Priscilla Schaffer (1941-2009): a Stalwart Herpesvirologist

Priscilla Ann Schaffer died from complications of Parkinson''s Disease on 18 November 2009. Priscilla was a colleague and a friend, as well as being a stellar member of the virology community. She was a longtime Journal of Virology reviewer, a member of the editorial board, and a frequent contributor. Her energy and enthusiasm for virology, her students, her colleagues, and life in general were exceptional. She will be missed. Her colleague Donald Coen has prepared a memorial celebrating her life and accomplishments.Lynn W. EnquistEditor in Chief, Journal of Virology     

Commentary: Personal Renewal

After John Gardner''s presentation on “Self-Renewal” to THE WESTERN JOURNAL OF MEDICINE Editors'' Meeting, ^* Joseph Murphy, MD, Special Editor for Wyoming, asked the former Secretary of Health, Education, and Welfare, “Where are you in your life''s cycle?” Dr Gardner, who is 80 years old, answered, “When Chief Justice Oliver Wendell Holmes, Jr, was in his 90s, he was asked a similar question and said, `I''m like a race horse cantering along after the race is over, cooling down.'' Well, I''m nowhere near cantering! I''m still in the race, pushing the world.” race, pushing the world.”John Gardner, who received his undergraduate degree from Stanford and PhD from the University of California, Berkeley, taught at the college level for several years before he joined the Carnegie Foundation. As president of Carnegie Corporation and Carnegie Foundation for the Advancement of Teaching, he began to “push the world” toward education and in 1964 received the country''s highest civilian honor, the Presidential Medal of Freedom. He has also pushed it toward political reform by founding Common Cause, toward grass-roots political action by founding the Urban Coalition, toward leadership training by founding the White House Fellows program, and toward volunteerism by founding the Independent Sector (a coalition of for-profit and not-for-profit organizations and foundations). His books, including Excellence, Self-Renewal, No Easy Victories, and On Leadership, have pushed readers to new understanding of themselves and of organizations to higher levels of creativity and energy to get important work done. His current research focuses on discovering and defining the characteristics of healthy, vital communities. His call to “keep on keeping on,” indeed, to push the world, leads to constructive change. Active people become effective people, infused with the energy and optimism that good hard work inspires. I think you will find this paper as invigorating to read as it was to hear.     

Evolution of cryptic gene pools in Hypericum perforatum: the influence of reproductive system and gene flow

Background and Aims Hypericum perforatum

(St. John''s wort) is a widespread Eurasian perennial plant species with remarkable variation in its morphology, ploidy and breeding system, which ranges from sex to apomixis. Here, hypotheses on the evolutionary origin of St. John''s wort are tested and contrasted with the subsequent history of interspecific gene flow.

Methods

Extensive field collections were analysed for quantitative morphological variation, ploidy, chromosome numbers and genetic diversity using nuclear (amplified fragment length polymorphism) and plastid (trnL-trnF) markers. The mode of reproduction was analysed by FCSS (flow cytometric seed screen).

Key Results

It is demonstrated that H. perforatum is not of hybrid origin, and for the first time wild diploid populations are documented. Pseudogamous facultative apomictic reproduction is prevalent in the polyploids, whereas diploids are predominantly sexual, a phenomenon which also characterizes its sister species H. maculatum. Both molecular markers characterize identical major gene pools, distinguishing H. perforatum from H. maculatum and two genetic groups in H. perforatum. All three gene pools are in close geographical contact. Extensive gene flow and hybridization throughout Europe within and between gene pools and species is exemplified by the molecular data and confirmed by morphometric analyses.

Conclusions Hypericum perforatum

is of a single evolutionary origin and later split into two major gene pools. Subsequently, independent and recurrent polyploidization occurred in all lineages and was accompanied by substantial gene flow within and between H. perforatum and H. maculatum. These processes are highly influenced by the reproductive system in both species, with a switch to predominantly apomictic reproduction in polyploids, irrespective of their origin.     

Long-term effects of St. John's wort (Hypericum perforatum) treatment: A 1-year safety study in mild to moderate depression

Long-term safety and the effects of a St. John's wort (SJW) extract Ze 117 (Hypericum perforatum) were evaluated in the treatment of patients with depression.An open multicentre safety study with 440 out-patients suffering from mild to moderate depression according to ICD-10 was conducted. Patients were treated for up to 1 year with 500 mg St. John's wort extract per day (Ze 117). Evaluation criteria were safety (adverse event frequency) and influence on depression (HAM-D, CGI). Two hundred and seventeen (49%) patients reported 504 adverse events, 30 (6%) of which were possibly or probably related to the treatment. Gastrointestinal and skin complaints were the most common events associated with treatment. No age-related difference in the safety of the applied medication was found. The long-term intake of up to 1 year of the study medication did not result in any changes in clinical chemistry and electrocardiogram recordings. Body mass index (BMI) did not change either. Mean HAM-D scores decreased steadily from 20.58 at baseline to 12.07 at week 26 and to 11.18 at week 52. Mean CGI scores decreased from 3.99 to 2.20 at week 26 and 2.19 at week 52. Therefore, St. John's wort extract ZE 117 is a safe and effective way to treat mild to moderate depression over long periods of time, and therefore seems especially suitable for a relapse prevention.     

