Why TED Talks are ChildX’s Play

When the TED (Technology, Entertainment, Design) talks began in 1984 they were intended to be a one-off event. So much for that idea! Today they are a global event, with TED-sponsored conferences held everywhere from Scotland to Tanzania and India. They have also spawned a mini-industry of copycat events. Well, their slogan is “Ideas Worth Spreading” so in a way they only have themselves to blame for having such a great idea.

Dr. Maria Grazia Roncarolo

Dr. Maria Grazia Roncarolo

The latest place for that idea to take root is Stanford, which is holding a TED-style event focused on critical issues facing child and maternal health. The event – April 2nd and 3rd at Stanford – is called ChildX where x = medicine + technology + innovative treatment + wellbeing. ChildX will bring together some of the leading experts in the field for a series of thoughtful, powerful presentations on the biggest problems facing child and maternal health, and the most exciting research aimed at resolving those problems. One of the main tracks during the two-day event is a section on stem cell and gene therapy. It will raise a number of key questions including:

  • What advances have occurred to enable these therapies to move from science fiction less than a decade ago to the promise of next generation transformative therapeutics?
  • In coming years, how will these therapies allow children with presently incurable diseases to become children living free of disease and reaching their maximum potential?

The moderator for that discussion is Dr. Maria Grazia Roncarolo, and you can hear her talking about the most recent advances in the clinical use of stem cell and gene therapies on this podcast. Anytime you get a chance to hear some of the most compelling speakers in their field talk about exciting innovations that could shape the future, it’s worth taking the time to listen.

Goodnight, Stem Cells: How Well Rested Cells Keep Us Healthy

Plenty of studies show that a lack of sleep is nothing but bad news and can contribute to a whole host of health problems like heart disease, poor memory, high blood pressure and obesity.

HSCs_Sleeping_graphic100x100

Even stem cells need rest to stay healthy

In a sense, the same holds true for the stem cells in our body. In response to injury, adult stem cells go to work by dividing and specializing into the cells needed to heal specific tissues and organs. But they also need to rest for long-lasting health. Each cell division carries a risk of introducing DNA mutations—and with it, a risk for cancer. Too much cell division can also deplete the stem cell supply, crippling the healing process. So it’s just as important for the stem cells to assume an inactive, or quiescent, state to maintain their ability to mend the body. Blood stem cells for instance are mostly quiescent and only divide about every two months to renew their reserves.

Even though the importance of this balance is well documented, exactly how it’s achieved is not well understood; that is, until now. Earlier this week, a CIRM-funded research team from The Scripps Research Institute (TSRI) reported on the identification of an enzyme that’s key in controlling the work-rest balance in blood stem cells, also called hematopoietic stem cells (HSCs). Their study, published in the journal Blood, could point the way to drugs that treat anemias, blood cancers, and other blood disorders.

Previous studies in other cell types suggested that this key enzyme, called ItpkB, might play a role in promoting a rested state in HSCs. Senior author Karsten Sauer explained their reasoning for focusing on the enzyme in a press release:

“What made ItpkB an attractive protein to study is that it can dampen activating signaling in other cells. We hypothesized that ItpkB might do the same in HSCs to keep them at rest. Moreover, ItpkB is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

Senior author Karsten Sauer is an associate professor at The Scripps Research Institute.

Senior author Karsten Sauer is an associate professor at The Scripps Research Institute.

To test their hypothesis, the team studied HSCs in mice that completely lacked ItpkB. Sure enough, without ItpkB the HSCs got stuck in the “on” position and continually multiplied until the supply of HSCs stores in the bone marrow were exhausted. Without these stem cells, the mice could no longer produce red blood cells, which deliver oxygen to the body or white blood cells, which fight off infection. As a result the animals died due to severe anemia and bone marrow failure. Sauer used a great analogy to describe the result:

“It’s like a car—you need to hit the gas pedal to get some activity, but if you hit it too hard, you can crash into a wall. ItpkB is that spring that prevents you from pushing the pedal all the way through.”

