In 2011, Elle Newnan was 37 and pregnant with her second child, a girl.
She underwent a routine genetics test, common for women old enough to be considered high-risk. It yielded some unnerving news: Her daughter had a genetic marker for Down’s syndrome.
Newnan and her partner never considered aborting the baby.
“We chose not to have any further testing because we wanted her either way,” she said.
But Newnan, whose name has been changed to protect her children, nonetheless worried about the long-term implications of the diagnosis.
“I couldn’t imagine what her life would be like when she grew up,” she said. “Would she be able to have a family? A job?”
Then Lucy was born. A healthy little girl — without Down’s.
Junk or invaluable?
With the unlocking of the genome, we’ve made amazing breakthroughs in our understanding of the human body. But as Newnan’s child and two new books demonstrate, there’s danger in that knowledge being overused and overtrusted.
There’s still much we don’t know.
Science reporter John Parrington’s “The Deeper Genome” tackles the science behind the puzzle of the human genome map. “Genomic Messages,” written by lawyer George Annas and geneticist Sherman Elias, looks at the ethical and practical effect of genomics, principally when it comes to our health and longevity.
In 2003, the Human Genome Project completed what is arguably the greatest human achievement since the moon landing: They mapped every gene of every chromosome in human DNA.
Laying out an estimated 20,000-25,000 genes, the HGP seemingly discovered something remarkable. Only a tiny percentage of our DNA seemed to actually be doing anything. Some scientists argued that as much as 98% of our DNA was “junk,” existing in our cells as a relic of our individual and collective genetic histories.
But just as the concept of junk DNA was being embraced by many in the scientific community, more than 442 researchers came together for a project called ENCODE, which stands for “encyclopedia of DNA elements.” They sought to identify every gene’s individual function in the human body.
With the 2013 release of ENCODE’s findings, a new and surprising theory emerged. It was possible that as much as 80%, perhaps more, of our “junk” DNA wasn’t junk at all. Every bit is doing something of value to make us who we are.
“ENCODE,” Parrington writes, “claimed that its findings were casting important new light on links between the genome and common diseases such as heart disease, diabetes, auto-immune conditions and mental disorders like schizophrenia.”
Unfortunately, ENCODE’s findings weren’t unanimously trusted. A particularly scathing article was published in a science magazine calling the study “absurd” and its suggested statistics “horrible.”
“A central criticism,” writes Parrington, “was that ENCODE researchers had confused [gene] activity with functionality.”
In other words, simply detecting motion in a piece of DNA didn’t necessarily mean it was doing anything important.
However, still others saw ENCODE as having turned the genome into, as Parrington writes, a “far richer, more complex and more powerful” entity.
DNA that moves
This rift between the experts is at the heart of authors Annas and Elias’ principal argument in “Genomic Messages.”
If our understanding of the human genome has scientists bickering over 98% of our DNA, why on earth are we suddenly relying on it to treat cancer, diagnose our unborn children and otherwise predict our futures?
The cost of mapping an individual genome has plummeted from 2007, when it cost $1 million for the first mapped individual genome. Today, for a mere $99, companies like the popular 23andMe offer services to their customers that include links to long-lost relatives.
But that knowledge isn’t always power.
The authors tell the story of a geneticist named Robert C. Green of Harvard Medical School, one of the first healthy people to have his genome mapped. He was found to carry a rare mutation that caused a condition called Treacher Collins syndrome.
Genetic information cannot explain everything in medicine, let alone in life.
- Annas & Elias
One look at Green and it was obvious he did not have the condition. Treacher Collins causes disfigurement due to atypical facial bone development. Green’s face was normal.
“Genes,” Annas and Elias write, “are not destiny.”
Just because we carry a gene that has been shown to cause various cancers or heart diseases doesn’t mean we’ll suffer from those defects. With that uncertainty, do we really want to know what’s genetically possible?
“As the quantity of genetic information grows, the right not to know will become as important as the right to know,” Annas and Elias write.
It seems almost inevitable that in the near future, genome mapping will be the norm, rather than the exception. With the advent of electronic health records, medical files are more likely to follow individuals from birth to death.
