Saying “no” to snow

In all my years of journalism, most of which has been at medical associations, healthcare organizations, health advocacy non-profits or a pharmaceutical business publication (that last one would be ddn, of course), I’ve covered a lot of conventions, conferences and shows. Some of them I’ve actually attended and some of them I’ve only written pre-show coverage for.

But I have to say that since entering this world of reporting and editing as a paid professional around 1992, I think that I’ve only encountered one major conference that was ever held in winter at anyplace with snow, and that was at Colorado Springs, which had skiing and upscale shops to make it a major draw for convention attendees.

Folks, where’s the love for New England in late January with the possibility of ice storms or Chicago in early February, with bone-chilling winds coming off Lake Michigan?

I know, I’m a pipe dreamer.

Also, I know this is kind of a throwaway post, but it’s been a long week and I promised a post every weekday (for as long as my New Year’s resolution resolve hold out), so that’s what I’ve got today.

Have a great weekend!

Did President Reagan suffer from Alzheimer’s disease while in office?

ddn has written countless stories about drug discovery and research efforts in the critical area of Alzheimer’s disease, and one area that researchers, clinics and drug manufacturers seem to be focusing on lately is pinpointing the onset of the debilitating disease. For example, in October, we reported on efforts by the Alzheimer’s Prevention Initiative (API) to test potential Alzheimer’s treatments and identify new biomarkers that could lead to earlier and more accurate diagnoses for Alzheimer’s patients. Researchers at the API told us that although there are many promising treatments being studied in Alzheimer’s symptomatic patients, by the time most people begin to show symptoms of the disease, it has already ravaged the brain, rendering these treatments ineffective.

This cold, hard reality has been making headlines lately with the release of a new book, “My Father at 100: A Memoir,” a close-up account of the life of President Ronald Reagan as seen through the eyes of his son, Ron Reagan. The book, which came out a few weeks shy of what would have been the former president’s 100th birthday on Feb. 6, is “an exploration of his character,” Ron Reagan says, but addresses the ongoing question of whether his father suffered with Alzheimer’s while in office.

President Reagan was diagnosed with Alzheimer’s in August 1994 at the age of 83, and he informed the nation about his diagnosis in a handwritten letter later that year. Although President Reagan’s White House doctors said they saw no evidence of Alzheimer’s while he was president, there was during his time in office widespread speculation that he demonstrated symptoms of mental degeneration. For example, former CBS White House correspondent Lesley Stahl wrote in her own memoir that at her final meeting with President Reagan in 1986, “Reagan didn’t seem to know who I was.” The president regained his alertness at the end of the meeting, Stahl wrote, adding, “I had come that close to reporting that Reagan was senile.”

Ron Reagan writes that that he noticed evidence of dementia as early as President Reagan’s first term. “I felt the first shivers of concern” during the 1984 reelection campaign, he writes, “that something beyond mellowing was affecting my father. My heart sank as he floundered his way through his responses. He looked tired and bewildered.” By 1986, President Reagan “had been alarmed to discover, while flying over the familiar canyons north of Los Angeles, that he could no longer summon their names,” his son writes.

Still, as he hits the press junket, Ron Reagan is careful to say that we cannot know for certain whether President Reagan exhibited signs of Alzheimer’s during his presidency. He also asserts that he believes if Reagan had gotten the diagnosis during his two terms, he would have stepped down.

In this video with TV personality Joy Behar, Ron Reagan clarifies his characterization of his father’s illness in his book.

“One can deduce that the disease must have been present, but I say specifically that I saw no dementia-like signs when he was in office,” he tells Behar. “Let’s recall that this was the oldest president ever elected (President Reagan was in his 70s). By the time he’s reaching his mid-70s, he’s losing his hearing, he’s been shot and nearly killed—which will take a little of the wind out of your sails—and of course I am worried about him all the time, because it’s a very tough job with a lot of stress. Every once in a while I would see—almost like when you are watching television, and it momentarily goes out of focus and snaps back. You think, ‘what did I just see?’ But I didn’t know what it was, I just knew I was concerned about him for all sorts of reasons. In retrospect, it’s possible that some of those early things were signs of Alzheimer’s, but I don’t know, and I can’t really make that claim.”

Some of the controversy, Ron Reagan tells Behar, may stem from “the confusion between Alzheimer’s the disease and dementia, which is a symptom of the disease—which usually arrives in the later stages.”

“Knowing what we know now about Alzheimer’s, that it’s a process that extends for years or even decades before symptoms arise, it’s kind of an academic question as to whether the disease was present when my father had” the debilitating disease, Ron Reagan says in this interview.

I think many of the researchers who read our publication would agree. What do you all think of Ron Reagan’s assertions? How does this “academic question” impact efforts to treat, manage or even reverse damage caused by Alzheimer’s?

Oncological pies in the sky

This just in from the Hastings Center, which deals with bioethics and public interest issues…

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Unrealistic Optimism Appears Common in Early Cancer Trials

Study suggests it may compromise informed consent

GARRISON, N.Y.—Can optimism be ethically problematic? Yes, according to a new study, which found unrealistic optimism prevalent among participants in early-phase cancer trials and suggested that it may compromise informed consent.

