Breakthrough in cell reprogramming

first_imgA group of Harvard Stem Cell Institute (HSCI) researchers has made such a significant leap forward in reprogramming human adult cells that HSCI co-director Douglas Melton said the institute will immediately begin using the new method to make patient- and disease-specific induced pluripotent stem cells, known as iPS cells.“This work by Derrick Rossi and his colleagues solves one of the major challenges we face in trying to use a patient’s own cells to treat their disease,” said Melton, who is also co-chair of Harvard’s Department of Stem Cell and Regenerative Biology. “I predict that this technique will immediately become the preferred method to make iPS cells from patients, and, indeed, at the HSCI we are turning our entire iPS core to using this method,” said Melton, who did not participate in the work.The findings were published online by the journal Cell Stem Cell.Rossi’s group, based at the Immune Disease Institute, at Children’s Hospital Boston, used synthetic mRNA to reprogram adult human skin cells, called fibroblasts, turning them into cells that are apparently identical to human embryonic stem cells, the initial building blocks of the body’s organs. They then used other mRNA to program the new cells, which they are calling RiPS (RNA-iPS) cells, to develop into specific cell types. In the current study, they created muscle cells.Because mRNA carries genetic instructions but does not enter the DNA of the target cells, the resulting tailored cells should be safe to use in treating patients, Rossi said, unlike the iPS cells now being created around the world.“The new report provides a substantial advance,” National Institutes of Health director Francis S. Collins told The Washington Post. “But this research in no way reduces the importance of comparing the resulting iPS cells to human embryonic stem cells. Previous research has shown that iPS cells retain some memory of their tissue of origin, which may have important implications for their use in therapeutics. To explore these important potential differences, iPS research must continue to be conducted side by side with human embryonic cell research.”“Our findings address three major impediments to clinical translational use of iPS cells,” Rossi said in an interview. “The method does not in any way breach genomic integrity, as it does not necessitate integrating genes or viruses into the target cells’ DNA; it is orders of magnitude more efficient at producing iPS cells than conventional iPS methods, which were notoriously inefficient; and it gives us a way to directly program and direct the development of the iPS cells toward clinically useful cell types.”The three problems the Rossi group indeed appears to have solved in one fell swoop are those with which stem cell biologists have been wrestling ever since Japanese researcher Shinya Yamanaka announced in 2006 that he had used four genes to convert fully developed adult skin cells into ones with all of the properties of embryonic stem cells. Those cells, which Yamanaka dubbed induced pluripotent stem cells, could, like embryonic stem cells, theoretically be directed to become any human cell type.But Yamanaka used viruses to insert the genes into the genome of the target cells, and that created at least two major impediments to using the iPS cells to treat human disease, which is the main goal of stem cell researchers.First, the use of the integrating viruses raised the real possibility that cancers might inadvertently be triggered. Second, inserting the genes into the genome could lead to changes that would alter the properties of the resulting iPS cells so they would not be identical to human embryonic stem cells.Ever since Yamanaka’s discovery, scientists have been looking for other ways to turn adult cells into iPS cells, both to study diseases by creating cell lines carrying the genes of diseased patients, and to create patient-specific cell lines to treat individual patients. Now, with Rossi’s RiPS cells, they may have found what they’ve been seeking.The Washington Post reported Wednesday that Yamanaka stated in an email he plans to try Rossi’s technique, and said “the standard method to generate [iPS cells] for clinical applications has yet to be established. I think this method has the potential for it.”