Smallpox and its control in Canada

Edward Jenner''s first treatise in 1798 described how he used cowpox material to provide immunity to the related smallpox virus. He sent this treatise and some cowpox material to his classmate John Clinch in Trinity, Nfld., who gave the first smallpox vaccinations in North America. Dissemination of the new technique, despite violent criticism, was rapid throughout Europe and the United States. Within a few years of its discovery, vaccination was instrumental in controlling smallpox epidemics among aboriginal people at remote trading posts of the Hudson''s Bay Company. Arm-to-arm transfer at 8-day intervals was common through most of the 19th century. Vaccination and quarantine eliminated endemic smallpox throughout Canada by 1946. The last case, in Toronto in 1962, came from Brazil.     

Smoking,restaurants and bars: the Toronto experience

Rural physicians and other professionals attending a recent conference in St. John''s reached consensus on a number of issues surrounding the role of nurse practitioners. The issue is important for rural doctors, since some people think NPs can help solve the physician shortage in rural areas.     

Pills for the Poor: John Wesley's Primitive Physick

While John Wesley''s Primitive Physick (1747) cannot be termed a classic of British medical literature, it must certainly be identified as one of the most popular volumes published in England during the eighteenth century. Although the work came under attack from contemporary surgeons, physicians, and apothecaries, who maintained that its remedies were founded upon ignorance, Wesley probably knew as much as most members of the medical profession; in fact, on no less than twenty instances throughout the volume, he paraphrases or cites directly from prominent physicians and theorists—such figures as Sydenham, Boerhaave, Cheyne, Mead, and Huxham. However, despite its obvious emphasis upon practical remedies, the underlying focus of Primitive Physick is upon the soul of man. Wesley had consulted some sources, common sense, and his own experience, tempering those with the general principle of “doing good to all men,” particularly “those who desire to live according to the gospel....” Thus, the Methodist patriarch''s own formula for life had as much to do with the spread of Primitive Physick throughout eighteenth-century Britain and America as did all of the remedies and suggestions imprinted upon its pages.     

Man-made eutrophication in a newfoundland (Canada) harbour

A comparative study in 1969-1970 of the phytoplankton and certain other parameters in St. John's Harbour and Aquaforte Harbour, located on the southeast coast of Newfoundland, led to the conclusion that St. John's Harbour which receives untreated sewage as a prime source of nutrients was by far the more eutrophic. Evidence for the eutrophic state was especially observed in the central basin (Station 1) of the harbour. Here the bottom waters were deficient in oxygen especially during the summer months. Secchi disc readings were generally lower at this station, and the annual standing crop of phytoplankton was almost three times that at unpolluted Aquaforte Harbour. Also the proportion of the biomass contributed by the nannoplankton was greater in St. John's Harbour. One euglenoid occurred in bloom concentrations throughout the summer months and may possibly be considered as an indicator of organically-polluted waters.     

