I thought I’d post a quick update in case anyone was wondering what was up … The good news is that my…
Stephen Aldrich is a retired entrepreneur educated as an evolutionary biologist at Harvard (1978), who was the founder and CEO of bio-era, a firm that provided insight into the economic and societal impacts of enabling biotechnologies.
In 2017, he was diagnosed with terminal metastasized (stage 4) adenocarcinoma of the esophagus. Steve refused to accept the palliative standard of care indicated for his diagnosis, and instead, decided to pursue integrative curative treatment independently. On the allopathic side, he began by having his whole healthy genome and whole cancer genomes and microbiomes sequenced very soon after his diagnosis, knowing that gathering this data could eventually be key to identifying treatment options that might work best given his particular genetic makeup, and the unique genetic makeup of his cancer. Control over his fundamental raw data sets has enabled Steve to identify and pursue cutting-edge personalized precision medicine treatment options from the beginning of his journey to regain his health.
The data on Steve’s cancer genome allowed him, with the help of an oncologist, to match his genetic profile with an attractive Phase II immunotherapy clinical trial testing two checkpoint inhibitors: Pembrolizumab and Epacadastat. This gave him the confidence to abandon chemotherapy and move on to the trial, which proved effective in halting all progression of his disease. While participating in the trial, Steve took advantage of his good health to further leverage his genetic data in order to design and test a personalized therapeutic vaccine. Once his vaccine had been designed and tested, Steve left the first trial testing two checkpoint inhibitors in order to enroll in a UCSD trial that will manufacture and administer his unique personalized vaccine.
Stephen Aldrich is embracing various lifestyle changes (see below). He works with an acupuncturist and a naturopathic oncologist.
Stephen Aldrich lives in Stockbridge, Vermont with his family, where he produces excellent maple syrup and fine apple cider.
MY ENTREPRENEURIAL RESPONSE TO TERMINAL CANCER
My name is Stephen Aldrich. I’m 63 years old, happily married with two fully grown children, and the retired founder and CEO of Bio Economic Research Associates (bio-era). My wife, Deborah, and I live very active and fulfilling community-based lives in a rural corner of central Vermont.
A FATAL DIAGNOSIS
On March 31st of last year (2017), following several months of nagging pain in my upper abdomen, I was diagnosed with metastasized (stage 4) adenocarcinoma of the esophagus. There is no known cure for this disease. Historically, about half of those who receive this diagnosis die within a year. Most of the rest die within the following year. The 5-year survival rate is well below 5%. Because there is no known curative course of treatment, the current standard of care is strictly palliative. Standard treatment is not intended to provide a cure, but may extend life for a few months – depending on the patient’s tolerance of, and responsiveness to, the current palliative standard of care — FOLFOX chemotherapy infusions every two weeks.
For me and my wife, receiving such news was completely devastating. Trying to wrap our minds around the implications was both heart and gut-wrenching – and completely disruptive. We had been deeply enjoying active and intensely involved, meaningful lives – only to have our joyful existence suddenly shattered by this horrible news. I was on the Board of our local public transportation company. I was the Chair of BALE, a local non-profit focused on Building a Local Economy, and I was the founding President of the White River Investment Club, whose mission is to empower members to help themselves and their communities through investing locally. Deborah was equally entangled – serving on the vestry of our local Episcopal Church, the board of our local Food Pantry, and as the founder and driving force behind a hugely successful “Community Meal” aimed at strengthening our local food economy and providing ALL local residents with free, wholesome, locally produced and deliciously prepared food. My diagnosis meant that all of these involvements would have to come to a sudden end.
Our immediate future also included cherished family plans, including a long anticipated trip to Spain for a family wedding (departing May 18th) and a summer rental by the shore in late June and early July.
All of these involvements and plans were now thrown into doubt and turmoil. Suddenly and without warning, we had to completely rethink and reorder our lives while simultaneously trying to process emotionally devastating news, deal with my rapidly deteriorating health, and learn enough about my illness to do something about it.
RECLAIMING THE RUDDER
There is a Taoist story of an old farmer who had worked his crops for many years. One day his horse ran away. Upon hearing the news, his neighbors came to visit. “Such bad luck!” they said sympathetically. “We’ll see…” the farmer replied. The next morning the horse returned, bringing with it three other wild horses. “How wonderful!!” the neighbors exclaimed. “We’ll see….” replied the old man. The following day, his son tried to ride one of the untrained horses, was thrown, and broke his leg. The neighbors again came to offer their sympathy on his misfortune. “We’ll see….” answered the farmer. The day after, military officials came to the village to draft young men into the army. Seeing that the son’s leg was broken, they passed him by. The neighbors all gathered round to congratulate the old farmer on how well things had turned out. “We’ll see…” was all he said.
The emotional roller coaster Deborah and I were riding provided plenty of reason to remember and take to heart the old farmer’s wisdom. From one day to the next, we were careening from hope to despair back to hope – only to have it happen all over again. The attitude of the old farmer is exactly right for that ride… steady as she goes…. with the humility to understand that no one knows how the future will pan out. For us, keeping this awareness top of mind has been critical to navigating the turbulent waters flowing from my cancer diagnosis.
A MODEST INITIAL GOAL
Deborah and I recognized right away that although we were initially the only ones who knew about my terminal prognosis, this would have to change quickly! We needed to figure out how to share the news with our two adult children first, then with our wider circle of family, friends and colleagues. Given the size of our social networks, we realized that we must manage communications with those who were concerned about my health. Neither of us could afford the time to always be repeating the same information about how I was doing! To help with this, we decided to open up a free, CaringBridge website where I could post information just once, and everyone concerned could ask questions or leave best wishes. This proved to be a very efficient way to keep everyone informed while controlling the message. It also provided a huge boost to our spirits (and my immune system, I’m sure!) to see the outpouring of prayers and support that flowed through the website directly into our hearts! The importance of receiving such messages of emotional solidarity, care and support cannot be overstated!