“Most approaches for generating iPS cells involve some sort of integration into the genome, usually viral,” Rossi said, “so clearly the development of a technology that does not breach genomic integrity is very important. Gene therapy trials unfortunately taught us the danger in leaving viruses in the genome, as some patients developed cancers that were driven by the integrated viruses. So when one thinks about strategies for regenerative medicine, you need to envisage utilizing cells whose genome has not been breached. We believe that utilizing RNA to generate transplantable cells and tissues is an ideal solution because, to the best of our knowledge, RNA is completely nonintegrative.”Rossi and his team created mRNA that carries the instruction sets from the four genes used by Yamanaka. So the mRNA tells the adult cells to reprogram, just as the Yamanaka genes do, but it does so without disturbing the integrity of the adult cell’s genome. The resulting RiPS cells may be more identical to human embryonic stem cells because their genomic integrity is maintained. When Rossi and colleagues compared the RiPS cells they made to human embryonic stem cells, they found a much closer match than when iPS cells were generated with viruses.Next comes the question of how to turn the RiPS cells, cellular blank slates, into the kind of cells that researchers need to treat patients — for example, the insulin-producing beta cells destroyed in diabetics, or the motor neurons that degenerate in the brains of patients with Parkinson’s.Here again Rossi and his team turned to mRNA. “Up to this point, it’s been extremely difficult to direct cells to differentiate towards particular fates, or cell types,” Rossi said. Current methods for directing cellular differentiation usually rely on tightly controlling the environment in which the cells are developing, tailoring the growth media and other factors to coax the iPS cells to develop into a particular cell type. “We thought to use mRNA encoding … factors in order to drive the fate of iPS cells to the desired cell fate. We are beginning to know more about what factors are needed to create certain types of cells. A great example was the demonstration by Doug Melton’s group that they could use just three specific factors to turn adult pancreatic exocrine cells into insulin-producing beta cells.”But those experiments again required the insertion of gene-carrying viruses into the target cells, said Rossi. To demonstrate that mRNA might be used to direct iPS cell fate, Rossi and his colleagues synthesized mRNA with the instruction set for making muscle cells, and showed that they could use this method to efficiently drive the fate of RiPS to muscle cells, without compromising the genome of these cells. “These results provide us with a new experimental paradigm that might safely be used in regenerative medicine,” Rossi said.Rossi’s group also reported it has found a method that is far more efficient than previous ones in producing iPS cells.“Up until now, iPS cell generation has been an extremely inefficient process,” Rossi said. “Our technique allows for iPS generation that’s significantly more efficient than conventional approaches.” It used to be that only 0.001 to 0.01 of starting cells could be reprogrammed to iPS cells. The study by Rossi and his colleagues, however, reported iPS conversion efficiencies in the range of 1 to 4 percent of starting cells. What that means practically is that iPS cells can be generated even if few starting cells are used. This efficiency may prove important for patients from whom only a few starting cells can be obtained.Another finding has implications far beyond stem cell science. The Rossi group reported that it found a way to overcome the natural cellular immunity to the insertion of foreign RNA.“I am sure we’re not the only lab to have the idea of using RNA for cellular reprogramming,” said Rossi. “The problem is that when you introduce RNA into a cell, the cell thinks it is being infected by an RNA virus and retaliates by producing a massive interferon response that effectively shuts down cellular function and can prompt the cell to altruistic suicide as it tries to stop the ‘virus’ from replicating. In order to use RNA for cellular reprogramming, we clearly needed to overcome this problem,” he said. “Our approach was to modify the RNA so that it no longer set off antiviral responses when introduced into cells. The modified mRNA enabled us to efficiently express proteins in cells for days and weeks without causing any adverse reaction in the cells.”“Although we developed this technology for cellular reprogramming, it actually has utility far beyond that,” said Rossi, who has patented the technology and is forming a company to develop it. “Basically our technology provides a means of transiently expressing any protein in a cell without eliciting the cell’s antiviral response pathways. This could have potential therapeutic benefit in patients suffering from protein deficiencies.”This work was supported with funding from Rossi’s “startup package,” the money that newly hired faculty receive to establish their labs, and with a seed grant from the Harvard Stem Cell Institute.Said Melton, “It’s wonderful to see that HSCI seed grant funds given to outstanding, innovative, and imaginative young scientists like Rossi can so quickly and dramatically change a field.”last_img read more

