Grudge Match

I haven’t spoken much about the drug research that is taking place in ALS Land, not because I don’t have skin in the game.  I am in the open label phase with the Biogen Idec dexpramipexole trial, and although we haven’t been unblinded yet, the rumors are rampant. There are other trials as well, one in Phase 2 that looks pretty interesting, and a seriously hyped stem cell trial in Phase 1.  Before ALS, I never thought about drug research.  That has changed in the last two years, although I don’t claim deep knowledge. In terms of drug research, I think exploration of intents and unintended consequences is instructive.  More specifically, how the larger interests of dis ease research, oversight, investment and profit affect me is something that I take very personally.

In ALS Land, the race is on for anything that will supplement the only drug currently approved for treatment.  That drug, Riluzole, was approved in the 90’s with less than stellar effects, but enough to throw us PALS a bone on the drug front.  Our reality is that in the 73 years since Lou Gehrig was diagnosed, no other drug has been developed.  There is a clear sense that this reality could change.  The three specific drugs or treatments mentioned above have us buzzing, and one of the drugs, NP001, has really caused a stir among the PALS community to the point of developing self-treatments.

The methodology adopted by the FDA in coordination with the scientific community for approval of a new drug is designed to keep the public safe and to definitively show that any positive effects are both significant and resultant of the drug.  The development of any drug requires hundreds of millions of dollars in resources—gargantuan infrastructures that can only be supplied by Big Pharma or the federal government.  This means that the entrepreneurial researcher-developer can only take a new idea so far, usually through Phase 1—determining safety and possible dosage, and perhaps to Phase 2—establishing whether a belief in the drug’s efficacy is well founded.  Phase 3—the gold standard randomly assigned, double blind, placebo controlled (meaning neither the researcher nor the participant know who is on the drug and removing the possibility of placebo effect), is almost always beyond the resources of start up or small operation entrepreneurs.  It is in Phase 3 that all promising ALS drugs have not been just downed, but crushed.  Thus, any drug that makes it to Phase 3 now attracts high interest, even though Phase 3 has not been kind to possible ALS drug treatments.

As an example, Biogen Idec paid 80 millions for the rights to dexpramipexole and took on the cost of a Phase 3 study with 900 international participants at 82 domestic and 10 international sites.  I don’t know the cost of the dex study, but I do know that Research and Development costs for Biogen were reported at over 1.25 billion in 2011 for all the trials they were running.  That represented over 26% of their revenue.  Biogen Idec is into Knopp, the drug’s developer, for up to 265 millions if the drug makes it through the regulatory gauntlet. All these figures illustrate the point that it costs a pile of money to develop treatments; thus introducing two specific considerations to the process–profitability and perseverance.

Clearly, there are two sets of desired outcomes.  The first is that we need more research and drug development in ALS.  This is the outcome I care most about.  It is literally killing me that we have nothing beyond Rilutek, the drug name for the Riluzole compound.  And Rilutek is expensive.  If it was not covered by insurance, I know I would probably not take on the 4300 dollar per month retail cost.  So that brings me to the second outcome that must align for a drug to be made available.  It has to show potential for profit.  Biogen estimates that their return on dexpramipexole could be as high as a billion dollars per year, representing an additional 20% in revenue over 2011 figures.  No wonder they are willing to put out such huge amounts of money.  And you can only imagine the costs and returns when you get out of the orphan diseases like ALS and into something like diabetes or breast cancer.

Stay with me; there is a point to all of this.

I need to establish a context for the way things are and why it would be so difficult to construct new ways of seeking effective treatments.  The current system is a Holy Alliance of government oversight, scientific rigor and capitalism.  Each fulfills a role that, when it works, can be very powerful.  We have seen great results of this triad in such areas as space exploration, food production, technology, and healthcare.  But as so often can happen, it is easy to emphasize one side over the other two.  And right now, it is hard to tell which–science, government or capitalism–has the upper hand.  If we overplay the science, then research for the sake of knowledge; brittle in its method, religious in its commitment, closed to further development, oblivious of the human costs its liturgies exact, is the result.  Overemphasis on regulation unnecessarily drives up costs and delimits access.  Too much attention to the bottom line means that the goal of new and more effective treatments can be lost to the call of profit.  When you consider the enormous resources brought to bear, the delicate dance that must be affected in order to bring a new drug to market is breathtaking.

See anything missing?

The Holy Alliance makes it easy to lose sight of the lives most affected by dis ease.  What happens if a startup has a good idea, gets it into phase 2, shows some efficacy, not a home run, not enough to attract the deep pockets of Big Pharma, but some?  Probably nothing, and that is the point.

