Philip Berroll

By P.H.I.Berroll

“What are you gonna do, kill me?” says John Garfield, as boxer Charlie Davis, to the mobster for whom he refuses to throw a fight. “Everybody dies!” The line is typical Garfield: defiant, but with an underlying sense of his own mortality.  It’s from the classic boxing drama Body and Soul (1947) – a highlight of the Film Society of Lincoln Center’s series, “Running All The Way: The Films of John Garfield,” which runs for three weeks starting August 9. This retrospective is long overdue for an actor who despite a substantial body of work – more than 30 films, some legitimate classics – has never quite earned the iconic status of some of his contemporaries in the decades since his untimely death.

Next to Humphrey Bogart, John Garfield was the dominant tough guy of American cinema in the 1940’s. But while Bogart’s characters often had a tenuous position in society, Garfield was usually cast as an absolute outsider – the drifter, the criminal, the soldier of fortune. With a nasal, sneering voice and a look of constant wariness, he personified the kid from the wrong side of the tracks: cynical, mistrustful, out for himself unless a better offer – usually from a woman – came along. Sometimes he was a victim of injustice; more often, he played men who just expected a raw deal from the world, and were ready to give as good as they got.

His persona was authentic; it was rooted in his poverty-stricken childhood on the Lower East Side, where he was born Julius Garfinkle in 1913. (Always proud of his heritage, he would become the first serious actor to play identifiably Jewish roles on screen.) Turning to the theater as a way out of the ghetto, Garfield made his Broadway debut while in his teens, and later became a leading player with the legendary Group Theater, working with other hungry young men like Elia Kazan, Clifford Odets, and Lee Strasberg.

Hollywood soon came calling.  Garfield’s 1938 debut in Four Daughters, one of 23 films to be shown in the Film Society series, was a sensation; as a working-class musician who disrupts the placid lives of a Middle American family, he was nominated for an Oscar.  His character in the film was a relatively nice guy, but his studio, Warner Brothers, saw him as the successor to the aging James Cagney – the new king of the street punks.  They cast Garfield in melodramas whose plots were about as subtle as their titles (They Made Me a Criminal; Dust Be My Destiny).  But he was occasionally allowed to show more range, as in The Sea Wolf, a first-rate adaptation of Jack London’s novel, where he plays a shanghaied sailor up against brutal captain Edward G. Robinson.

Exempt from the draft in World War II because he had a wife and children (and a serious heart condition), he made several war films, including Howard Hawks’ Air Force and the fact-based, poignant story of a blinded soldier, Pride of the Marines.  But it was four films made between 1946 and 1948 that cemented Garfield’s reputation.

The Postman Always Rings Twice is a gripping adaptation of James M. Cain’s lust-and-murder thriller, with Garfield and Lana Turner generating far more steam than the tepid Nicholson-Lange remake. Kazan’s Gentleman’s Agreement, the groundbreaking drama about anti-Semitism, featured the first use of the epithet “yid” in a Hollywood film – addressed to Garfield, who naturally responds with a punch.

He triumphed again in Body and Soul and Force of Evil, two films – scripted by the gifted Abraham Polonsky, who will be present at several of the screenings – dealing with the price of the American Dream.  In Robert Rossen’s Body and Soul, Charlie Davis achieves success in the ring, but alienates everyone who cares about him.  In Force of Evil, directed by Polonsky, Garfield is Joe Morse, an ambitious lawyer caught in a squeeze play when his gangster client muscles in on the Mom-and-Pop numbers racket run by Joe’s brother.

It’s impossible to watch these two films without a sense of tragedy, and not just for their often grim storylines. Even as they were in production, the Congressional witchhunt for Communists in Hollywood was beginning, and its ugliest outgrowth, the blacklist, soon followed.  Polonsky was an early victim; so were Rossen, Body and Soul co-stars Anne Revere and Canada Lee, and countless others among Garfield’s friends and colleagues.

