Ravinder Dhallan

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Ravinder (Rav) Dhallan is the chairman and chief executive officer of Ravgen.

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Early life and education

Dhallan earned an M.D. and a Ph.D. in biomedical engineering at Johns Hopkins University, then began a residency in radiation oncology at Massachusetts General Hospital. Later, after deciding to found the startup firm Ravgen, he studied business at the University of Pennsylvania's Wharton School, receiving an MBA in 2007. [1] [2]

Career

According to a 2007 CNN profile, after Dhallan had begun his residency and fathered two children, his wife suffered two miscarriages, which caused him to be “struck by how little information was available to women who experienced complications during pregnancy....so he resolved to invent a better prenatal diagnostic exam.” Amniocentesis provides 100% accurate results, but has a one-in-200 risk of causing a miscarriage and cannot be carried out until 15 or 18 weeks into the pregnancy; existing non-invasive prenatal screenings, meanwhile, have low accuracy rates. As an alternative to these procedures, Dhallan developed and patented Rapid Analysis of Variations in the Genome, which involves drawing two tablespoons of blood from the expectant mother, isolating fetal DNA cells, and checking them for chromosome 21, the marker for Down syndrome. The method is 99% accurate and can be performed eight weeks into a pregnancy. [1]

In order to develop and exploit his procedure, Dhallan founded and incorporated the biotech startup firm RavGen. Meanwhile, he left oncology to do a residency in emergency medicine at York Hospital in York, Pennsylvania. He then became an attending physician in the Department of Emergency Medicine at Holy Cross Hospital in Silver Spring, Maryland. [2] According to CNN, he discovered that “the emergency room turned out to be great training for the daily high-wire act of running a startup. 'You get perspective,' says Dhallan. 'Once you've dealt with life and death day in and day out, other problems seem trivial.' The ER also helped him develop strong leadership skills. 'If someone has been shot six times, everyone is looking at the physician's response,' Dhallan says. 'If I didn't look confident, then everyone would lose confidence.'” [1]

RavGen

RavGen is based in Columbia, Maryland. Dhallan founded it in 2000 after raising $15 million for research and development. [1] According to its website, it was founded “with the goal of changing the paradigm of prenatal diagnostics.” While the current paradigm focuses on Downs syndrome testing, “there are many other genetic conditions and reasons to offer patients prenatal diagnosis,” among them cystic fibrosis and sickle-cell anemia. Dhallan and his colleagues have developed “safe, noninvasive tests to expand upon the current options available to patients.” [2]

In an article for the Journal of the American Medical Association, “Methods to Increase the Percentage of Free Fetal DNA Recovered From the Maternal Circulation,” Dhallan and his colleagues maintained that “An alternative to existing methods for prenatal diagnosis is to use fetal cells and fetal DNA that exist in the maternal circulation.” [3] Dhallan's method of non-invasive prenatal testing was described in a 2007 article in The Lancet (Lancet. 2007; 369:474-81). “Currently,” explained a Lancet press release, “available tests for prenatal diagnosis of chromosomal abnormalities—eg, trisomy 21, which causes Down’s syndrome—are limited by several factors. Screening tests, such as ultrasound, are non-invasive, but diagnosis requires further invasive testing. Invasive diagnostic tests, such as amniocentesis and chorionic villus sampling, are associated with risks to the pregnancy.”

Now, however, Dhallan and his colleagues had extracted fetal DNA from blood samples of pregnant women and examined them for chromosomal abnormalities “by analysing an array of single nucleotide polymorphisms (SNPs, pronounced “snips”)—tiny variations in the DNA sequence of individuals. The researchers established the ratio of SNPs on different chromosomes, which enabled them to determine whether the fetus had chromosomal abnormalities. Of the 60 samples tested, the technique identified the number of chromosomes correctly in 58, including two cases of trisomy 21. Although one case of trisomy 21 was not identified, and one normal sample was incorrectly identified as being trisomy 21, the researchers stress that this is a preliminary study, and that further trials are needed to fine tune the technique.” [2] The Lancet article was followed by a letter in which Dhallan replied to critics questioning the value of the procedure. [4] The Washington Post and Los Angeles Times reported on Dhallan's innovation in February 2007. [5] [6]