More than a blog

Blogging is circumventing traditional communication channels and levelling the playing field of science communication. It helps scientists, journalists and interested laypeople to make their voices heard.Last December, astrobiologists reported in the journal Science that they had discovered the first known microorganism on Earth capable of growing and reproducing by using arsenic (Wolfe-Simon et al, 2010). While media coverage went wild, the paper was met with a resounding public silence from the scientific community. That is, until a new breed of critic, science bloggers, weighed in. Leading the pack was Rosie Redfield, who runs a microbiology research lab in the Life Sciences Centre at the University of British Columbia in Vancouver, Canada. She posted a critique of the research to her blog, RRResearch (rrresearch.fieldofscience.com), which went viral. Redfield said that her site, which is typically a quiet window on activities in her lab got 100,000 hits in a week.Redfield said that her site, which is typically a quiet window on activities in her lab got 100,000 hits in a weekThis incident, like a handful before it and probably more to come, has raised the profile of science blogging and the freedom that the Internet offers to express an opinion and reach a broad audience. Yet it also raises questions about the validity of unfettered opinion and personal bias, and the ability to publish online with little editorial oversight and few checks and balances.Redfield certainly did not hold back in her criticism of the paper. Her post said of the arsenic study: “Lots of flim-flam, but very little reliable information. [...] If this data was presented by a PhD student at their committee meeting, I''d send them back to the bench to do more clean-up and controls.” She also opined on why the article was published: “I don''t know whether the authors are just bad scientists or whether they''re unscrupulously pushing NASA''s ''There''s life in outer space!'' agenda. I hesitate to blame the reviewers, as their objections are likely to have been overruled by Science''s editors in their eagerness to score such a high-impact publication.”Despite the fervor and immediacy of the blogosphere, it took Science and Felisa Wolfe-Simon, the lead author on the paper, nearly six months to respond in print. Eventually, eight letters appeared in Science covering various aspects of the controversy, including one from Redfield, who is now studying the bacteria in her lab. Bruce Alberts, editor-in-chief of Science, downplayed the role that blogging played in drumming up interest in the controversial study. “I am sure that the number of letters sent to us via our website reflected a response to the great publicity the article received, some of it misleading [...] This number was also likely expanded by the blogging activity, but it was not directly connected to the blogs in any way that I can detect,” he explained.Bloggers, of course, have a different take on the matter, arguing that it was another example of a growing number of cases of ''refutation by blog''. The blogging community heralds Redfield as a hero to science and science blogging. By now, more traditional science media outlets have also joined the bloggers in their skepticism over the paper''s claims, with many repeating the points Redfield made in her original blog response.Jerry Coyne, an evolutionary geneticist at the University of Chicago in the USA, writes the blog Why Evolution is True (whyevolutionistrue.wordpress.com), which is a spinoff from his book of the same name. He said that bloggers, both professional scientists and journalists, have been gaining a new legitimacy in recent years as a result of things such as the arsenic bacteria case, as well as from shooting holes in the 2009 claims that the fossil of the extinct primate Darwinius masillae from the Messel Pit in Germany was a ''missing link'' between two primate species (Franzen et al, 2009). “[Blogging has] really affected the pace of how science is done. One of the good things about science blogging, certainly as a professional, is you''re able to pass judgment on papers instantly. You don''t have to write a letter to the editor and have it reviewed. [Redfield] is a good example of the value of science blogging. Claims that are sort of outlandish and strong can be discredited or at least addressed instantaneously instead of waiting weeks and weeks like you''d otherwise have to do,” he said.“... you''re able to pass judgment on papers instantly. You don''t have to write a letter to the editor and have it reviewed”Perhaps because of the increasingly public profile of popular science bloggers, as well as the professional and social value that is becoming attached to their blogs, science blogging is gaining in both popularity and validity. The content in science blogs covers a wide spectrum from genuine science news to simply describing training or running a lab, to opinionated rants about science and its social impact. The authorship is no less diverse than the content with science professionals, science journalists and enthusiastic amateurs all contributing to the melting pot, which also has an impact on the quality.Carl Zimmer is a freelance science journalist, who writes primarily for the New York Times and Discover Magazine, and blogs at The Loom (blogs.discovermagazine.com/loom). “Most scientists have not been trained how to write, so they are working at a disadvantage,” he said. “[Writing for them] would be like me trying to find a dinosaur. I wouldn''t do a very good job because I don''t really know how to do that. There are certainly some scientists who have a real knack for writing and blogs have been a fantastic opportunity for them because they can just start typing away and all of a sudden have thousands of people who want to read what they write every day.”Bora Zivkovic, who is a former online community manager at Public Library of Science, focusing mainly on PLoS ONE, is one of those scientists. A native of Belgrade, he started commenting in the mid-1990s about the Balkan wars on Usenet, an Internet discussion network. He began blogging about science and politics in 2004 and later about his interest in chronobiology, which stems from his degree in the topic from North Carolina State University. He still combines these interests in his latest blog, Blog Around the Clock (blogs.scientificamerican.com/a-blog-around-the-clock). Last year, Scientific American named Zivkovic its blog editor and he set up a blogging network for the publication. “There isn''t really a definition of what is appropriate,” he said. “The number one rule in the blogosphere is you never tell a blogger what to blog about. Those bloggers who started on their own who are scientists treasure their independence more than anything, so networks that give completely free reign and no editorial control are the only ones that can attract interesting bloggers with their own voices.”“The number one rule in the blogosphere is you never tell a blogger what to blog about”Daniel McArthur, an Australian scientist now based in the UK, who blogs about the genetic and evolutionary basis of human variation at Genetic Future (www.wired.com/wiredscience/geneticfuture), and about personal genomics at Genomes Unzipped (www.genomesunzipped.org), said that it is difficult to define a science blog. “I think it''s semantics. There are people like me who spend some time writing about science and some time writing about industry and gossiping about things in the industrial world. Then there are the people who write about the process of doing science. There are many, many blogs where [...] the content is much more about [the blogger''s] personal voyage as a scientist rather than the science that they do. Then there are people who use science blogging as an extra thing that they do and the primary purpose of their blog is to add political advocacy. I think it''s very hard to draw a line between the different categories. My feeling is that science bloggers should write about whatever it is they want to write about .”The ability to distribute your opinion, scientific or otherwise, online and in public is raising difficult questions about standards and the difference between journalism and opinion. Sean Carroll, who writes for the physics group blog Cosmic Variance (blogs.discovermagazine.com/cosmicvariance), is a senior research associate in the Department of Physics at the California Institute of Technology in the USA. “Some blogging is indistinguishable from what you would ordinarily call journalism. Some blogging is very easily distinguishable from what you would ordinarily call journalism,” he said. “I think that whether we like it or not, the effect of the Internet is that readers need to be a little bit more aware of the status of what they are looking at. Is this something reputable? Anyone can have a blog and say anything, so that one fact is both good and bad. It''s bad because there is a tremendous amount of rubbish on