Tag Archives: Rituximab

Biology, cancer

A Life in Remission

In the midst of an active research career in astrophysics, in 2008 I was diagnosed with non-Hodgkins Lymphoma, and my world ended.

For the next eight years I learned to live with the cancer growing slowly within me like some creature out of the infamous ‘Alien’ movie series. Annual tests showed the dozens of affected lymph nodes were very slowly growing in size by the millimeter, but with luck none of them would  turn dangerous for a decade or more. But no one could predict when my cancer would ‘transform’ and become dangerously aggressive, requiring immediate chemotherapy. Actuarial forecasts said that the probability of transformation increased by 5% per year, so that after 10 years I would have a 50/50 chance of my NHL becoming aggressive, but it could happen sooner. …or much later. As a scientist, this uncertain diagnosis was devastating.

A scientist conducts research based on the a priori assumption that they will live to see the end of their work and to publish the results.  I just know you are going to say ‘Well, no one knows when they are going to die’, but among those of us who deal with cancer, these kinds of sentiments seem insensitive and a bit flippant no matter how well-intended.

How does one function when one does not know when the monster will spring out of hiding and put the kibosh on your current work? Many of my projects required several years of work, followed by months of writing-up the results and interacting with referees and journal editors to publish the results. You simply cannot muster the stamina to carry-on your research and deal with referees when you are on a short, emotional leash.

Coping with an uncertain future in research

I immediately began to wean myself away from the rigors of research and instead moved into the area of education where NASA had a huge footprint. I won two grants to develop my SpaceMath@NASA resource, which grew every year to become a significant mathematics resource for educators. I even became known in some circles as Dr. Space Math! This was an intensely therapeutic undertaking for me because could write new math problems and design new math books whenever I chose to on my timetable, and if I literally died tomorrow, I would have left behind a complete archive of fun math resources. It was an open-ended commitment that suited my new frame-of-mind, and still made me feel as though I was contributing, intellectually, to a Greater Good: The education of our children.

As the years began to add up, 5…6..7…8  I started to realize that I might be in this cancer frame-of-mind for the long haul. But by this time my hiatus from research, and my ‘advanced age’ of 64, precluded any re-entry into the level of research I had enjoyed in my earlier years. It was very sad to see this part of my career waste away, but considering I was in my peri-retirement years, perhaps as it is for so many other scientists, this transition was inevitable.

In 2016 my NHL became aggressive after eight years of near-dormancy. I was quickly rushed into a course of immunotherapy with a monthly infusion of Rituximab and Bendemustine for six months. At the end, a PET scan showed in November, 2017 that there wasn’t a sign of  the NHL anywhere, and my oncologist, Dr. Bruce Cheson at MedStar/Georgetown University Hospital in Washington DC pronounced me in remission. For the next two years, if there was no further sign of the NHL, he would consider me cured!

All of a sudden my attitude seemed to change almost literally over-night. I was anxious to start new research projects that, at least for now, could be completed in six months or less including writing up the results and submitting to the Journals. I had been out of my own research area for too long, and besides no astronomer at the age of 65 worries about new research unless they are still employed at a stable faculty or government job…which I was not. But I did have a part-time position at NASA working on citizen science activities. I was also involved in some very fun research trying to determine how well smartphones performed as scientific data-gathering sensors. That was starting to generate a pipeline of short-term projects culminating in several papers every year. But now that I was in remission, I could start to think about more complicated projects to tackle once again.

So I, basically, have come full circle in research having wandered for eight years in the dreary and uncertain desert of non-research work.

It’s good to be back!!

 

Physics

Cancer and Cosmology

For the treatment of my particular cancer, small B-cell follicular non-Hodgkins Lymphoma, I will soon be starting a 6-month course of infusions of Rituximab and Bendamustine. The biology of these miracle drugs seems to be very solid and logically sound. This one-two chemical punch to my lymphatic system will use targeted antibodies to bind with the CD20 receptor on the cancerous B-cells. This will set in motion several cellular mechanisms that will kill the cells. First, the antibody bound to the CD20 receptor attracts T-cells in the immune system to treat the cancerous B-cell as an invader. Thus begins my immune system’s process of killing the invader. The antibody also triggers a reaction in the cell to commit suicide called apoptosis. Even better, Rituximab does not set in motion the process to kill normal B-cells!

