Friday, August 28, 2009
I'm heading off to vacation in Maine next week. Tropical Storm (soon-to-be Hurricane) Danny is going to Maine the same week, apparently. I find the weather to be a lot like Usher syndrome. It's this big mystery that I have no control over that effects my life every day. Usher, like Danny, also rudely intrudes at times, threatening to ruin my plans for the future. But what can I do? I can't control the weather.
Or can I?
You see we're still going to Maine. We'll either wait for the storm to pass or head up a little early, but we're going. I'll pack up all the yard furniture before we leave so I don't find a lawn chair in living room when we return. We'll bring lots of books and matches and candles in case the power is out in our rental cabin for an extended period. In short, we'll make do with what we have. We'll probably end up having a great time, actually, and if nothing else it will be a vacation to remember.
The point of this is that Usher is what you make of it. I can neither control the weather nor my daughter's vision loss. They both bring dark clouds and can bring darker moods. But I can control how I deal with them. I can cancel my vacations and stay inside with the windows shut bemoaning my luck or I can adapt to the situation, get out, and live on. And, as with our hurricane vacation, we'll probably still have a great time.
Like the weather, we all feel small and helpless in the face of the Usher diagnosis. I can neither change the course of Hurricane Danny nor the course of Bella's diagnosis. The only thing that would move Danny away from Maine is a high pressure system and I can't create that.
And here's where the analogy ends. We can create our own high pressure system when it comes to Usher and it's a lot easier than you think. Jennifer touched on it in her last posting. We can each create a little pressure, generate a little movement, with our actions. And they don't have to be big actions.
I talk all the time about getting the word out about Usher syndrome. You don't have to be a reporter on the Today show or know a movie producer or be a celebrity to make it happen. You can create that movement, that pressure, one person or one roomful of people at time. I've given a couple of dozen talks on Usher in the last few years. My audience has ranged from three people sitting around a conference table to a couple hundred in an auditorium. The point is, I'm not exactly Michael J. Fox when it comes to drawing power. But it all helps.
Like Danny has suddenly become in New England, we need Usher syndrome to be a household word. Right now you say Usher and people think of the singer or 'The Fall of the House of...', not syndrome. We don't need big fancy marketing campaigns to change that. We just need constant pressure. You don't have to sing from the rooftops. Jennifer gave some great examples in her last post. You just need to talk to your science teachers about Usher or give a talk at your local community college or write an article for the local paper.
We can change the course of this hurricane and we can do it using only the power of our lungs. Just take a deep breath and we'll all blow it out to sea.
Wednesday, August 26, 2009
Mark stated in last week’s post that he and I will be writing along different paths for a while. I think of us more as starting our blog collaboration at opposite ends of the same path. It may take us a while to travel to a central rendezvous point, but once there I hope we will have learned enough to strike out together on the route of a common purpose.
Mark has blogged several times in the past about the importance of funding research relevant to Usher syndrome. Indeed, research doesn’t happen without this funding—the treatments we’re all hoping for will not appear if no one works on the problem, obviously, and science is expensive. However, research funding is just one component in this process. In the next few posts, I’m planning to present an overview of biomedical research, and I’ll begin by discussing the general flow of information from the laboratory bench to the patient.
An extremely simplified diagram of the pathway to a cure might look something like this:
And of course, you must mentally insert Dollar, Euro, Pound, Yen, etc. signs at every interval. Lots of them.
However, even with plenty of money to grease the wheels, progress toward the top tier can be painfully slow. The way forward is often unclear, and can remain so for long periods of time. Moreover, the early stages of the pathway depicted above, the real life situation is nothing like a nice straight arrow, but much more akin to a convoluted, intersecting wad of spaghetti. Actually, even that is an oversimplification, as in reality there would be multiple wads of spaghetti, all equally and sufficiently funded, but only some of which would straighten out in a direction toward a treatment or therapy, in time.
You may well be wondering why, in this time of economic cutbacks, would anyone advocate pumping money into a system with such an inauspicious and seemingly inefficient starting point? Can’t the early stages of the pathway be optimized somehow? After all, things do tend to become more streamlined and targeted near the top of the chart, and necessarily so. Clinical trials are expensive and laborious, and finding human subjects can be very difficult, so it makes perfect sense to test only the treatment with the best results to date, and therefore the best chances of success. Why not put the bulk of our financial resources behind the research with the highest probability of advancement toward the cure? We can’t, because the earlier, less directed steps are crucial for illuminating the path to the desired goal. That streamlining effect on the top simply can’t happen without a broad basis of scientific discovery at the beginning of the process. The trial and error inherent in the earlier steps is what defines the research directions pursued in the upper tiers.
