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SAN FRANCISCO MEDICINE VOL.81 NO.1 January/February 2008 $5.00


Linked for Life

Health, Human Beings, and the Environment

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CONTENTS January/February 2008 Volume 81, Number 1 Linked for Life: Health, Human Beings, and the Environment FEATURE ARTICLES 9


A New Era for Environmental Health Philip R. Lee, MD; Steve Heilig, MPH; and Michael Lerner, PhD

4 On Your Behalf 5 Classified Ads

10 Toxic Dilemmas Donald Kennedy, PhD 5 Upcoming SFMS Events 11 Toys, Tots, and Toxic Chemicals David Wallinga, MD, MPA 13 Reproductive Health and the Environment Tracey J. Woodruff, MPH, PhD; Jackie M. Schwartz, MPH; Alison Carlson; and Linda C. Giudice, MD, PhD

6 Executive Memo Mary Lou Licwinko, JD, MHSA

17 Early Vulnerability, Lifelong Impacts Philippe A. Grandjean, MD, PhD

7 President’s Message Steven Fugaro, MD

19 Climate Change and Children’s Health Katherine M. Shea, MD, MPH, and Sophie J. Balk, MD

8 Editorial Mike Denney, MD, PhD

22 The Falling Age of Puberty in U.S. Girls Sandra Steingraber, PhD, Jeanne Rizzo, RN

40 Hospital News

24 Cancer and Environmental Chemicals Devra Lee Davis, PhD

41 In Memoriam Nancy Thomson, MD

26 Mercury Tales Jane Hightower, MD 30 Time to Update Environmental Regulations John Peterson Myers, PhD, and Fred S. vom Saal, PhD

42 Guest Column: Small-Town Medicine Alan G. Greenwald, MD Editorial and Advertising Offices

32 Nanoparticles and Health John M. Balbus, MD, MPH

1003 A O’Reilly San Francisco, CA 94129

33 Neurodevelopmental Disorders and Environmental Agents Elise Miller, MEd, and Steve Gilbert, PhD, DABT

Phone: 415.561.0850 ext.261 Fax: 415.561.0833 Email: Web:

34 Biomonitoring Update Davis Baltz, MA


35 Electromagnetic Fields David Carpenter, MD, and Cindy Sage, MA

$45 per year; $5 per issue

35 Chemical Exposures on the Job May Be Linked to Diseases in Nurses Charlotte Brody, RN

website,, or can be sent upon

Advertising information is available on our request. Printing:

36 The War Goes On: Tobacco Control in California Mi-Kyung Hong, MPH; Richard L. Barnes, JD; Stanton Glantz, PhD; and Steve Heilig, MPH

Sundance Press P.O. Box 26605 Tuscon, AZ 85726-6605

37 Agent Orange and Birth Defects Betty Mekdeci 39 Book Review: Exposed Steve Heilig, MPH

January/February 2008 San Francisco Medicine 

January/February 2008 Volume 81, Number 1

ON YOUR BEHALF A sampling of activities and actions of interest to SFMS members

Editor Mike Denney Managing Editor Amanda Denz Copy Editor Mary VanClay

Notes from the Membership Department

Cover Artist Amanda Denz

Upcoming Events Editorial Board Chairman Mike Denney Obituarist Nancy Thomson Stephen Askin

Shieva Khayam-Bashi

Toni Brayer

Arthur Lyons

Linda Hawes-Clever

Terri Pickering

Gordon Fung

Ricki Pollycove

Erica Goode

Kathleen Unger

Gretchen Gooding

Stephen Walsh

2008 membership activities will include a new event at the de Young Museum, the popular Summer Gallery Mixer, the return of the SFMS Night at the San Francisco Symphony, a Holiday Night at the Nutcracker, and much more! Remember—nonmembers are welcome at SFMS membership social/cultural events. This is a great way for them to get to know SFMS and its membership better.

SFMS Officers President Steven H. Fugaro

Attention, Young Physicians!

President-Elect Charles J. Wibbelsman

The San Francisco Medical Society has formed an active and vibrant Young Physicians section to better address the needs and concerns of members aged forty-five and younger. A variety of social and educational gatherings are a featured part of this newest component to SFMS membership. If you are interested in participating, contact Tom Lee, MD, at

Secretary Gary L. Chan Treasurer Michael Rokeach Editor Mike Denney Immediate Past President Stephen E. Follansbee SFMS Executive Staff Executive Director Mary Lou Licwinko Director of Public Health & Education Steve Heilig Director of Administration Posi Lyon Director of Membership Therese Porter

You Can Make SFMS Even Better!

Director of Communications Amanda Denz

Promoting membership just got easier! Did you know that your physician peers can now join the San Francisco Medical Society online? Joining SFMS/CMA is simple—go to and click “Join SFMS” on the top of the home page. It’s quick and easy, and new members get a 50 percent discount on their first year’s dues! Thank you to our members who have already referred their fellow physicians— physicians talking to physicians remains the strongest and best way for the Medical Society to grow its ranks and help shape the future of medicine. SFMS is always looking for feedback from its members, as well as suggestions as to how to make membership more interesting, valuable, and fun. Contact Therese Porter in the Membership Department at (415) 561-0850 extension 269 or tporter@

Board of Directors Term: Jan 2008-Dec 2010

Jordan Shlain

George A. Fouras

Lily M. Tan

Keith E. Loring

Shannon Udovic-

William A. Miller


Jeffrey Newman


Thomas J. Peitz

Jan 2006-Dec 2008

Daniel M. Raybin

Mei-Ling E. Fong

Michael H. Siu

Thomas H. Lee


Carolyn D. Mar

Jan 2007-Dec 2009

Rodman S. Rogers

Brian T. Andrews

John B. Sikorski

Lucy S. Crain

Peter W. Sullivan

Jane M. Hightower

John I. Umekubo

Donald C. Kitt CMA Trustee Robert J. Margolin AMA Representatives H. Hugh Vincent, Delegate Robert J. Margolin, Alternate Delegate

 San Francisco Medicine January/February 2008

Revised ’08 Medicare Physician Fee Schedule Now Available The revised 2008 Medicare physician fee schedule is now available at the NHIC website, In the waning hours of the 2007 legislative session, Congress passed a Medicare bill that postpones the 10 percent physician payment cut and instead provides a 0.5 percent increase for six months. The new fee schedule reflects this small increase. Physicians are encouraged to assess the impact the Medicare payment changes will have on their practices. It is important that physicians understand how the new fee schedule will affect their bottom line so that they can make informed decisions about Medicare participation for 2008. Because Congress acted very late in the session to stop the physician pay cut, the Centers for Medicare and Medicaid Services (CMS) have reopened the participation decision period for an additional 45 days. Physicians have until February 15 to make any changes to their participation status. However, all status changes will be effective January 1, 2008. Physicians are still faced with a 10 percent payment reduction on July 1, 2008, unless Congress revamps the hopelessly broken formula used to calculate physician pay (or acts again with another last-minute fix). With this cut looming, participation decisions become more complicated. While it is possible that CMS will again reopen the participation decision period, there is no guarantee that CMS will allow physicians to change their participation status in July, should the cut go into effect. For more information, contact CMA’s Reimbursement Help Line, (888) 401-5911 or

Volunteer with a Young Apprentice Would you like to share your career with a young person who dreams of working in your field? Spark is looking for volunteers in the Redwood City area this spring. Spark is a nonprofit program that matches

seventh- and eighth-grade students with hands-on apprenticeships in their dream job, where they spend a few hours per week with a local professional. Apprentices and mentors meet for one-and-a-half to twohour sessions over eight weeks (February through May) at the volunteer’s workplace or another public space between San Mateo and Palo Alto. For more information, watch the Spark video at SparkProgram, visit www.sparkprogram. org, or contact Elena Sevastopoulos at or (415) 626-5470 extension 103.

staff; $189 for nonmembers.

The CMA House of Delegates

April 18, 2008 Customer Service/Front Office Telephone Techniques 9:00 a.m. to 12 p.m. (8:40 AM registration/ continental breakfast) This half-day practice management seminar will provide valuable staff training to handle phone calls and scheduling professionally and efficiently. $99 for SFMS/CMA members and their staff ($89 each for additional attendees from the same office); $149 each for nonmembers.

Hugh Vincent, MD, and George Susens, MD (in background), SFMS delegates

2008 SFMS Seminar Schedule

May 16, 2008 Managing the Team (for office managers and administrators) 9:00 a.m. to 12:00 p.m. (8:40 a.m. registration and continental breakfast) Motivating and Managing Your Office Manager (for physicians) 12:15 to 1:45 p.m. (12:00 p.m. registration and lunch) These two seminars are designed to help physicians and their office managers set expectations, manage change, and design a practice culture that helps the practice thrive. $99 for Managing the Team for SFMS/CMA members and their staff ($85 each for additional attendees from same office); $149 each for nonmembers. $69 for Motivating and Managing Your Office Manager for SFMS/CMA members ($59 each for additional attendees from same office); $109 for nonmembers. $150 for both sessions for members; $225 for nonmembers.

Advanced registration is required for all SFMS seminars. Please contact Posi Lyon, or (415) 561-0850 extension 260, for more information. All seminars take place at the SFMS offices located in the Presidio of San Francisco. February 15, 2008 Repair Leaks and Boost Practice Profits in 2008: Billing, Coding, and Collection Strategies 9:00 a.m. to 4:00 p.m. (8:40 a.m., registration and continental breakfast) Devise strategies for repairing operational leaks that cause profit losses in your practice. A full day packed with the latest updates on new diagnosis and CPT codes; new Medicare requirements, the Office Inspector General (OIG) work plan for 2008, and successful Denial and Appeal Management Strategies. $199 per session for SFMS/CMA members and their staff ($185 each for additional attendees from same office); $250 each for nonmembers. March 24, 2008 Transitioning Your Practice: Retiring, Selling, or Buying a Practice 6:00 to 9:00 p.m. (5:45 p.m. dinner/registration) This is a not-to-be-missed seminar designed for all physicians who are contemplating retirement, bringing in an associate, joining a practice as an associate, relocating, buying or selling a practice, or changing careers. $139 for SFMS/CMA members and their

Dexter Louie, MD, SFMS Delegate

Stephen Follansbee, MD, SFMS ImmediatePast President, at the reference committee

Classified Ads BC FP, CA MD is looking for a job in the Bay Area— Stonestown Medical Building offers various sized medical suits for lease in upper floors and on ground floor. Contact Trask Leonard at (650) 282-4620 or Brian Lewis, MD, Chair of SFMS Delegation January/February 2008 San Francisco Medicine 

Executive memo Mary Lou Licwinko, JD, MHSA

Looking Backward and Forward


t is has been two years since the San Francisco Medical Society (SMFS) sold its Sutter Street mansion headquarters and moved its operation to the Presidio. At the time of the move from a building SFMS owned to a property it would rent, there was speculation about what this would mean for SFMS and its members. The past two years have proved to be particularly successful for SFMS in terms of membership growth, financial stability, and momentum building. SFMS has realized an increase in membership of a magnitude that it has not seen in many years, and this year’s membership numbers are looking even better. SFMS’s financial position is strong, and the organization is poised for another successful year. The year 2006 was an extraordinary one for SFMS. Led by then President Dr. Gordon Fung, SFMS moved to its new headquarters in the Presidio, restructured its financing, and stabilized staffing. Dr. Fung’s efforts were followed by those of 2007 SFMS President Dr. Steve Follansbee. Under Dr. Follansbee’s leadership, SFMS refocused its mission, made membership a priority, and seized the opportunity to reenergize. During Dr. Follansbee’s tenure, after being challenged by the California Medical Association (CMA) Executive Vice President Joe Dunne to get involved in the health care reform process, SFMS developed its own health care reform proposal, submitted it to the CMA, and published it in the July/ August 2007 issue of San Francisco Medicine. SFMS also held a successful event with Mayor Gavin Newsom, advocating for health care reform in San Francisco and stressing the need to attract more young physicians to the City. Also in 2007, SFMS experienced a 30 percent increase in new members and a feeling of new energy for the Society. SFMS 2008 President Dr. Steve Fugaro has already prioritized increasing both the membership and member activism, not only on behalf of all San Francisco physicians but on behalf of the community as well. In recognition of changes in the practice of medicine and the decreasing supply of primary care physicians in the Bay Area, last year Dr. Robert Margolin led efforts that resulted in a forum on the foundation and other models for delivering health care. Twenty-five physicians from around the Bay Area attended the event and discussed various models for delivering primary health care and changes in the practice of medicine, fueled in part by a new generation of physicians. The forum was so successful that this  San Francisco Medicine January/February 2008

year SFMS plans to expand it to a larger audience. San Francisco Medicine, the SFMS journal published ten times a year, also reached new heights in 2007. Under the leadership of the editor, Dr. Mike Denney, the journal tackled disaster preparedness and produced a comprehensive guide for physicians in the community. It also covered such weighty topics as money and medicine, the healing power of love, medicine in the time of war, innovations in food and health, and what it means to be a “compleat” physician. SFM once again showed why it is considered one of the premier county medical journals in the country. In terms of public health and educational programs, in 2007 SFMS cosponsored an international conference that examined the effects of the environment on fertility. More than 400 individuals from around world attended the conference. SFMS also cosponsored, with the Sutter Health Institute, a palliative care workshop on the state of the art of end-of-life care. In preparation for a 2008 program for San Francisco high school students, SFMS also spearheaded an effort to show the HBO series of short films entitled Addiction and to conduct an educational forum on the topic of addiction with the National Institute on Drug Abuse, the California Society of Addiction Medicine, and UCSF. The success of SFMS over the past two years has been due to the tremendous work of our leaders, including the SFMS Board of Directors and our community liaisons, all of whom I cannot thank enough for the time they volunteer. In addition, SFMS has been fortunate to have a topflight staff to handle all the day-to-day activities of the Society and make the operation look effortless. My thanks to my own great staff as well. I have just begun my tenth year as Executive Director of SFMS, and it is shaping up to be the best year yet.

The editors of San Francisco Medicine would like to extend a special thanks to Steve Heilig for his help assembling this issue!

president’s Message Steven Fugaro, MD

The Year of Membership


his is my first message as your SFMS President, but it is—remarkably—the fifth issue that San Francisco Medicine has devoted to the theme of environmental health. Steve Heilig and the Collaborative on Health and the Environment (CHE), along with the editorial staff of San Francisco Medicine, have drawn together an extraordinary collection of contributors and a comprehensive set of articles describing the current status of environmental scientific knowledge and human health. The authors include several nationally known scientists and clinicians, such as Donald Kennedy, PhD, who is the outgoing editor of Science. This issue also highlights a number of clinicians and scientists who have a very significant national and international impact on issues of environmental health. Among these San Francisco authors are local internist Dr. Jane Hightower, who provides an update on her pioneering work on mercury in our diet; Dr. Stanton Glantz, a UCSF professor, who reports on his latest efforts in the ongoing battle against the tobacco epidemic; and Dr. Philip Lee, emeritus professor at UCSF and former U.S. Secretary of Health, who editorializes about developing a chemicals policy for California and the United States. In fact, the CMA has recently adopted an SFMS-sponsored resolution calling for a comprehensive state and national chemicals policy incorporating current scientific knowledge to evaluate the health impact of new and existing industrial chemicals. SFMS is extremely proud to be involved in this effort to further our knowledge and awareness of environmental health. It is of course completely consistent with our mission—to advance the health of our patients and community while serving the needs of all San Francisco physicians. This focus on environmental health policy is but one example of the many ways that SFMS works to advance the health of our community. Other instances include the involvement of Steve Heilig and former SFMS President Dr. Gordon Fung with projects including the Mayor’s Universal Health Care Council and the proposed citywide Health Access Plan; a recent SFMS Board discussion on supporting a City of San Francisco plan to require cleaner-burning biodiesel in all construction equipment (to reduce air pollution and thus aid our asthmatic population); a planned citywide Town Hall Forum on addiction education for San Francisco youth; and the involvement of SFMS

and CMA in the ongoing efforts to reform health care in California and create statewide universal coverage. There are numerous other examples of SFMS involvement, but all illustrate a critical point: SFMS is committed to its goals of improving access to health care for our community, of serving as a leader in resolving health care issues, and of being an effective advocate in influencing decisions concerning health care policy. These goals can only be achieved by making yet another goal a priority: that SFMS membership will include the entire San Francisco medical community. We will only be effective if we are seen to represent the majority of San Francisco physicians, whether in private practice, at Kaiser Permanente, at UCSF, or in other types of practice. I have been impressed in my years on the Board that we truly have a “big tent,” in that physicians of all political persuasions, in all practice situations, and with varied opinions on many health care issues can all work together toward yet another SFMS goal—to be an effective advocate for all of our members. In order to further our goals as stated above, we must increase our membership and the overall proportion of San Francisco physicians who are members. Currently we have approximately 900 members, who represent about 30 percent of the physicians practicing in San Francisco. Clearly we can do better. To accomplish this, I am proposing that 2008 be a Year of Membership, during which we work to actively create a “culture of membership” and increased physician participation in SFMS. If each SFMS member could simply recruit one additional physician, we would have a membership of more than 1,800 doctors, representing the majority of physicians practicing in San Francisco. Joining the SFMS is remarkably easy. Prospective members can go to and click “Join SFMS” on the top of the home page. New members get a 50 percent discount on their first year’s dues. Even better, some medical groups, including Kaiser Permanente, have a policy of paying the entire annual dues for any of their physicians who elect to join SFMS. By increasing physician participation in the Medical Society, we can clearly enhance the effectiveness of our numerous initiatives and further our overall mission. The end result will be a better environment for all of us at the Medical Society, and certainly a greater opportunity to move toward a new era for environmental health. January/February 2008 San Francisco Medicine 

Editorial Mike Denney, MD, PhD

At the Edge of Chaos


haos theory refers to the unpredictable behavior of energy and matter within highly complex systems, such as the weather, the formation of waves at seashores, and traffic patterns on freeways. It is of interest to scientists in physical phenomena as mundane as the formation of the whirlpool that forms when water is released down the bathtub drain, as important as the electrochemical synaptic connections of the human brain, and as vast as the earth’s entire ecosystem. Perhaps the most fascinating aspect of complexity theory is a phenomenon called emergence. In her book Living at the Edge of Chaos (Daimon Verlag 1997), Helene Shulman clarifies that in any complex system at the edge of chaos, factors can interact in multifarious ways so that there spontaneously emerge novel, unforeseeable phenomena that are beyond the predictability of ordinary science. The concept can be grasped by visualizing a small round table over which is an apparatus that can emit one grain of sand at a time. Slowly, over time, as some grains of sand bounce away but others pile up on the table, a cone will begin to form. Then the system enters an unpredictable critical state in which one tiny grain of sand falls and results in a massive avalanche, thus destroying the cone. This concept of complexity has direct bearing upon biological systems. One example of this is the emergence of the first organic molecule that could replicate itself, which emerged about four billion years ago out of the inorganic chemical debris of the Big Bang.