Many cancer researchers and ethicists assume that hope and optimism in the research context are “always ethically benign, without considering the possibility that they reflect a bias,” write the authors of the study, which appears in IRB: Ethics & Human Research. “Others have claimed that unrealistic expectations for benefit are a result of misunderstanding and that the proper response to them is to provide patient-subjects with more information…” But the study cast doubt on both assumptions.

The study included 72 patients with cancer who were enrolled in early-phase oncology trials in the New York metropolitan area between August 2008 and October 2009. Questionnaires assessed signs of unrealistic optimism, as well as participants’ understanding of the trials’ purpose. Unrealistic optimism, which social psychologists define as being specific to a situation and consider a form of bias, is distinct from “dispositional optimism,” which is a general outlook on life and is neither realistic nor unrealistic. Individuals can have one form of optimism without the other.

Study respondents exhibited unrealistic optimism in response to three of five questions about the likelihood of particular events happening to them compared with other trial participants: having their cancer controlled by drugs administered in the trials, experiencing a health benefit from the drugs in the trials, and not experiencing a health problem from the drugs in the trials.

However, a substantial majority of the respondents – 72 percent – accurately understood that the purpose of the trials was to advance knowledge with the potential to benefit future patients and not necessarily to benefit them. Misunderstanding the purpose was not significantly related to unrealistic optimism, the study found.

The authors said that unrealistic optimism has the potential to compromise informed consent “by interfering with the ability to apply information realistically.” They concluded: “Improving the consent process in oncology research will require us to do more than address deficits in understanding. It will require us to pay more attention to how patient-subjects apply information to themselves and to become more aware of the social-psychological factors that might impair decision-making in this context.”

The authors are Lynn A. Jansen, PhD, of Oregon Health and Sciences University; Paul S. Appelbaum, MD, of Columbia University; William M.P. Klein, PhD, of the National Cancer Institute; Neil D. Weinstein, PhD, of the University of Arizona College of Medicine; Jessica S. Fogel, BA, of Columbia University; and Daniel P. Sulmasy, MD, PhD, of the University of Chicago.

The paradox of pain

The global market for pain-relieving drugs has either been approaching or surpassing the $50 billion as we’ve moved from around 2007 to the present day. It’s clearly a huge market, and especially attractive given the numbers of people who suffer from neuralgia, fibromyalgia and lower back pain.

I wrote recently about Pfizer extended its offer to acquire King Pharmaceuticals, largely out of a desire to get access to the latter company’s abuse-resistant pain medications.

And there we go with the crux of things: Abuse potential.

Bad enough that the pharma and biotech companies have to deal with ADME-Tox issues that can kill their drugs before reaching market (but no before eating up hundreds of millions in R&D costs), but now one of the more attractive markets is one in which some of the best pain-relieving drugs are potentially addictive. The question is: How many of the most promising experimental drugs in the pipeline now will be able to deal with the abuse and addiction issue while also answering patients’ needs for relief from their suffering.

This question weighs on my mind as I read a recent article from the Harvard Mental Health Letter:

Painkillers fuel growth in drug addiction, from the Harvard Mental Health Letter

BOSTON—Prescription painkillers kill about twice as many people as cocaine and five times as many as heroin. Nearly two million Americans are dependent on or abusing narcotic (opioid) pain relievers—nearly twice as many as are addicted to cocaine. Because opioid painkillers target the same brain receptors as heroin, causing euphoria, they carry the risk of addiction.

On television shows, drug addicts are often depicted as criminal characters making deals on dark street corners. In fact, people abusing opioid painkillers are most likely to obtain them from friends or family members rather than from any other source, reports the January 2011 issue of the Harvard Mental Health Letter.

Dr. Michael Miller, editor in chief of the Harvard Mental Health Letter, explains that treatment for a painkiller addiction is most successful when it consists of two phases: detoxification to reduce or eliminate withdrawal symptoms after opioid use stops, followed by a longer (and sometimes indefinite) maintenance phase. Although counseling is an important part of treatment, most people addicted to painkillers require treatment a medication such as methadone or buprenorphine during both detoxification and maintenance therapy. Although most people addicted to opioids make multiple attempts to kick the habit, it can be done.

This is a tricky situation, and as with so many things in my coverage of the pharmaceutical business realm, I find myself of multiple minds on the issue.

• Are pharmas too eager to tap into this market, even though many of the best pain relievers lead to addiction and abuse in far too many people?
• Are people themselves simply too eager to want a “magic pill” for everything rather than, as we might have been told once upon a time, “working through the pain”?
• Am I overthinking this issue?

I’m not a person who wants to see suffering, so it is troubling that on the one hand, people might have to deal with pain while on the other hand, they might trade in agony for addicition.

It’s quite the quandary, as well as the paradox of pain: In helping people, pharmas may be hurting them as well.

On the bright side, though, pharmas like Pfizer are increasingly attracted to products that will reduced potential for abuse while still providing relief. Certainly, that is a potential profitable combination for them, and I wish them well.