It also quickly became obvious that if I was to survive long enough to see my extended family one last time, I needed to get effective treatment fast. While my health had been bad for several months, I was now clearly in accelerating decline. It was tough enough that my doctors were saying I was going to die from this disease relatively soon, but if that was to happen, I wanted one last chance to share a celebratory “goodbye” with those I most loved – and that meant I needed to be healthy enough to travel to Spain in May – just a short six weeks following my initial diagnosis. My hope was that if I could get treatment fast enough, it MIGHT knock back my cancer (and my symptoms) just enough, so that I could make the trip. That was my initial and somewhat modest hope… to get conventional treatment ASAP, so that I could travel to Spain and share a celebratory “goodbye” with those I most loved.
But to accomplish anything at all, I quickly needed to disengage from my then current obligations! This alone was going to take considerable time and attention, and would leave me little capacity for figuring out the best treatments in response to my diagnosis. I needed help.
Just at this time, a close friend in whom I’d confided said, “this is going to be your research project of a lifetime”. But at that moment – still in shock from my diagnosis — I had no absolutely no appetite to research anything! It took me several days of living in my new reality before it dawned on me that I had spent the better part of my professional career building and managing research teams. I knew how to do this! I decided to form an “Advisory Board” composed of people with relevant expertise who had known me for many years. My board would combine allopathic medical practitioners, scientists on the cutting edge of emerging biotechnologies, terminal cancer survivors, and naturopathic alternative healers. I composed and sent off a letter explaining my situation and asking the recipients if they would be willing to help. Much to my surprise, all of the invitees graciously accepted! Shortly thereafter, I convened an introductory “getting to know you” conference call and secured an on-line collaboration workspace (www.samepage.com), and we were off and running.
The first order of business was to prepare for my initial evaluation at the Dana Farber. Luckily, we had been able to secure an appointment on April 13th with Dr. Douglas Rubinson, a dynamic, 40 year old, gastro-intestinal oncologist who’d earned his undergraduate degree at Princeton, his medical degree at Yale, and his Ph’D at MIT. I had two weeks to learn as much as possible before engaging with him. As the founder and CEO of Bio Economic Research Associates (bio-era), and had authored or co-authored numerous publications on enabling biotech, including “Genome Synthesis and Design Futures: Implications for the US Economy” (2007), my professional background was helpful, but the input of my advisory board proved invaluable.
Two members, Dr.’s Anthony and Carol Somkin, were longtime close friends with highly relevant professional experience. Carol had spent her career as a sociologist studying the interface between patients and the medical system. She immediately sent me “Radical Remission: Surviving Cancer against the Odds”, by Dr. Kelly Turner. This book became a kind of bible in guiding my overall response. Dr. Turner studied over 1,000 cases of radical remission in stage 4 cancer patients. Her book reports on what is common across all the diverse approaches taken by these survivors. Her key insight is that those who are successful at achieving full remission don’t just passively accept whatever their allopathic provider prescribes. Survivors take an active, self-directing interest in every aspect of their response to the illness. Dealing successfully with metastasized cancer is not a passive, part-time activity. Restoring health and wellness requires a full-time commitment to critically examine (and make changes if necessary) across nine key areas.
Dr. Steven Mirin, another close friend and advisory board member, had a career that included stints as a CEO specializing in turning around hospitals. He’d been very good at it, and coincidentally, had been retained not long beforehand by the Dana Farber to help restructure their management practices to better align their sometimes conflicting research and clinical care missions. Needless to say, his experience and advice were invaluable to my preparations.
Two other physicist-trained board members, Dr. Andy Erickson and Dr. Robert Carlson, helped me better understand the sometimes mind-numbingly complex (and impossible to pronounce) developments in cancer biology and immunotherapy.
Another very close longtime friend and evolutionary biologist, Dr. William Stubblefield, shared his knowledge with me on the immune system and the evolution of cancer. Bill was always ready to help me think through how knowledge of both can and should be brought to bear when considering treatment choices.
It was an enormous amount of material to digest, and without the help of my advisory board, I would not have been prepared going into my initial meeting at the Dana Farber.