Then Garfield himself fell under suspicion because of his work with the left-leaning Group Theater. But he refused to “name names” before the House Un-American Activities Committee – for a man of his background, an informer was the lowest form of humanity – and his career was destroyed. He died of heart failure in 1952, at the age of 39.

It is impossible to know how the rest of Garfield’s career would have played out had he lived. But his influence among latter-day tough guys like Al Pacino, Robert DeNiro and Harvey Keitel is clear. Check out the Film Society series and you can see where they learned some of their best moves.

Originally published in Resident weekly newspaper, 1998.

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By P.H.I.Berroll

Sol Wachtler had a grim statistic to share with his audience: “After the Vietnam conflict, we had over 200,000 veterans who went to prison.” He added, “We’re determined to see that this doesn’t happen again.”

Judge Wachtler, former Chief Judge of the New York State Court of Appeals, spoke during a panel discussion, sponsored by the Veterans Mental Health Coalition of New York City, at which speakers described efforts to steer nonviolent veteran offenders away from imprisonment and instead offer them support services and mental health treatment. One such program drew a good deal of attention: the Veterans Project, a groundbreaking North Shore-LIJ Health System initiative developed by Judge Wachtler, a lifetime North Shore-LIJ trustee.

The Veterans Project is a collaboration between North Shore-LIJ ‘s Law and Psychiatry Institute, the New York State courts, the Brooklyn, Queens and Nassau district attorneys’ offices and the U.S. Department of Veterans Affairs (VA) New York Harbor Health Care System. It is the first in the state – and the largest in the nation – to create a standardized approach to providing services and treatment to veterans involved with the criminal justice system, with the goal of preventing veterans who land in court or jail for minor offenses from getting into deeper trouble with the law. At a time when many veterans are suffering from post-traumatic stress disorder (PTSD) and depression – 20 percent of Iraq and Afghanistan veterans nationwide (300,000 men and women) have been diagnosed with those illnesses – there is an urgent need to steer them toward treatment rather than jail time.

During the panel discussion, held at Hunter College’s School of Social Work, several people involved in the Veterans Project – including Brooklyn District Attorney Charles J. Hynes, First Assistant D.A. Anne Swern, and veterans outreach specialists from New York Harbor – spoke in detail about their work. Several noted that a frequent challenge they face is convincing veterans to seek treatment; too many fail to do so, either out of embarrassment (they may worry about looking “weak” in front of their comrades) or fear that they will lose their benefits.

One way to counter this is through outreach from other veterans – the Veterans Project offers peer counseling to guide troubled former soldiers into treatment programs.  Another strategy is to reach out to veterans who have been arrested for misdemeanors such as subway fare-jumping. “We want to use the arrest,” said Ms. Swern, “as the opportunity to get them the services they need.”

Judge Wachtler and District Attorney Hynes, both of whom are veterans, spoke movingly of their desire to avoid repeating the tragedy of the Vietnam era.

“What this country did to [Vietnam veterans],” said the district attorney, “was an absolute disgrace – especially the criminal justice system.”

The Veterans Project is one of a number of innovative programs run by North Shore-LIJ’s Office of Military and Veteran’s Liaison Services (OMVLS), whose Director, Army Lt. Col. (Ret.) Randy Howard, moderated the Hunter event. Other OMVLS initiatives include a treatment program for Iraq and Afghanistan veterans suffering from PTSD and/or traumatic brain injury and programs to help returning service members find employment in the health system.

District Attorney Hynes and the other speakers touted the Veterans Project as a model that can – and should – be replicated across the country.

“If you’re in a county rather than Brooklyn, Queens or Nassau, you have a moral imperative to demand from your district attorney why such services aren’t in place,” said Mr. Hynes. “I believe that the day will come when we have district attorneys across the country committed to the proposition that no man or woman who served their country will ever be criminalized again.”