But I continue to wonder how soon we’ll get to that point, and how many people will face this paradox of pain (and and for how many years) until we get there.

Seeking the ‘eye of the tiger’

WASHINGTON—Science funding is getting an infusion of cash after Congress in December passed a $45 billion reauthorization of the America Competes Act—a bill designed to invest in research and science education, and to fund and foster innovations that will help keep the United States competitive in tech-driven industries.

It signals another key milestone for scientific research, and history teaches us that building and maintaining a competitive advantage is vital to our country.

The importance of maintaining a competitive advantage on the global stage can be defined by one striking moment that occurred Oct. 24, 1957: Sputnik I was launched, an event that marked a 20-year race for supremacy in space between the Soviet Union and the United States. For two decades, the two nations traded volleys in the space race, with the United States gaining the upper hand by the late 1960s. By the 1970s, space exploration stood as a symbol of the competitive nature between the world’s two superpowers for technological, military, cultural and intellectual supremacy.

In a less grandiose analogy, the United States must regain the “eye of the tiger.”

In Rocky III, the fictional boxer Rocky Balboa must come back from a rattling defeat to Clubber Lange and the death of his longtime manager, Mickey. He trains with his old nemesis, Apollo Creed, learning along the way that he needs to stay hungry and keep “the eye of the tiger.”

Sadly, the story has changed in recent decades, with the United States slowly losing its competitive edge. It seems as if we no longer place a premium on education, research and innovation. Evidence of this is seen in the World Economic Forum’s recent ranking of the quality of math and science education around the world—the United States stands 48^th. We are lagging behind other countries in the issuance of patents and ­even—in an era of high unemployment—American companies consistently suffer from a shortage of individuals with critical skills.

The America Competes Act can serve as an investment in regaining our competitive edge and becoming the world leader in education, research and innovation.

The bill, which has been in legislative limbo throughout the year, sets funding levels for the next three fiscal years for the National Science Foundation, the Department of Energy’s research programs, and the National Institute of Standards and Technology. It also funds education initiatives and a range of other programs.

The legislation provides a total of $23.5 billion for NSF, $16.9 billion for the DOE’s Office of Science, $2.9 billion for NIST, $600 million for education efforts and $1.4 billion for other programs.

The original America Competes Act was approved in 2007. The legislation is based on recommendations outlined in the “Rising Above the Gathering Storm” report released by the National Academy of Sciences in 2005. It urged the United States to work harder to support technological innovation and enhance science, technology and mathematics education.

“In acting to update and extend the America Competes Act, we will spur innovation, invest in cutting-edge research, modernize manufacturing, and increase opportunity,” says House Speaker Nancy Pelosi. “Simply put, we will continue to ‘rise above the gathering storm’—and keep America No. 1.”

Earlier this year, the bill stood in political limbo, with an earlier draft that was nearly double the cost of the version passed through the House and Senate. A compromise was reached during the lame duck session to cut down the term of the bill from five years to three, creating most of the savings from the original $86 billion draft.

“If we are to reverse the trend of the last 20 years, during which our country’s technological edge in the world has diminished, we must make the investments necessary today,” House Science and Technology Committee Chairman Representative Bart Gordon, D-Tenn., said in a statement.

“More than half of our economic growth since World War II can be attributed to development and adoption of new technologies. These investments are the path toward sustainable economic recovery and growth and the path toward prosperity for the next 50 years,” Gordon said.

Among the new programs in the act, 98 percent of which will fund new scientific research, is the creation of an inter-agency public access committee in the Office of Science and Technology Policy. The committee will coordinate federal science agency policies related to the stewardship and dissemination of research results, including digital data and peer-reviewed scholarly publications.

Another aspect of the bill welcomed by the research community is the authorization of the funding boost for NSF, NIST, and DOE, which “puts us on a path towards a continued increasing investment in those programs over the next 10 years,” Jennifer Zeitzer, director of legislative relations at the Federation of American Societies of Experimental Biolog.

“It’s a bipartisan bill, which we’re happy about because it sends a signal that investing in science and paying attention to science issues is something that both parties care about,” she said.

Rep. Dan Lipinski, D-Ill., a former professor and one of the few members of Congress trained as an engineer, says he was proud to have helped write and pass the measure, which he says “makes essential, job-creating investments in advanced research and science, technology, engineering and mathematics education.”

“I am grateful for the valuable feedback I received from the Association of American Universities and the Association of Public Land-grant Universities while writing the NSF title of this bill,” he adds in a statement. “Because of their expertise, and because of what I learned from scientists and research administrators across the country, I believe this legislation will have an enduring positive impact on university-based research and STEM education programs.”

The Business Roundtable lauded Congress for its swift action in passing the America Competes Reauthorization Act.

“The bill will attract more young Americans into technical fields, expand the employment horizons and earnings potential of millions of new American workers, and strengthen America’s future. The Act helps increase our nation’s competitiveness by driving recruitment of K-12 math and science teachers, enhancing the skills of existing teachers, and increasing investments in both scientific research and math and science education. The reauthorization of this act will ensure America remains a global leader in technology, innovation and science in the 21st century,” said Larry Burton, Executive Director, Business Roundtable.

