Reversing Fibrosis

The vocabulary of science

Reversing Fibrosis – the Ploidy Connection

Abstracts of scientific papers often seem baffling. Mainly, however, it’s just a question of vocabulary. A vocabulary list of 100 words and a handful of common prefixes and suffixes would take us through most of the literature relevant to MPNs. For the rest we have Google and Wikipedia. Those of us who are diligent caregivers quickly learn the most arcane terms because, like any foreign language the trick is to use it.

We can let others translate for us… but this MPN world is not a foreign land. It’s the country we inhabit and sometimes we need to read the road signs pointing to danger ahead.

So let’s start with a weird one: PLOIDY. It’s as specific and unusual a word we’re likely to find. And it’s central to a finding that came out of a study published this summer that studied the production and reversal of myelofibrosis in mouse populations,.

Science fiction, science fact

In our investigation of MPN therapeutic developments, it’s not often we come face to face with hard science. We encounter applied science all the time, in reports from fellow patients, talks by hematologists and papers by clinical investigators who have tested a drug in a controlled trial.

And yet the cure for our various myeloproliferative diseases resides in only two places – the oncology suites where stem cell transplant takes place and the labs where chemists, geneticists, and molecular biologists follow ideas through to exploration, animal studies and sometimes discovery. This is science stripped of its commercial endpoint.

As a result, most pure theoretical work escapes our attention until it surfaces in publication of a paper. Even then it’s beyond us until we can convert it to a narrative, a story. What follows is a story that follows publication* of a scientific study, “Control of Megakaryocyte Expansion and Bone Marrow Fibrosis by Lysyl Oxidase,” Katya Ravid, et. al., J. Biol. Chem. 2011 286: 27630–27638, June, 2011.

The study is scientific fact; this story introduces a little science fiction.

_______________

An introduction to ploid and friends

There are one or more proteins, enzymes or enablers, whose presence plays a role in developing greater numbers of those large megakaryocytes (MKs) that spew fragments or platelets into the bloodstream.

One such enzyme is called LOX, lysysl oxidase. And its presence in large numbers signals trouble. When well behaved , LOX plays an important construction role in the body, stabilizing platforms outside the cell, building catwalks and girders. It’s a potent initiator of essential activity among various cell types. But LOX enzymes running wild can be a trouble-making gang rampaging through the blood production system.

LOX boosts creation of megakaryocytes (MKs) by oxidizing a communications cell element called Platelet Derived Growth Factor (PDGF, a tyrosine kinase). PDGF then flashes the downstream green light to ramp up production of megakaryoctyes.

Megakaryocytes give rise to platelets, necessary for clotting and other functions. It’s a blood cell. Most cells have two full sets of chromosomes and are diploid – one chromosome from mom, one from dad. Germ cells, sperm and ova, are haploid, single chromosomes. Then there are multiples of “ploidiness” on the road to to polyploidy, or lots of chromosomes in a single cell. In the case of megakaryocytes, like this guy, to be polyploid has some advantages. Since the platelet fragments it releases – as many as 3000 for a 32-ploid megakaryocfyte – have no need of a nucleus, no need to reproduce, it’s more efficient to skip all the sex apparatus in the cell and just produce one large cell with lots of chromosomes. It’s the normal development path for an MK.

Enter the LOX gang. They steer clear of swollen polyploidal megakaryocytes which are no longer good candidates for proliferation but they’re all over the diploid and quatroid MK’s. They pinch and twist their bodies, twist their arms, suggest how good it would feel to oxidize a cute little PDFG signal tower just down the road… and they better get on it if they know what’s good for them. MK’s do just that and all that turning on of signals spurs production of more and more MK’s and produces a flood of platelets.

For us, oblivious to all this action, one nasty result is the development of ET, essential thrombocythemia, with its attendant risks of thrombosis and mini-strokes. Another result is more deadly.

MK in bone marrow

All this proliferation produces mountains of reticulin fiber outside the cell which, being part of the blood producing system, resides withiin the marrow in the bone capsule. This kind of reticulin fibrosis when discovered in bone marrow biopsy, unless accompanied by blood production outside the marrow (extramedullary hematopoeisis), may not be considered clinically significant. This is the cellular phase of myelofibrosis: increased and clustered megakaryocytes and reticulin fibrosis. But once LOX descends on the fibers, the game changes.

LOX as construction crew

LOX enzymes are part of the biologic construction crew picking up work around the body, building support structures. LOX earns its living by working on the connective tissue crew where its job is to cross -link collagen and elastin to make a mucky substance that can join objects together. One of the ingredients of collagen is hydroxylysine which LOX extracts. These residues reside on the inner walls of bone and quickly form a dense matrix of collagen cross-linked fibers and occupy soft and open spaces in the bone’s inner core. Healthy blood cells are pushed aside and eventually die from lack of food and oxygen supply.

This is the fibrotic phase of myelofibrosis: collagenous fibrosis with the absence of normal marrow elements. This time we are well aware of the action taking place in the dark vault of our bones as we suffer clinical response, myeloid metaplasia, splenomegaly, hepatomegaly. And all the rest.

LOX contributes to proliferation not polyploidy

Katya Ravid’s team in her Boston University lab reasoned if LOX was going to be absent in polyploidy MK’s, it must be abundant in the diploid and tetraploid megakaryoctyes, candidates for proliferation. They used specially bred transgenic mice with low ploidy MK’s, high levels of Platelet Derived Growth Factor and extensive fiber. As suspected, megakaryoctyes from these mice showed very high levels of LOX. Treating the mice with a LOX inhibitor – BAPN, beta-aminopropionitrile — resulted in dramatic (37%) reduction of bone marrow fibrosis and decrease in megakaryocyte numbers.

The success of BAPN in reducing fibrosis implicates LOX in the progression of MF. Ravid concludes: “Our results suggest that LOX is a novel regulator of megakaryopoiesis via its effect on PDGFT-B and a potential treatment target for primary myelofibrosis.”

The final scene, a new actor

There’s one last part to this story, another actor: Thrombopoietin. TPO is the primary growth factor driving development of megakaryocytes – proliferation, polyploidization, maturation, and death. TPO acts through a receptor gene to signal that same PDGF signal tower targeted by LOX to call for more MKs

TPO thus applies a natural brake on LOX since TPO “significantly attenuates LOX expression…” Low doses of TPO administered to the transgenic mice result in low detection of LOX. The pathway is direct. TPO promotes the development of polyploidy MKs. LOX activity results in proliferation of megakaryocytes, not polyploidy . Since the LOX focus is on diploid MKs, simply increasing the number of polyploidy MKs decreases proliferation of megakaryocytes

The vocabulary may be new and strange…and yet, within our own marrow and at this very moment, the battle for polyploidy vs proliferation is being waged. The outcome may well significantly determine our fate.

Take me back.

© Zhenya Senyak and MPNforum.com, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Bonnie Evans and MPNforum.com with appropriate and specific direction to the original content

Body-Mind-Spirit – September

by Patricia Wagner

Has your doctor ever explained to you that your mind affects your body? Perhaps you have been told that a cheerful attitude is better than a dour one by a kindly physician (or was that your mother?) This was likely couched in terms that implied “it can’t hurt but you know that this is in your genes”. Well, actually I think that we’ve been talking to the wrong type of doctor to learn how dramatically the mind indeed affects the body, in either creating or destroying health.

I’m thinking rather of stem cell biologists or quantum physicists. Were we to speak to someone of that persuasion, we’d have it confirmed with copious evidence that our beliefs affect our biology. As someone who has studied this subject from the perspective of the Ageless Wisdom mystery schools, this causes a great deal of personal delight for me. I hope, regardless of your orientation, that this will intrigue you as well.

NO SWIMMING UP THE “CRICK”

In 1953, with Watson and Crick’s seminal work, the “Molecular Structure of Nucleic Acids”, the concept of genetic determinism was codified into the education of future physicians. Through Crick’s theory, it became commonly accepted by all that the physical molecules of DNA control life. This theory states that information flows in one direction only: from the DNA to the RNA, and then to the protein that manifests itself as a human body in all its glory or lack thereof. Today, it is commonly accepted by all that our genetic information is inherited from our parents, and we must take the good with the bad. Some might even say that it makes sense to know in advance what this inherited programming might be, so as to head off trouble before it begins.