Ravgen has developed a new paternity test, described in a 2012 letter by Dhallan and several of his colleagues at Ravgen that was published in the New England Journal of Medicine (NEJM. 2012; 366:1743-1745). In the letter, entitled “A Non-Invasive Test to Determine Paternity in Pregnancy,” Dhallan and his team wrote that their “approach shows that noninvasive prenatal paternity testing can be performed within the first trimester with the use of a maternal blood sample.” [7] [2] A June 2012 New York Times article discussed Raygen's new paternity test, noting that it had been used to establish a motive in a 2008 murder case in Lancaster County, Pennsylvania. [8] Another 2012 article quoted Dhallan as saying, “It's not knowing who the father is that makes a pregnancy challenging and stressful for the mother....Knowing who the father is allows them to make informed decisions about their pregnancies. We've found it can be done very simply and eventually, inexpensively.” He added that “A quarter of women tell me straight up that my answer will impact whether they keep the pregnancy....By the time I did four cases, we had saved one baby. To me, every case is about life and death.” [9] [10]

Related Research Articles

<span class="mw-page-title-main">Amniocentesis</span> Sampling of amniotic fluid done mainly to detect fetal chromosomal abnormalities

Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is necessary to conclusively diagnose the majority of genetic disorders, with amniocentesis being the gold-standard procedure after 15 weeks' gestation.

<span class="mw-page-title-main">Genetic testing</span> Medical test

Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or through biochemical analysis to measure specific protein output. In a medical setting, genetic testing can be used to diagnose or rule out suspected genetic disorders, predict risks for specific conditions, or gain information that can be used to customize medical treatments based on an individual's genetic makeup. Genetic testing can also be used to determine biological relatives, such as a child's biological parentage through DNA paternity testing, or be used to broadly predict an individual's ancestry. Genetic testing of plants and animals can be used for similar reasons as in humans, to gain information used for selective breeding, or for efforts to boost genetic diversity in endangered populations.

<span class="mw-page-title-main">Prenatal testing</span> Testing for diseases or conditions in a fetus

Prenatal testing is a tool that can be used to detect some of these abnormalities at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Down syndrome, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.

<span class="mw-page-title-main">Chorionic villus sampling</span> Type of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus

Chorionic villus sampling (CVS), sometimes called "chorionic villous sampling", is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It entails sampling of the chorionic villus and testing it for chromosomal abnormalities, usually with FISH or PCR. CVS usually takes place at 10–12 weeks' gestation, earlier than amniocentesis or percutaneous umbilical cord blood sampling. It is the preferred technique before 15 weeks.

The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities.

The Pallister–Killian syndrome (PKS), also termed tetrasomy 12p mosaicism or the Pallister mosaic aneuploidy syndrome, is an extremely rare and severe genetic disorder. PKS is due to the presence of an extra and abnormal chromosome termed a small supernumerary marker chromosome (sSMC). sSMCs contain copies of genetic material from parts of virtually any other chromosome and, depending on the genetic material they carry, can cause various genetic disorders and neoplasms. The sSMC in PKS consists of multiple copies of the short arm of chromosome 12. Consequently, the multiple copies of the genetic material in the sSMC plus the two copies of this genetic material in the two normal chromosome 12's are overexpressed and thereby cause the syndrome. Due to a form of genetic mosaicism, however, individuals with PKS differ in the tissue distributions of their sSMC and therefore show different syndrome-related birth defects and disease severities. For example, individuals with the sSMC in their heart tissue are likely to have cardiac structural abnormalities while those without this sSMC localization have a structurally normal heart.