Nonetheless, it was a long and winding road to passage for the bill. The scientific community made an urgent call for it to be reauthorized in September—even issuing a stirring update to the original National Academies report—but despite their best efforts the legislation expired in October before the Senate had time to pass it.

The bill was revived in early December with Tennessee Republican Sen. Lamar Alexander among those credited for bringing the bill forward. Alexander is a strong supporter of the Department of Energy’s Office of Science, which is another of the agencies set to benefit from the funding increases mandated by America Competes.

“We’re very pleased. We think it’s a very, very important statement in support of research,” says Robert Berdahl, president of the Association of American Universities in Washington, D.C.

Society of Photographic Instrumentation Engineers (SPIE) leaders are among researchers, engineers, and others in the science and engineering community celebrating the passage today of the America COMPETES Act of 2010.

“We are delighted to see continued strong support for the National Science Foundation and the National Institute of Standards and Technology,” said SPIE CEO Eugene Arthurs.

“We are also happy to see approval for both continued and new spending for Department of Energy (DOE) research, and support for ARPA-E (Advanced Research Projects Agency-Energy),” Arthurs said. “This is a vital step in building a vigorous innovation pathway, linking the excellent R&D produced by DOE and other agencies to successful commercialization and the creation of jobs.”

Deborah L. Wince-Smith, president and CEO of the Council on Competitiveness, says the group applauds the passage of the America Competes Reauthorization Act with bipartisan support.

“By passing this legislation, Congress has taken a critical step in maintaining America’s leadership in innovation and entrepreneurship, which serves as the foundation for economic growth and long-term prosperity,” she says in a statement.

“The America Competes Act reauthorization paves the way for the vital funding of research, STEM education and American innovation, and will help keep America competitive through a time of great economic uncertainty. We encourage the 112th Congress to build upon this reauthorization and show their commitment to raising the standard of living for all Americans.”

Scripps researchers make metabolic breakthrough

Normally, this kind of story would be something you’d see in the “Bench Press” portion of our e-newsletter or website (click here) but in this post-Thanksgiving season, our cornucopia of stories was overflowing a bit, and I hate to throw out perfectly tasty and still-fresh leftovers, so enjoy this bit of research news right here at the blog.

Scripps researchers’ synthetic agonist of hormone-mediating proteins could yield treatments for metabolic disorders

By Amy Swinderman

JUPITER, Fla.—Scientists at the Scripps Research Institute have discovered the first synthetic agonist of retinoid-related orphan (ROR) nuclear receptor, protein molecules that mediate hormone activity inside the cell. Publishing their discovery in the November issue of the journal ACS Chemical Biology, the scientists say their finding could pave the way for the development of a therapeutic compound to treat numerous metabolic disorders and even cancer.

The lead author of the study, Dr. Thomas Burris, a professor in the Department of Molecular Therapeutics at Scripps’ Florida campus, and his colleagues have for years focused on nuclear pharmacology and chemical biology, and in particular have been investigating orphan receptors of the nuclear receptor (NR) superfamily. Members of the NR superfamily display a conserved domain structure with highly conserved DNA-binding and ligand-binding domains, and include the receptors for the steroid hormone, thyroid hormone and bile acids and oxysterols. Although many of the 48 NRs found in the human are characterized as ligand-activated transcription factors, a significant number of these proteins still have uncharacterized ligands.

The retinoic acid receptor-related orphan receptors RORα and RORγ are two of these orphan receptors that have been demonstrated to play important roles in regulation of metabolism and immune function. Last year, Burris and his colleagues identified a high-affinity synthetic inverse agonist of this same pair of nuclear receptors.

For this new study, the researchers extended that discovery with the identification of the compound T1317, as a molecular scaffold to synthesize an array of compounds and assess their activity against a number of receptors, including RORα and RORγ. The one compound that stood out was SR1078, which displayed a unique pharmacological profile that indicated it had a high potential for use as a chemical probe for assessing ROR receptor function in general.

The agonist, a compound known as T1317, is a molecular scaffold to synthesize an array of compounds and assess their activity against a number of receptors, including RORα and RORγ. For this study, the Scripps researchers describe the identification of a synthetic RORα and RORγ ligand, SR1078. SR1078 modulates the conformation of

RORγ in a biochemical assay and activates RORα and RORγ driven transcription.

“Pharmacokinetic studies indicate that SR1078 displays reasonable exposure following injection into mice, and consistent with SR1078 functioning as a RORα/RORγ agonist, expression of two ROR target genes, glucose-6-phosphatase and fibroblast growth factor 21, were stimulated in the liver,” Burris says. “Thus, we have identified the first synthetic RORα/RORγ agonist, and this compound can be utilized as a chemical tool to probe the function of these receptors both in vitro and in vivo.”

Those properties, Burris says, give SR1078 potential as a possible therapeutic compound for many different metabolic disorders. Nuclear receptors have become drug development targets for diseases like type 2 diabetes, atherosclerosis and metabolic syndrome, and have also been implicated in the progress of a number of cancers.

However, Burris cautions that this was a proof-of-principle study, and additional experiments are needed to examine the pharmacological profile of this compound in vivo.

