OVER THE YEARS, doctors have described more than 7,000 rare diseases, generally defined as those that affect fewer than one in 2,000 people. So while individually rare, such diseases are collectively a serious problem, a long tail of needs that is difficult to treat because patients are few and their symptoms are often detected too late. Three-quarters of rare diseases are genetic, and Global Genes, an American advocacy group, estimates that 400 million people worldwide are affected by them. For the medicine to work best, people with them should be noticed earlier, preferably in the first days of their lives.
To that end, doctors in many places want to sequence and examine the entire genomes of babies at birth. In the United States, there are projects to do just that at Boston Children’s Hospital, Columbia University, and Rady Children’s Hospital in San Diego. A pioneering group at Harvard, known as BabySeq, recently received money to expand their work on a small scale to include 1,000 babies. In Europe, a five-year project called Screen4Care is starting. And efforts are also underway in Australia, China and Qatar. But the project to follow is in Great Britain. There, a state-owned company called Genomics England, originally set up to run a study called the 100,000 Genomes Project, which investigated genetic diseases and cancer in adults, will soon start a pilot project aimed at sequencing the genomes of 200,000 babies. That could presage a national program.
Screening for genetic diseases in babies is not a new idea. In North America, Europe and the Middle East, in particular, newborns are often screened at birth for a handful of common inherited diseases, including sickle cell anemia, thalassemia and cystic fibrosis. But a whole genome sequence offers the possibility of detecting thousands of disorders instead of the few currently sought.
Early diagnosis means earlier treatment. This, in turn, means that children’s lives will be improved and even saved. But the power of the technology also means it’s possible, in theory, to detect conditions that would occur later in life, or even help parents avoid having other children with the same genetic mutation.
How many risk-associated variants it is appropriate to detect is an open question. BabySeq, which was the first project of its kind, tested about 1,000. It found that 11% of the 159 babies it examined harbored at least one variant associated with a childhood-onset disorder.
While techno-utopians may think it’s a good idea to try everything, parents of newborns are more cautious. On May 4, at a meeting in London by Genomics England, Rick Scott, the organization’s chief medical officer, said that discussions with parents and doctors had led his team to conclude that people want any genomic screening program for newborns. born to look for a more limited set of conditions than BabySeq looks for. The most compelling evidence was for variants associated with a high probability of childhood disease and that would benefit from early treatment.
Therefore, the set of variants that Genomics England will look for is being decided “with caution”, says Dr Scott. At the moment, the proposed list has several hundred items. If it is implemented in Toto, this would result in approximately one in 200 babies receiving a diagnosis of a rare genetic disorder. That list is likely to grow as understanding improves and new treatments arrive.
This public consultation has shown that some parents want to know as much as possible about their child, while others definitely don’t. One particular finding, according to David Bick, a clinical geneticist who advises Genomics England, is that parents want certainty. They feel there is no point in being told that a child is “fairly likely” to have a condition. Rather, they want a fairly clear “yes” or “no.”
Many also do not want to know about the adult diseases that their children may one day suffer. This means refusing tests that might indicate a newborn’s risk later in life for cancer, diabetes, or Alzheimer’s disease. That information would bring with it the burden of deciding what to tell your child and when. Rather, these parents feel that it should be up to the children themselves, if they so choose, to seek out such information when they are older, which would be easy if their genomes were already on file.
However, there are still some puzzles. For example, Pompe disease is a disorder in which a carbohydrate called glycogen builds up in the body’s cells. The infantile form of this disease must be treated immediately. The adult-onset form can be left until people who have it are 30 years old. Current genetic testing cannot distinguish between these forms. The cost of timely treatment for the young, therefore, is that some parents must know that their offspring will suffer eventually, though not immediately.
Tay-Sachs disease, a deadly childhood disease, poses another dilemma. Some parents don’t want to know about it, because it would ruin their early years experience with their child. Others feel that knowledge is power, and they also want to know.
One of the most difficult questions of all concerns Duchenne muscular dystrophy, a degenerative disease that begins in childhood. Screening for this would find it in six out of every 100,000 children screened. But only a small number of these have forms of the disease that are currently treatable, and the necessary drugs are not widely available. However, learning that one’s child has this disease could also allow children to join trials of new drugs.
Over the next year, Genomics England, together with doctors, patients and the general public, will grapple with such questions, armed with a set of principles (which are subject to discussion) about what tests should be done. These principles include the idea that screening should lead to better outcomes in those to whom it is applied; that this should not involve many invasive follow-up tests; and that there is strong evidence that the genetic variant being tested does cause the condition in question.
And there is another thing. This is the tough question of how to ensure data stays safe for life. Informed consent for all the various uses that could be made of such data is central to the UK plan. Other places may not be as scrupulous. Also, things change. The temptation to open genetic databases for police investigations could prove irresistible. Insurance companies would surely be happy to snoop too, if they were allowed to do so.
More importantly, these data are a veritable Aladdin’s cave for medical researchers, a cave to which only some parents will be willing to add their children’s sequences. (Informed consent means that the data should not be used in this way unless the parents have explicitly agreed.)
Combining the fruits of future scientific advances with people’s complete DNA sequences, collected at birth, could yield huge medical benefits. But it could also be a double-edged sword. Current knowledge of how genomes work is primitive. There is also a lot of so-called dark genetic matter in them, which does things that are currently unknown. Genomes can hide secrets of, for example, possible mental illnesses or behavioral predispositions that the owner of a genome would prefer to keep private. The current rules say they should. But for those who have opened the door for doctors and scientists to review their data, the question of whether that data will remain secure for life may be a gamble.