Dr. Francis Collins
In Memory of Andrew Lee
Posted on by Dr. Francis Collins
A lot of young people are driven—driven to get a good education, land a great job, find true love, or see the world. But, today, I want to honor the life of a young man who was driven by something even bigger. Andrew Lee was driven to cure kidney cancer—not only for himself, but for others as well.
I knew and loved Andrew. And so did the legion of doctors, nurses, researchers, and other team members who had the privilege of fighting cancer with him over four very challenging years. Andrew was 19, just finishing his freshman year of college, when he received a devastating diagnosis: stage 4 kidney cancer, a rare type called Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). There is no known cure for HLRCC, and doctors estimated his survival at about a year at best.
Still, Andrew and his family weren’t about to go hide somewhere and wait for the end. They began a journey that led him to take part in at least seven clinical trials, including ones at Yale University, New Haven, CT; Georgetown University, Washington, DC; and the NIH Clinical Center, Bethesda, MD. Experimental treatments slowed down the cancer, but sometimes made him terribly sick. Yet, Andrew always remained optimistic and cheerful. If a trial didn’t help him, maybe it would help someone else.
Andrew’s generosity didn’t stop there. Inspired by his father’s gift of a totally awesome 2015 Liberty Walk Nissan GT-R, he founded the Driven To Cure (DTC) nonprofit and traveled the country in his orange sports car to raise funds for kidney cancer research. According to the National Cancer Institute, nearly 63,000 Americans are diagnosed with kidney and renal pelvis cancers each year.
Andrew figured out how to put the “fun” in fundraising, drawing crowds at car shows and raising more than $500,000 in donations in just three years. His efforts were recognized by the Foundation for the NIH’s Charlie Sanders Award, which I had the privilege of presenting to him last fall.
But I think it was Andrew’s humanity that touched us the most. He always had time to share his story, to encourage another child or adult struggling with a frightening diagnosis. He’d give thrills to kids at The Children’s Inn at NIH when he rumbled into the parking lot with his 700 horsepower GT-R. At car shows, throngs of people were drawn in by the turbocharged ride and then captivated by the young man with the bright smile and compelling story. Andrew wrote: “I realized that the vehicle of my dreams was also the vehicle which gave me the opportunity to make a difference; to do something bigger than myself.”
Still, on the personal level, kidney cancer proved relentless. Options for treatment eventually ran out. As the disease progressed, Andrew and his family had to make another difficult transition—choosing to celebrate life, even in the face of its approaching end. He needed a wheelchair, so family and friends came up with one, keeping in mind one of Andrew’s last wishes. When Andrew needed 24-hour care and pain control, he was admitted to the NIH Clinical Center Hospice Unit, where comfort could be provided and his loved ones could gather around. That even included getting government permission for a visit from his dog Milo! Surrounded by friends and family, he died peacefully on April 21.
Andrew made friends with everyone—especially kids at The Children’s Inn. One special buddy was Isaac Barchus, who has a rare autoinflammatory disease called CANDLE Syndrome. When he was back home in Omaha, NE, Isaac enjoyed challenging Andrew to long-distance video games, especially FIFA Soccer.
Although Isaac can walk, it can be very painful, so he sometimes turned to an old, beat-up wheelchair to cover long distances. But not anymore. When Isaac turned 15 on June 7, Andrew’s father Bruce Lee fulfilled his son’s wish for the future of his wheelchair. He presented Isaac with Andrew’s wheelchair, which had now been painted the same orange color as Andrew’s GT-R and emblazoned with the feisty slogan on Andrew’s personalized license plate—F CANCR. What a cool birthday gift!
During his final weeks and days, Andrew and his dad often listened to the Andy Grammer song, “Don’t Give Up on Me.” Andrew’s family never gave up on him, and he never gave up on them either. In fact, Andrew never gave up caring, loving, and believing. He wouldn’t want us to either, as his favorite song reminds us: “I will fight, I will fight for you; I always do until my heart is black and blue.”
Yes, Andrew, our hearts are black and blue from losing you. But we won’t give up on all you stood for in your short but inspiring life. Race In Peace, dear Andrew.
