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Social Media and Emergency-Preparedness Efforts

social networks allows people who are recovering from disasters to rapidly connect with needed resources.4 Tweets and photographs linked to timelines and interactive maps can tell a cohesive story about a recovering communitys capabilities and vulnerabilities in real time. Organizations such as Ushahidi have helped with recovery in Haiti by matching volunteer health care providers with distressed areas.1 Social media have been used in new ways to connect responders and people directly affected by such disasters as the Deepwater Horizon oil spill, flash floods in Australia, and the earthquake in New Zealand with medical and mental health services.5 As with any new technology, there remain many hurdles between current use and optimal exploitation of social media. Although these media are used by people of both sexes and an expanding range of ages, it is important to recognize and explore the technologys limitations in reaching at-risk, vulnerable populations.2 Furthermore, it is not always possible to know whether social media users are who they claim to be or whether the information they share is accurate. Although false messages that are broadcast widely are often rapidly corhis tory of medicine

rected by other users, it is often difficult to separate real signals of a health crisis or a material need from background noise and opportunistic scams. Careful consideration must also be given to issues of privacy and the question of who should monitor data from social media (and for what). Studies are needed to evaluate the reliability and validity of public healthrelated information communicated through social media. Some relevant metrics (e.g., Twitter Analytics, Flikr Stats, and Google Analytics) already exist and are used by the business community, yet few published scientific studies have applied these tools to evaluating the capabilities or effectiveness of social media in public health emergencies. Also lacking are studies evaluating whether the integration of social media into public health efforts affects the costs, quality, or outcomes of health care. Of course, social media cannot and should not supersede our current approaches to disastermanagement communication or replace our public health infrastructure, but if leveraged strategically, they can be used to bolster current systems. Now is the time to begin deploying these innovative technologies while developing meaningful metrics of their effectiveness and of the ac-

curacy and usefulness of the information they provide. Social media might well enhance our systems of communication, thereby substantially increasing our ability to prepare for, respond to, and recover from events that threaten the publics health.
The views expressed in this article are solely those of the authors and do not necessarily reflect the views of the U.S. Government or the Department of Health and Human Services. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. From the Department of Emergency Medicine and the Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia (R.M.M); and the Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services, Washington, DC (R.M.M., S.E., N.L.). 1. Ushahidi-Haiti at Tufts University. Haiti: the 2010 earthquake in Haiti. (http://haiti .ushahidi.com.) 2. Edison Research. The social habit frequent social networkers. (http://www .edisonresearch.com/home/archives/2010/ 06/the_social_habit_frequent_social_ networkers_in_america.php.) 3. Semenza JC, Rubin CH, Falter KH, et al. Heat-related deaths during the July 1995 heat wave in Chicago. N Engl J Med 1996;335: 84-90. 4. Palen L, Vieweg S, Liu SB, Hughes AL. Crisis in a networked world: features of computermediated communication in the April 16, 2007 Virginia Tech event. Soc Sci Comput Rev 2009;27:467-80. 5. Google Crisis Response. Christchurch earthquake, Cyclone Yasi and Australian Floods, and the Deepwater Horizon Oil Spill. (http://www.google.com/crisisresponse/ response.html.)
Copyright 2011 Massachusetts Medical Society.

One Hundred Years of Salvarsan

Kent A. Sepkowitz, M.D. ne hundred years ago, the first reports of Paul Ehrlichs magic bullet, Salvarsan 606, a novel approach to the treatment of infectious diseases, appeared in the U.S. medical literArticles from ature. The initial artithe NEJM Archive are available at NEJM.org cle in the Journal was

published on March 9, 1911, and described the use of Salvarsan in a single case of chronic pemphigus affecting a farmer from Linn County, Kansas. A week later, Captain Harold Jones reported on 20 soldiers with syphilis whose names were given treated with
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Salvarsan at Walter Reed General Hospital.1 In the ensuing months and years, the medical literature was awash with articles, letters, and book reviews on the magic bullet. Results of its use in thousands of patients were provided;
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One Hundred Years of Salvarsan

battle lines were drawn between the old guard who stood by the time-tested mercurials and the young bucks who insisted that newer was better.2 When the dust finally settled, Salvarsan stood as the undisputed champion, and the way in which therapies were developed and distributed had undergone a profound change. The era of what Ehrlich had dubbed chemotherapy medical therapy with chemicals had begun. Ehrlichs work came at a heady moment in science. Louis Pasteur and Robert Koch had made their seminal observations about microbial pathogenesis; ether had become widely available, revolutionizing surgery; and the discoveries of Marie Curie and Wilhelm Roentgen had introduced the radiograph, radically altering the way the body was perceived. Medical science was the worlds new darling able, it seemed, to fix just about any problem. Modernity, with all its shiny-package appeal (and obligate nostalgia), had arrived. Ehrlichs imagination and wide interests were of a piece with the audacity of the moment.3 Fascinated by many phenomena, he was particularly intrigued by the discriminatory behavior of dyes in human tissue. He reasoned that since dyes were taken up preferentially by certain cells and cell structures and not by others, a magic bullet could be created that similarly struck only the intended target, leaving the surrounding cells untouched. Arsenic-based compounds had long been known to have activity against an array of medical conditions. Hippocrates had written of the benefit of a naturally occurring form, orpiment, and the element appeared in various con292