An orphan disease like ALS, with the complexity of its manifestations that we are just beginning to understand, is not susceptible to a knockout drug.  More likely it will be some drug combination, each compound fulfilling a specific role in a mighty cocktail targeting everything from genetic propensities to the macrophages that are eating axons to the energy needed to keep motor neurons alive. The current model does not encourage the kind of iterative approach that complex dis ease requires.  There isn’t enough profit, science does not like so many variables, government is uncomfortable with the regulatory complications a cocktail will require.  The current model engages three partners, none of who make dis ease management their primary concern.

Please recognize that for each of us already diagnosed, it is too late.  Even though hope is always present, it is not really possible for a drug to develop and then be brought to market in time for us unless we are in a trial. The realities of a system designed for blockbusters combined with the cross purposes of profit, regulation and science, plus the fact that those of us who live in the dis ease milieu have very little voice in actual research decisions, points to the surety that our fates are sealed by such a lack of creativity.  It is fundamentalism at its best–the religions of science and regulation and profit unable to conceive of new liturgies through novel methodologies or yet conceived ways to analyze and reanalyze data, because there is no reason except the dis ease to do so.

Which brings me to the title of this essay–“Grudge Match.”

The Google definition of “grudge match” is “A contest or other competitive situation involving personal antipathy between the participants.”  I admit my own bad feelings, dare I say grudges, for systems that have calcified with the inevitable drift toward self-service that all bureaucracies experience.  And I freely admit that my understanding is incomplete.  But I would point to two salient facts that the system is not as robust as the billions of dollars it costs.  First, there exists a Phase 4 in the drug approval process in which follow up takes place, and there have been some major clunkers revealed by Phase 4 analysis—hormone replacement therapy comes to mind.  Secondly, a system that slaves to market forces will always yield drugs for male erectile dysfunction over orphan disease management.  Neither of these bodes well for complex human dis ease conditions.

As a choral artist, I am well aware of the creative possibilities humans can forge together.  Perhaps we need to place as much emphasis on researching new, more robust and creative methodologies, achievable with the resources of an entrepreneur.  Perhaps we should make it the rule rather than the exception that members of different disease communities have much more to say about the direction of research.

Or the system could work and I swear, all grudges would be forgiven.

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(F)un(e)real

It is inevitable, even natural for those of us with mortal illness, to think about our own funerals at some point in the dis ease cycle. Before you become overly alarmed that this week’s entry will degenerate into maudlin, whimpering memorial instructions, let me assure you that I will not be discussing any postmortem planning today. That isn’t to say that I haven’t thought about it, but you will just have to wait until I have crossed the great divide for such discovery. Instead, I bring up funerals because this week, I had an experience not unlike attending my own wake, my own funeral, causing me to consider how we do death, how we do life in this strange human forms we occupy.

There isn’t a culture or society that doesn’t in some way mark life’s passage through significant ceremony. What might look strange from outside the culture is perfectly normal inside. In high school, I remember reading about a society that dug up the bones of their ancestors every five years to take them out to restaurants, give them cigarettes and take care of those earthly pleasures the deceased might be missing in the afterlife. From my high school perspective, this seemed quite bizarre. But as I began to turn critical lenses on my own culture, my own background, my own society, I realized that this was no more strange than embalming the body of a great philosopher to sit watch in the school hall where he was headmaster, or of the practice of specially built rooms with red and blue lighting to ensure some faked lifelike quality to the mortal remains of the deceased, or the ossuaries in countless European monasteries and cathedrals with their piles of sorted bones from the men and women who served within.

While seemingly strange from an outsider’s point of view, many traditions surrounding death are based on practical need. Jeremy Bentham’s earthly remains aside, the ossuaries and funeral homes and entertainment of ancestral remains resolved cultural issues surrounding the dignified and ceremonial marking of the life and death of humans. And in our culture, the particular tradition found in the practice of the wake has specifically changed in form and function to accommodate both the practical and the sacred needs a postmodern death presents.

It isn’t known for certain when the practice of the wake was started, but most experts would agree that the term wake is from the practice of the family remaining awake with the body over an extended period of time to ensure that the departed was actually deceased. Many pre-20th century horror stories are based in the fear of being buried alive. Such an ending was considered to be so horrific that it inspired tales of the undead wreaking havoc on those who had propagated the horrible act in the first place. And it inspired the practice of sitting with the body and checking from time to time for signs of life to avoid such events. Family wakes morphed into the practice of the visitation when friends view the body of the deceased and greet the family as a sign of respect. The practice continues to evolve, so that remembrance and laughter sometimes encouraged by Irish whiskey and bawdy humor, are considered to be as appropriate as traditional tears and sadness and feelings of loss. It is a shame that we don’t get to attend these events held in our honor while we are alive, for the practice of sharing the deep feelings of love and gratitude for the life well lived is generally reserved for “roasts” of the rich and famous, or as is the case of the wake, for postmortem remembrance.