Other examples might be the sudden extinction of life forms such as the dinosaurs, species that become unsustainable at a critical state when one tiny detrimental change occurred in a highly complex ecosystem. Recently the New York Times columnist Thomas L. Friedman, reporting from Bali, Indonesia, where representatives from 200 countries attended the United Nations climate conference, reported that some of the delegates were talking as though it is “too late for later.” He quoted Barnabas Suebu, the governor of Papua, as saying, “Think big, start small, act now—before everything becomes too late.” At the conference, some delegates, using ordinary cause-andeffect statistical science, predicted that the ice within the Arctic Circle could disappear by the year 2040. But if we add complexity theory and its concept of critical states to that thinking, we notice that our ecological crisis may be even more urgent. Indeed, it may seem that any minute one additional detrimental change in the environment, like the one grain of sand producing the avalanche on the sand cone, could trigger an ecological disaster. The world may already have reached a critical state at which there could occur a catastrophic and unpredictable emergence of properties that could not have been foreseen. We may be living at the edge of chaos.

Welcome New Members!

The San Francisco Medical Society would like to welcome the following new members:


Beverly Bolinger, MD, The Permanente Medical Group Jing Dai, MD, The Permanente Medical Group Kirk Murphy, MD Brigitte Prinzivalli-Rolfe, MD, The Permanente Medical Group Lisa Tang, MD, The Permanente Medical Group Referred by Chuck Wibblesman, MD Chunbo C. Cai, MD, The Permanente Medical Group Lisa Griffin, MD, The Permanente Medical Group Referred by Suketu Sanghvi, MD Timothy R. Hamill, MD, UCSF Medical Center Referred by Tom Addison, MD Linnea Hur, MD, The Permanente Medical Group Referred by Suketu Sanghvi, MD Shala Rahbar, MD Andrea H. Yeung, MD, Referred by Brian Schindler, MD

HOUSE OFFICER/RESIDENT Jessica Evert, MD, UCSF/SFGH—Family Practice  San Francisco Medicine January/February 2008

Guest Introduction Philip R. Lee, MD; Steve Heilig, MPH; and Michael Lerner, PhD

A New Era for Environmental Health


his issue of San Francisco Medicine is the fifth in the past decade to have an environmental health theme. Over that decade, the field has been transformed both by rapidly expanding scientific knowledge and fast-growing recognition that many of our educational, clinical, and other approaches to environmental health problems need improvement. Look at the headlines: known or suspected toxins in products both foreign and domestic, contaminated foods and water, climate change, and much more are ever more prominent and worrisome. There is no doubt that these problems have at least some impact on human health. We are proud that some of the world’s leading authors on a wide array of topics are featured in this issue of San Francisco Medicine. At a 2002 conference hosted by the San Francisco Medical Society, an international network known as the Collaborative on Health and the Environment was founded to bring different disciplines together with patients and others to address environmental health issues, with a particular focus on chemical contaminants. The science in that arena has exploded with data about the previously unsuspected ways that industrial chemicals in our bodies can impact our health. Policy makers are finally taking notice that our current approaches are archaic—and that we lag behind many other advanced nations in this regard. Recently, the California Medical Association’s House of Delegates adopted the following policy on this topic—initiated by the SFMS delegation. Our state may well lead the nation on a scientifically sound chemicals policy. A Modern Chemicals Policy for California and Beyond: California Medical Association, 2007 By Lucy Crain, MD, and Robert Gould, MD Whereas, the state, national, and global scale of industrial chemical production is immense and is expected to grow fourfold by 2050, and the chemical industry is an important industry with wide contributions to health and human development; and Whereas, ever-expanding research confirms that many chemicals that are useful to society are also known to be hazardous to human biology and health, particularly in utero and in developing children; and Whereas, for new and existing medications, the Food and Drug

tion has long required preapproval evaluation of safety as well as efficacy, and many industrial chemicals with known impacts on human biology are present in human bodies at levels similar to active doses of medications; and Whereas, numerous nations including Canada and the European Union are adopting more proactive health-oriented chemicals policies, based upon scientific knowledge, assessment, and accepted public health principles; and Whereas, there are long-standing deficiencies in the federal regulation of industrial chemicals, most notably in the Toxic Substances Control Act (TSCA), as confirmed by the National Academy of Sciences and others; and the University of California documented in a 2006 report to the California Legislature that TSCA’s deficiencies are important and can be remedied; and Whereas, these problems include the projected appearance of 600 new hazardous waste sites each month in the U.S. over the next twenty-five years; the appearance of hundreds of industrial chemicals in human tissues and fluids, including those of infants; and the development of chronic diseases caused by chemical exposures on the job among 23,000 California workers each year; and Whereas, the American Public Health Association’s leadership has recently endorsed a policy entitled Calling on the U.S. Congress to Restructure the Toxic Substances Control Act and Implement a Modern, Comprehensive Chemicals Policy; therefore, be it RESOLVED that the CMA call upon the State of California and United States to implement a state and national modern, comprehensive chemicals policy in line with current scientific knowledge on human health, and that requires a full evaluation of the health impacts of both newly developed and existing industrial chemicals now in use.

This policy will be taken by the CMA delegation to the AMA’s policy-making body in 2008. We hope the AMA will see the wisdom of adopting the SFMS/CMA stance and in advocating that our new political leaders make up for lost time. The ultimate aim is, and the result could be, a healthier nation and world, with the decrease in human suffering that entails. That seems to us a very worthy goal. For more information, see Philip R. Lee is Professor of Medicine Emeritus at both Stanford and UCSF, where he is also a Chancellor Emeritusformer United States Secretary of Health; Steve Heilig is with the SFMS; Michael Lerner is President of Commonweal. All are founding partners of the Collaborative on Health and the Environment, which Dr. Lee chairs. January/February 2008 San Francisco Medicine 

Health, Human Beings, and The Environment

Toxic Dilemmas Donald Kennedy, PhD


fter all these years of environmental regulation, the laws and rules regarding the introduction of toxic chemicals into consumer products and the environment are still ineffectual. After an earlier lifetime in which I worried about lead, polybrominated biphenyls in plastics, and the like, I got reacquainted with toxic dilemmas. It happened because of a reunion with an old friend who has a long familiarity with the use of such toxic substances as fire retardants in consumer products. Here’s the story. In the early 1970s, when I first got to know Arlene Blum, she was working with Bruce Ames at the University of California, Berkeley. They were applying the Ames test for mutagenicity to various lipid-soluble chlorinated and brominated compounds that are double trouble because they concentrate in food chains and wind up in people, and they aren’t biodegradable. They discovered widespread use of a compound called tris (2,3-ibromopropyl) phosphate as a fire retardant in children’s sleepwear. A mutagen and putative human carcinogen, it leeched into children’s bodies. After a 1977 paper by Blum and Ames in Science, its use was banned. Well, the alert chemical industry quickly substituted a dichlorinated tris, which Ames and Blum also found to be mutagenic and which was subsequently removed from sleepwear. The history of residential fire risk is an interesting one, because it involves the tobacco industry. Remember them? They designed cigarettes that, when dropped or put down, would smolder long enough to start a fire. For years, cigarette-lit fires were the greatest cause of fire-related deaths in the United States. After three decades of opposition from tobacco lobbyists, twenty-

two states and Canada finally passed laws requiring that cigarettes be made selfextinguishing. With fewer people smoking and better enforcement of building codes,

“The real problem is that the U.S. regulatory system for toxic industrial chemicals is not effective and is a threat to public health.” fire-related deaths are decreasing. I had missed this important development, having lost track of the topic. Arlene, a high-profile international mountaineer, was off leading expeditions in the Himalayas and elsewhere and was writing a memoir about it. Meanwhile, I had left the U.S. Food and Drug Administration and was back at Stanford. I hadn’t seen Arlene for twenty-five years or so, but a few months ago, she turned up with an extraordinary sequel to the tris story, which she tells of in a recent letter in Science. Fire retardants are now widely used in furniture foam, and the second most-used compound is none other than chlorinated tris! In less than three decades, this highly toxic mutagen has moved from your child’s nightgown to your sofa. Arlene is scientific adviser for a bill in the California legislature called AB 706, which would ban the use of the most toxic fire retardants from furniture and bedding unless the manufacturers can show safety. It has a good chance of passage next year; even the firefighters support it. Not surprisingly, chemical manufacturers have launched a

10 San Francisco Medicine January/February 2008

fear campaign in opposition, claiming that their products have dramatically reduced fire deaths in California, although the rate of decrease is about the same as that of states that do not regulate furniture flammability. But the problem is a national one. The Consumer Product Safety Commission (CPSC) Reform Act (S 2045) toyed with a provision that would rush us into a national furniture flammability standard. That’s premature, because it leaves no time to develop a safe way to reduce furniture flammability and puts potentially persistent toxic chemicals into U.S. homes. Congress should forget that approach. The real problem is that the U.S. regulatory system for toxic industrial chemicals is not effective and is a threat to public health. In Europe, the chemical industry is required to establish safety before a product can continue to be marketed. The U.S. Toxic Substances Control Act (TSCA) originally grandfathered existing chemicals, but none have been reexamined since the 1980s. Congress should abandon its attempt to attach a flammability standard to the CPSC and instead turn to the real task of reforming TSCA by introducing a true proof-of-safety provision. That would stop the chemical industry from making consumer protection look like a game of whack-a-mole. Donald Kennedy is the outgoing Editorin-Chief of Science and former President of Stanford University and Commissioner of the Food and Drug Administration. This editorial is reprinted from Science 318:1217 (2007) with permission of the author and the American Academy for the Advancement of Science.

Health, Human Beings, and The Environment

Toys, Tots, and Toxic Chemicals It’s Time to Act David Wallinga, MD, MPA


oy recalls due to lead have exploded to more than one hundred in 2007. Lead on toys is the tip of a bigger chemical iceberg, however. The real problem? “[T]he U.S. regulatory system for toxic industrial chemicals,” says Donald Kennedy, the former Commissioner of the Food and Drug Administration (FDA) and Science editor, “is not effective and is a threat to public health.”1 It is, in other words, a poorly regulated chemicals problem, not just a Chinese toy problem. If you think this is not a medical issue, think again. Industrial chemicals include not only lead and other metals but also solvents, phthalate plasticizers, and perfluorocarbons made into toys, lunch boxes, baby bottles, nonstick pans, and fabrics. Patients are exposed to them from birth. Early chemical exposures contribute to an array of chronic diseases and disabilities found in children and, the science strongly suggests, in adults. Among children, chemical exposures cause 100 percent of lead poisoning cases and contribute to an estimated 10 to 35 percent of asthma cases, 2 to 10 percent of certain cancers, and 5 to 20 percent of neurobehavioral disorders and disabilities. Yet weak laws require no toxicity testing of these chemicals before making them and entering them into commerce.

Gaps in Knowledge Dr. Kennedy’s dour assessment of TSCA, the Toxic Substances Control Act, is not unique. Its failures also have been enumerated by the National Academy of Sciences (1984),2 the General Accounting Office (1994, 2005),3, 4 the Congressional Office of Technology Assessment (1995),5 the U.S. Environmental Protection Agency (1998), 6 the University of California

(2006),7 and others.8, 9 TSCA is the 1976 law under which the EPA registers the 42 billion pounds of industrial chemicals produced or imported into

“Our collective failure to effectively regulate lead, plasticizers, and other industrial chemicals of concern in everyday products puts children in harm’s way. Again, physician support is critical if we are to have a chemicals policy that is effective.” the U.S. each day.10 One of TSCA’s chief failures: it perpetuates long-standing scientific ignorance about the hazards of these chemicals—what University of California, Berkeley, public health scientist Michael Wilson deems the “knowledge gap.”11 The ignorance is partly historical. Society’s longtime presumption was that industrial chemical use was medically harmless, especially for nonworkers. After World War II, the newly emergent chemical industry excelled at innovating new chemicals (90 percent of them derived from petroleum) and products, answering the pent-up appetites of a war-weary public. Because of presumed harmlessness, there was no health or safety testing of these new substances. Congress passed TSCA only after rising numbers of industrial chemicals were detected in polluted air and water. With

the law’s design, however, the Congress ensured our chemical ignorance would persist. On implementation, TSCA grandfathered in the 62,000 chemicals then in use, meaning no new toxicological testing was required for them. TSCA-registered chemicals produced or imported at “high volume,” meaning 1 million pounds or more per year, total 2,943 in number today. Largely untested grandfathered chemicals make up 92 percent of these high-volume chemicals. TSCA also fails to require makers of new chemicals—there are about 2,000 such chemicals per year—to generate or disclose to EPA or end users any toxicological data before these chemicals are marketed or used in products. Total TSCA-registered chemicals now number 81,600. Of those in actual use, fewer than half have been subjected to even token laboratory testing for toxicity. By never granting EPA the authority to make sure chemical toxicity information would be generated and distributed, TSCA ensures continued ignorance for every new generation of chemicals.

Safety Gaps TSCA’s knowledge gap also creates a safety gap. Congress mandates that regulatory agencies use a “risk-based” approach. To assess chemical risk requires information on toxicity or hazard, yet TSCA ensures that EPA lacks the authority to collect such data in the first place. Regulatory paralysis ensues. By 1994, the General Accounting Office (GAO) found that EPA had managed to review the risks of only about 1,200 (2 percent) of the 62,000 pre-TSCA chemi-

January/February 2008 San Francisco Medicine 11

cals. EPA told GAO it considered about 16,000 (26 percent) to be of potential concern to human health. How can one make “evidence-based” public health decisions when fundamental hazard information is lacking for tens of thousands of chemicals? Another way TSCA constrains EPA is in limiting its authority to take steps to actually control chemical hazards. Thus, since 1979, EPA has been able to use its existing authority to regulate only five of the 62,000 grandfathered TSCA chemicals: polychlorinated biphenyls (PCBs), chlorofluorocarbons (CFCs), dioxins, asbestos, and hexavalent chromium.12 Even for new chemicals, TSCA limits EPA’s authority. After a manufacturer registers a new product and EPA reviews it, TSCA prohibits the agency from requiring any additional toxicity testing. Every incentive is for manufacturers to do as little toxicity testing as possible prior to registration. Eighty-five percent of new chemicals registered under TSCA, the EPA reports, lack any data on chemical health effects.

TSCA’s costs TSCA’s costs are multiple. Workers pay because they typically face the highest exposures to often untested, ineffectively regulated chemicals. In California alone, preventable chronic disease attributable to workplace exposures to chemicals affects an estimated 23,000 persons each year.13 What are the costs to children? A landmark 1993 National Academy of Sciences study reported that children during development are uniquely vulnerable to harm from environmental chemicals.14 For example, the young brain’s inherent vulnerability stems from its rapid early development, much of it in utero, combined with the fact that, for optimal brain function, billions of neurons must successfully differentiate, migrate, and form synapses with other cells in an incredibly intricate and well-choreographed process. The precision required is why the young brain is vulnerable to toxic injuries that have no parallel in the mature adult brain. Like adults, children are exposed to a complex mixture of dozens or hundreds of industrial chemicals, including many neurotoxicants.15 Exposure starts before birth; one

analysis of just ten samples of newborn cord blood, supplied by the American Red Cross, detected a total of 287 industrial chemicals, including 217 that are neurotoxic in humans or animals.16 How many are causing developmental harm in children? There are data that 201 industrial chemicals are clinically neurotoxic in humans. The Congressional Office of Technology Assessment estimated in 1990 that 3 to 5 percent of the tens of thousands of industrial chemicals in commerce could be neurotoxic. For about 80 percent of the nearly 3,000 high-volume TSCA chemicals, no information is available regarding developmental or pediatric toxicity. The lack of required testing means the actual number of adult or pediatric neurotoxicants remains unknown. Only a handful of industrial chemicals (e.g., lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) have been confirmed as causing neurodevelopmental disability or disease in children. The evolution of science around these five followed a similar pattern. Widespread use and human exposure came first. Second, there was recognition of occupational or adult neurotoxicity. Only much later was there human or epidemiologic evidence to determine harm to children. With that came the realization that neurodevelopmental impacts occur at low prenatal exposure levels that would not be toxic to an adult. Neurodevelopmental harm, we now know, is often subclinical, i.e., not clinically apparent. Subclinical toxicity can manifest not on standard examination but as a finding of special IQ or neurobehavioral testing. Thus, the neurodevelopmental harm suffered by children exposed early in life to airborne lead from gasoline, PCBs, and/or methylmercury have been largely “silent,” unnoticed pandemics.17 The human and economic costs are real, however. From 1960 to 1980, about 100 million American children were exposed to airborne lead. Societal costs stem largely from diminished economic productivity, because these children are less intelligent on the whole due to their lead exposure; such costs are estimated at $110 billion to $319 billion per each year’s birth cohort.18 Today the costs of prenatal

12 San Francisco Medicine January/February 2008

methylmercury exposure are estimated at $8.7 billion yearly (the range running from $2.2 to $43.8 billion).19 Ineffective regulation and control of industrial chemicals carries other costs as well, imposed on government, on ecosystems, and on business. For example, the EPA expects 600 new hazardous waste sites to appear in the U.S. each month over the next twenty-five years, adding to the 77,000 already in existence.20 Total mitigation costs are expected to total around $250 billion. Costs like these will only deepen with global chemical production, projected to increase fourfold by 2050.21

A Healthier Way Forward Regulatory failure once allowed tobacco companies to market Joe Camel and nicotine addiction to children. Medicine played an important and appropriate role in changing that picture. After all, the American Medical Association’s mission statement includes the “betterment of public health.”22 Now, our collective failure to effectively regulate lead, plasticizers, and other industrial chemicals of concern in everyday products puts children in harm’s way. Again, physician support is critical if we are to have a chemicals policy that is effective. A better chemicals policy is feasible. Public health concern has erupted around chemical plasticizers, such as bisphenol A and phthalates, which disrupt hormone function in animals. Limited human studies appear confirmatory. These plasticizers are widely used in children’s products and are ubiquitous in human sera. Europe has phased out phthalates in children’s products. In October, California effectively phased out the manufacture or sale of young children’s products containing phthalates by 2009. Alternatives are readily available, as for most toxic chemicals. State legislation can help reduce exposure to certain hazardous chemicals. However, state initiatives are necessarily limited. Even after California’s phaseout, phthalate-containing products will remain for sale elsewhere in the U.S. Likewise, baby bottles of polycarbonate plastic, which leach bisphenol A, are no longer sold in Japan, yet

Continued on Page 18...

Health, Human Beings, and The Environment

Reproductive Health and the Environment What We Need to Know to Face the Challenges Tracey J. Woodruff, MPH, PhD; Jackie M. Schwartz, MPH; Alison Carlson; and Linda C. Giudice, MD, PhD


uccessful reproduction—from conception through pregnancy, child development, and adulthood—is an integral part of the continuing life cycle, and there are increasing indicators of declines in many aspects of reproductive health. Among men in the United States, these include about a 60 percent increase in the incidence of testicular cancer (1), declining sperm counts in certain areas (2), and reports of declining testosterone levels (3), suggesting a decline in male reproductive function over approximately the past thirty years. For U.S. women during the same time period, there has been a reported decline in age of onset of breast development and menarche, and more women, particularly women under the age of twenty-five, are reporting difficulty conceiving and maintaining their pregnancies (4). A woman’s lifetime risk of developing breast cancer has nearly tripled in this country in the past forty years (5). Thirty percent more babies are born prematurely, and the median gestational age at birth has decreased from forty to thirty-nine weeks (6). These rapid changes in health endpoints suggest that environmental—and thus modifiable and preventable—actors, rather than Mendelian inheritance, are involved in recent declines in reproductive health. Since World War II, chemical production in the United States has increased more than twenty-fold, and the number of chemicals registered for commercial use has grown by more than 30 percent since 1979 (7, 8). As of 2006, there are approximately 87,000 chemical substances registered for use in commerce in the United States (9). The scientific evidence linking environmental chemicals to all aspects of reproductive health continues to expand, and concern over the implications of these findings spurred

the 2007 Summit on Environmental Challenges to Reproductive Health and Fertility (9a). This unique gathering coalesced the field of environmental reproductive health by bringing together more than 400 scientists, researchers, health care professionals, trainees, health-affected groups, community and political representatives, and members of the media to discuss what is currently known about the impacts of environmental contaminants on reproductive health and fertility and to identify steps to reduce the impacts of environmental contaminants on reproductive health through research, education, communication, and changes in public health policy.