With this new understanding of how balancing stem cell activation and deactivation works, Sauer and his team have their sights set on human therapies:

“If we can show that ItpkB also keeps human HSCs healthy, this could open avenues to target ItpkB to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

The eyes have it: a video guide to stem cells

We are visual creatures. Our eyes are essential tools in getting information to our brain to help us learn and understand. For example, visuals are processed about 60,000 times faster in the brain than text is, and some 60 percent of us are visual learners, meaning we respond better to visual information than to plain text.

ben paylorThat’s why a series of 8 videos, just completed by Ben Paylor and Mike Long at InfoShots, are so wonderful. They are fun, simple and engaging videos that help make some of the complex science around stem cells readily understandable thanks to the use of eye-catching animation and simple, everyday English.

The videos are short, all around one minute (less time than it takes to make a cup of tea). Each video has a single theme – ‘What is a stem cell”, “What is stem cell tourism” – and they are all masterful at walking you through different aspects of stem cell research.

The last video in the series is about neural stem cells, which is highly appropriate considering this is Brain Awareness Week, a worldwide celebration of the brain.

The videos are a reminder that the most effective communication is often the most direct, cutting through the clutter and getting to the heart of the subject. The beauty of these is that Ben and Mike are keen to share them with as many people as possible and have made them available to anyone who wants to watch them or use them as a teaching tool.

Finally, credit for the videos also has to go to the Canada’s Stem Cell Network and the Canadian Stem Cell Foundation, which helped fund them.

Heartfelt award for brilliant young researcher

It can begin in so many different ways: a pain in the jaw, a sore neck, nausea, or more typically a crushing pain to the chest. But regardless of how it starts, surviving a heart attack is always devastating with the loss of as many as one billion heart cells and permanent damage to the heart muscle.

Dr. Reza Ardehali UCLA

Dr. Reza Ardehali
UCLA

But what if there were a way to reverse that damage, and regenerate the damaged tissue? A number of the researchers we fund are trying to find ways to do just that, and one, Dr. Reza Ardehali at the University of California, Los Angeles, has just been honored for his work in advancing that field.

Dr. Ardehali is being awarded the 2015 Douglas P. Zipes Distinguished Young Scientist Award at the American College of Cardiology’s 64th Annual Scientific Session and Expo on March 16. He is the first UCLA faculty member to receive this prestigious award.

Dr. Ardehali’s work focuses on trying to gain a deeper understanding of the role that stem cells play in the heart’s limited ability to regenerate after an injury. By identifying the mechanisms at work he hopes to be able to use that regenerative potential, and ultimately to amplify it, to treat people suffering from heart disease.

In a news release Dr. Ardehali says the award is a great honor and recognition for work that has the potential to help millions of people:

“The next step is to find out how we can regenerate injured hearts in adults by either transplanting stem cells or by enhancing the regenerative potential of the rare stem cells that already reside in the heart.”

We congratulate Dr. Ardehali on the award and look forward to following his work for many years to come.

The search for a cure: how stem cells could eradicate the AIDS virus

It’s hard to overstate just how devastating the AIDS crisis was at its peak in the U.S. – and still is today in many parts of the world. In 1995 almost 51,000 Americans died from the disease, the numbers of new cases were at almost record highs, and there were few effective therapies against the virus.

HIV/AIDS medications

HIV/AIDS medications

Today that picture is very different. New medications and combination therapies have helped reduce the death rate, in some cases turning HIV into a chronic rather than fatal condition. But even now there is no cure.

That’s why the news that the Food and Drug Administration (FDA) has approved a clinical trial, that we are funding, aimed at eradicating HIV in the body, was so welcome. This could be an important step towards the Holy Grail of AIDS therapies, curing the disease.

The project is headed by Dr. John Zaia at City of Hope near Los Angeles. The team, with researchers from Keck Medicine of the University of Southern California (USC) and Sangamo BioSciences, plans on using an individual’s own stem cells to beat the virus.  They will remove some blood stem cells from HIV-infected individuals, then treat them with zinc finger nucleases (ZFNs), a kind of molecular scissors, snipping off a protein the AIDS virus needs to infect those cells.

It’s hoped the re-engineered stem cells, when returned to the body, will help create a new blood and immune system that is resistant to the virus. And if the virus can’t infect any new immune cells it could, theoretically, die off. Check out the video we produced a few years back about the project:

Studies in the lab show this approach holds a lot of promise. In a news release announcing the start of the clinical trial, Dr. Zaia said now it’s time to see if it will work in people:

“While we have a number of drugs that are effective in holding HIV at bay, we have nothing that cures it. In addition, for many patients, these medications come with significant long-term problems so there is a real need for a therapy that can help eradicate the virus from a patient completely. That is where our work is focused.”