‘Why Books?’

first_imgWhy books?In a two-day conference of the same name, experts from Harvard and elsewhere are investigating the fate of print in a digital age. The field of battle, Thursday and today (Oct. 28-29), is the Radcliffe Institute for Advanced Study, the home of a prestigious fellowship program and one of Harvard’s most durable crossroads for interdisciplinary discourse.After a decade of debate, the consensus is that books are not going away — and that at best electronic communication will align powerfully with the tradition of ink and paper.“Why Books?,” two years in the making, was organized by a faculty committee headed by Leah Price ’91, RI ’07, and Ann Blair ’84, BI ’99. Price is a professor of English, Harvard College Professor, and the Radcliffe Institute’s senior adviser in the humanities. Blair, also a Harvard College Professor, is the Henry Charles Lea Professor of History.Today’s (Oct. 29) conference at the Radcliffe Gymnasium consists of a series of four panels — on future text formats; storage and retrieval; circulation and transmission; and reception and use. There is a conference hashtag for Twitter: #whybooks.“Why Books?” started Thursday (Oct. 28), logically, with explorations of both digital and print resources at Harvard. Conference attendees took in 13 workshops — visits to University facilities that make, store, conserve, distribute, and (yes) digitize books and other printed matter.At the Radcliffe Gymnasium, Marilyn Dunn, executive director of the Arthur and Elizabeth Schlesinger Library on the History of Women in America, demonstrated Harvard’s Web Archive Collection Service (WAX), a mechanism for harvesting and preserving Web content.At Harvard Law School, experts from the Special Collections staff made one presentation on 16th century law books and another on books that illuminated the pedagogy of Christopher Columbus Langdell (1826-1906), the Law School’s first dean and a pioneer in case-method teaching.At Harvard University Press, Art Director Timothy Jones outlined the challenges of book and editorial design as the world moves into a digital environment.At Harvard’s Weissman Preservation Center, those on tour observed conservators at work and learned about the art and science of preserving fragile books, maps, drawings, and other printed materials. (Some are so delicate they can’t be exposed to direct light.)At Bow and Arrow Press, visitors went back to the future, getting a hands-on history of a vintage letterpress operation from Zachary Sifuentes ’99, resident tutor in poetry and arts at Adams House.There were other workshops on e-books, preserving digital materials, printing before the industrial age, and how original manuscripts illuminate an artist’s creative methods and even the business environment they operated in. (That was at the Houghton Library, where visitors looked at written pages from William James, Samuel Johnson, and Emily Dickinson.)In a first-floor conference room at the Schlesinger, visitors roamed through a temporary exhibit called “A Taste of History,” a selection of cookbooks from the library’s famous collection.There was a 1679 edition of a cookbook by German author Anna Wecker, the world’s first female food writer. Its title in English reads “New, delightful, and useful cookbook,” and it was first published in 1596. In the back is an appendix on Parisian cooking — an early sign of the dominant French cuisine that would soon sweep Europe.Also on display was “What Mrs. Fisher Knows About Old Southern Cooking” (1881), the first cookbook by a freed slave; a 1943 wartime version of Irma S. Rombauer’s “The Joy of Cooking,” including what she called “emergency chapters” on meatless and sugar-free dishes; Julia Child’s copy of M.F.K. Fisher’s “How to Cook a Wolf”; and a tiny cookbook printed in 1601 in Venice, Italy, the Schlesinger’s oldest cookbook volume.“These are my babies,” said Barbara Wheaton, whose 1982 “Savoring the Past” legitimized culinary arts as a window onto history. The longtime Harvard food scholar, now honorary curator of the Schlesinger’s Culinary Collection, delivered a loving précis of a few of the volumes.Summing up the books with her was Marylène Altieri, the Schlesinger’s curator of Books and Printed Materials.“That any of the tradition gets written down is miraculous,” said Wheaton of books about cooking — volumes that often capture the voices of women and male artisans who otherwise would be lost to history. These were “people who didn’t expect that what they said would matter,” she said.Any conference on the fate of books would do worse than to start with books about cooking, said Wheaton.“One of the first things our ancestors did … was to talk about food” — a topic so vital to survival that it helped shaped language millennia before print arrived, she said. “To talk about getting it, to talk about preparing it, to talk about the sensations of eating it — with all the moral and sensual and practical questions that arise from getting enough stuff … to keep the organism going.”As for broader question of the fate of print that will come up in today’s “Why Books?” conference — “I think about it every day,” said Wheaton.“I’m absolutely nuts about computers and the Internet. I’m building a database that is better than having an expensive car because I can do such wonderful things with it,” she said. “But nothing replaces books. Ever.”Wheaton reached in front of her and touched the edges of Abby Buchanan Longstreet’s “Dinners, Ceremonious and Unceremonious,” an 1890 volume on table etiquette.“The thing itself,” she said of the volume. “This book is small and dainty and civilized. It has gold letters and a nice tasteful green (cover).”By holding it, and reading it, said Wheaton, “you’re going to have a decorous experience.”As her visitors filed out, she added: “Come back and read a book. Read 10.”Marylène Altieri (left), curator of Books and Printed Materials at the Schlesinger Library, introduces Barbara Wheaton (right), honorary curator of the Culinary Collection.last_img read more