So we are a product of our genes, you say? Well, about 10 years after we were informed of this linear progression from DNA to RNA to protein, a geneticist, Howard Temin, discovered that RNA could flow backward and alter the host’s DNA code. Although vilified within his field, in 1975 he won a Nobel Prize for proving that the HIV virus is caused by a “reverse transcriptase” enzyme that sends an upstream signal back to the DNA code, altering it.

In 1990, the “no swimming up the Crick” dogma was further undermined by a Duke University biologist, H. Frederik Nijhout. He reported that genes are simply blueprints, not the brains of the bodily operation. In fact, Nijhout’s work concluded that environmental signals control gene activity. In 2003, when Dr. Paul Silverman of the Human Genome Study also confirmed that the cell signaling process is dependent upon environmental stimuli to “trigger” nuclear DNA you’d think that this would have changed everything for the chronically ill amongst us. Sadly, funding for research into the ways to trigger our DNA back to health is sparse, and often discredited. Of course, drug companies wish to change the cellular soup in which we float with a profitable potion or two. Hmmm . . . . wonder if there may be a connection here? Hence, we are left to noodle this out on our own for now.

ARE DISEASES LINKED TO GENETIC DEFECTS?

The National Cancer Institute says that at least 60% of all cancers are due to environmental causes, not genes. Other research reveals that just because you have a culprit gene, doesn’t mean you’ll be affected by disease. And then there is our personal condition: an acquired mutation. Why? Sadly, research is only performed on the ill folks with a genetic disorder – not those who remained healthy in spite of their errant genes. Another study of adopted children found that these adoptees were succumbing to diseases of their parents which were thought to be genetic in nature. That’s the sort of nature or nurture we could do without.

The new field of epigenetics provides insight regarding these murky findings. DNA is not what controls the operation of the human cell. Nor is the nucleus of each cell. The “brains” are located in the cell membrane, specifically in the IMPs (Integral Membrane Proteins) which act like the gatekeepers for the cell, letting certain signals in and other signals out. This elegant and magical mechanism is what translates environmental influences into changed behaviors. Simply put, it is the IMPs that will allow malfunction to enter or depart, and it is the environment that affects the signaling.

Stem cell biologist, Bruce Lipton, Ph.D. defines the cell membrane as “a liquid crystal semiconductor with gates and channels”. In a word, the cell membrane is the structural equivalent of a computer chip! Two points need to be emphasized at this juncture: (1) a cell is a programmable chip and (2) the programming intelligence resides outside of the chip itself.

Remember our MPN doctors explaining to us “it’s not exactly a JAK2 gene, it’s more like this anomaly we found on a pathway”? Well, IMPs facilitate communication of vital information between cells via pathways, or well-worn roads shared by sometimes seemingly unrelated organs or glands. If a biological malfunction occurs anywhere on a pathway, this can affect everything else on the pathway. It’s why there is usually a “constellation” of symptoms for a disease. And you’ve heard those drug commercials that promise, for example, to fix your rheumatoid arthritis but may cause blindness or acute leukemia? If it shares a pathway, fixing one thing may well damage two more things. Finding a physical-level solution may be a very prolonged process, as we’ve been advised.

Sometimes problem-solving requires changing one’s perspective. So for now let’s look at this problem not as our doctors would, but rather from other scientific disciplines. As Einstein discovered, atoms are not made of matter, but rather nonmaterial energy. In fact, astrophysicist Sir James Jeans writes: “The stream of knowledge is heading toward a non-mechanical reality; the Universe begins to look more like a great thought than like a great machine. Mind no longer appears to be an accidental intruder into the realm of matter. . . we ought rather hail it as the creator and governor of the realm of matter.”

DRINKING THE ELIXIR

Maybe you, too, practiced “The Secret” to get that red Maserati of your dreams, and disappointingly failed. Do not dismiss this magic elixir of creative thought based on such experiences. Your conscious mind might well have focused on that car picture fixed by magnet to your refrigerator, but 95% of your mind and mine is functioning on the subconscious level. Your subconscious mind may not have been convinced that the Maserati was for you. Your subconscious is stuck mostly in grooves that were worn in before you even went to kindergarten.

Our learned perceptions of a lifetime aren’t always accurate or useful, so it seems. And here is the crux of the problem for those of us who wish to reprogram ourselves for total health: Yes, our cells respond to their environment but 95% of our controlling perceptions or beliefs are already programmed in and not easily changed by merely thinking more positive thoughts. And in the meantime, our pathways may be jammed with fear, anger, and generally flummoxed in a way that has upset our cells.

In a prior article I mentioned having reached the realization that allopathic medicine wasn’t enough. I’ve since worked with energy medicine, meditation, visualization, tapping, and much more. Under duress, I even confess to an occasional howl at the moon. (Its energy moves the tides, right?) Although no small feat, I have eradicated the “nocebo effect”. I’ve deprogrammed myself of prior strong impressions acquired through research on my dis-ease. I no longer feel powerless to stop the incessant clanking and wheezing of my errant genes or pathways, or whatever it is that allopathic medicine ultimately decides is the broken widget in my physical vehicle.

In fact, much of my physical, mental, and spiritual suffering has been alleviated. I see myself well, and my body is gradually responding to this vision. As Larry Dossey, M.D., has beautifully illustrated in “Prayer is Good Medicine”, prayer is not something we do – it is something we ARE. Since physicists acknowledge that mind is the primary environmental influence over matter, it makes sense that first we envision something as being true. Then it IS true.

This mind-over-matter, or shall I say wave-over-particle type of healing requires knowledge and skill. Given the “positive thinking” conundrum just mentioned, it takes a much deeper understanding of the role of the mind, and how the Universe’s energy works both in the macrocosm and the microcosm. Ultimately, it takes faith in conjunction with skill. It is a process we will explore in future articles , my brothers and sisters in this process of healing. Blessings, until then.
Take me back.

© Patricia Wagner and MPNforum.com, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Patricia Wagner and MPNforum.com with appropriate and specific direction to the original content

MPNLife – Fatigue and what you can do about it

PART TWO:

WALK AND RUN

by Jeremy Smith
In the previous MPN Life column, I introduced you to the Crawl phase of exercise. This month I will cover the final two phases Walk and Run.

I love the month of September. It marks the beginning of fall and the leaves begin their magnificent change in color. Every fall, even out here on the West Coast, I am reminded of my times of innocence with my brothers and parents living in Weston, Connecticut. A time prior to our parent’s divorce and later passing. Our return from summer vacation from either Cape Cod or Fire Island, just as Labor Day Weekend draws to a close.

The long hot and humid East Coast summers finally draw to a close. Best of all the leaves begin to fall. While it all happened so long ago when I close my eyes I can still see my Dad raking the leaves from our front lawn and in to one giant pile that my brothers and I could run and jump in to together. The smell of the leaves is still there when I landed at the bottom of the pile. I recall it sending with work of course. Someone would have to put all the leaves in to a trash bag and that was the three of us did. Of course we complained at first. Hey we are Jewish! But my brothers and I knew Mom would soon be setting the table for lunch and the smell of her home made meals would make all of our work so worthwhile.

So why all of this September talk and what does it have to do with exercise? Glad you asked. September is one of the best months for exercising and being outdoors. In addition to the changing of the leaves the temperatures begin to moderate and make for excellent outdoor excursions. I will take the outdoors any day over the gym. Just think about walking, running or cycling through here.

The stress of dealing with the combination of the MPN diagnosis and fatigue and can in many cases leads to varied forms of depression. For those on INFN these next two phases offer additional benefits to guard against depression.

