Dr. Anver Kuliev of Reproductive Genetics Institute at Chicago, has appeared in a recent news headline, Chicago lab key in helping create babies to aid siblings. This news has raised some unsettled issues concerning the appropriateness of "genetics action" and "genetics intervention" on human lives especially from unborn to new born babies. These issues are complex. The controversy debated by the general public seems to be focused on the motives and action results of these genetics activities. Often the debates are made emotionally, not based on scientific facts and rational thoughts. People sometimes do not have a clear understanding of what and how these genetics activities are done. In this article, we present some relevant information concerning the "genetics actions" and "genetics interventions" without taking a position on the debated issues. The information presented here should not be regarded as expert opinions. They are the results of limited literature research with the purpose of gathering the relevant information in one place for readers to gain a quick grasp of the concepts and facts about these genetics activities. Through the discussion and references provided here, readers can pursue more in-depth study of these topics. With better understanding of the scientific facts, people can arrive at rational conclusions on controversy issues.
In this article, definitions and concepts of the various genetics actions (experiments, diagnosis, procedures, etc) are discussed first. The possible applications of "genetics intervention" are then described. Hopefully the information presented here will lead readers to deduce or find answers to to the controversial questions.
Definitions, Concepts and Genetic Diseases
What are genetic disorders?
Both environmental and genetic factors have roles in the development of any disease. Environmental factors have to do with living condition and life style where air, water, diet, exercise, drugs, toxic materials and stress come to play. A genetic disorder is a disease caused by abnormalities in an individualís genetic material (genome), inherited from parents and ancestors.. There are four different types of genetic disorders: (1) single-gene, (2) multifactorial, (3) chromosomal, and (4) mitochondrial.
(1) Single-gene (also called Mendelian or monogenic) - This type is caused by changes or mutations that occur in the DNA sequence of one gene. Genes code for proteins, the molecules that carry out most of the work, perform most life functions, and even make up the majority of cellular structures. When a gene is mutated so that its protein product can no longer carry out its normal function, a disorder can result. There are more than 6,000 known single-gene disorders, which occur in about 1 out of every 200 births.
Some examples are
cystic fibrosis (See supplemental reading)
sickle cell anemia (Sickle cell anaemia is an
inheritable genetic condition in which there is an abnormality of
haemoglobin in red blood cells.Haemoglobin is the oxygen-carrying
protein in red cells. People with Sickle Cell Anaemia have a type of
haemoglobin known as Sickle haemoglobin (HbS) that is different from the
normal haemoglobin (HbA).
Marfan syndrome (Marfan Syndrome is an inherited disorder of the connective tissues. The gene which is abnormal usually controls production of a protein called fibrillin. Fibrillin plays an important part in the normal structure or 'scaffolding' of connective tissue throughout the body. When abnormal protein is produced, the structure of the connective tissue is abnormal and weak. Severity varies, but on average 1 in 10 is seriously affected.)
Huntingtonís disease (See supplemental reading)
Hemochromatosis (Haemochromatosis (or Genetic Haemochromatosis, GH) is a disorder which causes the body to absorb an excessive amount of iron from the diet. The iron accumulates mainly in the liver but can also affect the heart, pancreas and pituitary gland.)
Single-gene disorders are inherited in recognizable patterns: autosomal dominant, autosomal recessive, and X-linked (dominant and recessive). More information on the different modes of inheritance can be found n the references listed below (12-15). The supplemental reading on the right column gives explanation of some of the terminology and how gene works.
Examples of dominant single gene disorders or characteristics include:
(2) Multifactorial (also called complex or polygenic) - This type is caused by a combination of environmental factors and mutations in multiple genes. For example, different genes that influence breast cancer susceptibility have been found on chromosomes 6, 11, 13, 14, 15, 17, and 22. Its more complicated nature makes it much more difficult to analyze than single-gene or chromosomal disorders. Some of the most common chronic disorders are multifactorial disorders.
Some Examples Are heart disease, high blood pressure, Alzheimerís disease, arthritis, diabetes, cancer, and obesity. Multifactorial inheritance also is associated with heritable traits such as fingerprint patterns, height, eye color, and skin color.
