Doctor Durie

'The Seed and the Soil' in the search for the cure.

2011-12-15T00:21:52Z

In presenting "What is myeloma" to newly diagnosed patients, Dr. Morie Gertz uses the comparison of myeloma to "weeds" in a garden, which in this case is the bone marrow microenvironment. A recent book, Weeds: in defense of nature's most unloved plants, by Richard Mabey, provides wonderful insights into the analogy of myeloma cells as weeds.

So what is a weed? The first aspect is that it is not intentionally planted- so it is not a "plant" (or flower/tree/bush) which you wanted. Certainly, this applies to myeloma cells nobody wants them. There are truly intruders. Other aspects which apply are: aggressive, resilient- hard to get rid of and spreading in an unwanted fashion. What is the driving force behind all this? Why do weeds keep popping up?

The answers are interesting and important. Weeds love "disturbed ground": areas recently dug up, bulldozed, abandoned, or contaminated with toxic waste. Classic sites for weeds were bomb sites in London during the blitz of the Second World War. Weeds unseen for generations, suddenly grew in profusion. The weeds started a process of environmental healing: transitioning to new urban countryside. So weeds function in a restorative fashion.

So what is myeloma? Local sites of myeloma in damaged tissues do occur rarely but are quite remarkable. For example, a gentleman struck by lightning on his leg bone went on to develop myeloma at that site. Other examples include myeloma growing in the pocket for a cardiac pacemaker which became infected and myeloma growing alongside leaking silicone breast implants. So the point is a disturbed, activated, and damaged microenvironment can enhance myeloma growth.

Weeds also outgrow new favorable environments. If conditions are right, weeds can overtake any garden. Myeloma cells do the same and continue to grow when conditions favor antibody production or production of the "monoclonal spike" in an effort to combat infection. A "positive feedback loop" can be established whereby the disturbance, activation, or damage is not corrected (for example, breast implants are leaking and are not removed) and a favorable growth environment persists. The myeloma monoclonal protein (or antibody) cannot do its job: the local situation is not corrected. It is amazing to see the impact of what happens when the situation is corrected with immune modulating agents such as thalidomide, Revlimid, and Pomalidomide. The microenvironment is stabilized: growth slows or stops. There is an opportunity for abnormal cells to be eliminated. But, like weeds, myeloma cells are remarkably resilient. We need ways to wipe out every last cell and/or keep the microenvironment hostile for new growth.

In nature, mature forests teach us many lessons. Trees and shrubs dominate some weeds, those which are light dependent die off, others are not able to compete with large trees that change the soil chemistry. So re-achieving balance is a natural strategy. This provides hope and the expectation that correct maintenance strategies can work long term, if crafted with the aim of achieving the best immune and chemical balance. As we are learning from our fields and gardens, using stronger and stronger weed killers may not be the way to go. So let's keep an eye on the weeds and see what more they have to teach us and help us in the search for the cure.

Continuing the search to find a cure: thoughts before ASH 2011

2011-12-09T07:34:46Z

Almost a decade ago now, I collaborated with Faith Reidenbach in publishing an article in CURE magazine describing the status of myeloma therapy (DEEP IN THE BONE: Managing Myeloma: CURE magazine Vol I: pp 31-38 2002: @ curetoday.com). At that time, we were very excited about the recent availability of the novel agents, thalidomide (Thalomid®) and bortezomib (Velcade®). Dramatic responses had occurred and patients previously without options were having new remissions lasting over 2 years (unheard of at that time).

I discussed the role of thalidomide plus dexamethasone pre-autologous transplant and the pros and cons of long term low dose thalidomide maintenance. And so it began: the evaluation of combining novel and traditional high dose chemotherapy approaches.

So how far have we come in this last decade? Patients are definitely living longer and better lives with many fewer complications of myeloma and side effects from treatment. The average life expectancy has essentially doubled from 3 years to 6 years. Patients under age 50 years with good risk features (i.e. low ISS stage; normal [or good risk] chromosomes on FISH testing) can reasonably expect to live in excess of 10 years.

This is huge progress and pushes the search to find a cure in two directions. Firstly, get the maximum mileage from novel combinations to further extend survival. But, secondly look for something completely new to truly wipe out myeloma and establish a cure.

