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Northern Lights: Meeting The Enemy

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Published: Jan 9, 2014 4:09 pm

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.


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.

───────────────── ♦ ─────────────────

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

Nancy Shamanna is a multiple myeloma patient and a columnist at The Myeloma Beacon. You can view a list of her columns here.

If you are interested in writing a regular column to be published by The Myeloma Beacon, please contact the Beacon team at .

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11 Comments »

  • Terry L. said:

    Thanks, Nancy, for this interesting article. When the genome was mapped for myeloma a few years ago, I remember a myeloma expert (his name escapes me)saying that myeloma science just leaped from the transitor radio to 3D technology. Hopefully, this advancing technology will reap benefits soon vis-a-vis personal medicine which can target MRD, etc. Your quote from Pasteur was especially important for myeloma patients given the multitude of treatment options and schools of thought (i.e. Berenson v. Total Therapy, etc.). Best wishes from frozen Haddonfield, New Jersey! Terry L.

  • Randy Strode said:

    Nancy, thanks for the very interesting and informed article. Since I am a Registered Pharmacist, I too remember the many years taking classes in microbiology, biogenetics, pathophysiology, medicinal chemisty, and a multitude of other advanced science courses ... so reading about all these advances and research might appeal to me more than someone else. Now, not saying I'm thrilled at my recent diagnosis at age 60 living a very active lifestyle and dedicated work ethic, it is comforting to know that much is being done on the research side and development of new novel and targeted therapies is reassuring to me. Fortunately for me, it was this same early technological advances in medicine that allowed my myeloma to be detected at an early stage and with dna testing was found to be a standard genetic & less aggressive kind. That's also nice to find out and wouldn't have been possible years ago. It is through the dedicated scientists, pharmacologists, and researchers that we could possible see a cure for this disease sooner rather than years from now. We have hope everyone. We have a lot more options now than before. And keeping the faith with a positive attitude in the face of adversity really does help battle this disease.

  • Nancy Shamanna (author) said:

    Thanks Terry, it's always nice to hear from you. The research into myeloma is very interesting, and because we have a vested interest in the outcomes it's a good idea to try to follow it as best we can. I am sorry about the 'cold snap' in your area. I am beginning to think that our weather in Calgary is quite predictable compared to some areas. However I have left the snow drifts behind for the weekend and am visiting family on Vancouver Island now. It's always green here and they never really stop gardening!

    Hi Randy, thanks for your note. That's a good point for you to make that we would not know whether or not we had certain deletions in our chromosomes associated with myeloma were it not for DNA testing! You have such a strong science background being a pharmacist (stronger than mine actually) that I am sure it will be no problem for you to read scientific abstracts such as those that the Beacon has published from ASH 2013, and understand and even analyze them. Look forward to reading more of your comments too! BTW, the pharmacists in Alberta have just run out of the seasonal flu shot here and we have an epidemic of flu this season. That's why I always get my flu shot in October, as soon as it comes out! Since I have a 'chronic illness' and my family are health care workers, we all get the vaccination.

  • LibbyC said:

    Hey Nancy,
    Its been 15 years since I was reading DNA sequence - on X-ray film!!! Isn't it wonderful how far technology has come. Hopefully researchers will stay a couple of steps ahead of MM.
    Hoping you are not too cold overthere, we are about to have a couple of over 40 degree days (with no airconditioning!).

  • Nancy Shamanna (author) said:

    Hi Libby, I am sure you know that one of the scientists who worked on the molecule DNA, Rosemary Franklin, was an X-ray crystallographer. Many people were working to get the structure of this macromolecule, including James Watson, Francis Crick and Linus Pauling. Although Watson and Crick got almost all of the credit for discovering that the shape of the DNA molecule was the famous 'Double Helix', Franklin had also contributed to this discovery. The year was 1953 ... we have come a long way!

    I also spent a summer back in the 1970's trying to extract DNA from vats of bacteria, spun down in a centrifuge to break down their cell walls. One was to extract the clear jelly like substance on long glass rods! Then the DNA was to be examined by protein electrophoresis! I wasn't very good at the extraction technique though, and didn't get much in the way of results.

    Sorry it's too hot where you live! I suppose the best seasons all round are spring and fall, since temps are more moderate. Take good care of yourself and Happy New Year!

  • Nancy Shamanna (author) said:

    Hi again Randy Strode ... When I agreed that DNA testing is good for diagnosis, maybe should have mentioned that this is often 'FISH' testing (Flourescence In Situ Hybridization). A section of DNA called a probe that has a specific chromosomal deletion or translocation, will be dyed with a flourescent dye. Then the probe is combined with the DNA from the patient. If the patient has the same deletion, the dyed segment will match to it, and this floursescent part shows up. This is not the same as DNA sequencing. The sequencing seems to have more of a research application and isn't a routine test for patients. There is so much to learn, it's very interesting!

