After spending last week focusing on cancer awareness among minorities, I

read the archives at http://cancer-carnival.blogspot.com

decided to submit one of those articles to the Cancer Research Blog Carnival. It was accepted. (Yeeesssss!)  It’s been five quiet months of blogging and now I just might be starting to make a friend or two out there. Each month Cancer Research presents what’s new and now from cancer biology, cancer genetics, cancer therapeutics to cancer diagnostics and patient care. Head on over to Highlight HEALTH and check out the 21st edition of this blog carnival which is the standard for all things cancer. Be sure to read all the articles, the Health Advocate is in such excellent company.

“[T]here are those who say we cannot afford to invest in science, that support for research is somehow a luxury at moments defined by necessities.  I fundamentally disagree.  Science is more essential for our prosperity, our security, our health, our environment, and our quality of life than it has ever been before.”  These were the words of the President in a speech delivered at the National Academy of Sciences earlier this week.  He went on to set a goal for the US to increase investment in scientific research and development to 3% of the gross domestic product.  Previously, I have discussed this administration’s commitment to science and science education.  I’d like to include a presentation I made a few years ago on the crisis in science, technology, engineering and mathematics (STEM) education and the importance of a robust science sector to a strong economy.

human metastatic breast cancer cells (from abcam.com)

Two recently published cancer studies reveal differences in the severity of cancer (specifically breast and colorectal) between black Americans and other racial or ethnic populations are based in genetic variations.  I think we should pause a moment and recognize that today is National Day, an observance popular in K-12 education to recognize the day that the research scientists at NIH completed sequencing of the human genome.  The knowledge gained from that tremendous endeavor has informed the physicians and scientists is countless labs since and the current findings in the disparities between the burden of illness suffered by blacks with breast or colorectal cancer tumors is no different.

Dr. Carol Rosenberg and her colleges at Boston University School of Medicine have discovered that cancer tumors lacking genetic expression for estrogen receptors, progesterone receptors and HER-2 (human epidermal growth factor), so called “triple-negative” tumors were more common among black women.  Specifically, their study of 415 women (36% non-Hispanic white, 43% black, 10% Hispanic, and 10% other) revealed that black women have a three times greater risk of having triple-negative breast cancer tumors as compared to non-Hispanic whites.  Triple-negative phenotype tumors (which make up 15% of all invasive breast cancers) have been associated with poor prognosis and low 5-year survival rates.  The implications are significant to understanding the prevalence of an increased burden of illness and death suffered by black women developing breast cancer.

“The reasons explaining this finding are not certain, but it is possible that black women may be at intrinsically greater risk of these more aggressive tumors,” observed Dr. Rosenberg.

The proportion of black women suffering from triple-negative breast cancer tumors was the same when comparing women under or exactly fifty years of age to those over fifty, as well as women who were obese to those who we not obese.  The findings of this study were release late last month in the Journal of Breast Cancer Research.

Earlier this month, Upender Manne, PhD and his colleges at University of Alabama at Birmingham released the results of their investigation of colorectal cancer in Clinical Cancer Research.  Scientists have thoroughly documented he p53 gene and its association with colon cancer in the literature.  In the current study, statistically significant differences in colorectal cancer tumors where identified and described.  Dr. Manne and his team reviewed 373 patients (63% non-Hispanic white and 37% black surgically treated between 1985 and 1995 at the anatomical, cellular and genetic level.  The codon 72 of the p53 protein can contain the amino acid (a protein building block) proline (Pro) or arginine (Arg).  As a result, there are three different phenotypes of p53 protein Arg/Arg, Arg/Pro or Pro/Pro.  In previous studies, researchers have found the Arg/Arg phenotype of the p53 protein to have a higher potential for inducing apoptosis (or programmed death of cancer cells).  On the other hand, the Pro/Pro phenotype of the protein has been found to accompany a greater proliferation of cancer cells.  In general, mutations that disrupted or inactivated the p53 protein have been associated with progression of the cancer.

The racial difference in the prevalence of these phenotypes of p53 protein associated with the colon cancer tumors was statistically significant.  Nineteen (19%) percent of colorectal cancer tumors in blacks had the Arg/Arg phenotype protein compared to 36% of the tumors in whites; 64% of tumors in blacks had the Arg/Pro phenotype protein compared to 57% of the tumors in whites; and 17% of tumors in black had the Pro/Pro phenotype protein compared to 7% of whites.  The implication of the numbers is this:

blacks had a higher prevalence of the p53 protein phenotype (Pro/Pro) which is associated with more aggressive tumors and progression of the cancer.