TAKING AN ACTIVE ROLE IN DECISION-MAKING
I think another early choice I made helps illustrate the importance of taking charge of decision-making around treatment. In reviewing the pathology report of my initial biopsy, I noticed the pathologist had made a side-note identifying a Helicobacter pylori infection. I was familiar with H. pylori, and knew that it had been implicated as a causal factor in a surprising variety of human diseases of the gastro-intestinal tract, including cancer. One of the Advisory Board members at bio-era, Prof. Paul Ewald, was a “father” of evolutionary medicine, and a champion of the idea that many diseases with uncertain etiologies – both infectious and chronic – may have evolved their characteristic symptoms as adaptive traits serving their fitness interests as human parasites. The highly virulent human disease symptoms evoked by Cholera infection, for example, may have evolved because these severe symptoms increased the likelihood of the infectious agent reaching additional hosts. Paul has long pointed to H. pylori as another case in point, having been recognized only relatively recently as the true cause of stomach ulcers in humans, even though as much as an estimated 50% of the world’s human population harbors H. pylori without exhibiting obvious illness. The point of all this is simply that while my doctors were focused on other areas of concern, I insisted that I be treated to eliminate H. pylori — even though treatment entailed three antibiotics twice a day for ten days or more. I’m very glad I did. Within a couple of days of treatment, the pain at the site of my main tumor diminished dramatically. As I put it at the time, I had been feeling as if someone was pouring gasoline on my tumor, and that had now suddenly stopped. I felt much, much better – and no longer as if I was sliding down hill fast… How important was this to my subsequent recovery? No one has any idea, but my “gut” feeling is that it was pretty important…
RECIPE FOR ACHIEVING A RADICAL REMISSION: RECONSIDER EVERYTHING
For me, responding to my diagnosis meant having to quickly reconsider everything. Certainly, getting the best and most “advanced” scientific or allopathic care was an important priority – but there were other priorities too. Kelley Turner’s book, “Radical Remission” makes it very clear that people who survive terminal cancer diagnoses have more in common than just their doctors and their allopathic treatment choices. Her analysis of more than 1,000 cases of radical remission revealed that survivors were also doing the following things:
My friend and advisor, Anthony Somkin – a distinguished retired internist — sent me a beautiful short list of lessons he’d learned over his decades of treating terminal cancer patients. One of his lessons immediately attracted my attention:
OPENING UP TO THE IMPORTANCE AND EFFECTIVENESS OF COMPLEMENTARY CARE
Here’s one experience that reinforced this awakening:
One Monday morning in early April very shortly after my diagnosis, I suddenly just started feeling awful all over — deeply ill is probably the best general description. Abruptly feeling “deeply ill” when you have just recently received a terminal cancer diagnosis is both physically uncomfortable and psychologically and emotionally unsettling… “Am I declining suddenly and seriously? Is my tumor spreading everywhere, or suddenly ballooning?” These are tough thoughts to have passing through your mind — especially if you are alone for most of the day and into the evening. Anyway, with the help of what I’d learned from my two cancer survivor advisors regarding things they relied on under duress (focus on your breath, listen to soothing music, relax, and center yourself) — along with some emotional email therapy with a close relative, and a sleep aid — I was finally able to fade off.
Upon awakening the next morning, I felt somewhat better initially but things started to go south quickly. As it happened, my wife, Deborah, had already scheduled an appointment for me that day with a local “Integrative Health” specialist I’d seen once before. I described the whole thing to him, and he quickly suggested a treatment plan which included acupuncture. I’d never tried acupuncture, and have always been “skeptical”, but given how I was feeling, “what could it hurt?” So right then and there I lay down and put in my earbuds for some soothing, centering jazz, while the acupuncturist carefully applied the needles. Sometime later, he took out the needles, I took out the earbuds, and low and behold, I was feeling much, much better! Gone was the “whole body” distributed feeling of discomfort and pain — and the dark and sour mood that went with it! Instead, it was as if the general discomfort had been reduced and contained to a much more localized area. As I put it after arriving home, it was as if I now had a sprained ankle, rather than every bone in my body being broken! So, I became convinced through direct experience in the efficacy of “complementary care” options — and I have remained open ever since to actively pursuing their use.
The naturopath who prescribed the acupuncture, Dr. Chris Hollis, also recommended that I meet with one of two naturopaths in Vermont focused on cancer. Taking this advice transformed my general health. Dr. Casey Ellison, the bright, well-educated, warm and scientifically competent young naturopath I eventually connected with, offered me gentle but compelling reasons to transform my diet, and prescribed a personally tailored regime of medicinal herbs and immune boosting supplements. Incorporating and following her guidance eventually yielded many positive changes to my overall health and wellness. Once again, while no one can say how important this was to my recovery, my feeling is that it was very important!
HIRING THE BEST
And finally, realizing that even though I had a leg up on other patients because of my professional background and my advisory board, I also knew I needed even more help. Fortunately, Steve Mirin knew of a highly qualified independent oncologist I might want to consider for my medical team – Dr. Jason Sager, a 47 year old cancer specialist and former Chief Medical Officer for several major pharmaceutical companies who had started his own company, Sagely Health, to work directly on behalf of stage 4 cancer patients. Our subsequent working relationship provided me with a crucial counterweight to the intimidating authority of the Dana Farber. Eventually, I would decide to adopt the allopathic course of treatment that Jason and I mutually determined to be best.
DIAGNOSIS TO DANA FARBER: A BUSY TWO WEEKS
All this happened – or was put in place – within the period between my diagnosis on March 27th and my first appointment at the Dana Farber on April 13th, 2017. It was perhaps the busiest, most intense couple of weeks in my life! Because there was so little time, it had to be. I had to learn as much as possible as quickly as possible about my disease, how to live with it in the moment, and how best to respond — while simultaneously thinking through endless scenarios. I was aware that to have any chance of success, I had to make extraordinary demands of myself and those I came in contact with. And I was aware that my own perspective and attitude were going to be very important determinants of how I would do. For example, I knew that in this situation, panic and fear were enemies, as there is strong evidence that fear and anxiety can depress immune response. I certainly didn’t want that! Instead, I felt I needed to maintain the positive even keel of the old farmer in the Taoist tale.
Fortunately, Deborah and I had been morning meditators for many years, and we were now able to rely on our daily meditation practice to help us recapture, maintain and strengthen our mental, emotional, and spiritual equilibria. I had long ago noticed that in meditation, if I was fully in the present moment everything was fine – and in a certain sense, I was “untouchable”. For me, the present moment is literally the land of no suffering and no death, and from that position of awareness, there is no fear. In the present moment I am completely OK no matter what. So, I cultivated that awareness – and the peaceful, unattached, and loving attitudes that come with it. This helped immensely. Even so, the intense demands of this initial period exacted an enormous toll.