Originally published in the newsletter of North Shore-LIJ Medical Center, 2010.

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Carol Porter, DNP, RN sees her role at Mount Sinai as “conveying the nurse’s perspective to the Medical Center, and vice versa.” As Mount Sinai’s Chief Nursing Officer – and recently appointed Associate Dean of Nursing Research and Education – she has been a strong advocate for the importance of nurses in both medical research and clinical practice.

In this regard, one of her proudest achievements has been helping to establish Mount Sinai’s Center for Nursing Research and Education (CNRE) and serving as the CNRE’s first Director since its official launch in May 2010. An ambitious collaboration between the Mount Sinai School of Medicine and the Department of Nursing, the CNRE seeks to advance “bench to bedside” research – bringing the experience and insights of clinical nurses into medical research, while integrating the results of that research into both nursing education and patient care.

Ms. Porter and the CNRE are also working with Mount Sinai’s new Global Health program, headed by Dr. Philip J. Landrigan, to share ideas in nursing research, education and practice with other medical institutions around the world. At the recent annual Global Nursing Leadership Institute (GNLI) in Geneva, Switzerland, Ms. Porter, who was in attendance, says she was impressed “to hear how Mount Sinai nurses are held in high regard globally.”

Ms. Porter notes that a recent report, “The Future of Nursing,” from the Institute of Medicine (the health arm of the National Academy of Sciences), gives credence to the CNRE’s mission.

“The report recommends that nurses should be full partners with physicians and other health professionals in redesigning health care in the US,” she says. “We’re positioned very well for this – because the Center is already partnering with physicians at Mount Sinai.”

– Philip Berroll

Originally published in Mount Sinai Science & Medicine magazine, 2011.

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Their styles differ, but Dr. Peter Palese and Dr. Adolfo García-Sastre are focused on a common goal: a universal influenza vaccine.  

By P.H.I.Berroll

It would be hard to find two more sharply contrasting individuals than Adolfo García-Sastre, Ph.D. and Peter Palese, Ph.D. In appearance, Dr. Palese is every bit the sober, buttoned-down man of science; Dr. García-Sastre, bearded and long-haired, looks more like a rock musician, and in fact has several shelves of music cassettes – everything from Bach to Meat Loaf – stacked inside his desk. The Spanish-born Dr. García-Sastre is also an amateur entomologist with an extensive insect collection, while Dr. Palese, a native of Austria, cheerfully admits to having “very few” interests outside of medicine.

Yet for nearly 20 years, the two men have joined in a research partnership that has made them recognized leaders in their chosen field. Dr. Palese, who is Chairman of Mount Sinai’s Department of Microbiology, and Dr. García-Sastre – a professor of Microbiology and Medicine (Infectious Diseases) who also serves as Director of Mount Sinai’s Global Health and Emerging Pathogens Institute (GHEPI) – have both been in the forefront of efforts to understand and combat some of the world’s most deadly viruses. And they are now at work on a project of global import: the development of a universal influenza vaccine that can be used against multiple strains of this persistent and sometimes fatal disease.

“We can say that we have different personalities – though it depends on how you define ‘personality,’ Dr. García-Sastre says with a smile. “But motivation-wise, we are very similar. What we have in common is that we are passionate about research.”

A Vaccine for All Strains

The impact of a universal flu vaccine would be truly profound. At present, people need to be vaccinated every year at “flu season” because the virus evolves at a much faster rate than many other organisms, and pharmaceutical companies therefore have to keep updating their vaccines. And because that evolution has produced multiple strains of influenza, there is always a danger of targeting the wrong strain – resulting in an ineffective vaccine and an outbreak of epidemic proportions.

As Dr. Palese observes, “There is no other vaccine which has to be changed on a yearly basis, in contrast to things like measles or smallpox or mumps, whose vaccine strains from 50 years ago – or in the case of smallpox, 200 years ago – can still be used. So the hope is that we could get something which would be working and in use as an effective immune response against all strains of influenza.”