the Internet [...] and people who have trouble telling the rubbish from the good stuff will get confused. But it''s also good because it used to be the case that only a very small number of voices were represented in major media.”Zimmer contrasts the independence of blogging with traditional journalism. “You really get to set your own rules. You''re not working with any editor and you''re not trying to satisfy them. You''re just trying to satisfy yourself. In terms of the style of what I do, I will tend to write more—I think of [my blog posts] as short essays, as opposed to an article in the New York Times where I''ll be writing about interviewing someone or describing them on a visit I paid to them. One of the great things about a blog is that it''s a way of making a connection with people who are your readers and people who are following you for a long time.”One of the world''s most popular scientist bloggers is Paul Zachary Myers, known as PZ, a biology professor at the University of Minnesota in the USA. He blogs at Pharyngula (scienceblogs.com/pharyngula), a site named for a particular stage in development shared by all vertebrate embryos. “Passion is an important part of this. If you can communicate a love of the science that you''re talking about, then you''re a natural for blogging,” he explained. “[Pharyngula] is a blog where I have chosen just to express myself, so self-expression is the goal and what I write about are things that annoy me or interest me.”“Passion is an important part of this. If you can communicate a love of the science that you''re talking about, then you''re a natural for blogging”Myers'' blog, which is driven by a mix of opinion, colourful science writing, campaigning against creationism and an unflinching approach to topics about which he is passionate, draws about 3 million visitors a month. He said his blog attracts more traffic than other blogs because it is not purely about science. “I do a lot of very diverse things such as controversial religious stuff and politics, and whatever I feel like. So I tap into a lot of interest groups and that builds up my rank quite a bit. I''d say there are quite a few other science blogs out there that are pure science blogs, but pure science blogs—where they just talk about science and nothing but science—cannot get quite as much traffic as a more broadly based blog.”In an example of his sometimes-incendiary posting, Myers recently took on the Journal of Cosmology regarding an article on the discovery of bacteria fossils in a meteorite. He said that the counterattack got personal, but that he usually enjoys “the push back” from readers. “That''s part of the argument. I would say that everyone has an equal right to make their case on the web. That''s sometimes daunting for some people, but I think it''s part of the give and take of free speech. It''s good. It''s actually kind of fun to get into these arguments.”Beyond the circus that can surround blogs such as Pharyngula, scientist bloggers are debating whether their blogging counts as a professional activity. Redfield said that blogging can be taken into account among the outreach some governments now require from researchers who receive public funds. She said that some researchers now list their blogging activity in their efforts to communicate science to the public.Coyne, however, does not share his interest in blogging with other senior faculty at the University of Chicago, because he does not believe they value it as a professional activity. Still, he said that he recognizes the names of famous scientists among his blog readers and argues that scientists should consider blogging to hone their writing skills. “Blogging gives you outreach potential that you really should have if you''re grant funded, and it''s fun. It opens doors for you that wouldn''t have opened if you just were in your laboratory. So I would recommend it. It takes a certain amount of guts to put yourself out there like that, but I find it immensely rewarding,” he said. In fact, Coyne has had lecture and print publishing opportunities arise from his blogs.“It opens doors for you that wouldn''t have opened if you just were in your laboratory [...] It takes a certain amount of guts to put yourself out there like that...”Redfield said she finds blogging—even if no one reads her posts—a valuable way to focus her thoughts. “Writing online is valuable at all levels for people who choose to do it. Certainly, by far the best science writing happening is in the community of writers who are considered bloggers,” she said.In terms of pay, science blogging usually remains in the ''hobby zone'', with pay varying widely from nothing at all to small amounts from advertising and web traffic. ''GrrlScientist'', an American-trained molecular evolutionary biologist based in Germany, who prefers to go by her nom de blog, has been blogging for seven years. She writes the popular Punctuated Equilibrium blog (www.guardian.co.uk/science/punctuated-equilibrium) for The Guardian newspaper in the UK, as well as Maniraptora (blogs.nature.com/grrlscientist) for the Nature Network, and is co-author of This Scientific Life (scientopia.org/blogs/thisscientificlife) for the science writing community Scientopia. She said she earns a small amount from ad impressions downloaded when her blog is viewed at The Guardian. On the other end of the scale is Myers, who declined to disclose his income from blogging. “It''s a respectable amount. It''s a nice supplement to my income, but I''m not quitting my day job,” he said.Yet bloggers tend not to do it for the money. “I know that when I go to give talks, the fact that I have the blog is one of the first things that people mention, and lots of students in particular say that they really enjoy the blog and that they''re encouraged by it,” Carroll explained. “Part of what we do is not only talk about science, but we act as examples of what it means to be scientist. We are human beings. We care about the world. We have outside interests. We like our jobs. We try to be positive role models for people who are deciding whether or not this is something that they might want to get into themselves one day.”The rise of the science blogosphere has not all been plain sailing. Although the Internet has been hailed as a brave new world of writing where bloggers can express themselves without interference from editors or commercial interests, it has still seen its share of controversy. The blogging portal ScienceBlogs was the launchpad for some of the best and most popular writers of the new generation of science bloggers, including Myers and Zivkovic. But an incident at ScienceBlogs shook up the paradise and raised journalistic ethical quandaries.In July 2010, a new site, Food Frontiers (foodfrontiers.pepsicoblogs.com), appeared on ScienceBlog, sponsored by PepsiCo, the makers of the popular drink. The blog featured posts written by the beverage maker''s representatives and was blended in with the other blog content on the portal. “Pepsi''s blog looked like my blog or PZ''s blog,” Zivkovic explained, “with no warning that this was paid for and written by Pepsi''s R&D or PR people [...] talking about nutrition from a Pepsi perspective, which is a breach in the wall between advertorial and editorial. The moment the Pepsi blog went live, about 10 bloggers immediately left.” He said that the journalist-bloggers in particular pointed to a break of trust that would sully the reputation of ScienceBlogs writers and confuse readers.In his final blog at the site, titled ''A Farewell to Scienceblogs: the Changing Science Blogging Ecosystem'', Zivkovic nailed the danger of the ''Pepsigate'' incident to the validity of the blogosphere. He wrote: “What is relevant is that this event severely undermined the reputation of all of us. Who can trust anything we say in the future? Even if you already know me and trust me, can people arriving here by random searches trust me? Once they look around the site and see that Pepsi has a blog here, why would they believe I am not exactly the same, some kind of shill for some kind of industry?” (scienceblogs.com/clock/2010/07/scienceblogs_and_me_and_the_ch.php). Myers, who at the time was responsible for more than 40% of the traffic at ScienceBlogs, went ''on strike'' to protest. In the aftermath, the Pepsi blog was pulled.Redfield raises another interesting word of caution. “Most scientists are extensively worried about being scooped, so they''re scared to say anything about what''s actually going on in their lab for fear that one of their competitors will steal their ideas,” she said. In this context, social networking sites such as ResearchGate (www.researchgate.net; Sidebar A) might be a more appropriate avenue for securely sharing ideas and exchanging tips and information because it enables users to control who has access to their missives.“... they''re scared to say anything about what''s actually going on in their lab for fear that one of their competitors will steal their ideas”

