For half a century we’ve been screening newborns for genetic diseases. Now we’re beginning to study their genes.
You may never have heard of newborn screening for genetic disease, even though it now covers nearly all of the 4 million babies born every year in the United States. The US Centers for Disease Control and Prevention points to newborn screening as one of the ten great achievements of public health.
All the states and the District of Columbia screen newborns for at least a couple dozen conditions, most of them genetic, where medical care begun soon after birth can make an enormous difference. Many of these diseases are rare, like phenylketonuria (PKU), a metabolic disorder that occurs in one of 25,000 births. PKU leads inevitably to severe mental retardation, but that retardation that can be prevented with a special diet. Other disorders in the state newborn screening programs are far more frequent. Sickle-cell disease, which occurs once in 400 births among African-Americans, is the most common genetic disorder in the US.
Up till now, newborn screening has not been done by looking directly at an infant’s genes. Instead researchers check a tiny drop of blood taken from a baby’s heel for certain biochemical markers. These markers indirectly reveal the presence of abnormalities that can be treated effectively early in life.
That indirect approach could change, depending on the results of four new pilot projects funded by the US National Institutes of Health. The projects are studying whether extending newborn screening to studying the genes themselves makes medical—and ethical—sense.
Obtaining entire genomes may soon make economic sense. For years a goal of government-funded research has been to come up with ways of sequencing a genome for $1000. We’re not there yet; a whole genome costs between $3000 and $5000 at the moment, with the price steadily and quickly dropping. But $1000 is now the price for sequencing just the exome, the genes that code for proteins. The exome comprises only around 1 percent of human DNA, but includes most working genes.
Two of the new projects will study exomes. There is already evidence that whole exome sequencing can be useful for discovering the cause of disorders that have puzzled diagnosticians. A report in a recent New England Journal of Medicine showed that, out of 250 children that physicians selected for genetic testing because they suffered from a mystery ailment, 25 percent turned out to have a genetic disorder.
Each of the pilot projects will study a (relatively) small group of newborns, doing genome sequencing and analysis and research on patient care. The studies will also focus on the ELSI research that is now a fixture of studies of human genetics, in this case the ethical, legal, and social implications of using genomic information in the newborn period. The projects will be based at academic centers in San Francisco, Kansas City, Boston, and Chapel Hill, NC.
Ethical issues in newborn screening
I’ve been writing about newborn screening for many years. The technology for doing tests marches on, diseases get added to the screening testing, but one thing that does not change is the ethical issues. We have always wrestled with questions about whether and how to keep genetic information private, about what to tell parents when test results are ambiguous, about how to ensure that access to testing—and to follow-up care when it’s needed—are available to all.
Among the ELSI questions that the new genome projects will explore: How much information should parents be given about their baby’s genome? Does it make any sense at all to tell parents that their newborn possesses a gene that increases the risk of developing breast cancer or Alzheimer’s disease much later in life? Or even that their beautiful new baby is likely to display developmental problems a few months or years down the road?
Is that too much information? Will it affect parental attitudes toward their newborn? There are already data suggesting that it might. A recent Australian study reports that while parents of healthy babies are usually happy with newborn screening, parents of children with developmental disabilities would prefer to delay screening for a year or two because they believe an early diagnosis could affect their relationship with the child for the worse.
Yet putting information about future impact of a baby’s genes into a medical record could mean better health care in the future. Whether that’s true is one of the things the new genome screening studies will be trying to learn. We know very little about preventing breast cancer now, and nothing at all about preventing Alzheimer’s disease. But that may not always be so. Surely people at genetic risk for a devastating disorder should be alerted and educated when something can be done about it?
And what to do about giving that information to other family members for the sake of their own health? A newborn’s gene predisposing to breast cancer or Alzheimer’s disease came from Mom or Dad, who are much closer in age to profiting from the knowledge that they might be at risk. So are their brothers and sisters. “One of the issues in genetics is whether the child in front of you is your sole patient or whether the entire family is your patient,” says Robert C. Green, a lead investigator for the Boston project, known as BabySeq.
And what happens when newborn testing says a disorder is present when it isn’t? False positive results are inevitable. In an effort to make sure screening tests catch every case of disease, they are generally oversensitive. By design they generate a certain number of false positive results. A recent Canadian study considered parents who were initially told that their infants probably had cystic fibrosis, but who turned out, on retesting, to be OK. The parents don’t seem to have suffered long-term ill effects even though they were miserable temporarily while waiting for results of the second test.
The future of genetic screening of newborns
Some media reports on the pilot newborn genome studies implied that it is only a matter of time until whole-genome sequencing is a routine part of newborn screening.
Not so fast. For one thing, the technology has to get better and also better able to handle high volumes of testing. Perhaps more important, it also has to get a whole lot cheaper. Extended to each of the 4 million babies born annually in the US, even the (relatively) cheap $1000 exome sequencing available today would amount to $4 billion, not counting the cost of analysis.
Obviously that’s not going to happen. Not to mention that we don’t know how useful obtaining a genome at birth would be. Would it change medical practice? Would it change health behavior? Would it prevent disease, or at least delay it? If newborn genome sequencing improved general health significantly, even $4 billion a year could be cheap at the price. The pilot studies might glean some preliminary answers to those questions. But not for years.
Medical ethicist Jeff Botkin of the University of Utah told a session at the recent meeting of the American Society of Human Genetics that newborn genome sequencing makes enormous sense as a research tool. But he is doubtful about extending that to the whole country any time soon, or maybe ever. He said, “I think sequencing millions of asymptomatic babies is probably not the best use of our resources.”
Tabitha M. Powledge is a long-time journalist and editor specializing in science and medicine. She writes “On Science Blogs” for the PLOS Blog Network; new posts appear on Fridays.