Reflecting on the discoveries of the last century that have lead to improved human health, it’s easy in hindsight to identify the seminal discovery that paved the way for the eventual development of a new therapy (see, for example, the timeline to the development of Herceptin, a breast cancer drug.) However, in the here and now, we cannot predict which of the current experimental endeavors will yield the most useful tools for future treatment of human disease like Usher syndrome, and I would argue, quite emphatically, that it would be unwise to try. Efforts to streamline the early fact-finding, trial and error processes, however well-intentioned, may ultimately slow our progress. Imagine the long-term ramifications, for example, of a decision to reduce or eliminate funding to a line of research which might have made a key discovery about a cellular function, a delivery vector, something innovative which would turn out to have applications far beyond that for which it was specifically sought or developed. A fair number of treatments have emerged as a result of research focused from the start on a particular health concern, but many others have had their origins in deliberately untargeted research. The important point here is that we don’t know in advance where such inspired breakthrough discoveries might come from—indeed, there are numerous famous examples of major medical advances from unlikely origins (see some examples here and here). Thus, attempts to make predeterminations on which types of research will be the most fruitful for human health in the long run are risky indeed.
As Mark has written previously, the monetary amounts we’re talking about with respect to funding surpass the means of most individuals many times over, and beyond financial support, it’s hard to see a way in which the interested layperson can walk this path. So how can a non-scientist make any kind of impact on this vast and confusing system? How can one take this information and find that proactive outlet which, while it might not pay dividends for many years to come, could embody great benefit for future generations of children with Usher syndrome? Mark has previously mentioned some great ways to help contribute to amassing patient data, but here are a few more general ideas for your consideration:
1. Connect with researchers in your community.
If you live near a research university or a private research company, get online and look at the science happening there. Universities and BioTech companies often have community outreach programs in place already, designed to make their research and resources accessible to the layperson. Make your interest in Usher syndrome known up front, and they may be able to tailor the information that’s most applicable and interesting to you.
2. Connect your community with its scientists.
Scientists love to talk about their work, and we’re all very used to answering questions about how our work relates to human health. Consider inviting a scientist to speak at your next service organization meeting, or your church, or your school. Again, mentioning your interest in hereditary deaf-blindness will help make the message more relevant.
3. Support science education.
Science, along with many other subjects, is an underfunded pursuit in primary and secondary schools. Resources are stretched to the limit and teachers are faced with the challenges of instructing their students with minimal material support. Consider asking your junior high or high school science department for a ‘wish list’, and generating a community effort to supply some of these items. Alternatively, consider volunteering in the classroom to help with setting up science projects as needed.
4. Support science funding.
As already discussed, individual contributions to a specific research program from most of us are tantamount to a spit in the ocean, but the collective power of your tax dollars is, of course, what funds the National Institutes of Health, the National Science Foundation, and similar programs. Find out your representative’s voting record for research funding. Contact him or her and voice your support for scientific research funding.
I know that it might be a challenge to visualize how some of this more general science advocacy might have an appreciable impact on what you really care about, namely finding better diagnostic and treatment modalities for Usher syndrome. Please note that none of the above suggestions detract from whatever support, financial or otherwise, you’re already giving to clinical research or raising awareness of this particular disease. On the contrary, interfacing with the scientific endeavors underway within your communities could absolutely contribute to raising awareness of Usher syndrome. You never know when someone you come in contact with might be inspired to reexamine an old idea, or conceive a new one, with Usher syndrome in mind. Mark has made several prior mentions of the benefits of growing this Usher syndrome Coalition, so I hope this initial foray into the research arena might provide some of you with new strategies through which to advance this goal.
We’ve only just started on this journey. Next time I’ll talk more about the connectivity between these different tiers of research and the funding that ties it all together.
Monday, August 17, 2009
Jennifer and I will be writing along different paths for a while. Our posts will relate better over time, but I have to catch up on some of the postings I owe. First up is why funding organizations would be wise to invest in projects aiming to improve early diagnosis of Usher syndrome.
I’ll start with the horror stories and I have heard these numerous times. A researcher writes a grant proposal around early diagnosis of Usher syndrome. They submit the proposal to a funding organization who rejects it. In the rejection the funding organization states that it is an excellent grant proposal and would certainly help diagnose children with Usher syndrome earlier/more accurately/more frequently. However, they state, they do not feel that early diagnosis is appropriate/valuable/ethical at this time given that there is no cure for Usher.
Before we go further, let me take a moment to defend the funding organizations’ position because this type of response can seem bureaucratic, heartless, and near sighted. It’s actually the opposite. Funding organizations care deeply about the people that their funding aims to help. The last thing they want to do is fund a program that makes life worse for the people they are trying to help. That’s why they deny grant proposals for early diagnosis programs. They perceive that, as long as there is no cure for Usher syndrome, the emotional toll of an early diagnosis on a family outweighs the benefits for that family. In short, they think the program will make life worse for the people they, too, want to help.