  • Randy Strode said:

    I was already following along with you on your discussion of the DNA testing (FISH) testing. Much of the DNA stand testing and analysis has to be performed in a scientific lab using extremely sensitive and accurate technology, then the disease diagnosing and testing had to be developed from there to make them applicable in a clinical setting. From what I am discovering, our nemesis (myeloma) likes to mutate along these different DNA strands which can then cause patients to go out of remission, causing drugs that were previously very effective to all of a sudden not be so effective. That is why we can never stop searching, researching, and doing clinical trials. Things rarely stay status quo for long periods of time. Fortunately the disease will still respond fairly well to treatments both new and old after leaving remission. We just have to realize that we don't ever give up. More likely than not a real cure will come from utilizing both drug treatments and genetic therapies along with advanced nutritional products we haven't even had time to analyze yet.

  • Randy Strode said:

    As the pharmacy director for our company, I encouraged all of our company pharmacists to advance their education and clinical skills by getting certified to give immunizations many years ago. We too are experiencing the flu raging right now. Fortunately for our patients we had ordered a large supply this year in anticipation of this. Pharmacists in Illinois are legally able to administer 18 different immunizations under doctor protocol without making the patient go to the physician ahead of time. This has taken a huge burden off the primary care physicians so they can focus on other patients. I really try to stress to my patients to get their immunizations because that is one of the easiest ways to keep from getting some of these preventable illnesses.

  • Nancy Shamanna (author) said:

    Hi Randy, Thanks for sharing your information not only about myeloma research, but also about your pharmaceutical company. My husband is a primary care physician with his own practise, as well as working with rehabilitating victims of stroke at an auxiliary hospital, and I have some idea of what you are speaking of! A year after I had an auto stem cell transplant (January 2010), I started to get back my childhood vaccinations, from our public health clinic. At that time, 3 years ago now, I also took the pneumonia vaccine and do have the flu vaccine every year. That was reassuring to me, and although I haven't had titres taken, since some of the vaccines are given in a series, I hope they took effect on my immune system!

    The really scary thing about the flu this year is that it is H1N1 again, and it is affecting younger adults, in their 30's or 40's. The flu vaccine contains three strains, including the H1N1. So it is good to get vaccinated, in my opinion. I read last week that the supplies for this year have all been sold by the pharmaceutical companies, and any more purchases will be from the batches now being made for the winter in the Southern Hemisphere! I didn't realize that the flu shot is made in two batches like that, for each hemisphere.

    Sounds like a very interesting career that you have, and I hope that having myeloma isn't slowing you down TOO much. Best wishes on all of your 'journey' also, and hope you keep posting on the Beacon!

  • Randy Strode said:

    I was just recently diagnosed with mm in Dec 2013. I am really fortunate that I even went to the doctor for a case of bursitis in my shoulder. I have been an athlete all my life, so I am used to dealing with sore muscles, pain, and injuries and have a pretty high pain threshold. Even though I am not in as good a physical condition like I was in college playing football and other sports, I have always been pretty healthy and very active physically. And being a pharmacist, I knew how to take good care of myself, when I needed to see a doctor and not try to treat myself for different conditions, took my medications religiously.

    My orthopedic MD decided he wanted an MRI of my shoulder just to see if I had a torn rotator cuff. Wow! Then the bad news! My journey began and probably is similar to that of most mm patients. I am currently in 16 weeks induction of Velcade, dex, and cytoxan with a stem cell transplant in my future. So far I have had very few side effects, although I am seeing fatigue creep in when I work long days or a long week. I am determined that this disease is not going to define me. I might have to change a few things that I used to do but I have a mindset that I am going to fight and maintain a positive attitude through this journey. My hematologist/oncologist suggests that patients that can do that seem to do better also. But it's a challenge at times.

  • Nancy Shamanna (author) said:

    Thanks Randy for filling us in on your diagnosis and progress to date. It's an awful shock to find out that one has a type of cancer, but I think that with your background and the fact that your MM has been caught fairly early this would mean that you have a really good chance of getting through all of this and being well again.

    I am not up on all of the latest treatments but if you have any questions you should post them over to the forums. There are many very knowledgeable people who will chime in on practically any topic. I think that there is a thread ongoing now about the Velcade/Cytoxan/Dex treatment.

    You should take more rest than before, I think, since you are dealing with powerful myeloma drugs. And it's great that you do take good care of yourself, since that is also what is needed now! Best wishes!