Stem Cell Agency celebrates 50 clinical trials with patient #1

Yesterday the CIRM Board approved funding for our 50th clinical trial (you can read about that here) It was an historic moment for us and to celebrate we decided to go back in history and hear from the very first person to be treated in a CIRM-funded clinical trial. Rich Lajara was treated in the Geron clinical trial after experiencing a spinal cord injury, thus he became CIRM’s patient #1. It’s a badge he says he is honored to wear. This is the speech Rich made to our Board.

Rich Lajara

Hello and good afternoon everyone. It’s an honor to be here today as the 50th clinical trial has been officially funded by CIRM. It was feels like it was just yesterday that I was enrolled into the first funded clinical trial by CIRM and in turn became California’s’ 1st embryonic stem cell patient.

I became paralyzed from the waist down in September 2011. It was Labor Day and I was at a river with some close friends. There was this natural granite rock slide feature next to a waterfall, it was about 60 feet long; all you had to do was get a bucket of water to get the rocks wet and slide down into a natural pool. I ended up slipping and went down head first backwards but was too far over and I slid off a 15’ ledge where the waterfall was. I was pulled from the water and banged up pretty bad. Someone said “look at that deformity on his back” and tapped my leg and asked if I could feel that. I knew immediately I was paralyzed. I thought this was the end, little did I know this was just the beginning. I call it being in the wrong place at the right time.

So, after a few days in the hospital of course everyone, as well as myself, wanted a cure. We quickly learned one didn’t exist. A close family friend had been making phone calls and was able to connect with the Christopher & Dana Reeve Foundation and learned about a clinical trial with “stem cells”. One of my biggest question was how any people have done this? “Close to none”, I was told.

I was also told I most likely would have no direct benefit as this was a safety trial? So why do it at all? Obviously at that time I was willing to overlook the “most likely” part because I was willing to do anything to try and get my normal life back.

Looking back the big picture was laying the ground work for others like Kris or Jake (two people enrolled in a later version of this trial). At the time I had no clue that what I was doing would be such a big deal. The data collected from me would end up being priceless. It’s stories like Jake’s and Kris’ that make me proud and reinforce my decision to have participated in California’s first stem cell clinical trial funded by prop 71.

Like I said earlier it was just the beginning for me. A couple of years later I became a patient advocate working with Americans for Cures. I have been able to meet many people in the stem cell industry and love to see the glow in their face when they learn I was California’s first embryonic stem cell patient.

I can’t even fathom all the year’s of hard work and countless hours of research that had lead up to my long anticipated surgery, but when I see their glowing smile I know they knew what it took.

I also enjoy sharing my story and bridging the gap between myths and facts about stem cells, or talking to students and helping inspire the next generation that will be in the stem cell industry.  As a matter of fact, I have 13 year old sister, Maddie, dead set on being a neurosurgeon.

Fast forward to today. Life in a wheelchair is not exactly a roll in the park (no pun intended) but I have grown accustomed to the new normal. Aside from some neuropathic pain, life is back on track.

Not once did I feel sorry for myself, I was excited to be alive. Sure I have bad days but don’t we all.

In the last 14 years CIRM has funded 50 human clinical trials, published around 2750 new peer-reviewed scientific discoveries, and they’ve transformed California into the world leader in stem cell research. As I look around the posters on the wall, of the people whose lives have been transformed by the agency, I can’t help but be struck by just how much has been achieved in such a short period of time.

While my journey might not yet be over, Evie and 40 other children like her, (children born with SCID) will never remember what it was like to live with the horrible condition they were born with because they have been cured thanks to CIRM. There are hundreds of others whose lives have been transformed because of work the agency has funded.

CIRM has proven how much can be achieved if we invest in cutting-edge medical research.

As most of you here probably know CIRM’s funding from Proposition 71 is about to run out. If I had just one message I wanted people to leave with today it would be this. Everyone in this room knows how much CIRM has done in a little over a decade and how many lives have been changed because of its existence. We have the responsibility to make sure this work continues. We have a responsibility to make sure that the stories we’ve heard today are just the beginning.

I will do everything I can to make sure the agency gets refunded and I hope that all of you will join me in that fight. I’m excited for the world of stem cells, particularly in California, and can’t wait to see what’s on the horizon.