Critical New Science: Exposures to Environmental Contaminants Humans are exposed daily to a mixture of environmental contaminants in air, water, food, and consumer products. In a recent biomonitoring study of more than 150 contaminants, the U.S. Centers for Disease Control and Prevention reported that all 150 chemicals were detected in some portion of the U.S. population and that several of the chemicals, such as environmental tobacco smoke, lead, mercury, and phthalates, are detected in nearly all members of the population (10). While many environmental contaminants can affect reproductive health (see online appendix at for a list), there is an important class of chemicals, called endocrine-disrupting chemicals, that interfere with the production, release, transport, metabolism, binding, action, or elimination of natural hormones in the body. Two examples of endocrine-disrupting chemicals that have received much media attention recently, and that will be discussed in this

Key Definitions for Environmental Reproductive Health Environmental Reproductive Health: Interdisciplinary study of exposures to environmental contaminants, particularly during critical periods in development (such as prior to conception and during pregnancy), and their potential effects on all aspects of future reproductive health throughout the life course, including conception, fertility, pregnancy, child and adolescent development, and adult health. Environmental Contaminants: Synthetic chemicals and metals in our environment, including air, water, soil, food, consumer products, and the workplace. Reproductive Health: Ability to conceive and to carry a pregnancy, pregnancy quality and outcomes, pubertal effects, and adult reproductive health disorders.

article, are bisphenol A (also called BPA) and phthalates. BPA is found in hard plastic water and baby bottles and food containers, the lining of metal food and drink cans, pacifiers and baby toys, and dental sealants. Phthalates are a family of chemicals that are used to soften plastics used in medical devices, food wrap, flooring, wall coverings, personal care products (perfumes, lotions, cosmetics, hair spray), lacquers, varnishes, and wood finishes and coatings.

Implications of Exposures during Key Developmental Windows over the Life Course While exposures to environmental contaminants during any life stage can increase risk of adverse health effects, there are times during development when rapid and often

January/February 2008 San Francisco Medicine 13

unique changes occur, and these represent more susceptible windows. Exposures during these times can result in irreversible effects that can have either immediate, lifelong, or even intergenerational impacts on health. Windows of susceptibility can occur periconceptually (prior to, during, and shortly after the fertilization of the egg) and during pregnancy, infancy, childhood, and puberty. One example of the influence of the environment during a developmental window of susceptibility is the Barker hypothesis (or fetal origins of disease hypothesis): alterations in the fetal environment that impair fetal growth result in an increased risk, later in life, of adult onset of chronic conditions such as coronary heart disease and diabetes (11). Researchers during the past decade have explored the mechanisms whereby exposure to environmental contaminants during developmental windows of susceptibility results in compromised function or disease later in life. They have shown that such exposures can modify the epigenome (the collection of biochemical reactions that determine gene expression), permanently altering gene expression and leading to metabolic and hormonal disorders, reduced fertility and fecundity, and illnesses such as prostate, uterine, and cervical cancers later in life (9).

The DES Example We have learned much about the effects of exposure to endocrine-disrupting chemicals during susceptible developmental periods through an unfortunate experience with diethylstilbestrol (DES). DES is a synthetic estrogen (and thus an endocrine-disrupting chemical) that was given to pregnant women in the United States between 1938 and 1971 under the erroneous assumption it would prevent pregnancy complications. In fact, in utero exposure to DES can alter the epigenome and normal programming of gene families, such as Hox and Wnt, which play important roles in reproductive tract differentiation (9, 12-14). Thus, women exposed to DES in utero are at increased risk of clear cell adenocarcinoma of the vagina and cervix, fibroids, structural reproductive tract anomalies, infertility, and poor pregnancy outcomes, while men have an increased incidence of genital abnormalities and a possibly increased risk of prostate and

testicular cancer (15, 16). In addition, effects can be passed down to a second generation, including increased menstrual irregularities (17) and ovarian cancer (18) in the granddaughters and increased hypospadias in the grandsons (19, 20) of women who took DES during pregnancy.

Reproductive Effects of Early Life Exposures Through a combination of laboratory animal, human, and wildlife studies, much as been learned about how exposure to environmental contaminants can disrupt reproductive health, particularly during susceptible windows of development. These are illustrated briefly below, with a more thorough review in Woodruff et al. (9).

Prostate Development and the Environment Early-life exposures to environmental contaminants can also affect the developing prostate, which is particularly sensitive to estrogens. Rats exposed neonatally to bisphenol A (BPA), then exposed later in life to hormones that mimic the hormonal profile of the aging male, showed a significantly higher incidence of prostatic intraepithelial neoplasia (a preneoplastic lesion) compared to controls (23). This heightened predisposition results from permanent alterations to the prostate epigenome that continue the expression of the phosphodiesterase type 4 variant 4 gene (an enzyme responsible for Cyclic adenosine monophosphate (cAMP) breakdown) at a time when it is normally silenced with aging.

Males Testicular Disgenesis Syndrome Research over the past ten years has drawn a connection between various malformations and diseases of the male reproductive system that manifest at birth (cryptorchidism, hypospadias) or in early and later adulthood (testicular germ cell cancer and infertility). These conditions, which are risk factors for each other, are now considered part of a testicular dysgenesis syndrome (TDS). The TDS hypothesis proposes that disruption of testosterone function during early pregnancy can disrupt testis development, and lead to these and other disorders of the male reproductive tract (21). This hypothesis has been supported by both animal and limited human studies (21). Exposure of rats in utero to dibutyl phthalate (a type of phthalate that is known to disrupt testosterone) induces cryptorchidism, hypospadias, reduced anogenital distance (a measure of testosteronedependent male reproductive development), impaired spermatogenesis, and infertility in a dose-dependent manner (21). Prenatal exposure to dibutyl phthlate can also alter development and function of cells and pathways critical for the development and functioning of the male reproductive system (21). A study of pregnant women exposed to phthalates during pregnancy has also found a relationship between increasing levels of phthalates and decreases in the anogenital distance of their male babies (22).

14 San Francisco Medicine January/February 2008

Females Uterus Development and the Environment As described above, prenatal exposures to DES can modify the epigenome and cause reproductive tract abnormalities in women. Studies have now been extended beyond DES to demonstrate that other environmental estrogens can similarly reprogram gene expression in the uterus (9): exposure to genistein and BPA during the period of maximum sensitivity to developmental programming induces the expression of the estrogen-responsive genes calbindin and progesterone receptor, which results in greater incidence of fibroid tumors. Oocyte Development and the Environment Studies find that prenatal exposures to low doses of BPA perturb oocyte development in unborn female mice, essentially affecting the second generation (24). These perturbations result in an increase in chromosomally abnormal eggs and embryos, a marker for aneuploidy, which is a risk factor for miscarriages and other fetal abnormalities (24). The study also indicated that BPA acts by interfering with the function of one of the known estrogen receptors, ER-, which also suggests that other endocrine-disrupting chemicals that act in a similar manner may affect early oocyte development (24).

Reproductive Effects of Adult Exposures

While we have focused our discussion on exposures that occur during developmental windows, exposures to environmental contaminants during other life stages, such as adulthood, can also increase the risk of adverse reproductive health effects (9). These include impacts on male reproductive function, such as decreased or abnormal sperm count, and increased rates of infertility. Similarly, in women, chemical exposures can increase risk of early onset of puberty, menstrual and ovarian dysfunction, and infertility.

Moving Forward At the summit, participants collaborated to identify critical needs and directions for advancing reproductive environmental health through health care, research, policy, community action, and occupational health. Recommendations are briefly reviewed below.

Health Care Professionals The following actions will help integrate environmental reproductive health into health care: • Reproductive environmental health topics should be included in medical and nursing education, and continuing education should be provided at medical and nursing society meetings. This training should include information on the sources and effects of environmental and workplace exposures, particularly in relationship to windows of susceptibility. • Current standards of practice should be changed so that health care providers take a work history and inquire about patients’ exposures to chemicals, ideally before pregnancy. • Clear, simple health information tools should be developed to support conversations between health care providers and patients. These materials should discuss contaminants and sources of exposure, along with steps to reduce exposures. These tools can be modeled on the Pediatric Environmental Health Toolkit ( and the Hazard Evaluation System and Information Service for workplace hazards ( ohb/hesis).

Research Specific steps can be taken to expand the research base and support interdisciplinary collaboration: • Conduct longitudinal human and animal studies that observe the full life cycle (e.g., the National Children’s Health Study). • Increase funding for emerging areas of research, including effects from chemical mixtures, effects on the epigenome, fetal programming and transgenerational effects, low-dose effects, and cross talk among endocrine systems. • Develop and improve biomarkers of exposure, fertility, and early disease. • Develop methods to identify emerging contaminants of concern. • Establish technologies to promote collaboration, such as an Internet-based discussion forum and a Web-based database of tissue banks. • Increase government and university recognition of and support for collaborative, interdisciplinary research.

Policy Participants from all sectors represented at the summit identified four key policy needs: • Advance models for comprehensive chemicals evaluation at local, state, and national levels for more effective chemical regulation. • Increase resources and improve methods to enhance research on reproductive environmental health. • Improve the use of science and precaution in decision making by: acknowledging uncertainty in the science and allowing for action in the face of this uncertainty; increasing steps to limit undue influence or bias in the review and synthesis process; and incorporating low-dose effects and exposure to multiple chemicals into decision making and risk assessment. • Improve right-to-know information given to consumers and workers about environmental contaminants in products.

Community Action Summit participants gathered to talk about the science in the context of environmental justice, occupational health, and

reproductive justice. Participants recommended that community members, scientists, epidemiologists, clinicians, activists, communications strategists, and spokespeople work together toward a reformed and improved public health policy that adequately regulates chemicals and reduces exposures.

Safe Work Participants in the Safe Work group at the Summit identified the following unique needs of workers: • Reduce permissible exposure levels to harmful chemicals to be more consistent with environmental exposure limits and take into account toxicity of exposure to mixtures of chemicals used in the workplace. • Expand exposure assessment and monitoring in occupational settings. • Expand occupational health researchers’ access to workers so that health consequences can be identified and corrected. • Develop alliances that can improve health across different sectors. For example, make the connections between worker safety and hospital patient safety concerning phthalates.

Conclusion The summit provided a view of critical scientific information that underscored the need for further efforts in areas to improve reproductive health. One common theme throughout the summit was communication and collaboration. Communication and collaboration across scientific disciplines and among scientists, health care providers, health-affected groups, and the public (as well as efforts in research, education, and policy) are key to reducing the adverse impacts of environmental contaminants and enhancing the reproductive health of this and future generations. Tracey J. Woodruff, PhD, MPH, and Jackie M. Schwartz, MPH, are with the Program on Reproductive Health and the Environment, National Center of Excellence in Women’s Health, Department of Obstetrics, Gynecology and Reproductive Sciences, U.C. San Francisco. Alison Carlson is with the Collaborative on Health and the Environment. Linda C. Giudice, PhD, MD, chairs the Department of Obstetrics, Gynecology, and Reproductive Sciences, U.C. San Francisco. References, appendices, and acknowledgements appear online at

January/February 2008 San Francisco Medicine 15


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Health, Human Beings, and The Environment

Early Vulnerability, Lifelong Impacts Developmental Exposure to Environmental Chemicals in Disease Etiology Philippe A. Grandjean, MD, PhD


he timing of exposure to a toxic chemical is a major factor that determines the biological effects. This new insight has profound importance in biomedical research and public health. Fetal and early postnatal development likely constitute the most vulnerable time periods of human life, and toxic exposures during these susceptible life stages can therefore lead to much more serious adverse effects than exposures to the mature organism. Past research has primarily focused on spontaneous abortion, congenital malformations, and lowered birth weight as evident effects of toxic exposures during development. However, new research is pointing to a new paradigm, where seemingly subtle changes incurred during early development lead to functional deficits and increased risks of disease later in life.

Programming Effects on Human Health The developing embryo and fetus are extraordinarily susceptible to functional alterations of the intrauterine environment. Low birth weight has been used as a marker of fetal nutrient deprivation and has been linked to subsequent development of cardiovascular and metabolic disease in adults. This notion of fetal or developmental programming is now being expanded by studies that assess the effects in the offspring of maternal smoking and other toxic exposures. An important discovery was made as early as 1968, when fetal alcohol syndrome was first described. However, progress in the field of research has been slow, in part because of logistic difficulties when dealing with considerable time intervals between causative exposure and appearance of

verse effects. Recent studies are now further supporting the new paradigm of early developmental origins of organ dysfunctions and disease risks. Some environmental chemicals can alter gene expression by inducing changes to the DNA configuration. These epigenetic changes can cause lasting functional changes in specific organs and tissues, and they may even be heritable, thereby affecting successive generations.

The Faroes Conference Because of the substantial implications both for biomedical research and for public health, an international conference was organized to review the current research and stimulate cross-disciplinary research and collaboration in regard to developmental programming caused by environmental toxicant exposures. This meeting was held in May 2007 in Torshavn, Faroe Islands, a North Atlantic archipelago that occupies an important place in the history of medicine: in 1846, the pathologist Peter Ludvig Panum described that a measles epidemic there affected only those residents who were below the age of sixty-five and who had not been affected by the previous epidemic. This time, in 2007, the meeting examined the implications in later life caused by exposures to environmental chemicals during early development. The discussion addressed these issues from three different angles: a) The developmental perspective considered changing risks during different developmental stages, from preconception to adolescence; b) The environmental perspective considered the types of risks that children and the fetus may face in different exposure situations; and

c) The disease perspective considered the pathogenesis from its initiation and the etiological role played by environmental hazards. The three perspectives illustrate the multidisciplinary character of the research. The developmental origin of disease and dysfunction deserves consideration in toxicology, developmental biology, nutrition, epidemiology, clinical medicine, and related fields. The effects of developmental programming will depend on the particular organ system’s vulnerability in regard to the timing of exposure. Past studies have emphasized disease incidence and mortality as key outcomes. Thus, certain cancer forms may be initiated before birth or during early postnatal life. However, less serious deficits may be of great importance if they affect large segments of an exposed population. This concern is of importance in regard to adverse effects on the development of the central nervous system, the cardiovascular system, the endocrine system, and the immune system.

Illustrative Research Findings Changes in uterine environment can affect the developing male reproductive system, which can lead to the so-called testicular dysgenesis syndrome (testicular cancer, poor semen quality, and cryptorchidism). In animals, exposure to some phthalate esters has evoked similar outcomes. Unfortunate experience with an estrogenic pharmaceutical, diethylstilbestrol, has shown that maternal exposure to this compound may lead to vaginal, uterine, and breast cancer. New evidence on bisphenol A, a plastics component that also has estrogenic effects, shows increased susceptibility to breast cancer or prostate cancer

January/February 2008 San Francisco Medicine 17

from low-level exposure in animal studies. Obesity is another effect seen in rodents exposed prenatally. Inorganic lead is the paramount example of an environmental chemical that can cause lifelong deficits in brain function as a result of developmental exposures. New evidence suggests that certain pesticides, methylmercury, and many other substances can cause similar adverse effects. Environmental chemicals may also impact the development of the immune system. Early exposure to polychlorinated biphenyls has been linked to deficient responses to routine childhood immunizations, an adverse effect that could have serious public health implications. Possible associations have also been demonstrated between asthma and allergy development in regard to prenatal or early postnatal chemical exposures.

Conclusions The conference demonstrated that developmental programming is a crucial issue to consider in research and prevention, for five reasons: 1. There are critical periods of fetal

Toys, Tots, and Toxic Chemicals Continued from Page 12... they are widely available in the U.S. Despite years of warnings about TSCA’s ineffectiveness, there is little momentum in this country to reform TSCA at the federal level. Europe’s overhaul of its own industrial chemicals policy, called REACH (for Registration, Evaluation, and Authorization of Chemicals), went into force in June 2007. It requires that tens of thousands of chemicals made or imported into the European Union be registered. For registration, REACH puts the onus on manufacturers to first provide specified health and safety information. Certain chemicals determined to be of “very high concern” will be targeted for the substitution of safer alternatives; the law also will require companies to proactively tell consumers which products contain these chemicals. REACH directly addresses the kind of knowledge gap found in both TSCA and

development. Effects of physical, chemical, and biological influences will differ, often dramatically, depending on the timing of exposure. Thus, “the dose and the timing make the poison.” 2. Fetal programming produces longterm and typically permanent changes. 3. While maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, compensation may also produce secondary (typically negative) effects. 4. Continued postnatal exposure and compensation may have further deleterious effects. 5. Effects of the environment on the fetus are often different from those on adults or even infants, and the effects may differ between males and females. The evidence that supports the notion of developmental origin of disease and dysfunction is not yet comprehensive. However, given the substantial difficulties and delays in documenting later-life consequences of developmental exposures to environmental chemicals, the research results available offer strong support for this new paradigm. This thriving research

area of developmental programming is likely to expand further in the future, with substantial implications for public health. More research and communication among researchers is essential in order to ascertain the factors that affect development and the associated long-term risks. We hope our conference helped set the stage for future accomplishments in this field. The conference conclusions are available at, and the proceedings will be published in Basic & Clinical Pharmacology & Toxicology in February 2008. Dr. Philippe A. Grandjean is a Professor in the Environmental and Occupational Medicine and Epidemiology Program in the Department of Environmental Health, Harvard School of Public Health.

the prior E.U. chemicals law. By requiring the generation and distribution of toxicity information, REACH fills an important “technology gap” that Wilson also identifies in TSCA. That is, if neither consumers nor industry leaders know which chemicals are more toxic, the market fails to provide the incentive for innovation or investment in cleaner production that uses less toxic materials. National policy change is critical for public health. To make it happen may require American health professionals to play an active role, as they have around tobacco use and control. In part, what’s needed is a change in perspective. We can easily make toys and household products that are useful and safe. We should expect nothing less. David Wallinga, MD, MPA, is Director of the Food and Health Program, Institute for Agriculture and Trade Policy (www. References available at

Air Pollution and Postneonatal Infant Mortality in the United States 1999–2002

18 San Francisco Medicine January/February 2008

Environmental Health Perspectives Volume 116, Number 1, January 2008 Tracey J. Woodruff, Lyndsey A. Darrow, and Jennifer D. Parker Abstract Objective: Our goal was to evaluate the relationship between cause-specific postneonatal infant mortality and chronic early-life exposure to particulate matter and gaseous air pollutants across the United States. Conclusions: This study supports particulate matter air pollution being a risk factor for respiratory-related postneonatal mortality and suggests that ozone may be associated with SIDS in the United States.