coctions over the ensuing centuries. Arsenic was the key component in Fowlers solution, which was formulated more than 200 years ago and was used to treat leukemia and other ailments well into the 20th century. Indeed, arsenic-based therapies endure even today: arsenic trioxide was approved by the Food and Drug Administration in 2000 for the treatment of acute promyelocytic leukemia. A chemical conjunction of arsenic and a dye had been formulated in 1869 by the French scientist Antoine Bchamp, whose main interest was the silkworm. He recognized the promise of arsenicals and sought to attenuate their toxicity by adding the dye aniline. His work was mostly ignored for 40 years, until Walter Schild, a German physician, used the compound (now called Atoxyl to suggest reduced toxicity) to treat skin conditions.4 Then in 1905, Harold Wolferstan Thomas of the Liverpool School of Tropical Medicine studied the drug for the treatment of sleeping sickness, a lethal form of trypanosomiasis. Thomas was aware of veterinary literature demonstrating the efficacy (but also the toxicity) of arsenic compounds given for equine and bovine trypanosomiasis. He reasoned that a less toxic drug such as Atoxyl might allow repeated and prolonged administration, so he studied its effects in experimentally infected monkeys, rabbits, and various rodents. Ehrlich recognized the importance of Thomass work and assembled a team that included Sahachiro Hata and the organic chemist Alfred Bertheim. Once they had clarified the structure of Atoxyl, they set out to adjust

it chemically to increase its potency and reduce its toxicity. They approached the task with the thoughtful, methodical precision that characterized all Ehrlichs work: Bertheim synthesized more than 900 compounds, most derived from Atoxyl, while Hata studied candidate drugs in rabbits.4 The team inched forward, compound by compound, until they hit upon the right balance of activity and safety. Arsphenamine was the 606th compound tested and soon became known under the proprietary name Salvarsan 606. Because of solubility problems, Ehrlich et al. soon formulated neoarsphenamine (Neosalvarsan, compound no. 914). In the 1930s, the drug was further refined into Mapharsen, the active moiety of the original compound. This was the drug of choice for syphilis until the introduction of penicillin a decade later. The speed with which Ehrlichs big idea was transformed into a drug in hand for daily clinical use is staggering, making it an early poster child for translational medicine. Within a year after the first clinical reports came out, it had been given to thousands of people.3 Establishment of appropriate dosing and route of administration proved to be a substantial hurdle. There was also the matter of the brand name to be considered: as early as 1911, the number 606 had become so strongly associated with syphilis that it was reported ly dropped as a telephone number in several exchanges.5 Almost as swiftly as the drug was distributed, however, its limitations became evident. It was ineffective for late complications of syphilis, especially neurosyphi-

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One Hundred Years of Salvarsan

lis. Relapses requiring retreatment were common. Furthermore, the list of toxic effects mounted as more doses were delivered: renal failure, optic neuritis, seizures, fever, rash medical journals were chock-full of the latest. Whatever Salvarsans shortcomings, however, Ehrlichs pursuit of a cure for syphilis established the standard model for investigation of new compounds, an approach thats still in use. Furthermore, the ups and downs of Salvarsans fate are familiar to anyone who has performed clinical trials of a novel agent. After a long, hard slog, a new drug for a pressing disease is identified; hope abounds. Early success is reported perhaps this is the big one; hope abounds. The first reports of therapeutic failure arrive; hope falters. Reports mount of toxic effects, some of them severe; hope sinks and skids toward despair. Then,

over time, more experience allows the new drug to find its rightful place, to settle into the wide middle ground between salvation and catastrophe. But more than providing lessons for todays scientists regarding best practices for drug investigation and development, the Salvarsan story illuminates the one essential attribute that separated Ehrlich from the other brilliant scientists of a century ago: Ehrlich showed that one must dream big in order to move science forward. Though modest in demeanor, he acted boldly, daring to formulate a cure to the most common devastating infection of his time. To achieve that aim, he plowed through hundreds of compounds, battled back against criticism and doubt of colleagues, and made countless adjustments in mid-air to optimize the drug and its delivery. In the end, perhaps his dream

of the silver bullet was larger than his actual achievement; we still struggle to cure syphilis, and antibiotics have proven anything but perfect. But surely we must forgive Ehrlich his enthusiasm: without his boundless optimism, that cornerstone of all scientific inquiry, we might still be injecting mercury salts.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org. From the Memorial Sloan-Kettering Cancer Center, New York. 1. Jones HW. Report of a series of cases of syphilis treated by Ehrlichs arsenobenzol at the Walter Reed General Hospital, District of Columbia. Boston Med Surg J 1911;164:381-3. 2. French HC. Salvarsan (606) and mercury in the treatment of syphilis. Lancet 1911;178: 326-7. 3. Schwartz RS. Paul Ehrlichs magic bullets. N Engl J Med 2004;350:1079-80. 4. Riethmiller S. From Atoxyl to Salvarsan: searching for the magic bullet. Chemotherapy 2005;51:234-42. 5. Unfortunate connotation of 606. Boston Med Surg J 1911;164:591.
Copyright 2011 Massachusetts Medical Society.

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