Mixed messages

first_imgIs quality in the eye of the beholder?Researchers at Harvard Medical School (HMS) and Massachusetts General Hospital (MGH) have found wide disparities among four common measures of hospital-wide mortality rates, with competing methods yielding both higher- and lower-than-expected rates for the same Massachusetts hospitals during the same year.The findings, published Dec. 23 in a special article in the New England Journal of Medicine, stoke a simmering debate over the value of hospital-wide mortality rates as a yardstick for health care quality. The measure, which compares a hospital’s actual patient death rate with statistical predictions, is reported publicly in countries including England, Canada, and Denmark, but some hospitals and policy experts have questioned its value due to the complexity and variability of diagnoses.“It’s troubling that four different methods for calculating hospital mortality rates as a measure of quality should yield such different results,” said lead author David M. Shahian, HMS professor of surgery at Massachusetts General Hospital. “Measurement theory — not to mention plain common sense — suggests there is a problem.”The potential of performance evaluation to improve both the quality and the cost of health care has fueled interest in provider “report cards,” including mandates by state and federal law.In 2008, the Massachusetts Division of Health Care Finance and Policy engaged researchers Shahian; Lisa I. Iezzoni, HMS professor of medicine at MGH; and Sharon-Lise T. Normand, HMS professor of health care policy (biostatistics) and professor in the Department of Biostatistics at Harvard School of Public Health, to evaluate four vendor-created measures of hospital-wide mortality. The state was looking for a means to measure hospital quality for the public report cards mandated under its 2006 health care reform law.The researchers compared four measures of hospital-wide mortality provided by commercial vendors. These vendors all believed that their hospital-wide mortality measures were an accurate reflection of hospital quality. Each vendor received identical data — three years of patient discharge data from all 83 general acute care hospitals in Massachusetts, representing 2.5 million discharges — and used the data to calculate each hospital’s mortality rate. The researchers then compared results.“The results of the horse race are that it’s really not clear who won,” said Iezzoni, who also is the director of the Mongan Institute for Health Policy at MGH. “The problem is that we were measuring the success of each of these measures against a gold standard we simply do not have: an objective measure of hospital quality.”Without that gold standard, the researchers were left to compare vendor tools with one another. Their conclusion: Methods and results varied widely. For example, every tool excluded some discharges from its calculations based on the details of each. But where one tool excluded 5 percent of all discharges, another excluded 72 percent.Even so, a high degree of convergence — different methods yielding similar final results — could have supported the validity of this approach to estimating hospital quality. But that’s not what researchers found. For example: Of 28 hospitals designated by one method as having higher-than-expected hospital-wide mortality in 2006, 12 were simultaneously classified as having lower-than-expected mortality by at least one other method.In August, the researchers told the state that they could not recommend any of the four vendor-created tools. “But the results should not be interpreted as an indictment of any particular technique,” said Normand. “Rather, they call into question the concept of measurement of hospital-wide mortality, as four different methods yielded four different results. Thus, this may not be a good way to assess hospital quality.”The authors are longtime advocates of performance assessment and public reporting to provide transparency and accountability in health care.Normand developed the statistical models used by Medicare and Medicaid for public reporting of heart attack, heart failure, and pneumonia mortality rates. Shahian has been a leader in the public reporting initiative of the Society of Thoracic Surgeons. Together, they were leaders in developing and implementing public report cards for coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) in Massachusetts.But where mortality rates may reflect clearly the quality of care for some procedures, like coronary bypass, they may reveal less about care for other conditions, such as major trauma or advanced malignancy.“An alternative to hospital-wide mortality rates would be to construct a more limited portfolio of mortality results for individual common conditions such as heart attack, stroke, pneumonia, CABG surgery, and PCI,” said Shahian. “These have the advantage of large sample sizes at most hospitals, a generally accepted association between mortality and quality of care, and credible risk models to adjust for patient severity.”Iezzoni, an internationally recognized expert in risk adjustment, has edited “Risk Adjustment for Measuring Health Care Outcomes,” now in its third edition.“Underlying this finding is the more fundamental and as yet unanswered question about whether hospital-wide mortality rates provide meaningful insight into hospital quality,” she said.This work was funded by a contract with the Division of Health Care Finance & Policy, Executive Office of Health and Human Services (EOHHS), commonwealth of Massachusetts, Boston, Mass. The views expressed in this article are solely those of the authors and may not reflect the views of the division, the EOHHS, or the commonwealth.last_img read more

Getting students to perform

first_imgWhen he arrived at Harvard in 1999, Richard Wolf brought with him a deep knowledge of South Indian classical music and a desire to share it.In addition to asking his students for a rigorous analytical and ethnographic study of non-Western songs and musical styles, he wanted something else from them.To understand the nuances of the dynamic sounds created by Indian instruments, they had to learn how to play them, such as the elegant vina, a southern lute carved of wood, with strings that players bend with their fingers to reach notes and tones not found on a typical Western scale.“You can only learn so much by listening and analyzing and reading,” said Wolf. “To be able to actually play an instrument helps you listen better, and understand the music better.”So Wolf, with support from Harvard’s Department of Music and its Office of Undergraduate Education, acquired several vinas and South Indian mridangam drums, along with instruments from Iran and Africa, for his courses, which examine the musical traditions of South and West Asia, with a focus on India, Pakistan, Iran, and parts of Africa.Umayalpuram Mali, a visiting scholar and mridangam master from South India, will perform in the April 21 concert at Harvard’s Paine Hall at 7 p.m.“Since that time, my courses have had a hands-on component,” said Wolf of his efforts to make performance a regular part of his pedagogy. The practice has gained traction at Harvard, buttressed by the findings of President Drew Faust’s Arts Task Force, which called for a greater support of the arts and the inclusion of performance and art-making in the Harvard curriculum.In recent years, Wolf has made that hands-on component more central to his classes and encouraged students to “become a little bit more responsible for what they have been doing with it.”His classes now often culminate with a public performance, such as tomorrow’s concert featuring Wolf and Umayalpuram Mali, a visiting scholar and mridangam master, as well as several of Wolf’s students. The free performance will take place at the recently refurbished John Knowles Paine Concert Hall at 7 p.m.To help his students learn the complexities of the instruments, Wolf secures some of the best teachers in the world. Since his arrival at Harvard, he has enlisted a steady stream of visiting professional artists from near and far who work with students.“The students are really receptive and so willing to experiment,” said Mali, who is from South India, practicing with Wolf on the floor of his office in the basement of Memorial Hall. In residence for the spring semester, Mali has worked with students both in and out of class, helping them to understand the intricate music, which is learned by rote instead of written notation.Keeping the rhythm for the informal jam session — which, like much of the music, was grounded in improvisation — was Sarah Sussman, a graduate student in ethnomusicology who took Wolf’s class and now acts as a teaching assistant for the course.“You have to put in a lot of time and work,” she said, as she tapped out a steady beat with her hands, “but it definitely helps you understand the music.”In addition to being a professor in music at Harvard, Wolf is widely recognized for his talent in performing with the vina. As a student at Oberlin College, he studied music and math. After attending a vina concert in school, he applied his knowledge and experience with the guitar to understanding the plucked instrument, and was hooked on it.“I very much wanted to do original music and improvisation and was interested in new ways to satisfy that interest. When I was exposed to South Indian music, my fate was sealed.”last_img read more

