Medicine, roots and sunshine

Earlier this week, I had the honor of attending the 127th annual meeting of the American Clinical and Climatological Association in Tucson, Arizona as a new member. This organization was founded by a group of leading physicians who were interested in advancing patient care with a particular focus on the impact of climate on health (hence the name of the organization). Much of their effort was geared towards tuberculosis which was a scourge of the times and was treated at the time by placing patients in sanatoria where they could be exposed to fresh air and sunshine.

The “Climatological” – as it is known for short – has survived and thrived through the years despite the incredible changes that have taken place in science, medicine and society. My impression is that the organization has survived precisely because it has stuck to its roots, which are grounded in an interest of its members in the intersection of science, medicine and society. As most medical societies have become more and more subspecialized and technically focused, the Climatological has resisted this trend, and has members who share an appreciation for the privilege and humanity that comes with being a leading academic physician.

The organization is of relatively small size and there is a sense of comradery among its members even though they represent a broad variety of medical specialties. All new members (including me) are required to give a talk. These new member talks, as well as keynote talks from established members, covered an incredible range of topics including the molecular and cellular basis of disease, new approaches to therapy, oak trees, the blues, gulf war syndrome, the politics of Ebola, how gender issues impact on promotion within academic medicine, and the history of “heliotherapy” (treatment with sunlight). The latter was particularly appropriate given that the meeting was held in Tucson. Each talk was short, and followed by a robust yet cordial and illuminating question and answer session.

While climatological approaches to disease such as heliotherapy are not as prominent as they were in late 1800s when the society was founded, I am confident the founders of the Climatological would be pleased that the spirit of their organization has remained unchanged. Sunshine, in the form of open discussion of new ideas, and roots based on a common interest of its members in the intersection of science, medicine and society, have sustained not only this organization but the medical profession in general, and I am honored to be part of the tradition.


Recently, I signed on to Facebook and found that my daughter had tagged me in a picture she took of me relaxing at home slouched on the couch holding a glass of wine. It was nothing scandalous, and I don’t mind that my daughter posted it.

On the other hand, it made me bit uncomfortable to think of that picture being available for the whole world to see. I therefore untagged myself. (For the sake of staying focused on the topic at hand, I am skipping the part about how difficult it was for me to figure out how to remove my name from that picture.) When it comes to Facebook, my daughter and I have different perspectives on privacy.

This is a tiny and trivial example of a major issue in today’s world. The incredible speed of advances in computer technology and enhancements in our ability to collect, store, share, and utilize data, have led to complex challenges for how access to that information should be controlled. The news is full of stories about hackers downloading very private photos of celebrities or personal financial information from corporate sites, as well as government surveillance that may be aimed at protecting the “homeland” but could also be used for other purposes. Many of the questions now being discussed at length, often categorized under the word “privacy,” were unimaginable just a few years ago. How to control and use such data requires us to consider how the information is protected and controlled, and how to balance a person’s privacy with how access to the data may be for the common good.

Cancer research is not immune from this debate. Research that is dependent on big data unquestionably contributes to progress in cancer research. Molecular analysis and clinical information from large numbers of cancer patients help us determine what approach is most likely to work for future patients.

At the same time, each patient has the right to control whether or not his or her private medical information can be used for research. The underlying principle that guides use of data for cancer research is that patients get to decide whether or not we can use their data. If a patient provides consent to have their information used for research, that patient should be comfortable that the information will be protected and only used for the purposes they have approved. Fortunately, the vast majority of patients (in our experience more than 98%) understand the importance of such research and provide us with consent that allows us to use their data for research.

Cancer research is moving so fast it is hard to know what type of research might be beneficial in the years ahead. Going back to all patients to get a separate consent every time we want to use their data to study something new and promising would be such an administrative burden on researchers that it would prevent ideas from moving forward. We therefore obtain consent from patients to use their data for both current and future research projects, with the understanding that the patient has the right to tell us to “untag” their data and remove it from the research database any time they choose. This is an important safeguard, but is used very rarely. Less than 0.2% of patients who provide consent to participate in the research subsequently request that we stop using their data for research.