Like all Phase 1 trials this one is focused on making sure this approach is safe for people, and identifying what, if any, side-effects there are from the treatment. The first group of patients to be treated consists of people with HIV/AIDS who have not responded well to the existing medications.

This is the second trial that CIRM is funding focused on curing HIV/AIDS. Our first, involving the company Calimmune, began its human clinical trial in July 2013. You can read more about that work here.

We know that the road to a cure will not be simple or straightforward. There have been too many false claims of cures or miracle therapies over the years for any of us to want to fall victim to hope and hype. It may even be that the most realistic goal for these approaches is what is called a “functional cure”, one that doesn’t eliminate the virus completely but does eliminate the need to take antiretroviral pills every day.

But when compared to the dark days of 1995, a functional cure is a world away from certain death.

How the human genome is unlocking some of the secrets of stem cells, hopefully leading to new treatments

A little over a year ago we set aside $40 million to study how variations in the human genome – the complete map of our genetic information – can affect our ability to use stem cells to treat a wide variety of diseases and disorders.

Human-Genome-Project_finalThat money helped set up the Stanford/Salk Center of Excellence in Stem Cell Genomics (CESCG) with a goal of using genomic analysis to better understand how stem cells change as they grow and become different kinds of cells, and then use that knowledge to develop new treatments for a wide variety of conditions.

Now the CESCG has just announced it is investing $11.6 million on seven different projects aimed at gaining a deeper understanding of deadly or disabling diseases and conditions, such as heart disease and autism.

As Stanford’s Dr. Michael Snyder, a co-Principal Investigator on the project, said in a news release, a major part of CESCG’s mission is to “establish a Collaborative Research Program (CRP) to support the genomics research needs of stem cell investigators in California,”

‘We don’t just provide funds we also partner with the individual researchers, providing them with the support, expertise and resources they need to conduct successful genomics analyses. We received 30 applications from throughout the State, and after peer review 7 projects were identified as the best new collaborations for the Center.”

So how does this advance stem cell science? Well, in the past researchers often depended on animal models for their work; but because results in animals don’t always translate when applied to people this was not always an effective way to work. At the University of California, San Francisco and the University of California, Los Angeles researchers Arnold Kriegstein and Gay Crooks are using genomics to better understand normal human cell identities in the brain (UCSF) and the blood (UCLA) and then applying that knowledge to help develop more accurate and more detailed stem cell-based models for us to study.

Jonathan Thomas, the Chair of our Board, says one of the best ways to do great science, is to create a great team:

“The goal of the Board in creating this program and bringing together this group of researchers was to accelerate our fundamental understanding of human biology and the ways that disease work. That knowledge will help point the way not just to new treatments but also, hopefully, to ways that those treatments can potentially be tailored to meet the needs of individual patients.”

Meryl Streep, Lindsay Lohan and the importance of staying above the fray in science communications

Carl Sagan: photo courtesy Brainpickings.org

Carl Sagan: photo courtesy Brainpickings.org

Carl Sagan, the astronomer and cosmologist (among many other things) once said: “We live in a society absolutely dependent on science and technology, and yet have cleverly arranged things so that almost no one understands science and technology. That’s a clear prescription for disaster.”

The goal of two panel discussions at the American Association for the Advancement of Science (AAAS) conference in San Jose last week was to find ways to change that: to get the public to both understand and care more about science and technology; and to get scientists to do a better job of explaining both to them.

The first challenge of course is finding scientists who want to be part of this public conversation. Dr. Nalini Nadkarni, an ecologist who studies rain forests, said for young scientists in particular it’s not just a matter of having the right skills, it’s also a matter of finding the time:

“One of the challenges of scientific engagement is that just being a scientist is a full-time job, and it’s hard to think about doing public engagement when you are trying to build a career.”

Dr. Anthony Dudo, who studies the intersection of science, media and society, says one thing universities can do is encourage outreach and engagement, maybe even make it a factor in a teacher getting tenure. He says there are a lot of researchers who are happy to do this kind of outreach – either through public talks or media interviews – and they do it for all sorts of reasons.

“Many do it because it’s something they enjoy, they consider it a civic duty, something that sparks public interest in science and raises awareness about their field. In addition some say it can enhance their own scientific reputation and increase visibility for funding.”

