I recently had the opportunity to take a tour of the myeloma research laboratory at our local cancer center. During that tour, I got a close look at the latest myeloma research that is being done.

First, we were shown the DNA se­quenc­er. This is an expensive piece of equip­ment, paid for by generous donations. It cost about half a million dollars and is set up in a separate room to avoid any cross-con­tami­na­tion from other lab materials and people in the area.

There are many different types of DNA se­quenc­ers available. The one in this lab is an "Ion Proton" brand sequencer (see photo below), which works by analyzing differences in pH between the four bases contained in DNA and RNA.

DNA (deoxyribonucleic acid) is a double-stranded macromolecule that consists of four bases: cytosine, guanine, thymine and cytosine. DNA is found in the nuclei of cells and contains the ‘code’ for all of the proteins of an organism. RNA (ribonucleic acid) is a single-stranded macromolecule that is in the same ‘code’ as DNA. It performs the function of actually helping to make the proteins, in a part of the cell known as the ribosome.

The Ion Proton sequencer that I saw is the only one in Canada that is devoted solely to myeloma research. It is housed in a metal box, small enough to sit on a counter top, and has an electronic readout panel. It doesn’t look all that extraordinary at all, but it can read the sequences of DNA and RNA that make up a person’s genetic material, or genome.

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Ion Proton Sequencer
(Photo by Colorado State University)

Compare this modern-day unit to the research of the past. It took 16 years and 3 billion dollars for the first human genome to be analyzed; the project was com­pleted in the year 2001. Nowadays, a person’s entire genome can be determined, or sequenced, in just one day.

A lot of careful preparation goes into readying a DNA or RNA sample for se­quenc­ing. These samples are ob­tained from bone marrow aspirates, those very bone marrow biopsies that we patients love to hate. RNA and DNA are extracted and stored at -80 degrees Celsius (-112 degrees Fahrenheit).

The sample is put onto a special chip with millions of microscopic wells, and the chip is then placed into the se­quenc­er. The se­quenc­er tests all of the human genome, and the millions of wells in the chip allow this process to be completed in only one day.

The machine tests for one of the four bases that make up DNA and if that base is in the DNA sequence, a proton is released. This causes a change in the pH that translates into an electric signal.

This is an amazing technology that provides results for much less money than was spent originally. One of the little chips now costs about one thousand dollars.

In the research lab, the samples from one patient may be analyzed for both DNA and RNA to perform RNA se­quenc­ing and target se­quenc­ing. RNA se­quenc­ing reinforces the data obtained from the DNA se­quenc­ing. Target se­quenc­ing looks at the DNA sequences that are transcribed into mature RNA. The researchers need to have both target and RNA se­quenc­ing in order to analyze what the mutation is that is driving the tumor.

Researchers are currently trying to determine which mutations are driving the tumor or causing drug re­sis­tances. As we know to our dismay, multiple myeloma is a disease that firstly arises because of mu­ta­tions in our plasma cells or even from myeloma progenitor stem cells. Unfortunately, our plasma cells may continue to gather harmful mutations. Patients may become resistant to drugs that they first responded to. If the researchers could better understand which mutations are related to drug resistance, they could know how to better customize treatment.

After this amazing insight into the work at the research lab, I had the opportunity to look through a high-powered microscope and to see some live myeloma cells – The Enemy.

Through the eyepiece, and lit from below with a bright light, I saw a field of dancing cells. There were quite clear and seemed transparent. They had irregular edges and some were clumped together. I had seen photos of myeloma cells in textbooks before; they were cross-sectioned and had dark nuclear staining. The ones I saw under the microscope were clear, small cells bouncing about in the clear cell culture medium.

These cells are my nemesis, I thought to myself. My bone marrow was half full of them at the time of my diagnosis, and they were crowding out my healthy blood cells.

My life has come in a circle in some ways. Back in the 1970s, I received a bachelor of science in micro­biology. During my studies, I looked at lot of samples through microscopes. I also worked in a research lab for a couple of years after graduation. I helped to manage a bacterial culture collection of different strains of salmonella bacteria and assisted post doctoral fellows and Ph.D. students in their research.

Back then most procedures, including data analysis, were done manually. Fast forward to the 2010s, and computers are doing science faster than a team of human minds can do.

We live in a very exciting age for science now. We can expect great results from all of the research that is ongoing.

As a myeloma patient, I am not pleased to have to fight cancer on an ongoing basis for the rest of my life. However, I am thrilled to learn more about the state of modern cell biology, and I would not have gotten interested in this topic without my diagnosis.

I have the greatest respect for all the scientists and doctors (some of whom wear the two hats) who have been working away on these problems for decades now.

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The quotation for this month is from Louis Pasteur (1822 - 1895), a French chemist and microbiologist, who wrote "Fortune favors the prepared mind."