Links:
Remembering Andrew Lee (Foundation for the National Institutes of Health)
NIH Cancer Patient Receives Humanitarian Award (The NIH Record)
Driven To Cure (Silver Spring, MD)
Video: Fighting Cancer With a 700-hp Nissan GT-R (The Drive)
Video: Andy Grammer—”Don’t Give Up On Me” [Official Lyric Video] from the film Five Feet Apart
Hereditary Leiomyomatosis and Renal Cell Cancer (National Library of Medicine/NIH)
Kidney (Renal Cell) Cancer (National Cancer Institute/NIH)
CANDLE Syndrome (Genetic and Rare Diseases Information Center/NIH)
Treating CANDLE Syndrome (National Institute of Allergy and Infectious Diseases/NIH)
Playing With My Band
Posted on by Dr. Francis Collins
Combating Mosquitoes with an Engineered Fungus
Posted on by Dr. Francis Collins
Almost everywhere humans live on this planet, mosquitoes carry microbes that cause potentially deadly diseases, from West Nile virus to malaria. While chemical insecticides offer a line of defense, mosquito populations often grow resistant to them. So, it’s intriguing to learn that we may now have another ally in this important fight: a genetically engineered fungus!
Reporting in the journal Science, an international research team supported by NIH describes how this new approach might be used to combat malaria [1]. A fungus called Metarhizium pingshaense is a natural enemy of the mosquito, but, by itself, it kills mosquitoes too slowly to control transmission of malaria. To make this fungus an even more efficient mosquito killer, researchers engineered it to carry a gene encoding a toxin, derived from a spider, that is deadly to insects. Tests of the souped-up fungus in a unique contained facility designed to simulate a West African village found it safely and rapidly killed insecticide-resistant mosquitoes, reducing their numbers by more than 99 percent within 45 days.
Mosquitoes are the deadliest animals in the world. More than 3.2 billion people—about half of all humans—are at risk for malaria, and more than 400,000 die each year from the disease. Other mosquito-borne illnesses, including Zika and dengue viruses, sicken millions more each year. By combining existing insect control strategies with the latest technical innovation, it should be possible to lower those numbers.
In the latest study, Raymond St. Leger and Brian Lovett, University of Maryland, College Park, teamed with Abdoulaye Diabate and colleagues from Institut de Recherche en Sciences de la Santé/Cente Muraz, Burkina Faso, West Africa. The researchers employed a strategy that’s been in use around the world for more than 100 years to control agricultural pests.
The approach involves the fungal species Metarhizium, which kills a variety of insects. Earlier studies had shown that spores from a specific Metarhizium strain could make a big enough dent in a mosquito population to raise the possibility of using the fungus to reduce infective bites among humans [2]. But killing off the mosquitoes required very large quantities of fungal spores and usually took a couple of weeks.
Here’s where things turned innovative. To boost the fungus’s potency, St. Leger and colleagues used genetic engineering to add a toxin derived from the Australian Blue Mountains funnel-web spider. The toxin came with a major advantage: the U.S. Environmental Protection Agency (EPA) already has approved its use as a safe-and-effective insecticidal protein.
Besides giving the engineered fungus that ability to produce a spider toxin, the researchers added another clever element. They didn’t want the fungus to produce the toxin all the time—only after it comes in contact with a mosquito’s hemolymph, the insect equivalent of blood. So, they needed to insert a control switch, and the researchers knew just where to find the needed part.
Once inside a mosquito, the fungus naturally produces a structural protein called collagen that shields it from the insect’s immune system. A genetic switch that turns “on” when it detects an insect’s hemolymph controls that collagen production. To ensure that the spider toxin was produced at just the right time, the researchers hotwired their Metarhizium to begin producing it under the control of this same genetic switch.
The next step was to test this modified organism in a more natural, but controlled, environment. The researchers spent more than a year in Burkina Faso building a specialized facility called a MosquitoSphere. It’s similar to a very large greenhouse, but with mosquito netting instead of glass.
The MosquitoSphere has six separate compartments, four of which contain West African huts, along with native plants and breeding sites for mosquitoes. The researchers hung a black cotton sheet, previously soaked in sesame oil, on the wall of a hut in each of three chambers.
In one hut, the sesame oil contained genetically engineered fungal spores. In the second hut, the oil contained natural fungal spores. In the third hut, there were no spores at all. Then, they released 1,000 adult male and 500 adult female mosquitoes into each chamber and watched what happened over the next 45 days.
In the hut without spores, the mosquitoes established a stable population of almost 1,400. In the chamber with the natural spores, 450 mosquitoes survived. But, in the chamber with the engineered fungus, the researchers counted just 13 survivors—too few to sustain a viable population.
The researchers say they suspect the fungus would be relatively easy to contain in nature. It’s sticky and not easily airborne. The spores are also extremely sensitive to sunlight, making it difficult for them to travel far. Importantly, the fungus didn’t harm other beneficial insects, including honeybees.
Caution is warranted before considering the release of a genetically engineered organism into the wild. In the meantime, the genetically engineered fungus also will serve as a platform for continued technology development.