But there is a risk. Some scientists reported facing a backlash from colleagues who felt they were trying to hog the limelight. They fell victim to what is called the “Carl Sagan” effect, which holds that if someone is spending that much time and effort communicating science to the public they must not be a very good scientist to start with.

No one could accuse Stanford’s Dr. Noah Diffenbaugh of not being a good scientist – he specializes in studying climate change and you can read his extensive resume here –  but he is also a gifted communicator, something he says he feels is his duty:

“I feel it is my responsibility to answer questions from the public when asked, because my research group is publicly funded by taxpayer dollars through agencies like the NSF. And as a public citizen I feel responsible that if we are having a public dialogue about climate change that I should be part of that dialogue.”

But he says he is very careful to avoid taking sides in the debate. He tells of an interview he once heard where Oscar-winning actress Meryl Streep talked about the importance of keeping her personal life and beliefs private (as opposed to Lindsay Lohan’s very public private life). Streep says as an actress she wants people to be able to look at her on screen and focus on the character she is playing, and not be distracted by thinking about any very public shenanigans she may have been involved in. Diffenbaugh says a scientist’s credibility depends on them doing the same:

“I stick to the facts and don’t express personal opinions or offer advocacy positions. I feel strong that in public discussions about climate change that someone in the conversation needs to be focused on evidence. It’s a role that scientists are fundamentally equipped to play.”

But even the best communicators are finding it increasingly hard to get their message into the media these days. Fewer and fewer newspapers or TV stations have skilled, experienced health and science writers, which makes it difficult to reach the public.

Lisa Krieger is an award-winning science journalist at the San Jose Mercury News. She says she finds it challenging getting stories she wants to write into the paper because she is competing for shrinking space against stories that might seem more relevant to local readers:

“Basic science is hard to cover because readers want to know how it will benefit them directly and sometimes these things are years, or even decades, away from having any real impact on people. And that’s a hard sell to an editor to get those kinds of stories into the paper.”

Krieger says the key to getting the message out is making it personal, tell stories about real people, about the real impact something could have on someone.

While acknowledging the challenges, and risks, of being a public voice and face for science – particularly when there is so much political polarization around science these days – everyone agreed that we need more scientists who are willing and able to talk about their work in ways that will engage the public, help them understand what is being done and why they should care.

For Carl Sagan (yes, him again) the reason why scientists should engage with the public was simple; to share knowledge about the wonders of the world we live in.

“It is sometimes said that scientists are unromantic, that their passion to figure out robs the world of beauty and mystery. But is it not stirring to understand how the world actually works—that white light is made of colors, that color is the way we perceive the wavelengths of light, that transparent air reflects light, that in so doing it discriminates among the waves, and that the sky is blue for the same reason that the sunset is red? It does no harm to the romance of the sunset to know a little bit about it.”

Peering inside the brain: how stem cells could help turn skin into therapies for dementia

To truly understand a disease you need to be able to see how it works, how it causes our body to act in ways that it shouldn’t. In cancer, for example, you can take cells from a tumor and observe them under a microscope to see what is going on. But with diseases of the brain it’s much harder. You can’t just open someone’s skull to grab some cells to study. However, now we have new tools that enable us to skip the skull-opening bit, and examine brain cells in people with diseases like dementia, to see what’s going wrong, and maybe even to get some ideas on how to make it right.

AF_neuronTHMito(2)_webThe latest example of this comes from researchers in Belgium who have developed a new strategy for treating patients with an inherited form of dementia. They used the induced pluripotent stem cell (iPSC) method, taking take skin cells from patients with frontotemporal dementia, and turning them into neurons, the kind of brain cell damaged by the disease. They were then able to study those neurons for clues as to what was happening inside the brain.

The study is reported in the journal Stem Cell Reports, and in an accompanying news release the senior author, Catherine Verfaillie, says this approach allows them to study problems in the brain in ways that weren’t possible before.

“iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons.”

The researchers identified problems with a particular signaling pathway in the brain, Wnt, which plays an important role in the development of neurons. In patients with frontotemporal dementia, the neurons weren’t able to mature into cortical neurons, which play a key role in enabling thought, perception and voluntary movement. However, by genetically correcting that problem they were able to restore the ability of the neurons to turn into cortical neurons.

Philip Van Damme, a lead researcher on the project, says this may open up possible ways to treat the problem.

“Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration. Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia.”