<span class="mw-page-title-main">Nuchal scan</span> Routine ultrasound done between 11 and 14 weeks pregnancy

A nuchal scan or nuchal translucency (NT) scan/procedure is a sonographic prenatal screening scan (ultrasound) to detect chromosomal abnormalities in a fetus, though altered extracellular matrix composition and limited lymphatic drainage can also be detected.

Noninvasive genotyping is a modern technique for obtaining DNA for genotyping that is characterized by the indirect sampling of specimen, not requiring harm to, handling of, or even the presence of the organism of interest. Beginning in the early 1990s, with the advent of PCR, researchers have been able to obtain high-quality DNA samples from small quantities of hair, feathers, scales, or excrement. These noninvasive samples are an improvement over older allozyme and DNA sampling techniques that often required larger samples of tissue or the destruction of the studied organism. Noninvasive genotyping is widely utilized in conservation efforts, where capture and sampling may be difficult or disruptive to behavior. Additionally, in medicine, this technique is being applied in humans for the diagnosis of genetic disease and early detection of tumors. In this context, invasivity takes on a separate definition where noninvasive sampling also includes simple blood samples.

The genetics and abortion issue is an extension of the abortion debate and the disability rights movement. Since the advent of forms of prenatal diagnosis, such as amniocentesis and ultrasound, it has become possible to detect the presence of congenital disorders in the fetus before birth. Specifically, disability-selective abortion is the abortion of fetuses that are found to have non-fatal mental or physical defects detected through prenatal testing. Many prenatal tests are now considered routine, such as testing for Down syndrome. Women who are discovered to be carrying fetuses with disabilities are often faced with the decision of whether to abort or to prepare to parent a child with disabilities.

Confined placental mosaicism (CPM) represents a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the fetus. CPM was first described by Kalousek and Dill in 1983. CPM is diagnosed when some trisomic cells are detected on chorionic villus sampling and only normal cells are found on a subsequent prenatal test, such as amniocentesis or fetal blood sampling. In theory, CPM is when the trisomic cells are found only in the placenta. CPM is detected in approximately 1-2% of ongoing pregnancies that are studied by chorionic villus sampling (CVS) at 10 to 12 weeks of pregnancy. Chorionic villus sampling is a prenatal procedure which involves a placental biopsy. Most commonly when CPM is found it represents a trisomic cell line in the placenta and a normal diploid chromosome complement in the baby. However, the fetus is involved in about 10% of cases.

<span class="mw-page-title-main">Maternal–fetal medicine</span> Branch of medicine

Maternal–fetal medicine (MFM), also known as perinatology, is a branch of medicine that focuses on managing health concerns of the mother and fetus prior to, during, and shortly after pregnancy.

<span class="mw-page-title-main">Trisomy 16</span> Partial or complete triplication of chromosome 16

Trisomy 16 is a chromosomal abnormality in which there are 3 copies of chromosome 16 rather than two. It is the most common trisomy leading to miscarriage and the second most common chromosomal cause of it, closely following X-chromosome monosomy. About 6% of miscarriages have trisomy 16. Those mostly occur between 8 and 15 weeks after the last menstrual period.

Sequenom is an American company based in San Diego, California. It develops enabling molecular technologies, and highly sensitive laboratory genetic tests for NIPT. Sequenom's wholly owned subsidiarity, Sequenom Center for Molecular Medicine (SCMM), offers multiple clinical molecular genetics tests to patients, including MaterniT21, plus a noninvasive prenatal test for trisomy 21, trisomy 18, and trisomy 13, and the SensiGene RHD Fetal RHD genotyping test.

Ravgen Inc. is a privately owned biotech company founded by Chairman and C.E.O. Dr. Ravinder Dhallan. Ravgen Inc. is known for its research in the prenatal diagnostic field and its development of non-invasive prenatal diagnosis testing which was published in The Lancet, the Journal of the American Medical Association ., and the New England Journal of Medicine. These publications received worldwide press in The Times, The Washington Post, CNN Fortune Small Business, and The New York Times

Cell-free fetal DNA (cffDNA) is fetal DNA that circulates freely in the maternal blood. Maternal blood is sampled by venipuncture. Analysis of cffDNA is a method of non-invasive prenatal diagnosis frequently ordered for pregnant women of advanced maternal age. Two hours after delivery, cffDNA is no longer detectable in maternal blood.