 

Using laughter to help find a treatment for Alzheimer’s

Alzheimer's

In 1983, when President Ronald Reagan designated an annual National Alzheimer’s Disease Awareness Month fewer than two million Americans had Alzheimer’s. Today, that number is close to 5.5 million and estimates suggest it will rise to 16 million by 2050. There are no treatments. No cure. But around the globe people are working hard to change that.

At CIRM we have invested more than $60 million in 21 projects aimed at developing a deeper understanding of the disease and, we hope, one day developing effective treatments.

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Lauren Miller Rogen

One of those helping lead that fight is our Board member Lauren Miller Rogen. Lauren has a family history of the disease and uses that to fuel her activism not just on our Board but through Hilarity for Charity, the organization she co-founded with her husband, Seth Rogen.

Lauren was recently profiled by the stem cell advocacy group Americans for Cures, talking about the impact the disease has had on her family, her advocacy on behalf of families struggling to cope with the disease and why she feels humor is such a powerful tool to raise awareness and hope in the fight against Alzheimer’s.

It’s a great interview and you can read it here.

Caught our eye: new Americans 4 Cures video, better mini-brains reveal Zika insights and iPSC recipes go head-to-head

How stem cell research gives patients hope (Karen Ring).
You can learn about the latest stem cell research for a given disease in seconds with a quick google search. You’ll find countless publications, news releases and blogs detailing the latest advancements that are bringing scientists and clinicians closer to understanding why diseases happen and how to treat or cure them.

But one thing these forms of communications lack is the personal aspect. A typical science article explains the research behind the study at the beginning and ends with a concluding statement usually saying how the research could one day lead to a treatment for X disease. It’s interesting, but not always the most inspirational way to learn about science when the formula doesn’t change.

However, I’ve started to notice that more and more, institutes and organizations are creating videos that feature the scientists/doctors that are developing these treatments AND the patients that the treatments could one day help. This is an excellent way to communicate with the public! When you watch and listen to a patient talk about their struggles with their disease and how there aren’t effective treatments at the moment, it becomes clear why funding and advancing research is important.

We have a great example of a patient-focused stem cell video to share with you today thanks to our friends at Americans for Cures, a non-profit organization that advocates for stem cell research. They posted a new video this week in honor of Stem Cell Awareness Day featuring patients and patient advocates responding to the question, “What does stem cell research give you hope for?”. Many of these patients and advocates are CIRM Stem Cell Champions that we’ve featured on our website, blog, and YouTube channel.

Americans for Cures is encouraging viewers to take their own stab at answering this important question by sharing a short message (on their website) or recording a video that they will share with the stem cell community. We hope that you are up for the challenge!

Mini-brains help uncover some of Zika’s secrets (Kevin McCormack).
One of the hardest things about trying to understand how a virus like Zika can damage the brain is that it’s hard to see what’s going on inside a living brain. That’s not surprising. It’s not considered polite to do an autopsy of someone’s brain while they are still using it.

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Microscopic image of a mini brain organoid, showing layered neural tissue and different groups of neural stem cells (in blue, red and magenta) giving rise to neurons (green). Image: Novitch laboratory/UCLA

But now researchers at UCLA have come up with a way to mimic human brains, and that is enabling them to better understand how Zika inflicts damage on a developing fetus.

For years researchers have been using stem cells to help create “mini brain organoids”, essentially clusters of some of the cells found in the brain. They were helpful in studying some aspects of brain behavior but limited because they were very small and didn’t reflect the layered complexity of the brain.

In a study, published in the journal Cell Reports, UCLA researchers showed how they developed a new method of creating mini-brain organoids that better reflected a real brain. For example, the organoids had many of the cells found in the human cortex, the part of the brain that controls thought, speech and decision making. They also found that the different cells could communicate with each other, the way they do in a real brain.

They used these organoids to see how the Zika virus attacks the brain, damaging cells during the earliest stages of brain development.

In a news release, Momoko Watanabe, the study’s first author, says these new organoids can open up a whole new way of looking at the brain:

“While our organoids are in no way close to being fully functional human brains, they mimic the human brain structure much more consistently than other models. Other scientists can use our methods to improve brain research because the data will be more accurate and consistent from experiment to experiment and more comparable to the real human brain.”

iPSC recipes go head-to-head: which one is best?
In the ten years since the induced pluripotent stem cell (iPSC) technique was first reported, many different protocols, or recipes, for reprogramming adult cells, like skin, into iPSCs have been developed. These variations bring up the question of which reprogramming recipe is best. This question isn’t the easiest to answer given the many variables that one needs to test. Due to the cost and complexity of the methods, comparisons of iPSCs generated in different labs are often performed. But one analysis found significant lab-to-lab variability which can really muck up the ability to make a fair comparison.

