the Medical Research Council of Canada. It aims to create new health knowledge, and to translate that knowledge from the research setting into real world...
.
Research
The research group headed by Dr. Koren at The University of Toronto and the Hospital for Sick Children is studying the fetal effects of drugs and chemicals, as well the effects of medications and toxins in infants and children.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
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
in modulating fetal damage, and the way babies and children handle drugs. Dr. 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.
Together with colleagues at the University of Western Ontario, Dr. Gideon Koren is studying Ecological System Toxicology with a focus on the health risks to aboriginal Canadians
Aboriginal peoples in Canada
Aboriginal peoples in Canada comprise the First Nations, Inuit and Métis. The descriptors "Indian" and "Eskimo" have fallen into disuse in Canada and are commonly considered pejorative....
residing near oil refineries in Western Ontario.
FASD focus
Gideon Koren is the founder of the FACE (Fetal Alcohol Canadian Expertise) Network and founding editor of the peer reviewed Journal of FAS International (Fetal Alcohol SyndromeFetal alcohol syndrome
Fetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
). At the forefront of FASD (Fetal Alcohol Spectrum Disorder
Fetal alcohol spectrum disorder
Fetal Alcohol Spectrum Disorders describes a continuum of permanent birth defects caused by maternal consumption of alcohol during pregnancy, which includes, but is not limited to fetal alcohol syndrome...
) research and the development of screening and diagnostic techniques, 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 the electronic media.
Publications
Dr. Gideon Koren is a reviewer and editor for leading journals and has published over 1000 peer review articles and 15 medical books, among them:- Retinoids in Clinical Practice: The Risk-Benefit Ratio (Medical Toxicology). New York: M. Dekker, 1993. (ISBN 0824787781)
- The Children of Neverland: The Silent Human Disaster. Toronto: Kid in Us, 1997. (ISBN 0968180108)
- The Complete Guide to Everyday Risks in Pregnancy & Breastfeeding: Answers to Your Questions About Morning Sickness, Medications, Herbs, Diseases, Chemical Exposures & More. Toronto: R. Rose, 2004. (ISBN 0-7788-0084-9)
- Medication Safety in Pregnancy and Breastfeeding. New York: McGraw-Hill, Health Professions Division, 2007. (ISBN 0071448284)
- Medication Safety in Pregnancy and Breastfeeding: The Evidence-Based, A to Z Clinician's Pocket Guide. New York: McGraw-Hill Medical, 2007. (ISBN 0071448276)
Preventing renal damage
Dr. Koren has found a way to prevent severe kidneyKidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
damage caused by the cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
drug ifosfamide
Ifosfamide
Ifosfamide is a nitrogen mustard alkylating agent used in the treatment of cancer.It is sometimes abbreviated "IFO".-Uses:It is given as a treatment for a variety of cancers, including:...
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 kidney and have a major impact on the lives of these children.
Codeine during breastfeeding
Dr. Koren described a breastfed infant who died from opioidOpioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
following the use of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
by his mother. This was the first described death of an infant by a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
in breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
, secondary to the genetic predisposition of the mother to produce more morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
from codeine. Further research by his group has shown that this is not a rare phenomenon.
FAEE
Using the baby’s first bowel movement (meconiumMeconium
Meconium is the earliest stools of an infant. Unlike later feces, meconium is composed of materials ingested during the time the infant spends in the uterus: intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. Meconium is almost sterile, unlike later feces, is viscous and...
), Koren’s group showed that, by measuring a by-product of alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
(FAEE), they could detect objectively babies exposed to excessive maternal drinking in pregnancy.
Folic acid
Koren’s group has shown that the fortification of flourFlour
Flour is a powder which is made by grinding cereal grains, other seeds or roots . It is the main ingredient of bread, which is a staple food for many cultures, making the availability of adequate supplies of flour a major economic and political issue at various times throughout history...
with folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
in Canada has resulted in a dramatic decrease in neuroblastoma
Neuroblastoma
Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
, an early and very dangerous cancer in young children.
Drugs in pregnancy
Through over 500 research papers on drugs in pregnancy, Dr. Koren has identified drugs and chemicals that are damaging to the fetusFetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
(e.g., organic solvents, corticosteroids, lithium
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
, misoprostol
Misoprostol
Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D...
), and those that are safe to take (e.g., paxil, calcium channel blockers, prozac).
