In an earlier post I discussed cytomegalovirus (CMV) primarily in relation to its impact on the immunosuppressed—people with AIDS and those of undergoing a stem cell transplant, for example. As a prelude to that discussion, I mentioned that CMV causes mononucleosis.  This piqued a reader’s interest:

. . .[I] found it interesting that CMV was related to mono—I’ve had mono, though apparently tested negative twice before positive, but am CMV negative—thankfully!

Presumably, the test for mono the reader mentions was a test for Epstein-Barr Virus, and not CMV. Epstein-Barr Virus (EBV) is another herpes virus that is closely related to CMV, and EBV causes a disease named infectious mononucleosis.  CMV causes a disease very similar to mono, and many authorities call that disease infectious mononucleosis.  The Centers for Disease Control says the disease caused by CMV is a “mononucleosis-like illness,” whereas the National Institutes of Health states flatly that both EBV and CMV cause mono.  When I took microbiology, I apparently learned virology from the NIH school of thought.  But it seems more authorities discuss EBV in relation to mono, perhaps because EBV is more likely to cause disease at initial infection (even though many show no symptoms), whereas CMV usually causes no or very mild symptoms in people when they catch it.  But both are attributed with causing a disease of the same name.  So why the hell is that?

First, it’s important to note that these two viruses are quite closely related—on the evolutionary tree of life, I mean.  And so EBV and CMV share essentially all of their genes, with some minor variations (minor for sure when compared to the total genetic diversity of life, or even that among viruses). Because of this, it is no surprise that they cause similar disease.

Second, it’s also important to keep in mind that viral nomenclature is a complete mess.  The international rules of nomenclature that have been well-established in zoology and botany for nearly a hundred years (but deriving from rules that are centuries old) are simply not in place for viruses.  The best recent example of this is the HIVs.  When Montagnier in France first isolated a virus he suspected to cause the plague of immunodeficiency that was killing off mainly gay men, he named it LAV (for Lymphadenopathy Associated Virus).  Then Gallo in the USA named it HTLV-III (for Human T-Lymphotropic Virus III)—and that name is now used for a completely different virus. The virus that causes what would be named AIDS was also called ARV (Adenopathy Related Virus) for a time.  Ultimately, yet another name was established by international convention (sort of): HIV. But now we know that the thing we call HIV is in fact at least two distinct groups of viruses that entered the human population via separate events.  What a shambles.

I only point this out because this confusion about viral nomenclature spills over into disease nomenclature.  Lots of named diseases—”the flu,” “the cold,” “AIDS”—are in fact each caused by many different, often closely related but nonetheless distinct species.  And this unfortunate practice is not restricted to viruses:  Human “malaria” is caused by one of four quite distinct microorganisms, and the characteristics of the diseases they cause are just as distinct.  This is all to say that the tiny creatures that cause disease evolve just like the bigger creatures they live in. Species split, become isolated, acquire mutations independently, get different, and ultimately become two species.  Although the new species did “get different,” they also share almost all of their traits by inheritance.  Whatever characteristics the initial, ancestral species had, the two new descendant species will very likely share most of those same characteristics.  In other words, close relatives are a lot alike because they come from common stock—something we all know from our own families.  And this is why two differently named viruses can cause the same named disease (even though, in a perfect world, virologists would stop this nonsense).

So the reader is right:  One can have a diagnosis of mono without CMV, and it’s CMV—not EBV—that is so problematic for those with trashed immune systems.  All important points of clarification for those who might be facing a stem cell transplant.

The amazing Barbara Ehrenreich makes a connection, just after the crash of 2008, the 160th anniversary of the publication of the pamphlet that ignited the world:

The Manifesto makes for quaint reading today. All that talk about “production,” for example: Did they actually make things in those days? Did the proletariat really slave away in factories instead of call centers? But on one point Marx and Engels proved right: Within capitalist societies, or at least the kind of wildly unregulated capitalism America has had, the rich got richer, the workers got poorer, and the erstwhile middle class has been sliding toward ruin. The last two outcomes are what Marx called “immiseration,” which, in translation, is the process you’re undergoing when you have cancer and no health insurance or a mortgage payment due and no paycheck coming in.