(3) Chromosomal - Chromosomes, distinct structures made up of DNA and protein, are located in the nucleus of each cell. Because chromosomes are carriers of genetic material, such abnormalities in chromosome structure as missing or extra copies or gross breaks and rejoinings (translocations), can result in disease. Some types of major chromosomal abnormalities can be detected by microscopic examination. Down syndrome or trisomy 21 is a common disorder that occurs when a person has three copies of chromosome 21. See supplemental reading on sex chromosome on the right column.
Sex-lined conditions include:
Chromosome disorders are due to abnormalities in the normal group of 46 chromosomes inherited from parents.
For example, individuals may have more or fewer chromosomes than normal, or there may be structural changes in the chromosomes, where part of one chromosome may be lost or have attached to the end of another chromosome (a condition known as translocation).
Some of the commonest chromosomal disorders are a group known as the Trisomies. A Trisomy means a person has three copies of one of their chromosomes instead of two, e.g. Down's Syndrome is Trisomy 21. Edward's Syndrome is Trisomy 18 and Patau's syndrome is Trisomy 13. There may also be 3 copies of the sex chromosomes, e.g. in Klinefelter's Syndrome.
(4) Mitochondrial - This relatively rare type of genetic disorder is caused by mutations in the nonchromosomal DNA of mitochondria. Mitochondria are small round or rod-like organelles that are involved in cellular respiration and found in the cytoplasm of plant and animal cells. Each mitochondrion may contain 5 to 10 circular pieces of DNA.
Genotype and Phenotype
Genotype means all the genes you have inherited from both parents, whether they show as characteristics or not. For every gene from one parent there is an equivalent gene that codes for exactly the same thing - such as eye color - that came from the other parent. These pairs - or versions of genes that do the same biological job - are called alleles. If the information they carry is exactly the same they are called homozygous (alike) alleles. If the information is different they are called heterozygous (unalike) alleles. Genotypes are often described using the abbreviation of one or two letters of the alphabet, so the blue eyes gene may be bl, while brown eyes are br and green eyes are g.
Phenotype describes the way these genes are actually expressed in you - in other words your appearance and all the other biological traits you have inherited.
For example, if you inherit an allele for brown eyes (br) from each of your parents, then your eye color genotype will be br br i.e. you received homozygous alleles of eye color.
Dominate or recessive Genes
Dominant alleles are stronger - when one allele in a pair is dominant and the other recessive, the dominant one always wins. The characteristic it carries in its DNA code is the one that shows.
The existence of dominant or recessive genes explains how one could have blue eyes with two parents having brown eyes. Parents having brown eyes could carry brown genes but also could carry the allele or gene for blue eyes (inherited from their parents) and could pass it on to the child. If brown were dominant while blue was recessive, so blue didn't come out in the parents' eyes. But the blue allele could come out in their child because the child's eye-color alleles were homozygous - blue, no brown to dominate.
Very few human characteristics are determined by a single gene. Most are controlled by several genes and the majority of these are homozygous. We share 99.9 per cent of our genes with the rest of the human race. It is the minority of heterozygous genes that create the variations among people in the human race.
In some genetic conditions, inheriting just one copy of the mutated gene is enough to cause a disease. These are called dominant genetic disorders, because the abnormal gene dominates no matter what the second copy of the gene is.
One example, Huntington's disease. Huntington's Disease is a degenerative condition that affects the brain and central nervous system. It is caused by a faulty gene that leads to the production of an abnormal variant of a protein called Huntington. This abnormal protein accumulates in cells in certain areas of the brain, especially those areas controlling movement. This causes the cells to die and the gradual onset of physical, mental and emotional changes. symptoms don't usually appear until middle age, hence, the person may have passed the 'disorder' gene to his or her child.
Recessive inheritance of genetic disorder means that in order to have the disease, one would have to inherit two copies (alleles) of the abnormal gene, one from each parent. These recessive genes have no effect unless paired with a similar gene from the other parent. Hence, genetic tests (screening) are viewed as a possible means to prevent passing genetic disorder to offsprings. Some of the relatively more common genetic conditions, such as cystic fibrosis (Cystic Fibrosis (or CF) is a degenerative condition that affects the lungs and pancreas. Although it is a life-threatening condition, survival continues to improve. 75% of affected children now survive to young adulthood and the average survival is to the age of 31.), thalassaemia and sickle-cell disease, are passed on by recessive inheritance..