THE NEED FOR AN OVERALL RESPONSE STRATEGY
In another sense, this intense period of learning was also about searching for an overall strategy. Given what I had learned from Kelly Turner’s book and my own experiences, I understood that I needed to change and respond across many areas, but how so? For each area – what should I do? What were the options? How should I evaluate them?
As a former strategy consultant to Fortune 500 companies, I suppose it should be no surprise that I felt the need for a strategy to guide and inform my tactical choices and decisions. From my early exchanges with the doctors who were aware of my case, I was puzzled by the lack of interest they showed in the idea of a patient having a broad treatment strategy. They seemed to think that was really their job, and not mine. But actually, I found they really mostly didn’t understand “treatment strategy” in quite the same way I did.
In my view, a treatment strategy is a relatively high-level set of general principals to be followed by all those coordinating treatment of a disease. In other words, I wanted to find a treatment strategy that would serve as a guide for me and others to follow in making day-to-day tactical decisions aimed at achieving a particular outcome, i.e., the goal of the treatment.
So, the first and most important question seemed to me to be “What is the goal of the treatment?”
Historically, people with metastasized adenocarcinomas of the esophagus have very poor prognoses – i.e., they are generally expected to experience a steady decline in health culminating in death within six to eighteen months of their diagnosis. There are no known cures.
For such cases, the widely accepted and established allopathic first line standard of care is fundamentally palliative – meaning it is not designed or intended to fully eliminate the disease, but rather to delay disease progression with the goal of extending the patient’s quality of life for a few months. The system used to establish this standard is the FDA’s regulation of drug availability requiring all drug-therapy candidates to pass through several phases of controlled clinical trials in order to establish their safety and efficacy. In general, recommended standards of care are based on therapies that have passed through the first three phases of clinical trials and established a statistically significant AVERAGE or MEDIAN result that is the best within the class of available FDA approved alternatives. This system has endorsed FOLFOX as the first line standard of care treatment for metastasized adenocarcinomas of the esophagus.
FOLFOX is a combination of three chemicals administered through intravenous drip infusion over 48 hours, with the first two chemicals (Oxaliplatin and folinic acid) being infused over the first two hours, and 5-fluorouracil drip infused via portable pump over the next 46 hours. As with most chemo-therapies, the idea behind this treatment is that cancer cells are less robust than healthy cells, and therefore, upon exposure to toxins, they might be expected to have differentially lower tolerance and survivability. Thus, exposure to what may be toxic but tolerable levels of poisons to healthy cells, may deliver lethal exposure to cancer cells.
While this idea or strategy has been a principal driver behind the development of chemotherapies since the rise of Sidney Farber in the 1930’s, it is now known to have certain drawbacks and limitations – especially when used with palliative intent. It is widely accepted that FOLFOX is not curative of metastasized adenocarcinomas of the esophagus. It is also widely known that the longer a FOLFOX treatment regime is administered, the less effective it becomes. This is because genetically resistant clones arise out of the highly mutagenic core cancer and come to dominate in response to the continuous selective pressure imposed by the FOLFOX treatment. It is also widely known that FOLFOX toxicity toward healthy cells increases with exposure, and thus the more it is used to treat a cancer, the more intolerant the patient becomes to its further use.
GETTING EXPLICIT ABOUT TREATMENT GOALS
All these considerations lead us back to the most important question, “What is the treatment goal?”
Although the goal of the current first line standard of care for metastasized adenocarcinoma of the esophagus is strictly palliative, I was not bound by this! In my view, my treatment strategy should be guided by three goals which I here list in order of their priority…
There are two principal reasons why I dissent from the assumption that my diagnosis should dictate a palliative response.
First, driven by rapid advances in fundamental biotechnologies, the explosion of knowledge in the biological sciences and our understanding of cancer is driving revolutionary change in cancer treatment at break neck speed. The existing system is being overwhelmed with new knowledge at all levels, along with novel treatment approaches and therapies, and simply cannot keep up.
Second, our general understanding of how best to address rapidly evolving diseases – whether AIDS, or multidrug resistant bacteria – strongly suggests that the early and indiscriminate use of a broad spectrum selective agent such as FOLFOX may be both unnecessarily wasteful and counterproductive-over-the long-term. Our new understanding of how to address rapidly evolving disease agents depends, of course, on the GOAL of the treatment. Is your goal palliative or curative? In the latter case, the first line standard of care therapy for adenocarcinoma of the esophagus could be making your job much more difficult as time goes on. Not only does the treatment lose effectiveness with use while the patient’s intolerance grows, but the treatment may also be inflicting direct damage to the patient’s main ally and defense – the immune system. This is precisely the dilemma I faced in deciding whether or not I should continue with additional FOLFOX treatments.
These two considerations — the overwhelmingly rapid advance of enabling technologies, information, and knowledge regarding cancer and cancer treatments; and the irresistible evolutionary dynamics that must underpin all treatments aimed at eliminating or successfully managing the disease – suggested to me the need for some general strategic principals to guide my treatment.
