Rooted in Research: NIPT and the Story of Dave Peters
At SignatureDx, we’re driven to advance the field of early detection diagnostics through noninvasive technology. We uphold our core values in all aspects of our work, and our research collaborators share the SignatureDx passion to help change the paradigm of healthcare. A founding component of our research is women’s reproductive health, and further, noninvasive prenatal testing (NIPT).
In this blog series, we’ll introduce Dr. David Peters—Chief Science Officer and co-founder of SignatureDx—and how his research and personal experiences formed our company philosophy. Part 1 of this series will begin the story of Peters’ unique background and what led him to shift his scientific focus to the field of NIPT.
In its simplest form, NIPT is a screening tool which uses a maternal blood sample to identify fetal genetic traits and abnormalities that could be a risk to both the mother and baby. Previously common practices to identify these abnormalities include highly invasive and risky procedures such as chorionic villus sampling (CVS) or amniocentesis.1
To understand how NIPT screening progressed to where it is now, we must return to the 1990s—when the first groundbreaking discoveries in NIPT surfaced and David Peters had his sights set on a very different side of genomic research.
History of NIPT and SignatureDx
1994 - Dave Peters gets his PHD in Genomics
1997 - Fetal DNA discovered in maternal plasma
1998 - Peters starts his own lab
2001 - Peters confronts shortcomings of invasive prenatal testing
2009 - Peters and Chu identify aneuploidies in maternal plasma
2011 - NIPT gets widespread adoption
In 1994, Peters received his PhD in Genetics from the University of Liverpool. He then moved to Pittsburgh to begin his post-doctoral research in genomics and DNA sequencing. At this point, Peters’ scientific focus was far from the realm of prenatal medicine. Instead, he and his team spent their time studying everything from ovarian cancer to the many facets of vascular biology. Peters took particular interest in brain aneurisms, exploring the reaction between arteries in the interior wall of the brain and different fluid mechanical forces. Additional projects included NASA-funded collaborations involving how space flight affects blood flow and the way genes are regulated in the cells.
In the 1990s, genomics was studied through targeted sequencing, meaning Peters and his peers were trained to look at only one genome or one part of the gene at a time. At the beginning of 1995, Peters began research on early methods of massively parallel sequencing—also called next generation sequencing—which allowed scientists to analyze the entire genome in a less time-intensive manner.
Meanwhile in Oxford, a scientist from Hong Kong named Dr. Dennis Lo was hypothesizing the use of a technique called PCR (polymerase chain reaction) to amplify Y chromosome sequence from maternal plasma.2 This meant focusing on cell-free DNA instead of the parts of the cell itself, which is what scientists had attempted previously.
During pregnancy, the mother’s uterus and the placenta intertwine despite the presence of a barrier separating the two circulatory systems. As the placenta develops and grows, a small amount of its cells escapes into the mother’s blood.
By removing the cells and plasma from the sample, Lo was able to analyze the remaining liquid, which is made up of both fragmented maternal DNA as a product of dead cells and a small amount of placental DNA. In short, the presence of fetal DNA can be detected in maternal plasma.1,2
Lo’s discovery drastically altered the approach to prenatal testing and laid the groundwork for more advanced detection diagnostics. It also enabled the opportunity to identify other immature fetal cells and potentially determine genetic information about the baby. For example, when analyzing the mother’s sample, scientists can detect a paternally-inherited gene that the mother doesn’t have and conclude that the gene is part of the baby’s genetics.
According to Peters, these paternally-inherited traits in the sample stand out in the mixture like “a very dim star in a completely black sky”, because the mother’s genes do not share these traits. In the sample mixture, the maternally-inherited genes of the baby are more difficult to distinguish from the mother’s genes; explained by Peters as “a very dim star in a very bright sky…if you look up at a bright night sky full of stars everywhere, that one dim star is very hard to see because of all the background.”
From the point of Lo’s discovery, the NIPT field stagnated for several years, unable to solve the question of how to analyze the sample mixture to determine maternally-inherited traits and frequently maternally-inherited conditions such as Down Syndrome.
So what does Lo’s discovery have to do with Dave Peters? And further, with SignatureDx?
Despite the significance of his previous genomic research, Peters found his true scientific niche after his wife underwent amniocentesis while pregnant with their first child in spring of 2001.