However, regarding safety of Paxil (paroxetine) use in pregnancy, research literature much more recent (2010) than Dr. Koren's own 1998 paper (above) - found a specific association between Paxil use and infant cardiovascular defects. A previously unknown and particularly strong association between Paxil and hypospadias (penile malformation) was also concluded in this study.
Nausea and vomiting in pregnancy (NVP)
In a landmark paper, Dr. Koren 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. Another study of NVP conducted by the research group at Motherisk addressed the effects of nausea and vomiting of pregnancy and its treatment with diclectin on child neurodevelopment. The conclusion, published in The Journal of Pediatrics in April 2009, states that "NVP has an enhancing effect on later child outcome. Diclectin does not appear to adversely affect fetal brain development and can be used to control NVP when clinically indicated."Long-term safety
Dr. Koren established the only group worldwide that systematically studies brain development in children exposed in uteroIn utero
In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
to drugs. The group has tested IQ, language, attention and behavior in children exposed during pregnancy to antidepressants, cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, cyclosporine, antiepileptics, and many other drugs.
Neonatal pain
Dr. Koren and his group documented in 1997, for the first time, that neonates remember the painPain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
of circumcision
Circumcision
Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....
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.
Drugs that can kill toddlers
Dr. Koren established, for the first time, a list of drugs that can kill a toddlerToddler
A toddler is a young child, usually defined as being between the ages of one and three. Registered nurse, midwife and author, Robin Barker, states 'Any time from eight months onwards your baby will begin to realise he is a separate person from you...
even with only one adult tablet. These drugs need to be acknowledged by physicians because toddlers often accidentally consume adult medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
.
Publication bias
Koren’s group has pioneered the research into sources of misinformation and bias in information given to pregnant women, misinformation which leads many of them to avoid treatment even for life-threatening conditions. This has led to major changes in the methods of counseling pregnant women.Hair analysis
Dr. Koren’s laboratory pioneered the use of neonatal hairHair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
to show exposure to drugs of abuse in pregnancy. Drugs such as cocaine, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
, heroin, etc., accumulate in the neonatal hair during its growth and hence serve as a long term “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.
Early life and academic background
Born in the British Mandate of Palestine in 1947, just prior to the establishment of the State of Israel, Dr. Koren received his Doctor of MedicineDoctor of Medicine
Doctor of Medicine is a doctoral degree for physicians. The degree is granted by medical schools...
from the Sackler School of Medicine
Sackler Faculty of Medicine
Sackler Faculty of Medicine is a medical school which is part of Tel Aviv University in Tel Aviv, Israel.It was named after Arthur, Mortimer and Raymond Sackler, U.S. physicians who made substantial donations to the school...
at Tel Aviv University
Tel Aviv University
Tel Aviv University is a public university located in Ramat Aviv, Tel Aviv, Israel. With nearly 30,000 students, TAU is Israel's largest university.-History:...
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
Membrane biology
Membrane biology is the study of the biological and physiochemical characteristics of membranes....
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. He was later awarded the endowed Ivey Chair in Molecular Toxicology at the Schulich School of Medicine
Schulich School of Medicine & Dentistry
The Schulich School of Medicine & Dentistry is the medical school of the University of Western Ontario, and is one of 17 medical schools in Canada and one of six in Ontario....
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
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
and the Hospital for Sick Children
Hospital for Sick Children
The Hospital for Sick Children – is a major paediatric centre for the Greater Toronto Area, serving patients up to age 18. Located on University Avenue in Downtown Toronto, SickKids is part of the city’s Discovery District, a critical mass of scientists and entrepreneurs who are focused on...
.
Arts background
In parallel to his academic career, Gideon Koren is an established, award-winning composer and author. In 1971, while studying medicine at TAUTau
Tau is the 19th letter of the Greek alphabet. In the system of Greek numerals it has a value of 300.The name in English is pronounced , but in modern Greek it is...
, Gideon “Gidi” Koren founded the Israeli musical group, “The Brothers and 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.
In 1974, in collaboration with Israeli superstar Shlomo Artzi
Shlomo Artzi
Shlomo Artzi is an Israeli folk rock singer-songwriter, and composer.He was born on November 26, 1949, in Moshav Alonei Abba. In the course of his career, he has sold over 1.5 million albums, making him one of Israel's most successful male singers....
, Dr. 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
Musical theatre
Musical theatre is a form of theatre combining songs, spoken dialogue, acting, and dance. The emotional content of the piece – humor, pathos, love, anger – as well as the story itself, is communicated through the words, music, movement and technical aspects of the entertainment as an...