We discussed earlier why early diagnosis is a good thing for a family. Here’s some reasons why funding organizations should invest in early diagnosis:
The cure might only be found through early diagnosis
Funding organizations are eager to help fund efforts to find a cure for Usher syndrome. As we discussed previously, there are treatments available today but nothing that would be considered a cure. We can’t say ‘do this and you won’t lose your vision’. But that’s from the perspective of older patients (and by older I mean non-infants). These treatments might prove dramatically more effective if provided earlier in life.
I’ll give one example. Almost all ophthalmologists prescribe the use of sunglasses to people with Usher syndrome. There are studies under way that seem to indicate that the vision aspect of Usher syndrome is aggravated by prolonged exposure to bright light. In one particular still in progress study, mice with Usher that had never previously developed the vision loss associated with Usher syndrome did so once they were exposed to bright light.
This study is still under way, mind you, and what I’m about to write comes from this keyboard and this keyboard only. It is not fact or based on any science. But just imagine this scenario. What if we find out that bright light is actually the trigger to the vision loss and once that progression begins, it can’t be stopped. In other words, what if simply putting sunglasses on an infant with Usher syndrome is all it takes to keep the vision loss from starting?
Again, there is no evidence to support this and the truth is that the likelihood is miniscule. But the reason we don’t know for sure that it doesn’t help to put sunglasses on an infant is because we have done a poor job of identifying infants with Usher type 1 and an almost non-existent job of identifying those with Usher type 2 and type 3.
The truth is we don’t know if these treatments are more effective if administered earlier because we haven’t been identifying patients earlier.
We lack knowledge about the early progression of the disease
We do not know the answer to some very basic questions. We do not know, for instance, if children with Usher syndrome have some degree of vision loss at birth or not and if not, when they do start to present the vision loss. In short, we know next to nothing about the early progression of the disease.
This is critical information for funding organizations to have because it could greatly influence where they put their money when searching for a cure. I’ll delve in to the hypothetical again for a moment. Say, for arguments sake, that all Usher infants are born with perfect vision and the vision deterioration does not begin until they are, say, six months of age. Well, we should be looking for treatments that 1) focus on maintaining vision instead of restoring it or slowing the degradation and 2) can be administered to infants. However, if children with Usher are born with discernable vision loss, the focus should instead be on restoring vision or slowing the progression. It also may be less critical that we treat infants if their vision is usually no different than, say, a five year old.
The point is we simply don’t know enough about the early progression of the disease and as such, funding organizations may not be wisely investing their research dollars.
Cost savings by eliminating other diagnoses
Look back through this blog and you’ll see the topic of eliminating other diagnoses in discussions about why early diagnosis is important to physicians, therapists, early intervention staff, and families. Well, it’s important to funding organizations for many of those reasons, too, but for one that doesn’t matter much to those other parties; cost savings.
Let me use our experience with our daughter as an example. Bella was born with hearing loss. There are a lot of causes of hearing loss. One in particular (not Usher) can cause heart problems. So Bella saw a cardiologist and had tests to eliminate that as the cause. Cha-ching. Bella was a late walker. She had low tone. We went to see a specialist on low tone. Cha-ching. Bella had balance problems. She seemed to be knock-kneed. We went to an orthopedic specialist. Cha-ching. The orthopedist thought that maybe she needed cookies for her shoes. We got those made. Cha-ching. The cookies didn’t help. Hmmm. Perhaps it’s neurological. We went to see a neurologist. Cha-ching.
You get the idea. Were Bella simply identified as an infant as having Usher there would have been no need for a cardiologist or a neurologist or many of the other appointments we went to trying to figure out what was going on. That’s tens of thousands of dollars the system could have saved. Somewhere Barack Obama is crying.
Cost savings by delaying vision loss
Low vision is expensive. Ask any adult that lives with it. You need training and transportation and specialized computer equipment and, in some cases, specialized interpreters. It all costs lots of money and is a burden not only on the patient but on the system as a whole. As we have discussed numerous times, there are treatments today (vitamin A, DHA, sunglasses) that may very well slow the vision progression. Let’s say for the sake of argument that providing these treatments at a young age only buys the patient one additional year of useful vision. Even that small amount of time and the associated savings is still a lot of money when we’re talking about 50,000 people. It’s also another year for technology to improve or reduce in price. Most importantly, that one year might be the year we find a cure, eliminating the need for all of it.