As we look toward ASH for 2011, we see continued refinement of new combinations. Since it takes time to assess long term follow-up, it is hard to know for sure the added value of ever more complex regimens. Caution about potential toxicities is an increasing concern. Full discussion of ASH highlights will be posted next week.

The need for a continued search for a cure is emphasized by the current special issue of Science magazine: 25 November 2011, Vol. 334, pages 1046-1051, *Mysteries of the cell*. Five articles discuss what we still need to understand about how the cells of the body function. What is the exact structure of the cell membrane? How does a cell control its size? How does a cell organize the positioning of all the different pieces of the cell? How do cells know when they need to eat to get more energy and nutrients? And, finally, do genes function differently if in a new location within the cell? All crucial questions! So we need to be very humble as we pose new questions about myeloma. We have so much to learn about how both normal and cancerous cells work! It is truly amazing and encouraging that despite that, major progress is being made every single day as research moves ever forward.

But what about the cure? Not much to report yet. Dr. Ed Stadmauer reports that two trials, using re-infused T-lymphocytes from patients "armed" (with carefully selected warheads) against myeloma, are ongoing with early but promising results. A new vaccine trial at Hadassah University Medical Center in Jerusalem has been recently announced. The "one shot cure" approach announced by Dr. Russell at the IMWG Summit in London in the summer is proceeding with a first trial reaching the phase I patient stage and a second approach (probably the more promising of the 2) for now, just at the level of animal testing of the "oncolytic" (cancer destroying) virus.

The IMF is committed to both, track and report, on these two research directions which can lead to both longer survival and ultimately a cure. Stay tuned!

Norcia Italy: Center of a New Food Revolution Flavor and Health for the Future

2011-12-07T23:10:16Z

On the way to the Patient and Family Seminar in Rome, we had a side trip to Norcia, two hours northeast of Rome. Norcia is a beautiful small town (~5,000 inhabitants) where a young chef, Flavio Feadi, (Executive Chef at Palazzo Seneca) is creating food in a whole new way. Using fresh, local, organic produce is the key first step. In this amazing protected valley of Norcia, the healthy produce needed to create flavorful meals is less than 20 minutes away. One can start the day with free range eggs with a touch of olive oil and balsamic (from Modena), plus a touch of local cheese. For lunch, the wonderful small local lentils and beans are the building blocks for soups and side dishes.

But, a visit to the rolling hills close by reveals something truly unique: free range pigs! You have heard of free range chickens-- but pigs, that's unheard of! They roam, eating and reproducing in the woods above Norcia. They eat acorns plus other nuts, grasses, roots and herbs, resulting in products with both enhanced flavor and health value. This free range pig farm with approximately 300 pigs is unique in Italy: there are only 2 other similar farms in the whole of Europe! Norcia is so unique in fact that Michelle Obama's staffers recently visited to learn more.

These pigs live and sleep in the fields and woods completely unconstrained-- returning at a run to the whistle of the proud owner, Giusseppe. Meanwhile, across the valley, in higher more heavily wooded hills, organically fed sheep and goats wander the fields-- although they scuttle indoors if storms are coming. Caring attention from the farmer and his wife results in from wonderful milk and cheeses, including ricotta and harder aged varieties mixed with cow's milk as necessary.

In the valleys, are fields of corn and grains, such as oats (avena in Italy). Tomatoes love the climate as do the grapevines of all types spread across the rolling hills. The vines of Monte Falco have been selected with science and intuition to produce special local wine: Sagrantino (Rosso)--red wine with a bold/ strong flavor and an earthy taste. It was interesting to learn that Montefalco red wines have the highest levels of health giving polyphenols of any wine. In the valley, leading into Norcia, flows the Nera River with plentiful trout and freshwater crayfish for the catching. This is truly the 21^st century *land of milk and honey*. Close by are scattered hives of bees brought to areas of new blossoms to create unique flavorful honey.

If this was not enough, the specialty of this area of Norcia is Black Truffles (Tartuffinerie)! They grow 6-12 inches underground close to the small oak trees that cover the lower slopes the hills. There is a symbiosis: truffles get sugar from the trees; the truffles (a fungus) give much needed nitrogen (natural fertilizer) to the oak trees.

