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Transcript: NICHD Research Perspectives—September 4, 2013

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Announcer: From the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, welcome to another installment of NICHD Research Perspectives. This month’s podcast features an excerpt to the special media briefing about the launch of a new research program, on genomic sequencing and newborn healthcare. NICHD developed this program with the National Human Genome Research Institute. In this excerpt, representatives from both institutes discuss the program’s origins and goals.

Larry Thompson: Good morning everyone, and welcome to what I know will be a very interesting discussion this morning.  My name is Larry Thompson, I am the Communications Director at the National Human Genome Research Institute and I'll do the air traffic control for today's briefing.  Today's briefing focuses on the first grants awarded under the Genomic Sequencing and Newborn Screening Disorders research program co-sponsored by these two institutes - NICHD and NHGRI. Typically, we do not hold a telebriefing about grants announcements. But in this case, we felt a conversation was appropriate because some of the media, and some in the media and elsewhere, already have been asking questions about genomic sequencing for newborns and its implications. The institutes’ leadership felt it was appropriate at this time to provide some context about the research program and discuss what we hope to learn from it. We will start with opening remarks from the directors of the sponsoring institutes, Dr. Alan Guttmacher from NICHD and Dr. Eric Green from NHGRI.  We will also hear from Dr. Tiina Urv, Program Director of NICHD’s Intellectual and Developmental Disabilities Branch, and Dr. Anastasia Wise, a Program Director in NHGRI’s Division of Genomic  Medicine. They oversee the grants for their respective institutes and will discuss a bit about the grantees’ research goals.

Now I'd like to ask Dr. Guttmacher to make his opening statement. Dr. Guttmacher.

Dr. Alan Guttmacher: Thank you, Larry -- and hello to everyone on the line. As you've heard from Larry, my name is Alan Guttmacher, and I am the director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development here at the NIH. Hospitals take a drop of blood from the heel of just about every one of the 4 million babies born in the United States each year. That blood drop is then tested for pre-symptomatic evidence of a number of diseases, almost all of them rare genetic disorders. The strategy is compelling: early identification in the newborn period of certain metabolic or endocrine disorders allows parents and doctors to offer immediate treatment to interventions that can protect the baby from disability and even premature death.

The classic example for newborn screening is a metabolic disorder called phenylketonuria, or PKU.  In PKU, the baby is born with a pair of mutations that prevents him or her from metabolizing the amino acid phenylalanine.  Consequently, phenylalanine – which is in high amounts in virtually’everyone’s diet – builds up to harmful levels in these babies and can cause neurologic damage, intellectual disability and other serious health problems. By knowing the baby has the disease early, parents can modify the baby’s diet to remove phenylalanine and prevent damage; however if one waits until symptoms appear, the damage is irreversible, so prevention is the only truly effective solution.

Newborn screening is one of the most successful public health programs in our country. We have been screening newborns in the U.S. since the 1960s, and studies show that newborn screening prevents more than 12,500 debilitating disorders in children in our country every year, saving millions in lifelong medical costs as well. Newborn screening, however, does have limitations. Because it is states that administer and regulate newborn screening, laboratories test for different things in different states. Currently, recommendations are that states screen for 31 disorders—these are all well-defined disorders for which we have good screening and follow-up diagnostic tests, and effective therapies. But 31 is only a small fraction of the many inherited disorders that exist. In the future, it may be possible to screen for more disorders and therefore benefit more children. 

I happen to be a pediatrician and medical geneticist by training and was the founding medical director of the state of Vermont’s newborn screening program. I also used to be the deputy director of the National Human Genome Research Institute, and so I've had the privilege of watching the evolution of genome sequencing technology as well as newborn screening over many years. In discussions with my colleague Eric Green, and others, it seemed a natural collaboration for our two institutes to begin thinking together about a more comprehensive approach to newborn screening, through applications of genome sequencing. We can see the potential value of looking at an infant’s genome to examine all of the genes – or perhaps a particularly informative subset of them-- at the beginning of life, rather than one at a time, or looking solely at biomarkers, which are often only surrogates for genetic mutations.

