When doctors couldn’t stop her daughter’s seizures, this mom earned a PhD and found a treatment herself.
Savannah Salazar (left) and her mother, Tracy Dixon-Salazaar, who earned a PhD in neurobiology in the quest for a treatment of her daughter's seizure disorder.
Twenty-eight years ago, Tracy Dixon-Salazaar woke to the sound of her daughter, two-year-old Savannah, in the midst of a medical emergency.
“I entered [Savannah’s room] to see her tiny little body jerking about violently in her bed,” Tracy said in an interview. “I thought she was choking.” When she and her husband frantically called 911, the paramedic told them it was likely that Savannah had had a seizure—a term neither Tracy nor her husband had ever heard before.
Over the next several years, Savannah’s seizures continued and worsened. By age five Savannah was having seizures dozens of times each day, and her parents noticed significant developmental delays. Savannah was unable to use the restroom and functioned more like a toddler than a five-year-old.
Doctors were mystified: Tracy and her husband had no family history of seizures, and there was no event—such as an injury or infection—that could have caused them. Doctors were also confused as to why Savannah’s seizures were happening so frequently despite trying different seizure medications.
Doctors eventually diagnosed Savannah with Lennox-Gaustaut Syndrome, or LGS, an epilepsy disorder with no cure and a poor prognosis. People with LGS are often resistant to several kinds of anti-seizure medications, and often suffer from developmental delays and behavioral problems. People with LGS also have a higher chance of injury as well as a higher chance of sudden unexpected death (SUDEP) due to the frequent seizures. In about 70 percent of cases, LGS has an identifiable cause such as a brain injury or genetic syndrome. In about 30 percent of cases, however, the cause is unknown.
Watching her daughter struggle through repeated seizures was devastating to Tracy and the rest of the family.
“This disease, it comes into your life. It’s uninvited. It’s unannounced and it takes over every aspect of your daily life,” said Tracy in an interview with Today.com. “Plus it’s attacking the thing that is most precious to you—your kid.”
Desperate to find some answers, Tracy began combing the medical literature for information about epilepsy and LGS. She enrolled in college courses to better understand the papers she was reading.
“Ironically, I thought I needed to go to college to take English classes to understand these papers—but soon learned it wasn’t English classes I needed, It was science,” Tracy said. When she took her first college science course, Tracy says, she “fell in love with the subject.”
Tracy was now a caregiver to Savannah, who continued to have hundreds of seizures a month, as well as a full-time student, studying late into the night and while her kids were at school, using classwork as “an outlet for the pain.”
“I couldn’t help my daughter,” Tracy said. “Studying was something I could do.”
Twelve years later, Tracy had earned a PhD in neurobiology.
After her post-doctoral training, Tracy started working at a lab that explored the genetics of epilepsy. Savannah’s doctors hadn’t found a genetic cause for her seizures, so Tracy decided to sequence her genome again to check for other abnormalities—and what she found was life-changing.
Tracy discovered that Savannah had a calcium channel mutation, meaning that too much calcium was passing through Savannah’s neural pathways, leading to seizures. The information made sense to Tracy: Anti-seizure medications often leech calcium from a person’s bones. When doctors had prescribed Savannah calcium supplements in the past to counteract these effects, her seizures had gotten worse every time she took the medication. Tracy took her discovery to Savannah’s doctor, who agreed to prescribe her a calcium blocker.
The change in Savannah was almost immediate.
Within two weeks, Savannah’s seizures had decreased by 95 percent. Once on a daily seven-drug regimen, she was soon weaned to just four, and then three. Amazingly, Tracy started to notice changes in Savannah’s personality and development, too.
“She just exploded in her personality and her talking and her walking and her potty training and oh my gosh she is just so sassy,” Tracy said in an interview.
Since starting the calcium blocker eleven years ago, Savannah has continued to make enormous strides. Though still unable to read or write, Savannah enjoys puzzles and social media. She’s “obsessed” with boys, says Tracy. And while Tracy suspects she’ll never be able to live independently, she and her daughter can now share more “normal” moments—something she never anticipated at the start of Savannah’s journey with LGS. While preparing for an event, Savannah helped Tracy get ready.