Specifically, this Pro/Pro phenotype was 2.5 times more likely to be associated with death in black patients than those with the other phenotypes.  In stark contrast, these Pro/Pro phenotye p53 proteins were only 1.6 times more likely to be associated with death in white patients than those with the other phenotypes.  As Dr. Manne stated,

“African-Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality…and risk of death due to [colorectal cancer].”

This particular study, also identified additional, statistically significant

April 2009 issue

differences between tumors in blacks and non-Hispanic whites that create future opportunities to examine and disaggregate what Manne referred to as the “confounding from other lifestyle factors of the aggressiveness of the disease.”

Medscape Oncology contacted an independent physician, Dr. Hemant Roy of the Feinberg School of Medicine at Northwestern University to comment on the clinical significance of colorectal cancer study.  “Risk assessment is complex, and this and other genetic polymorphisms are an important piece of the puzzle…While this observation may not necessarily represent a stand-alone future test, it takes us closer to understanding risk and hence targeting screening.”  I think this observation speaks to the value of the molecular and genetic characterizations that come from health disparities research such as the two studies I discussed here, they decipher a piece of the entire puzzle that determine risk factors and help health care providers target and personalize the screening process.

Sources:

Stead LA, Lash TL, Sobieraj JE, Chi DD, Westrup JL, Charlot M, Blanchard RA, Lee JC, King TC, Rosenberg CL. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 2009 Mar 25;11(2):R18.

Beals JK. New Polymorphisms Affect Colorectal Cancer Risk, Progression in
Blacks.  In Medscape Medical News.  Cited April 24, 2009.  Available at <http://www.medscape.com/viewarticle/590604>

Katkoori VR, Jia X, Shanmugam C, Wan W, Meleth S, Bumpers H, Grizzle WE, Manne U.  Prognostic significance of p53 codon 72 polymorphism differs with race in colorectal adenocarcinoma. Clin Cancer Res. 2009 Apr 1;15(7):2406-16.

ARRA and You (Part IVb): Challenge Grant Research Priorities. Currently, science administrators at NIH are allocating grant funds favoring proposals that have a high impact in biomedical or behavioral science and/or public health. Invariably, the 15 areas of priority that NIH has identified will influence the heath sector for years, so I present and discuss them around the nature of this influence.

1. I’ll address Behavior, Behavioral Change and Prevention research first, not only because it doesn’t fit neatly into the categories
   

   pdf available at www.jgi.doe.gov/education/posters.html

   that follow, but also because prevention is the beginning of health care. The question: Which has the greatest impact on health and disease? Nature or nurture? Inspires an argument that may be as old as time, itself. (Okay, I exaggerate, but only a little). As scientist have forged ahead making great strides in their understanding of nature through the sequencing of the entire human genome and the burgeoning discipline of genomics which has sprung forth as a result. They continue to struggle to elucidate the factors that influence behavior. Since the main diseases that plague us today (think heart disease, diabetes and cancer) are exacerbated by our behavior, this path of inquiry is truly worthy. The aim of this research is to better understand the factors that influence behavior, as well as the methods that have the most robust impact, changing behaviors to those that promote health and prevent disease. To date, prevention is still the most efficient and cost-effective option for alleviating the burden of suffering and disability brought on by disease.

Prevention through biomedical interventions has progressed well through this first decade of the new century. In fact, the next six research disciplines operate in concert. I believe the application of these cutting-edge 21st century technologies will transform the way we diagnose and treat disease bringing them to a personal and molecular level.

1. Let’s turn our attention to those highly debated Stem Cells. They
   

   Colour-enhanced scanning electron micrograph by Annie Cavanagh and Dave McCarthy. Winner of 2006 Biomedical Image Award (Wellcome Trust Medical Photographic Library)

   are simple, undifferentiated cells in the embryo or adult that have the potential to become any specialized cell in a living organism under the chemical influence of specific compounds and hormones. The aim of this research is to better understand the abnormal structure or function that causes disease. Cells with normal structure and function can be generated to replace diseased cells, through the process of culturing or growing them in the laboratory.