When we began talking about a possible collaboration, it quickly became clear that we needed to understand many things before genome sequencing could be considered truly useful tool for newborn screening. For example:

  • We’d like to better understand even the disorders that we already screen for in newborn screening programs, and find ways to improve therapies for them.
  • We’d like to see if genomic sequencing can shed light on other disorders that we don’t screen for currently.
  • And we’d like to see how genomic data might inform clinical care for newborns more generally.

We also recognize that there are many ethical, social and legal questions that the use of genome sequencing technology on newborns may raise.  For example:

  • How do we protect the baby’s privacy and what are the appropriate consent processes?
  • Where will the baby’s genome data be stored and who will have access to it?
  • What conditions should be included in the tests and what criteria will be used to determine a positive result?  What should be the follow up for positive sequencing screening results?
  • What should doctors tell parents about what was found?
  • How much will all this cost? What will be its overall impact on health care and other spending?

These are obviously complicated questions and we, as a society, need to consider them thoughtfully – before we hope implementing any sort of newborn sequencing program on a wide scale. That is why I am so pleased that NICHD and NHGRI have partnered to bring the respective expertise of our two institutes and of our research and patient communities to this problem and to fund carefully selected studies to begin finding answers to these questions. Back to you Larry.

Mr. Thompson: Thank you very much Dr. Guttmacher. I would now like to ask NHGRI’s director, Dr. Green, to make his opening remarks.  Dr. Green.

Dr. Eric Green: Thank you, Larry, and good morning everyone. I want to start by echoing Alan’s satisfaction with this collaboration between our two institutes. In these tight budgetary times, it clearly makes sense for us to look for opportunities to combine our resources in pursuing major research projects aiming to answer important public health questions.

Aswe celebrated the 10th anniversary of the completion of the Human Genome Project, NHGRI finds itself moving more and more into research that involves applying genomics to a wide range of diseases and clinical areas for which other NIH institutes have subject-matter expertise. For example, our collaboration with the National Cancer Institute in overseeing The Cancer Genome Atlas project is an excellent example of such a strategic partnership.

Our collaboration with NICHD that we are discussing today falls into the same category. NHGRI brings genome-technology expertise and NICHD brings deep expertise in newborn genetic screening. The public – and particularly our children – will certainly benefit from our working together. As many of you know, genome-sequencing technologies have advanced dramatically over the past decade to the point where the prospect of incorporating complete information about an individual’s genome sequence into his or her medical record is under serious discussion and careful study. At the same time, the costs of collecting genome-sequence data are falling below the costs of conducting some individual genetic tests. It thus might soon make more sense – and might be more cost effective -- to conduct a comprehensive analysis of patients’ entire genome than to perform one-off tests of individual genes. And this situation might be very relevant at the newborn stage. Recognizing these trends, NHGRI and NICHD held a workshop almost two years ago to identify elements of a research agenda that could inform the possible application of new genomic sequencing technologies to newborn screening and child health. The fruits of that workshop are the awards that we announce today, which focus on a laudable goal: improving the healthcare of newborns.

I do want to note something about the scale of this research program. Our two institutes expect to commit roughly $25 million dollars over five years to the proposed projects, though we can really only commit to one year at a time, pending congressional appropriations. Our ability to identify funds for the project stem from our belief that there are a number of important and challenging questions to answer, such as:

  • Is genomic sequencing of newborns an appropriate application of genome-sequencing technologies and, if it is, what are the situations in which it works best?
  • What is the best way to deliver or present genome-sequence information to parents and clinicians?
  • Is complete genome-sequence information too much information to handle for either parents or clinicians?
  • What types of information do they want to receive?

Now fortunately, we already know a great deal about newborn genetic screening and how the information can be used, as Dr. Guttmacher has described, so we are optimistic that we will be able to answer many of these research questions. Another issue is understanding cost. The proposed research aims to inform a screening program, which means it will be associated with many negative results. Current newborn genetic screening costs about $100 per patient. Whole-genome sequencing, on the other hand, now costs about $5,000 but whole-exome sequencing now is down to about $1,000 or less. Will the additional information from more complete genome sequencing be worth the cost? We are continuing to support research to advance DNA sequencing technologies to bring down the costs further and also to reduce the time involved and to improve accuracy, but it may still be a bit too expensive in the short run for use in a population-wide screening program. Whereas traditional newborn screening only tests for a couple of dozen genetic diseases, genome sequencing has the potential to test for many of the nearly 7,000 - 8,000 inheritable diseases, so it could be tremendously powerful, perhaps saving many millions of dollars in healthcare costs.  So, it may be worth it. That’s something we hope to examine. The program we are talking about today, however, is not just looking at genomic sequencing as a replacement of, or an addition to, the existing newborn genetic screening program. Some of the projects are examining conditions for which doctors do not currently screen.