Recessive genes can be passed down from generation to generation by people who also carry one normal, dominant, copy of the gene. Often they are not even aware they are carrying the abnormal recessive gene. But when two carriers (people who each have only one copy of the defective gene) have a child together the condition may emerge in the baby. Even then there is only a one in four chance that their child will be born with the disease.
whether one is male or female is determined by one's sex chromosomes. (Note: Gay behavior may or may not have anything to do with one's sex genes. "Strict" gay people can not bear children hence can not pass on gene disorder)
In humans, the sex chromosomes come in two types called X and Y. If one has two X chromosomes (XX), she is female. But if one has an X paired with a Y chromosome (XY), then he is male. It is the presence of the Y chromosome that determines whether one is a boy or a girl.
Unlike all the other 22 chromosomes pairs in the set of 46 chromosomes, the X and Y chromosomes look nothing like one another. In humans, Y chromosome carries the gene that determines 'maleness' but little else.
For males, this means that almost every allele carried on the single X chromosome will express its effects, regardless of whether it is dominant or recessive, because there is no partner allele on the Y chromosome. Since for male (XY), Y chromosome is always inherited from the father. X chromosome is always inherited from the mother (Y came from father and father's X was absent, if not absent, then XX would mean a female not a male)
In some genetic conditions the abnormal gene is on one of the sex chromosomes, X or Y. By probability, these conditions tend to be more common among boys (passed from parents) because
It seems nature favors female (Is it because who is the one to bear offspring, or reproduce, naturally?), so the abnormal genes have less a chance to be passed on to a female. On the hand, if a female did carry any abnormal gene, giving birth to a boy would be very undesirable. With 'genetics action' possible to produce test tube baby and to do diagnosis prior to implantation, certainly the odds provided by nature can be altered. Is this right or wrong? Does human race have the right to improve the odds in the reproduction process? These are issues every human being has a right to express one's opinion.
People with Down's Syndrome have 3 copies of chromosome 21 instead of 2. This additional genetic material changes the finely tuned balance of the body and results in characteristic physical and intellectual features.
|What Can Genetic Tests Tell and Help?
Genetic tests may be offered to people in various situations. One of the commonest is when a couple know they might have a child with a serious genetic disorder - either because there is a history of a disease in the family, or they have already had a child with a disease. By examining the genes of the two parents, genetic testing can be used to assess the actual risk of any future child inheriting the disorder.
If a pregnancy does occur, the couple may then wish to have prenatal diagnosis to analyze the fetus's own genes. This may be able to tell them, to a high degree of certainty (although not absolutely 100%), whether the fetus actually has the abnormal genes. If it does, one option they may wish to consider is to terminate the pregnancy.
Many pregnant women in Britain are offered screening tests for Down's Syndrome. These tests measure levels of certain chemicals in the mother's blood (the Double or Triple test) or measure the depth of the pad of fat on the baby's neck (the Nuchal Test) to estimate the risk of Down's Syndrome. If the risk is high the mother may be offered either an amniocentesis which tests the cells in the fluid around the fetus for the chromosomal abnormality that causes Down's Syndrome or CVS (chorionic villus sampling) which looks at a tiny sample of cells from the placenta.
What is PGD ? Pre-implantation genetic diagnosis (PGD).
Pre-implantation Genetic Diagnosis or PGD is a complex test which examines the genes of a newly conceived embryo, and can detect certain genetic or chromosomal abnormalities. The test is done at a very early stage after conception - before the embryo has even had a chance to implant or settle into the lining of its mothers womb (hence the term pre-implantation). In order for this to be possible the embryo must be produced in the laboratory using the well-established techniques of in vitro fertilization (IVF or 'test tube babies'). Only those embryos which are found to be healthy are then put back into the mother.
This new, sophisticated technique is only available for a limited number of conditions. These include spinal muscular atrophy, sickle cell anaemia, cystic fibrosis, many X-linked conditions (if only boys are affected, female embryos can be expected to be healthy) and Huntington's disease. PGD involves fertilizing several of the mother's eggs by IVF in a laboratory, testing the embryos and then implanting only one or two healthy ones in the womb. It has a one in three success rate.
How is PGD done?
The procedure is as follows::
Advantages of PGD
There are many advantages to PGD, especially to parents who have watched a child suffer and struggle with a severe incurable illness. PGD may be less traumatic than amniocentesis (which is performed during the second trimester pf a pregnancy), as it is performed in the laboratory before the embryo has even implanted in its mother. A debatable issue: is it more acceptable to destroy a 3 day old embryo which has an incurable condition than a 17 week-old fetus carrying a gene disorder?