Undergraduate book collecting prize winners

first_img Read Full Story A grandmother’s gift was the inspiration for this year’s winner of the Visiting Committee Prize for Undergraduate Book Collecting.Catherine Katz ’13 was the first place winner for her entry “My Grandmother’s Childhood Library: Collecting Early 20th Century Stratemeyer Syndicate Children’s Series.” Katz said her grandmother’s gift of a half dozen original editions of favorite childhood stories helped foster an early love of books.Those stories included the Bobbsey Twins tales and Nancy Drew mysteries from the 1930s, and Katz said over the years she would hunt through book stores and antique shops in an effort to add to her growing collection. But upon reading revised editions of the Nancy Drew stories written in the ’50s and ’60s, Katz discovered an interesting change.“In the original stories Nancy was clever and adventurous. But in the 1950s and ’60s editions, she was more of an every person and just average,” Katz said. “They changed her to be more relatable to the times.”Established in 1977, the Visiting Committee Prize is awarded annually to recognize and encourage book collecting by undergraduates at Harvard. It is sponsored by the Members of the Board of Overseer’s Committee to Visit the Harvard Library.“Each year we receive some extraordinary entries which demonstrate the unique collecting interests of some of our undergraduates, and this year was no different. The collections submitted to the judges were impressive for their quality and thoughtful approach to collecting,” said Susan Fliss, Interim Librarian of Harvard College.last_img read more

Shedding light on gestational diabetes controversies, challenges

first_imgGestational diabetes—diabetes that women develop while pregnant—can lead to serious health problems for both babies and mothers. Babies can be born too large or have birth injuries. Mothers can face greater risk of needing a cesarean delivery. For both mothers and babies, the risk of developing type 2 diabetes later in life can increase. But there’s a lack of clear evidence—and thus a lack of consensus—about the best way to test for and diagnose gestational diabetes. And much more could be done in terms of preventing the ailment in the first place.Harvard School of Public Health’s Michelle Williams gave an overview of the controversies and challenges surrounding gestational diabetes at a summer Hot Topics lecture at the School on August 6, 2013.Watch a video of the Hot Topics lecture“Gestational diabetes is one of those conditions where we just can’t seem to decide how to define it and how we should screen for it,” said Williams, Stephen B. Kay Family Professor of Public Health and chair of the Department of Epidemiology. But the condition has been on the rise in recent years, in step with the worldwide rise in obesity. According to current estimates, 5%-7% of pregnant women in the U.S.—nearly a quarter of a million each year—develop gestational diabetes. Read Full Storylast_img read more