They are going to be diagnosed eventually
This is the most obvious and most often forgotten point in any discussion of the emotional impact of early diagnosis. You are merely putting off the inevitable. A child with Usher syndrome is going to have vision problems eventually. That child (or possibly an adult by this point) is going to see a doctor about that vision loss and is going to be diagnosed with Usher syndrome. Just because a child was not diagnosed with Usher as an infant doesn’t mean they didn’t have it as an infant. The family is going to have to deal with the emotional impact of the diagnosis at some point. Is it better for a teenager to find out he or she has Usher? A student going to college? A mom having a child? There is not good time to get the diagnosis. Which brings us to the next point.
Most families wish they had known earlier
No one wants to be diagnosed with Usher syndrome, but the lament I hear from families all the time is ‘I wish I had known earlier’. Parents alternately feel ashamed that they didn’t recognize the problem earlier and relieved that their nagging doubts were finally acknowledged. Families adjust to difficult diagnosis. Heck, all Usher kids have hearing loss. Very few of the families expected that. Yet no one advocates hiding that diagnosis from families. Early Usher diagnosis should be treated the same way. Yes, there is pain associated with it, but there is far more value in it for families, physicians, and for society as a whole than there is in delaying the diagnosis. Delaying the diagnosis, far from helping families, is doing them a disservice.
So funding organizations that have their heart in the right place should feel confident that putting money into programs that improve early diagnosis is not just right for science and for society as a whole, but for individual families as well.
Wednesday, August 12, 2009
Figure 1: Colorful liquids + Laboratory attire = Scientist in Action!
Aside from the fact that I seldom wear bowties, my own lab environment is quite similar to the one pictured here.
I am no one of particular importance. I am a miniscule cog in the giant mechanism of academic research science, and I’m ok with that because sharing the workload in this complementary yet orchestrated way is a crucial part of scientific advancement. The highly specialized nature of my work requires that I focus on a very small part of the big picture, but there is plenty of interesting and potentially significant work to be done in my tiny domain, and I hope to share some of this with you in the future.
Although I am acquainted with some young adults with Usher syndrome, I am quite far removed from the day-to-day realities of this disease in my professional realm. It is thus extremely beneficial for me to interact with the physicians, clinical researchers, patients and families who do deal with Usher syndrome on a personal, human level. I have gained much from these interactions and occasional collaborations, and by contributing to this blog I hope to give back a little to those from whom I have learned so much.
One of the frustrations that Mark has so eloquently expressed in this forum is over the current limitations of medical options for treating Usher syndrome. There are many fine ophthalmologists and audiologists out there who are providing the best available care, but the unfortunate truth is that treatments for Usher syndrome are not yet available, and the short answer for why this is the case is that we still lack the necessary information and/or techniques to create effective therapies or interventions. I fully appreciate how challenging it must be to face the effects of this disease knowing that medical science has yet to find the answers that really matter to you. It is for this reason that I hope my contributions to this blog will provide an additional source of encouragement by increasing your awareness of the breadth of research going on around the world that is contributing to our collective understanding of Usher syndrome and may aid in the discovery of new therapeutic applications.
Waxing expansive on the particulars of my job tends to be a total conversation-stopper at parties, and while it’s easier on my ego to attribute this phenomenon to a lack of shared knowledge or interest rather than poor social skills on my part (not that these are mutually exclusive conditions), I plan to apply this real life cautionary tale to my blogging efforts. In reporting scientific research findings relevant to Usher syndrome, I promise not to use scientific jargon without explanation, and to focus on delivering the main ideas without getting hung up on the details. Finally, although the aforementioned lack of shared knowledge or interest may initially present an obstacle in communicating the salient aspects of basic research and its connection to things that non-scientists care about, I don’t believe this is insurmountable. Knowledge can be conveyed, and if it’s done so in a sufficiently engaging way, interest will follow. To that end, I welcome and encourage questions, requests for clarity, more (or less) information, or coverage of different topics, so please don’t be shy about commenting!
So, that’s who I am and why I’m here. In my next post, I’ll attempt to provide a frame of reference for the different types of research that are conducted in our current system, and explain a bit about the flow of information between scientific discoveries and the application of those discoveries to human medicine.
It's been a few weeks since the last post but I have good news to report on the Usher blog. I'm no longer alone. Starting tomorrow I'll be joined regularly by Jennifer Phillips. I'll let her introduce herself in her first posting, but unlike me, Jennifer does not have a family connection to Usher syndrome. Her connection is professional and she'll be providing a scientific perspective that we hope will compliment my general Usher family perspective.
We expect to post entries weekly from here forward and we're both very excited about the collaboration. For a taste of Jennifer's past work, click here to view a four part series she wrote on the biology of Usher syndrome.
I still owe a number of posts as well and promise they will be coming soon. Watch for Jennifer's first post tomorrow.