PGD Can Help IVF and ART
The following is extracted from a speech by Dr. Anver Kuliev on the value of PGD: "Preimplantation genetic diagnosis (PGD), a new approach to detecting and avoiding transfer of embryos with genetic abnormalities, is an alternative to embryo transfer based on morphologic criteria currently in use in IVF practice. Since genetic factors contribute considerably to infertility problems, PGD has special value to ART (assisted reproductive technology) and IVF. Because more than half the women who seek IVF are of advanced reproductive age, PGD provides an obvious tool for preselecting embryos, avoiding transfer of those with age-related aneuploidies, which are major contributors to spontaneous abortions and implantation failure. The current IVF practice of "blind" selection of embryos for transfer is hardly an acceptable procedure to use in future IVF patients of advanced maternal age."
Not Possible To Test Every Gene
It would be an enormous task to screen for every possible genetic disorder. Also, most genetic conditions can't be detected by routine screening because doctors don't yet know precisely which gene they are looking for as it hasn't yet been identified. Some conditions could be due to one or more mistakes in different bits of the DNA code, so a very specialized genetic search would be required to rule out all possible abnormalities.
So PGD cannot be used to randomly look for possible abnormal genes because there are so many human genes to check. Instead those performing the test have to know what abnormality they are looking out for. So the genetic disorder, and the DNA code of the gene abnormality causing it, must already have been identified.
It is typically offered to prospective parents who are worried that they may pass a particular incurable genetic condition on to their child. They may already have had one or more affected children, and usually one or both partners have been genetically screened and found to be a carrier.
Down's Syndrome Can Be Screened
People with Down's Syndrome have 3 copies of chromosome 21 instead of 2. This additional genetic material changes the finely tuned balance of the body and results in characteristic physical and intellectual features.
From 11 to 14 weeks of pregnancy, a special ultrasound scan called a nuchal translucency (NT) test can be performed. This measures the fluid under the skin at the back of the baby's neck and can be used to determine your risk of having a baby with Down's syndrome.
There is also a blood test which can be performed either in combination
with the NT scan (the Combined Test) or on its own. The blood test
measures hCG (human chorionic gonadotrophin)
CVS ( chorionic villus sampling )
Depending on the position of the placenta the doctor will either pass a needle through the pregnant woman's abdomen, or will thread a fine tube through her vagina and cervix to reach the placenta. For a transabdominal CVS, a local anaesthetic to numb the wall of the abdomen will be given before the needle is inserted
The doctor will then extract a fragment of chorionic villi ó tiny fingerlike projections on the placenta. The cells taken from the placenta are full of genetic information that can be analyzed to reveal the chromosomal make-up and the sex of your baby.
Using ultrasound for guidance, the doctor will identify a pocket of amniotic fluid a safe distance from both the baby and the placenta. Then a long, thin, hollow needle is inserted through the abdominal wall and into the sac of fluid around the baby. Local anaesthetic is optional. With the needle, the doctor withdraws a small amount of amniotic fluid ó about an ounce. This fluid contains cells from the baby, chemicals, and micro-organisms that can answer many questions about the baby's health such as genetic disorder or birth defect.
Risks and Advantages of PGD
There are some risks with PGD, including those common to all IVF treatments. These include OHSS (ovarian hyperstimulation syndrome), ectopic pregnancy and multiple pregnancy. The risk of a miscarriage is not increased, nor is the risk of a birth defect. The embryo can continue to grow normally after losing a cell or two at this early stage. This is because at this stage of development each cell could give rise to a complete embryo by itself and does not have a specific job.
Performing PGD is not to guarantee a healthy baby but looks for the specific genetic problem under investigation (and can not randomly investigate every possible disease). PGD also does not detect other problems which may arise co-incidentally. So if the test is checking for Cystic fibrosis, it will not detect Fanconiís anaemia. Also it is not yet 100% reliable (although for many conditions the risk of misdiagnosis is small).
PGD may be complicated by the fact that in some conditions, such as cystic fibrosis, there are a number of different genetic abnormalities which can cause the condition and it may not be possible to rule them all out (although the test will focus on the specific genetic variant already identified in that family, so it should be fairly accurate).