Early in the morning or late in the evening, when it is cooler, small dogs, often cocker spaniels, go out with their owners to sniff for truffles. The relationship between the dog and its master is something to see, a loving and respectful partnership resulting in a prized truffle.

On the surface, there is just rocky ground. But suddenly the small dog picks up speed and heads for one of many of the small oak trees. Frantically, it starts digging--then, turns its head to the owner-- can he help with a small pick to clear stones? Then, more digging and then with tail wagging in triumph, truffles are proudly revealed for all to see. The owner must snatch the truffle quickly-- dogs DO love truffles, but not as much as pigs. Dogs have largely replaced pigs as truffle scouts for this reason. The dog goes from tree to tree, finding more black treasure-- worth 1000 Euro/truffle from Nov-Jan: high truffle season.

Back at Palazzo Seneca in Norcia, Flavio is quietly gathering herbs in his garden awaiting deliveries from the hills, valleys, and river. Avoiding heavy sauces, Flavio concocts fantastic dishes, blending the fine local produce into infinite combinations of delicious meals.

The focus is local, organic, and healthy. Chef Flavio gives an unwitting *tip of the hat* to American nutrition guru, Michael Pollan, who cautions us not to eat what our grandmothers wouldn't recognize and to shop only at the "edges" of our supermarkets, where fresh items can be bought. The unique difference is that Flavio can shop at the edge of his own valley, not a commercial supermarket!! This is the key to good nutrition: local, free range, and no added chemicals.

There is NO reason this approach cannot flourish elsewhere. It is not the wave of the future, but of NOW! Even within metropolitan London, as reported by Alice Rawsthorn (International Herald Tribune Mon Sept 19th), Paul Smyth is trying hydroponic farming and a range of other techniques to stock his East London Farm Shop. In the U.S. several cities now sanction chickens and goats as well as several types of agriculture within city limits. Affordable healthy food is becoming accessible. I am sure this is just the start of this burgeoning movement to achieve local, self-sufficiency with healthy food.

The side trip to Norcia was quite a trip!

New Myeloma Hotline in Italy: Expanding global access to information

2011-10-11T17:03:37Z

Myeloma patients need access to information about their disease to get the best care. The IMF has been enhancing educational activities in Europe for over 15 years. In 2011, there were 10 Patient and Family seminars (PFS), 7 Community Workshops, and 7 Doctor Community Workshops throughout Europe. These meetings bring myeloma information to thousands of patients and hundreds of physicians.

The last PFS was in Rome on September 30^th. This was the 9^th annual PFS in Italy conducted in close collaboration with Dr. Mario Boccaddoro, who heads a large myeloma program in Torino, as well as the Italian non-profit leukemia/lymphoma/myeloma foundation (AIL--Associazione Italiana contro le Leucemie), based in Rome. For the first time, the PFS was held at the AIL headquarters in Rome. This is a beautiful facility with both office space and an amphitheatre-style lecture hall. The building was donated to AIL (it was a cookie factory!), which then did a wonderful job in refurbishing the building with true Italian style and elegance. Professor Franco Mandelli, the head of AIL, gave a welcoming speech to the audience. The only downside to the event was that the seating space "maxed out" at ~150, and more than 100 additional patients wanted to attend! Something to consider in planning for future meetings. In the past, we have held our meeting at the Mussolini Auditorium, which is part of the University of Rome. It accommodated over 350 patients and was packed to capacity.

Nonetheless, it was a wonderful day with very active patient participation. There were presentations by myself, Susie, Mario, and several Italian myeloma specialists, including Professor Robin Foa, currently a director of the European Hematology Association (EHA). One thing is clear: myeloma patients around the globe have the same questions. Which treatment should I take? What are the side effects? What happens if it does not work? And of course, "When will there be a cure for myeloma?!"

A unique aspect of the Rome PFS was that Debbie Birns from the IMF Hotline team also participated, and had a chance to meet with Alessandra Malfintano, a new hotline coordinator just starting to work with Professor Mario Boccadoro in Torino. Alessandra is a clinical trials nurse for Dr. Boccadoro's group, and has been talking to myeloma patients on a regular basis about the research that is being done in Torino and about the risks and benefits of participating in various clinical trials. She is a bright, caring, and lovely young woman who is eager to pioneer the first myeloma hotline in continental Europe. Debbie was able to spend part of the day with Alessandra, giving her pointers on how to set up the new hotline and what kinds of questions to expect. Alessandra jumped right in and helped a man who approached during the lunch break, passing her first "test" with flying colors.