I cannot help but think that humans are impoverished by such practice.

One of the great gifts of ALS results from its speed of progression. ALS is not a gunshot severed, car accident, 100 days to live brain cancer; the sudden and heart wrenching black hole death that leaves lovers and loves alone in the endless caverns of their souls, pouring grief and remembrance and remorse and regrets for words and feelings unheard and unsaid in some vain attempt to mitigate the departure of their loved one. In each host body, ALS moves at its own speed–50 percent mortality after three years, 80 percent after five and 90 percent after ten. The greatest ALS gift I have experienced is the time afforded wakefulness, Irish whiskey notwithstanding, encouraging both formal and informal expressions of love before mortality, of declarations of meaning before death.

This past week, I was granted the privilege of love’s expression that is usually disavowed and kept separate by the professional environment. My friends and colleagues at St. Thomas offered up a time of remembrance and laughter and tears and joy, allowing us to say what was inexpressible when I left. An emotionally charged and highly meaningful event, it left me exhilarated and exhausted and highly reflective on the nature of life and love and the insistent teaching of dis ease. Indeed, my dis ease teacher asked, “What were you waiting for?”

I guess I was waiting for ALS.

It is so easy to withhold ourselves, for we are taught the benefits of remaining circumspect and less than forthcoming. When I write, I sometimes hold back things that I deem hurtful or embarrassing or that might make me too vulnerable to others, or them to me. Such prudence is a valuable skill to develop, especially in discharging leadership responsibilities where the inappropriate or premature disclosure of information can be harmful. But there is a price to such non-disclosure. We also lose the distinct, even sacred connections, human to human, that make for the spiritual life intertwined in the holiness of each other. If I extrapolate on the teachings of dis ease, the honest sharing of feelings is an opportunity often missed.

I cannot tell you how many times I hear from friends the following: “I read your blog, and I don’t know how you do it. I could never be so open but your openness helps me.” I am thankful for that sentiment, but it inspires in me the dis ease question, “Why not?” Dis ease strips away embarrassment and completes the lesson–we are meant to share this human existence in honesty and love, and our value is in the value we build in each other. To express our lives is an expression of love. To not express that love, to withhold it out of fear that others would think less of us, demeans our humanity, raising fundamental questions of being. What are you waiting for–to tell someone what they have meant to you, what they have done for you, how their presence and love and joys and sorrows and defeats and challenges and victories have fed your soul, nourished your life, taught you a humanness you couldn’t imagine any other way? What are you waiting for to say, “I love you.”

So, attending my own wake while still alive and present, with words and feelings and experiences shared before death’s loss made the event too late, was the circle completed, the human connection sanctified, the love expressed. And honestly, in spite of a few pictures that maybe revealed my lack of judgment about hairstyle in the eighties, it is the most sublime experience I could imagine. I am thankful and awed and blessed by my colleagues and students.

What was I waiting for?

Eventuality

In so many ways, it has been an “aha” week for me. As I complete my first month-and-a-little, post-work challenge, the struggle to find a rhythm, a personal harmonic in synchronous vibration with my disability’s fundamental tone—defined by dressing for ease and not for the job, more and more intimacy with personal care assistants, lunches with friends, longer naps than I ever thought possible, the need for more and more physical support–has been the true north of my journey. I say true north as my direction seems to have veered from the magnetic attraction of the destination, toward what is a much more real, more dis ease accommodating journey.

We humans love to describe life with the journey metaphor. And why not? The path is clear; birth, childhood, adolescence, adulthood, work, relational commitment, parenthood for some, empty nest, maybe grandparenthood, retirement, agedness, and off we go into the light. I may not have named all of the points or their exact order, but the birth – death existence is quite a trip, and one that we all face. The uniqueness of the journey is in the dash between our date of birth and eventual death. Each significant occasion that marks our lives, seemingly unique to us, can be generalized in broad paintbrush strokes to humanity’s experience. And each occasion is an opportunity for growth or calcification.

Life growth and death brittleness come in many guises. Each of us might know growth through our partners, our relationships, our families. But we might just as easily experience the ravages of a relationship gone bad or a partner without commitment. How many of us know the pain of family dynamics framed by substance abuse or addiction? Each of us can hope for health in our lives, but we also know with certainty that what lies ahead will be marked by dis ease through manner of ways the human body goes wrong. We hope for good jobs and are aware of the tenuous nature of employment. The journey is not easy or sequential. For some, it looks like a straight path while for others, life is defined by events that are out of our control, clear leaps and bounds from event to event. Thus while the dash looks like a straight line from birth to death, life’s eventualities belie the look.