A look at 2014: some of the lowlights of stem cell research this past year

It’s been quite a year in stem cell research. Here at the stem cell agency eight projects that we are funding have been approved for clinical trials and several more hope to get approval in early 2015. And Dr. Don Kohn and his team at UCLA announced that they have effectively cured Severe Combined Immunodeficiency or SCID  a fatal disease that leaves infants with no immune system.

But the news hasn’t been all good. A number of high profile retractions of studies published in prestigious journals have drawn attention to some of the less lovely aspects of science. There are many reasons why a researcher or scientific journal decides to retract a study – falsified data, inability of others to reproduce the findings etc. – but the end result is always the same, a stain on the reputation of science in general.

Of course the only thing worse than a retraction is bad science that is not retracted. That’s why websites such as Retraction Watch are so important. They keep an eye on the field and help draw attention to questionable papers (in all areas of science, not just stem cell research).

Ivan Oransky of Retraction Watch

Ivan Oransky of Retraction Watch

The two founders of the site, Evan Marcus and Ivan Oransky, do a remarkable job of highlighting work that doesn’t stand up to closer scrutiny. This year they worked with the magazine Science to highlight The Top 10 Retractions of 2014.  Sadly, two of the top 10 – including the number one story of the year – concern stem cell research.

The list is a reminder, as we look forward to 2015 for more progress in the field, that we need to always check the credibility of studies or sources we are using. Sometimes something that seems too good to be true, is too good to be true.

Tomorrow, we’ll take a look at the flip side of this discussion, the “Biggest Scientific Breakthroughs of 2014”. It’s always good to end the year on a positive note.

Maintaining the momentum: a good start but CIRM 2.0 is just the first step

Sir Isaac Newton

Sir Isaac Newton

Newton’s First Law of Physics states that an object either remains at rest or continues to move at a constant velocity unless acted upon by an external force. Well, for the stem cell agency the external force was an exercise in thinking differently about how we do business. That resulted in our governing Board approving CIRM 2.0 yesterday. And we intend to keep that momentum going for as long as we can.

CIRM 2.0 is a streamlined process that will make it easier and faster to apply for funding from the stem cell agency, and is designed to attract high quality clinical stage projects that are ready to start within 45 days of being approved for funding.

As our President and CEO Dr. C. Randal Mills said in a news release:

“Our mission is to accelerate the development of stem cell treatments for patients with unmet medical needs. With many of these diseases, time lost waiting for a treatment means lives lost. We must continue to find new and innovative ways to speed up our process and make it easier to get promising therapies into clinical trials, and to give them all the support they need to be successful. That’s why we undertook this radical overhaul of the way we do business.”

In the past it could take up to two years for a researcher or company to move from applying for funding to getting the money as part of an approved contract. CIRM 2.0 simplifies and accelerates the process, cutting that two years down to just four months. And instead of just one single round of funding with an application deadline every 12-to-18 months, CIRM 2.0 will have an open application process for clinical stage programs with deadlines every month. That means companies and researchers can apply when they are ready and won’t have to try and rush an application in prematurely, for fear it could be another year or more before the chance comes around again.

It’s a big change in the way we work and as Dr. Mills told the Board at yesterday’s meeting, there are bound to be problems:

“There will be bumps in the road, you can’t make radical changes of this nature and scope without running into problems. I know that, my team knows that and we are ready to handle whatever unforeseen consequences come up.”

We plan on monitoring 2.0 as we unveil it, constantly checking to see what’s working and to fix what isn’t. In the short term we will use several measures of how well it’s working such as how many high quality applications we get, how quickly we can move these applications through the approvals process and how long it takes to get successful applicants their money. In the long term the best indication of success will be the quality of the programs we fund and how well they do in completing clinical trials.

This first phase of CIRM 2.0 will cover funding for clinical work but it will later be expanded to include discovery (also known as basic research) and translational research (moving promising discovery research to the clinic). But as Dr. Mills says, even while we are implementing CIRM 2.0 we are already thinking about the next step.

“Soon as this is done we have to start working on how we can improve CIRM 2.0 and keep that sense of urgency and innovation in front of us so that we always look to build a better product and fulfill our mission in a better way. Because there are many sick people out there looking to us for help and until that changes we need to be always looking to improve. Which is why as soon as CIRM 2.0 is done, we’re looking to create CIRM 3.0”