A Stanford University research team, led by Dr. Joseph Wu, sought to eliminate these confounding variables so that any differences found could be attributed specifically to the recipe. So, they tested six different reprogramming methods in the same lab, using cells from the same female donor. And in turn, these cells were compared to a female source of embryonic stem cells, the gold standard of pluripotent stem cells. They reported their findings this week in Nature Biomedical Engineering.

Previous studies had hinted that the reprogramming protocol could affect the ability to fully specialize iPSCs into a particular cell type. But based on their comparisons, the protocol chosen did not have a significant impact on how well iPSCs can be matured. Differences in gene activity are a key way that researchers do side-by-side comparisons of iPSCs and embryonic stem cells. And based on the results in this study, the reprogramming method itself can influence the differences. A gene activity comparison of all the iPSCs with the embryonic stem cells found the polycomb repressive complex – a set of genes that play an important role in embryonic development and are implicated in cancer – had the biggest difference.

In a “Behind the Paper” report to the journal, first author Jared Churko, says that based on these findings, their lab now mostly uses one reprogramming protocol – which uses the Sendai virus to deliver the reprogramming genes to the cells:

“The majority of our hiPSC lines are now generated using Sendai virus. This is due to the ease in generating hiPSCs using this method as well as the little to no chance of transgene integration [a case in which a reprogramming gene inserts into the cells’ DNA which could lead to cancerous growth].”

Still, he adds a caveat that the virus does tend to linger in the cells which suggests that:

“cell source or reprogramming method utilized, each hiPSC line still requires robust characterization prior to them being used for downstream experimentation or clinical use.”

 

Trash talking and creating a stem cell community

imilce2

Imilce Rodriguez-Fernandez likes to talk trash. No, really, she does. In her case it’s cellular trash, the kind that builds up in our cells and has to be removed to ensure the cells don’t become sick.

Imilce was one of several stem cell researchers who took part in a couple of public events over the weekend, on either side of San Francisco Bay, that served to span both a geographical and generational divide and create a common sense of community.

The first event was at the Buck Institute for Research on Aging in Marin County, near San Francisco. It was titled “Stem Cell Celebration” and that’s pretty much what it was. It featured some extraordinary young scientists from the Buck talking about the work they are doing in uncovering some of the connections between aging and chronic diseases, and coming up with solutions to stop or even reverse some of those changes.

One of those scientists was Imilce. She explained that just as it is important for people to get rid of their trash so they can have a clean, healthy home, so it is important for our cells to do the same. Cells that fail to get rid of their protein trash become sick, unhealthy and ultimately stop working.

Imilce is exploring the cellular janitorial services our bodies have developed to deal with trash, and trying to find ways to enhance them so they are more effective, particularly as we age and those janitorial services aren’t as efficient as they were in our youth.

Unlocking the secrets of premature aging

Chris Wiley, another postdoctoral researcher at the Buck, showed that some medications that are used to treat HIV may be life-saving on one level, preventing the onset of full-blown AIDS, but that those benefits come with a cost, namely premature aging. Chris said the impact of aging doesn’t just affect one cell or one part of the body, but ripples out affecting other cells and other parts of the body. By studying the impact those medications have on our bodies he’s hoping to find ways to maintain the benefits of those drugs, but get rid of the downside.

Creating a Community

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Across the Bay, the U.C. Berkeley Student Society for Stem Cell Research held it’s 4th annual conference and the theme was “Culturing a Stem Cell Community.”

The list of speakers was a Who’s Who of CIRM-funded scientists from U.C. Davis’ Jan Nolta and Paul Knoepfler, to U.C. Irvine’s Henry Klassen and U.C. Berkeley’s David Schaffer. The talks ranged from progress in fighting blindness, to how advances in stem cell gene editing are cause for celebration, and concern.

What struck me most about both meetings was the age divide. At the Buck those presenting were young scientists, millennials; the audience was considerably older, baby boomers. At UC Berkeley it was the reverse; the presenters were experienced scientists of the baby boom generation, and the audience were keen young students representing the next generation of scientists.