This is an exciting and important new initiative. We expect that this will be the first in a series of hotline services to answer questions for patients across Europe.

So the Italian sojourn for the IMF was a great success. Individual patients getting personal questions answered. Myeloma patients feeling connected to the resources available in Italy and around the world. One more step towards providing the best care possible. One more reminder to stay focused on searching for a cure!

9/11 and Myeloma

2011-09-09T18:07:31Z

This Sunday marks the 10^th anniversary of the 9/11 attacks on the World Trade Center towers in New York. Among the casualties sustained that day, were a number of first responders who, instead of running away from dangerous ash clouds that enveloped the streets of Manhattan, ran toward them in the hopes that they would be able to help save lives. This country owes a debt of gratitude to these heroes, who put their own lives on the line to help others.

But all the gratitude in the world isn't going to cover the high costs of fighting the battle against cancers like multiple myeloma. Apparently, neither is the U.S. Government, which despite having enacted the $4.3 billion James Zadroga 9/11 Health and Compensation Act, has denied claims that toxic exposure from 9/11 attacks has any correlation to the increased rates of cancer appearing in the men and women who were directly exposed to the toxic environment surrounding the fallen towers in the aftermath of the tragedy.

I respectfully disagree.

Dr. Philip J Landrigan, head of a Sept 11^th treatment, monitoring, and research program at Mt. Sinai Medical Center, said in the NY Times that "we know full well that the responders were exposed to a whole soup of carcinogens." Carcinogens are chemicals known to cause cancer including myeloma, chemicals like those found in Agent Orange. As the direct link to multiple myeloma has been studied and established, the Veteran's Administration now fully compensates myeloma patients who were exposed to Agent Orange during the Vietnam War.

I believe the direct link between the "carcinogenic soup" that the first-responders were exposed to during 9/11 has also been established. We already know there was exposure to cancer causing chemicals at the World Trade Center. The levels of chemicals were measured in the blood and tissues of first responders, and a report detailing the findings in seven patients with myeloma was published just last year. Since then, even more cases have been discovered.

Image via Wikipedia

There are three papers published in the British journal The Lancet on September 1, 2011 evaluating nearly 10,000 male fire department personnel. The study affirms the toxic impact of the 9/11 exposures and the increased occurrence of lung problems, as well as a range of other medical problems including cancer. There is a specific increase in non-Hodgkin's lymphomas, a blood cancer similar to myeloma, which is also linked to the same causative factors. For myeloma, a rarer cancer, the numbers are currently small. Unfortunately, myeloma has been occurring in not just men but also in young women (which is very unusual for myeloma) who were first responders, but that data was not included in the recent Lancet publications.

I believe the case has been made. Representatives Carolyn Maloney, Jerrold Nadler, and Peter King, authors of the James Zadroga 9/11 Health and Compensation Act, also believe the case has been made. It took the emphatic support of Admiral Zumwalt, whose son developed lymphoma after service in Vietnam, to push through legislation to compensate Vietnam Veterans exposed to Agent Orange.

As Americans, we need to speak up on behalf of the brave men and women who heroically displayed the true American spirit by responding during a crisis a decade ago. I call upon not just the myeloma community, but also our entire nation, to demand justice for our men and women in civil service. We need to push for expanded coverage for cancer through the James Zadroga 9/11 Health and Compensation Act. If you want to help, contact the IMF Advocacy team at advocacy@myeloma.org.

Come on, Irene: Despite the hurricane's approach, the show must go on!

2011-09-01T21:31:48Z

Last weekend, the IMF held our fourth and final Patient & Family Seminar of the year in Philadelphia, PA. We had an uninvited guest make her presence known in the form of Hurricane Irene. As they say, "necessity is the mother of invention," so we came up with an abbreviated schedule with the intention of ending early and getting everyone on their way home before the storm hit.

