Women's Health in the Spotlight
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Julie Gerberding, New American Hero

Most people had never heard of Dr. Gerberding or the CDC until the SARS epidemic got everyone's attention.  Then every news outlet wanted to hear everything she had to say.  Dr. Gerberding seems to have found that she can put this media attention to good use.  Indeed, with SARS, Mad Cow, the ricin scare, and Avian Bird Flu, and the omnipresent fear of bioterrorism, the pubic wants to know and needs to know what Dr. Gerberding has to say. 

Now that the SARS/Mad Cow/ricin/Avian flu headlines are receding from memory, she is back with some important public health pronouncements.  She is talking openly about one of the sad chapters in medical history, that of the inadequate attention paid to women's health.  Now that about 50% of medical students are female, that is changing.  There is still a long way to go, and Dr. Gerberding is playing a big role.  For example, yesterday's NYT contained an article on the problems that infectious disease cause during gestation and delivery.  These are problems with huge humanitarian and financial impacts.  They are especially tragic because so many are preventable with good pre- and postnatal care. 

To address these issues, the CDC sponsored the International Conference on Women and Infectious Diseases in Atlanta GA on February 27th and 28th.  This is being held in conjunction with the International Conference on Emerging Infectious Diseases.  In May, the CDC will co-sponsor the 2004 National Sexual Violence Prevention Conference. 

The NYT article is drawn from the ICWID conference.  We will have to wait until May to hear what she has to say at the  NSVPC.   The CDC has, in the meantime, put out a report  on the economic impact of what they call Intimate Partner Violence.  This consists mainly of men being violent toward wives or girlfriends.  As we shall see, the economic impact is very great indeed.  The report indicates that their overall cost estimate does not include may costs, such as legal and criminal justice related costs.  It also includes only costs stemming from violence toward adult women.   They did not feel able to gather reliable information regarding victims under the age of 18. 

February 28, 2004
Action Urged on Diseases With Dangers for Women
By LAWRENCE K. ALTMAN

ATLANTA, Feb. 27 — New diagnostic tests and better information programs are urgently needed to improve the control of a number of infectious diseases that affect women and newborns, a top federal health official said here on Friday.

Sexually transmitted diseases and certain other common infections affect women disproportionately, compared with men, and can be dangerous, particularly in pregnancy, said the official, Dr. Julie L. Gerberding. Dr. Gerberding is director of the Centers for Disease Control and Prevention here.

Cultural, economic and social factors also have a critical role in the disparities between men and women. Women often serve as the brokers for their families' health care "but are last in line to address their own health problems for lack of time," Dr. Gerberding said at the opening of a two-day international meeting on women and infectious diseases.

A lack of scientific knowledge and the failure to apply what is known also increases the burden of such illnesses on women, she said.

The centers, the World Health Organization and the American Society for Microbiology are sponsoring the meeting to renew efforts to decrease infection death rates among women and newborns.

"Women disproportionately suffer the burden of poverty, are the victims of widespread and persistent discrimination in all areas of life and put their lives at risk every time they become pregnant," Dr. Gerberding said.

She added that although the problem of women and infection was more complicated than gender alone, it offered "some unique aspects."

One is that certain diseases can cause more serious illness and lead to more severe complications among pregnant women. Another is that women are at least four times more vulnerable to infection from H.I.V. and other sexually transmitted diseases.

For example, 60 percent to 70 percent of the women who are infected with gonorrhea or chlamydia may be unaware of it. Delayed diagnosis and treatment can lead to chronic pain, stillbirth, infertility and even death.

April 28, 2003
Contact: CDC Injury Media Relations:
770-488-4902

CDC Reports the Health-Related Costs of Intimate Partner Violence Against Women Exceeds $5.8 billion each year in the United States

The health-related costs of rape, physical assault, stalking, and homicide by intimate partners exceed $5.8 billion each year. Of this total, nearly $4.1 billion are for direct medical and mental health care services and productivity losses account for nearly $1.8 billion, according to a report by the Centers for Disease Control and Prevention (CDC). The report is being released today in conjunction with the CDC Injury Center’s national conference, “Safety in Numbers.”

“Violence against women harms more than its direct victim. It also harms the children, the abuser and the entire health of all our families and communities. For the health of our country, it is critical that we stop this cycle now,” Health and Human Services Secretary Tommy G. Thompson stated. “Just last week, the Department hosted a meeting of the National Advisory Committee on Violence Against Women and shared the many Department programs that are making a profound difference, providing the support and healing they need to rebuild their lives.”

CDC Director Dr. Julie Gerberding added, “Violent acts against women don’t end with visits to the emergency room. They are a major public health problem that we are committed to preventing. Intimate partner violence costs women and their families a high-price financially, physically and emotionally. We must continue to do all we can to prevent the pain, anguish and health problems that result from intimate partner violence.”

The report estimates the incidence, prevalence and health-related costs of non-fatal and fatal Intimate Partner Violence (IPV) against women. It also identifies future research needs and highlights CDC priorities for IPV prevention research. IPV is defined as violence committed by a spouse, ex-spouse, current or former boyfriend or girlfriend.

“CDC is actively involved in ongoing efforts to prevent violence against women,” said Sue Binder, M.D., CDC Injury Center Director.“ This report provides information that is crucial in helping communities demonstrate the impact violence against women has on society.”

CDC researchers examined the data from the 1995 National Violence Against Women Survey for the incidents of IPV, the costs, how health care was used, and how much work-related time was lost for women who were assaulted by intimate partners. This report reflects the most current and reliable data that is available on IPV and its related health costs.

Because of the data limitations, the costs presented in the report likely underestimate the economic burden of IPV in the United States. The report points out that these cost figures are not comprehensive, excluding such important costs as those related to the legal and justice systems. Therefore, the costs should not be used for analyzing benefit-cost ratios for IPV prevention programs. However, the report may be useful in calculating the health-related cost savings from reducing IPV and associated injuries and for evaluating the impact of IPV on specific sub-sectors of the economy, such as consumption of medical resources.

To help reduce IPV, CDC is currently:

• Developing a guide to identify promising prevention programs and interventions for batterers
• Funding programs to support rape prevention and education efforts in all 50 states, the District of Columbia and eight territories, providing for education in communities about the extent of sexual assault and the development of programs to prevent it. 
• Funding 14 state Domestic Violence Coalitions to develop and implement community coordinated responses. This initiative coordinates services and mobilizes communities to respond to and prevent domestic violence. 
• Funding projects to help monitor and track intimate partner violence in five states. The goal is to help reduce IPV through the collection of timely and credible data that are useful for planning, implementing and evaluating prevention programs.

The full report on the Costs of Intimate Partner Violence Against Women in the United States is available online at: http://www.cdc.gov/ncipc/pub-res/ipv_cost/ipv.htm.

For more information on intimate partner violence visit the CDC’s website at: http://www.cdc.gov/ncipc.