“We picked out a dress and it was the first time in our lives that we did something normal as a mother and a daughter,” she said. “It was pretty cool.”
A doctor pricks the heel of a newborn for a blood test.
Hours after a baby is born, its heel is pricked with a lancet. Drops of the infant's blood are collected on a porous card, which is then mailed to a state laboratory. The dried blood spots are screened for around thirty conditions, including phenylketonuria (PKU), the metabolic disorder that kick-started this kind of newborn screening over 60 years ago. In the U.S., parents are not asked for permission to screen their child. Newborn screening programs are public health programs, and the assumption is that no good parent would refuse a screening test that could identify a serious yet treatable condition in their baby.
Learning as much as you can about your child's health might seem like a natural obligation of parenting. But it's an assumption that I think needs to be much more closely examined.
Today, with the introduction of genome sequencing into clinical medicine, some are asking whether newborn screening goes far enough. As the cost of sequencing falls, should parents take a more expansive look at their children's health, learning not just whether they have a rare but treatable childhood condition, but also whether they are at risk for untreatable conditions or for diseases that, if they occur at all, will strike only in adulthood? Should genome sequencing be a part of every newborn's care?
It's an idea that appeals to Anne Wojcicki, the founder and CEO of the direct-to-consumer genetic testing company 23andMe, who in a 2016 interview with The Guardian newspaper predicted that having newborns tested would soon be considered standard practice—"as critical as testing your cholesterol"—and a new responsibility of parenting. Wojcicki isn't the only one excited to see everyone's genes examined at birth. Francis Collins, director of the National Institutes of Health and perhaps the most prominent advocate of genomics in the United States, has written that he is "almost certain … that whole-genome sequencing will become part of new-born screening in the next few years." Whether that would happen through state-mandated screening programs, or as part of routine pediatric care—or perhaps as a direct-to-consumer service that parents purchase at birth or receive as a baby-shower gift—is not clear.
Learning as much as you can about your child's health might seem like a natural obligation of parenting. But it's an assumption that I think needs to be much more closely examined, both because the results that genome sequencing can return are more complex and more uncertain than one might expect, and because parents are not actually responsible for their child's lifelong health and well-being.
What is a parent supposed to do about such a risk except worry?
Existing newborn screening tests look for the presence of rare conditions that, if identified early in life, before the child shows any symptoms, can be effectively treated. Sequencing could identify many of these same kinds of conditions (and it might be a good tool if it could be targeted to those conditions alone), but it would also identify gene variants that confer an increased risk rather than a certainty of disease. Occasionally that increased risk will be significant. About 12 percent of women in the general population will develop breast cancer during their lives, while those who have a harmful BRCA1 or BRCA2 gene variant have around a 70 percent chance of developing the disease. But for many—perhaps most—conditions, the increased risk associated with a particular gene variant will be very small. Researchers have identified over 600 genes that appear to be associated with schizophrenia, for example, but any one of those confers only a tiny increase in risk for the disorder. What is a parent supposed to do about such a risk except worry?
Sequencing results are uncertain in other important ways as well. While we now have the ability to map the genome—to create a read-out of the pairs of genetic letters that make up a person's DNA—we are still learning what most of it means for a person's health and well-being. Researchers even have a name for gene variants they think might be associated with a disease or disorder, but for which they don't have enough evidence to be sure. They are called "variants of unknown (or uncertain) significance (VUS), and they pop up in most people's sequencing results. In cancer genetics, where much research has been done, about 1 in 5 gene variants are reclassified over time. Most are downgraded, which means that a good number of VUS are eventually designated benign.
While one parent might reasonably decide to learn about their child's risk for a condition about which nothing can be done medically, a different, yet still thoroughly reasonable, parent might prefer to remain ignorant so that they can enjoy the time before their child is afflicted.
Then there's the puzzle of what to do about results that show increased risk or even certainty for a condition that we have no idea how to prevent. Some genomics advocates argue that even if a result is not "medically actionable," it might have "personal utility" because it allows parents to plan for their child's future needs, to enroll them in research, or to connect with other families whose children carry the same genetic marker.
