World Sickle Cell Day: A View from the Front Line

June 19th is World Sickle Cell Day. Sickle cell disease is an inherited blood disorder that causes normally round red blood cells to take on an abnormal sickle shape, resulting in clogged arteries, severe pain, increased risk of stroke and reduced life expectancy. To mark the occasion we asked Nancy M. Rene to write a guest blog for us. Nancy is certainly qualified; she is the grandmother of a child with sickle cell disease, and the co-founder of Axis Advocacy, a non-profit advocating for those with sickle cell disease and their families.

Nancy ReneOn this World Sickle Cell Day, 2017, we can look back to the trailblazers in the fight against Sickle Cell Disease.  More than 40 years ago, the Black Panther Party established the People’s Free Medical Clinics in several cities across the country. One of the functions of these free clinics: to screen people for sickle cell disease and sickle cell trait. This life-saving screening began  in 1971.

Around that same time, President Richard Nixon allocated $10 million to begin the National Sickle Cell Anemia Control Act. This included counseling and screening, educational activities, and money for research.

In the early part of the twentieth century, most children with sickle cell died before their fifth birthday. With newborn screening available nationwide, the use of penicillin to prevent common infections, and the finding that hydroxyurea was useful in fighting the disease, life expectancy began to improve.

For much of the twentieth century, people with sickle cell disease felt that they were fighting the fight alone, knowledgeable doctors were scarce and insurance was often denied.

Making progress

As we moved into the twenty-first century, patients and families found they had some powerful allies. The National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) joined the battle.  In 2016 the NIH held its tenth annual international conference on sickle cell disease that featured speakers from all over the world.  Participants were able to learn about best practices in Europe, Africa, India, and South America.

Sickle Cell centers at Howard University, the Foundation for Sickle Cell Disease Research, and other major universities across the country are pointing the way to the best that medicine has to offer.

Last year, the prestigious American Society of Hematology (ASH) launched an initiative to improve understanding and treatment of sickle cell disease.  Their four-point plan includes education, training, advocacy, and expanding its global reach.

Just last month, May 2017, the FDA looked at Endari, developed by Emmaus Medical in Torrance, California.  It is the first drug specifically developed for sickle cell disease to go through the FDA’s approval process. We should have a decision on whether or not the drug goes to market in July.

The progress that had been made up to the beginning of the twenty-first century was basically about alleviating the symptoms of the disease: the sickling, the organ damage and the pervasive anemia. But a cure was still elusive.

But in 2004, California’s Stem Cell Agency, CIRM, was created and it was as if the gates had opened.

Researchers had a new source of funding to enable  them to work on Sickle Cell Disease and many other chronic debilitating diseases at the cellular level. Scientists like Donald Kohn at UCLA, were able to research gene editing and find ways to use autologous bone marrow transplants to actually cure people with sickle cell. While some children with sickle cell have been cured with traditional bone marrow transplants, these transplants must come from a matched donor, and for most patients, a matched donor is simply not available. CIRM has provided the support needed so that researchers are closing in on the cure. They are able to share strategies with doctors and researchers throughout the world

And finally, support from the federal government came with the passage of the Affordable Care Act and adequate funding for the NIH, CDC, the Health Resources and Services Administration (HRSA), and FDA.

Going backwards

And yet, here we are, World Sickle Cell Day, 2017.

Will this be a case of one step forward two steps back?

Are we really going back to the time when people with Sickle Cell Disease could not get health insurance because sickle cell is a pre-existing condition, to the time when there was little money and no interest in research or professional training, to a time when patients and their families were fighting this fight alone?

For all of those with chronic disease, it’s as if we are living a very bad dream.

Time to wake up

For me, I want to wake up from that dream.  I want to look forward to a future where patients and families, where Joseph and Tiffany and Marissa and Ken and Marcus and all the others, will no longer have to worry about getting well-informed, professional treatment for their disease.

Where patients will no longer fear going to the Emergency Room

Where doctors and researchers have the funding they need to support them in their work toward the cure,

Where all children, those here in the United States along with those in Africa, India, and South America, will have access to treatments that can free them from pain and organ damage of sickle cell disease.

And where all people with this disease can be cured.

A call to put the ‘public’ back in publication, and make stem cell research findings available to everyone

Opening the door

Opening the door to scientific knowledge

Thomas Gray probably wasn’t thinking about stem cell research when, in 1750 in his poem “Elegy in a Country Churchyard”, he wrote: “Full many a flower is born to blush unseen”. But a new study says that’s precisely what seems to happen to the findings of many stem cell clinical trials. They take place, but no details of their findings are ever made public. They blush, if they blush at all, unseen.

