Should we sequence the full genome of babies?

The diagnosis was a puzzle to Jennifer Garcia and her husband John. The genetic defect that causes SCID was never discovered in their families and, in fact, they had never even heard of it. And more than that, weren't the scans Cameron underwent right after his birth supposed to detect the defect? Garcia began to investigate the issue, and what she discovered amazed her. It was possible to detect severe combined immunodeficiency in the screening tests conducted in newborns, at the same time dried blood sample taken at the Texas State Department of Health Services for early diagnosis of the other diseases on the list. However, at that time, the list of diseases tested for early diagnosis that was accepted in Texas and most other states in the US did not include SCID. When the genetic defect SCID is detected at an early stage, before a serious disease attacks the baby, it is usually possible to treat the condition, which could be fatal without treatment, with a bone marrow transplant, which allows the defective immune system to be replaced with a healthy one. More than 90% of the babies who undergo a bone marrow transplant in the first three and a half months of their lives recover. Cameron was already eight months old when the defect was diagnosed, terminally ill, and fighting for his life.

It is easy to understand why Cameron's mother emphasizes the disadvantages of avoiding scanning tests for early diagnosis of a disease that can be detected with the technological means at our disposal. Cameron was born just one month after the SCID was added to the nationwide list of recommended newborn screening tests. But it was more than two years before Texas hospitals began screening every newborn for SCID. It was entirely too late for Cameron, he died on March 30, 2011.

Since that night when Garcia left the hospital without a vault in her arms, she devoted her time to public activity in this area and the struggle she waged produced results: she managed to convince the health authorities in Texas to add the SCID to the list of screening tests for the early diagnosis of diseases in newborns. Knowing that all babies born in Texas hospitals are now screened for SCID eases Garcia's heartache, if only a little. "I wanted his short life to have meaning not only for our family ... I wanted people to know that this little baby changed things and opened the eyes of many people ...," Garcia said in a video where she talked about the importance of screening for SCID. "If we had known that Cameron had SCID, if only we could have discovered it at an earlier stage, before he was exposed to infection of any diseases, there is no doubt, and I say this with absolute certainty, that Cameron would be here with us today."

And what if we didn't have to go through the lengthy process of adding new diseases, one by one, to the list of defects diagnosed in newborn screening tests? What would happen if it were possible to detect many of the diseases diagnosed as part of newborn screening tests and many others in one single test?

The question is not hypothetical. In a groundbreaking study that is currently being conducted at four university medical centers in the US under the auspices of the US National Institutes of Health (NIHs), and is expected to bring about a revolution in everything we know about human health, starting from the first moments of life, the medical, behavioral, economic and ethical consequences of determining the sequence of the "A (Paving gardens) to map the complete genetic code of babies. The question is: is it really advisable to perform this on every newborn?

a difficult issue

The gene sequencing procedure has clear advantages. Through it, it will be possible to diagnose many more children who are at risk and enable early preventive treatment for those whose lives depend on early diagnosis, as was the life of Cameron Garcia. But inevitably, such a procedure will confront some of the parents with findings regarding their children's health problems that have not yet been answered and regarding incorrect genetic variants, called Variants, the meaning and effect of which are not necessarily clear - these may be variants pointing to some specific problem or DNA sequences from which it is impossible to derive unequivocal information regarding future problems.

In view of the findings that will be passed on to the parents, many of them may discover that the information they received regarding thegenome of their children is still largely unknown. Michelle Huckabee Lewis, a skilled pediatrician and lawyer engaged in policy research in the field of genetics at the Berman Institute forBioethics at Johns Hopkins University, fears that this could be problematic. "The teams specializing in genetics and the secondary areas of specialization will not be able to withstand the load in the face of the increasing demand due to a lack of manpower," she wrote inArticle which was published in the journal JAMA Pediatrics. "Furthermore, since the demand is expected to exceed the supply, more than once, specifically children who are not at immediate risk, those whose condition may become apparent only at a later stage in life, may win the line to a specialist doctor at the expense of those whose condition requires more urgent treatment."

What is the best way for doctors to take advantage of the abundance of data provided by DNA sequencing to provide optimal care to the youngest and most vulnerable patients?