This common sense approach to dealing with big data for cancer research allows us to use patient data for research, but only after we obtain consent from patients, promise to protect the information and offer patients the opportunity to change their mind if they decide that they don’t want us to use their samples for that research. We believe this provides an excellent balance between privacy and the common good.

Now, in order to be sure I practice what I preach… If someone can convince me there is societal value to having my name linked to the Facebook picture of me slouched on the couch with my wine glass, I would be happy to tell my daughter to put the tag back on the picture so all the world can benefit.

Just say yes…

I just watched a rerun of “the office.” On this show, as on TV and in the movies in general, administrators and supervisors are often portrayed as ignorant buffoons who have no idea what they are doing. True confession – there have been times when I have felt that way about those above me on the organizational ladder. I also understand why others might feel that way about me as a supervisor, particularly when they present me with a multidimensional problem that seems to have no good solution.

On the other hand, there are times as an administrator when the answer is clear immediately. My favorite example, and one that I am privileged to experience often in my current role, is when asked for something by someone who I know is very careful about what they ask for, and has a track record of success when given the support they request. This describes many of my colleagues at Holden Comprehensive Cancer Center. When I receive requests from such colleagues, I don’t ask myself “why should I say Yes” Instead, I ask myself “why would I say No.” On occasion, lack of resources has limited my ability to give a positive response. However, that is the exception and not the rule. Almost without exception, when I say “yes” to such requests, I have not been disappointed.

This is something I have learned over time. Early in my career, there were times when I would scramble to grab all the resources I could get. Now, I am more careful about what I ask for, and to make excellent use of the resources provided to me. The result – when I really need something from my supervisors, the answer to my requests is more often “yes”.

So, when the focus is long-term success, try and only ask for what you need, and be sure you use the resources provided to you effectively. By doing so on a regular basis, the next time you ask for something you need, I would hope your supervisor will be much more likely to “just say yes”

However, be careful if you work in the Cancer Center, have been a good citizen, and interpret this blog as meaning that I will be a softie when it comes to your next request. I might reply as Dunder Mifflin’s Michael Scott from the Office. His response to a request in the rerun I just watched… “Fool me once, strike one, but fool me twice, strike three.”

Hang together

During the signing of the Declaration of Independence, Benjamin Franklin highlighted the importance of the colonies working together by saying “We must all hang together, or assuredly we shall all hang separately.” This quote came to mind this past week when I was in Washington, D.C., for the Rally for Medical Research.

For many years, biomedical research groups each advocated for their own specific interests. Heart advocates highlighted the importance of heart disease and those touched by diabetes spoke about why research into diabetes was so important. In cancer research, the focus became even more granular, with separate groups advocating for more research funding for specific types of cancer. In addition, physicians, researchers, and patient activists often advocated separately.

Each of these efforts was important and well-meaning, but resulted in confusion. Our legislators, who make the decisions concerning federal research funding, don’t have the background to decide which research areas are more important. Those who understood the importance of biomedical research would not know which way to turn, and so would often focus their attention on the diseases that personally had effected their family and friends. The result was what could be called “disease wars” with advocates with an interest in one disease arguing why their disease was more worthy of support than another disease. The importance of increasing overall funding for biomedical research was largely lost in the noise.

What was also lacking in the discussion was the clear evidence that research in one disease often has a major impact on another. There are hundreds of examples. To mention just a couple: Research in bone marrow transplant for leukemia that focused on bone marrow stem cells has led to unexpected advances exploring the potential use of stem cells to regrow heart blood vessels in patients with coronary artery disease. Research into HIV/AIDS was instrumental in enhancing our understanding of the immune system, which has led to major advances in cancer immunotherapy that are now benefiting cancer patients.

Step by step, we have learned the lesson that Mr. Franklin tried to teach us. Last week, advocates for research in cancer, diabetes, heart disease, and many other diseases, including physicians, researchers and patients, joined forces and were successful in hanging together to highlight the importance of biomedical research. Working together provided a great opportunity to emphasize to our lawmakers the importance of biomedical research in both reducing pain and suffering and boosting our economy.

To learn more about this joint effort, go to and join us as we all “hang together” in support of biomedical research.