Bridging the divide

But regardless of the age differences there was a shared sense of involvement, a feeling that regardless of which side of the audience we are on we all have something in common, we are all part of the stem cell community.

All communities have a story, something that helps bind them together and gives them a sense of common purpose. For the stem cell community there is not one single story, there are many. But while those stories all start from a different place, they end up with a common theme; inspiration, determination and hope.

 

A visual guide on using stem cells to treat blindness

Some stories are so sweet or powerful or wonderful – or all three – that they just stick in your mind.

Rosalinda Barrero

Rosalinda Barrero

About 18 months ago Rosalinda and German Barrero came to talk to the CIRM Board about retinitis pigmentosa (RP), a devastating genetic disease that slowly destroys a person’s vision. Contrary to what everyone expected to hear, German said that he was grateful that Rosalinda had RP for one reason: that was how he met her! He said he was in his car, waiting to pick someone up when Rosalinda opened his car door and got in. She was apparently waiting to be picked up, and assumed the car that stopped right in front of her was her then boyfriend. It wasn’t her boyfriend. But the man inside, German, eventually became her husband.

You can see Rosalinda and German talking about RP here.

I think of that love story every time I hear about a new treatment or approach to treating RP, hoping that this will be the one that restores Rosalinda’s vision. Right now we are funding one of the most promising of those approaches with Henry Klassen at the University of California, Irvine, using stem cells to replace the cells destroyed by RP.

Klassen’s work is fascinating, and a new whiteboard video by our friends at Youreka Science and Americans for Cures helps explain what he’s trying to do and why this work could not only benefit people like Rosalinda, but others with vision or neurological problems as well.

It’s a simple, wonderfully visual way of leading you along, step-by-step, and explaining complex science in an engaging and, dare I say, fun way.

But the best thing about it, is that it highlights a treatment that could lead to an even happier ending for Rosalinda and German’s story.

By the way, the video was produced as part of the Americans for Cures Foundation’s Report Back to the Public program. For more information check out the Americans for Cures website.


Related Links:

HIV/AIDS: Progress and Promise of Stem Cell Research

Our friends at Americans for Cures and Youreka Science have done it again. They’ve produced another whiteboard video about the progress and promise of stem cell research that’s so inspiring that it would probably make Darth Vader consider coming back to the light side. This time they tackled HIV.

If you haven’t watched one of these videos already, let me bring you up to speed. Americans for Cures is a non-profit organization, the legacy of the passing of Proposition 71, that supports patient advocates in the fight for stem cell research and cures. They’ve partnered with Youreka Science to produce eye-catching and informative videos to teach patients and the general public about the current state of stem cell research and the quest for cures for major diseases.

Stem cell cure for HIV?

Their latest video is on HIV, a well-known and deadly virus that attacks and disables the human immune system. Currently, 37 million people globally are living with HIV and only a few have been cured.

The video begins with the story of Timothy Brown, also known as the Berlin patient. In 2008 at the age of 40, he was dying of a blood cancer called acute myeloid leukemia and needed a bone marrow stem cell transplant to survive. Timothy was also HIV positive, so his doctor decided to use a bone marrow donor who happened to be naturally resistant to HIV infection. The transplanted donor stem cells were not only successful in curing Timothy of his cancer, but they also “rebooted his immune system” and cured his HIV.

Screen Shot 2015-12-23 at 2.21.18 PMSo why haven’t all HIV patients received this treatment? The video goes on to explain that bone marrow transplants are dangerous and only used in cancer patients who’ve run out of options. Additionally, only a small percentage of the world’s population is resistant to HIV and the chances that one of these individuals is a bone marrow donor match to a patient is very low.

This is where science comes to the rescue. Three research groups in California, all currently supported by CIRM funding, have proposed alternative solutions: they are attempting to make a patient’s own immune system resistant to HIV instead of relying on donor stem cells. Using gene therapy, they are modifying blood stem cells from HIV patients to be HIV resistant, and then transplanting the modified stem cells back into the same patient to rebuild a new immune system that can block HIV infection.

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All three groups have proven their stem cell technology works in animals; two of them are now testing their approach in early phase clinical trials in humans, and one is getting ready to do so. If these trials are successful, there is good reason to hope for an HIV cure and maybe even cures for other immune diseases.

