Just a few blocks from the University of Wisconsin campus, brownstone apartment buildings stand blanketed by snow, cars and bikes lining Spring Street. I’ve hardly passed Union South, but already it feels like I’m in a different world. Stately libraries and academic buildings coagulate to form the university far behind me.

Standing at the corner of Spring Street and Brooks Street is a dark, squat building, unable to claim any description more colorful than “a box of bricks.” It’s out of place, as far from “residential” as it’s possible to be. But I have the address correct. This brick building I stand in front of was the headquarters of WiCell Research Institute in 1999. It is the place where, a little less than twenty years ago, a groundbreaking discovery in medical science took place.

In 1998, a year before the headquarters was established, UW cell biologist James Thomson became the first person to derive human embryonic stem cells — a type of self-replicating cell that, under the right scientific guidance, can be differentiated into other types of cells throughout the body, from the brain to the eye to the heart.

The discovery of this versatile cell that could continually propagate shook the scientific community, as well as the public. Though Thomson’s discovery sparked excitement from the academic community and inspired ideas about medical applications for stem cells, it also attracted its fair share of controversy.

At the time, the abortion debate punctuated headlines across the country. Some felt the application of these cells would be immoral, fearing the cells would eventually become human fetuses used for scientific research.

Scientists, on the other hand, were hopeful about the research’s potential to dramatically improve medical treatments and save lives. So the scientists pushed forward, even as critics claimed they were putting the worth of one life above another.

In order to support the continuation of stem cell research, UW created WiCell, a multifaceted organization that now distributes stem cell lines across the world. But first, the organization had to help develop a space for researchers to work without risk of backlash, Robert Drape, executive director of WiCell, said.

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“There was a concern that all federal funding might be taken away, so WiCell was formed to get the research off campus and then support investigators, help provide space for new technology,” Drape said.

Quickly after the WiCell headquarters was established, UW stem cell research exploded.

UW created the Stem Cell and Regenerative Medicine Center, part of the UW School of Medicine and Public Health.

Today, there are more than 90 faculty members associated with the SCRMC across the UW-System, and the center itself works not only with faculty members and labs but also with the public, conducting outreach and education projects.

Thomson himself became a subject of public attention. When I spoke with him over winter break, he said he was in the press a lot for several years around the founding of WiCell. And though he and his work have since received less media coverage, he said the attention “drowned out the fun of just doing the science.”

Though the anti-abortion movement was wary of Thomson’s discovery, stem cell science nonetheless soon developed in ways that would revolutionize cell and medical science.

A Growing Field

Twenty years later, Thomson is still using stem cells. After deriving the embryonic cells, his team focused on studying their characteristics. Soon, they learned how to grow them more efficiently. Having figured out the optimal culture conditions for the cells, they studied how they replicate and differentiate into forms applicable in different regions of the body.

That led to the therapeutic research they do now. His team is attempting to develop artificial arteries used in transplants for patients with arterial dysfunctions.

Deneen Wellik, a stem cell researcher who studies lung growth and disease, has also witnessed growth in her field. When the chair of the UW Department of Cell and Regenerative Biology received her Ph.D. from UW about 25 years ago, her field didn’t even exist.

Wellik told The Badger Herald stem cell research has changed from using only the basic, embryonic cells Thomson discovered to using specialized stem cells either in vitro or in vivo — inside or outside an organism — to developing medical treatments and cell therapies for patients whose cells don’t always act correctly.  

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“I think an additional focus in the last year has been how we might understand and then manipulate or coax these existing stem and precursor cells into new activities that might be more highly therapeutic,” Wellik said.

Wellik also spoke about the development of UW as a stem cell powerhouse. Funding and grants, she said, can lead to groundbreaking discoveries. She added independent grants that leave the project specifics and direction up to the scientists — the experts in their fields — are often the ones leading to new ideas.