Health, Human Beings, and The Environment

Climate Change and Children’s Health What Health Professionals Need to Know and How They Can Act Katherine M. Shea, MD, MPH; and Sophie J. Balk, MD


limate change is occurring at a pace that greatly concerns scientists and the public. In this article, we summarize conclusions about climate change and discuss health effects with a focus on children. We end with action steps for health professionals.

Climate Change Is Real and Indisputable Climate change refers to any significant change in measures of climate (such as temperature, precipitation, wind) lasting for an extended period (decades or longer). In February 2007, the Intergovernmental Panel on Climate Change (IPCC), an independent, international group of scientists considered the world’s authority on climate change, began releasing its Fourth Assessment Reports ( Its message is strong: warming of the earth’s climate is “unequivocal,” and human activity, particularly the burning of fossil fuels, is a major cause. Computer models can reliably reproduce past and present global climate conditions. Direct observations from around the world, combined with paleoclimatologic data from nearly a thousand millennia, paint a picture of normal climate variation. These data also indicate that warming over the past decades is well outside the norm in rate and scale. That part of the scientific debate is settled; the uncertainty centers on other questions: how hot will it get, how fast, how widely will climate variables fluctuate, what will be the consequences, and what can we do about it?1 Climatologists can approach answers to some questions, but incomplete understanding of major influences (such as melting of glaciers or response of ocean currents) remains, possibly leading to overly

vative predictions. At the least, warming will continue throughout the twenty-first century due to the long residence time of already emitted atmospheric greenhouse gases (GHG) and the slow response time of oceans. Climate effects will vary by region and be most dramatic in higher latitudes and coastal areas. Rainfall and freshwater availability, temperatures, agricultural growth zones, and sea level will change. Ecological and human health consequences are anticipated, and some are already being measured.2, 3 Children are likely to suffer disproportionately from the consequences of a rapidly warming world.4

Health Effects of Climate Change The World Health Organization recently estimated that 34 percent of childhood illness in the world (compared to 24 percent of all-age illness) and 36 percent of deaths in children under the age of fourteen are due to modifiable environmental factors.5 Because of physical, physiologic, and cognitive immaturity, children are more sensitive than adults to harm from environmental hazards. Climate change increases these hazards. Air quality is threatened for several reasons. Ground-level ozone production is favored at high temperatures even without additional precursor pollutants. For the 6.5 million U.S. children with asthma, ozone exposure increases the rate and severity of asthma attacks. Ozone may play a causal role in asthma onset when exposures are high and prolonged.6, 7 Population growth and a warmer climate create increased energy demands. If society meets this demand by burning more fossil fuels to create electricity to power air conditioners, all major air pollutants—including ozone—will increase.

Childhood exposure to specific air pollutants is related to decreased lung growth and permanent decrements in pulmonary function; increases in respiratory infection, asthma, infant mortality, and all-age mortality; and miscarriages, preterm delivery, and low birth weight.6 Mercury from burning coal ends up in the food chain, thus threatening the neurologic development of fetuses and young children. Climate change is expected to result in changes in the quantity, quality, and distribution of pollens and other aeroallergens.8 For example, ragweed pollen production increases with increased CO2 concentrations; a rise in ambient ragweed pollen as temperature increases is already being measured.8 Asthma and allergies are likely to worsen regionally in a warmer world. The IPCC report states that climate change will result in more frequent and stronger hurricanes, typhoons, tornadoes, and floods. In western parts of the country, we expect longer and more severe droughts with subsequent wildfires. Children, particularly very small ones, are at increased risk for death and injury from these events in part because they depend totally on adults for protection. Hurricanes Katrina and Rita taught us how completely a natural disaster can displace a population and destroy infrastructure. Psychological sequelae, such as posttraumatic stress disorder and behavior and sleep problems, are documented; children may be more susceptible than adults.9, 10 More extreme precipitation events are likely. Heavy rain correlates with waterborne illness as surface water and groundwater become contaminated.11 Infants and small children are at higher risk for diarrheal dehydration and hospitalizations from wa-

January/February 2008 San Francisco Medicine 19


Human Health Impact

Additional Child-Specific Risks

Fewer cold days and nights

Fewer cold-related deaths

Children will benefit

Increased frequency of warm spells and heat waves

Increased heat-related deaths and illness

Very young at higher risk of death; older children will have more heat stress due to time spent in exercise outside

Increased heavy precipitation events

Increased risk of injury, death, Very young vulnerable to hosinfectious, respiratory, GI, and pitalization and complications skin diseases from infection

Increased areas of drought, wildfires

Increased risk of food and water shortages, malnutrition and infection, concentration of toxic water pollutants, injury, and death

Growth retardation, developmental delay

Increased tropical storms and cyclones

Increased risk of injury, death, water-, food-, and vectorborne illness

Children may be more susceptible to injury, posttraumatic stress, certain infections

Increased air pollution

Exacerbation of respiratory illness, premature mortality

Children’s small airways more susceptible to asthma, infection

Changes in disMore severe and more prevatribution and po- lent allergies tency of allergens, mycotoxins

Allergies, cancer, birth defects

Increased sea level, saltwater intrusion into fresh water

Disruption of family and school infrastructure, other social disruption

Abrupt coastline change, forced migration, injury, drowning

terborne infections. Food-borne infections are likely to increase due to changes in eating behavior (more outdoor food preparation and dining), and because food-borne pathogens grow faster in warmer weather. Researchers in Peru found an 8 percent increase in hospitalizations for diarrhea with every degree centigrade increase above normal average temperature.12 In a Canadian Study, peak temperatures correlated with peaks in cases of campylobacter, E. coli, and salmonella infections.13 Patterns of vector-borne illness are expected to change. Insects and rodents respond quickly to changes in temperature and moisture by migrating and, during favorable conditions, by reproducing more rapidly, often resulting in localized “plagues.” Temperature increases accelerate the vector’s life cycle and shorten the incubation time of parasites living in the vector. Warmer weather and failure of winter kills will prolong the transmission season

and change the range of vectors, resulting in more illness. Some of these illnesses are particularly devastating to children. Malaria, for example, causes 350 to 500 million illnesses yearly and more than one million deaths, mostly in young children. Recent “homegrown” malaria clusters remind us that vector-borne illness is a reality for the highly industrialized world.14 Although we can expect that cold-related deaths will decline, heat-related deaths are likely to increase. While this is a concern primarily for the elderly, excessive heat is also a risk for infants and small children. Unlike adults, very small children do not have fully developed temperature regulation mechanisms and cannot change their environments without adult help. Older children spend more time in outdoor activity and have higher exposures. Some analyses suggest that heat-related mortality may be declining in the U.S., despite increasing temperatures, most likely because of the

20 San Francisco Medicine January/February 2008

widespread availability of air-conditioning.15 Unfortunately, this adaptive technology requires higher energy use, which may add to further warming.

What the Future Holds Our children and grandchildren will inherit a warmer world with more extreme weather events. Even if we abruptly reduced GHG emissions to zero, enough energy is stored in the climate system to guarantee at least another 0.6o C temperature increase in this century.16 Depending on how rapidly we react, the future may be radically different from what we know. Initially, poor children in developing countries (and in this country) will suffer disproportionately because of their limited capacity to adapt, but ultimately climate change will affect everyone. If business continues as usual—with countries using traditional fossil fuels—we are likely to witness crises in food and water supplies, large-scale species extinctions, forced migrations of populations because of sea-level rise, drought, loss of natural resources, and major global economic impacts.17 This doomsday scenario is not inevitable if we act quickly. James Hansen of NASA’s Goddard Space Institute estimates that if we can limit warming in the twenty-first century to 1o C, we can expect an eventual (in a few centuries) sea-level rise of less than six meters and climate-related extinction of ~10 percent of species. If emissions continue to increase at current rates, temperatures will rise by at least 3o C by 2100 with a sea-level rise of twenty-five meters and loss of 50 percent of species.18 There may be a “tipping point” temperature that, if exceeded, could trigger catastrophic change relatively quickly (in perhaps a few decades).19 Anthropogenic GHG emissions are the major cause of climate change. Carbon dioxide (CO2) is the GHG responsible for more than 60 percent of cumulative anthropogenic warming globally, and more than 90 percent of the warming over the last ten years.20 The U.S. produces more GHGs than any other country.18 (Figure 1) In 2005, almost 39 percent of U.S. CO2 emissions came from residential and commercial buildings, and transportation generated 33 percent (60 percent of these from

personal vehicle use).21 (Figure 2) Industry was responsible for the balance of~28 percent. Since 1990, U.S. CO2 emissions from transportation, residential, and commercial sources increased by 25 percent, 31.5 percent, and 34.6 percent respectively, but decreased by 3.1 percent from industrial sources. Thus our daily choices—what and how much we drive, how we heat and light homes and offices, how we build houses—are major components of the U.S. emissions story. There is reason for hope. Using technologies that can be deployed rapidly, scientists and policy analysts have developed approaches to stabilizing and reducing GHG emissions. Princeton University’s Carbon Mitigation Initiative proposed a plan based on the “stabilization triangle,” the difference between zero GHG emissions growth and projected “business as usual” growth over the next fifty years.22 The initial goal is to prevent doubling of CO2 from preindustrial levels—the doubling is a level above which it is believed that dangerous climate change is highly likely—buying time to develop new technologies for future reductions. Other approaches and technologies are proposed23 and more will be developed—but to avoid accelerating toward the “tipping point,” action must begin now on known strategies.

Figure 2 (Right) The U.S., the leading GHG emitter in the world, was responsible for 27.8 percent of the cumulative emissions from 1750 to 2005. Per capita emissions in the U.S. in 2004 were 20.18 metric tonnes/person compared to 3.62 in China, 1.04 in India, and 4.24 averaged globally (http://www.eia.doe. gov/environment.html).

What the Health Care Community Can Do Many needed changes must come from governmental action, but we have individual opportunities to mitigate human influences on climate change. In anticipation of more extreme weather events, we can work with local authorities to strengthen the public health infrastructure, including early warning systems and disaster preparedness and response plans. In areas where vectorborne illness is likely to increase, we can work to implement preventive strategies, such as eliminating breeding grounds for rodents or mosquitoes. In cities subject to heat waves and concentrated air pollution, we can develop educational programs on using the heat and air-quality indices. Each region faces different challenges;24 professionals who understand the vulnerabilities of children are needed everywhere. The voice of health care professionals is powerful. We can work to become role models and champions of GHG reduction. Table 2 lists actions to help create a culture of conservation and energy efficiency. Educating the families in our care is part of the process (see “Steps Families Can Take”), as is educating the next generation of health professionals. Responding to climate change often

requires changing long-established personal practices—this may be difficult, but actions that mitigate GHG may have additional benefits. Energy efficiency saves money. Reducing auto dependence promotes physical activity. GHG reductions will improve air quality and save lives, hospital visits, and money. We hope that this article persuades readers to join the campaign to reduce GHG pollution—and that we can prevent climate change from permanently degrading our children’s future. The responsibilities and opportunities are ours. Katherine M. Shea, MD, MPH, is Adjunct Professor of Maternal and Child Health at the Dennis and Joan Gillings School of Global Public Health and Project Director, Environmental Resources Program, Institute for the Environment at UNC, Chapel Hill in Chapel Hill, North Carolina. She can be reached at Sophie J. Balk, MD, is Attending Pediatrician at the Children’s Hospital at Montefiore and Professor of Clinical Pediatrics at Albert Einstein College of Medicine, Bronx, New York. A full list of references, additional tables, and an informational patient handout are available on our website,

Figure 1 (Upper Left) Sources of CO2 emissions can be presented by “end-use sector”—residential, commercial, industrial, transportation—or by fuel source. Electricity, which is used for lighting, heating, air conditioning, and running appliances, is separated out because it represents a very large portion of emissions. Emissions related to electrical generation vary by fuel type from very low emission (hydroelectric) to very high emission (coal). More than one-half of the electricity generated in the U.S. comes from burning coal. Direct fossil fuel combustion refers to natural gas and heating oil used in buildings and by industry, and from petroleum (gasoline and diesel) used mostly in transportation. Taken together, residential and commercial buildings are responsible for 39 percent of CO2 emissions, three quarters of which are from electricity use. Industry produces 28 percent of annual emissions, split evenly between direct combustion and electricity use. Transportation is responsible for 33 percent of CO2 emissions, the majority (60 percent) of which result from personal vehicle use.

January/February 2008 San Francisco Medicine 21

Health, Human Beings, and The Environment

The Falling Age of Puberty in U.S. Girls What We Need to Know Sandra Steingraber, PhD, and Jeanne Rizzo, RN


irls today get their first periods, on average, a few months earlier than did girls forty years ago, but they get their breasts one to two years earlier. Menarche and thelarche are occurring earlier and earlier in the lives of U.S. girls, but the age of thelarche is falling more rapidly than the age of menarche. Over the course of just a few decades, the childhoods of U.S. girls have been significantly shortened. What does this mean for girls today and for their health in the future? Among U.S. white girls, the average menarchal age has declined slightly over the past four decades and now stands at 12.6 years. Among U.S. black girls, average menarchal age is 12.1 years, and the ongoing rate of decline is swifter. This is also true among Mexican American girls. Similarly, the average age of thelarche and pubarche, the first clinical signs of pubertal onset, have continued to fall among all groups and with significant ethnic/racial differences. About half of all U.S. girls show signs of breast development by their tenth birthdays, with 14 percent attaining breast buds between their eighth and ninth birthdays. Although studies differ somewhat in their findings, the mean age of thelarche is about 10 for white girls and 9 for black girls. Pubertal onset and menarche are apparently not as tightly coupled to each other as in years past. However, the data quality on onset of thelarche and pubarche, and their changes over time, is not as reliable as that for menarche.

Possible Causes of Early Puberty The brain is the driving force that controls thelarche and menarche through the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The

GnRH-secreting neurons (of which there are about 1,000) are themselves regulated by a plethora of chemical cues. Some of these are hormones, some are enzymes, and some

“Interventions that reverse the trend toward ever-earlier puberty in girls are a public health imperative ... Many actions can be taken on the basis of what is already known.” are neurotransmitters. With its multitude of signaling pathways, the neuroendocrine apparatus by which pubertal onset is controlled is inherently susceptible to disruption. Several upstream factors can potentially alter the regulation of the GnRH, secreting neurons and thereby hastening the onset of puberty in girls. These include: • Obesity: Obesity disrupts the endocrine system; chubbier girls tend to reach puberty earlier. But obesity is a consequence of early puberty as well as a possible contributor, adding to the complexity of studying this phenomenon. • Endocrine-disrupting chemicals: Exposures to endocrine-disrupting chemicals we come into contact with regularly are also playing a role in accelerating puberty in girls. These include chemicals we are commonly exposed to in cosmetics, shampoos, cleaning products, baby bottles, and children’s teething toys. • Premature birth and low birth

22 San Francisco Medicine January/February 2008

weight: Both premature birth and low birth weight alter endocrine function and therefore raise the risk of early pubarche. In addition to other factors, a pregnant woman’s chemical exposures can directly affect her developing child, in some cases leading to premature birth and low birth weight. • Psychosocial stressors: These stressors, including family dysfunction and the absence of a father in the home, also disrupt the endocrine system and are possible contributing factors to early puberty. The mechanisms behind these psychosocial stressors are not yet clear. • Formula feeding: Breastfeeding appears to protect against early puberty in two ways: by contributing fewer calories than formula and by offering hormones and other growth factors that may protect against early puberty. Further study is needed to clarify the role of breast milk in pubertal development. • Physical inactivity: Leanness and exercise together appear to protect against early puberty. While it is difficult to sort these two factors out in studies, there is enough evidence for us take preventive action now. • Television viewing and media use: Little is known about the effects of sexualized media content on pubertal timing in girls. But increased time in front of the television or a computer can lead to obesity and physical inactivity, both factors that contribute directly to early puberty. Additional research is needed to explore the mechanisms by which chemical signals in the brain may disrupt pubertal processes.

Negative Consequences of Early Puberty Early puberty poses several risks for girls.

It is caused by a combination of factors, and the interactions among these factors can be complex. Most notably, early puberty raises the risk factor for breast cancer. When puberty arrives earlier, the window of exposure to estrogen opens wider and increases a girl’s chances of developing breast cancer in later life. Indeed, first menstruation (menarche) before age 12 increases the risk of breast cancer by 50 when compared to menarche at age 16 or beyond. Early puberty is also associated with many high-risk behaviors in later adolescence—such as smoking, drinking, drugs, crime, and unprotected sex—that have potential lifelong consequences. Girls who mature early are also more likely to suffer violent victimization and psychopathologies such as depression and anxiety. It is not clear whether the social or physiological experience of pubertal change is responsible for these negative outcomes. In either case, interventions that reverse the trend toward ever-earlier puberty in girls are a public health imperative.

What We Need To Know There are areas of research that need to be supported to fill the holes in the science of early puberty. These include: • Basic science: We need to explore the mechanism behind the initiation of puberty, the role of signaling devices such as hormones and enzymes, the impact of chemical exposure during pregnancy, and the effect of breastfeeding on endocrine system development. • Epidemiology: We need large studies that follow girls from conception to adulthood, such as the National Children’s Study, mandated by Congress in 2000 but not yet fully funded. Studies like those in the National Institute of Environmental Health Sciences and National Cancer Institutefunded Breast Cancer and Environment Research Centers will contribute to our understanding of obesity, endocrine-disrupting chemicals like bisphenol-A and phthalates, and pubertal onset. • Chemical testing: Chemicals are not tested for their ability to disrupt the endocrine system before they are allowed into the marketplace. The Environmental Protection Agency’s Endocrine-Disruptor

Screening Program, mandated by Congress, is eight years behind schedule, and not one chemical has been screened to date. We need this screening information in order to reduce the public’s exposure to these chemicals. • Chemical tracking: We also need to know more about the sources, emissions, and fate of endocrine-disrupting chemicals in commercial use in order to reduce exposures. We need full disclosure of ingredients in consumer products, especially children’s products. We need more complete inventories of emissions and better monitoring of air, food, and drinking water. The Toxic Release Inventory was one good example of chemical tracking, but it has been significantly weakened. • Biomonitoring: Biomonitoring, or measuring the pollution in people, helps prioritize research on emerging chemicals of concern by identifying which chemicals are in our bodies. While the U.S. Centers for Disease Control and Prevention (CDC) biomonitors a national sample of the population for chemical contaminants, it collects very little information on infants and children, and what it gathers cannot be disaggregated in a way that would give us a snapshot of chemical exposures at the state or local level. The California Environmental Contaminants Biomonitoring Program will address some of these gaps and build a replicable model for other states interested in creating their own statewide biomonitoring programs.