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.
In 1992 he founded the Bear Theatre at the Hospital for Sick Children
Hospital for Sick Children
The Hospital for Sick Children – is a major paediatric centre for the Greater Toronto Area, serving patients up to age 18. Located on University Avenue in Downtown Toronto, SickKids is part of the city’s Discovery District, a critical mass of scientists and entrepreneurs who are focused on...
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 Dr. Koren — has served as a model for other hospitals. In July 2007 the theatre celebrated 15 years and 750 shows. 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
Natan Yonatan
Natan Yonatan was an Israeli poet.His poems have been translated from Hebrew and published in more than a dozen languages, among them: Arabic, Bulgarian, Chinese, Dutch, English, French, German, Portuguese, Russian, Spanish, Vietnamese, and Yiddish....
’s poetry accompanied by a CD of his songs set to music by Koren and performed by the band. 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: Yehudah Amichai, Leah Goldberg
Leah Goldberg
Leah Goldberg was a prolific Hebrew poet, author, playwright, literary translator, and comparative literary researcher. Her writings are considered classics of Israeli literature and remain very popular among Hebrew speaking Israelis.-Biography:...
, Rachel
Rachel Bluwstein
Sela was a Hebrew poet who immigrated to Palestine in 1909. She is known by her first name, Rachel, or as Rachel the poetess .-Biography:...
, Natan Yonatan
Natan Yonatan
Natan Yonatan was an Israeli poet.His poems have been translated from Hebrew and published in more than a dozen languages, among them: Arabic, Bulgarian, Chinese, Dutch, English, French, German, Portuguese, Russian, Spanish, Vietnamese, and Yiddish....
, Ze’ev Jabotinsky and others. 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.
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. Dr. Olivieri of Toronto believed the drug was unsafe and ineffective. Following the initial controversy surrounding this drug trial in Toronto, Koren sent five anonymous harassing letters to colleagues and later denied having done so. 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. 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." Spokesperson for the University of Toronto, Professor David NaylorDavid Naylor
Christopher David Naylor, OC, FRCPC, FRSC is a medical researcher and president of the University of Toronto.-Biography:...
, current president of the University and then Dean of the Faculty of Medicine and Vice Provost for Relations with Health Care Institutions, and others went on record regarding Olivieri's having "advanced 'demonstrably incorrect' allegations against others" and having used “hundreds of thousands of dollars of legal fees and services” from teachers' union funds, and then being “unable to admit she made a mistake....” Prof. Naylor also went on record citing the bias of CAUT and its Inquiry as having favored Olivieri and her Union and pointing to the lack of independence of both committees. While Olivieri was admired in some circles for defending academic freedom when news of the controversy first broke, others continue to question her publicity-seeking, concerned that Olivieri was wrongly placed on a pedestal during the deferiprone controversy and that her science was wrong. Cumulative worldwide experience has confirmed Dr. Koren's position on deferiprone, indicating that deferiprone is safe and effective for some patients. As a direct result of Nancy Olivieri’s public media campaign, approval for the medication was stalled, meaning that North American children continued to be denied a medication which had since been approved around the world in dozens of countries and could be the only hope for survival for some children.
FDA Approval for Deferiprone
Finally, on October 14, 2011, "the U.S. Food and Drug Administration approved Ferriprox (deferiprone) to treat patients with iron overload due to blood transfusions in patients with thalassemia, a genetic blood disorder that causes anemia, who had an inadequate response to prior chelation therapy... The therapy is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug’s clinical benefit.The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients...."
On the contrary, the wisdom of the FDA's accelerated (Fast Track) approval of deferiprone, is severely scrutinized in Dr Sidney Wolfe’s (PUBLICCITIZEN) detailed letter (Oct. 12, 2011), to the FDA where he concludes. “…..given the lack of data from adequate and well-controlled clinical trials demonstrating the safety and efficacy of deferiprone, as well as serious questions raised by DSl's inspection of study LA01 regarding the integrity of clinical trial data presented to the FDA by the sponsor, we urge the FDA to reject approval of NDA #021825 for deferiprone…….FDA approval of deferiprone based on such inadequate data would indeed set a recklessly dangerous precedent for drugs reviewed under an accelerated approval process in the future”.