The two researchers and their teams have already made significant progress. “We have quite good evidence,” says Dr. Garcia-Sastre, “that when used for immunization, some types of influenza virus antigens  provide the broader immune response that can protect against multiple strains, unlike the traditional vaccines. We need to come up with better immunogens to make this a reality. But the possibilities are there.”

At the same time, they are also researching the possible development of other types of broad-spectrum antiviral drugs which could be used against viruses such as dengue, West Nile and Ebola, for which specific drugs do not currently exist. If proven effective, these antivirals could have a dramatic impact on global health not seen since the introduction of broad-spectrum antibiotics to combat bacterial infections.

“We now have solid evidence that many different viruses all use particular cellular pathways,” Dr. Garcia-Sastre observes. “And it’s possible that broad-spectrum antivirals could be effective by inhibiting those pathways.”

In addition, their work has implications for the fight against other “ever-changing” viruses such as HIV and hepatitis-C. “It’s a slightly different scenario in that these viruses have many different variants coexisting at the same time, whereas with influenza, it is a change from year to year,” says Dr. Palese. “But if we are able to succeed in making better and longer-lasting influenza virus vaccines, we could possibly try to apply that to these others.”

Working Separately and in Tandem 

Their partnership began as a student-teacher relationship. When Dr. García-Sastre came to Mount Sinai in the early 1990’s as a post-doctoral fellow, he worked in the laboratory of Dr. Palese – who soon recognized his younger colleague as “a very able and very effective and successful, imaginative researcher.”

After getting his own lab, Dr. García-Sastre continued to collaborate with his mentor on numerous research initiatives while both men also pursued independent projects, an approach which has continued to the present day. For example, Dr. García-Sastre is currently “very focused” on the body’s innate immune responses and their effect on viral replication, while Dr. Palese is researching viral packaging – the ability of a virus to package, transport, and deliver its genome to a host cell, which involves the precise manipulation of DNA throughout the life cycle of the virus.

“But in the big, overreaching aspects of influenza biology – such as influenza virus vaccines or multivirals – we fully collaborate,” says Dr. García-Sastre, “because these areas require information from multiple, specific research initiatives, resulting in a more comprehensive program. And especially in the last year, the National Institutes of Health (NIH) has put more emphasis on intercollaborative grouping between different researchers, which makes things easier from the point of view of funding.”

What was perhaps the pair’s greatest achievement to date came in 2005, when they led a team that reconstructed the virus responsible for one of history’s most devastating pandemics: the 1918 Spanish flu outbreak, which resulted in at least 40 million deaths worldwide. Their efforts earned them the 2005 Paper of the Year award from the prestigious British medical journal The Lancet.

“We decided to focus on that subjectin order to understand what made the 1918 virus so destructive – its mechanisms, its characteristics,” explains Dr. García-Sastre, “because by knowing that, we can be better prepared to fight future influenza viruses that may have the same traits.”

They began by taking the genetic material of the virus from human samples that were to some extent preserved from victims of the 1918 outbreak – “like Jurassic Park,” says Dr. Garcia-Sastre,“where they took the dinosaur DNA from mosquitos.” From there, they recovered the genetic information of the virus, which enabled them to reconstruct and study it.

Comparing the virus to that of a more recent global pandemic – the H1N1 (swine flu) outbreak of 2009 – they found enough similarities to determine that the vaccine developed to protect against H1N1 vaccine also worked against the 1918 strain. This discovery eliminated a serious concern among public health authorities about the possible use of the older strain in a bioterrorist attack.

“It was always one of our fears,” Dr. Garcia-Sastre says, “that if someone had the genetic information that was generated from the 1918 virus, they could reconstruct it for evil purposes. But now we know that everyone who gets vaccinated with the newer vaccine not only becomes protected against the 2009 virus, but also against the 1918 strain. That makes the use of the 1918 strain as a bioterrorist weapon very difficult.”