So, yes, we did end up with a smaller and shorter seminar than had originally been expected, but something rather large came out of it anyway. During the Friday night dinner, the Philadelphia Multiple Myeloma Networking Group presented a $48,000 check to the IMF from the proceeds of their 3^rd Annual Miles for Myeloma 5K fundraiser. This brings the total amount raised by this annual event to $200,000 toward research programs for the IMF!

In addition to the check presentation, the Philadelphia group announced that they had recognized a local doctor, Dr. Dan Vogl, with the "Brian Durie Humanitarian Award" earlier this year. I am honored that the group has decided to continue recognizing people who make a great impact on the lives of myeloma patients in their area. Dr. Vogl cares so deeply for his patients that he has voluntarily undergone a bone marrow biopsy so that he could experience what his patients feel firsthand.

At this point in the program, Susie Novis spoke about the IMF's Brian D. Novis Research Program, which awards grants of $50,000 or $100,000 to Junior and Senior level investigators in the field of myeloma research. Over the years, the IMF has awarded more than $4 million to these research projects, and many have gone one to receive further funding from other prestigious institutions.

The 2011 deadline for the Brian D. Novis Grant applications was on August 1^st, and we at the IMF were pleased to see that the program's reputation had grown to the point that we had more qualified applications than we have ever received in IMF's history!

We want to respond to this increase in applications by increasing the amount we can award this year. Susie began by pledging $1,000 to fund an IMF research grant. Andrew Kuzneski then spoke up and pledged $2,500. Then, from across the room, somebody spoke up and pledged $3,500!

The pledging continued until Doug Farrell stood up and offered to pledge $500 if we allowed him to sing. Earlier in the evening, we had mentioned the Farrell's annual "A Song For Ireland" fundraiser which has become quite successful over the years. We always welcome a chance to hear him sing in person, and he did not disappoint. Doug led a rousing sing-along rendition of "High Hopes" which ended in a fabulous round of applause.

It happened rather quickly, but we tallied that more than $10,000 was pledged that night. Along with the Philadelphia Networking Group's check presentation of $48,000, we were well on our way to funding a Senior level grant!

Despite the weather, the cancelled flights, and the east-coast evacuations, the IMF was able to hold a slightly altered but still very informative seminar in Philadelphia this year. For those who were able to make it there, we thank you for your understanding and patience as we all scrambled away to catch the last flights out of the airport before they shut down. For those who were unable to attend because of the hurricane, we hope that you will consider applying your registration fee to one of our four seminars coming up in 2011.

And to those who not only made it to the seminar, but also stood up to make a contribution, thank you for helping us do our best to find the cure for myeloma.

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If you would like to make a contribution to the IMF's research program, click here, or call the main office at 800-452-CURE.

China: the new frontier in the search for a cure for myeloma

2011-08-19T22:16:25Z

I have just returned from the IMF's visit in China where there are more myeloma patients than anywhere else in the world. It is with this in mind that the IMF has established the Asian Myeloma Network, to address the growing incidence in one of the world's most densely populated regions.

Upon our arrival in Beijing, we met with Professor Wenming Chen and co-hosted a two-day seminar for 180 of the top myeloma doctors in and around China. This was an emotional and exciting meeting. In typical Chinese fashion, during the opening session, when I presented an overview of current IMWG guidelines for myeloma, a large metal stand was constructed outside to take a panoramic picture of all attendees.

After the photo-op, we regrouped and I conducted an interactive session on bone disease diagnosis and management. This opened the discussion of what resources are currently available across China. I learned that while there are two or three centers capable of administering most of the treatments available in the West, most facilities were not as well-equipped. Velcade® and a local Chinese brand of thalidomide are both available, but Revlimid is not yet approved in China, and autotransplant is feasible only at a few centers.

After lunch, we set off across Beijing. Dense, brown smog settled over the city as we made our way to participate in a meeting of the "China Myeloma Patient Club"- an over 1500 patient-strong Chinese support group. With some trepidation we entered a hot (~90F), humid room where around 40-50 patients had gathered to get answers to prepared questions presented in slide fashion. This was an extraordinary scene with patients sitting around crowded tables eating sunflower seeds awaiting answers about how best to prevent or cope with treatment related neuropathy and a range of other issues.