“We’re certainly interested in merging the academic side of this with the drug development side,” says Burris, who spent 10 years working for pharmaceutical companies Johnson & Johnson and Eli Lilly & Co. “We’re still looking around for folks who will take it further, because of course on the academic side, we can only take it so far.”

The first author of the study, “Identification of SR1078, a Synthetic Agonist for the Orphan Nuclear Receptors RORα and RORγ,” was Yongjun Wang. Others authors include Naresh Kumar, Philippe Nuhant, Michael D. Cameron, Monica A. Istrate, William R. Roush and Patrick R. Griffin. The study was supported by the National Institutes of Health.

Research efforts can help fragile young lives

Whether we are researchers or journalists, as we explore the landscape of the drug development world we are reminded just how fragile human life can be.

This week, I came across a story that a team of pediatric cancer researchers have identified variations in a gene as important contributors to neuroblastoma, the most common solid cancer of early childhood.

The study team, led by researchers at The Children’s Hospital of Philadelphia, found that common variants in the LMO1 gene increase the risk of developing an aggressive form of neuroblastoma, and also mark the gene for continuing to drive the cancer’s progression once it forms.

The team’s work appears online in Nature. According to their report, a cancer of the sympathetic nervous system that usually occurs as a solid tumor in the abdomen, neuroblastoma accounts for 10 percent of childhood cancer deaths.

According to its website, The Cancer Center at The Children’s Hospital of Philadelphia cares for more children with cancer than any other pediatric hospital in the United States. It is ranked second in children’s cancer care in the U.S. by U.S.News & World Report.

It is so sobering to think that the youngest and most vulnerable—our children—sometimes are engaged in a fight for their lives as they battle myriad issues that come with adult-sized problems.

The researchers found a significant association between neuroblastoma and the LMO1 gene, located on chromosome 11, detecting the strongest signal among patients with the most aggressive form of the disease. This portion of the study identified SNPs, changes in a single letter within the DNA sequence, which predispose a child to developing neuroblastoma.

The research team utilized genetic tools to decrease LMO1’s activity, and showed that this inhibited the growth of neuroblastoma cells in culture. Increasing LMO1 gene expression had the opposite effect, causing tumor cells to proliferate.

Because other genes in the LMO family are known to be active in acute leukemias, other researchers have been investigating potential anti-leukemia drugs to target portions of the LMO pathway.

This is just one example of all of the great work going on in labs in hospitals, academic institutions and other facilities in the United States and around the world.

The research offers great hope for children battling cancer. It also is further proof that the work being done in research labs around the world are yielding results that can take steps to eradicate the diseases that take a great toll on us emotionally and physically, regardless of sex, age or race.

Further, the study by researchers at The Children’s Hospital of Philadelphia shows how we can expand our knowledge base for translating genetic discovery to clinical issues through integrative genomics, combining SNP discovery arrays with gene expression arrays and other functional approaches.

With the great results coming from this work, perhaps the suffering of some of the small and meek can be eased.

Putting a face on diabetes isn’t too hard

In my role with ddn, whether in the print publication or the online venues, I get to write about myriad diseases that affect the human population on this planet.

From Huntington’s and Alzheimer’s diseases to diabetes and cancer, companies that we cover each month are working to find new ways of battling these insidious diseases.

In talking with many of the people on the front lines of the research effort to develop these treatments, I get to put a name and face to efforts to improve our chances of surviving and thriving when these illnesses strike.

Over the years, the pages of ddn have featured stories about diseases that strike particularly close to home for those of us writing the articles. For me, it’s diabetes.

November is Diabetes Awareness Month, and it serves as a reminder for us all of a disease that is a growing problem.  According to some health studies, by 2050, one in three adults could be diabetic.

Today, nearly 24 million Americans have diabetes – including an estimated 6 million Americans who have it and don’t know it. It is estimated that another 57 million adults in the U.S. have pre-diabetes, placing them at increased risk for developing type 2 diabetes. Type 2 is the most common form of diabetes, accounting for 95 percent of all cases.

I don’t have to look too far to put a face on diabetes. My wife was diagnosed with type 2 diabetes just over a year ago. Her father was diagnosed five years ago, but he lived with the disease for many years and didn’t know it, choosing to ignore the warning signs.

As a result of years of living with uncontrolled diabetes, my father-in-law today is 64 years old, legally blind and must undergo kidney dialysis three times a week. For him, it’s a matter of life or death.

After being diagnosed, my wife felt as if she were just handed a death sentence. I knew from the stories I’d written that there are two ways to live – you can control the disease or it can control you.

We’ve learned that type 2 diabetics can take a number of oral medications to help their body metabolize sugars, increase insulin production or block the absorption of carbohydrates.

My wife also has a key advantage over her father in her fight against diabetes – early detection. While a diagnosis is a life-changing experience, knowing the what you’re up against is instrumental in effective treatment.

It also is key in thwarting the ravages of diabetes, which include neuropathy, which causes tingling, numbness and destruction of nerves. Because of neuropathy, diabetics must check their feet regularly to ensure they have no wounds. If undetected, a wound can lead to infection that could lead to amputation. Diabetes may also lead to kidney disease, heart disease and blindness.