Twitter away – cancer progress

On September 16, the American Association for Cancer Research (AACR) will release its 2014 Cancer Progress Report. Once it is released, a copy of the report can be found on line at   I had the privilege of again serving on the AACR Progress Report Steering Committee this year. It was exciting to summarize our progress. Highlights described in the report include the increasing number of people living with, through and beyond cancer; the approval by the FDA of 6 new cancer treatments based on proof they are effective; and advances in cancer prevention and screening. I will be joining a number of my colleagues in Washington, DC, on September 17 and 18 to highlight the report and advocate for biomedical research. In addition, I will be participating in a Twitter chat at 12 p.m. Central time on September 16 to discuss the report. You can follow along using the hashtags #CancerProgress14 and #abcDrBchat or by following our Twitter account, @UIowaCancer. Please join us as we twitter away – cancer progress.

Unfortunately, “twitter away – cancer progress” also has a negative connotation. At a time of such amazing potential, funding for cancer research is dwindling. Yes, we made progress over the past year, but that progress could have been so much greater if we had the resources to pursue more cancer research projects. Indeed, just this morning I wrote a letter of support for a research project submitted by an outstanding research team at Holden proposing a novel approach to treatment of pancreatic cancer. Their grant to the National Institutes of Health (NIH) and National Cancer Institute (NCI) was viewed by a peer-review team of cancer researcher experts as being outstanding – in the top 15 percent of all grants reviewed. Yet odds are it will not be funded because of the limited funding available through the NIH and NCI. Across the country, outstanding research projects with great potential are going unfunded. Perhaps most concerning, young researchers with outstanding promise who would love to work on cancer research are deciding to invest their careers elsewhere because they are unable to get support for their research projects, or see their mentors struggling to keep research projects going.

We need your help to assure next year’s cancer research progress report reaches its potential and outlines advances that are even more impressive than those in this year’s report. Please join us on September 16 as we tweet about cancer progress, and state your support for cancer research. That will help assure we don’t let a lack of funding today literally twitter away cancer progress in the years ahead.

Leveraging Differences

I was at a cancer research meeting out of town recently, and three men walked into the hotel conference room just before our session was about to start. They picked up donuts and coffee at the back of the room before heading toward some open seats. However, they seemed ill at ease as soon as they looked around the room. Very quickly, they turned around and left (but in their hurry to get out of the room, kept the donuts).

On my way up to my hotel room that evening, I was joined in the elevator by a group of men who were wearing name tags that indicated they were attending a trial lawyers’ convention taking place in the same hotel. At that point, I realized what had happened that morning. The three men must have been looking for the trial lawyers’ conference. After mistakenly walking into our meeting, they realized immediately that those around the room had limited fashion sense, with many, including me, being tie-less and wearing inexpensive blue blazers. This was a clear sign something was amiss, given that the standard attire for the trial lawyers centered more around impeccably tailored suits.

Both meetings continued the next day. Once I knew the signs, I was able to distinguish the trial lawyers from the cancer researchers from across the lobby.

At this point, I must ask forgiveness from my lawyer friends as I compare cancer cells to the trial lawyers who walked into our room.

Cancer cells are similar to normal cells in many ways. Most of the molecules and subcellular parts in cancer cells and normal cells are the same. However, cancer cells often go where they don’t belong, and are nourished by resources that are not intended for them. It can be hard to distinguish the cancer cells from normal cells – unless you know the differences.

We have made great progress over the past two decades in figuring out the differences between cancer cells and normal cells, and can increasingly guide the immune system to recognize these differences (molecules in cells – attire in my story). The next step is to figure out how to use this information to get rid of the cancer cells. The trial lawyers left our meeting as soon as they realized they were in the wrong room. Unfortunately, the same is not true of cancer cells – they do not leave voluntarily

At this time, I would like to point out to my lawyer friends that this is only a metaphor, and I am not really in favor of getting rid of trial lawyers.

Eliminating cancer cells, even if we know how they are different, is a very difficult problem. A key aspect of the immune system that is very finely tuned is its “off” switch. We don’t want our immune system to be fighting our own normal cells. Even if the immune system starts to reject the cancer, the immune response often gets turned off when the system perceives that maybe the cancer “belongs” and should not be removed. To the immune system, maybe that is a cancer researcher in an impeccably tailored suit who is actually in the right room.