I know that you know this. I am just saying it for me.

This week, I found a bit of peace. It came through a slight reframing, a deeper spiritual understanding of my own journey line toward the death that awaits me a whisper of time from now. And I realized that the core idea with which I left my working life, consisting of a list of things to do, accomplishments to be checked off day to day and week to week, was silly. I am not retiring at the age of 65 with a hope of 20 years ahead of me for travel and all of the things I haven’t done. I have not reached a pinnacle in my professional life that feels worthy of celebration and satisfaction. Ev and I will not be selling the home and moving to a desert island. Nor will I be devoting my leadership experience to serving on the board of some meaningful nonprofit. I’m not going to start training to compete in the 70 and older bracket of the Ironman. “My hands are tied, my body bruised, she’s got me with nothing to live for, and nothing left to lose;” Bono’s religious romantic tome to existence pretty well sums it up. It is harder and harder to communicate through my hands, my ALSFRS is down, I cannot bathe or dress myself, eating requires assistance, I tire easily. What was I thinking?

Sometimes, epiphanies are so quiet they scream.

None of us is granted such prescience as to know the exact moment of our ending until the moment happens. And there is my “aha.” I truly do not know how much time is left me in this wonderful life. I do know that I will die eventually. The epiphany moves me from a peace that waxes and wanes in its ALSness to a peace that waxes more and wanes a little less in its utter humanness. My problem has not been with an impossible concept of retirement, but more with the feelings of loss and grief at the lack of such possibility.

My problem has been me.

What I am trying to do, what this new realization seeks to teach me, is to recognize inevitable frameworks of eschatology. Tom Waits said it when he paraphrased the early Christian church, “Jesus gonna be here, He’s gonna be here soon.” It is not my place anymore to plan for an existence beyond the day, the hour, the very second of breath and life. Rather, it is enough to seek a good day no matter what.

Why didn’t I figure this out earlier?

One of the more interesting concepts to come out of late 19th and early 20th century anthropology is the so-called “cargo cult.” A cargo cult in its classic sense is when a pre-industrial population becomes aware of the availability of goods and services associated with industrial manufacturing societies, and seeks to attract those goods without the manufacturing culture required to make them. Often, this would be manifest in rituals such as building airstrips or docks even though the society owned no planes or seafaring ships. The cargo cult is useful for explaining some of the more bizarre behaviors we observe in the zigzag line of human existence. In an effort to bring the goods home, we come to believe that we can construct a plan for everything, accounting for every variable, smushing in every single experience that we think we deserve, usually within some ritual that becomes less and less tied to the actual facts our lives exhibit.

All my life, I have been waiting for the cargo.

It seems that no matter how clear the lesson, I still try to build my life like a runway to attract perfection, to exercise control in a way that results in the plane landing with all of the straight line journey items I could desire. You can name the journey as you like, but for me, it was leaving behind me the negatives, the things that didn’t work, the imperfections, the losses, by exercising the rituals of retirement so that the cargo would arrive.

This week I realized that I “retired” at the age of 85, not 65. That changes things. This week, I stopped waiting for the cargo to show up. This week, the steady progression of ALS, point after point, and the obvious tasks that are now beyond me, illuminated this new understanding. It is enough to have a good day, hour, minute, second. Therein is the rhythm I sought, the harmonic I needed.

And eventually the cargo actually arrives, and the journey ends with the perfect harmonic and a compelling rhythm wrapped up in melodic wonder.

The Voices

The Voices

I have been thinking about the connection between voice and breath as a way to understand this new existence framed by my now official disability status. For persons with ALS, the physical manifestation of voice holds added meaning–bulbar onset usually means we lose our voices quickly in the dis ease progression, while limb onset means we agonize and worry about the vocal loss freight train rumbling toward us at its own unstoppable pace. You can measure vocal loss by the tinny electronic voices synthesized for our use. Of even greater significance is the breath. We who attend ALS Clinics or who participate in Patients Like Me ALS forums are well aware of the Forced Vital Capacity measure. Once it drops below a certain percentage, we are ineligible for most drug trials, causing pulmonary specialists and neurologists to start talking bi-pap or worse. The irony of the juxtaposition of my former life as a choral musician focused on breath and voice, with my dis ease that seeks breath and voice eradication, does not escape me.