Sometimes, healthy embryos fail to implant back into the motherís womb after being disrupted by PGD, so the live birth rate may be even lower than that of IVF (which is around 30%). The procedure can be very stressful, some women get unpleasant side effects from the ovulation drugs, and it is expensive and not widely available.
Some people have religious or ethical objections to PGD, because they believe that we become human beings at conception, so destruction of unhealthy embryos is equivalent to murder. It has also been argued that some genetic diseases only cause symptoms when the person is in their 30s or 40s, by which time a cure might have been found. The procedure could be the start of a slippery slope to eliminate 'undesirable' features from society such as people with red hair or a particular sexual orientation. Perhaps embryos would be eliminated that might leave the individual at higher risk for heart disease, or stroke, or obesity, etc.
One plausible argument is that since we do not yet have full knowledge of how the human genetics worked in the past and at present environments and how it may work in the future environments, perhaps it is premature for human to perform human genetic engineering. Therefore it is important for us to understand what scientists have learned and factor that into the process of arriving at any conclusion.
What Did Dr. Anver Kuliev Do to Create Another Headline News?
|Create Babies To Help Siblings
Five healthy babies have been born to provide stem cells for siblings with serious non-heritable conditions. This is the first time "saviour siblings" have been created to treat children whose condition is not genetic, says the medical team at Chicago, led by Dr. Anver Kuliev of the Reproductive Genetics Institute.
Because of the use of PGD to test embryos for a tissue type to match to the ailing siblings, the term of "Designer Baby" was used in some news stories. Of course, this term is not appropriate for describing the PGD selected babies. A more appropriate term may be "Quality Inspected Baby" or "Spec baby", since what PGD is doing is to find embryos that meet a given spec. PGD has no way of interfering with the original design, it merely selected a desired pattern. Is this so horrible? The issues remain are that what is the appropriate procedure to handle the undesired embryos left in the inspection and selection process? Do we have the right to destroy the unselected embryos if they do contain some defects within or outside of the spec?
In a modern manufacturing plant, 'Six Sigma' quality control is often used to make sure the entire manufacturing, from selection of material suppliers, design of the manufacturing procedures and quality control of manufacturing processes to post production inspections, are all honed to produce six-sigma results. The manufacturers own their product design and have the rights to alter the design so long their production processes do not violate any environmental laws and their products meet government regulations.
For making babies, who other than the parents can own the rights to the design? Do we have any environmental laws governing the production of babies? Should we and can we define such laws? People who inherit a curiously defective gene from both their parents may have a natural resistance to infection by HIV, should they have more babies? Can Alcoholics or obese people with fat genes have babies? Who should define a list of genetic disorders that would be considered off-spec? Who should regulate the laws and rules in baby making?
Test Tube Baby and IVF Baby
A baby conceived by fertilization that occurs outside the mother's body; the woman's ova are removed and mixed with sperm in a culture medium - if fertilization occurs the blastocyte is implanted in the woman's uterus.
In IVF, eggs are gathered from the woman's ovaries and mixed with the man's sperm in a dish in the laboratory. "In vitro" is a Latin term literally meaning "in glass". It refers to the glass dish in the laboratory where fertilization takes place. Since test tube rather than a special dish is more familiar to the public, hence the term "test-tube baby" becomes popular. Thousands of IVF babies have been born worldwide since the technique was first used successfully in 1978.
The British government has announced that, from April 2005, the NHS will fund one free IVF cycle for couples experiencing fertility problems, provided the woman is under 40.
There are 4 million babies born in the US but there are 6 million infertile couple in US. Only 60,000 IVF cycles are performed (due to high cost).
When most people think of designer babies, they think of the ability of the parents to pick their babies eye color, height, intelligence, and other physical traits. With the rapid progress of genetics research, it is not inconceivable that this could become a reality in the next century, but our knowledge on genetics is still far from complete. Furthermore, there ethical issues the human race needs to address.
Most people may disapprove the idea of having designer baby and the government may not support research towards that goal..
A baby is selected via genetic screening according to a criterion to avoid genetic disorder during any assisted reproductive process.
We may have raised more questions than provided answers to the complex issues to human genetics. However, we hope that the discussions and references contained herein do offer readers a path to learn more facts so you can develop your own answers to the issues.