The questions of pressing concern to these patients were similar to ones asked at the recent IMF Support Group Leaders Summit in Dallas: Should they have a transplant? How about maintenance? After about an hour and a half, the meeting evolved into a "free-for-all" as patients approached all f us for answers, truly desperate for advice and comfort. The need for a presence like the IMF in this environment was apparent.

We then met the local nursing team and junior physicians working at this western Beijing Hospital. The genuine commitment to myeloma patient care was truly extraordinary. We pondered the events of the day as we tried to cool down on our long trek back across the city. What would be next?

That evening, Susie and I were asked to speak at a gala dinner, during which we took the opportunity to thank our host and congratulate the 11 founding members of the Chinese division of the IMWG. Day one in Beijing offered us a glimpse into the enthusiastic commitment to this first broad myeloma educational initiative in China.

The next day we met with the representative of the Chinese Health Promotion Foundation (CHPF), with whom we entered into a collaborative agreement earlier this year. We learned of an opportunity to submit a grant request for approximately $200,000 to support educational initiatives for 2012, which we submitted immediately upon our return to the States. We are very excited for the chance to further the IMF's mission to promote patient education and awareness in China.

We then headed off to Shanghai, home to 30 million people. We were introduced to Professor Jian Hou at the First Military Hospital. This hospital includes a transplant unit plus inpatient and outpatient services, and there is an off-site university translational research center with molecular biology laboratories where the group has conducted GEP, FISH, SNP and other "state of the art" molecular/genetic research projects. After touring the facilities I gave a lecture to about 60 Shanghai hematologists on "The Search for a Cure," which created considerable discussion both about past accomplishments and future possibilities. There was clearly great potential for cutting-edge research in Shanghai. Prof. Hou is the principal investigator for the "bridging study" which will lead to Revlimid approval in China, hopefully by 2013.

The day again culminated in a gala dinner. In this case, our visit coincided with a local celebration: the appointment of two young women doctors in the department to the Associate Professor level, which is a very important achievement. The President of the Chinese Hematology Society attended and quipped that "he had to wait for US visitors to get an invitation to a proper dinner at a top Chinese restaurant." It was a special evening of celebration and the start of ongoing collaborations. A meeting is planned for May 2012 in Shanghai, both to convene the Asian Myeloma Network investigators and initiate a series of preceptorship programs in China.

After an exhausting few days we collapsed into bed to awake ready for the trip home. China is indeed the new frontier with both incredible needs and incredible opportunities. It will be exciting to see the fruits of the next few years as the IMF seeks to facilitate outreach to physicians and patients throughout China. The search for the cure will certainly be ongoing in several expanding myeloma research groups across the country.

On the subject of rainbows and earthworms

2011-07-28T22:20:22Z

Reading about the newly re-discovered Rainbow Toad in Borneo reminded me of my January 27, 2011 post referencing Mae-Wan Ho's The Rainbow and The Worm: The Physics of Organisms, where she states that "Life is all the colors of a rainbow in a worm."

As I mentioned in that blog post, researchers in Singapore recently concluded that quantum entanglement plays a crucial role in explaining the stability and data storage of the DNA double helix.

Image via Wikipedia

I wrote:

Professor [Luc] Montagnier is convinced that crucial differences can be detected at the electromagnetic level in addition to methods using conventional sequencing and "chemical" testing which are central to the overall project.

And:

"...it seems that understanding life at the sub-molecular and electromagnetic level is now possible."

What if the spectrum of colors in the rainbow reflect the range of energies which control life processes? Imagine, for example, if all the energies that regulate the body functions could be thought of similarly to different wavelengths of light. If so, we would be able to modulate the body at the level of physics and cure cancer.

As it turns out, electromagnetic research is ongoing. Results so far have shown that researchers are getting data on electric pulses from myeloma DNA versus normal DNA, and there is an article in the current issue of Science Journal on the electric pulses from E. Coli bacteria. While it is still too early in the process to have any clear evidence, it will be interesting to see where the study leads.

My Search for a Cure

2011-07-25T17:04:07Z

At this month's Patient & Family Seminar in Dallas, TX, I posed this question to the panel of myeloma experts: "What myeloma research would you conduct if you were given $100 million?" Faculty member Dr. Rafat Abonour, from Indiana University, responded to the hypothetical question with an absolute departure from what I expected to hear.