We’ve learned from the endocrinologist that the goal of diabetes treatment is the prevention of long-term complications. We’ve also had to talk to dietitians and diabetes educators, learning that it truly takes a village to keep a diabetic well.

I’ve learned that even a simple trip to the optometrist can heighten anxiety in my wife. She has her father as a constant reminder of what can happen with this disease.

Type 2 diabetics can take a number of oral medications to help their body metabolize sugars, increase insulin production or block the absorption of carbohydrates, and that’s where we are at. Thanks to the work of countless researchers over the decades, these treatments are available to help diabetics keep their blood sugar levels in check.

Researchers today are at work to discover new drug candidates that have greater efficacy against these diseases. Stepping outside of my role as a journalist and speaking as a husband and father, I have to say just how grateful I am for the work of these researchers. Whether you work at the biggest pharma or the smallest of labs, your work is having an impact on the lives of people the world over.

Some of you may even be motivated in the lab by your own personal experience. We all can share that common bond in the human condition. The faces of these diseases are all around us, and the battle is no less important today. That key discovery that could deliver the knock-out punch to a disease could be occurring in a lab right now.

And to all of the researchers who toil each day to find the Holy Grail, I thank you.

For stem cell case plaintiff, faith and science go hand-in-hand

Yesterday, we shared a Q&A with the lead plaintiffs in the controversial federal lawsuit challenging federal funding for embryonic stem cell (eSC) research, Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle.

Both researchers agreed to field questions about their beliefs regarding eSC research. Deisher, who has been especially vocal about her Catholic faith and how it informs her research, also agreed to take a few questions about the connection she sees between her beliefs and science.

According to Deisher’s bio, she has 17 years of experience in scientific and corporate leadership positions involving research, discovery, production and commercialization of human therapeutics. She obtained her Ph.D. in molecular and cellular physiology from Stanford University. Prior to founding AVM Biotechnology in 2007, Deisher held positions at Repligen Corp. in Cambridge, Mass., ZymoGenetics Inc., Immunex and Amgen in Seattle and CellCyte Genetics Corp. in Bellevue, Wash. She has had 23 patents issued and has published numerous scientific manuscripts.

ddn: Do you find any conflict between your faith and the scientific research you engage in?

Deisher: I do not find any conflict between my faith, which is Catholic, and my research. My faith enhances my work. My Christian faith calls me to focus on drugs and treatments that are affordable so that the greatest number of people will benefit. My faith calls me to use reason and the order of natural law to determine, for instance, the stem cell most optimal for clinical use. My faith calls me to focus only on those treatments that will be effective. My faith also calls me to respect the intrinsic dignity of human life in my work.

ddn: How does your faith impact your research approach?

Deisher: My faith is completely complementary to my research, which focuses currently on stem cells for regenerative medicine and alternative vaccines.

Adult “self” stem cells, meaning a patient’s own stem cells, are affordable, compared to all other stem cell therapies. For the most part, therapies using adult stem cells will cost about $25,000 compared to Geron’s projected $500,000 for embryonic stem cell-based therapies. Adult “self” stem cells are found naturally in every organ, in each of us, and they are “preprogrammed’” to perform the functional regeneration that patients require. They also lack the issues of immune rejection or tumor formation that plague pluripotent stem cells such as embryonic stem cells. Adult “self” stem cells are far advanced in clinical trials, and in comparison to “patented” stem cell lines, they show more effectiveness in patients. Whether one believes in God or Darwin, one can arrive at an optimal stem cell for patients using objective measures, common sense and business criteria to generate the greatest good for the most people.

I would apply these same criteria to any type of treatment that I would work on, including biologics and small molecules: Will the therapy be affordable, or will only the very few benefit? Will the therapy be effective or merely enhance my stock price or financing temporarily? Will the therapy be undermined by adverse side effects? These criteria are sound business objectives and compatible with my faith.

Q+A with the stem cell case plaintiffs

On the cover of our November issue (which you can download here), you can read about a controversial lawsuit that is at the center of one of our nation’s hottest current debates: embryonic stem cell (eSC) research. (See the story here.)

The lawsuit, Sherley, et al., v. Sebelius, et al., alleges that the order signed by President Barack Obama in March 2009 lifting a previous ban on federal funding for eSC research violates the Dickey-Wicker amendment, a 1995 law prohibiting the government from appropriating funds for research that involves the creation or destruction of human embryos for research purposes. The lawsuit also contends that President Obama’s order has intensified competition for government research funds—which are already in short supply—for researchers engaged in other kinds of stem cell research.

The case has been making its way through the courts for a while, but it made headlines in August when the U.S. District Court for the District of Columbia issued a preliminary injunction in the case, essentially bringing funding for embryo-destructive research to a screeching halt while the case is under consideration.

With the research community in uproar over the decision, less than a month later, the U.S. Court of Appeals temporarily suspended the injunction, arguing that it would cause irreparable harm to researchers, taxpayers and scientific progress while the case is appealed.