When you exercise your body releases endorphins. These act as analgesics and when released can reduce the awareness of pain as well. The more you exercise and the greater your intensity the more impact endorphins have on your body. Intensity is an important word to get to know because it’s your friend. Without a goal of increasing your exercise intensity you will reduce your ability to restart your bodies immune system and slay fatigue.
According to WebMD lists some of the potential benefits from regular exercise as:

1. Reduced stress.
2. Less anxiety and feelings of depression.
3. Boost self-esteem.
4. Improved sleep.
5. Strengthens your heart.
6. Increased energy levels.
7. Lower blood pressure.
8. Improves muscle tone and strength.
9. Strengthens and builds bones.
10. Helps reduce body fat.
11. Makes you look fit and healthy.

Remember never skip a phase and if you are uncomfortable moving up stay with a phase until you are. You set the stage for which phases you want to place yourself and how rapidly you are capable of moving through each phase. At the beginning of any exercise program or changes to your existing program always check with your Doctor prior to changes in your exercise program.

WALK.

Walk is the most important phase of Crawl. Walk. Run. Walk is the first time you will increase the intensity of your exercise program. I will talk more about intensity, one of the single most important aspects to exercise a little bit later. If you work hard at this you will now begin slaying that beast called fatigue.

WARNING: When you move from Crawl to Walk this is the first time the risk of a potential injury really comes in to play. If you are doing things incorrectly in Walk, such as lifting too much weight or when cycling, riding with your knees bent outwards. You will create bad habits that will stay with you and unfortunately can increase your risk of injury. IF you have any questions about this let me know.

In Crawl you are training yourself to get ready for Walk. In Walk you are training for RUN.
Take your time with Walk and do not rush it. There is no time limit on the transition from Crawl to Wall to Walk to Run. Only you know how your body is feeling and reacting. This is a good time to take notes on where you are sore so you notice the changes in your body and don’t mistake it for something else. Always take time to appreciate your accomplishments as well and share them with our Facebook Forum group for inspiration and support.

Two of the biggest changes in the Walk phase are the intensity and time you devote to exercise. Lets talk about intensity first. Exercise intensity refers to how much work is being done when exercising, the rate as which you exert yourself during exercise. Results are most often measured as the percentage of maximum heart rate (MHR) and your heart rates beats per minute (BPM).

I do not expect any of you to hit a 90% plus heart rate in Walk. That is fir Run. At the 120 days point of Walk, you should be begin to reach the 80% level. This assumes you have no medical issues, which prevent you from achieving these results. Again always check with your Doctor prior to targeting these rates.

You can start with a three-day a week program and depending on your intensity and commitment you will see some reduction in your fatigue. You will definitely see improve overall results in your health but fatigue is a much more difficult challenge. Only a five or six day program will provide you with the amount of energy you need to blow off fatigue. The good news is if you really commit to this phase you will reduce your fatigue. Energy will begin to come back in ninety days.

THERE IS EXERCISE AND THERE IS EXERCISE

People love hearing gardening and walking are considered exercising. There has been some misperception presented in articles that link the simple act of burning calories to exercise. Gardening is a wonderful experience and you should continue doing it but don’t confuse burning calories with exercise. You burn calories while sleeping yet I don’t know anyone comparing sleeping to exercise. Raising your level of intensity is necessary to improving your health and ending fatigue.

Remember you are looking to being your heart rate up when you exercise and increase your intensity. This just doesn’t really happen very often while you are gardening unless you are chasing your husband or wife around the garden with a rake.

RUN

Run. The final and in some ways the most difficult phase to maintain unless you are committed to a 6-day a week plan. When I say a 6-day plan this does mean you cycle or swim six days a week. You want to mix up your workout program to include various types of cardiovascular work along with some weight training. The most common plans are divided up in to six days. For example you might do your cardio work on Tuesday, Thursday and Saturday. While you use weights Monday, Wednesday and Friday. As I mentioned in August studies point to those who exercise less than five or six days a week see the highest rates of discontinuation in their exercise programs.

By now you should be planning on a minimum of 45 minutes to 1 hour of exercise each day. Consumer Reports Health recently wrote about new studies that show the US Governments recommendation of 20 to 30 minutes of exercise need to be revised. Its just not enough time especially when you factor in the bodies ability to adjust itself along the way. You must extend your time spent exercising to improve your body’s ability to heal itself.

You must also build time in to your plan that includes resting your body, as it will need it for recovery. I try not to cycle back-to-back days at high intensity. Not allowing your body to restore itself and can weaken your immune system. I always take one day a week off and when my body needs it I rest two days.

You should be in shape now, and with your Doctors permission of course to begin testing your heart rate at 90% to 100%. New studies have found that increases in intensity do not need to be demonstrated through the entire time you are exercising. Short intense bursts of exertion, a maximum heart rate greater than 90%, for three to five minutes followed by 10 to 15 minutes of normal exertion are more effective than an all out exercise at 90% until you drop session.

NUTRITION

In the run phase you will need to spend additional time making sure you take of your nutritional needs. For example while training for my back to back weekend rides I made the mistake of not refueling properly, which brought on some really painful stomach pains. When I checked my Garmin 500 I had burned 2400 calories yet all I ate was a banana on the ride, one bar and three bottles of water. I had let my tank run dry. Sure I was hydrated just fine but I was starving myself.

When I rode the back to bike rides this month I burned 1589 Calories on Saturday and 1798 Calories on Sunday. But this time I had my water bottles filled with Heed (the Heed product I was using replaces your electrolytes) in addition to having three bars with me I stopped at every rest stop along the ride and made sure I replaced my calories.

MANAGING EXPECTATIONS

It’s very important to manage and balance your expectations. If you do not you may become discouraged. For example some people will be able to participate in Marathons and Triathlons while others may only be able to complete half marathons no matter how hard they try.
Some of you will run 8 miles while others may run 1 mile in a day or walk 1 mile in a day. All of this is excellent and you should not beat yourself up if you never make it to the top of the mountain again. This is not about training for the Olympics it’s about bettering your overall health, reducing fatigue and improving your quality of life. Which for one person might equate to running 1 mile a day or 1 mile a week.

LIFTING WEIGHTS AND ADDING MUSCLE

The Walk phase is not just about beating fatigue, losing weight and improving your cardiovascular levels. If I have made one mistake in my exercise life it’s not adding enough muscle. As we age study after study bares out the need for most of us to add muscle to our bodies. No I am not asking you to become Arnold Schwarzenegger but adding muscle and toning your body is very important to your health. A side benefit of building muscle is unlike fat muscle burns calories even when you aren’t exercising. This will help you more easily maintain your proper weight.

So how do you add muscle? I could write a column just on this subject but lets stick to the basics. Most people in a gym constantly are either looking at themselves in the mirror look or are checking each other out. If you remember being single, it pretty much the same thing. Ignore all of these idiots. We are not in a competition.

Rule #1 when you first start lifting weights if you have not lifted weights in a long time do not start out trying to lift buildings. I know gyms can be intimidating if you let it get in your head. Please let the other people in the gym injury themselves trying to impress you. Hiring a trainer can be a good place to start if you are doing your weight training at a gym. Whether or not you want to hire a trainer is up to you but make sure you ask the trainer for references prior to hiring anyone.

When you walk in to most gyms you will generally notice the free weight section and the machines. Companies like Naultius make the machines and there has been a debate for many decades over the advantages of free weights vs. machines. Nothing is better for building muscles than free weights and what most people do not realize is that most gyms have free weights as light as 5 LBS now. The picture below shows a woman working out on a bench with very light weights to tone her muscles.

Some of the strengths with machines are their ability to work with you on your legs. Below are some explanations of the equipment from the http://www.livestrong.com.

Hip Abductor Machines
A hip abductor machine uses a push force to strengthen and sculpt your outer thighs. The abductor machine is available in standing and seated versions as well.

Leg Press Machines
Seated leg presses can be performed using weight plates or weight stacks to target your quadriceps, hamstrings and glutes. Your foot placement on this machine will determine the area of concentration throughout your thighs. The most common placement is feet positioned shoulder width apart; the primary muscles trained are the quadriceps, while the secondary muscles involved include the hamstrings and glutes. Perform two to four sets of eight to 15 reps.