Because of sensitivities inherent in any research involving children, we also developed this research program in a careful and measured way. For example, every project we are funding has a component focused on the ethical, legal, and social aspects of using genomic sequencing in newborn care. NHGRI has a long history and deep expertise in studying such issues. Clinical studies under this program will also have a data safety monitoring board that is responsible for protecting patients. The monitors will review protocols, provide advice, and make sure that any adverse events are quickly and appropriately addressed. The individual projects funded by these grants will also train clinicians to interpret the genomic sequencing reports and ensure that genetic counselors are available. Because there are concerns about sharing newborns’ genome-sequence data, our institutes are not requiring applicants to deposit these data into databases like dbGaP, which archives study results related to the interaction of genotypes and phenotypes.

These pilot projects are focused on improving the care of the infants in this program – and that primarily means inherited diseases that tend to be rare but that need immediate intervention to prevent childhood disease. So for example, these studies are not looking at an infant’s risk of developing Alzheimer’s disease in their 80s. If researchers encounter incidental findings, they will only analyze the genes related to the symptoms that the children may present. The program is also not looking at all economic questions, such as whether insurers will cover these costs in the future. That falls outside this program. There has been considerable and important discussion at NIH, between our two institutes, and also in the public about doing genomic sequencing of newborns. That is an important discussion to foster and to advance, and we believe that the pilot studies that we are announcing today will be an important contribution to that discussion. I am happy about our partnership with NICHD, and excited to see these studies get underway. Thank you for your attention, I'll send this back to Larry.

Mr Thompson: Thank you Dr. Green. Four research groups will receive $5 million a year, $5 million a year hopefully for the next five years under this program. I would now like to ask the program directors from the two institutes to describe the bigger scientific questions that these four groups will examine and how they will go about it. First, Dr. Tiina Urv, NICHD’s program director on this collaboration will describe the projects led by Dr. Robert Nussbaum at the University of California at San Francisco and Dr. Cynthia Powell at the University of North Carolina at Chapel Hill, and then I will ask NHGRI’s program director Anastasia Wise to describe the work by Dr. Robert Green’s group at the Brigham and Women’s Hospital in Boston, and Dr. Steven Kingsmore’s group at Children’s Mercy Hospital in Kansas City, Missouri. Dr. Urv.

Dr. Tiina Urv: Thank you Larry and good morning to everyone. Each of the four research projects that we will describe for you bring together teams of researchers with different types of expertise. These teams will work together to answer the questions that Dr. Green just outlined. Each of the research projects consists of three parts: Genomic sequencing and analysis; research related to patient care; and the ethical, legal and social implications of using genomic information in the newborn period. The projects that will be funded, in no specific order are: “Sequencing of the Newborn Spot DNA to Improve and Expand Newborn Screening.” The Principal Investigator of this project is Robert Nussbaum, M.D., of the University of California, San Francisco. Dr. Nussbaum and his team will explore the potential of exome sequencing as a method of newborn screening. Exome sequencing is a strategy used to selectively sequence exons, the short stretches of DNA within our genomes that code for proteins. They will compare the results from current newborn screening methods to those from exome sequencing for metabolic and immunologic disorders.  Dr. Nussbaum’s team will also use the results from exome sequencing to try to predict which children with specific metabolic disorders, fatty acid oxidation disorders and severe combined immune deficiency are at the greatest risk of becoming severely ill.