Notice that the report was based upon data from 1995.  It is almost certain that the costs are much higher now.  The incidence of domestic violence increases with increasing unemployment and general financial stress.  Also, the costs of health care, and of health insurance, have increased considerably since 1995.  It is important to recognize the fact that IPV has a significant impact on all of us. 

Efforts to reduce the frequency of perinatal infectious disease, and the incidence of domestic violence, deserve greater attention among health care providers and among policy makers.  Dr. Julie L. Gerberding, M.D., M.P.H.,  is hereby nominated as a New American Hero.

Neurogenesis and Stem Cells in the News
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Making the World Safe for Rodents

After all the posting about the politically-motivated changes in the president's bioethics council , I thought I would put up some information to show why the subject is so important.  The first article, from the BBC, illustrates the therapeutic potential of a technique involving gene therapy.  The scientists inject genetic material into living tissue in an effort to alter the function of the tissue.  In the second article, several methods of using stems cells are discussed.  I edited out a lot of the second article, because it is long and packed with highly technical stuff.  I put some of the keys phrases in bold face, to make it easy to skim through and pick up the high points.  My intent here is to show that there is tremendous potential and that real progress is being made.  Citizens should be informated about this and the implications of this kind of research.  Politicians also need to have an awareness of the need for careful but honest consideration of the ehtical issues.

Scientists 're-grow optic nerves'
Scientists believe they have taken a big step forward in their effort to be able to repair damaged nerves.

Researchers at Harvard Medical School say they have had some success trying to regenerate optic nerves in rats.  Writing in the Journal of Neuroscience they said while they were unable to restore sight they achieved three times more regeneration compared to others.  Finding a way to re-grow nerves could lead to cures for a wide range of conditions from blindness to paralysis.

Permanent damage

Any injuries that cause damage to nerves tend to be permanent. This is because nerve cells cannot regenerate or repair themselves.  Scientists around the world are working on projects aimed at finding a way to get nerves to re-grow.  One of the reasons nerves are unable to regenerate is that proteins in the outer layer of nerve fibres are programmed to stop re-growth.
Scientists have developed ways to turn these proteins off. However, this has not proved enough to make nerves regenerate.  Dr Larry Benowitz and colleagues tried a two-pronged approach to try to stimulate re-growth.  First, they damaged the lens in the eyes of a group of rats with optic nerve damage. This nerve links the retina to the part of the brain that enables them to see.  Damaging the lens stimulates an immune response - cells travel to the eye and release growth factors to try to repair the damage. This causes nerve fibres to grow into the optic nerve.  Dr Benowitz then used a gene therapy technique to try to boost this growth by injecting a gene designed to turn the proteins that are programmed to stop re-growth off.  "When we combined these two therapies - activating the growth programme in nerve cells and overcoming the inhibitory signaling - we got very dramatic regeneration," said Dr Benowitz.  However, the scientists were unable to get the nerve fibres from the retina and those from the brain to hook up properly.  "It's a mapping problem," said Dr Benowitz. "We have to retain the proper organisation of fibre projections to the brain."

Further research

The scientists are now planning further studies to try to overcome this problem.  Kevin Shakesheff, professor of tissue engineering at the University of Nottingham, said scientists were still years away from being able to use these techniques in humans.  "There has been a lot of progress in this area," he told  "We have taken enough steps forward to indicate we can solve the problem. The science is really exciting.  "However, translating that excitement into clinical applications will take time."

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/3495717.stm

Published: 2004/02/29 01:46:14 GMT

© BBC MMIV

Conference Report - Stem Cells and Neurologic Repair
Highlights From the Annual Meeting of the American Society of Neuroscience; November 8-12, 2003; New Orleans, Louisiana
Posted 01/13/2004
Sara M. Mariani, MD, PhD

Introduction

Stem cells, neurogenesis, and repair -- this powerful combination of words announces how far neuroscience has come in the past few years in the search for new venues of treatment,[1-4] forecasting tissue repair in brains damaged by stroke or in spinal cords injured by trauma.[5] Replacement of selected cell populations is also being proposed and investigated for Parkinson's disease or Alzheimer's disease,[6-8] neurodegenerative diseases affecting mostly adults in the later decades of their lives. But what are we doing for infants and children with cerebral palsy or developmental disability, congenital defects of their central nervous system (CNS) that severely impair execution of many functions?

Notwithstanding all the efforts of their caregivers, quality of life for these young subjects can be, at times, substantially compromised; even more so when they age and develop secondary complications. Many advances have been made in their management and rehabilitation. Yet, often these children's life expectancies are lower than those of their peers.[9]

Cerebral palsy and developmental disabilities are conditions that affect children from all countries and all ethnic backgrounds. It is estimated that there are at least 14 million children living with these diseases in the United States alone. Is there a way to give them a second chance?

These issues were addressed at a symposium held during the 33rd Annual Meeting of the Society for Neuroscience, in New Orleans, Louisiana, entitled: "Stem Cells and Pediatric Disorders: Forging New Paths to Progress" under the auspices of the Children's Neurobiological Solutions foundation. Neuroscience is, nowadays, certainly one of the "hottest" research fields in biomedicine. Will the hopes raised indeed meet their promise?

Three leading researchers who are experts in cutting-edge research on brain repair using stem cells, Dr. Evan Snyder, Dr. Nick Gaiano, and Dr. Martha Windrem, gave an overview of the state of the art in this field, outlining successes and limitations of the strategies that are currently being evaluated in experimental animal systems.
[...]

Delivery of Cells

In the past few years, Fishell and colleagues[14] have shown that dissociated cells can integrate into host tissues following intra-CNS delivery, and that they can differentiate in response to local cues in the striatum and the neocortex. The surrounding microenvironment, however, has to be ready to accept and "accommodate" the transplanted cells. Very similar results have been obtained with intraventricular injections.

Other studies using intraparenchymal cell transplantation under ultrasound image guidance[15,16] showed substantial expression by grafted cells of an alkaline phosphatase reporter gene. Cells were widely dispersed in the CNS (eg, in the cortex and in the hippocampus), as they had been selected to display this intrinsic property. Cell source and final localization are critical factors in all these approaches if specific targeting is being sought.

Engraftment of Oligodendrocyte Precursors

[...]Following intraparenchymal injection, selected fetal A2B5+/PSA-NCAM- cells were found to migrate extensively, with migration and proliferation occurring predominantly in the white matter (corpus callosum). A few cells were found to migrate also into the gray matter (eg, striatum and neocortex). The proportion of viable, myelinating cells substantially increased over time.^[23] In quantitative terms, 50,000 OPCs were injected on each side of the brain in a very small volume of liquid, for a total of 100,000 cells per treated mouse.

Can these fetal OPCs indeed remyelinate extensive regions of the brain in Shiverer mice? By immunofluorescence microscopy, fetal OPCs appeared differentiated in myelin-producing cells in the cerebral cortex, but they remained in the precursor stage when infiltrating the striatum.^[24] Following differentiation, the OPCs gave rise to oligodendrocytes able to ensheath "naked" axons in the host, with production of MBP. Electron microscopy revealed that the newly formed myelin was compact in nature, with major dense lines.

