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 couple holds up a picture of their ultrasound.
By now you have probably heard something about CRISPR, the simple and relatively inexpensive method of precisely editing the genomes of plants, animals, and humans.
The treatment of disease in fetuses, the liminal category of life between embryos and humans, poses the next frontier.
Through CRISPR and other methods of gene editing, scientists have produced crops to be more nutritious, better able to resist pests, and tolerate droughts; engineered animals ranging from fruit flies to monkeys to make them better suited for scientific study; and experimentally treated the HIV virus, Hepatitis B, and leukemia in human patients.
There are also currently FDA-approved trials to treat blindness, cancer, and sickle cell disease in humans using gene editing, and there is consensus that CRISPR's therapeutic applications will grow significantly in the coming years.
While the treatment of human disease through use of gene editing is not without its medical and ethical concerns, the avoidance of disease in embryos is far more fraught. Nonetheless, Nature reported in November that He Jiankui, a scientist in China, had edited twin embryos to disable a gene called CCR5 in hopes of avoiding transmission of HIV from their HIV-positive father.
Though there are questions about the effectiveness and necessity of this therapy, He reported that sequencing has proven his embryonic gene edits were successful and the twins were "born normal and healthy," although his claims have not been independently verified.
More recently, Denis Rebrikov, a Russian scientist, announced his plans to disable the same gene in embryos to be implanted in HIV-positive women later this year. Futuristic as it may seem, prenatal gene editing is already here.
The treatment of disease in fetuses, the liminal category of life between embryos and humans, poses the next frontier. Numerous conditions—some minor, some resulting in a lifetime of medical treatment, some incompatible with life outside of the womb—can be diagnosed through use of prenatal diagnostic testing. There is promising research suggesting doctors will soon be able to treat or mitigate at least some of them through use of fetal gene editing.
This research could soon present women carrying genetically anomalous fetuses a third option aside from termination or birthing a child who will likely face a challenging and uncertain medical future: Whether to undergo a fetal genetic intervention.
However, genetic intervention will open the door to a host of ethical considerations, particularly with respect to the relationship between pregnant women and prenatal genetic counselors. Current counselors theoretically provide objective information and answer questions rather than advise their pregnant client whether to continue with her pregnancy, despite the risks, or to have an abortion.
In practice, though, prenatal genetic counseling is most often directive, and the nature of the counseling pregnant women receive can depend on numerous factors, including their religious and cultural beliefs, their perceived ability to handle a complicated pregnancy and subsequent birth, and their financial status. Introducing the possibility of a fetal genetic intervention will exacerbate counselor reliance upon these considerations and in some cases lead to counseling that is even more directive.
Some women in the near future will face the choice of whether to abort, keep, or treat a genetically anomalous fetus.
Future counselors will have to figure out under what circumstances it is even appropriate to broach the subject. Should they only discuss therapies that are FDA-approved, or should they mention experimental treatments? What about interventions that are available in Europe or Asia, but banned in the United States? Or even in the best case of scenario of an FDA-approved treatment, should a counselor make reference to it if she knows for a fact that her client cannot possibly afford it?
Beyond the basic question of what information to share, counselors will have to confront the fact that the very notion of fixing or "editing" offspring will be repugnant to many women, and inherent in the suggestion is the stigmatization of individuals with disabilities. Prenatal genetic counselors will be on the forefront of debates surrounding which fetuses should remain as they are and which ones should be altered.
Despite these concerns, some women in the near future will face the choice of whether to abort, keep, or treat a genetically anomalous fetus in utero. Take, for example, a woman who learns during prenatal testing that her fetus has Angelman syndrome, a genetic disorder characterized by intellectual disability, speech impairment, loss of muscle control, epilepsy, and a small head. There is currently no human treatment for Angelman syndrome, which is caused by a loss of function in a single gene, UBE3A.
But scientists at the University of North Carolina have been able to treat Angelman syndrome in fetal mice by reactivating UBE3A through use of a single injection. The therapy has also proven effective in cultured human brain cells. This suggests that a woman might soon have to consider injecting her fetus's brain with a CRISPR concoction custom-designed to target UBE3A, rather than terminate her pregnancy or bring her fetus to term unaltered.
