When my son Calvin was diagnosed with Bloom Syndrome, the phrase that his geneticist used was "when your son gets cancer." I am motivated by the urge to apply myself and my skills to that when. Both of Calvin's parents are highly educated scientists, and yet there is this infuriating feeling we have that we are not sufficiently knowledgeable about the particular science that is needed to keep our own son alive. This is a very frustrating thing, and not a feeling we are used to having. We have confidence that we can learn anything that can be learned by a person, but we need help and guidance from the talented people who have experience researching this topic. We are in a race against time, and are anxious to do what we can to help save our son's life. He does not currently have cancer, but our zeal to work on this topic burns brightly, and there is some hope that progress will benefit others in the patient community as well, even before that dreaded when. There is only so much we can learn from reading papers in a field outside of our own, and only so much those in that field can learn about the priorities of patients and their families from that same set of papers. Our goal is to focus efforts and consolidate data and expertise on this topic, and though I am not an expert in Bloom Syndrome yet, this modest task is something I know I can do. The clock is ticking faster for some patients than others, but we all recognize that such a rare disease requires an active and well-connected community so that mistakes are not repeated and successes are not forgotten.
Every night I read to my daughters at bedtime, then head back to the lab for a second shift. One night, my youngest daughter, then 4 and a half years old, asked, “Daddy, you leave for your research every night...but have you ever saved anyone’s life from the research you do in your lab, ever?” My answer was, unfortunately, “No. Not from my research.” I could have said that nobody really ever has, but the path from basic science to clinical applicability seemed too complicated to explain. It got me thinking: wouldn’t children with cancer ask the same question, too?
Fast forward to Spring 2014, at the annual Children’s Oncology Group meeting. The Chair announced dramatic cuts in the National Institute of Health’s budget for the COG...suggesting that not every childhood cancer could have an open clinical trial: only the ones with preclinical justification. The standard approach (inserting adult cancer drugs into trials for children) simply hadn’t worked. At the same meeting, the NCI announced that as a result of the sequester, the budget of the Pediatric Preclinical Testing Program was cut earliest, and deepest, of any NCI program (by 40 percent)!
Amongst colleagues who were leaders in pediatric oncology at academic centers, the feeling was that preclinical testing of basic science findings, to move exciting discoveries to clinical trials, was too tedious and narrow-scoped for university laboratories and government programs. As a result, the best and brightest scientific discoveries for childhood cancers never actually make it into the clinic. Rare cancers are the hardest hit, with survival rates remaining stagnant for decades. Knowledge that could save kids’ lives simply languishes in this black hole: the preclinical gap.
By chance, my reading material for the airplane ride home was A Life Decoded, the book by J. Craig Venter. In this story of the first group to sequence the human genome, Dr. Venter achieved remarkable speed and cost efficiency by “going outside the box” of academia. Curious, I drove straight from the airport to a biotech incubator. Renting a 250 sq ft lab space for per year: a mere $10,500.
The “what if’s” began: what if we could change the paradigm of research grants leading to publications (leading to more grants and papers, but never tangible results)? What if we could bridge the preclinical gap as a mission...with scientists partnering with families to achieve the cures they so desperately desired? What if science driving drugs into the clinic existed as a singular mission?
My research team and I simply wanted to know how a non-profit biotech could answer my daughter’s question. The result is the Children’s Cancer Therapy Development Institute (www.cc-tdi.org). We continue to pursue many of the same publication and grant funding goals as we had in academics (we have been a continually NIH-funded laboratory for 15 years, with our most recent NIH/NCI R01 (4th percentile) having begun in August 2015)... but we also value our pharmaceutical partners, give parents a seat at the table, and really listen to the clinical trialists. All in the name of converting scientific discovery into clinical trials for children with rare and underserved cancers.
Mary Beth Campbell
There is nothing in the world so overwhelming as a mother’s love for her child. When Calvin was diagnosed with Bloom Syndrome, I felt a range of emotions: shock and disbelief that he could have something so rare, guilt that he had inherited my faulty genes, and an all-encompassing sense of dread knowing that someday (perhaps someday soon) he will develop cancer and that this cancer may be his killer.
In the months since his diagnosis, however, another emotion has emerged: hope. Hope that there may be a cure – either for Bloom Syndrome itself or for the cancers that will one day emerge in Calvin’s body – and hope for a better understanding of Bloom Syndrome and the needs of Bloomies in order to lead happy, healthy lives.
In my professional role in technology transfer, I see every day how long and arduous the path from bench to bedside is. But I also know that what drives research from the lab to patients is the actual people involved: the basic scientists, the clinicians, the patients, and the entrepreneurs. When you can bring those people together, as we are proposing to do in the nano-course, great progress can be made.
Bloom Syndrome is a rare genetic disorder associated with short stature, early childhood nutrition challenges, a sun-sensitive rash, and -- most troubling -- an extraordinarily high risk of developing cancer (or diabetes) early in life. Of the ≈300 reported cases in the literature, 1/8 of patients developed childhood leukemia and the average lifespan of patients is currently 26 years.
Given its rare nature, less is known about Bloom Syndrome compared to more common conditions like Down Syndrome. Further complicating cancer treatment in patients with Bloom Syndrome, these patients lack a protein that is able to maintain the structure and integrity of DNA, requiring modification to standard cancer treatment protocols. The Bloom Syndrome Nano-Course at the Children’s Cancer Therapy Development Institute will bring together patients, families, physicians, and researchers for five days to discuss issues of cancer surveillance, cancer treatment, growth, dermatology, psychological development, and potential gene therapies. The output of the Nano-course will be a peer-reviewed roadmap for Bloom Syndrome research and clinical care guidelines. The published manuscript will then be available in the scientific literature for citation by those seeking support and publication of research addressing the needs outlined in the roadmap.
Why is this important?
Partnership between patient, research, and treatment communities serves to educate each other and consolidate resources. Once actively engaged with researchers and clinicians, a patient community can provide information about its most pressing needs to researchers, as well as serve as a source of data and valuable samples for research. Likewise, fostering a healthy network of connections between patients of rare diseases and those with treatment experience allows expertise to converge when and where needs arise, despite the dispersed the nature of the communities.
Who will benefit?
Bloom Syndrome patients, their families, and treating physicians. Researchers investigating phenomena relevant to Bloom Syndrome will also be able to use the roadmap to identify and seek funding to address the most pressing needs of the community.