You can read the whole blog entry here.  It’s an older post, but well worth the read . . . as is everything Ehrenreich’s ever written.

I’m 98.4632% sure that the comments submit button now appears.

A reader’s email:

Five hours!  Few of us healthy folks do that … at least not often enough! As we learned in desert survival school, if something CAN grow, something WILL. And that is the history of our planet.  More things grow than die.  In the midst of cancer treatment, it’s a tonic to know that.

So glad you got out amongst the living!   When you’re living “in the valley of the shadow of death”, you need to bask in the light whenever possible.

I might quibble with the assertion that “more things live than die.”  After all, every living thing dies, and 99% of all species that have ever arisen have gone extinct.  And even if the reader’s assertion were true, while such a rule would apply to “me” (the original “me,” that is) and my new stem cells, it would also apply to my cancer with equal force.  Cancer is life too, and it is struggling to live, just the same as the “me” that does not include the cancer—a majority of “me,” the original “me,” the un-mutated “me,” but not quite all of me.

But the central message of the email is clear:  I have reason for hope.  And despite my usually squinty-eyed, suspicious, sardonic predilection, I agree.  And I am glad to be among the living.

Today, Greg and I (masked and gloved) went to Walden Pond for a second visit, this time with our dear friends Alison and John.  We hiked the trails for a few hours.  There was life all around us—trees, insects, birds, and mammals were obvious everywhere we walked.  Walking with my loved ones, I thought of Thoreau.  Thoreau saw majesty in the smallest creatures.  As he famously wrote in Walking:  ”In wilderness is the preservation of the world.”  So much of my existence lately has been about killing bacteria, and killing viruses, and killing cells, and killing . . . and fear of death. Today was only about life, and living.  I needed today.

After Walden, we went into Concord and walked around, saw the beautiful Concord Library, Sleepy Hollow graveyard, and other historical landmarks.  It felt great to get out, especially at Walden and in Concord, where so much important American history took place—and where the words that would change my life and influence me to want to become a biologist and activist were written.

Were it not for Thoreau, and Emerson, and Alcott, and (to a lesser extent) Hawthorne—but especially Throreau—I might not have become a biologist, and so might well not be in a position to understand what is happening to me right now—my stem cell transplant.  I might not have become an activist, and so might not have the spirit to confront and challenge my physicians when needed. I can say honestly and with no hyperbole:  These qualities—a love and knowledge of Nature, and a rebellious bent—have been utterly essential to my survival since diagnosis.

So, today reminded me of my past, but also gave me hope . . . faith . . . for the future.  I remembered how important Nature is to me, and how important being with Nature is to me.  And I saw the power and majesty of Nature, if only briefly.  And today reminded me of rebellion, and of being young . . . and strong.  Today I walked, and hiked, and talked, and laughed for five hours. Five hours!  It was the most exertion I’ve had since the transplant, by far.

Today I felt strong.  Very strong.

It appears that I’m over whatever I had. My nose has stopped running, and my slight cough has resolved as well. I felt a bit under the weather yesterday, but I’m feeling better today—not as good as before this scare, but I’m getting stronger again.

So much of this process is unknown, but a lot is known. One of the things we know is that slightly immature T-cells are responsible for initiating immune responses against viruses. When these T-cells come in contact with other cells that are infected with viruses (or that are otherwise presenting “foreign” chemicals), they do a variety of things that ultimately cause the infected cells to die. But this process takes time, and the infection can spread in the meantime. So, one of the things these immature T-cells do to help with future infection from the same virus is they give rise to more specialized cells. Some of the resulting differentiated T-cells are known as Cytotoxic T-cells (or sometimes CTs, or CD8 cells, where CD refers to a group of proteins on the surface of the cell membrane, deemed Clusters of Differentiation. CTs, or CD8 cells are also sometimes also called T8 lymphocytes, but I’ll just stick to CTs).

CTs are one of many kinds of so-called memory cells; they retain a special chemical affinity (a “memory”) for cells infected with a specific virus, and when the CTs encounter infected cells again, they kill them on the spot—a much faster solution than the slower process that happens the first time infection occurs. This, coupled with other systems, is why once we’ve had a virus, we’re forever immune.