MONITORING DISEASE PROGRESSION
But before determining a guiding strategy, I needed some way of monitoring the status and progression of my disease. I had been flabbergasted to discover how limited the ability to reliably measure disease progression was for someone with my diagnosis. All cancer patients should be monitoring their disease, but many don’t have good ways to do so. For adenocarcinoma of the esophagus, there is no single blood marker that reliably reflects disease status or progression. It seemed “bizarre” to me that after 50 years of intense focus on developing protocols for cancer, we still don’t have cheap and reliable ways to monitor disease progression for many of them. As a consequence, patients can be left in the dark about how they are doing, at least until they have their next X-Ray, CT, PET, or NMR imagery at hand. In the meantime, they may not be able to answer even very basic questions like, “Is your treatment having a positive impact on your cancer?” I needed to figure out how to cheaply and easily monitor the status of my disease prior to considering a treatment strategy. The best I could do was monitor two cancer-related blood proteins: Carcinoembryonic antigen (CEA), and cancer antigen 19-9 (CA 19-9). While neither is a reliable marker by itself for my type of cancer, following how they are both behaving over time can provide some insight. If both are trending up fast – that’s a bad sign. If both are trending down, or are within normal limits – that’s good. With a plan to have blood drawn every two weeks in order to test my blood levels of these two proteins, I was ready to finally move on to considering what my treatment strategy should be.
MY TREATMENT STRATEGY
For help and inspiration, I turned to the ancient Chinese Taoist and military strategist, Sun Tzu, the presumed author of the renowned, “The Art of War”. In Sun Tzu’s writings I found much that was relevant for guiding my response to cancer. Thus, I proposed the following guiding strategic principals to my research advisors:
THE DANA FARBER
I was quite sick as Deborah and I made our way to our initial consultation with a young Dana Farber oncologist on Friday, April 13th, 2017. Just getting to the meeting was a physical struggle. I couldn’t walk any distance without breaking out into a profuse sweat, and I needed to stop repeatedly on the short walk to the appointment to rest and catch my breath.
I was reasonably prepared though, and when we were ushered in to the examination room to meet with the young Dr. Rubinson, I had a plan. First, I got him to agree on how the meeting should go. We agreed that first I would listen to his reflections on my situation, then I would read him a short two-page statement of my principal questions and concerns, and then I’d yield the floor back to him and he’d respond however he wanted… Although we agreed to this in advance, it didn’t quite go that way…
First off, his initial reflections were mostly general about the nature of my cancer, the treatment regime he was going to recommend, and the wonderful quality of care at the Dana Farber – “where the patient is always in charge and miracles DO sometimes happen…”, etc. I don’t doubt that most patients find this initial kind of pep talk comforting and reassuring to hear, but not me. I had approached the meeting by doing as much as I could to prepare for the moment, and I didn’t want to waste a second. I wanted to get right to the meat of the matter. What was his opinion on the most promising treatment avenues and when and how might I access them…? But it wasn’t my turn to talk yet, so I patiently listened to his reflections and held my questions. When he was through, I began to read my short set of questions and concerns. I began with this:
My number one concern is Deborah’s health. News of my illness and the subsequent disruption has had a significant impact on her well-being. Her systolic blood pressure has risen and stayed 35 points above her normal readings over the last two weeks… She has also complained to me several times about angina like pains. However, because we have been scrambling to deal with the consequences of my illness, my up and down but generally declining health, and my need to make this appointment (which could not have been accomplished without her non-stop, herculean efforts), Deborah’s health has been sacrificed on behalf of my own. Would it be possible for her to be checked out by a competent professional before we leave this building?
I paused and looked up for his response, which was “I’m sorry, that just isn’t possible…” In response to this I began to rise from my chair, stuck my hand out to shake his, and said, “Well, it has been a pleasure meeting you, but I guess we’re done here now…” Apparently, this gambit caused him to reconsider and he said, “Well, I guess I could check her out myself…” and so he did, to our great, great relief!
With that out of the way, I continued my reading…
At all times during the staging, evaluation, and treatment of my illness — wherever those various steps occur – I must politely insist that the number one priority and consideration of all my caregivers be the impact on the health, well-being and disruption of my immediate family members — Deborah, Noah and Mia. Extending my survival at the cost of my family’s overall well-being is off-the-table. Since I’m in charge of my care, that’s the law, and I intend to enforce it.
This intentionally bold statement was meant to alert everyone at the Dana Farber that I expected to be in charge of decisions regarding my treatment and care. Not surprisingly though (and despite their promotional slogans to the contrary), the Dana Farber and I would not see eye-to-eye on this. It is one thing for hospitals to adopt a “we do the right thing” marketing slogan about putting the patient in charge. It’s another thing entirely when a patient shows up with enough knowledge and motivated determination to actually exercise decision making authority. It quickly becomes apparent (as it did in my case), that nothing is set-up to accommodate that.
Toward the end of the meeting, Dr. Rubinson did briefly touch on the topic of emerging immunotherapies – but only in a general way. In passing he mentioned some company names, including Foundation Medicine and Foundation One. When I heard the names I interjected, “Oh, that’s interesting, because Craig Venter mentioned them when he recently tweeted on my case”. Hearing this comment, Doug suddenly stopped, looked at me directly and said, “How do you know Craig Venter?” To which I immediately replied, “I’ve had a long and interesting career which I’d love to tell you about sometime, but for the moment, let’s get back to your thoughts on promising immunotherapies”. Unfortunately, we had been the last appointment of the day, it was now past 5:00 pm, and we’d run out of time. I had one last question. I explained that I knew the Dana Farber planned to do genetic sequencing of my cancer cells, and I asked if and when I could get access to the results. Much to my surprise and dismay, I was told that if such genetic sequencing was done, the DF had no obligation to share either the results or the underlying data with me. I would only receive an “interpretation” of the results, which they would prefer to provide to me over the phone or at a future meeting.