This project also explores genetic variations that predict responses to drugs used in childhood such as codeine and some seizure medications. At the same time, the research team also intends to develop a participant protection framework for conducting genomic sequencing during infancy and will explore legal issues related to using genomic analysis in newborn screening programs. Together, these studies have the potential to provide public health benefit for newborns and research-based information for policy makers. The next study is “NC NEXUS, North Carolina newborn Exome Sequencing and newborn Screening Disorders,” The Principal Investigators for this project are Drs. Cynthia Powell and Jonathan Berg of the University of North Carolina at Chapel Hill.

There are many challenges that must be met in order to implement genomic sequencing technology in such a diverse newborn population. Drs. Powell and Berg’s research team will explore the usefulness of exome sequencing as a diagnostic tool to enrich the utility of current newborn screening. They will sequence the exomes of healthy infants and infants with known conditions, such as PKU, cystic fibrosis and other disorders involving metabolism along with other conditions where children could potentially benefit from being identified early. This group will also develop strategies to guide doctors, laboratories, and families in decisions regarding findings in ways that will respect the child and protect his or her future rights while also respecting the rights of the parents. The research will attempt to develop a tool to help doctors and parents understand what the results of exome sequencing mean and examine the extra challenges that the doctors face as this new technology is used. This group also places a special emphasis on including multicultural families. Thank you. 

Mr. Thompson: Thank you Dr. Urv. Dr. Wise.

Dr. Anastasia Wise:  Thanks Larry. Dr. Robert Green at Brigham and Woman’s Hospital and Dr. Alan Beggs of Boston Children’s Hospital aim to create and safely test new methods for using the information obtained from genomic sequencing in the care of both sick and healthy newborns. They will test a new approach to newborn screening, in which genomic data is available as a resource for parents and doctors throughout infancy and childhood to inform infants’ health care.

In project 1, they will perform genomic sequencing in a laboratory that meets the legally required testing standards called CLEA, and develop electronic reports to return clinically important genomic sequencing results to doctors in a manner that is clear and easy to understand. In project 2, they will explore how doctors act on these reports in both healthy and sick newborns as compared to current newborn screening results and if it influences their clinical care. In project 3, they will examine the impact on parents of receiving these genomic sequencing results as compared to receiving current newborn screening results in once again both healthy and sick newborns.  They will look at the results of stress, usefulness of the results, and behavioral changes. These studies will inform the greater community on the reliability, effective, and scalable approaches to interpret genomic sequencing results in the context of newborn screening and the care of both healthy and sick newborns. They will also investigate the benefits and risks of newborn genomic sequencing, particularly concerns about parental and doctor confusion and anxiety, before newborn genomic sequencing is introduced into clinical care.

Dr. Steven Kingsmore’s group at Children’s Mercy Hospital aims to examine whether incorporating rapid genomic sequencing results into the care of sick newborns improves their diagnoses or clinical management.  Many newborns require care in a neonatal intensive care unit, or NIC-U, and this group of sick newborns has a high rate of disability and death. Given the severity of illness, these newborns may have the most to gain from a fast genetic diagnosis through the use of genomic sequencing.

In project 1, the researchers will work to reduce the turnaround time for conducting genomic sequencing and receiving the results, while also maintaining the ability of their method to make the correct diagnosis.

In project 2, they will explore if their method increases the number of diagnoses, decreases the time it takes to reach a diagnosis, or changes the clinical care of these sick newborns. 

In project 3, they will study what doctors and parents think the benefits and risks are of genomic sequencing and if these perceptions change after receiving the newborn’s genomic sequencing results. Having rapid genomic sequencing results available may allow for earlier treatment of the sick newborns in this study and will provide genomic results and genetic counseling for their families. The data generated in these studies may also potentially benefit future newborns through the identification of genes associated with newborn diseases and the development of improved diagnostic tests. Thanks.

Mr. Thompson: Thank you very much Dr. Wise. I would like to thank my colleagues here for their willingness to speak about this important project, and thank the members of the media for their interest. And I'd like to thank everyone for your participation and take care, thank you very much.

Announcer: This has been a special NICHD Research Perspectives. Listeners interested in hearing the full media briefing on genomic sequencing and newborn healthcare—including the question and answer segment with reporters—may access the recording at NHGRI’s website, To listen to previous installments of NICHD Research Perspectives, visit If you have any questions or comments, please email


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Last Reviewed: 09/25/2013
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