2. The area of Genomics aims to examine the entire DNA sequence (the instruction book, if you will, of all life processes) from the number of genes in a living organism to the function of specific genes. The goal is to see how they interact with one another and influence the biological processes of the body as a whole. Ultimately, genomics examines this genetic information to determine biological markers predisposing an individual to disease.
3. The aim of Biomarker Discovery and Validation research is to identify biomarkers (measurable biological molecules found in body fluids such as blood, or tissues that serve as a sign of a normal or abnormal biological processes). The presence or absence of a biomarker indicates a specific disease or response to a treatment for a disease.
4. The scientists at the McGowan Institute of Regenerative Medicine eloquently define regenerative medicine as “a new way of treating injuries and diseases that uses specially-grown tissues and cells (including stem cells), laboratory-made compounds, and artificial organs.” The aim of research in regenerative medicine is to examine these “approaches for ways to amplify the natural healing process in the places it’s needed most, or take over the function of a permanently damaged organ.”
5. The aim of research involving Smart Biomaterials and Theranostics (a term which combines the medical activities of diagnosis and therapy) is to elucidate the process of diagnostic therapy for individual patients. It involves testing them for possible reactions to a new medication and tailoring the treatment for the patient based on those test results. According to Daniel G. Anderson, a research scientist from MIT “such smart biomaterials are revolutionizing the design of medical devices and drug delivery systems. Gone are the days when medical devices had to be manufactured from off-the-shelf materials.”
6. Enabling Technologies are new technologies such as rapid point-of-care genotyping, computational and statistical methods for DNA sequencing and epigenetic molecules, that enhance the capabilities and performance of biomedical research.  The aim of this research is to use these technologies to improve diagnosis and treatment of disease.

These next five disciplines of research operate to improve the biomedical and clinical research enterprise overall.  Specifically, information technology and these older research methodologies will combine to increase health care system efficiency.

1. Research of Information Technology for Processing Health Care Data aims to make patient health care data readily available to providers in the health care setting enabling them to provide safe and appropriate medical care.
2. Translational Science aims to optimize the process that moves biomedical research findings discovered in the lab to a clinical setting where they are used safely and ethically to further translate those research results into a practical application for patients and communities that need them.
3. The aim of Clinical Research is to determine the safety and effectiveness of medications, medical devices and medical diagnostic interventions.  It generally relates to the entire research life of a chemical compound or device from its initial development in basic research through its final testing in the four phases of human clinical trials.
4. By Enhancing Clinical Trials (which are a part of the broader Clinical Research discipline), the aim is to use pre-defined protocols to measure the results of medical interventions in assigned patient groups or to measure the results observed in defined patient groups.
5. Comparative Effectiveness Research as defined in a Congressional Budget Office study aims to ensure that interventions used in a clinical setting are indeed the most effective for patients.  This involves research comparing the effectiveness of various treatments for any given condition.
6. The aim of Science, Technology, Engineering and Mathematics (STEM) Education research is to develop and identify the most effective methods for teaching these subjects.  Innovative and effective methods of teaching STEM subjects are essential to sustain the biomedical research and health care delivery enterprises.  We must continue to inspire new generations to pursue careers in science and medicine, as well as foster a community that has sufficient science and health literacy to create policies that foster the biomedical research and the health care sectors.

Finally, research in the areas of health disparities and bioethics will work to increase the integrity of the health care system for all users.

1. Health Disparities as defined by the Health Resources and Services Administration (HRSA) refers to the “population-specific differences in the presence of disease, health outcomes, or access to health care.”  The aim of research in the area of health disparities among ethnic
   

   The Basics of Stem Cell Research (from NIH)

   minorities and medically under served populations is to elucidate and then alleviate the causes of increased burned of disease and poorer health outcomes for specific disease conditions, as well as bring greater parity for access to care among all populations.  This research ensures that the gains made in the aforementioned research disciplines such as biomarker discovery, genomics, theranostics and regenerative medicine truly benefit the entire population.

2. The aim of Bioethics research is to protect patients’ rights throughout the biomedical research and health care delivery enterprises. The verve of technology must always be tempered by sound ethics to guard against the unforeseen consequences of the new (as are many of the research areas previously described).  Framed around four principles that promote patient well-being (beneficence), protect them from harm (non-maleficence), respect their right to accept or deny treatment (autonomy) and generally promote the pursuit of what is right (justice), bioethics provides safeguards in medical research and medical practice.

These are the fifteen research areas upon which the nation’s premier clinicians and biomedical research scientists will focus their investigations.  As a result, passage of the Recovery Act has not only managed to rehabilitate the proximate future but most certainly transform our distant future, as well.  I believe there will be gains in health and medicine that heretofore could have only been imagined.  What do you think?  Are there research focus areas that excite you? Perhaps, you know someone suffering from a disease that will benefit from these areas of research.  Or are you a pessimist awaiting the apocalyptic signs of a Brave New World, concerned that we made the wrong decision by restoring funding to embryonic stem cell research?  Either way, leave me a comment voicing your hopes or concerns.