Family strife

first_imgDespite finding great success and strong customer loyalty in a fiercely competitive industry, Demoulas Super Markets, a regional grocery chain owned by two flanks of the Demoulas family, has been embroiled in a bitter internal feud that dates to the early 1990s.The first chapter of the dispute resulted in the most expensive lawsuit in Massachusetts history; now, tempers have boiled over again, with employees and customers protesting the ouster of CEO Arthur T. Demoulas and two top deputies by a board controlled by members backing a rival cousin. Demoulas’ firing prompted thousands of workers and their supporters to rally at corporate headquarters this week urging his reinstatement. Dozens of lawmakers have come out publicly in support of the protesting workers, some of whom have also been fired.Established in 1917, the privately held company has 71 Market Basket grocery stores across Massachusetts, New Hampshire, and Maine. It has approximately 25,000 employees and estimated total revenues of $4.3 billion in 2013.The Gazette spoke with John A. Davis, a senior lecturer of business administration and the faculty chair of the Families in Business program at Harvard Business School, about the dynamics of family-owned companies and the particular challenges they face.GAZETTE: What are some of the common issues that family owned businesses contend with, and how are they different from what other businesses confront?DAVIS: Family companies are the biggest sector out there among private companies, and account for approximately half of all the publicly listed companies in this country. So it’s a huge, huge sector. Maybe half of the biggest companies in the country are still family controlled, all the way up to companies like Wal-Mart.It’s a very quiet sector, but it’s also a very important one and, arguably, the single most important sector in our economy. If you take a look at the performance of family companies, most all of the research is demonstrating that by a significant margin, on average family companies perform better. They have a lot going for them, but there are high performers and weak performers. You’ve got companies like Mars, a huge, family controlled behemoth in the food products industry; most of your media companies are family controlled; you’ve got Fiat that’s doing quite well. Market Basket [appears to be] a very strong company — high quality, workforce loyalty. … But these family companies are vulnerable to things that not all companies are vulnerable to.All companies need a good ownership base, no matter what kind of company it is, even whether it’s public or private. You need to have an ownership base that is stable and supports management. Family companies do best when they are long-term oriented, [when] they make investments and develop relationships and loyalty for long-term returns. They are not speculators, in general. They’ll wait years sometimes for good returns because they want to do the game right. Now, if you have an unstable ownership base, which this company obviously does, it’s really hard to manage well in that environment. If the family is unstable, if the family is rivalrous, if family members block one another for whatever reason — it could be that they disagree on strategy or they just don’t like each other — if that starts getting played out in the ownership area, it doesn’t take very long at all before the management really feels it and it affects how things get done and it even affects if people are willing to invest their careers in the company.So you have to be very careful in a family business to make sure that the ownership base, and the family base, is united and disciplined. It is natural for owners and family members to disagree to some extent with one another. You don’t want 100 percent agreement, but you want unity. And that requires that when we disagree, we have mechanisms where we talk out our disagreements and get on the same page again and then march forward. And if you don’t have those consensus-building mechanisms, you’re usually in a bind.GAZETTE: What’s the best way to avoid or to resolve those kinds of problems?DAVIS: A very strong shareholder agreement, number one, that says that family disagreements don’t go to court. When families go to court, it rarely works out well. In most families, family members suing each other is an embarrassment — and should be. The temptation to retaliate is pretty high. The agreement among the owners states that, “In the event of these kinds of disputes, this is how we’re going to deal with it.” Best practices usually include working it out internally, maybe through a family council or the company board, then working with a mediator and then finally, binding arbitration. But we don’t go to court and if you choose to go to court, there are penalties for those owners for going to court. So it’s important that families set up these agreements and this family apparently didn’t.GAZETTE: In terms of smart corporate governance, is ensuring that some non-family members have a voice in executive decision-making the best strategy?DAVIS: Yes. I recommend a board with representatives of the owners but only a few, the CEO and no other managers, and independent members — people who are not owners and also not managers, people who are fair-minded, bring expertise and outside perspectives to whatever issues come up, and can help resolve internal conflicts so that the company can unite behind a particular strategy and march forward with a long-term plan. You want the family owner’s point of view on the board because when the board makes a decision, you want to know that the owners are going to line up behind it. But you don’t want the family to dominate the board because you’re trying to reduce and manage family politics, which is likely if not inevitable.The important thing to remember about families is that the issues don’t have to be big ones to get a family riled up. Sometimes [what seem] like little things really offend or create mistrust within a family. Because family feelings can be sensitive, and also because memories in families are remarkably long, you need to be able to be extra-careful in a family business that you have very solid governance to help make family members feel secure that their interests are well and fairly represented. We see good governance making a huge contribution in well-run family companies, to the benefit of the company and to the family.GAZETTE: You’ve written about the social psychology of family shareholder dynamics. Could you explain what those typically are and how they affect a business?DAVIS: In a family ownership group, it’s not just who owns how much, but how are they related? You have to understand the family relationships among the owners, how ownership is distributed, and the relative power of different owners and different ownership groups in the mix. A group of siblings will have a different kind of relationship typically than will a group of cousins. The nature of the family relationship — whether they’re tight and mutually supportive or rivalrous — makes a huge difference in the ownership group. The best predictor of how cousins will get along is how their parents, the siblings, got along. If the siblings set a good example for the cousins, the cousins will usually follow it. There are exceptions to every rule, of course, and I have seen cousin groups who get fed up with their parents’ bickering and come together and say, “We’re going to do this better, we can get along.” But those tend to be the exception.To understand the shareholder dynamics, you also need to understand how ownership is organized — is it organized within a family holding company or do owners have a shareholder agreement? The more clarity there is about who owns what and what are the rights and responsibilities that the owners have, the better. And again, good governance helps, meaning the rules, policies, agreements that we share and the forums like boards and shareholder meetings. Driving all this is good leadership. You need leaders that are seen as fair and wise, and understand how to make decisions so that we trust them. If we have good leadership, along with good safeguards in our governance system, we’re probably going to manage most of these ownership issues well.GAZETTE: It appears that much of the infighting in the Market Basket situation stems from issues connected to succession. Is there a lesson here for companies that envision passing along the business to heirs?DAVIS: Obviously, clarity about who will succeed the previous leader is important, but disputes are not always caused by the lack of a clear plan. Sometimes each side is really clear about who should be the successor, they just disagree. Families like this one need help in agreeing on their common purpose and what they can do to treat each other respectfully. They need to move on from their old disputes, but if they can’t move on, business decisions still need to be made. Families benefit from having a clear buy-sell agreement, so that if we can’t get along, one of us can buy the other out. You don’t want to play that card unless you mean it, but owners have to know it’s in the deck of cards and can be played. Because people need to know that if they don’t behave reasonably and respectfully that the other side can play it. And if the card is played, you restructure the ownership group, buy one party out, and then move on with, hopefully, more aligned owners that see things pretty much the same way and agree on the rules. That is probably needed here. It looks like this family, unfortunately, got off on the wrong foot and then went down this very argumentative and disruptive path and could never get off of it. They’re still on it.This interview has been edited for clarity and length.last_img read more