While Sherley v. Sebelius concerns the interpretation of law and competitive issues, the case has renewed the debate over the practice of stem cell research in the United States, a political and moral tug-of-war that has been waged for decades.

The debate centers on the creation of a human embryonic stem cell (eSC) line, which requires the destruction of a human embryo. Advocates of the pro-life movement are concerned with the rights and status of an embryo as an early-aged human life and equate eSC research with murder. Those opposing this view argue that these embryos are to be destroyed or stored for long periods of time past their viable storage life, and point out that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering.

Science holds pros and cons for both sides of the moral debate. Adult stem cell research has achieved great levels of success and potential, but these stem cells are generally limited to differentiating into different cell types of their tissue of origin. Although some researchers are of the opinion that the differentiation potential of eSCs is broader than most adult stem cells, they may be rejected by the immune system—a problem that would not occur if a patient received his or her own stem cells.

Dr. James Sherley

As the case continues to play out in court, media attention is turning to the lead plaintiffs in the case, Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle. Although the pair admit they did not know each other prior to the case unfolding—they were reportedly “recruited” by attorneys seeking to challenge President Obama’s order—they both have certain beliefs about the ethics involved in eSC research, and strongly support a focus on adult stem cells.

Sherley, whose research focuses on the molecular and biochemical mechanisms of adult stem cells, has long been vocal about his opposition to human eSC research. He has described the position that eSCs hold the promise to cure or treat debilitating diseases “misinformation,” maintaining that adult stem cell research is “a viable and vibrant path to new medical therapies.” Sherley also once made headlines for protesting a decision by the Massachusetts Institute of Technology (MIT) to deny him tenure by going on a 12-day hunger strike. Sherley, who is African-American, has also publicly said he believes that MIT did not give him the freedom to challenge scientific orthodoxy the way the institution would have for a white colleague.

Dr. Theresa Deisher

Deisher, who works exclusively with adult stem cells, founded AVM Biotechnology “in response to growing concerns about the need for safe, effective, affordable and ethical medicines and therapeutic treatments,” with help from private donors. According to the company’s website, “The use of aborted fetal tissue and embryonic cells in the discovery, development and production of vaccines and pharmaceuticals … make it difficult for many physicians, pharmacists, scientists and healthcare professionals to navigate their fields of expertise without sacrificing their consciences.” You can see some of Deisher’s writing on the subject here.

As media scrutiny has intensified in the wake of the case, Sherley and Deisher have backed away from many interviews, but were gracious enough to take questions from ddn regarding their views about eSC research. Here are their responses:

ddn: What should the goal of stem cell research be?

Sherley: Like other NIH-funded research, the goal should be to increase our scientific knowledge about the natural world through the conduct of ethical scientific research towards the goal of improving human health.

Deisher: The goal should be to develop safe, effective and affordable therapies for human disease, adhering to the highest scientific ethical standards.

ddn: Are you against embryonic stem cell research as a practice, or the federal funding of it, or both? Why?

Sherley: Specifically, I wish to educate and alert the public that, first and foremost, human embryonic stem cell research is unethical according to pre-existing NIH guidelines for human subjects research; that its funding by NIH is illegal according to U.S. law as articulated by the Dickey-Wicker amendment; and that it continues to be misrepresented by many of its proponents who misstate its potential for providing medical advances and present it as if there were no alternatives, when if fact both adult stem cell research and traditional disease research are not only effective alternatives, but better ones in many respects.

Deisher: Human embryonic stem cell research does not meet the high ethical standards test. A human being is necessarily destroyed in the process of obtaining human embryonic stem cells, which is not an acceptable outcome according to U.S. human subjects guidelines. Additionally, the research is not necessary, another requirement of our human subjects guidelines, as superior alternatives are available using adult stem cells. According to human subjects research guidelines, even if parents give consent, research cannot be done if it is not necessary. Human subjects guidelines should be applied to all research, regardless of funding source, and should be applied to regulate research on human embryos.

ddn: What are viable alternatives to embryonic stem cells? How soon will they bring about therapies? What is their commercial potential?

Sherley: The viable alternatives are both adult stem cell research and traditional disease research. In particular, adult stem cell research addresses the development of new therapies based on repairing tissues or replacing tissues with regenerative cells. Such therapies based on adult stem cells are already a part of standard clinical practice. Bone marrow reconstitution with blood stem cells is one of the best known examples, but there is a large body of clinical research underway both to make blood stem cell treatments even more effective and to develop new therapies based on other types of adult stem cells. This clinical research includes commercial development of therapies for diseases like diabetes based on developing adult stem cells that renew the cells that make insulin. It is important that the public understands that proposed treatments based on human embryonic stem cells invariably require that they be converted into either adult cells or adult stem cells, which are ultimately required for any therapy that will repair, replace, or treat tissues in children and adults. When the public knows this, it then becomes imperative for it to ask proponents of human embryonic stem cell research, “What is your motivation?”