This news disturbed me greatly. I knew enough about the state of sequencing technology to understand that the oncopanel promoted by the Dana Farber as its genetic screening for cancer patients fell significantly short of what I considered to be best practice. I wanted high-quality whole genome sequencing done on my cancer, and I wanted access to the underlying data. The major cancer centers – including the Dana Farber – do not generally do whole genome sequencing on behalf of cancer patients. In many clinical circles, whole genome sequencing is considered unnecessary and extravagant. Instead, cancer centers typically rely on a genetic screening protocol referred to as an oncopanel . An oncopanel begins with cancer specialists identifying specific genes that have a known or suspected role in cancer. The protocol then sequences just these genes, or tests to what extent they are present and being expressed by the cancer. My problem with this approach is that no matter how much expertise you have, you cannot know in advance what will or will not be turn out to be relevant. I will mention several examples of how this turned out to be the case for me, but the bottom line is that as far as I am concerned, it is ALWAYS preferable for a patient to have a high-quality whole genome sequence of their cancer available to them and their care providers as essential core baseline data.
I talked over how I might best respond to this distressing news with members of my Advisory Board on Saturday, April 14. Much to my dismay, their advice was simply to “ask politely” for biopsy tissue to be set aside for me so that I could get a “second opinion”. On Easter Sunday, April 25, 2017 I decided to make one last phone call – in effect, a “hail Mary” pass – a one in a million chance that making just the right call, and saying just the right thing, might kick-off an improbable cascade of effects that could deliver to me some much needed leverage – never mind that it was Easter Sunday, and I needed the help to arrive before early afternoon surgery the next day.
The call I made was to a former colleague from bio-era who was now a senior executive at a cutting-edge biotech company. He didn’t know I was sick, so when he answered the phone, I asked him if he was sitting down and had a few minutes to listen. Then I told him the sad tale leading up to my current dilemma. I hoped and assumed that after we’d said our goodbyes, he’d tell a particular someone else about it, who would then tell another particular someone else. At about 10:00 am the following Monday (Patriot’s Day), my wife Deborah and I were waiting at the West Concord station to catch a train to the Dana Farber where I was scheduled for an early afternoon needle biopsy of a retroperitoneal lymph node. Suddenly, my phone buzzed. I looked down and it was a text from J. Craig Venter, the world famous scientist who led the private sector effort to sequence the first human genome (his). To make a long story short, he was in San Diego and had just heard about my situation and was taking a personal interest. Would I be interested in having my whole healthy genome and my whole cancer genome sequenced, along with having the associated epigenetics, metabolomics, proteomics, transcriptomics done — and my entire microbiome sequenced? I couldn’t believe it! “Yes!” I texted back! “Thank you!”
At the Dana-Farber, I changed into a hospital gown in preparation for the biopsy surgery. While lying on the gurney waiting to enter the operating room, I was approached by an affable young man who explained that he was an intern from Dublin who just needed my final signature on the surgical consent form before we could proceed. To this I replied that before signing the form, I had a request to make…. I was hoping that the performing surgeon would please take some extra biopsy tissue and set it aside so that I might use it for the purposes of getting a second opinion on the genetic sequencing the Dana Farber was going to do, but to which I had been told I would not have access?
After a moment’s pause, the young intern told me he’d have to check this out with the performing surgeon and would get back to me ASAP. He left my side, and about 45 minutes later, the performing surgeon wheeled around the corner, obviously straight out of the operating room. He had a serious “all business” look on his face and he loudly demanded, “What’s the meaning of this?”
I explained again, and after a moment he quite calmly said, “Well, that seems like a reasonable request, but everything has to go through pathology around here, so I’ll have to check with them and get back to you.”… Another hour goes by before he comes back around the corner — obviously annoyed and somewhat agitated — and says, “Look, I apologize for this — and I’m going to see that this changes — but apparently there is no standard operating procedure for this kind of request [SHORT PAUSE] — so, how do you want it, saline or formalin?”
I had no idea how I wanted it! Lying there on the gurney I immediately texted the person at Craig Venter’s company, HLI, who had been assigned to handle my case and asked “how do you want the tissue for sequencing prepared for shipment?” The immediate response I got back was, “Snap frozen fresh”. I called out to the performing surgeon, “Can you do snap frozen fresh?” to which he replied, “Where do you want it shipped?” I immediately texted that question to HLI, but this time all I got back was radio silence. I called out to the performing surgeon that I was having some difficulty with communications and that if he gave me his email address I’d be sure to get him the delivery information he required before the end of the day. And so we proceeded on that basis. I signed the consent form, was wheeled into the Operating Room, a successful biopsy was performed, and as I was groggily recovering from the anesthesia, the performing surgeon walked by, stopped, turned toward my gurney, and called out, “And remember to get me that delivery address!”… I assured him I would!
Then I was back on the train to West Concord and on the phone with my HLI case manager… “Why didn’t you guys answer me when I asked for the delivery instructions?” “Oh Mr. Aldrich, you may not understand… First of all, as a matter of law, transactions involving biological samples exchanged between two CLIA certified laboratories must be direct. They cannot be mediated through a third party in any way. Second, we have not yet gotten a signed consent form from you, which we’ll need to receive before we can complete the transaction with the Dana Farber.” “Well, can you send me the consent form?” I asked. “Oh Mr. Aldrich, our consent form is 25 pages long, and normally, we require the patient to participate in an hour long teleconference with us and our genetics councilors in order to review all aspects of consent, and ensure everyone understands everything.“ “Well, how soon can we do that?” “How about 2:00 pm tomorrow?” And so that evening I carefully read over the consent form and noted that its provisions entitled me to full ownership rights and access to the underlying genetic data, and the following Tuesday morning, Deborah and I headed back to Vermont, arriving just in time to dial in to the 2:00 pm teleconference. What we learned stunned us both. It turns out that in the main, the two most important pieces of governing Federal legislation – GINA (the Genetic Information Non-Disclosure Act of 2008), and HIPPA, (the Health Insurance Portability and Accountability Act of 1996) only provide legal protections for the person whose genetic information is being tested or sequenced.