An electronic health record, writes the authors, “has the potential to bring a tremendous amount of ‘personalized’ information directly into the doctor-patient relationship.” With it will come plenty of information genomic medicine has speculated about, whether or not it has proven it to be true.
Parrington notes that there’s plenty about DNA we still don’t understand — like the potential for genes to move around the genome between generations.
Scientists previously assumed that when a gene was located it would stay put. Like a dot on a map, the landscape might change over the years, but for the most part, if you check Wisconsin, you will find the city of Madison.
But genes don’t seem to always conform to that assumption.
Scientist Barbara McClintock first noted the phenomenon in 1951. She announced, writes Parrington, “that portions of the genome could move about in the space of a few generations.”
It took years for McClintock’s theory to become popular among genomic scientists, and today it still has its detractors. But even with the instability of the genome as we know it, many people are continuing to choose treatments based on something fluid, not fixed.
The Jolie warning
Two years ago, actress and activist Angelina Jolie decided to have a preventative double mastectomy, as a carrier of the BRCA 1 gene, she was at high risk for breast cancer. Later, she had her ovaries removed.
It was hailed as a brave decision. But it also terrified some doctors, who worried that such a high-profile case would cause too many women to unduly follow suit.
“Genomic Messages” tells the story of one woman who had no significant history of breast cancer in her family, yet decided to be screened for the BRCA 1 gene after reading about Jolie.
When a “mutation of unknown significance” was found, the woman underwent a double mastectomy. Her mutation later proved unrelated to an increase in the occurrence of breast cancer.
Otis Brawley, the chief medical officer of the American Cancer Society, says in the book, “We have overemphasized and scared people too much.”
Following Jolie’s announcement, the FDA ordered 23andMe to stop sharing health-related DNA results with their clients. Previously, 23andMe claimed to be able to let people know their health status with regards to 254 diseases and conditions.
The FDA stopped this practice when it became concerned that false positives and patient self-diagnoses could prove fatal.
“It also seems reasonable to conclude,” Annas and Elias write, “that the FDA acted because the agency thought it was time to regulate the entire consumer genomics industry.”
Doctors agree that there is no way to remove the risk of cancer completely. The existence of the BRCA 1 or 2 gene in a person’s genome alone should never be the only piece of the discussion.
In Jolie’s case, family history was a major factor. Three members of her family had died of BRCA 1-related cancers. Doctors suggested that for her, the greatest chance of avoiding the same fate as her mother and grandmother would be for Jolie to undergo these procedures at least 10 years before the age her mother had been when she was first diagnosed, 49.
Jolie was 39 when she had her ovaries and fallopian tubes removed.
The worry is that other women will react to a genetic marker too early in life — or with no other issue, like family history, that increases the risk.
As Annas and Elias emphasize, “genetic information cannot explain everything in medicine, let alone in life. It is dangerous if tempting, to take the significance of DNA information to an extreme that suggests we can both discover our human essence and precisely predict our health future by deciphering the entirely of the information encoded in our genomes.”
Not foolproof
The stakes are even bigger for testing in the womb.
In 2013, a simple blood test became the overwhelming choice to screen for genetic conditions in the unborn. Using free-floating DNA in an expectant mother’s blood, doctors are able to easily extract genetic information without invasive procedures.
The test seems to be a valuable alternative for parents who are concerned about the future health and wellness of their unborn children. But prenatal diagnosis comes with its own set of risks.
“The amount of genomic information that can be obtained from fetuses, as well as the uncertainty of genetic findings,” Annas and Elias write, “is so great that it is often difficult for anyone to interpret their meaning.”
Of course, sometimes a serious condition can be discovered early, offering doctors the chance to treat and save a fetus while it is still in the womb. In other cases they might be able to develop a treatment plan for the baby after he or she is born. For parents, appropriate preparations can be made so that they have less to worry about when their ailing baby arrives.
Still, some people, given the weight of such a diagnosis, might consider terminating the pregnancy — even if the information was incorrect.
And then Lucy might not be here today.