The communications gap on vaccines

first_imgThe number of parents who refuse to vaccinate their children is on the rise, and with it the incidence of preventable diseases such as measles. The health community could reverse the trend by doing a better job of initiating conversation about vaccinations, said participants in a forum at the School of Public Health (HSPH) on Monday.Panelists at “Vaccinating Children: Public Health and Trust” called for rigorous cross-disciplinary research into vaccine hesitancy and the effectiveness of health-communication strategies. The data would be used to develop a toolkit for easing the worries of anxious parents.????Why would anybody hesitate to vaccinate their kids?” said Barry R. Bloom, Harvard University Distinguished Service Professor and Joan L. and Julius H. Jacobson Professor of Public Health at HSPH. “Where do they get their information? How good is the information? Is it social networks? Is it over the back fence? Is it from moms at school? It’s very hard to develop a strategy if in fact we don’t know the values people are bringing when they come to the pediatrician.”Bloom was joined by Jane Kim, an associate professor of health decision science at HSPH; Richard Malley, a senior associate physician in medicine in the Division of Infectious Diseases at Boston Children’s Hospital, a Harvard affiliate; and Seth Mnookin, associate director of the graduate program in science writing at the Massachusetts Institute of Technology. The event was moderated by Philip J. Hilts, former director of the Knight Science Journalism Fellowships at MIT.The vast majority of parents follow the recommended vaccination schedule for their children, but the number of holdouts is significant enough to have caused outbreaks of measles, a disease that the World Health Organization declared eliminated from the United States in 2000. Between 20 and 30 percent of parents selectively vaccinate, delay some vaccines, or have some misgiving about vaccinating their children, according to a recent report from the American Academy of Arts and Sciences.Concerns about the safety of vaccines began to bubble up nearly 20 years ago with media coverage of a study that claimed a link between autism and the measles-mumps-rubella vaccine. Doubts persisted even after the study was revealed as a fraud, in part because of misinformation spread online. Pediatricians who downplay or fail to mention the risk of adverse effects while discussing vaccinations with parents may unwittingly fuel anxiety, Malley said.Medical professionals who acquaint themselves with parents’ cultural backgrounds and knowledge of medical issues can offer relevant and targeted information rather than a one-size-fits-all approach, the panelists said. A relatively simple way to learn views on vaccinations is to cover the topic in new-patient questionnaires, Kim noted.Among the barriers to meaningful conversation is time. Wellness visits are on the clock, and shots are usually left until the end. Inoculating the child at the beginning of the visit would give parents and pediatrician more time to talk about the vaccinations, the panelists said. Another possible solution: wider discussion of vaccinations during prenatal visits, when parents are often more receptive to new information and have more time to develop informed decisions.Malley suggested extending outreach beyond pediatricians by educating general practitioners on ways to reinforce accurate information about vaccinations. Bloom called for a checklist that medical office workers, school nurses, obstetricians, gynecologists, and other health professionals could consult to improve communications with parents.Critical to developing a comprehensive communications strategy is research into why parents are anxious and how they make decisions about whether to vaccinate their children on time, on a delayed schedule, or not at all, the panelists agreed. The cost of funding such studies pales in comparison to what the public spends to contain an outbreak of disease, said Mnookin, who noted that when measles resurfaced in San Diego several years ago, the price tag was $10,000 per patient.“We have an opportunity now to not make the mistakes we have made, and we should seize it,” he said. “We’ve seen how quickly you can have outbreaks and how expensive it can get.”The Forum at the Harvard School of Public Health was covered via webcast.last_img read more