The problem is that whole genome sequence data could easily be used to discriminate against 1st degree blood relatives – meaning your biological full brothers, sisters, sons, and daughters. Apparently, it was possible and legal under current law to do this in order to make a profit. For example, if I shared my healthy whole genome sequence data with a life insurance company that happened to also service my biological brothers and sisters, they were not explicitly prohibited by law from using my genetic information as a basis for adjusting the cost of my brothers and sisters life insurance policies. Once I understood this, I immediately concluded that I couldn’t in good conscience proceed without the full support and consent of my seven siblings living scattered about the globe. And after discussing this with HLI, we agreed to convene a global conference call between me, my siblings and the HLI team several days later. In the end, we held the call, everyone agreed, and I formally enrolled in the HLI Comprehensive Cancer Study by signing the consent form. Let the sequencing and data-gathering begin!
For the next couple of months, while HLI worked to complete its data gathering on me, I began to explore how I could best put the data to work on my behalf. By this time I had a basic understanding of the significance of first generation immunotherapies – and in particular, the notable success achieved by monoclonal antibody check-point inhibitors. But I was also extremely aware and interested in the many exciting developments with Chimeric Antigenic Receptor (CAR) T cell therapy, Tissue Infiltrating Leucocyte (TIL) therapy, and the development of personalized therapeutic vaccines. I had also become aware of an astounding reformulation of our understanding of our relationship with the trillions of bacteria with whom we are in intimate symbiosis – so intimate that we now know they are critically important for mediating immune response. This knowledge would prove to be practically important later on….
In partnership with my independent consulting oncologist, Jason Sager, I freely vented and explored the treatment possibility space. Some of my ideas he seemed to like, and others struck him as perhaps too far-fetched. For example, rather than going to all the bother and complications of genetically modifying a eukaryotic T cell, I wondered out loud why we couldn’t just design a plasmid to express my cancer neoantigens. Plasmids are small, circular strands of DNA used by bacteria to express and share genetic information. Plasmids are not organized into a nucleus, they are “free standing” within the bacterial cytoplasm. As opposed to the length of the human genome (roughly 3 billion amino acids long), a typical plasmid is only a few hundred thousand base pairs. This is well within the reach of today’s largely automated DNA design and synthesis technologies, and so for some years now, there has been a rapidly maturing industry that can design, manufacture, and ship to your doorstep a custom designed plasmid. Or, should you prefer, the plasmid can be inserted into a host vector bacteria and be ready to go directly to work when it arrives in the mail. In short, this technology is already well-developed. My thought was that it ought to be possible to direct this existing capability toward the quick development of potentially curative personalized therapies. Why not? Why not design and synthesize a plasmid aimed at provoking a protective immune response against my cancer, insert the designed plasmid into gut bacteria we might culture, grow up a colony, swallow them, and provoke a protective immune response that way?
It seemed logically straightforward and doable to me, but complex biological systems usually are not, and my more sober consulting oncologist was skeptical. He suggested running the idea past his mentor, and later on (and somewhat to his surprise I think) he reported back that his mentor had been quite enthusiastic. Despite this, he favored an alternative approach — personalized therapeutic vaccines.
Indeed, he introduced me and my situation to the CEO of a German company that specialized in designing personalized therapeutic vaccines, and remarkably, she offered to design such a vaccine for me at cost. She proposed to use my whole cancer genome sequence data to identify neoantigenic peptides (short chain amino acids) that were likely being expressed by my cancer. Neoantigens are mutated antigens, or mutated foreign proteins. While your immune system creates T cells educated to recognize a specific antigen expressed by your cancer cells as “foreign”, unfortunately, your cancer cells keep mutating in ways that can alter what your immune system army has been trained to see. By mutating the antigen, the cancer can successfully by-pass your immune system response by making your T cells blind to the cancer. Because they don’t recognize the mutated antigen, they can’t initiate a protective immune response. The idea behind the kind of personalized therapeutic vaccine I was considering is to identify your mutated cancer antigens, then design and manufacture a vaccine that will amplify T cells that recognize your cancer’s neoantigens.
I immediately accepted her gracious offer – which would require that I deliver the sequence data being gathered at HLI to the Center for Genomics and Transcriptomics (CeGaT) in Germany. Having carefully read the 25 page HLI consent form before signing, I was aware that I had the right to share the underlying data, and I assumed it would be a trivial thing for HLI either to transfer the files or provide internet access to them to the appropriate folks at CeGaT. This assumption turned out to be very wrong.
The challenge of assembling and transferring my data was bigger than expected and required much more time than I imagined it should. In the end, after about eight weeks, a hard drive containing about 1 Terabyte of a surprising variety of file types had to be FedEx’d from HLI to Germany. This experience helped me understand two things: (1) why Federal Express leads the world in the volume of genomic data transported from one place to another; and (2) that I never wanted to go through such a hassle again. We needed to fix this! If my genomic data sets were going to be centrally important to my treatment decisions, then there OUGHT to be a way for me to electronically store the underlying data, address the data with useful applications, and provide collaborative access to the data and applications to any other helpers or care providers. There was a clear need for patients to control the storage, use and collaboration around their data! Awareness of this inspired me to look for facilities that might already exist that could help. I looked, but I didn’t really find anything suitable. So, I asked myself who would eventually provide such a solution to patients like me, and I figured the answer was that the bioinformatics companies who were serving the genomics research community with data-storage, query and analysis solutions we’re the most likely providers. I did some research and soon contacted On-Ramp Bio (winner of the BIO-IT 2018 Best in Show award for “Rosalind” — their bioinformatics platform). I also called my old colleague and friend, Andy Singleton – a software entrepreneur. So began collaborations that have resulted in two separate efforts to build a secure, on-line user friendly facility for patients to store, analyze, and enable collaboration around their fundamental health data — a proprietary On-Ramp Bio approach, known as Rosalind Patient, and an open-source approach, myCancerDB.com.