Sidebar A | ResearchGate—social media goes pro

Whenever she is looking for ideas for a research project, biologist Anne-Laure Prunier, who works in the Department of Cellular Biology and Infection at the Institut Pasteur in Paris, has recently turned to ResearchGate (www.researchgate.net), the scientists'' version of the social networking site Facebook. “Every time I have used ResearchGate, I found it really useful,” she commented.ResearchGate, based in Berlin, Germany and Cambridge, USA, is a free service that launched in January 2009. It was co-founded by Ijad Madisch, who earned his MD and PhD from the University of Hannover''s medical school in Germany and is a former research fellow at Harvard Medical School. He explained that his goal in starting the network was to make research more efficient. “During my research in Boston, I noticed that science is very inefficient, especially if you''re doing an experiment and trying to get feedback from people working on the same problem. You don''t have any platforms, online networks where you can go and ask questions or if you''re trying to find someone with a specific skill set. So I decided to do that on my own.”As a result, the site offers researchers functionality similar to Facebook—the modern template for social networking. Through ResearchGate, members can follow colleagues, be followed by those interested in their research, share their conference attendance and recent papers—their own or those that interest them—and most importantly, perhaps, ask and answer questions about science and scientific techniques.“You can get in touch with a lot of different people with a lot of different backgrounds,” Prunier explained. “When I have a very precise technical question for which I don''t find an answer in my institute, I turn to ResearchGate and I ask this question to the community. I have done it three times and every time I have gotten a lot of answers and comments, and I was able to exchange information with a lot of different people which I found really useful.”By May 2011, ResearchGate had reached one million members across 192 countries. The largest numbers of registrations come from the USA, the UK, Germany and India. Biologists, who are second only to medical doctors on the site, make up more than 20% of members. In addition to blogging, ResearchGate is just one example of how the Internet—originally invented to allow physicists to share data with one another—is changing the way that scientists communicate and share information with each other and the public.Carroll, on the other hand, who has been blogging since 2004, said that physicists are very comfortable about publicly sharing research papers with colleagues online. “The whole discussion gets very heated and very deep in some places about open access publishing. Physicists look on uncomprehendingly in fact because they put everything for free on line. That''s what we''ve been doing for years. It works.” But he said they are more cautious about blogging for a general audience. By contrast, he believes biology is especially well-suited to being blogged. “[Biologists are] actually more comfortable with talking to a wider audience because biology, whether it is through medicine or through debates about creationism or life on other planets or whatever, gets involved with public debate quite often.”Zivkovic agrees: “PZ [Myers] and me and a number of others are interested in reaching a broad lay audience, showing how science is fun and cool and interesting and important in various ways. Connecting science to other areas of life, from art to politics and showing the lay audience how relevant science is to everyday life”. Even so, he pointed out that although blogging is popularizing science with the public, there is a less-mainstream sphere serving professional scientists as a forum for surviving the cut and thrust of modern science. “There is a strong subset of the science blogosphere that discusses a life in science, career choices, how to succeed in academia [...] A lot of these are written by people who [...] believe that if their real names were out there it could jeopardize their jobs. They''re not interested in talking to lay audiences. They are discussing survival techniques in today''s science with each other and providing a forum for other young people coming into science.”Ultimately, whether you read popular science blogs, trawl deeper for survival tips, or write your own, the science blogosphere is expanding rapidly and is likely to do so for years to come.     

Will hospital closures mean physician unemployment in Ontario?

Dr. Duncan Sinclair, the former dean of medicine who heads the commission charged with restructuring Ontario''s health care system, said something dramatic was needed to revamp the system. He wasn''t kidding. His commission recently called for the closure of 3 hospitals in Ottawa and 10 more in Toronto. In a wideranging interview with Charlotte Gray he talks about the commission''s goals and their potential impact on physicians.     