What they overcame

first_imgThe images and the music haunt you long after they become memory. The blurry footage shows three body bags being loaded onto steel tables from cars as the song “We Shall Overcome,” the anthem of the Civil Rights Movement, plays in the background.The scenes are part of the 2014 documentary “Freedom Summer” by Stanley Nelson Jr., a searing look at the efforts of student volunteers who traveled to Mississippi in the summer of 1964 to help African-Americans register to vote. The brief clip shows the recovered remains of three young Civil Rights workers who were murdered by the Ku Klux Klan. It also shows the impassioned eulogy for one of the men, James Chaney, delivered by Civil Rights activist Dave Dennis.For Nelson, whose films vividly capture the African-American experience, the excerpt “was just pure emotion. We weren’t trying to give you any kind of new information,” he said. “We were trying to give you a sense of the feeling of that summer and how people felt when the bodies were discovered.”Part of what drew Nelson to filmmaking was the realization that African-Americans rarely appeared on TV and film during his youth in the 1960s and ’70s. Jon Chase/Harvard Staff PhotographerDelivering that emotion is a part of what it takes to make a great work, said the filmmaker, who discussed his career with Harvard President Drew Faust during the final William Belden Noble Lecture last night at Memorial Church.Past lecturers in the series, established by Nannie Yulee Noble in 1898 in memory of her husband, have included former President Theodore Roosevelt, theologian H. Richard Niebuhr, Sen. Eugene McCarthy, and Archbishop of Canterbury Robert Runcie. This year’s series included screenings of three of Nelson’s films: “Wounded Knee: We Shall Remain,” “Freedom Riders,” and “Freedom Summer.”Part of what he said drew him to filmmaking was the realization that African-Americans rarely appeared on TV and film during his youth in the 1960s and ’70s, Nelson told Faust during the hour-and-a-half discussion. When they did, he said, they were being mocked, or exploited in “Blaxploitation” films in which the main characters were often pimps or hustlers.“Those weren’t the people that I knew,” said Nelson, who signed up for a film class in college in the hope of bringing more positive images of African-Americans to the screen. The class fueled his interest in movie-making. After graduating from film school at the City College of New York, Nelson worked for William Greaves, a pioneer of African-American filmmaking, who became an important mentor. The fact that Greaves was “making a living making documentary films” inspired Nelson. “I saw an example,” he said.In his documentaries, Nelson tries to evoke the same kind of cinematic flair found in mainstream Hollywood films, “making them visually and aurally exciting,” and offering the viewer “that sense right from the beginning.” That strategy is on full display from the beginning of “Freedom Riders,” his 2010 film that tracks the trek of Civil Rights activists in 1961 into the Deep South to challenge segregation laws.In the first frames, giant blue neon letters spell out the name “Greyhound.” Later, black-and-white photos of protesters flash across the screen, as do shots of their applications to the Congress of Racial Equality (CORE), the group that spearheaded the freedom rides from Washington, D.C., to New Orleans in 1961.Unsure whether the technique would work, Nelson chose to include in the opening sequence the same protesters reading what they had written on their applications five decades ago.“I’m a senior at American Baptist Theological Seminary and hope to graduate in June,” reads U.S. Rep. John Lewis, a central figure in the Civil Rights Movement and a freedom rider. Lewis later suffered a fractured skull during a march from Selma to Montgomery, Ala., in 1965. “I know that an education is important and I hope to get one,” his application continued. “But at this time, human dignity is the most important thing in my life.”“A lot of times, you have ideas and they don’t work. Or you have ideas and you are scared to try them,” said Nelson. “… I’ve learned just try it and see what happens.”In many of his films, Nelson forgoes an omniscient narrator, opting instead to allow people who experienced the story to relate it in their own words. He uses music in his works “to help move the film forward,” and he can spend years investigating a story he wants to tell. That detailed research can be tedious and time-consuming, but it can also lead to gold.While researching “Freedom Riders,” he and his colleagues pored over FBI transcripts from a hearing about a bus carrying freedom riders that had been firebombed by a mob in Birmingham, Ala. As the flames ripped through the bus, a young boy who lived nearby captured the moment on film with his new birthday present, an 8-millimeter camera, his father testified. The man said the FBI confiscated the footage. Nelson pressed the organization to produce the film, sending the bureau a copy of the transcript when it denied the footage existed.“Six months later, they called and said they found the footage,” he said.“You have to continue to look with a positive approach and mind-set. You never know what you might find.”Nelson also offered his opinion on the mainstream film “Selma,” calling it “true to the feeling of the movement.”“I think it’s great to get the story out there any way you can,” he added.The session’s host, the Rev. Jonathan Walton, the Pusey Minister in the Memorial Church and the Plummer Professor of Christian Morals, asked Nelson about “the moral impulses” behind his own work. He replied, “The whole point is to kind of drive us forward. … I do hope that there is something that people get out of these films that relates to their lives today.”He said that “Freedom Riders” and “Freedom Summer” have been used by activist groups around the country and the world, and were even watched by the protesters who occupied Tahrir Square during the Egyptian Revolution of 2011.How had Nelson “kept the faith regarding Civil Rights” while making his films, an audience member asked.“The stories make me keep the faith,” Nelson said. “The stories are incredible. They don’t make me lose faith, they make me keep the faith.”During the evening, Nelson also showed a clip of his forthcoming work, “The Black Panthers: Vanguard of the Revolution.” The film will run at the Brattle Theatre on April 27 as part of Boston’s Independent Film Festival.last_img read more