[...]The myelin newly produced by the grafted human cells interacted with the native axons to form Caspr+ paranodes and physiologically functional nodes of Ranvier. Of note, while untreated Shiverer mice are severely compromised at 4 months of age, mutant mice xenografted with human OPCs showed a significantly prolonged survival, comparable to that of wild-type mice, suggesting a functional and long-term correction of their myelination defect.^[21,24] [...]

Neurogenesis and Brain Repair

[...] Snyder's group^[26] showed that stem cells recovered from the brain were able to differentiate into progenitor cells able to generate neuroblasts as well as glioblasts, using lacZ as a tracking gene. These finding raised considerable interest and paved the way for further studies on the regeneration potential of the brain, and how to harness it using transplantation and/or manipulation of stem cells.  [...]

Enzyme Replacement

Examples of diseases amenable to this therapeutic approach are the lysosomal storage diseases (eg, Tay Sachs disease), in which congenital deficiency of key metabolic enzymes leads to abnormal intracellular accumulation of unprocessed substrates, and ensuing cellular toxicity and death. If affected cells can be engineered to produce the missing enzyme or the end product, this would lead to normal or reduced production of the toxic substrate.

Pilot studies in suitable animal models showed that intraventricular injection into newborn mice was associated with expression of the therapeutic enzyme all over the brain, and elimination of the storage disease. For example, expression of hexoaminidase-beta alpha chain (with green fluorescent protein tracking) in the brains of Sandhoff mice (an experimental model of Tay Sachs disease with abnormal accumulation of neutral glycosphingolipids) successfully shifted the survival curve in treated mice vs controls, indicating a beneficial effect on overall survival.^[27]

Neuronal Replacement in the Brain

If cells could be grafted into sick tissues to correct a genetic defect, then, researchers argued, stem cells or progenitor cells could potentially be used, after appropriate selection and in vivo differentiation, to restore myelination in brains that had an intrinsic deficit in this critical developmental process.
And, indeed, similarly to the results of the studies presented by Dr. Windrem, transplantation of progenitor cells in Shiverer mice, which suffer from a congenital defect in myelination, led to significant reduction in shivering following in vivo remyelination by grafted cells.^[28]

Neuronal Replacement in the Spinal Cord

Can NSCs, be of help in repairing defects of the spinal cord by cell replacement? Studies in rats with extensive spinal resections have shown a certain  degree of functional recovery following cell replacement in vivo.^[31] But the surprising finding was that, apparently, the cells responsible for this improvement were derived from the host, not from the donor.

Thus, it seems that grafted cells may actually affect neurologic repair in more than one way, not only by differentiation and proliferation in vivo, but also by inducing some level of neuroprotection in vivo, possibly by mitigating the loss of connectivity associated with damage or resection, and by reducing formation of scar tissue.[...]

Conclusions

Preliminary studies are ongoing to evaluate feasibility and potential benefits deriving from intrauterine delivery of NSCs in the subventricular zone of fetal monkeys, but far more experiments and refinements are needed before this strategy may offer a reasonable therapeutic option in humans.[...]

So we see that progress is being made with gene therapy techniques, and with stem cells.  Clearly, these are techniques that have ethical implications, and there is a role for a Bioethics Council.  So far, under the political restrictions in the USA, humans are no better off; but we stand to have the healthiest population of lab rats and mice in the entire world.   This should put our minds at ease, in this age of Weapons of Mass Destruction.  If there is ever an all-out release of nuclear weapons, or if a devastating biological weapon ravages the planet, at least the surviving mice and rats of the USA will be here to fend off all those foreign rodents. 

No More on Ron Suskind and Paul O'Neill

I have posted a few things about the book, The Price of Loyalty.  I was going to write a grand summary, of sorts, but I have decided not to.  The reason is that so many others are tracking the subject, and this blog is not really about politics.  Except when I can't stop myself. 

See         Ron Suskind's own site
               Brad DeLong's commentary
               Economists for Dean commentary
               American Footprint
               Hullabaloo

There are others, but I think those are the main ones.  Brad DeLong in particular has written quite a lot on the subject, and does a better job than I would.  Hullabaloo comments on things in the O'Neill memos that Suskind has posted on his web site. 

By the way, If you use a blog aggregator like Bloglines, you can search for text that occurs in other people's blogs.  It's pretty useful. 

Strange Way To Run An Ethics Board
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Crotalus horridus, (timber rattlesnake) ventral view

(Link found via Calpundit; other bloggers weigh in at Norwegianity, On the Third Hand, Cyborg Democracy, |span|; conservative blogs are oddly silent on the issue, at least those searchable via RSS feeds.  The apparently nonpartisan blog, The Longevity Meme, also has an article on the subject; also see Gina Smith's BIOTECH, for background.)

Bush Ejects Two From Bioethics Council
Changes Renew Criticism That the President Puts Politics Ahead of Science

By Rick Weiss
Washington
Saturday, February 28, 2004; Page A06

President Bush yesterday dismissed two members of his handpicked Council on Bioethics -- a scientist and a moral philosopher who had been among the more outspoken advocates for research on human embryo cells.  In their places he appointed three new members, including a doctor who has called for more religion in public life, a political scientist who has spoken out precisely against the research that the dismissed members supported, and another who has written about the immorality of abortion and the "threats of biotechnology."

The turnover immediately renewed a recent string of accusations by scientists and others that Bush is increasingly allowing politics to trump science as he seeks advice on ethically contentious issues.  [...] 

One of the dismissed members, Elizabeth Blackburn, is a renowned biologist at the University of California at San Francisco. She said she received a call yesterday morning from someone in the White House personnel office.

"He said the White House had decided to make some changes on the council. He wanted to express his gratitude and said I'd no longer be on the council," Blackburn said.

She said she had no warning and had not heard from the council's director, University of Chicago ethicist Leon Kass. She said she believed she was let go because her political views do not match those of the president and of Kass, with whom she has often been at odds at council meetings.

"I think this is Bush stacking the council with the compliant," Blackburn said. [emphasis mine]

The other dismissed member, William May, an emeritus professor of ethics at Southern Methodist University, is a highly respected scholar whose views on embryo research and other topics had also run counter to those of conservative council members. Efforts to reach him last night were unsuccessful.

Asked why Blackburn and May had been let go, White House spokeswoman Erin Healy said the two members' terms had expired in January, and they were on "holdover status." Asked whether, in fact, all the council members' terms had formally expired in January, she said they had.

Here are the White House's blurbs on Drs. Blackburn and May:

Elizabeth Blackburn, Ph.D.
Council Member

Elizabeth Blackburn, Ph.D., Professor, Department of Biochemistry and Biophysics, University California San Francisco.