The problem for me is, I don’t really have any T-cells at all. My new immune system is not developed enough to have created any mature T-cells or even any of the slightly immature T-cells needed to initiate the response described above. And that means I don’t yet have any Cytotoxic T-cells from my donor marrow. As CTs are long-lived memory cells, I presumably have circulating in my peripheral blood some of my original, native T-cells that survived the stem cell transplant, but that doesn’t appear to be true. We know this because of the results of my most recent chimerism tests—genetic tests that determine the proportion of peripheral blood cells that are of my genotype versus my donor’s genotype. (Remember that my blood is a chimera right now, like Dictyostelium—part original cells, part donor cells).

Those genetic tests, performed a month ago, show that when considering all of my T-cells, 97% are donor genotype. Those 97% are very immature (too immature to give rise to CTs), and the remaining 3% are what’s left from my former immune system. And while this 3% no doubt includes mature T-cells, and some CTs, they just aren’t very clinically effective for most people (so says my physician). Hammered from the chemotherapy of the transplant? The radiation? Too few to mount a defense? I’m not sure, but they’re impact is apparently thought to be minimal in any event.

But something has changed. I had these symptoms, and now they’re gone. Maybe I beat a virus somehow; maybe it was allergies. I guess I don’t care too much, except from an academic position. But one thing is certain: It couldn’t have been that crystal I shoved up my butt. I only did that an hour ago.

A good friend recently pointed out his surprise at my use of the word communist in this post, given my political leanings. He’s right; that wasn’t the right word. What I meant was totalitarian.  I do think that the cells in our body are locked in a kind of communism, but the negative aspect I was pointing out isn’t necessarily linked to that.  Obviously, communism has lead to totalitarianism often, but I hope it’s clear from my blogs that hyper-individuality in the midst of society has its serious costs as well. We’ve seen the cost of extreme individuality in the stock market (no surprise, from a historical perspective; it’s all right there in Marx), and we see its costs in cancer.

The experiment of America, of Federalism, is partly about grappling with these seemingly incongruous interests. The Founders tried to find a solution, and the Transcendentalists tried to find a solution. But so did the Bolsheviks. And so does Polistes, and so does Dictyostelium, and so do all living things.  For social creatures, negotiating the individual and the group is an everlasting struggle of life.

This conflict plays out in our bodies as well, at times.  That was the only message I intended.

My last post was an honest and authentic expression of my thoughts and feelings about my current state of being.  I wasn’t hiding anything.  But there is something else going on.

This morning I awoke with a runny nose and some congestion.  This could be a minor bacterial infection, which would not likely be a problem to snuff out.  But, given that my mucus is clear, bacterial infection seems unlikely.  Viral infection is more consistent with that sign.  It could be one of a number of common viruses that cause runny nose.  For some of these, anti-viral treatments are available.  For many, the viruses don’t even have names, but they don’t cause dangerous infections either.  I’m hoping for one of these, of course.  It could be the flu, and (despite rapidly increasing resistance) that is treatable with osteltamivir.  But it could be something much more dangerous:  the seemingly innocuous, simple, common cold.

While the common cold causes the mildest of infection in immunocompetent people, in me, it could be a disaster.  Permanent scarring of the lungs is one outcome; death is another.  As no treatment for the common cold exists (though a number of experimental therapies are soon to help out), recovery relies on one’s immune system entirely.  Chicken soup may soothe, but it doesn’t cure.

Viral infections are defeated by lymphocytes.  The two main groupings of lymphocytes are T-cells and B-cells.  T-cells circulate in our blood, looking for proteins that are not self.  When one is found, the T-cell starts dividing, and some of those T-cells seek out B-cells.  The T-cells notify B-cells of the presumptive invader, and through one of the most amazing biological processes ever elucidated, germ-specific antibodies are produced.  Those antibodies ultimately cause cells infected with viruses to die (among other things).