This is where very exciting recent research advances become important. We have figured out the nature of the immune system “off” switch (two molecules in this category are called CTLA-4 and PD-1) and now have treatments in the form of monoclonal antibodies that prevent these molecules from turning off the immune system. The result is that a robust anti-cancer immune response can be maintained, in some cases long enough to give the immune system time to reject the cancer. Indeed, a new drug that enhances the ability of the immune system to reject cancer cells was approved by the FDA just last week.

We still have a lot to learn about the best way to use this new class of immune system drugs (together called “checkpoint blockade”) to treat patients. Nevertheless, this is a true breakthrough in our ability to not only distinguish cells who belong from those that do not belong, but to actually maintain the immune response long enough to leverage those differences so they result in elimination of the cancer cells.

One final disclaimer – I really do hope my lawyer friends forgive me for one concluding lawyer joke.

Take that cancer. And you suit-wearing, donut-eating trial lawyers …

Valued and different

My three offspring have each chosen their own path in life.

Aaron, my older son, is a stage actor. Miriam, my daughter, is in her last year of medical school here at the University of Iowa. Nathan, my younger son, is a wild land fire fighter working on a helicopter fire attack crew in Idaho.***

My wife and I continue to do our best to support each of our children as they find their own path. This includes providing guidance and support for the day-to-day challenges and decisions they face, as well as helping them think about the long-term and how they can best reach the goals they have set for themselves.

It is not always easy to determine whether we should focus on today’s needs or tomorrow’s goals, but we do our best to strike a balance between focusing on the present and planning for the future. Our support has been different for each based on their specific needs. At any one point in time, our support and effort has focused more on one or another, not because one is favored over the others, but because that is where we think we can be most helpful. No one is more valued than the others, they are just different.

In some ways, the Cancer Center also has three offspring –our missions that focus on clinical care, research, and cancer prevention. Each is vital if we are to reduce the burden of cancer, yet each is different.

Providing state-of-the-art clinical cancer care is of obvious importance, and we are always striving to enhance the quality of that care. Supporting cancer research is also vital as we work to discover improved approaches to reducing the burden of cancer in the future. Finally, there are our cancer prevention efforts, such as those supported through the Iowa Cancer Consortium. Preventing cancer in the first place is the best way to reduce pain and suffering from cancer.

Just like society needs actors, doctors and fire fighters, reducing the burden of cancer requires cancer care, cancer research, and cancer prevention.

With respect to the Cancer Center, I will repeat the paragraph from above …

It is not always easy to determine whether we should focus on today’s needs or tomorrow’s goals, but we do our best to strike a balance between focusing on the present and planning for the future. Our support has been different for each based on their specific needs. At any one point in time, our support and effort has focused more on one or another, not because one is favored over the others, but because that is where we think we can be most helpful. No one is more valued than the others, they are just different.

***As a father, I am taking the liberty of throwing in shameless plugs:

  • Aaron’s next role is as “Brick” in “Cat on a Hot Tin Roof” with the Iowa City Community Theater – check it out
  • Miriam will soon be looking for a top notch Ob/Gyn residency in case you have any suggestions
  • To keep Nathan out of harms way, please, please, be careful with fire if you live out west

If we can put a man on the moon…

In September 1962, President John F. Kennedy said, “We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard.” In December 1971, Richard Nixon said we are “totally committed to provide the funds that are necessary, whatever is necessary, for the conquest of cancer.”

To state the obvious, we have succeeded in going to the moon, but not in conquering cancer. Indeed, just about everyone involved in cancer care or cancer research has been asked the following question, “If we can put a man on the moon, why can’t we cure cancer?”

We have learned a lot since the 1970s about the difference between these two challenges. It turns out that cancer research is not rocket science – it’s much more complicated than that.

Going to the moon – There is only one moon, and by studying it, we know how big it is, where it is, and can predict precisely where it will be at any time in the future.

Curing cancer – Every patient is different and every cancer is different. Each behaves in a unique manner. Cancer is not predictable.


Going to the moon – The principles of physics apply, which are consistent and measurable.

Curing cancer – The principles of biology apply, which involve great complexity and are very difficult to describe accurately in mathematical terms.


