A Fierce Mother vs. a Fatal Mutation
Editor's Note: In the year 2000, Amber Salzman was a 39-year-old mom from Philadelphia living a normal life: working as a pharmaceutical executive, raising an infant son, and enjoying time with her family. But when tragedy struck in the form of a ticking time bomb in her son's DNA, she sprang into action. Her staggering triumphs after years of turmoil exemplify how parents today can play a crucial role in pushing science forward. This is her family's story, as told to LeapsMag's Editor-in-Chief Kira Peikoff.
For a few years, my nephew Oliver, suffered from symptoms that first appeared as attention deficit disorder and then progressed to what seemed like Asperger's, and he continued to worsen and lose abilities he once had. After repeated misdiagnoses, he was finally diagnosed at age 8 with adrenoleukodystrophy, or ALD – a degenerative brain disease that puts kids on the path toward death. We learned it was an X-linked disease, so we had to test other family members. Because Oliver had it, that meant his mother, my sister, was carrier, which meant I had a 50-50 chance of being a carrier, and if I was, then my son had a 50-50 chance of getting the bad gene.
You know how some people win prizes all the time? I don't have that kind of luck. I had a sick feeling when we drew my son's blood. It was almost late December in the year 2000. Spencer was 1 and climbing around like a monkey, starting to talk—a very rambunctious kid. He tested positive, along with Oliver's younger brother, Elliott.
"The only treatment at the time was an allogenic stem cell transplant from cord blood or bone marrow."
You can imagine the dreadful things that go through your mind. Everything was fine then, but he had a horrific chance that in about 3 or 4 years, a bomb would go off. It was so tough thinking that we were going to lose Oliver, and then Spencer and Elliott were next in line. The only treatment at the time was an allogenic stem cell transplant from cord blood or bone marrow, which required finding a perfect match in a donor and then undergoing months of excruciating treatment. The mortality rate can be as high as 40 percent. If your kid was lucky enough to find a donor, he would then be lucky to leave the hospital 100 days after a transplant with a highly fragile immune system.
At the time, I was at GlaxoSmithKline in Research and Development, so I did have a background in working with drug development and I was fortunate to report to the chairman of R&D, Tachi Yamada.
I called Tachi and said, "I need your advice, I have three or four years to find a cure. What do I do?" He did some research and said it's a monogenic disease—meaning it's caused by only one errant gene—so my best bet was gene therapy. This is an approach to treatment that involves taking a sample of the patient's own stem cells, treating them outside the body with a viral vector as a kind of Trojan Horse to deliver the corrected gene, and then infusing the solution back into the patient, in the hopes that the good gene will proliferate throughout the body and stop the disease in its tracks.
Tachi said to call his friend Jim Wilson, who was a leader in the field at UPenn.
Since I live in Philadelphia I drove to see Jim as soon as possible. What I didn't realize was how difficult a time it was. This was shortly after Jesse Gelsinger died in a clinical trial for gene therapy run by UPenn—the first death for the field—and research had abruptly stopped. But when I met with Jim, he provided a road map for what it would take to put together a gene therapy trial for ALD.
Meanwhile, in parallel, I was dealing with my son's health.
After he was diagnosed, we arranged a brain MRI to see if he had any early lesions, because the only way you can stop the disease is if you provide a bone marrow transplant before the disease evolves. Once it is in full force, you can't reverse it, like a locomotive that's gone wild.
"He didn't recover like other kids because his brain was not a normal brain; it was an ALD brain."
We found he had a brain tumor that had nothing to do with ALD. It was slow growing, and we would have never found it otherwise until it was much bigger and caused symptoms. Long story short, he ended up getting the tumor removed, and when he was healing, he didn't recover like other kids because his brain was not a normal brain; it was an ALD brain. We knew we needed a transplant soon, and the gene therapy trial was unfortunately still years away.
At the time, he was my only child, and I was thinking of having additional kids. But I didn't want to get pregnant with another ALD kid and I wanted a kid who could provide a bone marrow transplant for my son. So while my son was still OK, I went through 5 cycles of in vitro fertilization, a process in which hormone shots stimulated my ovaries to produce multiple eggs, which were then surgically extracted and fertilized in a lab with my husband's sperm. After the embryos grew in a dish for three to five days, doctors used a technique called preimplantation genetic diagnosis, screening those embryos to determine which genes they carry, in order to try to find a match for Spencer. Any embryo that had ALD, we saved for research. Any that did not have ALD but were not a match for Spencer, we put in the freezer. We didn't end up with a single one that was a match.