So T-cells initiate (and later suppress) immune response.  B-cells primarily give rise to antibodies. The problem for me is that I don’t have very many of either of these cells.  Unlike neutrophils (white blood cells that primarily fight bacterial infection) and platelets, many developmental intermediates come between stem cell and mature lymphocyte, and it can take up to nine months for mature lymphocytes to appear after transplantation.  I do have a few lymphocytes from before the transplant, but it’s not clear that they will be of much use.

At this point, I just have to wait.  If matters get worse, I’ll get a nose swab tomorrow.  That might reveal a treatable virus or an untreatable virus.  Maybe I don’t have a virus.  I just don’t know right now, but in addition to being energetic and happy, I’m starting to get pretty scared.

I feel amazing.

I am so energetic, I can barely contain it.  Anyone who has spoken to me on the phone lately can attest.  For the last two weeks, my energy and strength has been rising every day, and now I feel better than I’ve felt in years.  In early 2007, I was in a brief remission, and I felt wonderful, like I’d felt years before—before the fatigue set it, which happened three full years before my diagnosis in 2006.  I now feel as good as I did during my remission, which can only be good news.

Reasons for my quick recovery are many: Being able to eat, no more diarrhea, and, most recently, the cessation of a particularly nasty treatment.  That treatment, with the drug ganciclovir, is for infection with CMV, cytomegalovirus, the a virus that in healthy people causes mononucleosis^‡.  I was taking this drug probably because of a hospital error.  In order to explain, a brief digression into biology is required. (Regular readers shouldn’t be much surprised.)

CMV is one of the most commonly transmitted viruses on the earth.  The probability of contracting CMV rises with every year over one’s lifetime, and virtually everyone has it by middle age.  Despite this, I luckily tested negative in my pre-transplant blood tests.  Even more luckily, my donor was also negative.  This was great news, as CMV can cause blindness, serious lung problems, meningitis, and death in immunosuppressed people—facts that I remember all too well from my AIDS activism days in the late ’80s and early ’90s.  My early blood tests found no antibodies for CMV, and a highly sensitive test for CMV’s DNA, called PCR (for polymerase chain reaction), also showed negative initially.  However, three weeks into my transplant, a weekly PCR test was positive.  This was somewhat odd.

CMV is a herpes virus, and like all herpes viruses (including the virus that causes chickenpox [Herpes zoster]; Epstein-Barr virus; and of course, Herpes simplex I and II), CMV can hide inside cells that it infects, inserting itself into our cellular DNA.  When this is the case, a DNA test of blood might well be negative.  So if the CMV became active later, a previously negative PCR could become positive.  That part wasn’t the odd piece.  The odd part was my antibody negativity.

Antibodies are those amazing, disease-specific chemicals that our body produces in response to invasion by viral infections.  For every virus that infects us, we have a different antibody (well, almost).  But I was antibody negative for CMV, and that was the weird piece.  If I had been infected before, and the CMV had become quiescent, and then reactivated three weeks after my transplant, I would’ve been antibody positive the whole time.  But despite my suspicions of the apparently discordant blood tests, the positive PCR meant action had to be taken, and fast.  Because of the great risk of CMV infection, my physician rightly put me on ganciclovir immediately.

The great thing about ganciclovir is that it is very successful in defeating CMV.  I remember when ganciclovir came to market; it was a revolution for people with AIDS.  Prior to ganciclovir, having AIDS often meant the loss of sight, or worse.  And nothing could be done to stop CMV.  Ganciclovir changed all that.  But the bad news about ganciclovir is that it suppresses the production of blood cells, especially white blood cells.  After I began taking the ganciclovir, all of the components of my blood—my platelets, red blood cells, and white blood cells all crashed.  After an unusually fast and strong engraftment of my donor’s stem cells, which resulted in my having normal or near-normal blood counts for the first time in years, I was back to square one, and continuing to take the drug kept me there.  And to boot, after this blood cell crash, I contracted that awful C. difficile infection. Administration of ganciclovir has a known association with infections like C. difficile.  I had to be treated for the apparent CMV infection, but the treatment made me fragile.