Wellik cited high-risk, high-reward grants that award money to cutting-edge, frontier research. Darcie Moore, UW neuroscience professor, is one researcher on campus who received a grant of this kind recently from the National Institutes of Health.

Moore’s research focuses on aging in brain cells. Since beginning her time at UW in 2016, she has observed how UW and its programs have been evolving to keep up with the rapidly changing field.

“It’s always been an incredibly strong stem cell university, it’s been internationally recognized because of the work of people like Jamie Thomson and Su-Chun Zhang,” Moore said. “I think [UW] is continually involved in the political and ethical ramifications that are involved in this type of research as well, so they are really keeping up with the times and playing a leading role.”

Research and Development

At UW, stem cell researchers come from all disciplines of biology and medical science.

Some are medical doctors working to combat disease and to develop artificial, transplantable organs or pharmaceuticals — others are regenerative biologists studying the brain and neural connections, or the eyes, ears, etc. Some study cells on the molecular level — others are engineers who work to develop clinically applicable products.

Many labs are a combination of disciplines and specialties.

Krishanu Saha is a biomedical engineer. He works with genes, using stem cell models to test their response to different viruses in hopes of developing new cell therapies. Like Wellik, he also sees stem cell science changing, especially to keep up with new technological developments in computer sciences.

“Overall, there are more engineers working with stem cells,” Saha said. “The field has become more quantitative, much like other areas of biology. The measurements that we can do nowadays with the stem cell culture can arguably track every single transcript in every single cell at many time points. That really was not feasible twenty years ago.”

Saha said he works with machine-learning specialists to understand patterns within his data and develop his research. This also means that many of the new trainees in his lab learn new computational methods to apply to the biological work they do. Their hope is to eventually develop clinically applicable therapies using their research.

Like Saha, Eric Shusta is also a biomedical engineer. He works with stem cells in drug development, taking advantage of the fact that embryonic cells prove to be an efficient test material for creating medical treatments and drugs that could be used on humans. He explained that stem cells can help predict a chemical’s effect on a human in ways that animal-testing alone cannot.

“Humans are not mice or rats, and often many drugs fail that work in a mouse, but not then subsequently in a human,” Shusta said. “So the idea here is we’ve got this bridge going from mice to a human clinical trial.”

When stem cell research brings to life therapies or pharmaceuticals like Saha and Shusta work on, UW has resources to aid the researchers in patenting and clinically developing their innovations. The main UW organization helping researchers take that next step is the Wisconsin Alumni Research Foundation.

WARF is a patenting entity that works on licensing and supporting UW research developments, especially when those developments move to clinical trials and commercial applications. Senior licensing manager Andy DeTienne spoke about a sharp increase in the development of therapeutic projects utilizing stem cells.

“[We’ve seen] a strong move in the therapeutic development area toward clinical trials,” DeTienne said. “For many, many years there were only one or two clinical trials utilizing stem cells as the base material for those trials, now there’s been an increase in that over the last couple of years.”

Into the Future

Considering all the strides stem cell research has made in the last 20 years, the researchers the Herald talked to all sounded excited about potential pharmaceuticals, transplants and cell therapies that could use stem cells to dramatically improve the medical field.

Wellik draws on her observation that the field has trended more toward the study of endogenous stem cells in the years since Thomson’s discovery. These are tissue-specific cells, meaning that they are — while fundamental and unspecific — especially medically applicable on certain kinds of body tissues.

Moving forward, Wellik predicts more researchers will begin to focus on coaxing these cells to differentiate in ways that could prove highly effective as medical treatments. She also foresees researchers attempting to culture embryonic stem cells with different cell types to develop new therapies.

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“I think together those approaches are going to lead to extremely significant insights and abilities to manipulate populations,” Wellik said. “Not just by transplanting them, but by learning how to coax them into new activities in organisms — to try and repair, or improve maintenance or cure disease.”