The study, in the journal Stem Cell Reports, says that only around 45 percent of stem cell clinical trials ever have their results published in peer-reviewed journals. Which means the results of around 55 percent of stem cell clinical trials are never shared with either the public or the scientific community.

Now, this finding apparently is not confined to stem cell research. Previous studies have shown a similar lack of publication of the results of more conventional therapies. Nonetheless, it’s a little disappointing – to say the least – to find out that so much knowledge and potentially valuable data is being lost due to lack of publication.

Definitely not full disclosure

Researchers at the University of Alberta in Canada used the US National Institute of Health’s (NIH) clinicaltrials.gov website as their starting point. They identified 1,052 stem cell clinical trials on the site. Only 393 trials were completed and of these, just 179 (45.4 percent) published their findings in a peer-reviewed journal.

In an interview in The Scientist, Tania Bubela, the lead researcher, says they chose to focus on stem cell clinical trials because of extensive media interest and the high public expectations for the field:

“When you have a field that is accused of over promising in some areas, it is beholden of the researchers in that field to publish the results of their trials so that the public and policy makers can realistically estimate the potential benefits.”

Now, it could be argued that publishing in a peer-reviewed journal is a rather high bar, that many researchers may have submitted articles but were rejected. However, there are other avenues for researchers to publish their findings, such as posting results on the clinicaltrials.gov database. Only 37 teams (3.5 percent) did that.

Why do it?

In the same article in The Scientist, Leigh Turner, a bioethicist at the University of Minnesota, raises the obvious question:

“The study shows a gap between studies that have taken place and actual publication of the data, so a substantial number of trials testing cell-based interventions are not entering the public domain. The underlying question is, what is the ethical and scientific basis to exposing human research subjects to risk if there is not going to be any meaningful contribution to knowledge at the end of the process?”

In short, why do it if you are not going to let anyone know what you did and what you found?

It’s a particularly relevant question when you consider that much of this research was supported with taxpayer dollars from the NIH and other institutions. So, if the public is paying for this research, doesn’t the public have a right to know what was learned?

Right to know

At CIRM we certainly think so. We expect and encourage all the researchers we fund to publish their findings. There are numerous ways and places to do that. For example, we expect each grantee to post a lay summary of their progress which we publish on our website. Stanford’s Dr. Joseph Wu’s progress reports for his work on heart disease shows you what those look like.

We also require researchers conducting clinical trials that we are funding to submit and post their trial results on the clinicaltrials.gov website.

The International Society for Stem Cell Research (ISSCR), agrees and recently updated its Guidelines for Stem Cell Research and Clinical Translation calling on researchers to publish, as fully as possible, their clinical trial results.

That is true regardless of whether or not the clinical trial showed it was both safe and effective, or whether it showed it was unsafe and ineffective. We can learn as much from failure as we can from success. But to do that we need to know what the results are.

Publishing only positive findings skews the scientific literature, and public perception of this work. Ignoring the negative could mean that other scientists waste a lot of time and money trying to do something that has already demonstrated it won’t work.

Publication should be a requirement for all research, particularly publicly funded research. It’s time to put the word “public” back in publication.

 

 

What…exactly…do you do? How 12 year olds helped me learn how to talk about science

Jackie Ward in her lab at UC San Diego

Jackie Ward in her lab at UC San Diego

Jackie Ward is a graduate student at the University of California, San Diego (UCSD), and received a training grant from CIRM while studying for her PhD. At UCSD Jackie uses stem cells as a model to study rare neurodegenerative diseases in the lab of Albert La Spada. Her work as a PhD student focuses on a rare form of inherited neurodegeneration called spinocerebellar ataxia. From time to time Jackie shares her experiences with us. Here’s her latest.