He said, "If I had $100 million, I'd give it to Brian Durie. I know he'd find a cure."

Since that moment, I have been contemplating what I would do with that kind of funding. While the International Myeloma Foundation's research program is focused on collaboration and results through translational research, our annual budget limits our ability to research every possibility that presents itself.

Recently, I was pondering the "Black Swan" approach to research, a term coined by philosopher and essayist Nassim Taleb. This theory dictates that one must be open to the "highly improbable" in order to make significant advances. Taleb explains that at one point, it was mistakenly believed that all swans were white. This idea did not change until somebody traveled to Australia and discovered black swans by accident.

Image via Wikipedia

But what if someone had predicted the possibility of black swans prior to coming face to face with one? What if the hypothesis that black swans could exist had not been summarily dismissed based on lack of evidence or relevant data? The result would have been the same - they exist; but, instead of happening upon the truth by accident, it might have been sought out and discovered earlier.

I believe that this approach applies to cancer research as well. Each week I read about new ideas in medical journals, on the web, or in newspapers that make me take pause and wonder "what if?"

What if these "out of the box" projects had enough funding to see them through? What if an idea without any scientific evidence or data to back it up, could actually lead to a cure? Would it be worth pursuing?

With that in mind, I have decided to begin sharing my thoughts on some of the projects I read about during the course of my week. Using my newly established twitter account (@BrianDurieMD) I will post links to interesting abstracts, articles, stories, and blogs about projects that I might fund with my hypothetical $100 million.

I invite you to follow me on twitter and revisit this blog as I continue searching for a cure. After all, who really knows what color the next swan will be?

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You can follow along as Dr. Durie spends his hypothetical $100 million in search of a cure at @BrianDurieMD on twitter. Find the IMF online at @IMFMyeloma and on facebook at facebook.com/myeloma. And, if you are so inclined to make a contribution to the IMF's actual research program, we'll be more than happy to accept it at donate.myeloma.org.

The Physics of Myeloma: Is That Where the Answer Lies?

2011-01-27T19:54:22Z

Normally we talk about the "chemistry of life" and we are quite familiar with the development of new chemicals to treat cancers including myeloma. About two years ago, the IMF entering into a research agreement with Prof. Luc Montagnier in Paris, France, the Nobel Laureate, (who discovered the AIDS virus.) We agreed to investigate nucleotide sequences in the blood of patients with MGUS, smoldering myeloma and active myeloma to assess the presence or absence of DNA sequences including virus and/or bacterial related sequences, hints of which we have detected in prior studies. A number of genetic fragments have been identified using whole gene sequencing techniques. Using samples obtained in collaboration with Dr. Shaji Kumar and colleagues at the Mayo Clinic in Rochester, Minnesota, the research is moving forward rapidly.

However, a new facet has emerged: Professor Montagnier is convinced that crucial differences can be detected at the electromagnetic level in addition to methods using conventional sequencing and "chemical" testing which are central to the overall project. In an interview with the Science magazine (science mag.org) December 24, 2010 (330: p 1732 2010) Prof. Montagnier revealed that he will be the leader of a new research institute at the prestigious Jiaotong University in Shanghai, China.¹ The main focus will be to investigate "electromagnetic waves produced by DNA in water" or what has been called "water memory," as reported by French immunologist Jacques Benveniste in the journal Nature in 1988. This topic has been the subject of great controversy, especially in France, but the Chinese are open to, and apparently very keen to fund further research. Abnormal signals have been found coming from "bacterial DNA in the plasma of many patients" with a range of chronic diseases and cancer.