Shusta, however, suggested that biomedical engineers like himself may have a different vision for the future of stem cells than regenerative biologists like Wellik. Shusta added while regenerative biologists may focus more on developing therapies, he focuses on the role of stem cells in clinical pharmaceutical trials and drug development.

Because of that, Shusta said he sees stem cell labs expanding to biotech and pharmaceutical companies, especially since companies without their own labs usually contract outside companies to run stem cell tests for them. He also predicts stem cells becoming a link between preclinical tests and clinical trials.

“I think it’s going to be an integral tool in all drug development,” Shusta said. “There’s been a big transition on that over the last few years, and I think we’re going to see that continue as the ability to model different cell types in a dish using [differentiable] stem cells gets more and more routine.”

Researchers and commercial organizations will likely take stem cells to new heights and in new directions, and WiCell is expected to grow and change alongside them — just as they have in the past — Drape said.

Once a small brick lab building on Spring Street, WiCell is now an international cell bank that distributes Thomson’s five original lines of embryonic stem cells all over the world.

Though Tenneille Ludwig, head scientist at WiCell and a former researcher in Thomson’s lab, said she can’t necessarily predict WiCell’s specific functions twenty years from now, she believes one thing has remained constant: WiCell has supported stem cell research from the beginning, and it’s expecting to do the same in the coming years.

“We’re on that fine line between academia and industry, which gives us the ability to be nimble,” Ludwig said. “I expect that we will change in whatever way the university needs us to, to support the work that they do.”

Outreach and Education

Ever since Thomson’s initial and controversial discovery, scientists have had difficulty communicating their work to the public. Wellik said this difficulty may sometimes lead to a lack of public enthusiasm toward their work.

Though in Wellik’s experience, the public is very open to the idea of less invasive, less painful medical treatments  — the eventual goal of most stem cell research — it’s often difficult for scientists to provide information about the highly technical research behind them.

“I think there are opportunities to communicate [this research], but I don’t know what the best ways are,” Wellik said. “It’s a very important question that I think deserves a lot of time and attention. I think that our field would be aided greatly by an enhanced ability to communicate with the public.”

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Moore said that often, new developments seem scary to the public because they open up many new questions. The public raises — sometimes very valid — questions and concerns about the ethical ramifications behind research projects.

She said scientists and professionals at the university are always trying to answer these questions and address these concerns — as they should — but the public doesn’t always understand that researchers are motivated by good intentions.

“Scientists are generally cautious,” Moore said. “There might be a few rogues out there, but typically we are people who are trying to understand science, and get the most useful knowledge that can be used to treat people without causing harm.”

In response to skepticism as such, Moore’s lab, the SCRMC and several other researchers the Herald spoke with engage in public outreach. This work exposes people to and provides information on stem cell research to increase public understanding of the field. The public outreach, Wellik said, often includes a service project that applies the research to help others in the community.

Moore described the importance of outreach regarding not only education but also policy implementation. She said research cannot help anyone if people are unaware of it, or if they’re scared of its potential ramifications.

“Outreach and helping communicate the science to all people is actually very critical,” Moore said. “Because if we do things and no one is aware of what that is, or if they’re unaware of the science behind it, then it will actually never be implemented in any way to be beneficial to others.”

Wellik said that outreach and science communication are what allow discoveries like Thomson’s to positively impact the public. Imagine if the university hadn’t created WiCell 20 years ago and if Thomson’s lab had lost their funding.

Science evolves every day — sometimes slowly, with small steps, sometimes with great leaps. But experts like Moore and Wellik said both researchers and the public must learn to communicate and cooperate. Where stem cell science will be in twenty years is difficult to predict, for Thomson’s groundbreaking discovery itself was unpredictable.

“It is often the unexpected finding of one individual or a small group of individuals that fundamentally changes our understanding and/or our ability to do research,” Wellik said. “Jamie Thomson’s discovery twenty years ago is one of the perfect examples.”