One of the many questions I get over my annual trek home during the holidays is “What…exactly…do you do?” This is usually couched somewhere between “have you learned to surf yet?” and “how’s the weather?” In the past, I preferred to talk about my surfing skills (very minimal) and the sunshine (always amazing, thanks San Diego), more than what I do every day. It’s amazing how this seemingly innocuous question can be the most difficult to answer. Because we’re used to presenting our work in lecture formats or lengthy scientific papers, summing it up in three sentences of non-jargon can be difficult. A similar thought was outlined recently at UCSD, by the actor and science advocate Alan Alda. The title of his presentation, “Getting the Public Past a Blind Date with Science,” highlighted the uncomfortable feelings many people have towards science. Like any relationship, sustained communication and trust is necessary for success. Unfortunately, on many scientific issues, that relationship has suffered. As a PhD student, I am constantly surrounded by my peers—other scientists who know exactly what I mean when I use terms like “reprogramming” or “retinal photoreceptor.” While these scientist-to-scientist conversations are vital to our work, we often forget that it is equally, or perhaps more, important to have conversations with people who have no idea what we do. As any CIRM- or NIH-funded lab is well aware, a significant portion of our funding comes from taxpayer dollars. It’s these “investors” to whom we ultimately report back. This conversation is challenging. Not only do we have to change our language, we have to remember what it was like to not know everything we do now. The best practice I’ve gotten in this regard is talking to kids. Seventh graders seem to be less afraid to ask you questions or call you out on something that doesn’t make sense to them. (Now that I think about it, it might be beneficial to include some 13-year-olds on our grant review panels.) My graduate program allows students to fulfill their teaching requirement by doing science outreach activities. I chose to do this with the Salk Institute’s mobile science lab, where real scientists are connected to local middle schools to discuss their jobs and lead hands-on science labs. I didn’t realize how valuable this experience was until it started to become easier for me to answer the “what do you do” question. I changed the words I use. I replaced the word “reprogram” with “rewind” and “retinal photoreceptor” with “eye cell.” Unexpectedly, I think this practice helped me become a better communicator when I talk to other scientists now too. I try not to assume a certain level of knowledge with anybody. While I still love talking about pretending to surf and gloating about the weather, I’ve become more fond of the “what do you do” question. I hope to only improve with time. It’ll be my small contribution for getting science to that second date.

Stem Cell Stories that Caught our Eye: Parkinson’s, Multiple Sclerosis and the Art of Science

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

Three parent embryos called safe. A scientific review panel in the United Kingdom has issued a report saying that a controversial fertility treatment that uses three parents is likely to be safe. The in vitro fertilization technique is being developed to help women who carry rare genetic mutations have healthy children. While we inherit most of our DNA from the chromosomes in the nucleus of mom’s egg and dad’s sperm, a small organelle outside the nucleus, called the mitochondria, also carries a few genes. Those we inherit only from mom, since her egg hosts those at the point of fertilization. This technique puts mom’s nucleus into the egg of a healthy donor that has had its nucleus removed but still has the healthy mitochondria. Gretchen Vogel, who worked with me as an intern several years ago, did a nice job explaining the process in Science Insider.

Embryonic cells show promise in multiple sclerosis. The vast majority of stem cell clinical trials registered at clinicaltrials.gov use a type of stem cell found in bone marrow, fat and cord blood called mesenchymal stem cells (MSCs). But many in the field believe that sometimes those cells are a little too mature to get the job done well. They suggest that in some situations these cells are often only minimally effective at the goals for their use: reducing inflammation and secreting factors that stimulate natural healing. So several groups have started maturing embryonic stem cells into early stage MSCs hoping their youth would make them more robust in these functions. Now, a team from the company ImStem Biotechnology and the University of Connecticut has shown that this is indeed the case—at least in the model in this study. They published in Stem Cell Reports that embryonic-derived MSCs were better at reducing the damage of multiple sclerosis in mice. The company’s press release was picked up at SFGate.

You can read about CIRM-funded work in the field on our multiple sclerosis fact sheet.

Transplanted cells survive 14 years in Parkinson’s. A Parkinson’s pioneer I wrote about often at Harvard has published important data showing transplanted nerves can survive and continue producing the dopamine needed in Parkinson’s for many years. Ole Isacson, of Harvard-affiliate McLean Hospital, reported that five patients who had nerves transplanted as much as 14 years before, all showed evidence that those nerves where still functioning at the time of their death. Those deaths, by the way, were unrelated to their Parkinson’s. As many teams are preparing to transplant nerve cells from much more readily available stem cells, the fact that these cells can persist is definitely good news. HEALTHCANAL ran the institution’s press release.

CIRM gathered most of the world leaders in the field last year to discuss next steps and we produced this white paper “Cell Therapies for Parkinson’s Disease from Discovery to Clinic.”

Adult stem cells alert to damage. I often find myself explaining adult stem cells to patients and family members calling CIRM seeking some clarity for an admittedly confusing field. In explaining that we have tissue-specific stem cells in most parts of our bodies all the time, I end up talking about those cells waiting around for a signal to respond to damage or inflammation. A longevity researcher at Stanford, Thomas Rando, has given a name to this in a new paper published in Natiure last week. He calls it the “alert” state. Krista Conger provides a good explanation of his findings in the school of medicine’s blog Scope.