John P. Peters and the committee of 430 physicians

John Peters and his committee had a few basic goals. One was that local, state, and federal governments needed to provide money to construct facilities, support medical research and education, and care for the poor. And they wanted experts to call the shots. Over time, Peters and the committee got what they wanted for the most part: Hill-Burton money for building the hospitals, the rise of the National Institutes of Health, Medicare, Medicaid, a Veterans Administration system, and new and expanded medical schools. The experts calling the shots included David Kessler at the Food and Drug Administration and Surgeon General C. Everett Koop. In the halcyon days of American health system reform, back in 1993, Yale''s Paul Beeson wrote about the Committee of 430 Physicians and its goals in the Pharos of Alpha Omega Alpha. Beeson was optimistic and he quoted from my 1991 JAMA health system reform editorial as a sharp contrast to what Fishbein had written - although coincidentally, we both quote Lincoln. My editorial began, "''with malice toward none, with charity for all...'' so spoke Abraham Lincoln in his second inaugural address recognizing that he had no political consensus regarding either the constitutionality of states seceding or the morality of slavery being abolished. Nonetheless, he knew what was right and was able, through persuasive, often inspiring rhetoric, to conclude a bloody and decisive Civil War and constitute the foundation for this great republic.... Yet access to basic medical care for all of our inhabitants is still not a reality in this country. There are many reasons for this, not the least of which is a long-standing, systematic, institutionalized racial discrimination.... An aura of inevitablitiy is upon us. It is not acceptable morally, ethically, or economically for so many of our people to be medically uninsured or seriously underinsured. We can solve this problem. We have the knowledge and the resources, the skills, the time, and the moral prescience. We need only clear-cut objectives and proper organization of existing resources. Have we now the national will and leadership?" Beeson''s answer to that question in 1993 was, "Yes, but not by one comprehensive act." He quoted Peters from his 1938 Annals of Internal Medicine article: "a sweeping program suddenly imposed in this country as a whole out of the head of any Jove would undoubtedly create confusion if not chaos. Thoughtful investigation and experiment promises more than grandiose projects born of emotional preconceptions. The programs must be built of an evolutionary manner, step by step." Very wise, very valid. But how long must our people wait?     

THE WORK OF AN Rh COMMITTEE—Experiences in a Private General Hospital

An Rh committee was formed at Saint John''s Hospital in Santa Monica to provide preadmission consultation on all potential Rh and ABO problems and to maintain a file of information on Rh-negative patients in the delivery room. It is urged that no patient go to the delivery room without the known Rh-ABO type as part of the labor record. All obstetrical patients at the hospital are given “obstetrical information cards” for use as a memorandum on the labor record. A pink card identifies the Rh-negative patient.The program keeps the staff “Rh-conscious” and has improved teamwork among the obstetricians, pediatricians, nurses and the laboratory.     

Focusing by shape change in the lens of the eye: a commentary on Young (1801) ‘On the mechanism of the eye’

In his Bakerian Lecture paper of 1801, Thomas Young provided the best account up to that time of the eye''s optical system, including refraction by the cornea and the surfaces of the lens. He built a device, an optometer, for determining the eye''s state of focus, making it possible to prescribe appropriate correction lenses. His main contribution, however, was to show that accommodation, the eye''s focusing mechanism, was not the result of changes to the curvature of the cornea, nor to the length of the eye, but was due entirely to changes in the shape of the lens, which he described with impressive accuracy. He was wrong, however, in believing that the reason the lens bulges when focusing on near objects was because it behaved as a contracting muscle. Half a century later, Helmholtz showed that the lens bulges not by its own contraction, but when it is relaxed as a result of contraction of newly discovered circular muscles in the ciliary body. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