Between Complacency and Fear

Drs. Palese and García-Sastre often venture outside the lab to offer their expertise to a variety of government agencies – Dr. Palese is a member of the National Academy of Sciences (NAS), and Dr. García-Sastre is Director of the Center of Excellence in Influenza Research and Surveillance (CEIRS), which is funded by the NIH. In that capacity, both men have experienced the tendency of the public and the media to lurch between a false sense of security and unjustified panic regarding influenza outbreaks.

“It’s a very interesting psychology,” says Dr. García-Sastre. “When the first deaths from H-5 [avian flu] virus were reported, even though there were very few, it made people afraid to go to countries such as Hong Kong where the flu was found. It’s very difficult to get infected with bird flu; you go to Hong Kong, you’re more likely to die in a traffic accident than from H-5 infection. But the public has an inherent fear of infectious diseases. The same thing happened with Ebola and West Nile virus. It’s the fear of the unknown, with the potential high mortality factor, which makes people very scared.”

Dr. Palese speaks of the “hysteria” surrounding the 2009 pandemic, when he was part of a committee reporting to President Obama on best responses: “This report had a possible, non-predictive scenario to help plan for the fall flu season – that many people infected, that many people symptomatic, etc. And the next thing we know, the headline on page one of USA Today reads ‘Flu Could Infect Half the USA; 90,000 Deaths, 2 Million Patients Possible.’ We made clear that this virus was probably not comparable to 1918, and that we were making vaccines for it – but that was not on page one of USA Today.”

Still, Dr. Palese does take seriously the possible use of viruses in bioterrorism: he has been on several panels advising government officials on dealing with potential bioterrorist threats.

“I’m worried about nuclear proliferation and nuclear terrorism as well,” he says, “but I feel that the biological threats are even worse, because of how easily a virus can be developed. At this point, it’s really a catch-up situation where we’re trying to ramp up the production of vaccines and other anti-bacterial, anti-viral substances.”

But both men retain a sense of optimism – based in large part on the progress that has already been made against a number of once-deadly viruses. “The impact that vaccines have had in human health has been enormous,” notes Dr. García-Sastre. “You don’t see kids dying any more from poliomyelitis, except in very rare cases. You don’t see people dying any more from smallpox. And I think that hopefully we can come up with new vaccines against some of the other agents that are still making a big impact on human health, like influenza and HIV and tuberculosis and malaria.”

They have also come to see the humor in their odd-couple partnership. Dr. García-Sastre acknowledges with a laugh that compared to his colleague, he appears “relaxed.”

And when asked about their differing styles, Dr. Palese responds, “You mean that he never wears a necktie? Well, it’s a free country.”

Originally published in Mount Sinai Science & Medicine magazine, 2011.

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Dr. William Oh’s research aims to end the uncertainty over prostate cancer testing – and greatly reduce the number of deaths from the disease.  

By P.H.I.Berroll

Every year, across the United States, millions of men go into their doctors’ offices for a blood screening – the Prostate-Specific Antigen (PSA) test – to see if they are at risk for prostate cancer. The need for the test is clear: prostate cancer is the tenth-leading cause of cancer death in the U.S.; close to 200,000 men each year are found to have the disease, and more than 27,000 will die from it. One man in six will get prostate cancer during his lifetime, and for one man in 35 it will be fatal.

But the test’s reliability has increasingly been in dispute. A finding of high levels of PSA in the blood is often followed by a biopsy – a painful, invasive procedure with some risk of complications – to detect cancerous cells; yet in nearly two-thirds of biopsies, no such cells are found. This high rate of “false positive” test results underscores the need for a more accurate method for detecting prostate cancer.

That is the central focus of Dr. William Oh’s work.