The promise is that my many enlarged lymph nodes chock-a-block with the cancerous B-cells will be dramatically reduced in size to near-normal levels as they are depopulated of the cancerous cells. So why do some patients not all show the same dramatic reductions? About 70% respond to this therapy to various degrees while 10% do not. Why, given the impeccable logic of the process, aren’t the response rates closer to 100%?

Meanwhile, in high-energy physics, supersymmetry is a deeply beautiful and lynch-pin mathematical principle upon which the next generations of theories about matter and gravity are based. By adding a teaspoon of it to the Standard Model, which currently accounts in great mathematical detail for all known particles and forces, supersymmetry provides an elegant way to explore an even larger universe that includes dark matter, unifying all natural forces, and explaining many of the existing mysteries not answered by the Standard Model.
Called the Minimal Supersymmetric Standard Model (MSSM), Nature consistently rewards the simplest explanations for physical phenomena, so why has there been absolutely no sign of supersymmetry at the energies predicted by MSSM, and being explored by the CERN Large Hadron Collider?

In both cases, I have a huge personal interest in these logically compelling strategies and ideas: One to literally save my life, and the other to save the intellectual integrity of the physical world I have so deeply explored as an astronomer during my entire 40 year career. In each case, the logic seems to be flawless, and it is hard to see how Nature would not avail itself of these simple and elegant solutions with high fidelity. But for some reason it chooses not to do so. Rituximab works only imperfectly, while supersymmetry seems an un-tapped logical property of the world.

So what’s going on here?

In physics, we deal with dumb matter locked into simple systems controlled by forces that can be specified with high mathematical accuracy. The fly in the ointment is that, although huge collections of matter on the astronomical scale follow one set of well-known laws first discovered by Sir Isaac Newton and others, at the atomic scale we have another set of laws that operate on individual elementary particles like electrons and photons. This is still not actually a problem, and thanks to some intense mathematical reasoning and remarkable experiments carried out between 1920 and 1980, our Standard Model is a huge success. One of the last hold-outs in this model was the discovery of the Higgs Boson in 2012, some 50 years after its existence was predicted! But as good as the Standard Model is, there seem to be many loose ends that are like red flags to the inquiring human mind.

One major loose end is that astronomers have discovered what is popularly called ‘dark matter’, and there is no known particle or force in the Standard Model to account for it. Supersymmetry answers the question, why does nature have two families of particles when one would be even simpler? Amazingly, and elegantly, supersymmetry answers this question by showing how electrons, and quarks, which are elementary matter particles, are related to photons and gluons, which are elementary force-carrying particles. But in beautifully unifying the particles and forces, it also offers up a new family of particles, the lightest of which would fit the bill as missing dark matter particles!

This is why physicists are desperately trying to verify supersymmetry, not only to simplify physics, but to explain dark matter on the cosmological scale. As an astronomer, I am rooting for supersymmetry because I do not like the idea that 80% of the gravitating stuff in the universe is not stars and dust, but inscrutable dark matter. Nature seems not to want to offer us this simple option that dark matter is produced by ‘supersymmetric neutralinos’. But apparently Nature may have another solution in mind that we have yet to stumble upon. Time will tell, but it will not be for my generation to discover.

On the cancer-side of the equation, biological systems are gears-within-gears in a plethora of processes and influences. A logically simple idea like the Rituximab treatment looks compelling if you do not look too closely at what the rest of the cancerous B-cells are doing, or how well they like being glommed onto by a monoclonal antibody like Rituximab. No two individuals apparently have the same B-cell surfaces, or the same lymphatic ecology in a nearly-infinite set of genetic permutations, so a direct chemical hit by a Rituximab antibody to one cancerous B-cell may be only a glancing blow to another. This is why I am also rooting for my upcoming Rituximab treatments to be a whopping success. Like supersymmetry, it sure would simplify my life!

The bottom line seems to be that, although our mathematical and logical ideas seem elegant, they are never complete. It is this incompleteness that defeats us, sometimes by literally killing us and sometimes by making our entire careers run through dark forests for decades before stumbling into the light.

 

Check back here on Wednesday, December 28 for the next installment!

Rainbow image credit: Daily Mail: UK
http://www.dailymail.co.uk/news/article-1354580/UK-weather-Rainbow-dominates-skyline-winter-storms.html