The Role of Hemoglobin's C-terminal Region: the Work of Eraldo Antonini

Studies on Carboxypeptidase Digests of Human Hemoglobin(Antonini, E., Wyman, J., Zito, R., Rossi-Fanelli, A., and Caputo, A. (1961) J. Biol. Chem. 236, PC60–PC63)The Effect of Oxygenation on the Rate of Digestion of Human Hemoglobins by Carboxypeptidases(Zito, R., Antonini, E., and Wyman, J. (1964) J. Biol. Chem. 239, 1804–1808)Eraldo Antonini (1931–1983) received his degree in Medicine and Surgery from the University of Rome in 1955. He then began studying hemoglobin and myoglobin with Alessandro Rossi-Fanelli at the Institute of Biochemistry of the University of Rome and at the Regina Elena Institute for Cancer Research.Open in a separate windowEraldo Antonini (right) in Caprarola in 1971 for Jeffries Wyman''s (left) birthday party, with Robert W. Noble (back).In 1961, Antonini and Rossi-Fanelli published a paper describing the effect on human hemoglobin''s activity when the C-terminal amino acid residues are removed from the molecule''s α and/or β chains. This paper is reprinted here as a Journal of Biological Chemistry (JBC) Classic. In the study, the scientists used carboxypeptidase A to digest the C-terminal tyrosine and histidine on the molecule''s β chain and carboxypeptidase B to remove the C-terminal lysine, tyrosine, and arginine on the molecule''s α chain. The resulting protein appeared intact but had an increased oxygen affinity, lowered cooperativity, and dramatically reduced Bohr effect.This observation inspired Max Perutz, who wrote: “Several years later, my electron density maps showed that these residues form salt bridges with neighboring subunits in deoxyhaemoglobin which get broken on transition to oxyhaemogloblin. Remembering Antonini''s observation, I realized at once that these bridges must represent the additional bonds between the subunits in the T structure predicted by Monod, Wyman and Changeux''s theory of allostery. Antonini had also demonstrated that the release of Bohr protons is colinear with oxygen uptake. When Kilmartin''s and my work proved that most of the Bohr protons originate from the salt bridges, it became clear to me that oxygen uptake is linked to the rupture of these bridges” (1).In the second JBC Classic reprinted here, Antonini follows up on the first paper by doing a reciprocal experiment in which he looks at differences in digestion rates of oxy- and deoxyhemoglobin, reasoning, “If enzymatic modification can affect conformation and changes of conformation resulting from combination with ligand (oxygen), one might expect that the rate of attack on the hemoglobin by the enzymes should depend on the presence or absence of ligand; this would determine conformation, and conformation, in turn, would control the rate.” Again using carboxypeptidases A and B, he showed that the rate of digestion is different for the oxy- and deoxy- forms of the molecule, indicating a differential accessibility of the C-terminal residues to these enzymes.This work was later extended and perfected by John V. Kilmartin on a suggestion by Perutz, who pointed out the crucial role of the C-terminal residues for the molecular mechanism of cooperativity and the Bohr effect. Kilmartin was able to differentiate the role of the C-terminal histidine from that of tyrosine by preparing and characterizing a modified hemoglobin devoid of histidine.Over the next several years, Antonini continued to study hemoglobin, looking at the properties of the α and β chains, the acid-base equilibria of hemoglobin, the Bohr effect and its dependence on temperature, the oxidation-reduction equilibria, ligand-induced conformational changes in hemoglobin, and the kinetics of the reaction of myoblogins and hemoglobins with ligands. This work culminated in the publication of Hemoglobin and Myoglobin in Their Reactions with Ligands in 1971 (2), which was a landmark in the field.In the 1970s, Antonini expanded his scientific interests and started focusing on electron-transfer metalloproteins (such as cytochrome c oxidase) and on proteolytic enzymes. He eventually became Professor of Molecular Biology at the University of Camerino and was later made Professor of Chemistry and Director of the Institute of Chemistry in the Faculty of Medicine and Surgery at the University of Rome. He also received the Feltrinelli Prize from the Accademia Nazionale dei Lincei in 1974.One of Antonini''s coauthors on the two JBC Classics reprinted here is JBC Classic author Jeffries Wyman (3) who came to Rome in 1961 for a week-long visit and ended up remaining for 25 years and working with Antonini. This collaboration produced a series of outstanding papers and conceptual advancements that have had a long lasting influence on protein chemistry.^1,2     

Making sense of shadows: Dr. James Third and the introduction of x-rays, 1896 to 1902.

The discovery of x-rays was announced by German physicist Wilhelm Conrad Röntgen in December 1895. This review of the introduction of the use of x-rays in Kingston, Ont., shows the rapidity of their adoption in Canadian medicine. By February 1896 "x-ray photographs" were being taken by Captain John Cochrane of the Royal Military College of Canada in Kingston. Initially a scientific and popular curiosity, the new rays were quickly applied to medicine, and by the fall of 1896 the Kingston General Hospital had acquired its own x-ray apparatus. The hospital superintendent, Dr. James Third, became a leading practitioner and promoter of radiographic diagnosis and radiation therapy. He published, in 1902, the first comprehensive review of the diagnostic and therapeutic uses of x-rays by a Canadian physician. Third''s writings reveal his technical knowledge, his organized approach to the application of radiography to clinical medicine and his cautious attitude. Like other physicians who have witnessed the introduction of new diagnostic techniques, Third feared that the new technology would usurp the physician''s clinical skills.     