Dr. Oh, who came to Mount Sinai last year after 12 years at Boston’s Dana-Farber Cancer Institute and Brigham and Women’s Hospital, is continuing a groundbreaking project that he began at Dana-Farber: the development of a new blood test which in combination with the PSA screening could sharply increase the accuracy of prostate cancer diagnoses – and eliminate tens of thousands of unnecessary biopsies.

“If you are biopsying 100 men and only finding cancer in a third of them, that’s a pretty poor hit rate,” he points out. “And when you multiply 100 times thousands – because there are 200,000 cases a year, which means that there are at least 600,000 biopsies a year, in the U.S. alone – we’re talking about a substantial cost to society and to individuals. So if you could reduce the number of unnecessary biopsies, it would improve quality of life, decrease health care costs and make many people happier.”

The upbeat, energetic Dr. Oh has a wide range of responsibilities at Mount Sinai – he is Chief of the Division of Hematology and Medical Oncology in the Department of Medicine, Co-Director of the Prostate Cancer Program, Associate Director for Clinical Research for the Tisch Cancer Institute, Ezra M. Greenspan, MD Professor in Clinical Cancer Therapeutics and Professor of Medicine and Urology. A native New Yorker, he returned to his home town for “the opportunity to build a program that could lead the world in developing new therapeutics for cancer patients.”

As Dr. Oh explains it, the problem with the current test lies in its focus on PSA levels rather than cancer. “It’s not a prostate cancer-specific antigen test, it’s a prostate-specific antigen test,” he notes. “So other things like infection or inflammation or enlargement of your prostate can make your PSA rise. And that decreases what we call the specificity of the test. Basically, it’s less specific for prostate cancer alone, and this leads to false positives.”

In addition, he says, the test fails to distinguish between “aggressive cancers that will prematurely end someone’s life” and slow-growing cancers that pose no threat during a patient’s natural lifespan. “We’re finding cancers in older men who are being over-treated because the cancers grow so slowly,” he says. “Let’s say a healthy man in his eighties is diagnosed with prostate cancer – the cancer is predicted, if left alone with nothing done about it, to potentially be lethal in 30 years, when he would be 110 years old. The problem is our tests right now don’t help us make those distinctions.”

The Genes Are the Key

Dr. Oh’s original study measured the accuracy of a blood test developed at Source MDx, a medical research company in Boulder, CO, which isolated six genes that, as a group, were highly sensitive in predicting which patients had prostate cancer and which were disease-free. Dr. Oh and his team found that the new test produced a dramatic jump in accuracy – especially when PSA measurements were added.

“What we found,” says Dr. Oh, “was that using the six-gene model combined with PSA, we were able to determine – more than 90 percent of the time – whether or not somebody had cancer. (Earlier studies had found that the PSA test by itself is 60 to70 percent accurate.) So we were able to greatly reduce the number of what we predict would be false positives.”

At Mount Sinai, Dr. Oh is joining researchers at other leading U.S. medical centers to determine if these findings remain valid – using a clinical trial which will involve almost 1,000 men. To date, more than 200 have enrolled in the study.

“In this trial,” the doctor explains, “men who are about to get a prostate biopsy – usually because of an elevated PSA – are going to get a blood test similar to the one in our earlier study to determine whether we can more accurately predict whether the biopsy will be positive or negative. In other words, we want to see whether or not our test will be better than the PSA test, either alone or in combination, at predicting whether somebody’s going to get a positive biopsy. We believe that we can use a test like this to get a more accurate prediction.”

For now, Dr. Oh rejects what he calls the “nihilistic” view that because of the PSA test’s shortcomings, men should avoid having it. “Our findings are very encouraging,” he says, “but until we can verify them, it is important to recognize that the PSA test, despite its limitations, is still the best test available for diagnosing prostate cancer at this time.”

But looking to the future, Dr. Oh predicts, “We will look at prostate cancer the same way we now look at certain infectious diseases such as tuberculosis or syphilis” – illnesses that a century ago were often fatal, but were conquered when doctors “figur[ed] out ways of diagnosing them early and then figuring out how to treat them or at least control them.”