In any case, it seems that this is the direction in which the health services are headed. "We are moving towards a world where the technology will be perfected and the costs will be reduced so much that the determination of the DNA sequence will become a very tempting procedure and suitable for application not only in the sick population but also in the healthy population," says the geneticist Robert C. Green. Green co-leads The BabySeq project, a newborn screening study conducted in part at Harvard Medical School's Brigham and Women's Hospital and Boston Children's Hospital, one of four federally funded research sites.

As part of the BabySeq project, the question of how parents and doctors can use genomic information to improve children's health care is examined. Green and his partner to lead the project, Alan Beggs, conducting a study in a group of 240 sick newborns and 240 healthy newborns. They determine the DNA sequence of half of the randomly selected newborns in each group to assess if there is a difference in the parents' reaction to the findings in each of the groups. Do parents of sick babies think that the additional information obtained in this way is useful, while parents of babies who are considered healthy find it difficult to deal with it? Would parents of children in any group prefer to receive the relatively limited information provided by conventional newborn screening tests? What is the best way for doctors to take advantage of the wealth of data provided by genetic sequencing to provide optimal care for the youngest and most vulnerable patients? We want to answer some questions, says Green: "Does this cause concerns and fears? Is there any benefit? Could this leave people completely confused or rather the opposite?"

In a preliminary study, Green and his colleagues conducted a survey among parents immediately after the birth of their children and asked them if they were interested in having the newborn's DNA sequence determined. Three months later they returned and asked the parents the same question after explaining to them in more detail what types of data might be obtained in this procedure about their children - for example, a risk of getting cancer or a tendency to Parkinson's disease.

The percentage of parents who were interested in determining the sequence also at this stage remained almost the same. "This shows that there is a huge hunger for information among parents, even when it comes to healthy babies," says Green. "And it will be difficult to go against this trend."

However, it seems that determining the DNA sequence of a baby and "passing the findings as they are to the family, without judgment," as Green describes it, "could be an extremely dangerous thing." The combination of worried parents, on the one hand, and doctors trying to interpret findings that are not unambiguous, on the other hand, seems particularly sensitive. "People tend to accept relatively easily findings concerning themselves, compared to findings concerning their children," says Green. "The main question in this context is the question of damage. Depending on who you talk to, people have different theories about the expected harm, related to worry, distress and misinterpretation of the information. And all these questions become more valid when it comes to babies, whose choice is not in their hands. This is the first opportunity to examine possible damage."

Building a model of the future

When I visited Boston in the spring of 2015, the project was in its infancy, preparing to "recruit" the first baby. I expected to meet one or maybe two researchers, but to my surprise, I was greeted by half a dozen staff members - experts inNeonatology, geneticists, genetics counselors - who gathered in a hospital conference room. They say it takes a whole village to raise one child. It seems that this is also the case in order to reach an agreement on the details of determining the DNA sequence of the child. My hosts explained to me that as part of the BabySeq project (by the end of 2016, about 100 families had registered to participate) the findings that would be given to the parents would be limited togenetic changes related to diseases that appear in childhood. The parents of the babies and their pediatricians will also participate in the study, with the aim of evaluating the medical consequences and the impact on the attachment between parents and their children and to examine how useful the data obtained is and how they are integrated into the child's medical care. And in other words, does the flow of information obtained from determining the genome sequence translate into better medical care for the child? Does the benefit justify the costs, both financial and emotional?

"Imagine a world where the DNA sequence of each baby is easily and quickly determined. How will this information be used by doctors to facilitate the treatment of babies, to diagnose their condition, to issue prescriptions for medicines for them?" Green asks. "We are trying to build a model of such a world, at a time when determining the DNA sequence is not a simple or cheap procedure and when doctors are not yet skilled in dealing with the information that this procedure provides. We are trying to build a model of the future."

But if Green is right in his predictions, it is not an ethereal or overly distant future. "Within five years, I believe, the determination of the DNA sequence will be conducted free of charge for anyone who wants it," says Green with confidence.

The article is adapted from the book The Gene Machine: How Genetic Technologies Are Changing the Way We Have Kids—And the Kids We Have (in free translation: The Gene Machine: How genetic technologies are changing the way we bring children into the world and our children), by Bonnie Rochman, published in agreement with Scientific American/Farrer, Strauss and Girou Ltd. (USA) and Renmin University Press (China). Copyright © 2017 by Bonnie Rochman. All rights reserved.