Where Are the Lab-Grown Replacement Organs?
The headline blared from newspapers all the way back in 2006: "First Lab-Grown Organs Implanted in Humans!" A team from Wake Forest University had biopsied cells from the bladders of patients with spina bifida and used them to create brand new full-size bladders, which they then implanted. Although the bladders had to be emptied via catheter, they were still functioning a few years after implantation, and the public grew confident that doctors had climbed an intermediary step on the way to the medicine of science fiction. Ten years later, though, more than 20 people a day are still dying while waiting for an organ transplant, which leads to a simple question: Where are our fake organs?
"We can make small organs and tissues but we can't make larger ones."
Not coming anytime soon, unfortunately. The company that was created to transition Wake Forest's bladders to the market failed. And while there are a few simple bioengineered skins and cartilages already on the market, they are hardly identical to the real thing. Something like a liver could take another 20 to 25 years, says Shay Soker, professor at Wake Forest's Institute for Regenerative Medicine. "The first barrier is the technology: We can make small organs and tissues but we can't make larger ones," he says. "Also there are several cell types or functions that you can reliably make from stem cells, but not all of them, so the technology of stem cells has to catch up with what the body can do." Finally, he says, you have support the new organ inside the body, providing it with a circulatory and nervous system and integrating it with the immune system.
While these are all challenging problems, circulation appears to be the most intractable. "Tissue's not able to survive if the cells don't have oxygen, and the bigger it gets, the more complex vasculature you need to keep that alive," says Chiara Ghezzi, research professor in the Tufts University Department of Biomedical Engineering. "Vasculature is highly organized in the body. It has a hierarchical structure, with different branches that have different roles depending on where they are." So far, she says, researchers have had trouble scaling up from capillaries to larger vessels that could be grafted onto blood vessels in a patient's body.
"The FDA is still getting its hands and minds around the field of tissue engineering."
Last, but hardly least, is the question of FDA approval. Lab-grown organs are neither drugs nor medical devices, and the agency is not set up to quickly or easily approve new technologies that don't fit into current categories. "The FDA is still getting its hands and minds around the field of tissue engineering," says Soker. "They were not used to that… so it requires the regulatory and financial federal agencies to really help and support these initiatives."
A pencil eraser-size model of the human brain is now being used for drug development and research.
If all of this sounds discouraging, it's worth mentioning some of the incredible progress the field has made since the first strides toward lab-grown organs began nearly 30 years ago: Though full-size replacement organs are still decades away, many labs have diverted their resources into what they consider an intermediate step, developing miniature organs and systems that can be used for drug development and research. This platform will yield more relevant results (Imagine! Testing cardiovascular drugs on an actual human heart!) and require the deaths of far fewer animals. And it's already here: Two years ago, scientists at Ohio State University developed a pencil eraser-size model of the human brain they intend to use for this exact purpose.
Perhaps the most exciting line of research these days is one that at first doesn't seem to have anything to do with bioengineered organs at all. Along with his colleagues, Chandan Sen, Director of the Center for Regenerative Medicine and Cell-based Therapies at Ohio State University, has developed a nanoscale chip that can turn any cell in the body into any other kind of cell—reverting fully differentiated adult cells into, essentially, stem cells, which can then grow into any tissue you want. Sen has used his chip to reprogram skin cells in the bodies of mice into neurons to help them recover from strokes, and blood vessels to save severe leg injuries. "There's this concept of a bioreactor, where you convince an organ to grow outside the body. They're getting more and more sophisticated over time. But to my mind it will never match the sophistication or complexity of the human body," Sen says. "I believe that in order to have an organ that behaves the way you want it to in the live body, you must use the body itself as a bioreactor, not a bunch of electronic gadgetry." There you have it, the next step in artificial organ manufacture is as crazy as it is intuitive: Grow it back where it was in the first place.
Here's how one doctor overcame extraordinary odds to help create the birth control pill
Dr. Percy Julian had so many personal and professional obstacles throughout his life, it’s amazing he was able to accomplish anything at all. But this hidden figure not only overcame these incredible obstacles, he also laid the foundation for the creation of the birth control pill.
Julian’s first obstacle was growing up in the Jim Crow-era south in the early part of the twentieth century, where racial segregation kept many African-Americans out of schools, libraries, parks, restaurants, and more. Despite limited opportunities and education, Julian was accepted to DePauw University in Indiana, where he majored in chemistry. But in college, Julian encountered another obstacle: he wasn’t allowed to stay in DePauw’s student housing because of segregation. Julian found lodging in an off-campus boarding house that refused to serve him meals. To pay for his room, board, and food, Julian waited tables and fired furnaces while he studied chemistry full-time. Incredibly, he graduated in 1920 as valedictorian of his class.
After graduation, Julian landed a fellowship at Harvard University to study chemistry—but here, Julian ran into yet another obstacle. Harvard thought that white students would resent being taught by Julian, an African-American man, so they withdrew his teaching assistantship. Julian instead decided to complete his PhD at the University of Vienna in Austria. When he did, he became one of the first African Americans to ever receive a PhD in chemistry.
Julian received offers for professorships, fellowships, and jobs throughout the 1930s, due to his impressive qualifications—but these offers were almost always revoked when schools or potential employers found out Julian was black. In one instance, Julian was offered a job at the Institute of Paper Chemistory in Appleton, Wisconsin—but Appleton, like many cities in the United States at the time, was known as a “sundown town,” which meant that black people weren’t allowed to be there after dark. As a result, Julian lost the job.
During this time, Julian became an expert at synthesis, which is the process of turning one substance into another through a series of planned chemical reactions. Julian synthesized a plant compound called physostigmine, which would later become a treatment for an eye disease called glaucoma.
In 1936, Julian was finally able to land—and keep—a job at Glidden, and there he found a way to extract soybean protein. This was used to produce a fire-retardant foam used in fire extinguishers to smother oil and gasoline fires aboard ships and aircraft carriers, and it ended up saving the lives of thousands of soldiers during World War II.
At Glidden, Julian found a way to synthesize human sex hormones such as progesterone, estrogen, and testosterone, from plants. This was a hugely profitable discovery for his company—but it also meant that clinicians now had huge quantities of these hormones, making hormone therapy cheaper and easier to come by. His work also laid the foundation for the creation of hormonal birth control: Without the ability to synthesize these hormones, hormonal birth control would not exist.
Julian left Glidden in the 1950s and formed his own company, called Julian Laboratories, outside of Chicago, where he manufactured steroids and conducted his own research. The company turned profitable within a year, but even so Julian’s obstacles weren’t over. In 1950 and 1951, Julian’s home was firebombed and attacked with dynamite, with his family inside. Julian often had to sit out on the front porch of his home with a shotgun to protect his family from violence.
But despite years of racism and violence, Julian’s story has a happy ending. Julian’s family was eventually welcomed into the neighborhood and protected from future attacks (Julian’s daughter lives there to this day). Julian then became one of the country’s first black millionaires when he sold his company in the 1960s.
When Julian passed away at the age of 76, he had more than 130 chemical patents to his name and left behind a body of work that benefits people to this day.
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.