Assuming she receives the adequate information to make an informed choice, she too will face an ethical conundrum. There will be the inherent risks of injecting anything into a developing fetus's brain, including the possibility of infection, brain damage, and miscarriage. But there are also risks specific to gene editing, such as so-called off-target effects, the possibility of impacting genes other than the intended one. Such effects are highly unpredictable and can be difficult to detect. So too is it impossible to predict how altering UBE3A might lead to other genetic and epigenetic changes once the baby is born.
There are no easy answers to the many questions that will arise in this space.
A woman deciding how to act in this scenario must balance these risks against the potential benefits of the therapy, layered on top of her belief system, resources, and personal ethics. The calculus will be different for every woman, and even the same woman might change her mind from one pregnancy to the next based on the severity of the condition diagnosed and other available medical options.
Her genetic counselor, meanwhile, must be sensitive to all of these concerns in helping her make her decision, keeping up to date on the possible new treatments, and carefully choosing which information to disclose in striving to be neutral. There are no easy answers to the many questions that will arise in this space, but better to start thinking about them now, before it is too late.
Lab-grown insect meat could be the protein source of the future.
Agriculture in the 21st century is not as simple as it once was. With a population seven billion strong, a climate in crisis, and sustainability in farming practices on everyone's radar, figuring out how to feed the masses without destroying the Earth is a pressing concern.
Tufts scientists argue that insect cells may be better suited to lab-created meat protein than traditional farm animal cells.
In addition to low-emission cows and drone pollinators, there's a promising new solution on the table. How does "lab-grown insect meat" grab you?
Writing in Frontiers in Sustainable Food Systems, researchers at Tufts University say insects that are fed plants and genetically modified for maximum growth, nutrition, and flavor could be the best, greenest alternative to our current livestock farming practices. This lab-grown protein source could produce high volume, nutritious food without the massive resources required for traditional animal agriculture.
"Due to the environmental, public health, and animal welfare concerns associated with our current livestock system, it is vital to develop more sustainable food production methods," says lead author Natalie Rubio. Could insect meat be the key?
Next Up
New sustainable food production includes what's called "cellular agriculture," an emerging industry and field of study in which meat and dairy are produced via cells in a lab instead of whole animals. So far, scientists have primarily focused on bovine, porcine, and avian cells to create this "cultured meat."
But the Tufts scientists argue that insect cells may be better suited to lab-created meat protein than traditional farm animal cells.
"Compared to cultured mammalian, avian, and other vertebrate cells, insect cell cultures require fewer resources and less energy-intensive environmental control, as they have lower glucose requirements and can thrive in a wider range of temperature, pH, oxygen, and osmolarity conditions," reports Rubio.
"Alterations necessary for large-scale production are also simpler to achieve with insect cells, which are currently used for biomanufacturing of insecticides, drugs, and vaccines," she adds.
They still have some details to hash out, however, including how to make cultured insect meat more like the steak and chicken we're all familiar with.
"Despite this immense potential, cultured insect meat isn't ready for consumption," says Rubio. "Research is ongoing to master two key processes: controlling development of insect cells into muscle and fat, and combining these in 3D cultures with a meat-like texture." They are currently experimenting with mushroom-derived fiber to tackle the latter.
People would still be able to eat meat—it would just come from a different source.
Open Questions
As the report points out, one thing that makes cellular agriculture an attractive alternative to high-density animal farming is that it doesn't require consumers to change their behaviors. People would still be able to eat meat—it would just come from a different source.
But the big question remains: How will lab-grown insect meat taste? Will the buggers really taste as good as burgers?
And, of course, there's the "ew" factor. Meat alternatives have proven to work for some people—Tofurky is still in business, after all—but it may be a hard sell to get the masses to jump on board with eating bugs. Consuming creepy crawlies sounds simply unpalatable to many, and the term "lab-grown, cellular insect meat" doesn't help much. Perhaps an entirely new nomenclature is in order.
Another question is whether or not folks will trust such scientifically-created food. People already use the term "frankenfood" to refer to genetic modification -- even though the vast majority of the corn and soybeans planted in the U.S. today are genetically engineered, and other major crops with GM varieties include potatoes, apples, squash, and papayas. Still, combining GM technology with eating insects may be a hard sell.
However, we're all going to have to get used to trying new things if we want to leave a habitable home for our children. If a lab-grown bug burger can save the planet, maybe it's worth a shot.