And what Dr. Oh has learned about the complexities of prostate cancer can be applied, he feels, to other forms of the disease. “People have spoken of a ‘war’ on cancer, but it is much more like battling terrorists – you can’t always see them, they’re all over the place, and they may use different techniques to fight you,” he says. “The mistake that was made 40 or 50 years ago was to think of cancer as one disease; what we’ve learned is that there isn’t a single thing driving most cancers – there are many different pathways that the cancers can take to grow. Armed with that understanding, I think that we are really making progress. And I believethat in the future, this will continue – we’ll be able to cure more people, keep them alive longer and give them a better quality of life.”

Originally published in Mount Sinai Science & Medicine magazine, 2010.

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By P.H.I.Berroll

When asked about the impact of cardiovascular disease on world health, Jagat Narula, MD, PhD replies calmly but bluntly: “It is the most important scourge against mankind – the same for developing countries as for developed countries, and the same for men as for women.”

Dr. Narula does not make such pronouncements lightly. A dedicated researcher, educator and clinician – he is Philip J. and Harriet L. Goodhart Professor of Medicine and Cardiology and Associate Dean for Global Health at Mount Sinai School of Medicine, and in May of this year was named Director of Cardiovascular Imaging Program in the Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Center for Cardiovascular Health – he has devoted his professional life to studying and combating heart disease. In his current research, he is working to develop potent new tools for cardiologists worldwide: sophisticated molecular imaging techniques which can provide a window into the heart – and predict and prevent heart attacks before they occur.

“The levels are becoming epidemic,” he says, “and basically, prevention is the only way that we will be able to reduce them. I think that prevention through personalized medicine will have the biggest influence on cardiology in the next ten years.”

From detection to prevention

Dr. Narula emphasizes prevention because heart disease is often a “silent killer,” undetected until it is too late. “The disease, in its most serious form, is asymptomatic,” he explains. “More often than not, patients don’t come to you and ‘declare themselves’ or present with chest pains – instead, there can be an acute coronary event, including sudden cardiac death.”

Over the years, researchers have pinpointed the most common factors that put people at high risk for the disease, such as smoking, diabetes, high blood pressure and hypertension. When those factors are treated and modified, the incidence of the disease is reduced.

However, Dr. Narula notes, some people are more in need of preventive measures than others. “In the United States and Western Europe, you could say the population is divided into three tiers,” he says. “About 50% are at low risk for coronary disease; 10% are at high risk; but 40% are intermediate – they may have a problem, or they may not. So we need to glean them further, into those who are low-risk and those who are high-risk. Basically, I would like to have a two-tier rather than a three-tier system. You want to identify those who have a problem. And imaging can enable us to do this.”

In his research, Dr. Narula focuses on cost-effective measures that are especially suitable for this intermediate group – in his view, costly, time-consuming procedures such as MRIs and angiographies are not necessary in these cases – and can be used to screen large groups of people.

One technique involves taking an ultrasound image of the carotid arteries, which supply blood to the brain, or blood vessels in the iliofemeral region of the legs, in order to find signs of atherosclerosis – a condition, commonly known as “hardening of the arteries,” which if left untreated can eventually cause cardiac infarctions or strokes. A second procedure is taking a CT scan of a patient’s heart and using the scan to determine the amount of calcium in the coronary artery. “If the calcium is more than what is good for your age and gender,” says Dr. Narula, “that’s a very good indication that [coronary] disease is there.”

Dr. Narula says that advances in coronary disease studies in recent years have helped open the door to new avenues of research.

“There’s been a gradual evolution in the knowledge of the disease,” he notes. “For example, until a few years ago, we used to see a chest pain as just a simple strangulation of the coronary arteries. Now we have started to realize that atherosclerosis, which affects the blood vessel walls, is equally important when it comes to acute coronary events.”