Finding a certain gene variant in one child might inform parents' decisions about whether to have another—and if they do, about whether to use reproductive technologies or prenatal testing to select against that variant in a future child. I have no doubt that for some parents these personal utility arguments are persuasive, but notice how far we've now strayed from the serious yet treatable conditions that motivated governments to set up newborn screening programs, and to mandate such testing for all.
Which brings me to the other problem with the call for sequencing newborn babies: the idea that even if it's not what the law requires, it's what good parents should do. That idea is very compelling when we're talking about sequencing results that show a serious threat to the child's health, especially when interventions are available to prevent or treat that condition. But as I have shown, many sequencing results are not of this type.
While one parent might reasonably decide to learn about their child's risk for a condition about which nothing can be done medically, a different, yet still thoroughly reasonable, parent might prefer to remain ignorant so that they can enjoy the time before their child is afflicted. This parent might decide that the worry—and the hypervigilence it could inspire in them—is not in their child's best interest, or indeed in their own. This parent might also think that it should be up to the child, when he or she is older, to decide whether to learn about his or her risk for adult-onset conditions, especially given that many adults at high familial risk for conditions like Alzheimer's or Huntington's disease choose never to be tested. This parent will value the child's future autonomy and right not to know more than they value the chance to prepare for a health risk that won't strike the child until 40 or 50 years in the future.
Parents are not obligated to learn about their children's risk for a condition that cannot be prevented, has a small risk of occurring, or that would appear only in adulthood.
Contemporary understandings of parenting are famously demanding. We are asked to do everything within our power to advance our children's health and well-being—to act always in our children's best interests. Against that backdrop, the need to sequence every newborn baby's genome might seem obvious. But we should be skeptical. Many sequencing results are complex and uncertain. Parents are not obligated to learn about their children's risk for a condition that cannot be prevented, has a small risk of occurring, or that would appear only in adulthood. To suggest otherwise is to stretch parental responsibilities beyond the realm of childhood and beyond factors that parents can control.
The Brave New World of Using DNA to Store Data
A panoramic view of DNA
Netscape co-founder-turned-venture capitalist billionaire investor Marc Andreessen once posited that software was eating the world. He was right, and the takeover of software resulted in many things. One of them is data. Lots and lots and lots of data. In the previous two years, humanity created more data than it did during its entire existence combined, and the amount will only increase. Think about it: The hundreds of 50KB emails you write a day, the dozens of 10MB photos, the minute-long, 350MB 4K video you shoot on your iPhone X add up to vast quantities of information. All that information needs to be stored. And that's becoming an issue as data volume outpaces storage space.
The race is on to find another medium capable of storing massive amounts of information in as small a space as possible.
"There won't be enough silicon to store all the data we need. It's unlikely that we can make flash memory smaller. We have reached the physical limits," Victor Zhirnov, chief scientist at the Semiconductor Research Corporation, says. "We are facing a crisis that's comparable to the oil crisis in the 1970s. By 2050, we're going to need to store 10 to the 30 bits, compared to 10 to the 23 bits in 2016." That amount of storage space is equivalent to each of the world's seven billion people owning almost six trillion -- that's 10 to the 12th power -- iPhone Xs with 256GB storage space.
The race is on to find another medium capable of storing massive amounts of information in as small a space as possible. Zhirnov and other scientists are looking at the human body, looking to DNA. "Nature has nailed it," Luis Ceze, a professor in the Department of Computer Science and Engineering at the University of Washington, says. "DNA is a molecular storage medium that is remarkable. It's incredibly dense, many, many thousands of times denser than the densest technology that we have today. And DNA is remarkably general. Any information you can map in bits you can store in DNA." It's so dense -- able to store a theoretical maximum of 215 petabytes (215 million gigabytes) in a single gram -- that all the data ever produced could be stored in the back of a tractor trailer truck.
Writing DNA can be an energy-efficient process, too. Consider how the human body is constantly writing and rewriting DNA, and does so on a couple thousand calories a day. And all it needs for storage is a cool, dark place, a significant energy savings when compared to server farms that require huge amounts of energy to run and even more energy to cool.
Picture it: tiny specks of inert DNA made from silicon or another material, stored in cool, dark, dry areas, preserved for all time.