So he had a transplant at Duke Children's Hospital at age 2, using cord blood donated from a public bank. He had to be in the hospital a long time, infusing meds multiple times a day to prevent the donor cells from rejecting his body. We were all excited when he made it out after 100 days, but then we quickly had to go back for an infection he caught.
We were still bent on moving forward with the gene therapy trials.
Jim Wilson at Penn explained what proof of concept we needed in animals to go forward to humans, and a neurologist in Paris, Patrick Aubourg, had already done that using a vector to treat ALD mice. But he wasn't sure which vector to use in humans.
The next step was to get Patrick and a team of gene therapy experts together to talk about what they knew, and what needed to be done to get a trial started. There was a lot of talk about viral vectors. Because viruses efficiently transport their own genomes into the cells they infect, they can be useful tools for sending good genes into faulty cells. With some sophisticated tinkering, molecular biologists can neuter normally dangerous viruses to make them into delivery trucks, nothing more. The biggest challenge we faced then was: How do we get a viral vector that would be safe in humans?
Jim introduced us to Inder Verma, chair of the scientific advisory board of Cell Genesys, a gene therapy company in California that was focused on oncology. They were the closest to making a viral vector that could go into humans, based on a disabled form of HIV. When I spoke to Inder, he said, "Let's review the data, but you will need to convince the company to give you the vector." So I called the CEO and basically asked him, "Would you be willing to use the vector in this horrific disease?" I told him that our trial would be the fastest way to test their vector in humans. He said, "If you can convince my scientists this is ready to go, we will put the vector forward." Mind you, this was a multi-million-dollar commitment, pro bono.
I kept thinking every day, the clock is ticking, we've got to move quickly. But we convinced the scientists and got the vector.
Then, before we could test it, an unrelated clinical trial in gene therapy for a severe immunodeficiency disease, led to several of the kids developing leukemia in 2003. The press did a bad number and scared everyone away from the field, and the FDA put studies on hold in the U.S. That was one of those moments where I thought it was over. But we couldn't let it stop. Nothing's an obstacle, just a little bump we have to overcome.
Patrick wanted to do the study in France with the vector. This is where patient advocacy is important in providing perspective on the risks vs. benefits of undergoing an experimental treatment. What nobody seemed to realize was that the kids in the 2003 trial would have died if they were not first given the gene therapy, and luckily their leukemia was a treatable side effect.
Patrick and I refused to give up pushing for approval of the trial in France. Meanwhile, I was still at GSK, working full time, and doing this at night, nonstop. Because my day job did require travel to Europe, I would stop by Paris and meet with him. Another sister of mine who did not have any affected children was a key help and we kept everything going. You really need to continually stay engaged and press the agenda forward, since there are so many things that pop up that can derail the program.
Finally, Patrick was able to treat four boys with the donated vector. The science paper came out in 2009. It was a big deal. That's when the venture money came in—Third Rock Ventures was the first firm to put big money behind gene therapy. They did a deal with Patrick to get access to the Intellectual Property to advance the trial, brought on scientists to continue the study, and made some improvements to the vector. That's what led to the new study reported recently in the New England Journal of Medicine. Of 17 patients, 15 of them are still fine at least two years after treatment.
You know how I said we felt thrilled that my son could leave the hospital after 100 days? When doing the gene therapy treatment, the hospital stay needed is much quicker. Shortly after one kid was treated, a physician in the hospital remarked, "He is fine, he's only here because of the trial." Since you get your own cells, there is no risk of graft vs. host disease. The treatment is pretty anticlimactic: a bag of blood, intravenously infused. You can bounce back within a few weeks.
Now, a few years out, approximately 20 percent of patients' cells have been corrected—and that's enough to hold off the disease. That's what the data is showing. I was blown away when it worked in the first two patients.
The formerly struggling field is now making a dramatic comeback.
Now I run a company, Adverum Biotechnologies, that I wish existed back when my son was diagnosed, because I want people who are like me, coming to me, saying: "I have proof of concept in an animal, I need to get a vector suitable for human trials, do the work needed to file with the FDA, and move it into humans." Our company knows how to do that and would like to work with such patient advocates.
Often parents feel daunted to partake in similar efforts, telling me, "Well, you worked in pharma." Yes, I had advantages, but if you don't take no for an answer, people will help you. Everybody is one degree of separation from people who can help them. You don't need a science or business background. Just be motivated, ask for help, and have your heart in the right place.
Having said that, I don't want to sound judgmental of families who are completely paralyzed. When you get a diagnosis that your child is dying, it is hard to get out of bed in the morning and face life. My sister at a certain point had one child dying, one in the hospital getting a transplant, and a healthy younger child. To expect someone like that to at the same time be flying to an FDA meeting, it's hard. Yet, she made critical meetings, and she and her husband graciously made themselves available to talk to parents of recently diagnosed boys. But it is really tough and my heart goes out to anyone who has to live through such devastation.
