The Northern white rhinoceros Nola, the last one in the U.S. at that time in 2015, pictured here with author Jeanne Loring and Oliver Ryder (in truck), with a film crew and keepers in the San Diego Zoo's savanna. Nola sadly passed away that year.
Because of human activities that destroy habitats, creatures are now becoming extinct at a rate that is higher than any previously experienced. Some animals, like the giant panda and the California condor, have been pulled back from the brink of extinction by conserving their habitats, breeding in captivity, and educating the public about their plight.
But not the northern white rhino. This gentle giant is a vegetarian that can weigh up to 5,000 pounds. The rhino's weakness is its horn, which has become a valuable commodity because of the mistaken idea that it grants power and has medicinal value. Horns are not medicine; the horns are made of keratin, the same protein that is in fingernails. But as recently as 2017 more than 1,000 rhinos were slaughtered each year to harvest their horns.
All 6 rhino species are endangered. But the northern white has been devastated. Only two members of this species are alive now: Najin, age 32, and her daughter Fatu, 21, live in a protected park in Kenya. They are social animals and would prefer the company of other rhinos of their kind; but they can't know that they are the last two survivors of their entire species. No males exist anymore. The last male, Sudan, died in 2018 at age 45.
We are celebrating a huge milestone in the efforts to use stem cells to rescue the rhino.
I became involved in the rhino rescue project on a sunny day in February, 2008 at the San Diego Wild Animal Park in Escondido, about 30 miles north of my lab in La Jolla. My lab had relocated a couple of months earlier to Scripps Research Institute to start the Center for Regenerative Medicine for human stem cell research. To thank my staff for their hard work, I wanted to arrange a special treat. I contacted my friend Oliver Ryder, who is director of the Institute for Conservation Research at the zoo, to see if I could take them on a safari, a tour in a truck through the savanna habitat at the park.
This was the first of the "stem cell safaris" that the lab would enjoy over the next few years. On the safari we saw elands and cape buffalo, and fed giraffes and rhinos. And we talked about stem cells; in particular, we discussed a surprising technological breakthrough recently reported by the Japanese scientist Shinya Yamanaka that enabled conversion of ordinary skin cells into pluripotent stem cells.
Pluripotent stem cells can develop into virtually any cell type in the body. They exist when we are very young embryos; five days after we were just fertilized eggs, we became blastocysts, invisible tiny balls of a few hundred cells packed with the power to develop into an entire human being. Long before we are born, these cells of vast potential transform into highly specialized cells that generate our brains, our hearts, and everything else.
Human pluripotent stem cells from blastocysts can be cultured in the lab, and are called embryonic stem cells. But thanks to Dr. Yamanaka, anyone can have their skin cells reprogrammed into pluripotent stem cells, just like the ones we had when we were embryos. Dr. Yamanaka won the Nobel Prize for these cells, called "induced pluripotent stem cells" (iPSCs) several years later.
On our safari we realized that if we could make these reprogrammed stem cells from human skin cells, why couldn't we make them from animals' cells? How about endangered animals? Could such stem cells be made from animals whose skin cells had been being preserved since the 1970s in the San Diego Zoo's Frozen Zoo®? Our safari leader, Oliver Ryder, was the curator of the Frozen Zoo and knew what animal cells were stored in its giant liquid nitrogen tanks at −196°C (-320° F). The Frozen Zoo was established by Dr. Kurt Benirschke in 1975 in the hope that someday the collection would aid in rescue of animals that were on the brink of extinction. The frozen collection reached 10,000 cell lines this year.
We returned to the lab after the safari, and I asked my scientists if any of them would like to take on the challenge of making reprogrammed stem cells from endangered species. My new postdoctoral fellow, Inbar Friedrich Ben-Nun, raised her hand. Inbar had arrived only a few weeks earlier from Israel, and she was excited about doing something that had never been done before. Oliver picked the animals we would use. He chose his favorite animal, the critically endangered northern white rhinoceros, and the drill, which is an endangered primate related to the mandrill monkey,
When Inbar started work on reprogramming cells from the Frozen Zoo, there were 8 living northern rhinoceros around the world: Nola, Angalifu, Nesari, Nabire, Suni, Sudan, Najin, and Fatu. We chose to reprogram Fatu, the youngest of the remaining animals.
Through sheer determination and trial and error, Inbar got the reprogramming technique to work, and in 2011 we published the first report of iPSCs from endangered species in the scientific journal Nature Methods. The cover of the journal featured a drawing of an ark packed with animals that might someday be rescued through iPSC technology. By 2011, one of the 8 rhinos, Nesari, had died.
This kernel of hope for using iPSCs to rescue rhinos grew over the next 10 years. The zoo built the Rhino Rescue Center, and brought in 6 females of the closely related species, the southern white rhinoceros, from Africa. Southern white rhino populations are on the rise, and it appears that this species will survive, at least in captivity. The females are destined to be surrogate mothers for embryos made from northern white rhino cells, when eventually we hope to generate sperm and eggs from the reprogrammed stem cells, and fertilize the eggs in vitro, much the same as human IVF.
The author, Jeanne Loring, at the Rhino Rescue Center with one of the southern white rhino surrogates.
David Barker
As this project has progressed, we've been saddened by the loss of all but the last two remaining members of the species. Nola, the last northern white rhino in the U.S., who was at the San Diego Zoo, died in 2015.
But we are celebrating a huge milestone in the efforts to use stem cells to rescue the rhino. Just over a month ago, we reported that by reprogramming cells preserved in the Frozen Zoo, we produced iPSCs from stored cells of 9 northern white rhinos: Fatu, Najin, Nola, Suni, Nadi, Dinka, Nasima, Saut, and Angalifu. We also reprogrammed cells from two of the southern white females, Amani and Wallis.
We don't know when it will be possible to make a northern white rhino embryo; we have to figure out how to use methods already developed for laboratory mice to generate sperm and eggs from these cells. The male rhino Angalifu died in 2014, but ever since I saw beating heart cells derived from his very own cells in a culture dish, I've felt hope that he will one day have children who will seed a thriving new herd of northern white rhinos.
Dr. May Edward Chinn, Kizzmekia Corbett, PhD., and Alice Ball, among others, have been behind some of the most important scientific work of the last century.
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.
Alice Ball
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.
Henrietta Lacks
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
Andre 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
TIME Magazine
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.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013. He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
Show links
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business