When you direct a choir, one of the most important things you work with is refining the voice, the instrument of the choral experience. The voice is unique, intimate, indicative. In times of anger or sadness or lust or joy or any number of other descriptors that define the human experience, the voice more often than not shows first effect and last recovery. Under such circumstances, even the most rigorously trained cannot hope to vocally project without betraying emotion’s effects. While most of us learn to pay attention to a person’s body language, my choral identity taught me to listen more than look as a way of checking for truth. This was pretty useful as a high school principal as I could often detect small telltale signs when one of my kids was struggling to keep something out of their voice in order to obfuscate the full story. And it was a skill I continued to cultivate even as a college professor and administrator. It just helped me to be more empathetic, to hear the story around the words, to help construct a narrative we all could live with, agree on, even discard when no longer needed. All of this came from my early vocal training.

Humor me. I need to go back to the basics to sort this out.

The voice is dependent on breath. In an amateur choir, if you care about the quality of the collective sound, you probably spend more time on breathing and its association with vocal production than everything else combined. The breath is the foundation, the root, the connection we must establish and maintain for the voice to have presence, space, focus. If you are not connected, then the voice becomes reedy, airy, unsupported, out of kilter with the body and, believe it or not, disconnected from the soul of the music. Breath brings richness and presence and confidence to the most unsubstantial voice, and I often found great joy when a singer suddenly discovered the power she or he could project by attending to the breath. One of the outcomes of teaching choral musicianship was literally supporting my beloved singers in finding their voices, but even beyond this discovery was the hidden knowledge of the breath. In breathing is the most basic component by which we define life. You can perceive the sacred and profane in vocal production, determined by the holy life force found in the breath.

Or, another way to say it–if Pavarotti’s voice was God manifest, then the air he breathed was the Holy Spirit.

As a well inculcated western white male, the breath under my life-voice has always been a combination of my family, friends, work and holy spaces. It should be no surprise that I struggle to find my way into this new disability space since I was blessed with the good life’s work–preparing professionals to raise children to meet their potential, to effect wise leadership, to heal the rendered soul so life can move on. For me, the loss of my formal work is a kick in the gut, wind knocked out of me experience so that my underlying breath is out of kilter, and my new voice feels reedy in its quality. It isn’t that I am not breathing; I am just not supporting from the diaphragm, both literally and symbolically, as I used to do.

You probably noticed I did not post last week, with no explanation offered. I laid out two different blog entries using Dragon speech-to-text software, and in spite of vocally composing the pieces, I could not find my voice in the composition. It was like speaking down the large end of a megaphone–jumbled dumps of words with no center, no focus, no spirit crowding into the small space at the end–words tumbling out with no spiritual grounding, no real meaning except a chastising self-accusatory rant. Better not to put that out into the ethers.

And of course I set myself up with airy expectations of what one does when one “retires.” By now, I would have learned the software on which I must become more and more reliant. By now that book would be intellectually plotted. By now, I would have answered so many nice notes to thank people for their kind wishes and love, not to mention returning phone calls and thanking the countless lunch buddies generously checking on me and making sure I was fed. By now, I would have conceptualized the meta-analysis that would lead to revisiting failed ALS trials in combinations ripe for new conceptualization and success. By now, by now, by now…. Really, it is only today that I can admit the ravaged voice of intention without breath support.

In the past with this sort of challenge, I turned to concrete tasks. And last week was no exception. I organized and fixed the database that holds all the recorded music we own. I should have done this years ago. The ease with which I can find my daily soundtrack is delightful. But even here, I cannot escape the reality of loss. My left hand has now become a one finger wonder and as I type, it refuses to follow through or hover, dragging creatively random spellings into my attempts to standardize the labels that imbue databases with their utility. So the tried and true is another lesson in loss.

I am missing something.

In a choir, in any musical ensemble that strives for wholeness, holy unity, there is something else that brings you closer to the face of God. Like life, choral singing requires a delicate balance between the empowerment of voice and the responsibility to the ear. And there it is. We listen so that we can be one voice comprised of many, powerful in our foundations and sensitive to each other and the call of the musical task at hand. And I must do the same.

If I listen, this is what I hear.

There is nothing wrong with sitting quietly on a cloudy day just listening, listening to the sounds around me, listening to music or poetry or words or the inner voice that speaks when all is quiet. Find the quiet center. Find the purest tone. Find the holy. Find the always present voice, often drowned, over washed by the noise of productivity’s need. If the norm is loss, let go of the need to gain. Let go of the need to hold onto that whose ending is already written in the stars. Live through the ending, knowing that there is beauty in every moment of every breath, in every song, in the silent spaces, voices and breath and music.

If I listen.