What We Can Do Now Many actions can be taken on the basis of what is already known. Strategies to tackle childhood obesity and inactivity include changes to the built environment to encourage exercise; the resurrection of daily physical education in school; the elimination of high-calorie, low-nutrient foods from school lunch programs and school activities; the development of school and community gardens; the establishment of urban farmers’ markets; and partnerships between local farmers and neighborhood supermarkets to provide fresh, local produce in low-income communities. One obesityprevention program in Boston-area schools already has demonstrated that coordinated

efforts to promote healthy eating, increase physical activity, and decrease television viewing have the power to delay menarche in sixth- and seventh-grade girls. In addition to both good nutrition and access to prenatal care, strategies to lower rates of preterm and low-weight births include eliminating exposure to tobacco smoke, chemical solvents, and sources of air pollution and mercury contamination. Strategies to lower the burden of endocrinedisrupting chemicals to which girls have documented exposures include phaseouts of phthalates and bisphenol A; investments in organic agriculture; watershed protection; and nonchemical pest control in homes, schools, and day care centers. Early puberty is a problem that does not arise from a single toxicant, lifestyle, or dietary shortcoming. Rather, many different environmental stressors—some psychosocial, some nutritional, some chemical—interact in the bodies of young girls in ways that result in accelerated sexual maturation, with its attendant risks for health and well-being. The Falling Age of Puberty in U.S. Girls is a report researched and written by Dr. Sandra Steingraber. It was commissioned and published by the Breast Cancer Fund to explore the state of the evidence on early puberty in the U.S. Below is a synopsis. The full report and accompanying Advocate’s Guide is available online at Sandra Steingraber, PhD, is a biologist and distinguished visiting scholar at Ithaca College in Ithaca, New York. She is the author of the books Living Downstream, Having Faith, and Post-Diagnosis. Jeanne Rizzo, RN, is the Executive Director of the Breast Cancer Fund in San Francisco, a breast cancer organization focused solely on identifying and eliminating the environmental and other preventable causes of the disease. With coalition partners, BCF advocates for the elimination of carcinogenic and endocrinedisrupting chemicals through state and federal legislative efforts and corporate accountability campaigns, such as the Campaign for Safe Cosmetics.

January/February 2008 San Francisco Medicine 23

Health, Human Beings, and The Environment

Cancer and Environmental Chemicals Past Time for Politeness Devra Lee Davis, PhD If you want to go fast, go alone. If you want to go far, go together. —African proverb


y very good friend Andrea Ravinette Martin—the charismatic founder of the Breast Cancer Fund—used to say, “The only way I will know I have really survived breast cancer is when I die of something else.” She did: when she was fifty-six, a new and unrelated malignancy of the brain turned her into a breast cancer survivor. Three years before a tangled web of glioblastoma multiforme invaded her brain, Andrea was in excellent health. As part of a pilot research study of the Environmental Working Group, she was tested for chemical contaminants. She had never worked in a factory. She had no chemically intensive hobbies, like boatbuilding or oil painting. Yet it turned out that Andrea was a walking toxic waste site. Her body contained nearly one hundred different chemical residues, half of which caused cancer when tested in experimental animals. Many of these toxins didn’t exist when she was born in the middle of the past century. Had they played any role in causing either her breast or brain tumors? Did her frequent use of those clunky first-generation cell phones have anything to do with it? It is sad that we don’t know. It is appalling that we can’t find out. Look around and it seems that cancer has become the price of modern life. In America and England, one out of every two men and one out of every three women will develop cancer in their lifetime. In America alone, there are currently more than 10 million cancer survivors. Cancer is the leading killer of middle-aged persons and, after accidents, is also the leading killer of children.

Yes, deaths have dropped, chiefly because fewer are smoking and more are surviving colorectal, prostate, and breast cancer. But more new cases of the disease are arising that have nothing to do with smoking, aging, or screening. How did this happen? How did a disease that was once so atypical become so ordinary? Are we simply talking more about an illness that has always been around? Some 2,500 years ago, the Greek physician Hippocrates depicted a tumor as a muddled irritable cavity with spindly legs, flaring out of control in all directions. Fascinated with its evil, animal-like appearance, he termed it cancer, karkinoma, from the Greek word for crab. Like Hippocrates, we are drawn to things of menacing beauty. To an epidemiologist like myself, explanations of run-amok cancer processes that routinely capture Nobel Prizes and promising headlines address the how but not the why of cancer. They can tell us about how cells and organs behave when they spin out of control but say nothing about what makes these things happen to specific groups of people located in a certain area at a certain time. Why have so many types of cancer not known to be tied with smoking increased from decade to decade in industrial countries and in those areas of the developing world that are becoming industrialized?

24 San Francisco Medicine January/February 2008

Why do one fifth of all colorectal cancers in Egypt occur in persons under age thirty, a rate that is ten times higher than in the U.S.? Why are so many people in their thirties and forties in many industrial countries coming down with often fatal cancers of the bone marrow and pancreas—diseases that used to occur only in those in their sixties or older? What can we do to reverse the trend? How can we get better at keeping cancers from happening in the first place? Despite impressive progress in finding and treating some forms of the disease, more than half of all those diagnosed with cancer will not last a decade with their illness. We have all been told what we are supposed to do to reduce the risk of cancer on our own. We are supposed to eat right and exercise. Even prayer and meditation are touted as good things to do. Smoking, of course, is forbidden. And we are certainly not to drink much alcohol or engage in dangerous sex. But we all know people who lead perfectly clean, even exemplary lives, like my dear friend Andrea, and still get cancer. They take good care of themselves, yet somehow cancer hits. The first thing most cancer patients, and their sometimes unthinking friends, ask is, what did I do to make this happen? The answer, often, is not a bloody thing. Sometimes cancer is due to a genetic susceptibility that we get from our fathers or mothers, but mostly it isn’t. We know that no matter how careful anyone is about their good and bad habits, where and when we are born and what we work and play with has a lot more to do with whether we get cancer than who our parents happen to be. For instance, inherited defects do not account for most breast cancers. Nine out of ten women who develop breast cancer are

born with perfectly healthy genes. When I was a girl, one in twenty women got breast cancer in her lifetime; by the time Andrea and I reached middle age, one in seven did. Nobody can explain why. We do know that we live in a sea of synthetic estrogens and other hormones and routinely are exposed to myriad materials that never previously existed. The producers of these agents take comfort in the fact that any one of them, tested by itself, looks fairly benign when gauged by various scientific measures of carcinogenic potency. Still, it defies common sense and basic biology to assume that just because a single agent looks all right when tested on its own, we can safely endure encounters with hundreds of such materials all at once. You would never take all the different pills in your medicine chest in one swallow, even though ingesting one or a few is fine. Why, then, should we accept that there is no danger in being subjected to combinations of agents without precedent in human history? Biologist Tyrone Hayes of the University of California at Berkeley thinks the tadpoles of the seed-corn fields of York County, Nebraska, are trying to tell us something: one in every three dies when exposed to mixtures of ordinary chemicals in those fields. The start of my own scientific career coincided with a short-lived period during the late 1970s during the presidency of Jimmy Carter, when the federal government appeared serious about uncovering the causes of cancer. The National Cancer Institute and other federal agencies began a series of programs to assess the true effects of tobacco and certain widely used industrial chemicals. In 1978, these programs became more than rhetoric. Until that time, the government pretty much took industry reports on the safety of chemicals at face value, without requiring any documentation. This changed when it was learned that the company doing much of the testing for industry, Industrial BioTest, could not even find or account for all the animals it had supposedly studied. Industrial Bio-Test had tested one out of every three chemicals on which the government had any data at all. But without adequate records to show that the testing had been done properly (or at all), the reports of safety

based on this work were worthless. In 1979 the government set up its own experimental laboratory to test the cancercausing capacity of chemicals in specially bred homogenous rodents, under the U.S. National Toxicology Program. Animals were reared with well-established body sizes, types, and inclinations, so that their responses to potential cancer-causing agents could be studied carefully in order to predict and prevent cancer and other chronic ailments in humans. Even before the Industrial Bio-Test scandal, Congress had begun passing rules that appeared to require the government to act to keep cancer-causing hazards out of the market. With more than 80,000 chemicals in widespread use and complete toxicity test results available on fewer than 1,000, these laws, like the Toxic Substances Control Act of 1976, forced the government to come up with some rational way to review chemicals and separate the good from the bad, the ugly, and the ones we don’t even know what to do about. This was supposed to lead to efforts to come up with standard methods for evaluating risks, for making sense of experimental information, and for estimating ways to protect public health. Instead, the law has generated so much talk and so little action that insiders refer to it as the “Toxic Substances Conversation Act.” After the 1980 presidential election, even these meager efforts began to unravel. The early Reagan administration followed the lead of the Carter administration in its tobacco-friendly positions and also jettisoned programs that sought to rein in cancer-causing industrial sources. The new administration curtailed funding for testing chemicals under the National Toxicology Program, while federal support for scientific research aimed at designing “safe cigarettes” grew. The problem with “safe cigarettes” was that, well before the 1980s, it was widely known that there is no such thing. Inhaling thick clouds of smoke into your lungs and raising levels of carbon monoxide in your blood and that of your children, spouses, and office mates, whether from burning tobacco, wood, or coal, is simply an unhealthy thing to do. The best wars, to take a line from President McKinley’s Secretary of State,

are short, splendid little affairs, all pageantry and little fighting. The protracted war on cancer has been none of the above. How did we get to this point? From the start, this national campaign was blocked from dealing with some known causes of the disease, such as tobacco, solar and X-radiation, and synthetic hormones in the workplace and the general environment. Proof that the world in which we live and work has a lot to do with whether or not we get the disease was either overlooked or kept out of sight altogether, often by folks who had major economic interests in seeing this happen. Instead, the entire project focused on devising ways to find, treat, and cure the disease. We are spending more money than ever to find and treat cancer—some $100 billion in direct treatment costs alone. Today, one subsidiary of the global chemical firm Industrial Chemicals, Inc., makes a number of cancer-causing pesticides, such as atrazine—a compound banned in much of the industrial world—while another division of ICI, AstraZeneca, produces tamoxifen, one of the most widely prescribed cancer drugs in the world. Could this paradoxical strategy have anything to do with the fact that both the incidence of cancer not tied to smoking and its treatment options keep steadily increasing, while efforts to restrain environmental causes of the disease remain stymied? Of course not. Remember that we live in a highly technological, interconnected world. It is safer, and better for your reputation in polite society, to keep reminding yourself that the disease is just so damned complex. Dr. Devra Lee Davis is Director of the Center for Environmental Oncology at the University of Pittsburgh Cancer Institute. This article is adapted from her book The Secret History of the War on Cancer, Basic Books, 2007, with permission of Basic Books and Devra Davis. For further information, visit

January/February 2008 San Francisco Medicine 25

Health, Human Beings, and The Environment

Mercury Tales Jane Hightower, MD


n this issue of San Francisco Medicine, we learn about the many chemicals and toxicants that face us today. Physicians now must sort through the toxicants that we eat, breathe, and absorb through our skin, as some can cause adverse health effects. When looking at the toxicant mercury, I realized the history of its use in medicine was vast, as practitioners have been poisoning patients with it for centuries. Liquid mercury (quicksilver) was experimented with by the alchemists beginning centuries ago. They are the ones who discovered how to turn poor-grade gold ore (essentially a rock) into pure gold by combining mercury and various other earth salts. Making gold from a rock had mystical value, and the “elixir” that resulted in the process was thought to have medicinal qualities. Creating gold from a rock was called the Magnum Opus, and those who could achieve it were thought to gain eternal youth. They also were thought to pose a threat to some governments, since one’s ability to fabricate gold—currency—could compete with the ruling powers. As a result, alchemists were revered in some societies and executed in others (Goldwater 1972). Multiple forms of mercury have been used for medicinal purposes over the centuries. In one report comparing Kentucky and New Jersey physicians between 1854 to 1887, mercury ranked second only to opium and morphine in the total number of prescriptions written. The mercurials, including corrosive sublimate or mercuric chloride and calomel or mercurous chloride, were used for many conditions, from “promoting the flow of the liver” to antisepsis, and even liver spots. Before 1938, all one had to do was believe that a remedy worked to avoid being

accused of fraud. But calomel met its match in 1863, when Dr. William A. Hammond, the Surgeon General, removed calomel from the Union Army surgeons’ supply table, as directed in his infamous Circular Number 6. His reasoning was that it was being overused to the point of causing the side effects of melancholy, hypersalivation, and gangrene of the mouth. The army doctors, who, Hammond thought, were in many cases unqualified, were furious. The “regulars” (also referred to as allopaths) thought Hammond had “done great and inexcusable injustice to a noble, humane, scientific, and self-sacrificing profession.” They also thought he was caving in to the homeopaths, who thought mercury was toxic in all forms. The Transactions of the American Medical Association in 1864 describe the process whereby the AMA formed a committee just to address this circular. They gathered up some of the army surgeons and asked their opinion. The army surgeons said they never saw any cases of mercurialism and that Hammond’s circular was an “unwarranted assumption of authority, and a reckless attempt to cut the Gordian knot of intricate pathology by the exercise of official power.” Hammond was court-martialed shortly thereafter, and many historians have stated that his removal of calomel from army use that was the last straw that led to his disgrace. In 1878, a Senate hearing concluded that his court-martial was a political one and that there was no dereliction of duty or improper misconduct. He was fully exonerated and restored to the U.S. Army with the rank of Brigadier General, retired (American Medical Association 1864, Flannery 2004). It is curious that, while today mercury

26 San Francisco Medicine January/February 2008

is being removed from our allopathic medicines, a patient brought to me a homeopathic remedy that contained mercurious solubilis. Another common mercurial was bichloride of mercury, or corrosive, or sweet sublimate. Many physicians thought that it had antiseptic capabilities. It was not until the 1930s that experiments revealed that it only had some bacteriostatic properties and was not adequately bacteriocidal. Regardless, I found in our local San Francisco history that Dr. Levi Cooper Lane, who founded and built the Levi Cooper Lane Hospital in 1875, believed in the virtues of bichloride so much that he had it added to the plaster mixture that went onto the walls of the entire hospital. That hospital is now in some unfortunate landfill, and in its place is my office building at 2100 Webster Street. Even in the “new” Stanford hospital, built in 1917, surgeons would wash their hands in bichloride. Some would pour it on the floor, thinking it would ward off the post-op infections that were a terrifying complication of the time. I could not find whether the surgeons had symptoms of mercurialism, but this practice faded as better rubber gloves became available and bichloride’s lack of effectiveness became evident (Brewer 1939, Deforest 1944, Morton 1948, Deforest 1949, Stanford University 1959). As for the surgical practice of yesteryear, an 1895 JAMA printed a story of how a doctor in training was asked to give a patient a shot of whiskey after a minor procedure. Unfortunately, the whiskey was stored next to the bottle of bichloride. Even the patient agreed that it did not taste like whiskey. Fast action was called for, and in four minutes, the patient was asked to swallow the albumen of half a dozen eggs to coat the

ach, then in another minute a stomach tube was introduced to “thoroughly wash out” his stomach. No mercurialsm was noted in the patient, the author boasted, and the patient “suffered no inconvenience from the energetic treatment” (no author, 1895). Merthiolate, otherwise known as thimerosal, contains ethylmercury and has posed a different conundrum. Eli Lilly patented it in 1928 as an antiseptic and for treatment of nose and throat infections. The Lilly scientists later declared many uses for their wonder remedy, including that it was a cure for the common cold. This was quickly refuted by another study. Because of the antisepsis claims very early in its use, it wound up in our vaccines from their beginning. The antisepsis claim continues to be made even though there is evidence to the contrary. Mercury has been shown to stimulate antibody formation; one could ask, then, whether thimerosal remained in the vaccines as an adjuvant, and not necessarily as an antiseptic. The only metal that is currently FDA approved as an adjuvant is aluminum, which was introduced to replace thimerosal. To call mercury an adjuvant would require testing to establish safety and efficacy. Its antiseptic claim was grandfathered in. Fortunately, the vaccine manufacturers have found an alternative, and we have more requirements for the assessment of safety and efficacy (Bassler 1935, LeBlanc 1936, Pichichero 2005). As for the over-the-counter mercurials, they had also been grandfathered in before the FDA rules of proving safety and efficacy. They continued to be in use despite having been linked to the occurrence of the neurologically disabling and sometimes fatal acrodynia (pink) disease in children. In the 1980s, the FDA advisory committee said that the mercurials should go through an assessment of safety and efficacy, and the manufacturers were notified of this. It was not until 1998, when the remaining twenty over-the-counter mercurials, made by eight different companies and including the popular tincture mercurochrome, met their demise. When the FDA gave final rule to have these agents removed from over-the-counter use, no challenges were brought forth by the manufacturers to prove safety or efficacy. These agents just quietly

disappeared (Federal Register 1998). As for the treatment of syphilis, many mercurial agents, including the blue pill, were used until penicillin was discovered to be a cure. Hence the common saying, “a night with Venus means a life with Mercury.” But the mercurials were never proven to cure syphilis; many who had the condition would go on to have tertiary syphilis, or the disease would seem to remit spontaneously. Meanwhile the treatment with these agents was often thought to be worse than the disease itself. The tale of mercurial diuretics will certainly be of interest to many physicians, as some still remember using these agents early in their careers. It was in 1919, when a child was given the mercurial Novosurol for his syphilis, that an astute nurse noted a marked diuresis. The doctors tried it on other patients in the hospital and it was noted to have the same effect. A new diuretic was born. The mercurial diuretics lasted for decades, despite some fatalities and adverse effects. For many of these moribund patients, it was either mercury or death—sometimes both (Vogl 1950). As for the prescription mercurial agents in general, the World Health Organization asked for the phase-out of mercurial medications in 1972. The prescription-only mercurial agents disappeared as more effec-

tive agents replaced them (World Health Organization 1972). Perhaps you may wonder how much mercury was contained in one dose of diuretic or a syphilis pill. It was 40,000 to 66,000 mcg. Although the absorption or bioavailability is unknown, it was thought to be near lethal doses. So here we are today, arguing over the amount of methylmercury contained in a serving of fish. This can be anywhere from undetectable to greater than 170 mcg per six-ounce serving. The varying toxicities of the many types of mercury makes it difficult for researchers and policy makers to sort out how much mercury can lead to adverse health effects, especially for those chronically exposed. To date, there is no known level of methylmercury that has been determined to be without harm. This article will serve to give an understanding of why the medical community has been puzzled by it all. Dr. Jane Hightower, a San Francisco internist, is currently serving on the Board of Directors of SFMS. In Spring 2008 her latest book will be released, entitled Diagnosis Mercury: Money, Politics and Poison (Island Press). References to this article are available online at

Johnson KC and Glantz SA. Evidence secondhand smoke causes breast cancer in 2005 stronger than for lung cancer in 1986. Abstract. Objectives: To compare the strength of evidence from epidemiologic studies of secondhand smoke for the U.S. Surgeon General’s 1986 conclusion that secondhand smoke caused lung cancer with the California Environmental Protection Agency’s (CalEPA) similar 2005 conclusion on breast cancer in younger, primarily premenopausal women. Methods: We reviewed each report for criteria used to assess causality; numbers of studies, statistically significant increases in risk, and pooled summary risk estimates. Results: Both the Surgeon General and CalEPA used updated Bradford Hill criteria for assessing causality and found that the evidence met those criteria. Six of 13 lung cancer studies (46 percent) had statistically significant increases (one of three cohort studies). Pooled risk estimates for lung cancer for spousal exposure were 1.53 for 10 combined case control studies and 1.88 for 7 studies with dose-response results. The CalEPA reported 10 of 14 studies (71 percent) had statistically significant increases in breast cancer risk (two of four cohort studies). Pooled relative risk estimates for younger, primarily premenopausal women were 1.68 (95 percent CI: 1.33, 2.12) for all exposed women and 2.19 (1.68, 2.84) for five studies with better exposure assessment. Conclusions: The evidence from epidemiologic studies of secondhand smoke in 2005 for breast cancer in younger, primarily premenopausal women was stronger than for lung cancer in 1986. This paper, in press at Preventive Medicine, is now available online at http://dx.doi. org/10.1016/j.ypmed.2007.11.016. January/February 2008 San Francisco Medicine 27

Get Paid What You’re Worth

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Health, Human Beings, and The Environment

Time to Update Environmental Regulations Should public health standards for endocrine-disrupting compounds be based upon sixteenth-century dogma or modern endocrinology? John Peterson Myers, PhD, and Fred S. vom Saal, PhD


ealth standards established in the United States for exposure to toxic chemicals rest upon a core assumption: high-dose testing procedures used in regulatory toxicology adequately predict potential low-dose effects. Scientific discoveries over the past decade have profoundly challenged that assumption as information has grown about the commonness of contaminants that behave like hormones. Endocrinologists long ago discovered that hormones have effects at low serum concentrations that can differ dramatically, and unpredictably, from those caused at high levels (1). Indeed, sometimes they can be diametrically opposed. This endocrinological reality stands in direct conflict with any assumption that high-dose studies predict low-dose impacts. If contaminants with hormonal characteristics, known as endocrine disruptors, behave similarly, then the regulatory tests used to establish safety standards may be blind to important impacts. A growing body of research now confirms that endocrine disruptors, like hormones, can also contradict the expectations of traditional regulatory testing. This creates the strong likelihood that some health standards currently used to set exposure limits for the American public are too weak. To the nonendocrinologist, it seems logical that higher doses would lead to greater effects. This assumption has been at the core of toxicology for centuries, beginning with Paracelsus’s sixteenth-century observation that “All things are poison and nothing is without poison; only the dose permits something not to be poisonous.” His quote has been paraphrased to “the dose makes the poison” and is generally interpreted to mean that the higher the

exposure, the greater the impact. For many contaminants, toxins, poisons, and pharmaceuticals, this assumption has helped protect public health. But sub-

“It is time that the FDA and EPA move beyond sixteenth-century dogma and begin using twentyfirst-century scientific knowledge.” stantial evidence is now in hand showing that people are exposed to hundreds (if not more) chemicals that can behave like hormones. Some endocrine-disrupting chemicals are produced in very high volumes. The compounds of greatest concern include plastic monomers and plasticizers used widely in common consumer goods, leading to virtual ubiquitous exposure in the U.S. and other developed countries. For example, the plastic monomer bisphenol A (BPA) was discovered to be an estrogen in the 1930s, but now it is used as the basic chemical building block for polycarbonate plastic and an epoxy resin used to line most food cans sold in U.S. supermarkets today. The chemical characteristics of polycarbonate and the epoxy resin guarantee that normal use will contaminate food and water that comes into contact with BPA-based materials, especially if heated. Most plastic baby bottles are made with polycarbonate, and baby formula cans are lined with the resin. This will result in substantial, unavoidable exposures for infants fed warmed formula.