Researchers first succeeded in encoding data onto DNA in 2012, when Harvard University geneticists George Church and Sri Kosuri wrote a 52,000-word book on A, C, G, and T base pairs. Their method only produced 1.28 petabytes per gram of DNA, however, a volume exceeded the next year when a group encoded all 154 Shakespeare sonnets and a 26-second clip of Martin Luther King's "I Have A Dream" speech. In 2017, Columbia University researchers Yaniv Erlich and Dina Zielinski made the process 60 percent more efficient.
The limiting factor today is cost. Erlich said the work his team did cost $7,000 to encode and decode two megabytes of data. To become useful in a widespread way, the price per megabyte needs to plummet. Even advocates concede this point. "Of course it is expensive," Zhirnov says. "But look how much magnetic storage cost in the 1980s. What you store today in your iPhone for virtually nothing would cost many millions of dollars in 1982." There's reason to think the price will continue to fall. Genome readers are improving, getting cheaper, faster, and smaller, and genome sequencing becomes cheaper every year, too. Picture it: tiny specks of inert DNA made from silicon or another material, stored in cool, dark, dry areas, preserved for all time.
"It just takes a few minutes to double a sample. A few more minutes, you double it again. Very quickly, you have thousands or millions of new copies."
Plus, DNA has another advantage over more traditional forms of storage: It's very easy to reproduce. "If you want a second copy of a hard disk drive, you need components for a disk drive, hook both drives up to a computer, and copy. That's a pain," Nick Goldman, a researcher at the European Bioinformatics Institute, says. "DNA, once you have that first sample, it's a process that is absolutely routine in thousands of laboratories around the world to multiply that using polymerase chain reaction [which uses temperature changes or other processes]. It just takes a few minutes to double a sample. A few more minutes, you double it again. Very quickly, you have thousands or millions of new copies."
This ability to duplicate quickly and easily is a positive trait. But, of course, there's also the potential for danger. Does encoding on DNA, the very basis for life, present ethical issues? Could it get out of control and fundamentally alter life as we know it?
The chance is there, but it's remote. The first reason is that storage could be done with only two base pairs, which would serve as replacements for the 0 and 1 digits that make up all digital data. While doing so would decrease the possible density of the storage, it would virtually eliminate the risk that the sequences would be compatible with life.
But even if scientists and researchers choose to use four base pairs, other safeguards are in place that will prevent trouble. According to Ceze, the computer science professor, the snippets of DNA that they write are very short, around 150 nucleotides. This includes the title, the information that's being encoded, and tags to help organize where the snippet should fall in the larger sequence. Furthermore, they generally avoid repeated letters, which dramatically reduces the chance that a protein could be synthesized from the snippet.
"In the future, we'll know enough about someone from a sample of their DNA that we could make a specific poison. That's the danger, not those of us who want to encode DNA for storage."
Inevitably, some DNA will get spilt. "But it's so unlikely that anything that gets created for storage would have a biological interpretation that could interfere with the mechanisms going on in a living organism that it doesn't worry me in the slightest," Goldman says. "We're not of concern for the people who are worried about the ethical issues of synthetic DNA. They are much more concerned about people deliberately engineering anthrax. In the future, we'll know enough about someone from a sample of their DNA that we could make a specific poison. That's the danger, not those of us who want to encode DNA for storage."
In the end, the reality of and risks surrounding encoding on DNA are the same as any scientific advancement: It's another system that is vulnerable to people with bad intentions but not one that is inherently unethical.
"Every human action has some ethical implications," Zhirnov says. "I can use a hammer to build a house or I can use it to harm another person. I don't see why DNA is in any way more or less ethical."
If that house can store all the knowledge in human history, it's worth learning how to build it.
Editor's Note: In response to readers' comments that silicon is one of the earth's most abundant materials, we reached back out to our source, Dr. Victor Zhirnov. He stands by his statement about a coming shortage of silicon, citing this research. The silicon oxide found in beach sand is unsuitable for semiconductors, he says, because the cost of purifying it would be prohibitive. For use in circuit-making, silicon must be refined to a purity of 99.9999999 percent. So the process begins by mining for pure quartz, which can only be found in relatively few places around the world.