During the pregnancy, Peters and his wife were exposed to prenatal healthcare in both Pittsburgh and the United Kingdom. Peters remembers the high-quality genetic counseling they received in Pittsburgh when discussing potential birth risks and recommended testing.
The genetic counselor told Peters’ wife that the chance of their baby having Down Syndrome was the same as the risk of losing their baby if she received amniocentesis to test for Down Syndrome. Peters was stunned that this incredibly invasive and risky procedure was standard practice for prenatal testing.
“So that was a real wake up call. [My wife] had the test anyway, but that’s kind of what got me thinking that we could do better.”
With the very personal experience of his wife’s amniocentesis at the forefront of his inspiration, Peters focused on fetal-maternal relationships and worked to find the answer of how to detect Down Syndrome in maternal plasma—“the dim star in the bright sky”. The field had struggled for years to move past this halt because there were no tools equipped to answer the questions that arose in the research.
The standstill of NIPT research after Lo’s discovery is attributed in part to most scientists only using the narrow scope of targeted genomic sequencing to solve what Peters refers to as “the impossible problem.”
From the late 1990s to the end of the 2000s, the NIPT field was in a transitionary phase; eventually moving from a lens of reductionism to an approach of massively parallel sequencing to look more broadly across the genome. So, in 2006, when Peters moved back to Pittsburgh from Liverpool to work at Magee-Womens Research Institute, he brought with him a fresh perspective to solve a problem that had personally touched his life.
He was among the first generation of geneticists to approach this issue with massively parallel genomic sequencing because he had not worked in the prenatal field previously and was coming from a completely different side of genomics.
“So that was a real wake up call. [My wife] had the test anyway, but that’s kind of what got me thinking that we could do better.”
During his research, Peters worked closely with statistician Dr. Tianjiao Chu—who later became a co-founder and Chief Analytical Officer of SignatureDx. In 2009, Chu was able to create the tools Peters needed to find the “dim star in the bright sky”. These tools came in the form of a proprietary analytics model that allowed Peters to search for the maternally-inherited fetal DNA in the sample mixture. Through their collaboration and dedication, the team was able to identify Down Syndrome and even applied the technology to identify other fetal aneuploidies—also described as chromosomal abnormalities.3
Peters’ story doesn’t stop here. After implementing this advancement into their lab, Peters and his team began exploring ways to take noninvasive technology a step further for prenatal health by identifying pregnancy-related complications for the mother as well as the baby before the onset of any symptoms. Look out for Part 2 of the “Rooted in Research” blog series to continue the story of Dave Peters and SignatureDx and learn just how far our research can reach.
During his research, Peters worked closely with statistician Dr. Tianjiao Chu—who later became a co-founder and Chief Analytical Officer of SignatureDx. In 2009, Chu was able to create the tools Peters needed to find the “dim star in the bright sky”. These tools came in the form of a proprietary analytics model that allowed Peters to search for the maternally-inherited fetal DNA in the sample mixture. Through their collaboration and dedication, the team was able to identify Down Syndrome and even applied the technology to identify other fetal aneuploidies—also described as chromosomal abnormalities. 3
Peters’ story doesn’t stop here. After implementing this advancement into their lab, Peters and his team began exploring ways to take noninvasive technology a step further for prenatal health by identifying pregnancy-related complications for the mother as well as the baby before the onset of any symptoms. Look out for Part 2 of the “Rooted in Research” blog series to continue the story of Dave Peters and SignatureDx and learn just how far our research can reach.
References
- Abboud, Alexis, "Dennis Lo (1963- )". Embryo Project Encyclopedia (2014-11-04). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/8233.
- Lo, Y. M., Corbetta, N., Chamberlain, P. F., Rai, V., Sargent, I. L., Redman, C. W., & Wainscoat, J. S. (1997). Presence of fetal DNA in maternal plasma and serum. Lancet (London, England), 350(9076), 485–487. https://doi.org/10.1016/S0140-6736(97)02174-0
- Magee-Womens Research Institute & Foundation. (n.d.). Dr. David Peters: Developing prenatal tests that are safer, less invasive: Magee-Womens Research Institute & Foundation. Magee. Retrieved from https://mageewomens.org/researcher-stories/dr-david-peters-1
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