Leg Extension Machine
The leg extension machine isolates the tops of the thighs, or the quadriceps. To effectively strengthen each leg, choose an iso-lateral version or work one leg at a time. To add variety to your routine, alternate between full range and short range of motion, vary your lifting speed or hold and squeeze the muscle at the top of the movement before releasing. Perform two to four sets of eight to 15 reps.

Leg Curl Machine
The leg curl machine isolates the backs of your thighs, or the hamstrings. To prevent static activity and boredom, incorporate both full and short range of motion. Also, consider keeping your toes dorsa-flexed during the movement to maintain full contraction of the muscles; this results in minimal rest for the hamstrings. Perform two to four sets of eight to 15 reps.

RESULTS

As you progress through Walk and Run and increase your intensity your overall health is going to improve, your going to lose weight, provided you eat right as well. You are going see some pretty impressive results on your lab tests. Lower blood pressure and LDL as well as an increase in your HDL. It is a long list of results. However, do not expect miracles. You Bone Marrow will not heal itself. But the blood that flows through your veins will find it much easier to the move through your arteries and your hearth will purr along like a new engine in your vehicle. You brain should also become more focused and memory should improve.
When I made it to the Run phase my LDL dropped by half and I doubled my HDL. My average blood pressure is 110 over 55 to 60 when I stick to working out hard six days a week. In addition the debilitating fatigue I had is but a memory.

My improved cardiovascular and nutritional changes allow me to participate in events with my family and friends. The picture below was taken this year of me with my son and brother in-law on our 37-mile ride through Healdsburg, CA. In case you were wondering I have kicked my son’s rump up and down every hill. Where he crushes me is out in the flatlands. But I am working on it!

I still have a lot of room for improvement and five years ago I would have never thought I would be able to ride at this level again. Most importantly I am having a hell of a lot of fun while improving the quality of my life.

I challenge you to find out which level you can reach. Whether it be Crawl Walk or Run it does not matter. All that matters is you remember this is about fighting back and creating the quality of life you want. Exercise can allow us all to reach that goal however you define it.

Please communicate via email or MPN Forum or at our Facebook Forum http://www.ourmpnforum@groups.facebook.com with your questions, comments and stories of success.

Take me back.

© Jeremy Smith and MPNforum.com, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Jeremy Smith and MPNforum.com with appropriate and specific direction to the original content

Jeremy – In the beginning

CLASSIFED AD:

“MAN SEEKING OTHER PV PATIENTS TO CHAT ONLINE. WILLING TO BRING MODEM TO SHARE. MEET ME AT AMERICAN ONLINE.”

When I was first diagnosed with Polycythemia Vera, there was big gaping hole inside of me. No one in my inner circle could grasp what was going on inside my head. I had been stripped of my future and all hope. All of a sudden I was an Alien on a Planet I used to call home. Up had become down and down was now up. I had become a stranger among friends in search of Planet Normal.

While everyone around me felt connected and their life was as it was, mine had been stolen from me. There were times I would think to myself. “If I could meet just one person like me we could connect, relate and shoot the breeze.” A sense of normalcy would return to my life.” What I could not know then was that normal, as I once knew it, would never return.

As I walked the halls at Stanford waiting for my test results I would observe the paintings on the walls provide free by donors. I felt like Charlie Bucket from Charlie and the Chocolate Factory. He in search of the golden ticket, me in search of a fellow PV comrade in arms.

Every time I had a phlebotomy I would look over at other patients who were hooked up to IV’s with a sense of hope that in this group of folks I would find the one person who had PV. I would often ease drop on conversations between nurses, patients and family members. I kept waiting to hear the words “phlebotomy in room five.” Or “I am taking Hydrea,” it never came.

THE ARRIVAL OF THE WORLD WIDE WEB:

THE PERFECT PLACE TO MEET

In early 1993 I purchased my first Mac and hooked up a 56 baud modem and dug through my desk draws filled with a few of those America Online free welcome kits. AOL used to mail out millions of them to consumers. Sometimes they were metallic silver in color other times some bright pink fluorescent colors that could not be missed from as far as 100 yards away.

In the beginning, like most of the millions on AOL I would hang out in the chat rooms trying to figure out how the technology worked. This led to conversations or online chats and messaging. I remember my first on line message “What are you wearing? “At first I was not sure why anyone would want to know what I was wearing. I thought to myself Levi 501’s, Converse sneakers and a brown t-shirt. What a strange question I thought. However I quickly found out what all these things meant.

To me it was amazing to be able to talk with people from all over the World. Then one day, and I can’t remember for the life of me how it happened or who introduced me to it, I found a chat group for MPD Patients. At the time I didn’t even know what MPD meant.

As I recall there were a total of five people in this group plus myself. There was David, Robert Tollen, Joyce Niblack and the kindness most soulful person I ever met in the MPD or MPN Chat world, Alice M. Wahl. Alice was such a wonderfully magical and inspiring human. She made me laugh when I was sad. And helped me through some of my more difficult times.

There is something about being lost and finding a group of people you connect with that goes beyond words. When you find the right chat community you click with it becomes a brotherhood. Like a police force, fire department or group of soldiers. This brotherhood that develops among strangers is as if we are all serving together in an MPN/MPD War. We all have each others backs and closeness develops that is quite unique.

I think the year was either 1995 or 1996 but I was a scheduled speaker at a technology event in Arlington, VA. I mentioned this to the group and right away Alice messaged me. “I will be greatly and forever insulted with you Jeremy Smith if you do not make time for dinner with us while you are in town as you are going to be close by. ” You never say No to Alice.

Next month I will be taking you to the Twilight Zone and through the sad break up of our lovely group. The emergence of what we now call MPD/MPN Lists and the battle for list supremacy between Joyce Niblack and Robert Tollen.

Take me back.

Harriet

. “An honest appraisal of the development of MPD lists would be a heated story of various arguments, prejudice and moments of true insanity.”

— Judy Cuckston, founder of MPDchat

.

MPN On-line Support – The Beginning

As Judy’s sidekick and manager of MPDchat until a few months ago, I can well understand her assessment. Along with her vaunted good humor, civilized conversation, and fierce intellectual prowess, Judy was intimately aware of the personal sacrifice list owners and managers make to maintain patient support on a daily basis. Like all of us, she was also aware of the ferocious contradictions of lists designed to support sick patients erupting in contention.

So let’s get this one issue out of the way up-front and then get on to the real power and wonder of our on-line MPN patient support world.

We’re not going to talk much in this introduction about strife and contention among lists, the 300 pound gorilla slamming against his cage. Of course he’s there jumping up and down, slinging waste at the bystanders. But he’s only a sideshow exhibit for those who want to stand by his cage and gawk. For the rest, the MPN convention & circus is in town, with friends, neighbors and newcomers all shuffling by the exhibits eating cotton candy, greeting each other and marveling at feats of science and magic, joy and suffering under the big top.

Judy is right, of course. But only partially. Her view is that of someone who is part of the history but blessedly free of the disease, without an MPN patient to care for and no pressing need under her left ribcage to know what’s happening. She opened her doors, laid out a spread for us on MPDchat and left to attend to other affairs and maybe play through the back nine now and then. .

For most of us populating these on-line lists, patients and caregivers, a clear-eyed, engaged view of MPN developments is a critical and immediate matter of life and death. And if we have to sit through occasional exhibits of clowns getting shot out of cannon, well, so what. Usually, it’s worth it.

In the very beginning, in the time of deepest darkness and isolation before the Internet really took hold, there was another dominant voice, a voice of reason and compassion committed to lead us to understanding and bring us together. It is that voice that launched on-line MPN patient support, a voice that can still be heard today on all the lists, through all the rattling of cages. Hers is the voice of an educator and a healer, aptly enough, come down to us from Mt.Sinai.

Her name was Harriet.

[Photo courtesy The Mount Sinai Archives]

In the beginning

For weeks, we could find no photograph of her.