Tragically, my nephew Oliver passed away 13 years ago at age 12. My other nephew was 8 when he had a cord blood transplant; our trial wasn't available yet. He had some bad graft vs. host disease and he is now navigating life using a wheelchair, but thank goodness, it stopped the disease. He graduated Stanford a year ago and is now a sports writer for the Houston Chronicle.
As for my son, today he is 17, a precocious teenager applying to colleges. He also volunteers for an organization called the Friendship Circle, providing friends for kids with special needs. He doesn't focus on disability and accepts people for who they are – maybe he would have been like that anyway, but it's part of who he is. He lost his cousin and knows he is alive today because Oliver's diagnosis gave us a head start on his.
My son's story is a good one in that he had a successful transplant and recovered.
Once we knew he would make it and we no longer needed our next child to be a match, we had a daughter using one of our healthy IVF embryos in storage. She is 14 now, but she jokes that she is technically 17, so she should get to drive. I tell her, they don't count the years in the freezer. You have to joke about it.
I am so lucky to have two healthy kids today based on advances in science.
And I often think of Oliver. We always try to make him proud and honor his name.
[Editor's Note: This story was originally published in November 2017. We are resurfacing archive hits while our staff is on vacation.]
Salzman and her son Spencer, 17, who is now healthy.
(Courtesy of Salzman)
Today’s podcast guest is Rosalind Picard, a researcher, inventor named on over 100 patents, entrepreneur, author, professor and engineer. When it comes to the science related to endowing computer software with emotional intelligence, she wrote the book. It’s published by MIT Press and called Affective Computing.
Dr. Picard is founder and director of the MIT Media Lab’s Affective Computing Research Group. Her research and engineering contributions have been recognized internationally. For example, she received the 2022 International Lombardy Prize for Computer Science Research, considered by many to be the Nobel prize in computer science.
Through her research and companies, Dr. Picard has developed wearable sensors, algorithms and systems for sensing, recognizing and responding to information about human emotion. Her products are focused on using fitness trackers to advance clinical quality treatments for a range of conditions.
Meanwhile, in just the past few years, numerous fitness tracking companies have released products with their own stress sensors and systems. You may have heard about Fitbit’s Stress Management Score, or Whoop’s Stress Monitor – these features and apps measure things like your heart rhythm and a certain type of invisible sweat to identify stress. They’re designed to raise awareness about forms of stress such as anxieties and anger, and suggest strategies like meditation to relax in real time when stress occurs.
But how well do these off-the-shelf gadgets work? There’s no one more knowledgeable and experienced than Rosalind Picard to explain the science behind these stress features, what they do exactly, how they might be able to help us, and their current shortcomings.
Dr. Picard is a member of the National Academy of Engineering and a Fellow of the National Academy of Inventors, and a popular speaker who’s given over a hundred invited keynote talks and a TED talk with over 2 million views. She holds a Bachelors in Electrical Engineering from Georgia Tech, and Masters and Doctorate degrees in Electrical Engineering and Computer Science from MIT. She lives in Newton, Massachusetts with her husband, where they’ve raised three sons.
In our conversation, we discuss stress scores on fitness trackers to improve well-being. She describes the difference between commercial products that might help people become more mindful of their health and products that are FDA approved and really capable of advancing the science. We also talk about several fascinating findings and concepts discovered in Dr. Picard’s lab including the multiple arousal theory, a phenomenon you’ll want to hear about. And we explore the complexity of stress, one reason it’s so tough to measure. For example, many forms of stress are actually good for us. Can fitness trackers tell the difference between stress that’s healthy and unhealthy?
- Dr. Picard’s book, Affective Computing
- Dr. Picard’s bio
- Dr. Picard on Twitter
- Dr. Picard’s company, Empatica - https://www.empatica.com/ - The FDA-cleared Empatica Health Monitoring Platform provides accurate, continuous health insights for researchers and clinicians, collected in the real world
- Empatica Twitter
- Dr. Picard and her team have published hundreds of peer-reviewed articles across AI, Machine Learning, Affective Computing, Digital Health, and Human-computer interaction.
- Dr. Picard’s TED talk
If you look back on the last century of scientific achievements, you might notice that most of the scientists we celebrate are overwhelmingly white, while scientists of color take a backseat. Since the Nobel Prize was introduced in 1901, for example, no black scientists have landed this prestigious award.
The work of black women scientists has gone unrecognized in particular. Their work uncredited and often stolen, black women have nevertheless contributed to some of the most important advancements of the last 100 years, from the polio vaccine to GPS.