30 San Francisco Medicine January/February 2008

Many studies have shown that BPA is capable of causing a wide range of adverse effects in laboratory studies at serum concentrations beneath the median level found in people throughout the developed world (2). The adverse effects caused by fetal exposure and infant exposure to BPA in animal experiments include breast cancer, prostate cancer, impaired fertility, cystic ovaries, uterine fibroids, hyperactivity, and obesity. The current EPA and FDA health standards for BPA, however, are based upon traditional toxicological testing conducted in the 1980s. Modernizing the BPA standard based on current science would require lowering acceptable exposures by a factor of at least 5,000-fold and would require elimination of BPA from many common products. Driven by a need to be cost effective, regulatory toxicology has applied the “dose makes the poison” concept in practice by testing first at high doses and then testing at successively lower doses until no response, or little response, is seen. Often only three or four doses are used, and for the vast majority of chemicals these are rarely, if ever, low enough to be comparable to levels experienced by the general public. The assumption is that this high-dose testing protocol predicts the types of effects that might take place at much lower levels. And because “the dose makes the poison,” the expectation is that by working down the dose-response curve from a level that clearly causes an effect to one that does not, this process can identify exposures beneath which there will be no harm. Endocrinology, however, is replete with cases in which hormone action at low levels differs dramatically from hormone action at high levels. For example, administering newborn mice a high dose (1,000 µg/kg/day)

of the estrogenic drug diethylstilbestrol (DES) causes weight loss in adult mice. In contrast, a dose of 1 µg/kg/day causes grotesque obesity in adulthood (3). Another example with clinical implications comes from the well-known “tamoxifen flare.” Tamoxifen is useful clinically because at high doses (administered daily at 20 to 40 mg) it is an antiestrogen, suppressing proliferation of breast cancer cells and producing tumor regression (4). Early during treatment, however, when tissue levels are still rising, tamoxifen administration can cause several estrogenic effects, including a slight increase in tumor size. Research by Wade Welshons at the University of Missouri has explored the molecular mechanisms of the tamoxifen flare and finds that at serum concentrations 10,000 times beneath the level used to suppress breast cancer cell proliferation, tamoxifen acts as an estrogen, actually promoting proliferation (Welshons, pers. comm.). Ironically, his calculations show that if one were to use standard riskassessment procedures with the tamoxifen dose-response curve—identifying the highest exposure with no discernable effect and then applying a series of safety factors that take into account various sources of uncertainty— the concentration with maximum proliferative effect would be identified as a safe level of exposure. In the tamoxifen flare, the doseresponse curve showed inhibition at high levels and proliferation at low—that is, completely opposite effects. This is a special case of what are called nonmonotonic doseresponse curves: dose-response relationships in which the slope of the line plotting response as a function of dose changes its sign (positive to negative or the reverse) somewhere over the range of doses used. Clinicians who treat women and men for hormone-stimulated diseases (uterine fibroids, prostate cancer) advise their patients who take a hormone (Lupron) that some adverse effects occur during the initial phase of treatment. This is due to the fact that as the amount of the drug increases after injection, the low doses of Lupron result in the ovaries producing estrogen or the testes producing testosterone; only after reaching a high dose is the drug’s desired effect, inhibition of estrogen or testosterone

production, achieved—opposite effects occur at low and high doses. This is not just true for hormonally active drugs but for all hormones and hormone-mimicking chemicals used in products. As research has progressed in the toxicology of endocrine-disrupting compounds, nonmonotonic curves have been reported regularly (5). One of the earliest examples involved the response of the mouse prostate to exposure to several different estrogenic compounds during fetal development (6). These experiments examined the adult prostate weight following fetal exposure, separately, to estradiol or diethylstilbestrol (DES); analogous nonmonotonic findings now exist for BPA in human prostate cancer cells (7). Each experimental series, conducted over an extremely wide range of doses, showed that the highest exposures did not differ from the controls, but that intermediate doses led to significant increases in prostate weight and also to sensitivity to androgen stimulation. The dose-response curve took the shape of an inverted U, a descriptor now used in the literature to describe this type of nonmonotonic doseresponse curve. If the dose range had been extended even higher, the response would have fallen significantly beneath the controls as exposure moved into a concentration at which the compounds were overtly toxic. This was demonstrated at the level of individual genes involved in regulating prostate growth (8). Other endocrine-disrupting compounds demonstrating nonmonotonic patterns include the phthalate DEHP; the pesticides DDE, dieldrin, endosulfan, and hexachlorobenzene; and arochlor 1242, a PCB (5). Some of the reported effects include strong exacerbation of allergic reactions following exposures well beneath current safety standards. Extensive evidence is now available on the molecular and physiological mechanisms that are responsible for these findings. At very low doses, hormones can stimulate the receptors in cells that allow the hormone to cause effects in the cells (called “receptor up regulation”), while at higher doses, receptor “down regulation” occurs and the number of receptors available to mediate the action of the hormone is reduced (1, 9).

Also, there are myriad hormonal feedback mechanisms between the brain, pituitary gland, and hormone-producing organs (thyroid gland, adrenal glands, ovaries, testes) that contribute to the presence of nonmonotonic dose-response curves. The chemical risk assessment establishment has been unresponsive to the fact that one of its core assumptions has been invalidated. Hence, no standard for any contaminant has incorporated these wellestablished findings from endocrinology. Instead, standards continue to be based upon testing procedures that assume highdose testing can adequately predict low-dose results. The American public depends upon regulatory agencies to set public health standards that will avoid harmful exposures. It is time that the FDA and EPA move beyond sixteenth-century dogma and begin using twenty-first-century scientific knowledge to accurately determine the safety of the chemicals being used in plastic, toys, food containers, pesticides, cosmetics, building materials, clothes—in other words, countless products and materials we incorrectly assume are safe. Given the wide range of health effects now shown to be caused in animals by exposure to these contaminants, modernizing the standards may reap large benefits for public health. Dr. John Peterson Myers is Founder, CEO, and Chief Scientist of Environmental Health Sciences and the publisher of His research on endocrine disruption began in 1989. Along with Theo Colborn and Dianne Dumanoski, he published Our Stolen Future in 1996. Dr. Fred vom Saal is Professor in the Division of Biological Sciences, University of Missouri, Columbia. References to this article are available online at

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January/February 2008 San Francisco Medicine 31

Health, Human Beings, and The Environment

Nanoparticles and Health Thoughts on Some Early Findings John M. Balbus, MD, MPH


he promise of nanomedicine relies in great measure on the tiny size of a range of different types of nanoparticles and the unique properties that emerge at this scale. These properties influence the ways that nanoparticles move through the body, which differ from the behavior of both individual chemical molecules in solution and larger particles. These properties also lead to unique interactions with receptors and biomolecules (such as DNA) and physicochemical attributes (such as fluorescence) that make these materials useful for medical purposes. While these properties in nanoparticles may bring medical benefits, they also may result in unusual toxicity or pathways for exposure. The good news is that the regulatory requirements for testing novel therapeutic and diagnostic tools are likely to uncover most significant toxicity for nanoparticles used in medicine, at least for the routes of administration tested; the bad news is that nanoparticles with similar properties are being used for a host of nonmedical applications, and the requirements for testing before commercialization are extremely limited (with pesticides being an exception). To the extent that medical and nonmedical nanoparticles are similar, however, the knowledge about potential risks gained from testing medically-oriented materials can be combined with the limited data on nonmedical nanoparticles to try to design safer, less toxic nonmedical materials. Testing on medical nanoparticles will provide limited information about target organ toxicity arising from inhalational or dermal exposure, and essentially none on environmental transport and ecological toxicity, which are critical issues for nanoparticle safety. Nonetheless, with hundreds of

nanoparticle products on the market, the sooner any toxicity information is gathered, the better. This article reviews some of what has emerged from initial studies of

“A handful of early studies suggest that some nanoparticles have the potential for novel and serious long-term types of toxicity, but what we mostly have are still huge gaps in our knowledge.” nanoparticles. Two points are worth noting at the outset. First, it is impossible to generalize about nanoparticles. Not only are there many different types made from different materials—ranging from pure carbon nanotubes to cadmium-based quantum dots to aminebased dendrimers—but it is also clear that subtle changes to nanoparticles’ coatings and structures can result in huge changes in their behavior and toxicity. Second, practically nothing is known about the long-term health impacts of any type of nanoparticle. A handful of early studies suggest that some nanoparticles have the potential for novel and serious long-term types of toxicity, but what we mostly have are still huge gaps in our knowledge. Some early surprises have come from studies of nanoparticle behavior in the environment. For example, carbon-based nanoparticles like carbon nanotubes and buckyballs (also known as fullerenes) are very poorly water soluble as individual particles and might be expected to adhere to

32 San Francisco Medicine January/February 2008

soil and be relatively immobile in an aqueous environment. Two studies, however, showed that buckyballs are capable of forming toxic nanocrystals that are stable when suspended in water (Fortner et al., 2005), while individual carbon nanotubes can be stabilized by high organic content in natural river water (Hyung et al., 2007). Many nanoparticles agglomerate readily and, if suspended in air, tend to be larger than the nano-size range (i.e., over 100 nanometers). If nanoparticles do stay suspended in the nano-size range, especially if they are smaller than roughly 30 nanometers, they can deposit in the nasopharynx, from which they can migrate through the olfactory nerves into the brain (Oberdorster et al., 2004; Elder et al., 2006; Ji et al., 2007). Initial studies have demonstrated the critical importance of subtle surface changes to the toxicity and behavior of nanoparticles. One study showed that the coatings on fullerenes can change the cytotoxic dose by seven orders of magnitude (Sayes et al., 2004). Other studies have shown that surface coatings can influence skin penetration of quantum dots (Ryman-Rasmussen et al., 2006) and distribution and retention of carbon nanotubes injected into the bloodstream (Liu et al., 2007). One of the ways surface coatings moderate the behavior and toxicity of nanoparticles is by influencing protein binding. Many studies have demonstrated that nanoparticles immediately become coated with proteins as soon as they encounter biological fluids. Some of these, like apo-lipoproteins, may facilitate uptake into vascular endothelial cells or across the blood brain barrier (Kim et al.; 2007, Liu et al., 2006). The small size of nanoparticles results in highly curved surfaces that could distort native protein architecture as

teins bind to them, raising the potential risk of generating novel epitopes and consequent autoimmunity (Lynch et al., 2006). Carbon nanotubes, which are in many ways the poster children of nanotechnology, have demonstrated some unusual properties in toxicity assays. Shvedova et al. (2005) found that carbon nanotubes caused deposition of collagen in the interstitial areas of alveoli without inducing inflammation. This unusual direct stimulatory effect is seen in a variety of different settings (e.g., WorleKnirsch et al., 2006) and may well have beneficial biomedical applications (Meng et al., 2006), such as stimulating nerve regrowth in patients with spinal cord trauma. But the

potential for causing pulmonary fibrosis or other types of granulomatous lesions must be thoroughly assessed in the development of any carbon nanotube application, especially one that might result in worker or consumer exposure. Nanoparticles hold great promise for enormous advances in treatment and diagnosis of human illness. But their unique properties also carry the potential for unusual toxicity or exposure. As the makers of nanomedicines test and tinker with their technologies to create the most effective and least toxic products, the rest of the nanotechnology world must take notice and apply all available information

to the safe development of nonmedical nanoparticles. A physician and public health professional, Dr. John Balbus works and consults on a broad range of environmental health issues, including air pollution, built environment and health, climate change, nanotechnology, toxicology, and antibiotic resistance. Prior to joining Environmental Defense, Dr. Balbus was on the faculty at the George Washington University Schools of Medicine and Public Health and Health Services, where he was founding Director of the Center for Risk Science and Public Health and founding Codirector of the Mid-Atlantic Center for Children’s Health and the Environment. Board-certified in both Internal and Occupational and Environmental Medicine, Dr. Balbus combines experience as a clinician with expertise in environmental health sciences. He is currently a member of the National Academy of Science Board on Environmental Studies and Toxicology; the Institute of Medicine Roundtable on Environmental Health Sciences, Research and Medicine; and the EPA Children’s Health Protection Advisory Committee. He holds adjunct faculty appointments at the Johns Hopkins Bloomberg School of Public Health and at George Washington University. References to this article are available online at

Neurodevelopmental Disorders and Environmental Agents A New Consensus Statement

Elise Miller, MEd, and Steve Gilbert, PhD, DABT


he Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders, developed by the Collaborative on Health and the Environment’s Learning and Developmental Disabilities Initiative, was finalized in November 2007 and presented at the XVI International Neurotoxicology Conference in San Antonio, Texas. The statement, which has a glossary and more than 200 references, was drafted and reviewed by a committee of highly respected scientists and health professionals in the

neurodevelopmental environmental health field. Based on detailed documentation, they agreed to the following: Given the established knowledge, protecting children from neurotoxic environmental exposures from the earliest stages of fetal development clearly is an essential public health measure if we are to help prevent learning and developmental disorders and create an environment in which children can reach and maintain their full potential. Once the document was finalized, other

national and international scientists and health professionals were asked to sign on as well. For the full statement and signatories, please see This document, along with other scientific consensus statements generated through the Collaborative on Health and Environment initiatives, serve to provide the best available scientific evidence on environmental contributors to various diseases and disabilities for researchers, health professionals, policy makers, advocates, and other concerned citizens.

January/February 2008 San Francisco Medicine 33

Health, Human Beings, and The Environment

Biomonitoring Update Measuring What is Inside Us Davis Baltz, MA


he field of biomonitoring continues to develop rapidly. Since San Francisco Medicine last reported on biomonitoring in the January/February 20061 issue ( and select the January/February 2006 issue from the list), there have been significant advances in the use of this scientific data-gathering tool. Biomonitoring is the measurement of chemicals and their breakdown products or metabolites in human tissues such as blood and urine. Chemicals can also be detected in meconium, umbilical cord blood, and breastmilk, providing important information on prenatal and early life exposures to chemicals in the environment that may be harmful. For example, researchers recently showed toxic flame retardants (PBDEs) and long-banned industrial chemicals (PCBs) were nearly universally found in umbilical cord blood (1). With its real-world exposure data, biomonitoring is important because it provides baseline data on chemical exposure and allows us to track exposure trends over time. This is particularly important as evidence mounts that chemicals can contribute to disease (2). One of the most important developments in the field is the approval of the nation’s first state biomonitoring initiative, the California Environmental Contaminant Biomonitoring Program (3). The bill creating the program, authored by Senators Don Perata and Deborah Ortiz, was signed by Governor Arnold Schwarzenegger on September 29, 2006. Despite a tight budget process, adequate funding has been secured to launch the program, and a Scientific Guidance Panel has been named by the

governor and legislature. The program’s first priority will be to generate a statistically significant statewide “snapshot” of environmental chemical exposure among Californians. In addition, the program will begin to plan for and then conduct smaller, localized, communitybased studies. Thus, California will be able to track statewide exposure trends over time, as well as investigate highly exposed communities. Significantly, the program contains an important right-to-know provision whereby individual study contributors will receive their own results if they choose. Another important aspect is that there are no restrictions on the chemicals that can be considered for testing. For example, there is no requirement for a risk assessment to be performed before chemicals can be scrutinized. Canada has also committed to begin to conduct biomonitoring on a national scale by adding a biomonitoring component to its Canadian Health Measures Survey (CHMS) (4). Beginning this winter, the CHMS is being conducted across Canada over a two-year period, involving a sample of 5,000 Canadians of both sexes ranging in age from six to seventy-nine. Another significant development was the July 2006 report by National Research Council of the National Academy of Sciences, Human Biomonitoring for Environmental Chemicals (5). While recognizing that biomonitoring by no means answers all questions about chemicals and human exposure to them, the NRC notes the immense value of biomonitoring and further concludes that strategies for communication should be developed at the individual,

34 San Francisco Medicine January/February 2008

community, and population levels; and that states that fail to share results raise ethical concerns. The report recommends that biomonitoring studies should also include the collection of demographic, socioeconomic status, and lifestyle factors. Meanwhile, the CDC (Centers for Disease Control and Prevention) continues its national monitoring program (6). There have been three biennial reports since 2001. At the time of writing, it appears that the timeline for the next CDC National Exposure Report will slip from 2007 to June of 2008 and provide data on 275 chemicals. Public health advocates and communities have increasingly used biomonitoring to point out the widespread nature of exposure as well as the regulatory failures that have allowed exposure to continue. For example, a November 2007 national report entitled Is It in Us? (7) generated extensive media attention by reporting on the levels of toxic flame retardants (polybrominated diphenyl ethers), bisphenol-A, and phthalates in a cross section of Americans. Among other findings, the study showed that average levels of bisphenol-A found in study participants were higher than those that cause damage in laboratory animal studies. Davis Baltz is Special Projects Advisor for the Collaborative on Health and the Environment. References to this article are available online at

Health, Human Beings, and The Environment

Electromagnetic Fields A Biologically-based Public Exposure Standard David Carpenter, MD, and Cindy Sage, MA


n international working group of scientists, researchers, and public health policy professionals, the BioInitiative Working Group, has released its report on electromagnetic fields (EMF) and health. It raises serious concern about the safety of existing public limits that regulate how much EMF is allowable from power lines, cell phones, and many other sources of EMF exposure in daily life. The authors reviewed more than 2,000 scientific studies, reviews, and meta-analyses and concluded that the existing public safety limits are inadequate to protect public health. From a public health policy standpoint, new public safety limits and limits on further deployment of risky technologies are warranted based on the overall evidence. The report documents scientific evidence

that power line EMF exposure is responsible for hundreds of new cases of childhood leukemia every year in the United States and around the world. Risks for brain tumors and acoustic neuromas (from cell and cordless phones) and Alzheimer’s disease are documented and there is evidence that EMF is a risk factor for both childhood and adult cancers other than leukemia. This report stands as a wake-up call that long-term exposure to some kinds of EMF may cause serious health effects. We need to educate people and our decision makers that “business as usual” is unacceptable. Coeditor Cindy Sage presented the evidence from the BioInitiative report at the Royal Society of London’s November 2007 meeting that discussed the inadequacy of existing international public safety standards.