The molecular genetics of bacteriophage: the work of Norton Zinder

In 1966, Norton Zinder and Joshua Lederberg discovered that Salmonella could exchange genes via bacteriophages. They named this phenomenon “genetic transduction.” This discovery set Zinder on a lifelong journey researching bacteriophage. In the two Journal of Biological Chemistry (JBC) Classic papers reprinted here, Zinder and Nina Fedoroff present their findings on the phage f2 replicase.Properties of the Phage f2 Replicase. I. Optimal Conditions for Replicase Activity and Analysis of the Polynucleotide Product Synthesized in Vitro (Fedoroff, N. V., and Zinder, N. D. (1972) J. Biol. Chem. 247, 4577–4585)Properties of the Phage f2 Replicase. II. Comparative Studies on the Ribonucleic Acid-dependent and Poly(C)-dependent Activities of the Replicase (Fedoroff, N. V., and Zinder, N. D. (1972) J. Biol. Chem. 247, 4586–4592)Norton David Zinder was born in New York City in 1928. He attended the prestigious Bronx High School of Science and went on to Columbia University where he received his B.A. in biology in 1947. Zinder then joined the graduate program at the University of Wisconsin-Madison, studying under geneticist Joshua Lederberg.Open in a separate windowNorton ZinderLederberg recently had found that Escherichia coli could mate and exchange genes (conjugation), a discovery for which he would be awarded the 1958 Nobel Prize in Physiology or Medicine. Zinder''s assignment was to continue Lederberg''s investigations using Salmonella. To do this, he needed to obtain large numbers of mutant bacteria. Rather than using the traditional method of exposing the Salmonella to mutagens and testing the survivors, Zinder decided to use a nutritionally deficient medium and penicillin (negative selection) to select for mutants (1). However, when he began investigating conjugation in Salmonella, most of his attempts at crossing the mutants failed. Fortunately, one mutant strain produced some prototrophs; but puzzlingly, Zinder''s markers did not segregate. Further experiments showed that the mutants were exchanging genes via bacteriophages (2). Lederberg and Zinder named this new phenomenon “genetic transduction.”Zinder received his M.S. in genetics in 1949 and completed his Ph.D. in medical microbiology in 1952. He then accepted a position as assistant professor at Rockefeller University (then known as Rockefeller Institute for Medical Research). By 1964 Zinder had become a full professor of genetics, and approximately 10 years later he was named John D. Rockefeller, Jr. Professor of Molecular Genetics. In 1993 Zinder was appointed dean of graduate and postgraduate studies.At Rockefeller, Zinder continued his studies of the molecular genetics of phages. He discovered the f2 phage, which was the first bacteriophage known to contain RNA as its genetic material, and demonstrated that RNA phage replication is not dependent on DNA (3).Zinder''s two Journal of Biological Chemistry (JBC) Classics reprinted here look at the phage f2 replicase. In the first paper, Zinder and his graduate student Nina V. Fedoroff show that the enzyme, purified on the basis of its poly(G) polymerase activity, could carry out the in vivo synthetic reactions involved in phage RNA replication. They also report that phage replicase activity is stimulated by salt and by a brief preliminary incubation at high ionic strength. The second paper, also by Zinder and Fedoroff and printed back-to-back with the first, compares the f2 poly(G) polymerase and replicase activities under a variety of conditions. They examined the effects of ionic strength, temperature, magnesium ion concentration, and template and substrate concentrations on the enzymes'' activities. Based on their results, Zinder and Fedoroff suggest a distinction between initiation and polymerization sites on the enzyme complex.Zinder remains at Rockefeller as John D. Rockefeller, Jr. Emeritus Professor and continues to research bacteriophage. Currently he is using genetics, biochemistry, and molecular biology to analyze the filamentous bacterial virus, f1, and its interactions with its host, Escherichia coli. His other studies relate to protein-DNA recognition, membrane anchoring, and questions of protein structure.In recognition of his many contributions to science, Zinder has received numerous honors and awards. These include the 1962 Eli Lilly Award in Microbiology and Immunology from the American Society of Microbiology, the 1966 Award in Molecular Biology from the National Academy of Sciences, the 1969 Medal of Excellence from Columbia University, and the 1982 Award for Scientific Freedom and Responsibility from the American Association for the Advancement of Science. Zinder became a member of the American Academy of Arts and Sciences in 1968 and of the National Academy of Sciences in 1969.Zinder''s coauthor on the two JBC papers also has gone on to a distinguished career in science. Fedoroff received her Ph.D. in 1972 and was a staff scientist at the Carnegie Institution of Washington. She joined the faculty of the Pennsylvania State University in 1995 and became the Evan Pugh Professor, Penn State''s highest academic honor, in 2002. She currently holds the Verne M. Willaman Chair of Life Sciences. In 2007, U. S. Secretary of State Condoleezza Rice named Fedoroff her science and technology adviser. She remains in this position today, serving U. S. Secretary of State Hillary Clinton. Fedoroff is a 2006 National Medal of Science laureate and a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the Phi Beta Kappa and Sigma Xi honor societies. Her current research focuses on the mechanisms that allow plants to withstand the environmental challenges of a changing climate.     

Newfoundland pathologist driving force as province finally adopts medical examiner's act.

Newfoundland''s former chief forensic pathologist is pleased that the provincial government has adopted a new medical examiner''s act that he helped develop. He hopes the new act will help clear up confusion about who does what when a body is found in the province.     

The main components of St John's Wort inhibit low-density lipoprotein atherogenic modification: A beneficial “side effect” of an OTC antidepressant drug?

Hypericin and pseudohypericin are polycyclic–phenolic structurally related compounds found in Hypericum perforatum L. (St John's wort). As hypericin has been found to bind to LDL one may assume that it can act as antioxidant of LDL lipid oxidation, a property which is of prophylactic/therapeutic interest regarding atherogenesis as LDL oxidation may play a pivotal role in the onset of atherosclerosis. Therefore, in the present paper hypericin, pseudohypericin and hyperforin, an other structurally unrelated constituent in St John's wort were tested in their ability to inhibit LDL oxidation. LDL was isolated by ultracentrifugation and oxidation was initiated either by transition metal ions (copper), tyrosyl radical (myeloperoxidase/hydrogen peroxide/tyrosine) or by endothelial cells (HUVEC). LDL modification was monitored by conjugated diene and malondialdehyde formation. The data show that all compounds (hypericin, pseudohypericin and hyperforin) at doses as low as 2.5 μmol/l are potent antioxidants in the LDL oxidation systems used. The results indicate that the derivatives found in Hypericum perforatum have possible antiatherogenic potential.