That seems so astonishing, gone only these few years. She touched the lives of so many, a doctor and teacher for more than four decades, devoted to her hospital, her medical school, her patients.

She had a husband, children, grandchildren, pioneered MPN patient education, chaired Government and medical study groups, published widely. But no photograph could be found.

Not in the archives of patient support Lists. Not in the New York Times photo morgue. Not at The Mt.Sinai Hospital press room or the files of the MPD Foundation or even Google Images. .

It was not hard to imagine Harriet S. Gilbert, the woman who signed her letters and newsletter, ad sanum sanguinum. (toward healthy blood)

Here’s what we know. She was born in 1930. A child of the Great Depression. She died October 3, 2003 on the eve of the Patient-Doctor MPD Conference inScottsdale,Arizona. . She was 73 years old,

In between those two dates she mothered four children, cared for thousands of patients, published more than 70 scientfic papers on aspects of hematology and adopted myeloproliferative disease as her own cause. Dr. Gilbert conceived and organized the first conference that brought together MPN patients and doctors (1998) and was among the earliest researchers and supporters of interferon therapy.

She worked hard and did not seek fame or recognition. Her modesty is overwhelming. At first, we didn’t know why she followed this path down our back alley of hematology any more than we knew what she looked like. .

Even without her photograph or full biography, we knew her as the visionary Founder, the original source of MPN patient education and support. She was the first crusading MPD educator at a time of near total patient and even hematological ignorance of these diseases.

That might be the primary impact on us, as patients, but it is hardly the sum of Harriet Gilbert’s work. She became one of the world’s leading authorities on myeloproliferative disease, a full professor and research physician raising a family, a senior member of the critically important Polycythemia Vera Study Group, a mentor to residents, famously devoting herself to clinical patients. And she did all this long before women had easy access to positions of power and authority in the medical establishment..

Our search for a photograph finally ended up on the desk of Barbara Niss, archivist of The Mount Sinai Hospital. She provided us with images and a few biographical details

She graduated from Columbia University College of Physicians & Surgeons in 1955. She did an internship, residency and then fellowship in Hematology here at The Mount Sinai Hospital finishing her training here in 1961. She joined our staff in 1963 and rose to the rank of Professor of Medicine, Division of Hematology/Oncology. She was one of the first executive officers of the Polycythemia Vera Study Group… and a member of the Advisory Committee on Data Analysis and Management of the NIH. She was an Associate Editor of The Mount Sinai Journal of Medicine for many years where ‘she provided valued expertise, warmth and friendship’ according to a note they published after her death.

“I have scanned and attached two other images of Dr. Gilbert.,” wrote Niss, ” One is a much younger portrait shot, probably from the 1960s. The other shows her and Dr. Louis Wasserman, the chairman of the Department of Hematology

Courtesy, The Mount Sinai Archives

until 1973. He was also very involved in the Polycythemia Vera groups and was himself a well known researcher in leukemia. It would probably be safe to say he was her mentor.”

Dr. Louis R. Wasserman may in fact be our missing link, the connection between this brilliant and dedicated woman and the murky, unknown world of myeloproliferative disease. The Polycythemia Vera study Group (PVSG) was formed in the 1960’s and conducted randomized clinical trials and other studies of PV. For those interested, a book review on the PVSG findings ( lead editor, Louis Wasserman), appeared in the NEJM and describes im some detail the work of this seminal and extraordinary group, work that continue today, http://www.nejm.org/doi/full/10.1056/NEJM199503303321322

Harriet Gilbert went far beyond the confines of the university and the clinic.

Her vision and her life’s work transformed us from lost individuals into a dynamic, supportive international community of informed patients and caregivers..

_____________________________

(E-mails from Harriet Gilbert, Courtesy of Robert Tollen, MPDSUPPORT.ORG)

Date: Fri, 13 Dec 1994 21:06:38
From: MPD GROUP
Subject: MPD GROUP
Dear Members who have addressed mail to the MPD Group,

This letter is from Dr. Harriet Gilbert, President and Director of the MPD Research Center. Some time ago I set up the MPD GROUP on AOL and exchanged some E-mail with you. I then “dropped out” because of other commitments to the MPD cause. Today I returned to AOL and read the mail in the MPD GROUP mailbox. I can’t believe how informative and exciting it was to read your communications. You are all an exceptionally bright and aware group of people and I had many surprises as I read through your letters.
=====================

COULDN’T BELIEVE MY EYES

Date: Mon, 16 Dec 1994 23:32:53
From: MPD GROUP
Subject: RESPONSE TO YOUR WELCOMING MESSAGES Dear MPD GROUP members,

I couldn’t believe my eyes when I signed on the day after my first letter and found so much mail waiting for me. How come your responses are so prompt? What is your modus operandi to handle mail? Do you sign on every day? Please give me some advice and guidelines about the most expeditious way to proceed. By the way, I am composing this off-line and I hope that things will work when I sign on and attempt to send it.

….Let’s begin with some general comments:

I would like to thank Robert for the welcome back message and for providing the names that go with the “handles”. I find that I have communicated with most of you in the past through the MPD Research Center, so I feel that I already know you. I want to acknowledge Robert as the one who sent me the trial subscription to AOL. Without you I never would have become a member and it would have been a missed opportunity.
=======================
MY ADDRESS

Date: Fri, 20 Dec 1994 02:55:56
From: MPD GROUP
Subject: QUICK FIX ON YOUR QUESTIONS
Dear Members:

Thanks for the mail and the information that is accumulating at a dizzying pace. I have made up a spreadsheet (Excel) that itemizes your histories, treatment, comments, and questions. I will try to deal with them in detail as time goes by but I want to acknowledge some of them now and deal with them temporarily.

Re my location: I have my main office in NYC at 950 Park Avenue. My hospital affiliation in NY is Mount Sinai Medical Center. I have a subsidiary office where I go one day a week in the Baychester area (Pelham Parkway) of the Bronx and I am affiliated with the Albert Einstein College of Medicine, the Weiler Hospital branch of the Montefiore Medical Center, and the Bronx Municipal Hospital Center in the Bronx.

======================

ULTERIOR MOTIVES

Date: Wed, 22 Jan 1995 23:32:57
From: MPD GROUP
Subject: “ULTERIOR MOTIVES”
Dear Members:

How heartwarming your responses are! I am becoming addicted to AOL and our group. I can’t wait to steal the time to log on and read your mail. I’m sorry that I can’t spend more time answering your questions and responding to your stimulating comments. Part of my problem is that I have “writer’s block” and I find it hard to keep from editing and reworking what I write. I also am compulsive about getting my facts straight and communicating them clearly. The dialogue that I am having with you is very helpful in getting me to write more freely and not obsess over every detail. I have so much to tell you and I want to get on with it! There’s time for reworking and refining the what I write later.

Re my ulterior motives: Part of my inspiration to found the MPD Research Center and establish the Patient Support Group was to be able to provide patients with the information they need in terms that they could understand. The first (and only) issue of the newsletter, The MPD Voice, was my intial attempt to do that. In that issue I mentioned my desire to write a handbook on MPD. Unfortunately, the work entailed in maintaining the newsletter was too much for me, alone, and with the departure of my MPD Research Fellow, it fell by the wayside.

… I thank you for the stimulation that you provide and the renewed enthusiasm that you have given me in the pursuit of my dreams about contributing to the lives of MPD patients in any way that I can.

======================

THE APARTMENT HOUSE

Date: Wed, 11 Jun 1995 19:29:16
From: MPD GROUP
Subject: THE FUNCTION OF THE AOL GROUP & SCOPE OF ITS CONSTITUENCY

Dear Members,.

…The more patients with MPD you see, the more the overlap between these syndromes becomes apparent, in that there are all combinations and permutations of proliferation that are seen amongst the group with MPD and a single patient may show transformation from one syndrome to another during the long course of their disease.

All of these syndromes have in common the expansion of a single clone of stem cells (the parent cells that live in the bone marrow and have the ability to produce several types of circulating blood cells – RBC, platelets, WBC) that has mutated and developed a growth advantage that enables it to crowd out and/or suppress the many other normal clones that usually grow in the bone marrow and produce the RBC, platelets, and WBC, all descended from different stem cells.