Sources:

What is Regenerative Medicine. In McGowan Institute for Regenerative Medicine. Cited April 10, 2009.  Available at <http://www.upmc.com/Services/MIRM/RegenerativeMedicine/Pages/default.aspx>

Anerson, D.G. Burdick, J.A. and Langer, R.  (2004).  Materials Science. Smart Biomaterials. Science. September 24;305(5692):1923-4.

Re-engineering the Clinical Research Enterprise: Translational Research.  In NIH Roadmap for Medical Research.  Cited April 10, 2009.  Available at <http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp>

Skeen, J. (Ed.). (2007, December). Research on the Comparative Effectiveness of Medical Treatments:  Isuues and Options for an Expanded Federal Role [Electronic Version]. Available from the Congressional Budget Office, Ford House Office Building, 4th Floor Second and D Streets, SW Washington, DC 20515.

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by John Deering, originally uploaded by the Health Advocate.

This is another featured satire where I don’t necessarily agree with the politics but the image certainly made me laugh (out loud). You can find my opinion regarding a Brave New World in Friday’s post. Once you’ve read that let me know what you think. Will the biomedical science and technology of today bring us a bright future or a dark, brave new world?

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ARRA and You (Part IVa): Challenge Grant Research Priorities. The impact of the American Recovery and Reinvestment Act of 2009 on the health sector is so broad ultimately, it will touch all our lives. From COBRA insurance premium assistance and funding to the states for Medicaid and SCHIP to improved funding for research in the health and biomedical sectors, there appears to be no area left unaffected by the comprehensive legislation. As part of the Recovery Act, NIH has designated no less than $200 million, in the upcoming fiscal year, to fund research in areas that “address specific scientific and health research challenges in biomedical and behavioral research.” Science administrators hope to take advantage of opportunities to fill gaps in knowledge, develop new technologies, refine research methods and generate data. These areas of priority to which challenge grant funds will be awarded will influence this sector for years to come in the following three ways.

1. Application of cutting-edge 21st century technologies will transform the way we diagnose and treat disease to a more personal and molecular level.
2. Information technology and older research methodologies will combine to increase health care system efficiency.
3. Research in the areas of bioethics and health disparities will work to increase the integrity of the health care system.

In what ways do you think ARRA funding will impact biomedical research and the health care system on the whole?  Keep an eye out for the next post, in which I’ll discuss each priority research area further.

Source:

NIH Challenge Grants in Health and Science Research. In Office of Extramural Research. Cited on April 6, 2009.  Available at <http://grants.nih.gov/grants/funding/challenge_award/>

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Featured Health Observance.  April is Cancer Control Month. Since 1938, this annual proclamation has given Americans an opportunity to focus on advances against cancer, as well as, rededicate themselves to fighting the disease both through research and prevention.  President Obama observed:

“As researchers work daily to better understand this disease, Americans can take steps to decrease their risk of developing cancer. Individuals of all ages should seek regular and appropriate check-ups. These check-ups should include [Common Screening Tests], such as mammograms, the Pap test, and tests for colorectal cancer, all of which can help detect cancer during its early stages.  Healthy personal habits can also reduce the risk of cancer. Smoking accounts for thousands of cancer deaths every year, and quitting — even after many years — can greatly reduce the risk of cancer. Physical inactivity and obesity may cause a substantial proportion of colon, breast, endometrial, kidney, and esophageal cancers in the United States, so maintaining physical activity and a healthy diet can help prevent cancer, among other diseases. Finally, moderating alcohol intake and sun exposure can help protect Americans.”

In keeping with the broader concept of primary prevention and leading lives filled with health promoting activities, enBloom will also feature the following health observances this month so keep an eye out for ways to take part and educate yourself around these issues.

• April  1-30.  National Donate Life Month (This month’s first Friday feature is a continuation of the February discussion of National Donor Day and March discussion of World Kidney Day.)
• April 16.  National Healthcare Decision Day
• April 19-25.  National Minority Cancer Awareness Week

Source: National Cancer Control Month, 2009. In The White House Blog. Available at<http://www.whitehouse.gov/the_press_office/Presidential-Proclamation-Marking-National-Cancer-Control-Month/>

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by Gary Markstein, originally uploaded by the Health Advocate.