<span class="mw-page-title-main">Diana W. Bianchi</span> American medical geneticist and neonatologist

Diana W. Bianchi is the director of the U.S. National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, a post often called “the nation’s pediatrician.” She is a medical geneticist and neonatologist noted for her research on fetal cell microchimerism and prenatal testing. Bianchi had previously been the Natalie V. Zucker Professor of Pediatrics, Obstetrics, and Gynecology at Tufts University School of Medicine and founder and executive director of the Mother Infant Research Institute at Tufts Medical Center. She also has served as Vice Chair for Research in the Department of Pediatrics at the Floating Hospital for Children at Tufts Medical Center.

A termination for medical reasons (TFMR) is an induced abortion motivated by medical indications involving the fetus or mother. In most countries, health risks are the only basis for obtaining a legal abortion. Prenatal screening can allow early diagnosis, and abortion if desired or necessary. Some medical organizations advocate the offer of diagnostic testing by chorionic villi sampling, and amniocentesis to all pregnant women, as a matter of course.

Rh factor testing, also known as Rhesus factor testing, is the procedure of determining the rhesus D status of an individual.

<span class="mw-page-title-main">Trisomy X</span> Chromosome disorder in women

Trisomy X, also known as triple X syndrome and characterized by the karyotype 47,XXX, is a chromosome disorder in which a female has an extra copy of the X chromosome. It is relatively common and occurs in 1 in 1,000 females, but is rarely diagnosed; fewer than 10% of those with the condition know they have it.

Noninvasive prenatal testing (NIPT) is a method used to determine the risk for the fetus being born with certain chromosomal abnormalities, such as trisomy 21, trisomy 18 and trisomy 13. This testing analyzes small DNA fragments that circulate in the blood of a pregnant woman. Unlike most DNA found in the nucleus of a cell, these fragments are not found within the cells, instead they are free-floating, and so are called cell free fetal DNA (cffDNA). These fragments usually contain less than 200 DNA building blocks and arise when cells die, and their contents, including DNA, are released into the bloodstream. cffDNA derives from placental cells and is usually identical to fetal DNA. Analysis of cffDNA from placenta provides the opportunity for early detection of certain chromosomal abnormalities without harming the fetus.

References

  1. 1 2 3 4 Palmer, Lisa (7 September 2007). "A better prenatal test?". CNN.
  2. 1 2 3 4 5 "Company Overview". Ravgen.
  3. ↑ "Methods to Increase the Percentage of Free Fetal DNA Recovered From the Maternal Circulation". Journal of the American Medical Association.
  4. ↑ "Non-invasive prenatal diagnosis of Down's syndrome — Authors' reply". The Lancet.
  5. ↑ Gardner, Amanda (Feb 2, 2007). "Experimental Prenatal Test Helps Spot Birth Defects". Washington Post.
  6. ↑ Roan, Shari (Feb 12, 2007). "The next step in fetal diagnosis; A pregnant woman's blood could be all doctors need to find many genetic disorders". LA Times.
  7. ↑ Guo, Xin; Bayliss, Philip; Damewood, Marian; Varney, John; Ma, Emily; Vallecillo, Brett; Dhallan, Ravinder (2012). "A Noninvasive Test to Determine Paternity in Pregnancy". New England Journal of Medicine. 366 (18): 1743–1745. doi:10.1056/NEJMc1113044. PMID   22551147. S2CID   205047785.
  8. ↑ Pollacl, Andrew (Jun 19, 2012). "Before Birth, Dad's ID". NY Times.
  9. ↑ "Who's the Dad? First-Trimester Blood Test May Tell". HealingWell.
  10. ↑ Palmer, Lisa (7 September 2007). "A better prenatal test?". CNN.
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