Professor Blackburn, a distinguished cell biologist whose research is on telomerase and chromosome telomere structure, holds a number of awards and prizes, including the California Scientist of the Year Award (1999); American Association for Cancer Research-Pezcoller Foundation International Award for Cancer Research (2001); the General Motors Cancer Research Foundation Alfred P. Sloan Award (2001); and the 26th Annual Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research (2003). She is an elected Foreign Associate of the National Academy of Sciences (1993), and was elected as a Member of the Institute of Medicine (2000). Dr. Blackburn is an elected Fellow of the American Academy of Arts and Sciences (1991); the Royal Society of London (1992); the American Academy of Microbiology (1993); and the American Association for the Advancement of Science (2000). She has also served as President of the American Society for Cell Biology (1998).


William May, Ph.D.
Council Member

William F. May, Ph.D. Cary M. Maguire Professor of Ethics Emeritus, Southern Methodist University. Professor May, a distinguished and widely respected medical ethicist, was until last June head of the Maguire Center of Ethics at SMU. He is also a founding fellow of the Hastings Center for Bioethics. His numerous books include Beleaguered Rulers: The Public Obligation of the Professional (2001) and The Physician's Covenant : Images of the Healer in Medical Ethics (1983); and The Patient's Ordeal (1991).

Now, let's think about this for a bit.  The White House spokesperson, Erin Healy, stated the two members' terms had expired in January, and they were on "holdover status."  This is a lie of omission.  She, and by extension, her boss George W. Bush, are lying about the Ethics Board.  Why even bother to have an ethics board?  They hire these folks at taxpayer expense, purportedly to provide counsel on ethics, when in fact that is not their purpose.   Although we can't be certain what the motive was for these two dismissals, Dr. Blackburn's statement, "I think this is Bush stacking the council with the compliant,"  is fairly telling.  Also, there is the timing of the dismissals.  Gina Smith's site refers to the fact that the Council had just released a report on stem cells.  Apparently, the report -- more than 400 pages -- contained no conclusions.  (Your tax dollars at work, again.) Unfortunately, the source (biomedcentral) for Smith's post is a website that is "under construction" at this time.  Google's cached version is available, however.  (Don't you just love Internet technology?)  It includes the following:

[...]council member Robert P. George, director of the James Madison Program in American Ideals and Institutions at Princeton University, labeled the report “descriptive not prescriptive.” He told The Scientist that for now, making recommendations is difficult given the “unbridgeable divisions within the council” with regard to issues such as determining the moral status of the embryo—disagreements, he suggested, that reflect divisions in the public at large.[...] [emphasis mine]

Underscoring the point that the whole exercise was a waste of money, the biomedcentral article includes the following:

Goldstein, who is chair of the Public Policy Committee at the American Society for Cell Biology, also criticized the science section of the report. “The administration has wasted its money by having a duplicate scientific review,” he said, suggesting that NIH and the National Academy of Sciences would have been better qualified to assemble such a synthesis.

This indicates that the report was not really an ethics report.  It was a scientific review.  We already have agencies that do scientific reviews.  The Council for Bioethics is not needed for that purpose.  Although I cannot read minds, and thus cannot be certain of the reason for the two dismissals, there is clear and convincing evidence that the dismissals were politically motivated.  There is Dr. Blackburn's comment ("I think Bush is stacking the Council"), Dr. George's reference to "unbridgeable divisions" within the Council, the timing of the dismissals (right after the stem cell report), and the fact that the report does not end up with any conclusions. I was upset before, when I learned about how the Administration misrepresents science (1 2).  But misrepresenting ethics has got to be worse: lower than a rattler's belly, as they say in Texas.

Crotalus horridus, (timber rattlesnake) ventral view

Yet More on Sleep Problems
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Bad News for the Midnight Blogger
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Good News for Basic Science Research

[left brain stuff:] Following up on my recent articles regarding sleep problems, here are four pieces that illustrate some intriguing links between brain activity, hormones, metabolism, and inflammation.  The findings suggest that sleep deprivation can increase insulin resistance, reduce plasma leptin concentrations, and increase the concentration of pro-inflammatory chemicals (cytokines) in the bloodstream.  If you aren't up to date on physiology, take my word for it.  All of these things are bad.  The Science News article refers to studies that link sleep apnea to increased cytokines.  The Lentz 1999 article in the Journal of Rheumatology shows that sleep deprivation (without sleep apnea) can increase C-reative protein, a cytokine associated with cardiovascular disease.   The following information is pretty technical.  Some persons might prefer to skim down to the bottom to see what to make of all this.

Week of Sept. 7, 2002; Vol. 162, No. 10 , p. 152

Missed ZZZ's, More Disease? Skimping on sleep may be bad for your health Kristin Cobb As bleary-eyed college students in exam week will attest, lack of sleep impairs mood, performance, and judgment. They might guess, however, that the fast food and candy gobbled down during an all-nighter are far worse for bodily health than are the lost hours of slumber. After all, scientists have long been preaching that too many Big Macs and too few workouts are bad for you, but they have yet to demonstrate any definitive health costs of chronic sleep loss. PERCHANCE TO SLEEP Loughborough Sleep Research Centre, UK Bolstered by new evidence, however, some scientists are suggesting that poor sleep habits are as important as poor nutrition and physical inactivity in the development of chronic illness. They say that this country's sleep debt may be contributing to its current epidemics of obesity, diabetes, and cardiovascular disease. People in the United States sleep an average of 7.0 hours on weeknights, 1.5 hour less than they did a century ago, according to the National Sleep Foundation in Washington, D.C. One-third of the population sleeps 6.5 or fewer hours, far less than the 8 hours that many sleep specialists recommend. Several recent studies report that reducing sleep to 6.5 or fewer hours for successive nights causes potentially harmful metabolic, hormonal, and immune changes, at least in test volunteers in the sleep lab. "All of the changes are what you find in normal aging," says sleep researcher Eve Van Cauter of the University of Chicago.   [...]Van Cauter and her colleagues helped launch the field with a surprising 1999 study that showed that sleep deficits of several hours a night can impair the body's processing of the sugar glucose. The study reported that 11 healthy, lean young men showed signs of insulin resistance after several nights of sleep restriction. Insulin resistance, a condition in which the body handles glucose poorly because cells respond inefficiently to insulin, is a precursor to type II diabetes. [...]Men who were held to 4 hours a night had markedly reduced 24-hour leptin concentrations compared with when they were fully rested, Van Cauter's research team reported at the 2001 Association of Professional Sleep Societies meeting in Chicago. Leptin is a hormone that signals satiety and regulates energy balance; mice that lack leptin overeat and become morbidly obese. [...] Inflammatory ideas: Modest sleep deprivation may also be associated with low-grade inflammation, which can lead to a host of cardiovascular problems, according to Alexandros N. Vgontzas of the Pennsylvania State University College of Medicine in Hershey. [...]After a week of sleeping 6 hours per night, the test volunteers had higher blood concentrations of the cytokine IL-6, than they did in their pre-deprivation state. [...]Unremitting low-grade inflammation can damage the inner walls of the arteries, which sometimes leads to vessel narrowing, high blood pressure, stroke, and heart disease. Also, cytokines have been associated with insulin resistance, diabetes, and obesity. Cytokines cause fatigue. By overproducing cytokines, a person's body is probably trying to say, "Go to sleep," Vgontzas says. [...] Several recent studies have linked sleep apnea to elevated blood concentrations of IL-6, TNF-a, and C-reactive protein and to high blood pressure, cardiovascular problems, and stroke.[...]