Think of the bone marrow as a large apartment house or multiple dwelling with many families living there. The parent or stem cell living in each apartment produces a family of children (mature blood cells) that go out and circulate in the neighborhood (blood stream and tissues of the body). The stem cell also reproduces itself so that there are always several producers who can carry on the family line of that clone. Each family represents one clone of bone marrow stem cells and the descendant of that clone. The bone marrow (apartment house) is polyclonal since it has many families or clones all producing children and reproducing themselves. Picture one family moving in – let’s say drug dealers and users. They are prolific in their reproduction and they also are stonger and have more clout than the other families. Pretty soon they begin to take over the other apartments in the building, putting their descendants into these apartments. The polyclones – other families that are unrelated and are each carrying on their particular line of descendancy – begin to move out or they stay but stop reproducing (maybe they don’t want to bring up children in that hostile environment, or maybe the bad clone keeps them from doing their business or shopping or good living and they just go into hiding in their apartment. What you might end up with is a building that looks like it houses only the druggie clone, all carrying the same genetic message, all possessing the same DNA that conferred the growth advantage to the clone in the first place.

Now if you wanted to rehabilitate the building you could gas everybody in it, sacrificing the good, as well as the bad families, and import multiple new normal families taken from somebody else’s building to set up housekeeping in their apartments. You would have established a polyclonal building and destroyed the bad druggie clone. That is the theory of bone marrow transplant. Of course, you would have to make sure that you eliminated every last druggie family from the building or else, if they come out of hiding from some closet or from behind the walls, there goes the neighborhood!

Another approach would be to try to coax the druggie clone to leave by making the environment hostile. Or you could interfere with the fertility of the druggies and keep the population down. The problem is, it isn’t easy to be selective in raising the discomfort factor for the bad clone without destroying the good clone and having everybody move out or stop reproducing. Hydroxyurea is not selective and it acts on both the druggies and the good families. So the proportion of families that come from the druggie clone to families that are polyclonal remains the same, even though the cell counts (number of people living in the building) is decreased and the problem is controlled.

Anagrelide goes into the apartment building and is able to pick out all the children of all the families – druggie and normal clones – that have brown eyes (let us say brown eyed children are equivalent to megakaryocytes). Anagrelide will inhibit the function of those children with regard to their ability to make platelets. …

Interferon comes into the building like the angel of death sent by God to slay the first born of every Egyptian family while sparing the Israelites. It recognizes the members of the MPD clone and destroys it, selectively. Of course nothing is perfect and some MPD families survive, while some polyclone families may die, but the proportion of druggies born from the reproduction of that single bad clone falls, leaving normal polyclonally derived progeny to reoccupy the building ….I hope that the imagery helps you. I have found it useful with patients of all levels of sophistication.
======================
ON ALTERNATE TREATMENTS

Date: Tue, 10 Jun 1995 22:34:20
From: MPD GROUP
Subject: MANY THOUGHTS FROM DR. GILBERT

I must remind you that it is because you are intelligent and motivated to learn but lack the medical background to grasp fully the full significance of the information with which you are besieged that you feel frustrated and not in control of your disease. It is not appropriate to set to arguing amongst yourselve about the relative merits of various forms of therapy for the various MPD syndromes. How can you expect yourselves to answer this unanswerable question and make decisions about your therapy that are derived from “truth” when THERE IS NO TRUTH? You must realize from the lack of unanimity amongst experienced and well-informed hematologists and oncologists, some of whom have hands-on experience in treating MPD patients and evaluating the results of therapy that THE ANSWERS ABOUT THE EFFECTS AND SIDE EFFECTS OF HYDROXYUREA, INTERFERON, ANAGRELIDE, AND ALL THE REST OF THE CURRENT THERAPIES ARE NOT KNOWN. There is a need for randomized studies to answer some of the questions that you pose. If the picture were so clearcut you would not find reputable and expert clinicians differing with one another as much as they do.

I’m sorry to bear such bad tidings. It would be far more comfortable to tell you that treatment A is the best and that B and C are dangerous and terrible. However, it’s not true and anyone who presents the dilemma as anything but a dilemma and as a clearcut, simple choice is not doing justice to his intellect or his patient. The cutting edge is where you want your physician to be so that you may benefit from every advance in the field. BUT, you want your physician to be wise, flexible, open-minded, and aware of the imperative to custom design therapy for each patient ad hominum and not ad hoc. Rather than beating the drum for one or another approach to therapy, I would rather expend my energy to educate you to the fact that there are knowns and unknowns about each therapy and each approach to management and to encourage you to learn what you can, keep an open mind, take a mature approach to the field of medicine and not entertain the unrealistic hope that your doctor is a god who can hand you unqualified health and guarantee you that he knows the best and only therapy for your disease.

======================

FIND YOURSELF A DOCTOR

Date: Tue, 10 Jun 1995 22:34:20
From: MPD GROUP
Subject: MANY THOUGHTS FROM DR. GILBERT

By and large, I believe that you all have a realistic appreciation that medicine is as much an art as it is a science. You can bear with the medical profession’s inadequacies and fallibility because you know that health care is given by human beings and not deities…Find yourselves a doctor with whom you feel comfortable and who you can trust and use that person for all he/she is worth to guide you through controversies and doubts. You will benefit from this approach to your care and will not be afraid to engage in a healthy exchange of ideas, feelings, and information as you face your disease head on with your eyes wide open. I believe in your magnificence. Please don’t let me down
======================

IN THEIR ALIVENESS MAY APPEAR BRASH AND CONFRONTATIONAL

Date: Tue, 10 Jun 1995 22:34:20
From: MPD GROUP
Subject: MANY THOUGHTS FROM DR. GILBERT

Each of you, without exception, is a remarkable and unique person. It is almost a given that a person who is well into adulthood, which you all are, and who develops an interest in electronic communication and has the initiative and intelligence to use e-mail as you do would be “one step ahead of the pack”. The remarkable thing is that through the single common denominator of the disease you share you are able to communicate you knowledge, feelings, opinions, and even biases in such an explicit, vital, and fervent way. If each of you could take a few steps back and reexamine your communications and interactions, each of you would give yourself a huge pat on the back for being so feeling, caring, honest, and impassioned in your search for truth, health, and self-improvement.

Intelligent, impassioned, committed and fervent people are “alive” and in their aliveness they may appear to be brash, confrontational, insulting, ironic, cruel, uncaring, etc. Please try to remember your specialness as a group and as individuals in that group. Through my reading of all the mail nigh these many months I cannot find anything venal or indicative of unkind or unethical motives in any of your E-mails. On balance, they are caring, honest, heartfelt, intelligent, and sincere expressions of the individual who is generating them. At some times I have felt the vibes of frustration from each of you and believe that this is the result of your intelligence and need to know and understand yourselves and your disease. It is the human condition to survive and in service of that motivation, to believe that you are doing all you can to act in your own best interest.

======================

NEED A LIST
Date: Wed, 24 Mar 1996 04:47:34
From: MPD GROUP
Subject: Re: (Just one daily email)
To: MensaBrain@aol.com

Dear Robert:

It’s Dr. Gilbert back again. I heard from several members of the “old” group that there is a new format for communicating with you folks and I certainly would like to join in. The pressure of research, teaching, practice, and administrative commitments has kept me off the AOL circuit for some time now but I’m definitely up for reactivating my participation. Perhaps the new system will facilitate my keeping up with the mail.

======================

Robert Tollen started the first patient-run on-line MPN support list. Briefly joining him was Joyce Niblack who had met Dr. Harriet Gilbert in 1990. Tollen and Niblack were strong personalties who did not get along. Joyce, after a short time, left the group and worked with Gilbert as a patient volunteer. These two ultimately developed the two strongest lists, competed for members and status and are the progenitors of on-line MPN patient support through MPD-SUPPORT and MPN-NET.
Take me back.