Brain tumor specialist Dr. Lennart Hardell, MD, PhD, Professor at University Hospital in Orebro, Sweden, spoke on his chapter on brain tumors and acoustic neuromas. His work on cell phones, cordless phones, and brain tumors is widely recognized to be pivotal in the debate about the safety of wireless radiofrequency and microwave radiation. Olle Johansson, PhD, of the Karolinska Institute presented his BioInitiative chapter on EMF effects on immune function and electrical hypersensitivity. The full report may be accessed at Dr. David Carpenter is Director of the Institute for Health and the Environment at the University of Albany, New York. Cindy Sage is with Sage Associates in Santa Barbara, California.

Chemical Exposures on the Job May Be Linked to Diseases in Nurses First-ever national survey finds widespread exposure to chemicals and radiation and almost no mandatory workplace health protections Charlotte Brody, RN


first-ever national survey of nurses’ exposures to chemicals, pharmaceuticals, and radiation on the job suggests there are links between serious health problems such as cancer, asthma, miscarriages, and children’s birth defects and the duration and intensity of these exposures. The survey included 1,500 nurses from all fifty states. The results were released online at Every day, nurses confront low-level but repeated exposures to mixtures of haz-

ardous materials that include residues from medications, anesthetic gases, sterilizing and disinfecting chemicals, radiation, latex, cleaning chemicals, hand and skin disinfection products, and even mercury escaping from broken medical equipment. There are no workplace safety standards to protect nurses from the combined effects of these exposures on their health. The Centers for Disease Control proposed a National Occupational Exposure Survey for the health care industry in 2002. To date, no such survey has been initiated

to better understand the range of potentially hazardous chemical exposure in the health care industry and related illnesses. The project was conducted by the Environmental Working Group, American Nurses Association, Health Care without Harm, and the Environmental Health Education Center at the University of Maryland School of Nursing. Charlotte Brody, RN, is Executive Director of Commonweal and co-director of Health Care Without Harm,

January/February 2008 San Francisco Medicine 35

Health, Human Beings, and The Environment

The War Goes On Tobacco Control in California Mi-Kyung Hong, MPH; Richard L. Barnes, JD; Stanton Glantz, PhD; and Steve Heilig, MPH Smoking seems insane now—we have to adapt. —Lisa Zane, Parisian singer and ex-smoker, on the new Franch ban on smoking in bars and cafes.


he human casualties of the ongoing “tobacco wars” far outstrip those of any other battle. This war is fought on many fronts against not only the innate addictive and health-destroying effects of tobacco itself, but against the profit-seeking and well-funded efforts of those who sell it. What follows is a brief update on the war on one state front. Tobacco control, to be truly effective, relies on decreasing two primary exposures— that of smokers themselves and that of “environmental” tobacco smoke, now inarguably shown to be a serious hazard. While smoking prevalence in California continued its decline, to an historic low of 13.3 percent in 2006, the decline was slower than in earlier years, reflecting the fact that tobacco control efforts in California were drifting, with no clear indication that the state would regain leadership in tobacco control. Political leaders continue to emphasize approaches that are not proven to be effective, such as school-based education programs, while moving slowly with those that are effective, particularly a strong media campaign. There have also been marked reductions in funding for important and innovative tobacco control research. However, on the brighter side, the Attorney General’s office has vigorously enforced tobacco industry compliance with the Master Settlement Agreement. Campaigns to end tobacco industry violations with regard to youth marketing tactics and youth access to tobacco products were successful. Former Attorney General Bill Lockyer was active in the campaign of a multistate group of Attorneys

General to get smoking out of movies targeted at children; but current Attorney General Jerry Brown has not participated in this effort. The tobacco industry intensified its efforts to influence California politics with its campaign contributions to legislators, legislative candidates, political parties, and constitutional officers. The industry steadily increased these contributions from $4,086,553 in 2003­–2004 ($1,083,448 to candidates) to $4,359,205 in 2005–2006 ($1,895,584 to candidates). Campaign contributions from the tobacco industry continue to heavily favor Republicans. In 2005–2006, $1,797,484 was contributed to the Republican candidates and officeholders and to the California Republican Party compared to $98,100 to the Democrats. Of the fifty-six legislators who took no tobacco industry contributions in 2005-2006, fifty-two were Democrats. Perhaps there is a link here to Governor Schwarzenegger’s veto of two important tobacco control bills in 2006, a ban on Internet sales of cigarettes, and a mandate for health insurance coverage of smoking cessation services. Still, six tobacco control measures were passed in the 2007 session. Among these is a prohibition on smoking in any motor vehicle with any minors present. A most significant event was the 2006 defeat of Proposition 86, which would have increased cigarette taxes by $2.60 a pack. What began as a well-planned initiative by health groups for a $1.50 tobacco tax increase became an excessive, badly structured initiative that the tobacco industry attacked in its $66 million campaign. Voters rejected Proposition 86, with 51.3% voting “no.” Innovations in local tobacco control policy making have focused on preventing exposure to environmental smoke, especially where people live. Momentum for nonsmok-

36 San Francisco Medicine January/February 2008

ing multiunit housing has been building, with surveys showing that 80 percent of nonsmoking tenants in California wish to live in smokefree buildings. In 2004, the Thousand Oaks City Council became the first in the nation to pass a mandate requiring that one-third of new multiunit affordable housing units funded by the city be nonsmoking. Another important first came in 2006 when the City of Calabasas mandated an all-inclusive smoke-free policy in the entire city except in small designated smoking areas in shopping malls. Then, in October 2007, Belmont became the first city in California to ban smoking in the residential units of all multiunit housing. Adding to this expansion, smoke-free ordinances for public beaches have also been passed by many local communities in California. The history of tobacco control in California has been local activism and voter initiatives, with statewide legislation following. Local activism is still the key source of innovation. Here perhaps more than anywhere, prevention is crucial to decreasing suffering in the future, both in terms of avoiding the cultivation of new smokers and decreasing exposure to environmental tobacco smoke. The current effort to regulate tobacco via the FDA is very complex, but the fact that major tobacco companies support this proposal should give us pause, at minimum. Finally, for those who might see smokers in clinical settings, experience and research continues to confirm that asking about smoking and urging and helping smokers to quit is one of the best interventions known to help patients. For a recent report on many of these issues, see: Hong MK, Barnes RL, and Glantz S. Tobacco control in California 2003–2007: Missed opportunities. Center for Tobacco Control Research and Education. 2007. http://repositories.

Health, Human Beings, and The Environment

Agent Orange and Birth Defects The Legacy Continues Betty Mekdeci


he soldiers are dying. As if that weren’t tragic enough, the children they have left behind are suffering. Sometimes at Birth Defect Research for Children we hear from veterans, but usually it is wives and children who send us poignant messages: “I lost my husband from a cancerous brain tumor thirteen months ago. My son has many disabilities, including Tourette’s syndrome, mental retardation, mild cerebral palsy, and hydrocephalus, and he is profoundly deaf. He will never be able to live on his own.” “My father passed away in 1998. He had many health problems, including type II diabetes. He was only fifty years old. Agent Orange has been a part of my life from the moment I was born. I was born without my right leg, several of my fingers, and the big toe on my left foot. My mother had three miscarriages. My younger brother (age twenty-nine) has to wear bifocals and suffers from chronic joint pain.” “I served four tours in Vietnam. We have three children: one daughter with a heart defect, another with scoliosis and digestive problems, and a son born with a defective optic nerve that has left him blind in the right eye. There is no history of birth defects on either side of our family.” Since 1991, we have recorded thousands of such cases in our National Birth Defect Registry. Some 2.8 million Americans served in the Vietnam theater of operations. Three to 6 percent of Vietnam veterans’ children are born with some kind of birth defect (Emory University School of Medicine reports a 3 to 4 percent birth defect rate among the general population). An impressive body of scientific evidence points to increases in

birth defects and developmental problems in the children of Vietnam veterans and others exposed to dioxin-like chemicals. Agent Orange was a combination of two defoliants, 2,4,5-T and 2,4-D, contaminated by dioxin (TCDD), a toxic byproduct of the chemical production process. More than 19 million gallons of herbicides were sprayed in Vietnam between 1962 and 1971. More than 11.2 million gallons sprayed after 1965 were dioxin-contaminated Agent Orange. Agents Purple, Pink, and Green used before 1965 were even more highly contaminated with dioxin. According to Barry Commoner and Thomas Webster in their 2003 book Dioxins and Health, “The current scientific evidence argues not only that dioxin is a potent carcinogen but that the noncancer health and environmental hazards of dioxin may be more serious than believed previously.” They report that dioxin appears to act like a persistent synthetic hormone that interferes with important physiological signaling systems that can lead to altered cell development, differentiation, and regulation. The most troubling consequence is the possibility of reproductive, developmental, and immunological effects at the levels of dioxin-like compounds present in the bodies of the average person. Since studies of Vietnam veterans exposed to herbicides in Vietnam have found much higher levels of dioxin in their bodies than are found in the average person, these effects also should be detectable in their children. In 1996, the National Academy of Sciences found “limited/suggestive” evidence of an association between Agent Orange exposure and spina bifida, a neural tube defect, in the children of Vietnam

veterans. In 2000, Dr. H. K. Kang of the Environmental Epidemiology Service of the Veterans Health Administration published a study that found that the risk of moderate to severe birth defects was significantly associated with the mother’s military service in Vietnam. As a result of these findings, the V.A. now funds assistance programs for spina bifida in the children of male or female Vietnam veterans and for all birth defects without other known causes in the children of female veterans. The Australian Department of Veterans Affairs (without acknowledging a link to Agent Orange exposure) provides treatment to the children of Vietnam veterans with spina bifida, cleft lip or palate, acute myeloid leukemia, and adrenal gland cancer. Other studies offer evidence that many more birth defects may be associated with dioxin-contaminated herbicide exposure in Vietnam. In 1990, an independent scientific review of the literature concluded that elevated incidences of birth defects in the children of Vietnam veterans were found in several studies. These included spina bifida, oral clefts, cardiovascular defects, hip dislocations, and malformations of the urinary tract. In addition, defects of the digestive tract and other neoplasms, such as neuroblastoma, also were higher in Vietnam veterans’ children. More recent studies have found additional evidence of increases in birth defects in the children of both male and female veterans. Researchers collaborated on a metaanalysis of Agent Orange and birth defects in the International Journal of Epidemiology. They identified all studies from 1966 to 2002 that had examined an association between Agent Orange or dioxin and birth defects. The study authors identified twenty-two

January/February 2008 San Francisco Medicine 37

studies, including thirteen Vietnamese and nine non-Vietnamese studies. Their review indicated that parental exposure to Agent Orange was associated with an increased risk in birth defects. The association increased with greater degrees of exposure, rated on intensity and duration of exposure. Although other researchers have pointed out weaknesses in the studies of birth defects from Vietnam, the birth defect association with Agent Orange exposure was statistically significant even when the Vietnamese studies were excluded. Important new research on birth defects in the children of Vietnam veterans was recently presented at the 2006 meeting of the Society for Epidemiological Research in Boston, Massachusetts. Drs. Del Junco, Sweeney, and Papke conducted a case control study of neural tube defects (anencephaly, encephalocele, spina bifida) in the offspring of Vietnam veterans. They found that paternal blood levels of TCDD were significantly associated with neural tube defects in their children and, although the small sample size limited statistical power, that a particular paternal genotype (genetic predisposition) could enhance this association. A manuscript describing these findings is currently under preparation for submission.

Litany of Birth Defects Since 1990, Birth Defect Research for Children has collected data on birth defects and developmental disabilities in the children of Vietnam veterans. When compared to children of civilians in the registry, the children of Vietnam veterans have shown consistent increases in learning, attention, and behavioral disorders; all types of skin disorders; problems with tooth development; allergic conditions and asthma; immune system disorders, including chronic infections; some childhood cancers; and endocrine problems, including thyroid disorders and childhood diabetes. More and more studies of prenatal exposures to dioxins and similar chemicals are adding support for these associations. According to Linda Birnbaum of the U.S. Environmental Protection Agency, dioxin can modulate growth and development. In the embryo and fetus,

dioxin-altered programming can result in malformations, anomalies, fetal toxicity, and functional and structural deficits that often are not detectable until later in life. In a paper published in Environmental Health Perspectives, Birnbaum discusses research that demonstrates that prenatal exposures to endocrine disruptors such as TCDD can alter hormones and reproductive tissue development and can increase susceptibility to potential carcinogen exposure in the adult. Increased susceptibility to chronic childhood infections and cancers later in life may be a result of dioxin’s effects on the developing immune system. Researchers in 2000 investigated the immunological effects of everyday exposures to PCBs and dioxins in preschool-age Dutch children. The researchers found that prenatal exposure to these chemicals was associated with changes in the T-cell population. They concluded that the effects of prenatal background exposure to PCBs and dioxins persist into childhood and could be associated with a greater susceptibility to infectious disease. Another 2003 study by a team of researchers from Quebec reported findings of a chemical imbalance that could be a marker for prenatal immune damage caused by organochlorines (which include dioxin-like compounds). The researchers found that the lymphocyte cells of newborns exposed to higher concentrations of these chemicals during prenatal development secreted fewer cytokines than those of a control group of newborns. These alterations of the immune system could lead to increased susceptibility to infection. A growing body of evidence is linking prenatal exposures to dioxin-like chemicals to learning and behavioral deficits. At a Children’s Health Meeting in 2000 sponsored by the National Institute of Environmental Health Sciences, Jerry Heindel reported on several studies of pregnant women who had consumed several meals of PCB-contaminated fish per month during pregnancy and who gave birth to infants with small but detectable learning and behavioral deficits. The children with the highest exposure averaged six points lower in IQ compared to children with lower levels of exposure.

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Thomas Zoeller, an endocrinologist at the University of Massachusetts, has found that dioxin-like PCBs activate cellular machinery that can alter the structure of other, nondioxin-like PCBs. Some of these dioxin-induced metabolites can act directly on the thyroid hormone receptor. In the fetal brain, this could alter the course of development, leading to learning and developmental disabilities. The new research on dioxin and dioxin-like chemicals holds the promise of unraveling the intricate ways in which these chemicals can alter embryonic development. The research should continue, but it is now thirty-five years since Agent Orange was first sprayed in Vietnam. And the calls keep coming. In Dioxins and Health, Thomas Webster and Barry Commoner comment, “Much of the media coverage of the dioxin debate has consisted of trying to convince the public that their common sense is wrong and that experts know best. In this case, the public’s view has been largely correct. Dioxin is a dangerous and unwanted chemical pollutant.” Vietnam veterans who would like to add information about their children’s birth defects or disabilities to the National Birth Defect Registry sponsored by Birth Defect Research for Children can register online at Betty Mekdeci is the executive director of Birth Defect Research for Children. This article originally appeared in longer form on the website for The Vietnam Veterans of America. To see the full length version, please visit

Book Review

Exposed EXPOSED: The Toxic Chemistry of Everyday Products and What’s at Stake for American Power, by Mark Schapiro


n 2007, many Californians received dramatic mailings from a group named Californians for Fire Safety warning that if legislation banning some fire-retardant chemicals is passed, we would all be at much greater risk of burning to death. But these “Californians” are actually chemical industry lobbyists; firefighters themselves support the proposed legislation, and the chemicals in question have already been banned elsewhere due to concerns about health impacts such as increased cancer, birth defects, and reproductive problems. This latter point—that we in the U.S. allow use of substances deemed too toxic in other nations, especially European countries—is the primary focus of San Francisco journalist Mark Schapiro’s Exposed (Chelsea Green, 219 pages, $22.95). And while environmental science underlies the book’s argument, it is notable that Schapiro’s perspective is more a “business” one than otherwise. His startling message is that by lagging behind on environmental innovation, American industries are jeopardizing their financial futures. And since money talks, he may have produced a book with more eventual impact than a crate of dire environmental warnings. Public health researchers at U.C. Berkeley “estimate that forty-two billion pounds of chemicals enter American commerce daily—enough chemicals to fill up 623,000 tanker trucks, a string of trucks that could straddle the globe three times, every day” notes Schapiro. Further, “fewer than five hundred of those substances … have undergone any substantive risk assessments.” At the same time as this massive post-World War II production has taken place, research has demonstrated health hazards even—especially, in some cases—at very low doses. And children, fetuses, and pregnant women are especially vulnerable. Schapiro writes that, ironically, although we like to think of our nation as more advanced in such arenas, “It is now fair to ask: Is America itself becoming a new dumping ground for products forbidden in other countries because of their toxic effects?” Consider cosmetics. A survey of common products “found hundreds of varieties of skin and tanning lotions, nail polish and mascara and other personal-care products that contain known or possible carcinogens, mutagens, and reproductive toxins.” Contrary to common assumption, most cosmetics are not effectively tested or regulated for their health effects. European authorities, however, started to demand toxicity information before multinational companies could continue to market their products there,

Steve Heilig, MPH

and this development did garner corporate attention and action. Chemicals put on the European Union “negative list” were removed from products—without seeming to hurt the bottom line. Back at home, however, such as when a Safe Cosmetic Act was proposed for California, chemical lobbyists convened en masse in Sacramento to argue that there were no risks from the chemicals used. The example of cosmetics can be seen as one of voluntary exposure, although consumers would seem to have a right to know exactly what they put onto or into their bodies. But Schapiro provides similar case studies of other chemicals or categories of substances, such as phthalates used in plastics, persistent organic pollutants including pesticides, and genetically modified foods, where much of our exposures occur even if we do not actively use the product. Meanwhile, federal agencies we might expect to protect us, such as the Environmental Protection Agency, have been “eviscerated from within” by the current Federal administration. The advent of the European Union has tilted balances of power in many ways, including how “chemical politics” now take place. When the E.U. developed far-reaching new regulations to reduce exposure to harmful substances, American chemical lobbyists swarmed across the Atlantic to fight them. But E.U. markets are now bigger than those in America, and as one diplomat there states, “We are not going to ask the United States for permission.” “U.S. environmental policies are not sparking innovation; they are fighting it,” Schapiro holds. European experts calculate that their new safer chemical policy will “be repaid many times over by its benefits.” “Europe is looking at the future,” Schapiro concludes. “This is not utopian; it’s more like a realpolitik for the twenty-first century.” How ironic then, that short-sighted, self-serving perspectives in what was once the “New World” have become outmoded, and that they are putting Americans at risk not only in terms of our health but of our economic future. A previous version of this review appeared in the San Francisco Chronicle. Brominated flame retardants—safety at what cost? Albert L. Juhasz, et al. The Lancet. December 1, 2007. “The bioaccumulative nature of PBDEs and the increasing concentrations of these compounds in human samples mirror previous reports for polychlorinated biphenyls (PCBs) and DDT before their bans ... exposure of fetuses in utero or infants via breast milk and dust to PBDEs might lead to neurological deficits, which have been observed after exposure to the structurally similar PCBs.”