(The following abstracts can be found on Medscape Medline)

Effect of sleep loss on C-Reactive protein, an inflammatory marker of cardiovascular risk
J Am Coll Cardiol 2004 Feb 18;43(4):678-83     (ISSN: 0735-1097)
Meier-Ewert HK; Ridker PM; Rifai N; Regan MM; Price NJ; Dinges DF; Mullington JM
Department of Cardiology, Lahey Clinic Medical Center, Burlington, and Tufts University Medical School, Boston, Massachusetts, USA.

OBJECTIVES: We sought to investigate the effects of sleep loss on high-sensitivity C-reactive protein (CRP) levels. BACKGROUND: Concentrations of high-sensitivity CRP are predictive of future cardiovascular morbidity. In epidemiologic studies, short sleep duration and sleep complaints have also been associated with increased cardiovascular morbidity. Two studies were undertaken to examine the effect of acute total and short-term partial sleep deprivation on concentrations of high-sensitivity CRP in healthy human subjects.

METHODS: In Experiment 1, 10 healthy adult subjects stayed awake for 88 continuous hours. Samples of high-sensitivity CRP were collected every 90 min for 5 consecutive days, encompassing the vigil. In Experiment 2, 10 subjects were randomly assigned to either 8.2 h (control) or 4.2 h (partial sleep deprivation) of nighttime sleep for 10 consecutive days. Hourly samples of high-sensitivity CRP were taken during a baseline night and on day 10 of the study protocol.

RESULTS: The CRP concentrations increased during both total and partial sleep deprivation conditions, but remained stable in the control condition. Systolic blood pressure increased across deprivation in Experiment 1, and heart rate increased in Experiment 2.

CONCLUSIONS: Both acute total and short-term partial sleep deprivation resulted in elevated high-sensitivity CRP concentrations, a stable marker of inflammation that has been shown to be predictive of cardiovascular morbidity. We propose that sleep loss may be one of the ways that inflammatory processes are activated and contribute to the association of sleep complaints, short sleep duration, and cardiovascular morbidity observed in epidemiologic surveys.

Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women.
J Rheumatol 1999 Jul;26(7):1586-92    (ISSN: 0315-162X)
Lentz MJ; Landis CA; Rothermel J; Shaver JL
Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle 98195-7266, USA.

OBJECTIVE: To determine whether disrupted slow wave sleep (SWS) would evoke musculoskeletal pain, fatigue, and an alpha electroencephalograph (EEG) sleep pattern. We selectively deprived 12 healthy, middle aged, sedentary women without muscle discomfort of SWS for 3 consecutive nights. Effects were assessed for the following measures: polysomnographic sleep, musculoskeletal tender point pain threshold, skinfold tenderness, reactive hyperemia (inflammatory flare response), somatic symptoms, and mood state.

METHODS: Sleep was recorded and scored using standard methods. On selective SWS deprivation (SWSD) nights, when delta waves (indicative of SWS) were detected on EEG, a computer generated tone (maximum 85 decibels) was delivered until delta waves disappeared. Musculoskeletal tender points were measured by dolorimetry; skinfold tenderness was assessed by skin roll procedure; and reactive hyperemia was assessed with a cotton swab test. Subjects completed questionnaires on bodily feelings, symptoms, and mood.

RESULTS: On each SWSD night, SWS was decreased significantly with minimal alterations in total sleep time, sleep efficiency, and other sleep stages. Subjects showed a 24% decrease in musculoskeletal pain threshold after the third SWSD night. They also reported increased discomfort, tiredness, fatigue, and reduced vigor. The flare response (area of vasodilatation) in skin was greater than baseline after the first, and again, after the third SWSD night. However, the automated program for SWSD did not evoke an alpha EEG sleep pattern.

CONCLUSION: Disrupting SWS, without reducing total sleep or sleep efficiency, for several consecutive nights is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. These results suggest that disrupted sleep is probably an important factor in the pathophysiology of symptoms in fibromyalgia.

The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia.
J Rheumatol 2003 May;30(5):1070-4    (ISSN: 0315-162X)
Scharf MB; Baumann M; Berkowitz DV
Tri-State Sleep Disorders Center, Cincinnati, Ohio 45246, USA.
OBJECTIVE: Fibromyalgia (FM) is associated with the sleep phenomenon of alpha intrusion, and with low growth hormone secretion. Sodium oxybate has been shown to increase both slow-wave sleep and growth hormone levels. This double blind, randomized, placebo controlled crossover trial was conducted to evaluate the effects of sodium oxybate on the subjective symptoms of pain, fatigue, and sleep quality and the objective polysomnographic (PSG) sleep variables of alpha intrusion, slow-wave (stage 3/4) sleep, and sleep efficiency in patients with FM.

METHODS: Patients received either 6.0 g/day sodium oxybate or placebo for 1 month, with an intervening 2 week washout period. Efficacy measures included PSG evaluations, tender point index (TPI), and subjective measurements from daily diary entries. Safety measures included clinical laboratory values, vital signs, and adverse events.

RESULTS: Twenty-four female patients were included in the study; 18 completed the trial. TPI was decreased from baseline by 8.5, compared with an increase of 0.4 for placebo (p = 0.0079). Six of the 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to 10% relief with placebo (p < 0.005). Alpha intrusion, sleep latency, and rapid-eye-movement sleep were significantly decreased, while slow-wave (stage 3/4) sleep was significantly increased, compared with placebo (p < 0.005). Two of the 5 subjective sleep related variables were significantly different from placebo: morning alertness (improved by 18% with sodium oxybate, compared with 2% for placebo; p = 0.0033) and quality of sleep (improved by 33% and 10%, respectively; p = 0.0003).

CONCLUSION: Sodium oxybate effectively reduced the symptoms of pain and fatigue in patients with FM, and dramatically reduced the sleep abnormalities (alpha intrusion and decreased slow-wave sleep) associated with the nonrestorative sleep characteristic of this disorder.