Here’s your latest dose of laughs. While this piece by Markstein made me laugh, I really don’t agree with the politics behind it. Those of you who read Monday’s post will understand since that post was a response to this cartoon. After you’ve enjoyed this piece of satire and read my response to it, be sure to drop me a comment telling me just what you think about ARRA provisions for research funding and the like.

Science is a wonderful thing if one does not have to earn one’s living at it.  ~Albert Einstein

ARRA and You (Part III):  Employment, Economic Recovery and the Research Sector. As I continue to discuss the broad impact of the American Recovery and Reinvestment Act of 2009, I must take issue with Einstein’s observation quoted above.  In fact, there are critics of the ARRA who make light of the idea that one part of the American economy that the Act is stimulating is the science and research sector.  Denying the significant contribution of this sector to the economy is simply a refusal to face facts.  This is an observation I also made in an previous post.  There is serious labor economics at work here.   The National Science Foundation’s (NSF) biennial report Science and Engineering Indicators, 2006 (the most current available) concluded,

“Although workers with science and engineering skills still make up only a fraction of the total U.S. civilian labor force, their effect on society belies their numbers. These workers contribute enormously to technological innovation and economic growth, research, and increased knowledge. Workers with S&E skills include technicians and technologists, researchers, educators, and managers. In addition, many others with S&E training use their skills in a variety of nominally non-S&E occupations (such as writers, salesmen, financial managers, and legal consultants), and many niches in the labor market require them to interpret and use S&E knowledge.”

This sector is so vital that more countries have created their own science and technology infrastructure to attract investment dollars and talent. (For some scientists, that has meant returning home to India, China, or southeast Asia after having remained in the US upon earning a PhD in a science or engineering discipline.)

In one example, during 2004, the South Korean government sponsored a greater percentage of research than the US (see 7-11 above).  More importantly, these trends reinforce one another. The resulting impact on the US economy has been significant.  Because research and development spending has been crossing borders internationally, business and investment spending has also crossed these borders.  Talented scientist have crossed borders internationally in search of intellectually and financially fulfilling work, which has been less and less available within the US in the face of the 8 year hiatus on federal funding for stem cell research and decreasing trends in federal funding of research, in general.  It makes good economic sense to refuel American investment in research and development, to retain or reclaim that business and investment spending that has wandered internationally.

The science and engineering sector continues to grow (see 3-05 below) and continues to be the place where jobs will be found.  The NSF report noted, “employment in S&E occupations in the 1990s continued to grow by 3 to 4 times the growth of other jobs.” Like, manufacturing, scientific research is a solid foundation upon which an economy can be built.  The financial industry must ultimately be based upon something tangible like the products yielded from science and research, such as computers, medical diagnostic equipment, or genetically engineered insulin.  Another reason the ARRA investment in the science and research sector makes good sense can be found within the trends describing scientists’ age.  The number of people with science and engineering degrees currently living and working in America expected to reach retirement age is  increasing substantially.  At the same time, the number earning these degrees and entering the workforce has slowed.  The result could be diminished US success against the increasing international competition discussed earlier.  Hopefully, the capital infused into the American science and engineering sector will stave off this threat for a generation while we improve our science, technology, engineering and math education and convince more American youth just how rewarding careers in science and technology can be.

Using the ARRA to stimulate the research sectors is good for the economy.  But what exactly are some of the areas that scientists in the health and biomedical sectors are researching?  Again, we can look at the ARRA to see what new priorities have been set and we will do so in future posts:

• Challenge Grant Research Priorities
• Comparative Effectiveness Research
• Preventive Health Interventions

Sources:

National Science Board. 2006. Science and Engineering Indicators 2006. Two volumes [Electronic Version]. Arlington, VA: National Science Foundation (volume 1, NSB 06-01; volume 2, NSB 06-01A). Available at<http://www.nsf.gov/statistics/seind06/>

National Science Foundation, Division of Science Resources Statistics
Universities Report Continued Decline in Real Federal S&E R&D Funding in FY 2007. Arlington, VA (NSF 08-320) [August 2008]. Available at <http://www.nsf.gov/statistics/infbrief/nsf08320/>

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by Clay Bennett

Tell me me what you think. Was the previous administration antagonistic towards the science, research and development sectors of the American economy? I’ve already voiced my opinion of the matter in a previous post. Please leave me a comment (or send me an email, if you prefer) to tell me why you agree or disagree with me.

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