Going to the moon – We made amazing progress in a short period of time.

Curing cancer – Progress has been slower than predicted because cancer is much more complex than we ever imagined.


Going to the moon – Each space flight provided the public with clear evidence of progress towards the stated goal on the new and exciting media of the day (live TV). The public remained engaged.

Curing cancer – Progress is complicated to explain to the public and cannot be effectively illustrated in a video clip or explained in a short sound bite. Many in the public do not recognize we are making progress.


Going to the moon – We landed men on the moon 7 times and declared victory.

Curing cancer – Even millions of successes are not enough.

However, there are some similarities between going to the moon and conquering cancer.

For both, there is a direct link between societal commitment and progress.

For both, we are in a race. The space race was with the Russians. With cancer, we are racing against time for ourselves, our children, and our grandchildren.

In looking forward at how we can reduce the burden of cancer, I will paraphrase both Kennedy and Nixon. We need to do research and apply those research advances to the prevention, early detection, and treatment of cancer not because it is easy, but because it is hard, and we need to revitalize our commitment to providing the funds that are necessary, whatever is necessary, for the conquest of cancer.

Only that way will we be able to say at some point in the years ahead that, through commitment and persistence, “we put a man on the moon and, although it took a bit longer, we conquered cancer as well.”

Not as smart as I think I am.

Many years ago, while I was doing my research training, I was told by a nationally admired, very senior cancer researcher that cancer therapy with monoclonal antibodies was a “failed hypothesis” and that I would throw my career away if I insisted on working in that field.

Thinking back, this was some of the most helpful advice I ever received – not because I followed his advice (indeed, I did not), but because his advice taught me that even the smartest , most experienced, greatly admired role model can be wrong. It taught me to recognize I will not be as smart as I think I am.

On multiple occasions over the subsequent 25 years, I have listened to colleagues and trainees express a desire to press on despite initial negative results. I have been tempted to say “nice idea, but don’t waste your time since the results so far demonstrate the idea is a failed hypothesis.” However my early experience taught me to be very cautious about such a knee jerk response.

Here are some examples…

When it was first suggested to combine antibody therapy with chemotherapy, I thought it was a crazy idea. We need the immune system to help antibodies work and chemotherapy is known to suppress the immune system. Nevertheless, I agreed to move ahead with such studies. , .   Iowa was part of the first studies to look at this approach which we now know can work well in many cancers and are now part of standard therapy.

Many research groups, including my own, have been intrigued by the potential of retargeting killer T lymphocytes, a white blood cell, to kill cancer cells. Initial clinical studies exploring this approach were negative. Now, after 20 years of research, studies based on this concept are finally showing promise including use of bifunctional antibodies and of T cells genetically modified to attack the cancer cells (so-called Chimeric Antigen Receptors or CARs).

Finally, wouldn’t it be fantastic if we could design a virus that would attack cancer cells but not normal cells? As with the other examples outlined above, initial trials exploring such “oncolytic viruses” were discouraging. On the other hand, these studies taught us much about the biology of both cancer and viruses. Investigators persisted, and there is now growing evidence that such treatment may be effective.

Persistence can pay off. Research hypotheses can also fail and not be worth pursuing. How do we know if a failure represents a temporary detour or a true dead end? First, we look at the science on which the proposed approach to treatment is based. Sometimes, the science lags behind the ability to conceive of a practical application, and the science needs to advance before a concept can be applied effectively to cancer treatment. We also look carefully at the results of the unsuccessful clinical studies . While the primary therapeutic end point of such clinical trials may not have been met, there are often hints in the correlative science that speak to how the treatment can be modified and improved. Following these hints can help move the treatment forward.

So, when a young researcher tells me she has decided not to pursue an intriguing idea because a senior advisor said it has been studied already and has already proven to be a failed hypothesis, I advise her to think again. On the other hand, maybe she should not listen to me either, since I know I am not as smart as I think I am.

Climate change in clinical research – mastering buckets and umbrellas

This spring, we once again had heavy rains in Iowa with rivers and reservoirs approaching capacity, umbrellas in our hands and buckets on the floor to catch water from leaky roofs. The climate certainly seems to be changing, and there is new urgency in developing a master plan to respond to this new reality. Fortunately, this year’s flooding caused less damage than in prior years in part because communities and organizations have started to work together to manage the increased water flow.