1. Chicago lab key in
helping create babies to aid siblings
Five "designer babies" created for stem cells http://www.newscientist.com/news/news.jsp?id=ns99994965
Babies bred for stem cells http://www.news24.com/News24/Technology/News/0,,2-13-1443_1522481,00.html
Vol. 4, No. 2 - February 2001
... Atlas of Preimplantation Genetic Diagnosis, edited by Yury Verlinsky, Anver Kuliev. 1170. Atlas of Transvaginal Color Doppler, 2nd edition edited by Asim Kurjak, Sanja Kupesic. 1171. Atlas of the ...
... St. Chicago, IL 60657 Fax: 773-871-5221 Steering Committee: Jacque Cohen (USA) Joy Delhanty (UK) Robert Edwards (UK) Luca Gianaroli (ITALY) Jamie Grifo (USA) Alan Handyside (UK) Anver Kuliev (USA ...
PREIMPLANTATION DIAGNOSIS OF THALASSAEMIA Author: Dr Anver Kuliev WHO Collaborating Centre Chicago, Illinois One of the limitations of the present medical genetics practices is that the couples at ...
Diagnosis of Genetic Disease: A New Technique for Assisted Reproduction
Yury Verlinsky; Anver Kuliev
6. Should IVF Centers Offer Preimplantation Genetic Diagnosis? Yes. (Google Cache) http://220.127.116.11/search?q=cache:w3eRAjAGmu4J:www.medscape.com/viewarticle/451547_print+Anver+Kuliev+Chicago&hl=en
7. Genetic test averts birth defect disorder in baby http://health_info.nmh.org/HealthNews/reuters/NewsStory040920038.htm
diagnosis of autosomal dominant retinitis pigmentosum using two simultaneous single
cell assays for a point mutation in the rhodopsin gene M.Strom ,
Svetlana Rechitsky, George Wolf, Jeanine Cieslak, Anver Kuliev and Yury ...
Masonic Medical Center, 836 Wellington Avenue, Chicago, IL 60657
9. Preimplantation Diagnosis for Sonic Hedgehog Mutation Causing Familial Holoprosencephaly Yury Verlinsky, Ph.D., Svetlana Rechitsky, Ph.D., Oleg Verlinsky, M.S., Seckin Ozen, M.D., Tatyana Sharapova, M.S., Christina Masciangelo, M.S., Randy Morris, M.D., and Anver Kuliev, M.D., Ph.D.
Atlas of Preimplantation Genetic Diagnosis
... By Yury Verlinsky,Anver Kuliev,Yuri Verlinsky ... genetic diagnosis, Verlinsky and Kuliev
(Reproductive Genetics ... Reproductive Genetics Institute, Chicago, IL Atlas
11. Reach Out to American Communities: National Children's Study Assembly Meets in Atlanta http://www.phgu.org.uk/newsletter/index.shtml http://18.104.22.168/search?q=cache:5yyGTnhK-tcJ:www.phgu.org.uk/newsletter/index.shtml+Mohammed+Taranissi+JAMA&hl=en
12. Inheritance of Single Gene Defects - From the The Merck Manual of Diagnosis and Therapy, Chapter 286, General Principles of Medical Genetics
13. Genetic Disorders: Types of Inheritance - From Gene Stories provided by BBC.14. Inheritance Patterns of Monogenic Disorders - From the Genetic Interest Group in the U.K.
15. Genetics - From the Medical Encyclopedia at MEDLINEplus.
16. Dominant Inheritance http://www.bbc.co.uk/health/genes/disorders/dominant.shtml
17. Recessive Inheritance http://www.bbc.co.uk/health/genes/disorders/recessive.shtml
18. 'God is Not in Charge, We Are' http://www.mindfully.org/GE/2003/IVF-Baby-Turns-25-24jul03.htm
Dr. Chang is the co-founder of Medical World Search which offers an intelligent medical search engine, called MWSearch. MWSearch is an independent search service without affiliation with any healthcare organization or drug companies. Medical World Search ( www.mwsearch.com ) has been offered for public use since 1996.
In early 90's, while working as a research scientist at IBM T. J. Watson Research Center, Dr. Chang led a group of researchers developing an advanced clinic information system with the purpose of supporting efficient and reliable healthcare practice. The system has been adopted by Kaiser Permanente and other healthcare organizations. Dr. Chang writes articles for MWSearch from time to time.
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