Science as art takes to the runways. I have always had a bit of a bully pulpit about wanting to tear down the wall between C.P. Snow’s two cultures: science and humanities. So, I love the fact that more and more groups are seeing that contemporary imaging technologies in the lab often naturally bridge the gap between art and science. Two of the nation’s airports this week opened new exhibits featuring the art of science. Dulles airport outside of our nation’s capital teamed up with the National Institutes of Health for an exhibit described in the NIH blog. And the Southern California biotech trade association BioCom created a display in the San Diego airport timed to the BIO International Convention scheduled to convene there June 24. This display incudes an image from CIRM that a Salk Institute researcher had submitted to the imaging contest we ran my first year here in 2008. All those contest images are available free for educational uses at our Flickr site.

Stem Cell Stories that Caught our Eye: Parkinson’s, Multiple Sclerosis and the Art of Science

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

Three parent embryos called safe. A scientific review panel in the United Kingdom has issued a report saying that a controversial fertility treatment that uses three parents is likely to be safe. The in vitro fertilization technique is being developed to help women who carry rare genetic mutations have healthy children. While we inherit most of our DNA from the chromosomes in the nucleus of mom’s egg and dad’s sperm, a small organelle outside the nucleus, called the mitochondria, also carries a few genes. Those we inherit only from mom, since her egg hosts those at the point of fertilization. This technique puts mom’s nucleus into the egg of a healthy donor that has had its nucleus removed but still has the healthy mitochondria. Gretchen Vogel, who worked with me as an intern several years ago, did a nice job explaining the process in Science Insider.

Embryonic cells show promise in multiple sclerosis. The vast majority of stem cell clinical trials registered at clinicaltrials.gov use a type of stem cell found in bone marrow, fat and cord blood called mesenchymal stem cells (MSCs). But many in the field believe that sometimes those cells are a little too mature to get the job done well. They suggest that in some situations these cells are often only minimally effective at the goals for their use: reducing inflammation and secreting factors that stimulate natural healing. So several groups have started maturing embryonic stem cells into early stage MSCs hoping their youth would make them more robust in these functions. Now, a team from the company ImStem Biotechnology and the University of Connecticut has shown that this is indeed the case—at least in the model in this study. They published in Stem Cell Reports that embryonic-derived MSCs were better at reducing the damage of multiple sclerosis in mice. The company’s press release was picked up at SFGate.

You can read about CIRM-funded work in the field on our multiple sclerosis fact sheet.

Transplanted cells survive 14 years in Parkinson’s. A Parkinson’s pioneer I wrote about often at Harvard has published important data showing transplanted nerves can survive and continue producing the dopamine needed in Parkinson’s for many years. Ole Isacson, of Harvard-affiliate McLean Hospital, reported that five patients who had nerves transplanted as much as 14 years before, all showed evidence that those nerves where still functioning at the time of their death. Those deaths, by the way, were unrelated to their Parkinson’s. As many teams are preparing to transplant nerve cells from much more readily available stem cells, the fact that these cells can persist is definitely good news. HEALTHCANAL ran the institution’s press release.

CIRM gathered most of the world leaders in the field last year to discuss next steps and we produced this white paper “Cell Therapies for Parkinson’s Disease from Discovery to Clinic.”

Adult stem cells alert to damage. I often find myself explaining adult stem cells to patients and family members calling CIRM seeking some clarity for an admittedly confusing field. In explaining that we have tissue-specific stem cells in most parts of our bodies all the time, I end up talking about those cells waiting around for a signal to respond to damage or inflammation. A longevity researcher at Stanford, Thomas Rando, has given a name to this in a new paper published in Natiure last week. He calls it the “alert” state. Krista Conger provides a good explanation of his findings in the school of medicine’s blog Scope.

Science as art takes to the runways. I have always had a bit of a bully pulpit about wanting to tear down the wall between C.P. Snow’s two cultures: science and humanities. So, I love the fact that more and more groups are seeing that contemporary imaging technologies in the lab often naturally bridge the gap between art and science. Two of the nation’s airports this week opened new exhibits featuring the art of science. Dulles airport outside of our nation’s capital teamed up with the National Institutes of Health for an exhibit described in the NIH blog. And the Southern California biotech trade association BioCom created a display in the San Diego airport timed to the BIO International Convention scheduled to convene there June 24. This display incudes an image from CIRM that a Salk Institute researcher had submitted to the imaging contest we ran my first year here in 2008. All those contest images are available free for educational uses at our Flickr site.