[right brain stuff] The information summarized above shows that sleep deprivation, regardless of cause, has multiple adverse effects on the human body.  There is plenty of animal evidence also, but I thought I would spare you from the rat facts.  Aside from the obvious -- that people need their sleep -- what can we learn from this?  One thing is illustrated nicely by the last abstract.  This shows how observations from basic science (preclinical studies) can lead to the formulation of an hypothesis regarding a potential treatment.  Since there was evidence that decreased slow-wave sleep can contribute to some of the chemical changes observed in patients with fibromyalgia, it seemed reasonable to speculate that increasing slow-wave sleep might be therapeutic.  There are not very many drugs that do this.  Most sleeping pills, as well as alcohol, increase stage 1 and 2 sleep, but decrease stages 3 and 4 (slow wave) sleep.  Sodium oxybate  (Xyrem) is the most efficacious drug that increases SWS.  Don't rush out to get this; Xyrem is the pharmaceutical form of GHB, also known as the date rape drug.  Doctors and patients have to enter a special registry to prescribe and use it.  It can be given only to persons with cataplexy caused by narcolepsy.  (Note that it was produced under the orphan drug program, which was the subject of my 2/23/2004  post)

It is common for scientists to face criticism for doing basic science research, when it is not obvious at the front end how there will be any practical use for it.  But fibromyalgia is a common problem.  Finding a good treatment would create significant economic benefit for everyone.  Xyrem probably will not become a standard treatment, because of the serious problems that would result from drug diversion.  But there are some other drugs that could be helpful as well.  Both olanzapine (Zyprexa) and tiagabine (Gabitril) have been shown to increase SWS.  There was one study that showed improvement in fibromyalgia with olanzapine (Kiser et. al., J Pain Symptom Manage 2001 Aug;22(2):704-8); although they did not assess sleep architecture in that study, I would bet that if they had, it would have shown a correlation between increased SWS and pain relief.  Other studies have shown that tiagabine can be useful in treatment of pain, but I could not find one that studied fibromyalgia pain specifically. 

Getting back to the economic benefit from basic research, look at the following abstract:

Economic cost and epidemiological characteristics of patients with fibromyalgia claims.
J Rheumatol 2003 Jun;30(6):1318-25    (ISSN: 0315-162X)
Robinson RL; Birnbaum HG; Morley MA; Sisitsky T; Greenberg PE; Claxton AJ
Eli Lilly and Company, Indianapolis, Indiana 46285, USA. rlrobinson@lilly.com.

OBJECTIVE: Fibromyalgia (FM) is characterized by widespread pain that can lead to significant patient disability, complex management decisions for physicians, and economic burden on society. We investigated the total costs of FM in an employer population.

METHODS: Administrative claims data of a Fortune 100 manufacturer were used to quantify direct (i.e., medical and pharmaceutical claims) and indirect (i.e., disability claims and imputed absenteeism) costs associated with FM. A total of 4699 patients with at least one FM claim between 1996 and 1998 were contrasted with a 10% random sample of the overall beneficiary population. Employee-only subsets of both samples also were drawn.

RESULTS: Medical utilization, receipt of prescription drugs, and annual total costs were proportionately similar yet significantly greater among FM claimants than the overall sample (all p < 0.0001). Total annual costs for FM claimants were $5945 versus $2486 for the typical beneficiary (p < 0.0001). Six percent of these costs were attributable to FM-specific claims. The prevalence of disability was twice as high among FM employees than overall employees (p < 0.0001). For every dollar spent on FM-specific claims, the employer spent another $57 to $143 on additional direct and indirect costs.

CONCLUSION: Hidden costs of disability and comorbidities greatly increase the true burden of FM. Regardless of the clinical understanding of FM, when a claim for FM is present, considerable costs are involved. Findings suggest that within the management of FM there may be large cost-offset opportunities for reductions in patient, physician, and employer burdens.

I couldn't find an article that shows what I really want, which is the total cost to society imposed by the decreased productivity and the treatment costs associated with fibromyalgia.  But the study noted above indicates that the cost is large, and that treatment might be worthwhile from a pure economic standpoint (not to mention the humanitarian standpoint).  I can't advance this claim too strongly, on the basis of the one study; it was funded by Eli Lily, the makers of olanzapine; Zyprexa costs $307.99 for thirty 10mg tablets, at CVS online.   Still, the point that there are potentially huge economic benefits from basic science research, is  valid. 

More on Sleep Disorders
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No Medical Condition is Simple
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Flexible Thinking in Medical Treatment

[left brain stuff:] A while back (February 4, 2004) I blogged about a report on a study of obstructive sleep apnea.  The study showed that there are abnormalities in brain waves of patients with sleep apnea who are asleep -- even when they are not actually having apnea.  The study is important because it illustrates that obstructive sleep apnea is more complex than originally thought.  Now we see a report that shows a link between a different sleep disorder -- restless legs syndrome -- and mood and anxiety symptoms. 

Anxiety and Depression Common Among Patients With Restless Legs Syndrome

(from Medscape; free registration required)

NEW YORK (Reuters Health) Feb 25 - Patients with restless legs syndrome exhibit relatively high levels of anxiety and depression, according to a report in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

"Restless legs syndrome (RLS) is an important and common cause of insomnia, and previous studies indicate that psychiatric well-being may be impaired among RLS patients," Dr. Serhan Sevim and colleagues from Mersin University, in Turkey, write. In a population-based survey, they examined the association between anxiety/depression and RLS.

The researchers obtained data on 3234 subjects enrolled in the Mersin University Neuro-Epidemiology Project. A total of 103 subjects had RLS, and were assessed for symptoms of anxiety and depression using the Hamilton Anxiety and Depression Scales. These patients were compared with 103 contemporaneous controls.

Compared with controls, RLS patients had significantly greater anxiety and depression symptoms. The mean Hamilton anxiety score was 8.03 in the RLS patients compared with 5.91 in the controls; the mean depression scores were 9.27 vs 5.88, respectively.

A correlation was observed between the severity of RLS and of anxiety and depression symptoms, researchers report.

"We conclude that assessment of psychiatric status of RLS patients can be helpful and sometimes necessary to determine additional features and treatment strategies of this troublesome condition," Dr. Sevim and colleagues note.

They add that a longitudinal assessment would be necessary to establish temporality; ie, to determine whether anxiety or depression are a consequence of RLS.

J Neurol Neurosurg Psychiatry 2004;75:226-230.

[right brain stuff:] In my view, the key phrase in this report is: "We conclude that assessment of psychiatric status of RLS patients can be helpful and sometimes necessary to determine additional features and treatment strategies of this troublesome condition," Dr. Sevim and colleagues note.  In a way, this is a cautionary tale.  It is very easy for a physician to assess and treat the main complaint of the patient, and ignore everything else.  The take-home message here is that is is essential to assess the overall level of function of the patient after the treatment has been instituted.  If a patient has depression and RLS, and you treat the RLS only, you may think you have done a great service; but in actuality, the patient still is not going to do well. 

In the case of comorbid RLS and depression, there is another risk.  If the patient presents with a chief complaint of depression, and you treat the depression but not the RLS, you actually could make the patient worse.  The reason is that most antidepressants can increase the severity of RLS.  This may be due to the fact that serotonergic drugs can decrease dopamine synthesis (Baldessarini RJ, Marsh E (1990), Fluoxetine and side effects. Arch Gen Psychiatry 47(2):191-192 [letter]).  See this  Psychiatric Times article for an overview of the relationship between antidepressants and movement disorders. 