My thoughts…

What I liked most about this video was the very end. It concludes by saying that these accomplishments were made possible not just by funding promising scientific research, but also by the hard work of HIV patients and patient advocate communities, who’ve brought awareness to the disease and influenced policy changes. Ultimately, a cure for HIV will depend on researchers and patient advocates working together to push the pace and to tackle any obstacles that will likely appear with testing stem cell therapies in human clinical trials.

I couldn’t say it any better than the final line of the video:

“We must remember that human trials will celebrate successes, but barriers will surface along with complications and challenges. So patience and understanding of the scientific process are essential.”

The Critical Role of Patient Advocates in Accelerating Stem Cell Cures

At CIRM, our goal is to bring stem cell therapies to patients with unmet medical needs, and we do that by funding the most promising and innovative research in regenerative medicine. A critical component of this goal is to support our patient advocates and make sure that their voices are heard.

At this year’s World Stem Cell Summit, patient advocates from around the world, representing a breadth of diseases and disorders, came together to share their stories, goals, and needs with the larger scientific community.

One session that particularly stood out, was “Accelerating Cures: The Critical Role of Patient Advocates” on Day 3 of the conference. This panel featured key leaders in patient advocacy:

  • Don Reed, the “Grandfather of Stem Cell Research Advocacy”, Vice President of Public Policy at the Americans for Cures Foundation
  • Frances Saldaña, an advocate for Huntington’s disease (HD) and founder of HD-Care at UC Irvine, which is a support group to advance HD research and clinical care
  • Tory Williams, the Executive Director of the Alabama Institute of Medicine (AIM) which raises funds and awareness for stem cell treatments and cures of disease and injury and the author of “Inevitable Collision

The panel was moderated by our fearless leader and head of communications, Kevin McCormack. Each speaker shared their story about how they became a patient advocate and what they are currently doing to push the pace of stem cell research.

Don Reed, Kevin McCormack, Frances Saldana, Tory Williams.

Don Reed, Kevin McCormack, Frances Saldana, Tory Williams.

Don Reed described the heartbreaking story of his son Roman Reed, who suffered a severe spinal cord injury while playing football. Through Don and Roman’s relentless efforts, “Roman’s Law” was passed in 1999, which raised $17 million in California state funding for spinal cord injury research. Don was also a key instigator for the passage of Proposition 71, which gave $3 billion dollars to our agency to fund stem cell research. He continues to be a passionate advocate for stem cell research and spinal cord injury patients, and recently published a book called “Stem Cell Battles: Proposition 71 and Beyond” which you can read more about in our recent blog.

Next, Frances Saldana told a compelling story of raising a family of three beautiful children with a husband who had Huntington’s disease. Unaware of his condition when they were together, Frances’ world took a devastating turn when he died of HD, leaving her to question whether her children would face the same fate. Sadly, all three of Frances’s kids carried the HD mutation. Having to deal with the passing of her two daughters, and a son who is battling the end stages of this disease, Frances decided to share her experience with others and to create a support organization called HD-Care so that others wouldn’t have to face similar experiences alone. HD-Care is conducting an aggressive campaign to bring visibility to HD and supports cutting-edge research in the field including the work done by CIRM-grantee Dr. Leslie Thompson at UC Irvine.

Frances told the audience that her happiest moment since this all began was when her daughter Margie, already suffering from symptoms of HD, spoke at CIRM in 2007. She saw the Board and the scientists and thought, “somebody cares, and somebody will find a cure.” It was a new chapter for her, she explained, and she knew something good was going to happen.

Lastly, Tory Williams, introduced the Alabama Institute of Medicine, which is a non-profit organization that supports the stem cell community with education and public dialogue. She started the institute following both personal and family experiences with cancer and after TJ Atchinson, a close family friend, suffered a severe spinal cord injury. Along the way, she forged a close relationship with Roman Reed who helped her pass TJ’s law in 2013, which is an Alabama state law that promotes spinal cord injury research.

“The goal [of AIM],” said Williams, “is to make a difference in people’s lives affected by disease and injury by helping to advance medicine to eradicate these debilitating issues.”