January/February 2008 San Francisco Medicine 39

hospital news Saint Francis

Wade Aubrey, MD

At Saint Francis Memorial Hospital, we recently celebrated the fortieth anniversary of the Bothin Burn Center and its tradition of excellent care. Established in December 1967, the Bothin Burn Center is the largest tertiary service, acute burn facility in the Bay Area. The Center is the first burn center in Northern California to be verified by the American Burn Association and the American College of Trauma Surgeons. It is the only verified burn center in San Francisco. The anniversary was celebrated with a party on December 15 attended by staff, former patients and their families, and local community leaders who included San Francisco Fire Chief Joanne Hayes-White, Police Chief Heather Fong, and Supervisors Aaron Peskin and Tom Ammiano. We also toasted the installation of the center’s new Medical Director, Clyde Ikeda, MD, and unveiled plans for the center’s upcoming expansion. The renovation will expand the unit from ten beds to fourteen and will add an outpatient burn clinic. It will also offer a day room for patients and their families, generously donated by Lisa Nash, survivor of the 2005 PG&E explosion, and her family. As the sign above the burn center nursing station says, “Those who treat burns will reap their reward in heaven.” We’re extremely grateful to our Burn Center staff and physicians for the care they have provided over these past forty years. In closing, I’d like to wish all our San Francisco colleagues a happy, healthy, and prosperous New Year.


Robert Mithun, MD

We hear about it every day—health care costs are on the rise and many employers are no longer offering insurance to their employees. Because the burden of health insurance has been placed directly on the employee, many workers are unable or unwilling to provide the coverage they and their families need. The emotional, physical, and financial impact of this reality affects not only performance but also total health. One of the ways that Kaiser Permanente is helping employers cope with their rising health care expenditures is by analyzing their total health care costs. This includes their direct and indirect health care costs. Direct costs, which include medical and pharmacy, account for only a portion of a company’s outlay. The indirect costs, which include absenteeism and presenteeism (when an employee is present at work but not fully productive because of poor health), can cost two to three times more than direct costs. Once employers look at their total cost picture, they are able to implement health promotion and wellness programs to address these costly health conditions. There are three general categories that we as an organization have identified as targets for intervention and change: presenteeism, absence and disability management, and chronic disease management. We now have extensive health promotion and wellness programs, which we coordinate with our Department of Health Education, to offer our employer groups. With the addition of these health promotion and wellness programs, companies are finding that their employees are much healthier and more productive in their work environments. The companies also benefit from lower total health care costs, which contribute to healthier, more competitive companies.

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Ronald Miller, MD

The UCSF Cancer Center has been renamed the Helen Diller Family Comprehensive Cancer Center as a tribute to the Bay Area philanthropist. A resident of San Mateo County, Mrs. Diller has a history of giving to programs in education, science, and the arts throughout the world. She is recognized for her creativity in looking for opportunities to contribute and for her deep involvement in the areas she supports. At a ceremony announcing the name change, UCSF Chancellor J. Michael Bishop, MD, said the new name will be synonymous with a new era of cancer discovery. UCSF was designated as a Comprehensive Cancer Center by the National Cancer Institute in 1999. It ranks first in California and sixth nationwide in NCI research grants. Michael Callaham, MD, has been named the first chair of the new Department of Emergency Medicine. The formation of this new academic department—expected January 1, pending Academic Senate approval—will unify UCSF’s research and training programs at UCSF Medical Center on the Parnassus campus and at San Francisco General Hospital. A new emergency medicine residency program will welcome its first trainees in summer 2008. Emergency medicine is one of the top residency choices for UCSF medical school graduates, but until now, these trainees have had to go elsewhere. UCSF has a new partnership with California Cancer Care and Marin General Hospital to provide surgical services for breast cancer patients in Marin County. Under the agreement, UCSF breast surgeon Cheryl Ewing, MD, now has a practice at the CCC Greenbrae office. She will perform surgical procedures at Marin General Hospital, where she also will serve as medical director of the Breast Health Program, working with BHP medical oncologist Bobbie Head, MD, PhD, and radiation oncologist Francine Halberg, MD. The agreement is effective through 2012.

In Memoriam Nancy Thomson, MD


Diana Nicoll, MD, PhD, MPA

The Honorable Nancy Pelosi, Speaker of the U.S. House of Representatives, visited the San Francisco V.A. Medical Center (SFVAMC) during the Veteran’s Day holiday. The Speaker stopped at the Center for the Imaging of Neurodegenerative Diseases (CIND) for a briefing on some of the latest medical and neurological research being conducted at the Medical Center. SFVAMC Associate Chief of Staff for Research Lynn Pulliam, MS, PhD, gave an overview of the research program. In a confidential briefing, CIND Director Michael Weiner, MD, presented preliminary results from a study of veterans of the first Gulf War. SFVAMC Medical Service Chief Paul A. Volberding, MD, said that SFVAMC’s research leadership is a direct result of the medical center’s institutional partnership with U.C. San Francisco. “We presented to Speaker Pelosi recent results concerning our studies of veterans of the first Gulf War. These include effects of stress and exposure,” said Weiner. “We are very grateful to Speaker Pelosi for all her support in allowing us to perform research on the effects of military service on our veterans.” “Strong investments in science help us in every way,” said Speaker Pelosi during the briefing. “Science for the defense of our country, to grow the economy, for a healthier America, and to preserve the planet. We have a moral responsibility to support scientific research.” Following the research briefing, Speaker Pelosi toured and met with patients at the facility’s Nursing Home Care Unit. SFVAMC has the largest medical research program in the national V.A. system, with more than 200 research scientists, all of whom are faculty members at UCSF.

Leland David Duffield, MD Leland “Lee” David Duffield, MD, passed away October 29, 2007, in Sonoma, at the age of 87. A third-generation San Franciscan, he was born at Mt. Zion Hospital on April 2, 1920, to George William Duffield and May Agnes Ganxert. Lee graduated from St. Monica’s School in 1933 and St. Ignatius High School in 1937. He went on to USF, graduating in 1941, and received his medical degree from Stanford University School of Medicine in 1945. Following medical school, he interned at St. Mary’s Hospital. He also taught anatomy at the University of the Pacific Dental School on a part-time basis for approximately ten years. He was a veteran of World War II with the Navy Medical Corps, where he worked at various dispensaries. He entered as an ensign in 1942 and was promoted to lieutenant in 1944. He also served as a surgeon assigned to various naval ships during the Korean War. Lee served as a general practitioner for more than sixty years with the Golden Gate Medical Group at St. Luke’s, serving on various committees and advisory boards. In recognition of his many years of service, he received an award in 2005 as the longest-practicing physician at the hospital. Unfortunately, he was forced to retire on September 30, 2007, after being diagnosed with a terminal disease. Lee met his late wife, Mary Lou, on a blind date while he was an intern. They were married in 1947, after his return from World War II. The couple enjoyed playing golf, combining vacation trips with golf venues such as St. Andrews in Scotland, Costa del Sol in Spain, and multiple golf courses throughout Hawaii and Florida. Lee had a golf marker from every course and proudly displayed them in his Sonoma home. He also made trips with his family to places such as New York, Costa Rica, and Alaska. He was a true fan of the San Francisco Giants

and even made several trips to spring training with other males of his family. He was an avid reader of biographies and historical books and loved Sudoku puzzles, feeling that doing one a day kept the mind alert. He is survived by his children, Carol, Sandy, Joan, and Bob; their spouses, five grandchildren, and two great-grandchildren. His youngest daughter, Mardi, predeceased him. He will be remembered by his family and the loving friends, golfing buddies, medical professionals, and patients who were touched by his personal, unassuming, gentle demeanor.

Aileen L. Webb, MD Aileen L. Webb, MD, passed away November 21, 2007, at Sonoma Hills Retirement Center, surrounded by her loving family. She was 89. She had lived in Oakmont from 1989 to 2004 but prior to that had lived in San Francisco for thirty years. Aileen was born in Oakland to the late Dr. Walker and Hazel Layne, on November 14, 1918. She graduated from U.C. Berkeley, where she met her eventual husband, Eugene McDaniel Webb. They both graduated from McGill University Medical School in Montreal, Canada. Dr. Webb completed her residency at Franklin Hospital and became a boardcertified pathologist in 1945. After taking an eighteen-year hiatus to raise their three children, she opened a private practice, Bay Area Cytopathology, in Oakland in 1972. She retired in 1992. She was a member of the University of California Alumni Association, Alpha Chi Omega Sorority, McGill University Alumni Association, the San Francisco Medical Society (1967), the CMA, the AMA, the American Pathologists, and the College of American Pathologists; and she was a Fellow of the American Society of Clinical Pathologists. She had also been an active volunteer in the Meals on Wheels program for many years.

January/February 2008 San Francisco Medicine 41

Small-Town Medicine


moved to Port Townsend, Washington, a year and a half ago, after practicing in San Francisco for more than a quarter century. My reasons for a change in venue were both practical and personal. I weathered the transition of San Francisco hospitals operating from an autonomous, independent style to what I believed to be a more corporate one driven by practice guideline reimbursement schemes and bottom lines. It definitely had a more demanding effect on the way I worked. I was tired of driving around to all the campuses of my aggregated hospital and covering emergency departments on two sides of town. My practice economics were a constant challenge as insurance reimbursement decreased and the worker’s compensation industry continually revised itself. In short, it just wasn’t as much fun to practice medicine. I was frustrated and probably grumbled about it as much as most did. Since I wasn’t anywhere close to retirement, I thought that it could be better practicing somewhere else. A small community could be a good choice: I could simplify life and practice by having one hospital and working closer to home. I wasn’t trying to go back in time, but I was trying to change a few of the difficult variables in the equation. Well, my move here provided a five-minute commute from home, without freeways or bridges. In the summer I cycle or walk across the wetlands and check on the herons. My office is smack in the middle of the hospital, just steps from the ED, OR, and cafeteria. I am in a rural practice at Jefferson Healthcare, a critical access hospital. Those of you who have been to Port Townsend know that it is a historical Victorian seaport on the Olympic peninsula and a popular tourist destination. It is a beautiful small town of 8,000, rich with arts and cultural events throughout the year. We have one of the few wooden boatbuilding schools in the world and, as a result, many talented artisans. It is a sailor’s paradise situated along the entrance to the Puget Sound. Seattle is southeast, one and a half hours away by car and ferry. Vancouver Island and Victoria are northwest and two hours away by car and ferry. Jefferson Healthcare is a critical access county hospital and has a catchment of 80,000 people. Jefferson County extends across the Olympic peninsula, through the national park to the Pacific Ocean. The residents of our town are generally well educated and fairly well off. A few neighboring towns are popular retirement areas for the financially affluent who enjoy the mild weather and life on the water. Many of the county residents, however, are determined to live in a relatively isolated and rough way. It is common for me to care for patients who live in “sheds” without running water. The payer mix is top-heavy with Medicaid, Medicare, and many uninsured patients. The hospital has twenty-four beds, including a handful of ICU beds, and a clean, modern physical plant. The medical staff is relatively young and mainly consists of family practice MDs who run the gamut of general medical care, including OB. Our staff has two orthopedists, two general surgeons, a urologist, and a gynecologist who takes some C-section call. There are no dermatologists, cardiologists, or any internal medicine 42 San Francisco Medicine January/February 2008

Alan G. Greenwald, MD

specialists of any kind in town. The nearest hospitals are an hour away in opposite directions. Every day, complex cases are transferred by helicopter to Harborview and Virginia Mason in Seattle. Jefferson Healthcare is a vertically integrated county hospital system, which is run by an elected health care board of commissioners. A critical access hospital is exempt from DRG reimbursement for CMS and private payers. It is also exempt from the new medical severity DRG system as well. This means that the hospital can bill fee for service. What makes this a special and an exciting place for me to practice is that the mandate of the commissioners is to provide access for all the residents of Jefferson County. Simply put, the hospital makes it possible for any patient to be seen by doctors and get care in the hospital. As a critical access hospital, the reimbursement from CMS and other insurers is at a higher rate. The increased revenues from this system allow the hospital to “fuel” the physician practices. The hospital surplus is driven into physician salary guarantees and stipends. At this time, the majority of physicians on staff are either salaried or on guarantees. According to the CEO of the hospital, it is simply a matter of buying county residents access for medical care. The bottom line for the physicians who are integrated with the hospital is that we are able to care for outpatients without concern for their insurance status. This is as close as it gets to a universal health coverage system. Anyone involved in medical politics in San Francisco, who has testified at the Health Commission for preservation of the health care “safety net,” or who has helped their hospital preserve/establish a nonprofit clinic will appreciate the beauty of this reality. When my salary guarantee expires, I anticipate receiving a monthly stipend based on my overall practice RVUs in order to cover the expense of the low and underinsured patients. This works in Jefferson County, since there is really only one player in the health care delivery system. Most of the physicians in the county are salaried or on guarantees from the hospital. Many physicians here believe that the payor mix would not sustain their practices without the additional support. I am currently hospital based, using clinic space within the hospital. I operate my own business independently of the hospital and at present am economically self-sufficient (covering my guarantee). Excess hospital capacity and lower revenues in urban areas drove the trend to aggregation and corporate alignment of hospital in the 1980s and 1990s. In the single-hospital towns of the Olympic Peninsula, the corporate entities have come and gone without the same success. Maybe there was a clash of philosophies with the communities, or they were too remote to manage. Rural hospitals also must be run efficiently and must strive to comply with national standards of excellence in patient care. Jefferson Healthcare has aligned with a purchasing cooperative in order to have increased buying power. We also participate in a consortium of rural hospitals to establish best practice standards and to share in peer review. Scaling down to my smaller perspective, I have been able to bring the best

technology and orthopedic implants into my work with little difficulty. I have made several other observations about small-town practice over the past year. It is very evident that my effect on this community is proportionately greater than any I had in San Francisco. I am one of only two orthopedists here. If I don’t fix Grandma’s broken hip or replace her worn joints, she would have to travel a long way to be cared for by someone else. Townspeople know that it would be a great inconvenience for them to go out of town for their care and really appreciate having good doctors here. The idea of competition with doctors fifty miles away doesn’t give me much stress at all. I know that I do a good job for this town and get acknowledgement from my patients every day in the office. I enjoy seeing my patients and their families regularly when I am out in the community. For some doctors the lack of anonymity might be an inconvenience. I suppose that one could live out of town for more privacy. However, I find value in living and working in the same community. It is gratifying and good for business. On the other hand, it is important to understand that because there is little privacy in a small town, anything that is said out loud is likely to travel. Bad news and, especially, bad results are quickly talked about. Probably the most challenging aspect of practice in this particular small town is dealing with the diversity. I thought that San Francisco had the most diverse population, with its many different races, religions, ethnicities, and gender groups. Well, just about everyone in Port Townsend is white, European, and appears to be the same. However, they each have a unique way of looking at life and they celebrate their differences. Maybe the force that attracts people to this town is its tolerance of emotional and intellectual diversity. I have come to learn that it is a challenge to treat people differently in order to get the same good results. Overall, there have been great rewards for embracing this small town and its quirkiness. The bonuses are the convenience of a simpler lifestyle, giving me more time to be at home. The community values the work that I perform, and I really enjoy being appreciated. I am in a close partnership with my hospital. The health care system here allows me to achieve my philosophical goals of providing good medical care for everyone in my community. The hospital has been extremely generous to me. I have an autonomy and greater control over the style and operation of my practice that I was not able to appreciate in the city. Alan Greenwald practiced orthopedic surgery in San Francisco from 1980 to 2006. He served as SFMS president in 2005. He was elected President of Jefferson County Medical Society in 2007. He enjoys being a single father, caring for his two-year-old daughter Jacqueline.

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California Medical Association Policy, 2007: The width is 3.5 by 4” high CANCER AND ENVIRONMENTAL CHEMICALS CALL KaeLewis, with any questions or concerns 415-567-5888 AUTHOR: Brian MD* ENDORSED BY: San Francisco Medical Society Whereas, a large and growing body of peer-reviewed research increasingly indicates that some of the many industrial chemicals now in use and present in human bodies can contribute to the initiation and growth of various cancers, as recognized by many prominent scientists; and Whereas, various scientific organizations and cancer advocacy groups have adopted proactive policies urging better research and preventive strategies regarding chemicals and cancer; and Whereas, one prestigious national group, the Canadian Cancer Society, has adopted a formal policy stating “ Wherever possible, exposure to substances that are known, or believed, to cause cancer should be identified and eliminated by substituting safer alternatives. When elimination is not possible, exposure should be reduced to the lowest possible levels” and “Current scientific evidence is the cornerstone of our information and positions about cancer. However, we believe it is important in some circumstances not to wait for perfect scientific clarity to take action to protect Canadians. As a result, we also strongly support the precautionary principle that states, ³ when an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause-and-effect relationships are not fully established scientifically.²; now be it RESOLVED: That CMA recognizes the important and growing body of scientific evidence linking some common environmental chemicals to human cancers, and encourages educational and advocacy efforts; and be it further RESOLVED: that this matter be referred for national action (AMA). *Clinical oncologist, Clinical Professor of Medicine, University of California, San Francisco; Chairman, San Francisco Medical Society delegation to the CMA.

January/February 2008 San Francisco Medicine 43

What Do You Do With Your Patient Who...

...has persistent atrial fibrillation? rapidly deteriorating and has end-stage heart disease? ...has extensive vascular disease with cardiovascular involvement?

Refer To The Experts!

We are pleased to welcome world-class talent new to CPMC’s Heart and Vascular Center. G. James Avery, II, M.D., Preben Brandenhoff, M.D., J. Donald Hill, M.D. Cardiothoracic surgeons, specializing in end-stage disease management, heart transplant/LVADs

Andrea Natale, M.D. Cardiologist and electrophysiologist specializing in atrial fibrillation and arrhythmias

Daniel Nathanson, M.D. Vascular surgeon specializing in endovascular surgery

Tomomi Oka, M.D. Cardiovascular throracic surgeon

John Rhee, M.D. Interventional radiologist specializing in endovascular procedures California Pacific’s Heart and Vascular Center offers quality, comprehensive, patient-centered cardiovascular care by a team of pioneering physicians intergrating leading-edge technology.

Please Join Us in Welcoming these renowned physicians January 31, 2008 Hors d’ ouevres and Cocktails 5-7 PM CPMC – Enright Room 2333 Buchanan Street San Francisco

RSVP by January 23 to 415 600-5876 or

January/ February 2008