On a more abstract level, this illustrates the problems that can arise when a strictly linear problem-solving approach is employed in medical practice.  The usual heuristic  of symptoms --> diagnosis --> treatment  is overly simplistic.  It is more appropriate to uses a looping strategy in which the treatment is followed by reassessment, then revision of diagnosis and/or treatment if the results are not satisfactory.  The reassessment step sometimes requires flexible thinking, as it is essential to avoid the trap of reassessing only the original chief complaint. 

Sometimes, the symptoms --> diagnosis --> treatment  process is complicated by the fact that there is more that one possible diagnosis. In that case, it is important to consider the diagnostic possibilities and see if there are two (or more) possible diagnoses can be treated in the same way.  When that turns out to be the case, it may be appropriate to institute treatment that will cover the set of possible diagnoses that all have a common treatment

For example, on the surface it appears that it should be easy to distinguish a patient with RLS from one with depression, but for various reasons, this is not always the case.  If you cannot tell whether the patient has depression, RLS, or both, it could be that the most reasonable course of action would be to give the patient a dopaminergic antidepressant.  This could result in significant clinical improvement regardless of the diagnosis.  Such a strategy could be viewed as shortcut, a way to institute treatment without going through all the steps that would be required to establish a firm diagnosis.  If a shortcut is used, though, it is even more important to examine carefully the outcome of the treatment and revise your interventions if necessary. 

For an good brief review of RLS, see this  Journal of Postgraduate Medicine article.  A more thorough review can be found here, at eMedicine.

On the Wisdom of Self-Medication

Note to the person who found this blog by running a Google search with the phrase "is self medicating for tapeworms a good idea?"  The answer is: No.  It is not a good idea to self-medicate for tapeworms. 

The American Madrasas
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A New Form of Human Cloning

A post on Pharyngula (PZ Myers) caught my attention.  Other blogs have posted agreement (1 2 3 4), and dissenting opinions (1 2 3), but Myers' post is the most thoughtful:

Here's an idea: let's model our educational system after the madrasas!

Hmmm. Rod Paige  calls the largest teachers' union in the United States a "terrorist organization". His backhanded apology consists of this: "It was an inappropriate choice of words to describe the obstructionist scare tactics the NEA's Washington lobbyists have employed against No Child Left Behind's historic education reforms."

Earlier he says, "The reason that Christian schools and Christian universities are growing is a result of a strong value system...That's not the case in a public school, where there are so many different kids with different kinds of values...All things equal, I would prefer to have a child in a school that has a strong appreciation for the values of the Christian community, where a child is taught to have a strong faith."

Somehow, I get the feeling that this man is not on my side. Or on the side of any educators, unless they happen to be Christian, Republican, non-union, teaching in a private, Christian school, and obligingly uncritical of education policies. I wonder if we'll continue to get complaints about too many teachers voting Democratic.

How did such a sycophantic, divisive hack get to be Secretary of Education? Oh, yeah...that's the kind of person our president favors.

In response, I posted this comment:

At first, I was going to take offense at the use of the “madrasa” analogy.  After all, comparing the current education policy to the kind of institution that gives rise to terrorists is a bit like calling the NEA terrorists.  On further reflection, though, I agree that the analogy is appropriate.  A madrasa is a school wherein all teaching is grounded in a fundamentalist ideology.  No doubt some of them are intellectually honest institutions of learning; but some of them, at least as portrayed in Western media, are devoted to the strict delivery of only one intellectual viewpoint. 

One of my objections to the emphasis on standardized testing, and the linkage of school funding to testing outcomes, is that it forces teachers to focus most of their attention on lesson plans that boost test scores.  If the financial stakes are high enough, this emphasis on test scores inevitably will lead to compromises in education.  Critical thinking, creative lesson planning, and individualized education all must take a back seat to the business of rote memorization.  This very well could lead to a generation of students who can recite the capitols of all fifty states, but who cannot recognize an ad hominem argument, or who cannot tell when a politician is being dishonest, or who cannot watch a television advertisement and see how the sponsor is trying to influence their behavior. 

There really is something madrasa-like about that kind of education.  If it is effective enough, there may be no need for human cloning.  We all will think exactly alike.

I would like to elaborate: I have seen a lot of education, after spending twenty-five years as a student: in Catholic school, a private secular school, various public schools (in two different school systems), college, medical school, and residency.  In college, I tutored Chemistry.  I also have taught at the University of Michigan Medical School, and have worked in two different college counseling services.  I have a son who has attended three Montessori schools (one Christian, two secular), a private middle school, and a public high school.  I observed special education teachers in the classroom, when I was a psychiatry resident.  My mother is has a teaching certificate, and is a private tutor for special education students and a tutor at a Community College.  My wife was a tutor and a peer educator when she was in college.  On the basis of these experiences, I have become convinced that the most effective teaching style always includes a personal relationship between student and teacher.  This is directly analogous to the psychotherapeutic concept of the therapeutic alliance¹.  I don't think it matters much if a teacher teaches new math, old math, or Babylonian math.  If the teacher and student join together toward a common goal, true learning will take place.  If the teacher is allowed to develop a lesson plan that fits her or his own style, and reflects her or his own interests, the students will pay attention.  They pay attention because kids instinctively recognize genuine caring and effort.  Furthermore, it is neither realistic nor helpful to establish a fixed curriculum.  What is relevant for students this year will be obsolete next year.  What is relevant in a rural school may be irrelevant in a suburban school.  For a teacher in a rural school, it might make sense to teach Chemistry using fertilizer to illustrate acid-base chemistry.  Try that in a suburban school, and students will spend the hour sending instant messages to each other on their wireless-enabled Palm Pilots.   (Did you hear what Hillary said to Heather...) 

One of the reasons that the Government has taken responsibility for public education is that a well-educated public can make better decisions about how they want to govern themselves, and how they want to be governed by others.  Although the concept of checks and balances originally was meant to describe the relationships between the three branches of government, it is equally valid to think of checks and balances between the citizens and their elected officials.  This will not work if the citizens cannot think independently.  Standardized testing has only a limited role in this process.  Therefore, the No Child Left Behind initiative does not really contribute much to one of the main goals of education.  Likewise, our current Secretary of Education does not contribute much to one of the main goals of education.

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¹(link) [...] Studies have considered the relationship between therapy approaches, therapeutic alliance and successful treatment outcome. Frank & Gunderson (1990) found no significant difference between two types of psychotherapy in relation to outcome, but did find a strong relationship between therapeutic alliance and outcome.
[...]
In a meta-analysis of 24 studies, Horvath and Symonds (1991) found a correlation between therapeutic alliance and outcome across all types of measure of outcome, which was not a function of the type of therapy practiced. [...]