Laurel Barchas, Student Society for Stem Cell Research

Laurel Barchas, Student Society for Stem Cell Research

When the session was opened up to questions, the atmosphere in the room turned electric. Patients and scientists stood up to tell their stories and asked hard questions. One question came from Laurel Barchas, one of the founders of the Student Society for Stem Cell Research, who asked how we as a society can advocate for mental illness and similar diseases where the symptoms are not visible and where patients are either embarrassed or hesitant to make their disease public. Another question was how emerging countries like Mexico who don’t have the same benefits and infrastructure as the US can promote and support patient advocacy.

The mood of the advocates was positive but measured. They know that new treatments and cures take time but they also pointed out that many people don’t have much time so we have to work as hard as we can to help them.

The panel ended with the consensus that the voices of patient advocates are invaluable, and that they will be the key to accelerating stem cell therapies into cures. Frances Saldaña urged other patient advocates that the key to progress is to be aggressive, and be unafraid to be out there. Don Reed concluded on a similar note with quote from Shakespeare’s Hamlet:

“Whether ’tis Nobler in the mind to suffer

The Slings and Arrows of outrageous Fortune,

Or to take Arms against a Sea of troubles,

And by opposing end them.”


Related links:

Type 1 Diabetes Trial Explained Whiteboard Video Style

There’s a saying, a picture is worth a thousand words. With complicated science however, pictures don’t always do these topics justice. Here’s where videos come to the rescue.

Florie Mar, founder of Youreka Science.

Florie Mar, founder of Youreka Science.

Today’s topic is type 1 diabetes and a CIRM-funded clinical trial headed by the San Diego company ViaCyte hoping to develop a cure for patients with this disease. Instead of writing an entire blog about the latest on this clinical trial, we are featuring an excellent video by Youreka Science. This nonprofit organization is the brainchild of former University of California, San Francisco graduate student Florie Mar who has a passion to bring scientific concepts to life to reach both students and the general public.

Youreka’s style uses whiteboard videos to explain disease and basic science research with drawings, words, and lay person-friendly narrative. This particular video, “Progress and Promise of Stem Cell Research: Type 1 Diabetes” was developed in collaboration with Americans for Cures and explains how CIRM-funded stem cell research is “leading to groundbreaking advances in diabetes.”

We are also excited about this ViaCyte trial as it’s being conducted in one of the CIRM Alpha Stem Cell Clinics located at the University of California, San Diego. The goal of the Alpha Clinics is to accelerate the development and delivery of stem cell therapies to patients by providing stem-cell focused clinics for conducting high quality trials.

In brief, the video explains ViaCyte’s stem cell derived therapy that replaces the insulin-producing cells that are lost in type 1 diabetes patients. For more details, check out the video!

 

And to hear from Viacyte’s chief scientific officer as well as two people living with type 1 diabetes, check out a CIRM video we produced a few years ago.


Related Links:

Seeing is believing: using video to explain stem cell science

People are visual creatures. So it’s no surprise that many of us learn best through visual means. In fact a study by the Social Science Research Network found that 65 percent of us are visual learners.

That’s why videos are such useful tools in teaching and learning, and that’s why when we came across a new video series called “Reaping the rewards of stem cell research” we were pretty excited. And to be honest there’s an element of self-interest here. The series focuses on letting people know all about the research funded by CIRM.

We didn’t make the videos, a group called Youreka Science is behind them. Nor did we pay for them. That was done by a group called Americans for Cures (the group is headed by Bob Klein who was the driving force behind Proposition 71, the voter-approved initiative that created the stem cell agency). Nonetheless we are happy to help spread the word about them.

The videos are wonderfully simple, involving just an engaging voice, a smart script and some creative artwork on a white board. In this first video they focus on our work in helping fund stem cell therapies for type 1 diabetes.

What is so impressive about the video is its ability to take complex ideas and make them easily understandable. On their website Youreka Science says they have a number of hopes for the videos they produce:

“How empowering would it be for patients to better understand the underlying biology of their disease and learn how new treatments work to fight their illness?

How enlightening would it be for citizens to be part of the discovery process and see their tax dollars at work from the beginning?

How rewarding would it be for scientists to see their research understood and appreciated by the very people that support their work?”

What I love about Youreka Science is that it began almost by chance. A PhD student at the University of California San Francisco was teaching some 5th graders about science and thought it would be really cool to have a way of bringing the textbook to life. So she did. And now we all get to benefit from this delightful approach.