The system can be readily adapted to target mosquitoes or other insects , perhaps using different natural toxins if insects might grow resistant to Metarhizium just as they have to traditional insecticides. Interestingly, the researchers note that the engineered fungi appear to make mosquitoes sensitive to chemical insecticides again, suggesting that the two types of insect-killers might be used successfully in combination.
References:
[1] Transgenic Metarhizium rapidly kills mosquitoes in a malaria-endemic region of Burkina Faso. Lovett B, Bilgo E, Millogo SA, Ouattarra AK, Sare I, Gnambani EJ, Dabire RK, Diabate A, St Leger RJ. Science. 2019 May 31;364(6443):894-897.
[2] An entomopathogenic fungus for control of adult African malaria mosquitoes. Scholte EJ, Ng’habi K, Kihonda J, Takken W, Paaijmans K, Abdulla S, Killeen GF, Knols BG. Science. 2005 Jun 10;308(5728):1641-2.
Links:
Transgenic Fungus Rapidly Killed Malaria Mosquitoes in West African Study (University of Maryland News Release)
Malaria (National Institute of Allergy and Infectious Diseases/NIH)
Funnel-Web Spiders (Australian Museum, Sydney)
Video: 2016 Grand Challenges Spotlight Talk: Abdoulaye Diabaté (YouTube)
Raymond St. Leger (University of Maryland, College Park)
NIH Support: National Institute of Allergy and Infectious Diseases
NIH Big Read 2019
Posted on by Dr. Francis Collins
Putting 3D Printing to Work to Heal Spinal Cord Injury
Posted on by Dr. Francis Collins
For people whose spinal cords are injured in traffic accidents, sports mishaps, or other traumatic events, cell-based treatments have emerged as a potential avenue for encouraging healing. Now, taking advantage of advances in 3D printing technology, researchers have created customized implants that may boost the power of cell-based therapies for repairing injured spinal cords.
Made of soft hydrogels that mimic spinal cord tissue, the implant pictured here measures just 2 millimeters across and is about as thick as a penny. It was specially designed to encourage healing in rats with spinal cord injuries. The tiny, open channels that surround the solid “H”-shaped core are designed to guide the growth of new neural extensions, keeping them aligned properly with the spinal cord.
When left on their own, neural cells have a tendency to grow haphazardly. But the 3D-printed implant is engineered to act as a scaffold, keeping new cells directed toward the goal of patching up the injured part of the spinal cord.
For the new work, an NIH-funded research team, led by Jacob Koffler, Wei Zhu, Shaochen Chen, and Mark Tuszynski of the University of California, San Diego (UCSD), used an innovative 3D printing technology called microscale continuous projection printing. This technology relies on a computer projection system and precisely controlled mirrors, which direct light into a solution containing photo-sensitive polymers and cells to produce the final product. Using this approach, the researchers fabricated finely detailed, rodent-sized implants in less than 2 seconds. That’s about 1,000 times faster than a traditional 3D printer!
In a study published recently in Nature Medicine, the researchers placed their custom-made implants, loaded with rat embryonic neural stem cells, into the injured spinal cords of 11 rats. Other rats with similar injuries received empty implants or stem cells without the implant. Within 5 months, rats with the cell-loaded implants had new neural cells bridging the injured area, along with spontaneous regrowth of blood vessels to feed the new neural tissue. Most importantly, they had regained use of their hind limbs. Animals receiving empty implants or cell-based therapy without an implant didn’t show that kind of recovery.
The new findings offer proof-of-principle that 3D printing technology can be used to create implants tailored to the precise shape and size of an injury. In fact, the researchers have already scaled up the process to produce 4-centimeter-sized implants to match several different, complex spinal cord injuries in humans. These implants were printed in a mere 10 minutes.
The UCSD team continues to work on further improvements, including the addition of growth factors or other ingredients that may further encourage neuron growth and functional recovery. If all goes well, the team hopes to launch human clinical trials of their cell-based treatments for spinal cord injury within a few years. And that should provide hope for the hundreds of thousands of people around the world who suffer serious spinal cord injuries each year.
Reference:
[1] Biomimetic 3D-printed scaffolds for spinal cord injury repair. Koffler J, Zhu W, Qu X, Platoshyn O, Dulin JN, Brock J, Graham L, Lu P, Sakamoto J, Marsala M, Chen S, Tuszynski MH. Nat Med. 2019 Feb;25(2):263-269.
Links:
Spinal Cord Injury Information Page (National Institute of Neurological Disorders and Stroke/NIH)
Stem Cell Information (NIH)
Koffler Lab (University of California, San Diego)
Shaochen Chen (UCSD)
Tuszynski Lab (UCSD)
NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Child Health and Human Development
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