Two weeks ago, my DNA test for CMV was negative, as it had been every time after the first test.  I asked my physician why I would not have anti-CMV antibodies if I had CMV (again, antibodies are always produced when we’re exposed to an infection, and we keep them forever).  After some discussion, my physician agreed that this was odd, and hypothesized that perhaps I’d acquired the CMV infection from one of my many pre- and post-transplant blood transfusions.  But that didn’t explain everything, and I left that meeting unconvinced.

Over the next week I puzzled over all my clinical data.  Why was I antibody negative?  Maybe it was because my immune system was so shot that it couldn’t produce any antibodies.  That is very likely true, but even so, I should still have residual (and easily detectable) antibodies from before the transplant, as they remain in the blood months after they are created.  Considering the DNA tests, I wondered how the ganciclovir could have eradicated the infection so quickly; I’d started taking the drug on a Thursday evening, and by the following Tuesday morning all evidence of the viral DNA was gone.  Ganciclovir is a good drug, but that good?  I asked about this the following week (last week).  My physician—who is remarkable in being open to discussion and input—considered my concerns and took a third look at the data, treating them all together.  The negative antibody test, the lone positive PCR result, and the rapid PCR negativity that never reversed—they just didn’t add up.  After this, my physician concluded that the first CMV test may well have been a false negative positive (this can happen with PCR, because this DNA test is extremely sensitive, and in labs where these tests are run routinely [like mine], contamination can be a serious problem).  As a result, we decided to stop the ganciclovir.  My blood cells, in theory, should begin to rise again.

So, yesterday when Greg and I went to the hospital for my weekly appointment, we were a bit disappointed that my blood cells had not rebounded more.  My hematocrit (one measure of red blood cells) was a bit higher, my white blood cells had gained 500 cells per squared cm (up from ~1,100), but my platelets were down from 80,000 to 50, 000 (both well below normal)—a mixed result.

But given how amazing I feel, I wasn’t too worried about this.  I did ask about the possibility of graft failure—a topic I’ll take up a bit later—but looking at the data on the proportion of “my” blood cells that are truly mine verses from my doner, everything looked excellent.

Stem cell transplant is an unlikely business.  Juggling all the variables—the risk of infection, the risk of Graft Versus Host Disease, the many drugs, the side effects of those drugs—managing all these can all be . . . well . . . at times impossible for both the physician and patient.  This procedure is truly at the bleeding edge of our knowledge, and much of what goes on, and why certain aspects of the therapy work or don’t, is yet unknown. When in a situation like this, in my experience two factors are indispensable: patient self-advocacy, and physician finesse.  Having cut my teeth on AIDS activism, I have no problem telling physicians that this is my body, and we must work together, as co-equal partners, to manage my illness, treatments, and recovery.  My current physician agrees, unusually, and we cooperate to achieve our common goal.  That cooperation is a big part of why I’m so energetic and healthy today.

And it’s good to feel great for the first time in a long time.

^‡UPDATE:  See this post.

I do.

Being from Louisiana, and now living just south of the arctic circle, I need the sun.   But I can’t be out in it.   Sunlight can stimulate my immune system (particularly the immune-boosting helper T-cells), which will lead to that conflict I wrote about in the last post, known as Graft Versus Host Disease in medical circles.   Unlike the case of an organ transplant—where there is risk of Host (the person’s immune system) Versus Graft (the transplanted organ) Disease—Graft Versus Host Disease (GVHD) is the reverse, sort of.   In this case, my new immune system (the graft) attacks my entire body (the host). Scary, eh?

Even scarier, if GVHD happens, the risk of relapse is much lower in my cancer.   So ideally, GVHD will happen a bit, but not too much.   Walking that tightrope is up to my oncologist, and he says he can do it. Again . . . scary.   But if all goes well, GVHD won’t happen for many months, during which the immunosuppressive drugs I’m on are slowly removed.

But direct sunlight could counteract the effect of the immunosuppressives, awaking my sleeping, new immune system.   For now, I’m something of a vampire, coming out of my lair only at dusk, making sure to avoid direct sunlight.   So because of all this, a good friend of ours, Karole Moe, who is an amazing artist and who just happens to live in Boston, dropped off some sunlight for us:

A Pollock-esque joy.  Bright rays fill the foreground, and dusky wisps fade into the background. Few things make me genuinely happy these days.   This does every day.