Testimony prepared for: 
The Congress of the United States
House of Representatives
Committee on Appropriations
Subcommittee on Labor, Health and Human Services, Education and Related Agencies
Jannine D. Cody, Ph.D.
President
The Chromosome 18 Registry & Research Society
Catherine M. Cody
Elizabeth C. Cody
April 5, 2000, 10 a.m.
Chairman Porter and members of the subcommittee:
Thank you for allowing us this opportunity to speak to you today. My name is Jannine Cody and I am President of the Chromosome 18 Registry & Research Society. We are a parent support group for families of people with chromosome 18 abnormalities. I am here with my husband and daughters, members of our Board of Directors and families from the DC area. My daughter Elizabeth has a missing piece of chromosome 18, a condition called 18q-.
Elizabeth with Catherine
When I was born, I had a cleft palate and my feet turned in. This is because I have 18q-. Now, I am 15 years old and have had 19 surgeries - 3 for ear problems and the rest on my mouth. I don't like to think about how many more surgeries I need. I have also had to have growth hormone shots everyday since I was 2.
I am in the 9th grade at Roosevelt High School and am in the hearing impaired class. I am in the Pep Squad and my favorite class is art. I think I want to be an art teacher when I grow up.
The good part of 18q- is that I got to be on the news, and my picture was in the newspaper. And I get to come here.
I was here two years ago to explain the obstacles we face as parents of children with chromosome 18 abnormalities.
Although there are five major syndromes of chromosome 18, to date the vast majority of the research, and therefore the new information, has been on 18q-. This is entirely due to the financial generosity of one family.
Our plan for helping our kids is very simple and follows two parallel approaches. First, we just need more information about individuals with these syndromes. Our parent support group can gather some of the most basic information. However, the kind of information that can provide the most insight comes from sophisticated medical evaluations that should be done as a part of a clinical research project.
The second approach is to learn about the biology of the specific genes involved in these syndromes. Normally, each of us has two copies of every chromosome. Individuals with 18q- have a missing piece from one copy of chromosome 18, but the other chromosome is normal. So our scientific quest is quite straightforward. If we can find out which genes are missing and which of those are the ones that cause a problem when there is one copy instead of two, then all we have to do is to make the remaining gene do the work of two, probably with conventional drug therapies.
We do have some glimmers of hope. From the clinical approach, we have learned that most kids with 18q- are growth hormone deficient. In fact, as far as I know, Liz was the first child with 18q- to receive growth hormone therapy. We have found that kids with 18q- who are treated with growth hormone not only begin to grow at a normal rate, but have IQ increases of up to 47 points (an IQ of 100 is average intelligence and IQs between 70 and 120 are considered normal.) An increase of 47 points means that kids who would have been mentally retarded will now have normal IQs. Kids who would have grown up to live in a closely supervised group home will now have the opportunity to be independent, taxpaying citizens. Unfortunately, while the endocrinologists argue over what constitutes growth hormone deficiency, our kids are failing to get a treatment that has been shown to be effective.
With regard to our second approach, based on the molecular biology, we have much frustration. One example involves the gene BCL2. It is one of the genes on 18q that we do know something about. One function of this gene is to keep brain cells from dying. We also know of a class of drugs that up-regulate this gene and make it work harder. But we don't know if this gene is one of those responsible for some of our kids' problems. Without research funding, we will not know if this is another treatment for our children.
With regard to the other syndromes of chromosome 18, we don't even know enough about those syndromes to have these kinds of dilemmas. Starting a new area of research on previously unstudied disorders is Herculean. Even if you can find a niche at NIH, and a program announcement with parallel goals, the grant review process is the most subjective, "objective" process imaginable. Reviewers who don't know anything about the syndrome (because little is known) find it uninteresting. They often make assumptions from syndromes they do know about and erroneously apply them to ours.
In recent years there has been great progress in the understanding of Rett Syndrome, Fragile-X Syndrome, and autism, to name a few. These are some of the hottest areas in neurodevelopment. These advances started in this room.
I once read a description of the mindset of management and leadership that seems analogous to this situation. Management oversees the logging operation. They concern themselves with questions like, "Are the trees being cut in the most efficient way? Are they falling in the right place? Are there enough trucks to haul away the logs?" But the leadership concerns themselves with questions like, "Are we in the right forest?" Leadership sees the bigger picture and takes into consideration a wide variety of outside influences. This committee provides the leadership to NIH.
The human genome project was not feasible when it was first proposed. It was the vision and the will to see it done that created the scientific advancements that are making it possible. Mario Cappechi, who developed a method to delete single specific genes in mice, was not funded by the NIH to do this work because the grant reviewers said it was impossible. Craig Venter's grant reviews, saying that his method to sequence the genome of an entire organism was impossible, arrived the day before his team submitted the paper with the finished work.
I had hoped to come here today to tell you about our progress thanks to NIH support, but I can't - because we are doing the impossible.