Here are five black women who have changed science forever.
Dr. May Edward Chinn
Dr. May Edward Chinn practicing medicine in Harlem
George B. Davis, PhD.
Chinn was born to poor parents in New York City just before the start of the 20th century. Although she showed great promise as a pianist, playing with the legendary musician Paul Robeson throughout the 1920s, she decided to study medicine instead. Chinn, like other black doctors of the time, were barred from studying or practicing in New York hospitals. So Chinn formed a private practice and made house calls, sometimes operating in patients’ living rooms, using an ironing board as a makeshift operating table.
Chinn worked among the city’s poor, and in doing this, started to notice her patients had late-stage cancers that often had gone undetected or untreated for years. To learn more about cancer and its prevention, Chinn begged information off white doctors who were willing to share with her, and even accompanied her patients to other clinic appointments in the city, claiming to be the family physician. Chinn took this information and integrated it into her own practice, creating guidelines for early cancer detection that were revolutionary at the time—for instance, checking patient health histories, checking family histories, performing routine pap smears, and screening patients for cancer even before they showed symptoms. For years, Chinn was the only black female doctor working in Harlem, and she continued to work closely with the poor and advocate for early cancer screenings until she retired at age 81.
Pictorial Press Ltd/Alamy
Alice Ball was a chemist best known for her groundbreaking work on the development of the “Ball Method,” the first successful treatment for those suffering from leprosy during the early 20th century.
In 1916, while she was an undergraduate student at the University of Hawaii, Ball studied the effects of Chaulmoogra oil in treating leprosy. This oil was a well-established therapy in Asian countries, but it had such a foul taste and led to such unpleasant side effects that many patients refused to take it.
So Ball developed a method to isolate and extract the active compounds from Chaulmoogra oil to create an injectable medicine. This marked a significant breakthrough in leprosy treatment and became the standard of care for several decades afterward.
Unfortunately, Ball died before she could publish her results, and credit for this discovery was given to another scientist. One of her colleagues, however, was able to properly credit her in a publication in 1922.
onathan Newton/The Washington Post/Getty
The person who arguably contributed the most to scientific research in the last century, surprisingly, wasn’t even a scientist. Henrietta Lacks was a tobacco farmer and mother of five children who lived in Maryland during the 1940s. In 1951, Lacks visited Johns Hopkins Hospital where doctors found a cancerous tumor on her cervix. Before treating the tumor, the doctor who examined Lacks clipped two small samples of tissue from Lacks’ cervix without her knowledge or consent—something unthinkable today thanks to informed consent practices, but commonplace back then.
As Lacks underwent treatment for her cancer, her tissue samples made their way to the desk of George Otto Gey, a cancer researcher at Johns Hopkins. He noticed that unlike the other cell cultures that came into his lab, Lacks’ cells grew and multiplied instead of dying out. Lacks’ cells were “immortal,” meaning that because of a genetic defect, they were able to reproduce indefinitely as long as certain conditions were kept stable inside the lab.
Gey started shipping Lacks’ cells to other researchers across the globe, and scientists were thrilled to have an unlimited amount of sturdy human cells with which to experiment. Long after Lacks died of cervical cancer in 1951, her cells continued to multiply and scientists continued to use them to develop cancer treatments, to learn more about HIV/AIDS, to pioneer fertility treatments like in vitro fertilization, and to develop the polio vaccine. To this day, Lacks’ cells have saved an estimated 10 million lives, and her family is beginning to get the compensation and recognition that Henrietta deserved.
Dr. Gladys West
Gladys West was a mathematician who helped invent something nearly everyone uses today. West started her career in the 1950s at the Naval Surface Warfare Center Dahlgren Division in Virginia, and took data from satellites to create a mathematical model of the Earth’s shape and gravitational field. This important work would lay the groundwork for the technology that would later become the Global Positioning System, or GPS. West’s work was not widely recognized until she was honored by the US Air Force in 2018.
Dr. Kizzmekia "Kizzy" Corbett
At just 35 years old, immunologist Kizzmekia “Kizzy” Corbett has already made history. A viral immunologist by training, Corbett studied coronaviruses at the National Institutes of Health (NIH) and researched possible vaccines for coronaviruses such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).At the start of the COVID pandemic, Corbett and her team at the NIH partnered with pharmaceutical giant Moderna to develop an mRNA-based vaccine against the virus. Corbett’s previous work with mRNA and coronaviruses was vital in developing the vaccine, which became one of the first to be authorized for emergency use in the United States. The vaccine, along with others, is responsible for saving an estimated 14 million lives.
Sarah Watts is a health and science writer based in Chicago.