Eventually, I will be an initial beneficiary of these new facilities, but both are intended to be broad solutions for cancer patients holding large, fundamental health data sets. The benefits they will deliver to late stage cancer patients are direct and real. For example, my vision is that users should be able to:
These are just a few examples.
On July 10th, 2017 I was restaged at the Dana Farber. My cancer was determined to be in partial remission. At that meeting, it became apparent that Dr. Sager and I disagreed with the course of treatment being recommended by my Dana Farber oncologist. My Dana Farber oncologist was urging me to continue with a minimum of 8 additional FOLFOX infusions (I’d already had 4). Jason and I thought it would be better to suspend the FOLFOX infusions in favor of enrollment in a Phase II clinical trial in Farmington, CT testing a combination of two immunotherapy check-point inhibitors – Pembrolizumab (Keytruda), and an experimental drug, Epacadastat. In the end, I decided to leave the care of the Dana Farber and pursue the immunotherapy trial in Connecticut. I enrolled in early August 2017. Since my enrollment over one year ago, I have enjoyed overall good health with no symptoms of overt disease and minimally inconveniencing side effects. Technically, my disease status is classified as “stable” – meaning that the cancer is still there, but has not progressed. Apparently, either Pembrolizumab and/or Epacadastat are at least partially “effective” therapies against my cancer, and I am very pleased to have added them to my arsenal. In the meantime, I have been working to improve the monitoring of my disease status, while identifying other effective therapies. If my cancer progresses, I intend to have a well-stocked arsenal that I can deploy in response. I believe my having direct control over the storage, query, and application of my fundamental health data sets – including my whole cancer genome – has been centrally important for achieving this.
Most recently, after working with Saskia Biskup at CeGaT in Germany, and then Stephen Shoenberger at the La Jolla Institute of Allergy and Immunology in San Diego on the design and testing of a personalized therapeutic peptide vaccine based on my unique cancer genetics, I have been accepted into a small, Phase I clinical trial that will manufacture and administer the resulting vaccine in conjunction with Pembrolizumab. As a part of this trial, I should receive my first vaccine injection in early January 2019. At this point, enrollment in such a clinical trial is the only “legal” way patients can get such a vaccine manufactured and administered here in the United States. Hopefully, my story will help change that for future patients. The technology for creating personalized vaccines is accessible and mature enough to pose little in the way of a barrier to getting many more – if not all – cancer patients the benefit of such therapy. Let’s make it happen!
For more on my journey, please visit my blog.
Along with pursuing advanced cutting-edge science-based treatment options, Steve has pursued a holistic approach to healing that integrates allopathic with naturopathic complementary, and alternative treatments. Inspired by the empirical research into cancer survivors done by Dr. Kelley Turner (see her New York Times best-selling book, “Radical Remission”), Steve has pursued major changes to his lifestyle in the following nine areas.
Adopted a whole foods, plant-based, lower protein diet that avoids all refined sugar, processed food, meat, dairy, and alcohol.
Daily use of immune and nutrition boosting, cancer fighting herbs and supplements.
Daily practice to increase positive emotions, especially love, joy, laughter, and gratitude.
Daily practice to release suppressed or negative emotions, especially fear, anxiety, and grief.
Greater awareness of, and attention to, intuition.
Regular spiritual practice, including morning meditation; fasting; forest bathing; communion; and prayer. Preaches occasional Sundays at Christ Church in Bethel, VT.
Deepen community involvement and practice by loving others, giving back and paying forward.
Work to align your deepest purposes and reasons for living with all that you do.
Embrace full responsibility for your illness and your health! Don’t run away from the problem — run towards the solution!
Whole Cancer Genome Sequencing
Every cancer patient deserves the benefit of whole healthy genome and whole cancer genome sequencing. Help transform the Standard of Care by asking your oncologist to sequence your whole genomes to identify life-saving options!
Personalized Vaccine Cancer Research
Personalized therapeutic vaccines must be designed and manufactured for each individual patient. Help enable as many in need as possible to gain the benefit of this potentially life-saving therapy.
Donate: La Jolla Institute
Build an Information Infrastructure
Steve has encountered significant obstacles to making his genomic data as used and useful as it can and should be. Seeing that there was an unmet need for people dealing with incurable cancers to leverage their genomic data sets to identify and analyze their potential treatment options, Steve is supporting two separate efforts to bring such a facility into reality ASAP. As he is fond of saying, “I just want to solve the problem, I don’t care who wins the race.”
myCancerDB.com is an open-source effort to develop the data infrastructure and services needed for cancer patients to securely store their large raw genomic data sets, to access tools and resources for analyzing their data to identify appropriate treatment options, and to support the monitoring of their disease progression and response to treatments throughout their cancer journey.
Rosalind Patient is a proprietary effort to do the same thing being led by by OnRamp Bioinformatics — a bioinformatics software company based in San Diego, CA, with an award-winning genomics analysis platform called “Rosalind” — winner of BIO IT’s “Best in Show” award for 2018.
Visit: OnRamp Bio
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