Fall, Leaves are turning

As the flooding and scorching, quaking, wildfires of the Summer

start to recede under the blessings of Autumn, here’s a collection of stories, opinion, and news to help us turn over a few leaves ourselves.

First, a bit of history. We will look at the early days of MPN on-line patient support groups, the opening act of our series that traces their evolution from their fumbling beginnings in the earliest days of e-mail to today’s robust international traffic on the main MPN/MPD daily Internet support Lists… And you can get a sneak peak into practical genetics as Zhen opens his 23andMe report and shares the shock of intimate recognition….Then there’s our report from the Frontiers of Science featuring two blockbusters, an introduction to Ploidy and the reversal of fibrosis…and Strange Bedfellows, as blood and bone stem cells buddy up in a new niche.

Chromosomes, stems cells and megakaryocytes come into new focus. Our regular contributors have put on their wooly sweaters and hats to offer new pathways to health…Jeremy gets us off our knees and on our feet to beat fatigue..Patricia puts on her lab coat to show us our beliefs drive biology… Dr. Michael asks if patients even want to be empowered…and Dr. Arch is back in his Corner, holding forth on a range of issues. So come on in, look around and have your say, Comments wide open … Thursday, September 15.

Arch’s Corner – Septemer

Before boring y’all with my column for this month, I need to explain my take on 23andme …and me. I fully accept my friend Zhen’s right and acknowledge his talents and abilities to make cogent editorial decisions for the MPN internet magazine that he began and shepherds so well. That said, IMO, continued silence implies my agreement and I do not agree with the excess of early attention paid to 23andme. It seems to me that
23and me, no matter how distinguished the individuals and institutions involved might be, is a commercial company whose profit plan rests on collecting human data, both laboratory and personal, from volunteer
patients with a group of genome driven diseases, among them MPN.

The current quid pro quo for the patients is a tiny selection of their
genome offered free of charge with the hope that a better understanding
of these diseases will result. As I understand their offer, there is no
expert professional interpretation or guidance for individuals or their
families and no hands on clinical interface or medical care. I
understand that this information will be processed and sold to research
or other groups and might or might not lead to advances in the
understanding of these diseases. I don’t know if pertinent info from the
processsed data will be made available to each volunteer’s physician for
clinical care. To a degree 23andme seems much like the usual drug and
device trials.

The potential risks and benefits of volunteering your personal and
family medical history along with your DNA have been discussed, cussed,
polled and evaluated at length by our editor, his forum associates and
many readers of this magazine. There remain some questions re ethical
and scientific concerns raised by authoritative people. Some of these
questions could reflect the changes in methods and mores of 21st.C.
medical R.& D. and that some of us haven’t “got with the program” yet.
Perhaps these questions were not given equal editorial space for their
conclusions to be fully aired. However I’m not competent even to
consider if they are valid or could affect 23andme’s results. Maybe I
ought to “get with the program”.

In summary then, I believe MPNforum has gone beyond a duty to inform its
readers of 23andme’s existence. Right or wrong, I believe that this
forum has helped to give the company and its proposals premature
credibility and publicity, bordering on an endorsement that is not yet
earned. I further believe there are many other early research efforts
with as much or more potential than 23andme that haven’t been given
similar attention here. For example, reports of successful research on
altering T cells to destroy cancer cells or the emerging anuploidy
studies. However IMO, for all such early research reports, it suffices
to provide the MPN community with a reliable journal, net or other valid
source by name and/or abstract. These are only my opinions and clearly
in our editor’s province, not mine.

I’m not suggesting that 23and me should end up as ’23Skidoo’. In fact I
might sign up out of pure curiosity, if I were a patient instead of a
caretaker. BTW, how does 23 and me know that I don’t have MPN or RA or
Damfino’s disease? From my doctor? My hospital? My insurance agent? My
Medicare bureaucrat? My nosy neighbor? Or because they take my word for
it and if I lie, I’ll be charged a pretty hefty fee for the lab test
plus shipping & handling with no reduction for my worry and fear.

I reckon most MPD List members might not care, but I wonder if their
family members who share their ’46andwe’ genes want their family
genetics and past medical histories and potential futures shared with
23andme, its customers, assorted pfishermen and unknown hackers. Some
say it can’t hurt and might do some good. I guess so.

That’s my Tale ‘O Woe re 23andme and I’m stuck with it. I think it’s
reasonable. ie. it pleases nobody! I’ll gladly eat a large serving
of crow followed by humble pie if in years to come MPN is a thing of the
past owing partially to the good people at 23andme and the hopeful
thousand that only spit and wait. Just be sure to spit to leeward,
Y’all!

*************************************
Now for my column. There’s no need to groan! By George, I’ve helped to enable the publicity, if not the praise and thanksgiving for 23andme. So much so (and so needlessly) that there’s little space left in my corner.
Oh well, its importance is over-rated. I mean my corner, of course. I so
wanted to wax importantly about making premature end of life decisions
and pretend to know what to do about all that. I have urged previous
list mates to make wills and revocable powers of attorney. I’ve also
urged them to make living wills. Now I have some reservations about
handcuffing my doctors, my caretakers, my clergy and my family at the
moment they’ve assumed will be my death.

‘ARS MORIANDI’ (the art of dying) is all well and good in its time, but
for me, maybe just not now. I mean with all the advances in medicine
nowadays, yesterday’s hopelessness is often today’s successful
resuscitation and definitive follow up therapy. I remember well when
pneumonia was “The Old Man’s Friend”, but In the words of the old song,
“It ain’t necessarily so” today. When my Hg is 2.1, my marrow full of
reticulum and my energy non-existent I still wouldn’t mind a few more
days or months, even years to see the sun also rise and watch what
happens on this ole planet. I sure wouldn’t want to usurp the Almighty’s
decision re the date and time of my demise. I don’t want to know. I’m
gonna take a look at my living will and I suggest y’all do the same.

Cheer up folks, that’s more than enough musing (ok wadding) for my
corner this month so I’ll stop and enjoy our glorious Fall turning its
corner. Be warned, I just might expand on ‘Ars Moriandi’ a bit further
next month, but at my present youthful age, I want my living will to
give me a chance to be ‘Redivivus’. (ok I looked that one up).

p.s. Any connection, implied or otherwise, between 23andme and Ars
Moriandi is purely coincidental. 🙂
Take me back.

© Dr. Arch and MPNforum.com, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Dr. Arch and MPNforum.com with appropriate and specific direction to the original content

Bare, Naked DNA

My 23andMe DNA Report

Last night, late, my Gmail inbox flashed the news: “Your 23andMe Results are Ready!”

Finally, I could see what all the fuss is about. And share it right here in the privacy of our MPNforum’s tabloid pages..

After making sure the curtains were drawn, I shooed the cat out of the room, checked the closets, looked under the desk and then closed the door securely. This may be all about MPN research, but that’s down the road a bit. What has been delivered to me for immediate attention is a thick stack of searchable data about that most intriguing of all subjects: Me. -­

My DNA has been unraveled enough to tell the story of my history, some of my traits, and my risk of acquiring one or more diseases. Could there be a more absorbing way to spend an evening or two?

Admittedly this may be less interesting to you but, if you intend to go down this path you can at least get a glimpse of what’s in store when 23andMe rings your bell and uncovers your own deep past and lifts the curtain to your possible future.

I opened the computer file and scrolled down first to check out my ancestors. Just out of respect, you know. There they were, scowling and winking back at me:

Dad: J2a1b1

Mom N1b2

Choked me right up. My haplogroup. Tomorrow, I might have a gold medallion stamped with those magical characters. And hang it on a gold chain around my neck,. Think of it. J2a1b1 and N1b2 stitched on a sampler, framed, placed in a niche with candles and incense burning before it.

Naturally I was taken a bit aback when I realized I was the product of a mixed marriage. Worse, there is an off chance that a future stormtrooper will force me to wear those symbols stitched to a piece of yellow cloth Because, for all the differences in my maternal and paternal lines, their long common history is plainly written in my genes. Officially, I am a total Jew. It says so in black and white. A Sephardic and Ashkenazi Jew mixed in one package.