Deisher: Adult stem cell therapies are in late-stage clinical trials, having advanced extremely rapidly since their discovery in the late 1990s, entering clinical trials by 2002.  Prior to the late 1990s, scientific dogma held that adult stem cells did not exist outside of the blood system. These novel discoveries have brought promise to many patients suffering from grievous illness; unfortunately, the United States lags behind the rest of the first world in advancing these therapies because our academic scientists and elected officials have preferentially advanced human embryonic stem cell research, which is currently helping no one. Other alternatives include therapies that block tissue destructive pathways. For instance, Enbrel is a drug for rheumatoid arthritis that blocks the joint destroying action of a molecule called TNF. Once the destructive pathway is blocked, naturally present regenerative processes are able to replace the damaged joints.

ddn: Describe some of your current work in this area.

Sherley: My laboratory’s research is focused on developing methods for production of adult stem cells, discovering biomarkers that can be used to quantify adult stem cells, and elucidating cellular mechanisms that are important for adult stem cell function, health and longevity.

Deisher: My research focuses on the efficient delivery and retention of stem cells in diseased organs.

ddn: What should the government’s role be in stem cell research being done in the United States?

Sherley: Through its agent the NIH, its role should be the same as for other areas of research: Adhering to U.S. law, foster and fund ethical, high-quality research that has potential to positively impact human health.

Deisher: (References the NIH’s mission statement, which states, “NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life and reduce the burdens of illness and disability. The goals of the agency are: To foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health; To develop, maintain and renew scientific human and physical resources that will ensure the nation’s capability to prevent disease; To expand the knowledge base in medical and associated sciences in order to enhance the nation’s economic well-being and ensure a continued high return on the public investment in research; and to exemplify and promote the highest level of scientific integrity, public accountability and social responsibility in the conduct of science.”)

Highlighted in red are NIH mandates that are not met by NIH funding of human embryonic stem cell research. The government’s role should be to actively promote research and clinical trials in areas that would not be adequately advanced by private industry. Adult stem cells from a patient’s own blood, bone marrow or other organs are not patentable, and therefore, absolutely require federal funding to bring these remarkable treatments to U.S. citizens. As taxpayer funds are used by the government for these purposes, one would hope that affordability would also be an important criterion for federal funding of clinical trials. Adult stem cell therapies are affordable, and will cost on average about $25,000, while embryonic stem cell therapies, if ever available, will be expensive and beyond the means of almost all U.S. taxpayers. Geron Corp. issued public statements in January 2009 estimating the cost of human embryonic stem cell-based therapies for spinal cord injury to be just under $500,000. Geron received significant NIH funding for this work.

ddn: How does the 2009 executive order from President Obama impact your access to research funds?

Sherley: Because the president’s order led to NIH instituting the illegal funding of human embryonic stem cell research, it injures all U.S. scientists working in other fields who compete for the same limited NIH resources. However, the greater injury is sustained by scientists whose research focuses on the recognized alternative to human embryonic stem cells, adult stem cells, because of the juxtaposition of all stem cell research applications in the NIH review process. At each phase of the NIH review process, bias and contempt, inspired by an illegal implementation of the president’s order, can occur against their research applications, even though they may be of the highest quality.

Deisher: The executive order initiated a process where preference in NIH requests for grant proposals and ultimate grant funding is now directed towards embryonic stem cell research. The 2009 executive order amplified congressional obsession with funding embryonic stem cell research, apparent since 2006. Every adult stem cell scientist and clinician is injured by the preferential emphasis and funding of embryonic stem cell research. Most egregiously, U.S. citizens are being denied adult stem cell therapies that are in development in Europe and other countries for heart attack, blindness, paralysis, stroke, diabetes, multiple sclerosis, lupus and other grievous human illness.

ddn: What can Americans do to get past the moral arguments in favor of or against embryonic stem cell research, in order to make sure that we are still working toward finding cures for devastating diseases and conditions?

Sherley: Americans would have no dilemma to ponder, if they were better informed that human embryonic stem cells have very little potential to lead to cures for devastating diseases and conditions. The No. 1 sales pitch pushed for these cells, the “ability to make any cell in the body,” is their fatal flaw for providing new medical therapies. For effective tissue and organ therapies, regenerative cells are needed that can continuously replace the mature cells found in just the sick or ailing tissue or organ. Human embryonic stem cells cannot do this. Adult stem cells can. Since human embryonic stem cells make other cells that are not needed, if they were used, they would give the patient another well-known, very difficult-to-treat disease.

Deisher: Science should never be above moral scrutiny and one only needs a brief history lesson to know this. On another note, I hear arguments regularly that we should not deter human embryonic stem cell research because of the moral objections of a minority. This is absurd, as our entire scientific research ethical oversight is predicated on respect for the moral objections of a minority in our country. Respect for animal rights and concern for ethical research conduct using animals in experiments regularly deters experiments that are scientifically and economically expedient. Respect for ethical concerns as they relate to human subjects research should receive no less deference. However, Americans do not need moral arguments to oppose embryonic stem cell research; embryonic stem cells are known to form tumors, they would require lifelong immune suppression that itself can cause hypertension, osteoporosis and other nasty side-effects, and human embryonic stem cell products would be too expensive for Americans to afford.

Deisher was also kind enough to field questions about how her Catholic faith informs her approach to stem cell research. We’ll bring you that Q&A very soon.