Tag Archives: Rituximab

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