The FDA briefing notes associated with the decision reveal that the request for regular or normal approval for marketing of deferiprone was declined by the FDA following scientific review because the evidence presented in the Apotex New Drug Application failed to adequately demonstrate safety and efficacy. Also the FDA site inspection of Olivieri’s trials showed that Apotex had wrongly omitted or misrepresented 45% of the Olivieri data in its submission to FDA.
FDA then informed Apotex that additional satisfactory randomized controlled evidence and a full, detailed audit of the Olivieri trials were required if Apotex was to pursue regular approval. The company declined and instead pursued 'accelerated' approval (known as conditional approval in Canada and other jurisdictions), which requires the lowest level of evidence.
Conditional or accelerated approval usually occurs BEFORE there has been time for conclusive clinical trials to be completed on promising new drugs, not AFTER a 20 year drug development program has generated randomized, controlled evidence which fails to demonstrate safety and efficacy.
In the end, the US FDA "accelerated approval" for last resort treatment with deferiprone was based on a single arm, non-controlled, non-randomized retrospective re-analysis of 264 patients selected from 746 patients in pooled data from studies previously conducted, showing a 20% reduction in serum ferritin in 52% of patients, the clinical significance of which is uncertain. There was "a lack of data to verify absence of a mortality disadvantage when deferiprone is used over a long period of time". The further studies to which the company must commit as part of accelerated approval are not yet described.
Awards and distinctions
- Ontario Ministry of Health Career Scientist, 1986
- Research Institute Distinguished Service Award, 1993
- American Society of Clinical Pharmacology and Therapeutics Rawls-Palmer Progress in Medicine Award, 1997
- Canadian Society for Clinical Pharmacology Senior Investigator Award, 1999
- International Association of Therapeutic Drug Monitoring Irving Sunshine Award for Outstanding Contributions to Clinical Toxicology, 1999
- Medical Research Council of Canada Senior Investigator Award, 2000
- Canadian Society for Clinical Pharmacology Distinguished Achievement Award, 2002
- International Association of Therapeutic Drug Monitoring Pippenger Award for Outstanding Contributions to Clinical Toxicology, 2003
- Spirit of the Community Humanitarian Award, Toronto, 2007
- Distinguished Scientist, Canadian Society for Clinical Investigation, 2010
- The Poulsson Medal for 2011, given by the Norwegian Society for Pharmacology and Toxicology, presented to Dr. Gideon Koren in recognition of his outstanding scientific contributions in the area of drug safety during pregnancy. This is the first time the award has been given to a Canadian scientist.
- Sumner J. Yaffe Lifetime Achievement Award in Pediatric Pharmacology and Therapeutics, Pediatric Pharmacy Advocacy Group, 2012
Currently held positions
Selected list of currently held positions (2010):- Founder and Director, MotheriskMotheriskMotherisk, created in 1985, is a clinical research and teaching program at The Hospital for Sick Children in Toronto, Ontario, Canada that provides information and guidance to pregnant or lactating women and to health care professionals regarding risks to the fetus from exposure to drugs,...
Program, Hospital for Sick ChildrenHospital for Sick ChildrenThe Hospital for Sick Children – is a major paediatric centre for the Greater Toronto Area, serving patients up to age 18. Located on University Avenue in Downtown Toronto, SickKids is part of the city’s Discovery District, a critical mass of scientists and entrepreneurs who are focused on... - Ivey Chair in Molecular Toxicology, University of Western OntarioUniversity of Western OntarioThe University of Western Ontario is a public research university located in London, Ontario, Canada. The university's main campus covers of land, with the Thames River cutting through the eastern portion of the main campus. Western administers its programs through 12 different faculties and...
- Holder, The Research Leadership for Better PharmacotherapyPharmacotherapyPharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....
during Pregnancy and Lactation, Hospital for Sick Children - Founder and Head, Fetal AlcoholFetal alcohol syndromeFetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
Canadian Expertise (FACE) - Chair, Steering Committee, Breaking the CycleCanadian Mothercraft SocietyThe Canadian Mothercraft Society is a non-profit, charitable NGO that serves children ages 0 to 6, their families, their teachers, and their community....
, Toronto - Editor in Chief (North America), Therapeutic Drug Monitoring
- Editor in Chief, Fetal Alcohol Research (FAR)
- Director of Research, The Canadian Foundation on Fetal Alcohol Research (CFFAR), 2008–present
- Director, Playwright and Producer of Tails in the Bear Theatre (Hospital for Sick Children)1992–present