CAMBRIDGE — Anne Morriss’s first step toward starting a company to test the DNA of women and their prospective sperm donors began with a question so surreal she could barely make sense of it.
A voice on the phone asked whether her baby boy, just a few days old and sleeping peacefully in the next room, was still alive.
“Can you go check and confirm and come back to the phone?” Morriss recalls the caller asking.
Only afterward would the man, phoning with results from the state’s newborn screening test, explain that her son had tested positive for a rare and potentially fatal genetic disorder that prevented him from converting certain fats into energy.
For the first few years of Alec’s life, he would need to be fed every few hours. A stomach bug could be deadly.
The news five years ago came as a shock; when Morriss and her spouse, Frances Frei, decided to start a family using a sperm donor, they had been selective. They found a reputable sperm bank. They combed through pages of data on athletics, eye color, and bone structure of the donors, and tried to divine qualities less easily quantified.
“We were looking for empathy, intelligence,” Morriss said.
Like most new parents, they were excited — and not thinking too hard about the genomic lottery they were entering.
Now Morriss has cofounded a company aimed at reducing the odds of having an unhealthy child when using a sperm donor. Named GenePeeks, it will test a woman’s DNA and the genes of potential donors to produce a personalized list that strikes out donors who may be a bad match for about 600 genetic childhood diseases. The test, costing about $2,000, will be offered starting in December to customers of a New York sperm bank.
It is unclear how common Morriss’s experience is, but diseases such as her son’s are rare for a reason. Although virtually every person probably harbors at least one flawed copy of a gene that could cause a disease, such illnesses are recessive traits, meaning they will not develop unless a child inherits two flawed copies of a gene, one from each parent. That means risk factors can lurk in perfectly healthy people’s DNA for generations — until someone happens to pick a reproductive partner with the same mutation. Even then, they would have only a one-in-four chance of having an affected child.
Technology is already being used in an attempt to lower those odds even more. Prospective parents can be tested to see if they or their partners — or sperm donors — carry risk factors for specific panels of diseases, often chosen based on their ethnicity. Sperm banks often test for the most common genetic diseases.
But in the delicate first weeks and months of Alec’s life, Morriss saw that the technological possibilities were racing far ahead of the limited genetic screening that sperm banks were doing. The DNA sequencing technology that was so much in the news for its potential to revolutionize medicine could scour millions of spots in the genome, for risks for every single known genetic disease. It offered the possibility of one day searching for risk factors for diseases that involve a complex mix of many genes, such as asthma or autism.
If she could choose a donor’s SAT scores, why not also choose one that had the smallest risk of passing on a horrible disease?
Current genetic screening “doesn’t account for this quiet scientific revolution that has made the cost of getting information from DNA so low — which has opened up the incredible possibility of managing risk for these diseases,” Morriss said.
A mutual friend introduced Morriss, a former consultant, to Lee Silver, a Princeton University biologist who had thought up a novel way to give prospective parents better guidance about potential offspring. Together they founded GenePeeks. Silver’s technique uses computer modeling to mimic what happens when people reproduce: Half of a woman’s DNA combines with half of her partner’s. Silver argues that by looking not just at the genes the parents carry, but at the possible combinations, it will be possible to identify pairings that are likely to result in illness.
The company is starting with a conservative approach; it will simply expand on the kind of screening that is already done, looking more exhaustively for recessive genetic diseases. Morriss and Silver hope to eventually test the risk for more complex diseases, depending on the state of scientific understanding.
The technology skirts some of the most thorny issues that emerge when it comes to DNA analysis and reproductive genetics. Because no one receives any genetic information back, the company will not have to wrestle with reporting disease risks back to the women or sperm donors.
But it is unclear how big the problem is, and whether the service is worth the high price. Nobody systematically tracks genetic problems in the offspring of sperm donors. But the Donor Sibling Registry, a database that has helped connect more than 10,000 children who were conceived with sperm donors, has accumulated reports of more than 100 medical conditions, many of which have genetic causes.
Dov Fox, an assistant professor at the University of San Diego School of Law who studies bioethics, said it is unclear whether genomic understanding will evolve to allow testing such as GenePeeks offers to ever be informative for common diseases caused by a blend of genetic and environmental risk factors. And he, like others, worries that one day such technology will be extended to not just avoiding disease, but selecting the babies parents want. GenePeeks will not cross that line, Morriss said.
But as technology evolves, such concerns are emerging more often. A patent granted last month to consumer genetics company 23andMe protects a method for selecting donors whose sperm and eggs might combine to create offspring with certain traits.
The characteristics that parents may be able to choose include not only freedom from genetic illness, but "traits, such as height, eye color, muscle development, personality characteristics,” a group of scientists wrote in the journal Genetics in Medicine earlier this month. The company has said in a statement that it does not plan to pursue those ideas, which were included in the five-year-old patent application at a time when the company was considering other possible strategic directions.
Still others point out that too much trust in the technology may be the biggest problem. Prospective parents may shell out money for a test, expecting certainty of good health. Dr. Dolores Lamb, a professor of molecular and cellular biology at Baylor College of Medicine and a past president of the American Society for Reproductive Medicine, said that even if doctors sequenced the entire DNA of a fetus, they could not rule out all disease.
“I guess the problem today is that even using our most advanced genetic testing . . . you still can’t guarantee you’re going to have a perfect baby,” Lamb said. “That’s what everybody wants.”
There is one other question that comes up. Alec is now 5. If the technology had existed and Morriss had used it, she would not only have prevented the disease; she would have prevented Alec. Morriss and Frei would have a different child.
“We are aware that we are strolling into a very intense debate, scientifically, ethically, morally,” Morriss said. “I think about it in simple terms, which is if we can reduce the number of kids that have to get these diseases, then we should.”
Alec is thriving in kindergarten and, with an energy shake or smoothie before bedtime, can sleep through the night without needing to be fed. But the family is still cautious because ordinary childhood sicknesses could trigger a health crisis.
“The way I think about that is the other child that would have been born with another donor, I would love just as much,” Morriss said. “But he wouldn’t have to go through the world, scared of the doorknob with the flu virus that could kill him.”