The climate for cancer research is also changing dramatically, and this is having a major impact on how we conduct clinical cancer research. We now know that cancers are driven by genetic changes, and cancers that look the same under the microscope can have very different genetic drivers. There is growing evidence that patients benefit from treatments that are tailored to each patient based on the genetic makeup of their cancer. This major leap forward in our understanding of the biology of cancer is taking place at a time when financial support for cancer research is shrinking. Researchers are overflowing with ideas and desperately want to move their research discoveries downstream to where they can help more patients. This requires doing clinical cancer research in new ways, and is where umbrellas and buckets come in.

In an “umbrella trial,” patients with a given type of cancer are assigned a specific treatment arm based on the molecular makeup of their cancer. Umbrella trials have many different arms under the umbrella of a single trial. Patients are assigned to an arm on the trial based on the molecular makeup of their cancer. Umbrella trials allow us to test a variety of targeted drugs at the same time in the patients who are most likely to benefit, i.e. those with cancers that have the specific molecular abnormality targeted by the drug. However, such studies are not easy – their modular structure is quite complex and can lead to various arms being moved in and out of the study as new drugs become available and results from testing of other drugs become clear.

In a “bucket trial” (also called a basket trial), cancers of different types are tested to see if they have a particular molecular abnormality. If they do, the patients with that abnormality are eligible to be treated with a new drug that targets that particular abnormality. The advantage of this approach is that it allows us to test new treatments across cancer types. On the other hand, we often have to test many patients to find the handful that have the abnormality targeted by the new treatment. This is inefficient for the research team that needs to explain the trial, get informed consent, and do the molecular testing on “a bucketful” of patients to find just a few who are eligible for the study. It can be incredibly frustrating for a patient who agrees to be tested, only to be told she is not eligible to be treated on the study because her cancer does not have the appropriate target.

Putting aspects of umbrella trials (exploring different treatments based on the molecular makeup of the cancer) and bucket trials (looking across different cancer types for response to a given targeted therapy) together can result in a “master protocol” such as the NCI MATCH trial that I discussed in a previous blog. In a master protocol, patients with a variety of cancers undergo molecular testing and are assigned a treatment arm based on the makeup of their tumor. Given the hundreds of possible genetic abnormalities that we now know can drive cancers, a truly comprehensive master protocol would have a very large number of arms and would be changing constantly. Each arm would only cover a small fraction of all the patients, yet a large fraction of patients would be eligible for at least one arm. Such a protocol would require unprecedented cooperation by cancer centers across the country if it is to be successful, yet would also accelerate progress.

Our current system for providing administrative and regulatory oversight of clinical trials was designed before umbrellas, buckets and master protocols were being considered. It was designed when most clinical trials involved testing a given treatment in a given cancer type at a single institution. Every clinical trial available at a given institution was only made available to patients after it was reviewed by an institutional committee responsible for assuring the trial was scientifically strong and another committee that assured protection of patient rights.

With the new trial designs, even the largest cancer centers will likely enroll only 1 or 2 patients onto many arms of a study. Putting each arm of each study through the scientific and ethics committees of each institution separately, as we have done for decades, would require a huge and duplicative administrative effort that, in this era of shrinking resources, would prevent such studies from being successful. What is needed is a new approach to administration, oversight and regulation of clinical cancer trials that is more efficient yet still assures safety and protection of patient rights. This requires reassessing the value of long standing policies, and working together more effectively, not only in conducting clinical cancer trials, but also in administering and overseeing them.

It is not an easy transition, but the cancer research community has started working within our own institutions, with each other, with the NCI and with other regulatory agencies to adjust to the new climate and enhance the efficiency of performing molecularly targeted, collaborative, modular clinical cancer trials such as umbrella trials, bucket trials and master protocols. Included in this effort is development of systems that allow for strong central review and oversight of clinical trials so the effort does not need to be duplicated independently at multiple individual institutions.

The climate is indeed changing, and we need to stay ahead of these changes if we are to guide the flood of new discoveries into improved care for our patients.