PREVENTING MEDICAL ERRORS:

Prescription for health: Taking control of care

I saw an article in the Freep this morning, while drinking coffee at Panera, on Eisenhower Parkway, where Lone Star used to be, in Ann Arbor.  The newpaper article is about medical errors.  I encourage everyone to read it, especially if they are having problems with the health care system.  It contains many tips such as:

• Are you sure doctors are operating on the correct site? Ask your operating team to mark the area before they render you unconscious. Many hospitals now require teams to mark the correct site with an X.

There are a few things I would like to add.  Always read the label on the bottle when you pick up prescriptions.  If you have a family member in the hospital, visit often, say hello to the nurses and other staff, and leave flowers, pictures, etc. in the patient's room.  It is much harder for the staff to depersonalize a patient if there are fresh reminders every day of the patient's status as a real person. 

Sometimes the simplest things can make the biggest difference. Sometimes only you can prevent ...

Arrgh.  Yet another Internet Quiz!

You're The Hobbit!
by J.R.R. Tolkien
All you wanted was a nice cup of tea when some haggard crazy old man came into your life and told you it was time to do something with yourself. Now you're all conflicted about whether to stick with your stay-at-home lifestyle or follow this crazy person into the wild. While you're very short and a little furry, you seem to be surrounded by an even greater quantity of short folks lately. Try not to lose your ring, but keep its value in perspective!
Take the Book Quiz at the Blue Pyramid.

Thanks to Allison at Hartsongs, who cites Pax Nortona

Pharmaceutical Development
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An Immodest Proposal for Bigger Government

Last week's New Yorker Magazine did not escape the attention of the blogosphere.  The attention all went to Jane Meyar's article of Dick Cheney and Halliburton.  I even chimed in on the topic, at the risk of being just another faint voice crying out in the distance.  I would like to point out that the same issue of New Yorker that carried the Meyar article also had an article by James Surowiecki: The Pipeline Problem.  The article addresses one of the more pressing domestic issues in the USA during this early part of the 21st century; that of new drug development. Most of the attention is focused on the cost of new medications, the implications for Medicaid and Medicare funding, and the impact on health insurance premiums.  Looking beyond the economic issues, one realizes that patient care is what the industry provides.  That is what we pay them to help us with.  The first paragraph of Surowiecki's article is intended to develop the setting for his main argument, that we are in the midst of a major restructuring of the pharmaceutical industry:

Merck is one of history's most innovative corporations. It devotes three billion dollars a year and ten thousand people to the research and development of new drugs. So here's a question: How many drugs for diabetes do you think all these men and women, this army of scientists, managed to come up with in the past four years? None. How many anti-cancer drugs? Zero. How many drugs that fight infectious diseases? Zero. Since 2000, in fact, Merck has introduced just three new drugs. Drug development is hard, but, by any measure, eking out less than one product a year is no way to make a living in the major leagues.

The case Surowiecki develops is that big companies have difficulty with innovation.  Thus, the main function of the big companies is to watch the little guys until they come up with something promising, then buy them out.  The little guys seem to be good at innovation, but they have neither the funding nor the capabilities to deal with the FDA that are needed to bring a product to market.  Surowiecki likens this to the movie industry picking the plums from the small independent studios:

So maybe it's time to move on. Peering into the future, one can see the faint outlines of a pharmaceutical industry that looks a bit like the movie business, with big pharmaceutical “studios” marketing, distributing, and perhaps even underwriting the costs of smaller drug “producers.” The only difference is that the drug studios might actually make money.

It turns out, though, that the issue is more complicated.  We all know that the major studios are notorious for passing over many good films, looking for the few that have the potential to be box office supernovae.  We all decry the loss of films with artistic merit.  But we don't get too upset; after all, there are venues for independent producers.  Technological innovations, and the profusion of distribution media, allow for some of the little-known artistic films to get out to an audience that is willing to do a little work to find them.  Not so the drug industry. 

If a small lab comes up with a promising drug, but the bean counters at the big companies do not think it has potential, it is likely to sit on a shelf and be forgotten.  After all, the small company cannot set up a lab in their basement, produce the stuff, and distribute on the Internet.  They can't package it into cassettes and ship them off to the rental stores.  A small film producer can get some digital video equipment and do exactly that, but a pharmaceutical company that tried to do that would run afoul of the FDA, the DEA, the DOJ, etc., and would be shut down in a matter of days by a small army of guys with alphabet soup on their Kevlar vests. 

This is not a diatribe against the FDA.  The FDA gets a lot of flak, on two fronts.  If there is a delay is getting a drug to market, people criticize the FDA for being too restrictive.  If a drug gets to market and there are unanticipated risks, the FDA get criticized for being too lax.  There probably is no way out of this box; there will be problems either way, if they become either more or less restrictive.  The FDA has responded in part by establishing the Office of Orphan Products Development.  This is an effort to help assure that some drugs that are useful, but which might not be profitable enough for the major players to invest in, will have a chance to get to market and actually help people.  They have had some significant successes. 

Proponents of smaller government might argue that the Federal Government has no business getting into the drug industry.  This is a big debate, beyond the scope of this article.  Leaving the debate aside for a moment, I would like to make a pitch for a limited expansion of government.  The OOPD has a limited mandate.  They provide grants  specifically for drugs or medical devices that have an intrinsically small market.  Some diseases are so rare that there never will be very many customers for the treatments specific to those diseases.  However, the orphan drug development process leaves out the drugs that could have a large market, but which are not developed by the big companies because they might not be profitable.  There are many reasons why a drug might not be profitable, and a small market is only one such reason. 

What are some of the other reasons?  Some drugs take so long to develop, that there is only a limited patent life remaining by the time they could be approved for distribution.  If such a drug is in the pipeline, the company might kill it because the limited patent life might not permit a good return on their investment.  Another problem, especially with some of the new biotech products, is that there are so many people involved, each with a patent on some part of the process, that by the time all of the players get their piece of the pie, there isn't much of the pie left for the company to make enough profit.  As a result, there are perfectly good drugs that only get so far in development, before the spreadsheet starts to show a negative number, and the development  funding is pulled. 

It is hard to fault the company for this behavior.  After all, they routinely make decisions involving hundreds of millions of dollars.  They have an obligation to their shareholders.  But I can't help but think about all the human tragedy that could be averted if there were some way to get these products on the shelves.  It is possible that an expansion of the mandate for the OOPD could result in a few of these products being rescued.  Yes, it would mean expanding the FDA, adding more federal employees, and all the burdens associated with bigger government.  But we can't expect private companies to do this.  We could set up a review process to extend patent life on a case-by-case basis.  This would have to be done carefully, because there would be a potential for abuse of the system.  Companies are already drawing well-deserved criticism for legal wrangling to extend patents. 

In my view, the opportunity to help more patients is in itself enough reason to justify an expansion of the OOPD.  There is another argument to be made, though, an argument that might catch the attention of the smaller-government proponents.  In some cases, these new drugs could lower the cost of Medicaid and Medicare.  It would be possible to focus the attention of the OOPD on those medications that could do exactly that.  Thus, it is conceivable that the whole thing could be done at no net cost to the federal government. 
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