That wasn’t the surprising part as my mohel let me know that right from the painful beginning. My father was born in Russia, my mother in New York but for four centuries before that both families lived within 50 versts of each other in a much contested bloody strip of land on the shifting Northwestern borders of Russia. The surprising part was my chromosome ancestry record on both sides is 99% identical. (You can CLICK to enlarge those exhibits.)

The usual assumption among many Jews is we lived happily in the Holy Land, some making sacrifices, some changing money in the Temple, until booted out in the bloody Roman wars just after the time of Jesus. How we went from the desert to the freezing forests of Poland is the source of countless fairy tales and at least one good Broadway musical.

The stark haiku of my 23andMe haplogroup report, however, fleshes out a different story, a story of two migrations. The first took Dad J3a2b2 and the northern tribes of Samaria to Nineveh after a massive defeat to Sennacherib and the Assyrians. Shortly afterward these nomadic tribes emerged as the Jewish Khazars in the Caucasus. Their comings and goings alongside the Huns camped between the Caspian and Black seas, show up in my 23andMe ancestry map..

Several centuries later, the Judean migrations, ethnic cleansing encouraged by Titus and his Roman legions, drove Mom N1b2 to New York City and Tel Aviv via North Africa and Europe. All this is written in the Book of DNA, translated by 23andMe. Having spent years in the Moffitt Library and the Russian steppes tracking this history down, I can only marvel at the record revealed so easily. All that sweat, vodka and troika miles when the whole story can now be read in a drop of spit.

Predisposition to disease

I pulled myself out of the history book of my genome and turned to read some possible future scenarios. This is the much discussed “dangerous” part of the 23andMe Report….our predispositions, risk factors for disease, based on association of certain disease states with specific genetic markers uncovered in controlled studies. This is the stuff we’re supposed to keep out of the hands of insurance agents, employers, and prospective dates for an evening of light entertainment.

Good start: High probability, no disease

To start with, I had a good feeling for the reliability of this section since the top two conditions for which I am at high risk – psoriasis and rheumatoid arthritis, neither of which I do have – share a JAK-STAT pathway with myelofibrosis, which I do have. (There’s a bit about that in the Ruxolitinib report.)

I’ll spare you the walk down the whole menu of diseases – but do e-mail me if you’re interested in anything specific, I’d be happy to reveal all. I do want to focus in on just one that interested me: Thyroid cancer.

Thyroid cancer

I have Grave’s Disease, a nasty condition that sends the thyroid into overdrive along with the circulatory system, knocks out the body’s thermostat and pops out eyes among other exciting visual effects. It was brought under control when my thyroid was iodine irradiated which I’m reasonably sure sent me down this MPN path some 22 years ago. But 23andMe knows nothing of that. I have not yet filled out a survey. They have my name, date of birth and e-mail address.

The Thyroid Cancer page in the Disease Risk section is more like a chapter than a page. You open up to a short discussion of the thyroid, complete with function, incidence of thyroid cancer cases each year in the United Sates, followed by a “Preliminary Research report on 3 markers.”

These markers are short areas of DNA, SNPS that have been found to be associated with a predisposition for thyroid cancer. Just for a refresher, SNPs (pronounced SNIPS) are single nucleotide polymorphisms. Nucleotides are one of those letters that make up DNA. (OK, they’re not letters in real life but complex molecules denoted by single letters) . Each letter represents a molecule making up one half of a base pair that encodes our genome in that famous double helix chain of Watson and Crick. A, adenine, forms a base pair with T, thymine and G, guanine forms a base pair with C, cytosine. Those four letters – plus U, Uracil in RNA – is all of it, all our traits, all the code that goes into manufacturing each of us. And why two letters? Separate contributions from Mom and Dad.

Behind three doors

The report on thyroid cancer looks at three SNPs. In each case you get your ranking – high, average, low – and the impact of the anomaly,

Thyroid Report -- CLICK to enlarge

for example a T in the wrong place. You also get a reference to the source document that uncovered the association between the SNP and disease, and the odds of developing the disease based on the variation.

Behind the first door

SNP 1: Marker rs944289. The wild card here is the T. Each T increases the odds of thyroid cancer by about 1.4 times. Here, I hit the jackpot. Two T’s, nearly three times the average risk. The source study, published in Nature Genetics involved 1006 patients or European ancestry and 38,346 healthy controls. Julius Gudmundsson, et al., published in 2009

SNP 2: Marker rs965513 Here the Black Queen is the A. Each A increases the odds of thyroid cancer by 1.8 times. I slip into average risk with an AG, but still that A gives me nearly double the risk. Julius Gudmundsson did this research as well, same publication, different patient group, 962 Europeans, same controls. .

SNP 3: Marker rs2961920 Now we’re looking at papillary thyroid cancer, 608 patients and 901 healthy controls. The poison pill in this SNP is the combined AC genotype. Carry that SNP and you have three times the odds of thyroid cancer as the lowest ranking CC and 1.5 times that of mid ranking AA. This is a new investigator, Jazdzewski K et al. (2008) publishing in the Proceedings of the Natl Acad Sci. USA . I place right in the middle, double the risk of CC and half the risk of AC.

That’s it? This is the news we’ve been fighting over?

What have I learned? I think the report shows an elevated risk for thyroid cancer. Thyroid cancer isn’t that common — about 3% of all cancers — and there’s a high survival rate for most common thyroid cancers.

I check my reactions.

Strongest reaction Rushing down to the ER, report in hand.

Medium reaction Something to be aware of but no actio.n required

Minimal reaction Whatever. Toss it.

My strongest reaction is none of the above. At best I’m mildly interested. But how is it possible not to be impressed with the quality and depth of 23andMe’s work. After reading about the dangers of providing DNA results directly to consumers and the importance of having a mediating physician to interpret results, I wonder what alternative universe other people live in.

My own physicians rarely ask me to remove my shirt. I can’t remember the last time I sat in a waiting room with one of those open paper robes on. Mostly it’s an interview and a lot of computer keyboarding after an assistant records my blood pressure temperature and weight . The 23andMe report goes beneath the skin, into the nucleus of the cell, counts the sequence of molecules in key SNPS, pulls out anomalies that indicate demonstrated or suspected health effects and presents findings in a careful, balanced, sane way. What’s there to argue about? Even N1b2 didn’t do that for me when I was kid.

Double checking

There is a chance, of course, they just make this stuff up. Slim, but considering the passionate stances taken by folks over the 23andMe MPN initiative why not put to bed any eventuality. Actually, anyone can easily do it. Just Google the SNP number.

To confirm the quality of 23andMe data, I went to sources quoted in the report and to independent large scale NIH databases, SNPedia, GenBank, then to the articles in Nature Genetics, the research studies prepared by Julius Gudmonsson and took an independent readings on thyroid cancer from the Cleveland Clinic. Try it yourself.

It all checks out.

About the only new information I got googling around was that SNP Rs2961920 is part of Gene MIR146A on Chromosome 5. Now I do feel better knowing my SNP has a permanent home address but that’s about it. I’m pretty sure 23andMe wasn’t withholding this information.

Traits

There are other aspects to the 23andMe report and service but one that most of us will turn to is an assessment of our traits based on our genes. I found this one slightly off in some cases but absolutely mind blowing in one instance.

Despite my famed much-discussed great wealth, I was concerned over a $91 water bill I received from the City…along with a reminder that “It is not necessary to flush for everything.” With that in mind, I can’t tell you how stunned I was when I turned to TRAITS and there, right up top, right hand column, it clearly said “DOESN”T FLUSH” How on earth could they know this?

Alcohol Flush Reaction

Does Not Flush

Note: There is another way for you to get a realistic sense of what’s these reports actually contain so you can judge for yourself. Just go to www.23andme.com and type Demo in the search box.

Take me back.

© Zhenya Senyak and MPNforum.com, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Zhenya Senyak and MPNforum.com with appropriate and specific direction to the original content.