As I pondered this interesting new initiative, I opened the morning newspaper to read that an elite group of geophysicists (including NASA scientists) had just detected the release of anti-matter into extraterrestrial space from the upper surfaces of clouds during electrical storms.² (Yes, anti-matter: think Angles and Demons and the plot to blow up the Vatican.) Electrons move one way and positrons another: a phenomenon called pair production (particle-antiparticle pairs), which is a relativistic or quantum process.³

What could this possibly mean? I had visions of the thunderstorms on Earth millennia ago when many have proposed life emerged. I recalled the famous book by Edwin Schrodinger (Schrodinger's cat fame): What is Life? in which he discussed the physical basis of life systems at the level of elementary particles.⁴ A group of German researchers recently published a book with the same title, which updates these same concepts; that the capture, storage and use of energy and information are key.⁵ Electromagnetic communication is what brings and keeps everything together and running. Cooperation between cells or bacteria has been the basis for several recent studies including the direct exchange of electrons between bacteria.^6-8 Mae-Wan Ho in The Rainbow and the Worm: The Physics of Organisms explores the quantum nature of life processes.⁹ She answers the question of "What is life?". "Life is all the colors of a rainbow in a worm". Elisabeth Rieper and colleagues at the Center for Quantum Technologies in Singapore recently concluded that quantum entanglement plays a crucial role in explaining the stability and data storage of the DNA double helix.¹⁰

I was absolutely certain that I was uncertain what all this means!

But, it seems that understanding life at the sub-molecular and electromagnetic level is now possible. Uncertainty is the fundamental basis for a new research project. So, I wish Prof. Montagnier "fair winds and following seas" as he heads into new areas of water research. This could be a new French revolution of ideas. But will it be Viva la France or la Chine? I see a new iPad APP in my future: "The Electromagnetic techniques for myeloma diagnosis and treatment."

References

Enserink M. French Nobelist escapes 'intellectual terror' to pursue radical ideas in China. Science. 330:1732; 2010.
Maugh TH. What's in a thunderstorm? Antimatter for one. LA Times, January 11, 2011.
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Red Wine and the Hedgehog

2011-01-12T20:08:07Z

It is important to remember that new drugs are new. In May 2010 Glaxo (GSK) suspended a study with SRT501, Sirtris' formulation of Resveratrol, the minor ingredient in red wine linked to longevity and possible anti-myeloma activity. Now, in December 2010, Fierce Biotech posted that Sirtris (bought by Glaxo for $720 million in 2008) had abandoned SRT501 altogether because of lack of efficacy, and in the case of the myeloma trial, life threatening kidney toxicity. One criticism of the halted myeloma trial was that over ten times the active dose of resveratrol was used and most likely accounted for the kidney toxicity.

Resveratrol is a natural product found in grapes and present in red wine. This natural product is available over the counter, for example, in the Biotivia Transmax product (500mg capsules). The question is whether this natural compound, which extended the life of obese mice in Prof. David Sinclair's original studies, or whether patentable drugs activating just the SIRT I pathway should be the focus for research.^1-5 The new synthetic small molecules target the SIRT I pathway whereas the original resveratrol hits many targets which may account for its benefit. And what should the dose be?

Assessing anti-aging and possible anti-myeloma effects takes time and patience which is an increasingly rare commodity in the highly charged culture of drug development. The human body is a delicate machine. Giving more of a drug is not necessarily better: maybe there is an ideal lower dose given over time. This was recently illustrated with the impact of a baby aspirin in reducing the occurrence of heart disease and cancer after at least 5 years of use.^6-8

Another example is hedgehog inhibitors. ⁹ Matsui and colleagues¹⁰ showed that a critical pathway in the activation of the myeloma stem cell is the Hh (Hedgehog) pathway. Blocking this could prevent myeloma "reseeding" in the bone marrow after successful treatment, and possiblly lead to a cure. A chemical was immediately available capable of blocking the hedgehog gene and called cyclopamine named after the birth defect (of a single eye) in sheep grazing on wild corn lily containing the agent. Again the same story emerged: drug companies tried to replicate the effects of cyclopamine (which has some potentially dangerous side effects) with synthetic compounds. In this case, simply blocking this one pathway turned out to be not that effective in myeloma. But wait, at the recent ASH meeting in Florida another researcher, Dr. Guido Tricot, showed that blocking 2 pathways, Hh plus Wnt, showed remarkable benefit in the laboratory. Tricot tested a combination of cyclopamine plus itraconazole to block Hh and another compound CY10404 (cox-2 inhibitor similar to Celebrex®) to block the additional Wnt pathway. Perhaps persistence and patience can pay off in coming up with an effective strategy.

So new ideas are new. It takes time to figure out the best way forward. This is frustrating, but necessary. The very good news is that these are exciting new ideas and progress is being made. Stay Tuned.

References

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