The next step, in Dr. Narula’s view, is to subject imaging procedures to “rigorous clinical and outcome-based trials” so that cardiologists have a better idea of how to apply the results of imaging to specific preventive measures.

“As the knowledge is evolving,” he says, “that kind of investigation or studies need to be there before we are able to say, ‘this is the way we should be evaluating our patients,’ and then suggesting means of prevention.”

Fighting ‘diseases of affluence’ 

Dr. Narula is also working on a global scale to prevent heart disease, through his involvement in international-oriented programs such as the Heart Attack Prevention Program for You (HAPPY). Co-founded by Dr. Narula and Dr. Leonard Hofstra of the University of Maastricht in The Netherlands, HAPPY provides free cardiovascular screenings for people in developing countries. He is also the founding Editor-in-Chief of a new journal – Global Heart, published by the World Heart Federation – which aims to narrow the coronary disease research gap between the West and the developing world. Heart disease has increased sharply in those countries in recent years, as rapid urbanization has led to the erosion of traditional diets and the spread of Western habits like smoking cigarettes and consuming high-fat meals.

“In these countries, where we were used to dealing with things like infectious and post-infectious diseases and child health issues, there is now a tremendous increase in diabetes, hypertension and other coronary risk factors,” Dr. Narula observes. “These countries already are burdened with the diseases of poverty; now they also have the diseases of affluence.”

Asked about his goals for the future, Dr. Narula says simply: “I want Mount Sinai to be the world’s best imaging center – the hub of imaging.” He adds, “I’m very keen to develop the imaging fellowship here, so that we can bring in cardiologists from outside and train them in integrated cardiovascular imaging, so that they can use imaging tests to improve the quality of patient care. Then they can become the partners of the invasive cardiologists, the surgeons, etc.,   to help them deliver the best results.”

In addition, he would like to see imaging training become an integral part of the basic medical school curriculum, both at Mount Sinai and other schools.

“Imaging has got to become part of a patient’s standard physical examination,” he asserts. “Therefore, I feel that imaging should be taught from day one of medical school.  Because I believe, and I have often said – though people have not always liked to hear it – that if you’re not an imager, you’re not a physician.”

But in terms of his specific research, Dr. Narula prefers not to speak of short- and long-term goals. “Your goals are driven by your strategy, and my strategy is the use of imaging for better definition, management and prevention of a disease,” he says. “That’s what I’ve been working towards for many years now – and the sooner I get there, the better.”

Originally written for Mount Sinai Science & Medicine magazine, 2011.

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Dr. Ihor Lemischka takes a low-key approach to groundbreaking stem cell research.

By P.H.I.Berroll

In 2007, Ihor Lemischka, Ph.D. was a professor of molecular biology at Princeton University, where he had worked for more than two decades. His research in stem cell biology and its possible medical uses had brought him international renown.

But he was not satisfied.

“Princeton has no medical institution,” he explains. “And in stem cell research, you sort of hit a glass ceiling when you don’t have access to a medical institution or school. I was mostly working with mouse cells, and I really wanted to get more involved in studying human stem cells and human diseases.”

So when Dr. Lemischka was offered the directorship of Mount Sinai’s Black Family Stem Cell Institute, he eagerly accepted – and now says, “My only regret is that I didn’t do it sooner.”

At Mount Sinai, Dr. Lemischka, who is also Professor of Gene and Cell Medicine at the Mount Sinai School of Medicine, is building what he calls “a world-class stem cell institute” where he is taking his research to the next level – to the threshold of a revolutionary breakthrough in the treatment of genetics-based disease.

Dr. Lemischka, a low-key personality who speaks in calm, measured tones, is careful to avoid hyperbole in discussing his work. But as he describes its potential – the hope that it could lead to a cure for such devastating conditions as diabetes and Parkinson’s and Alzheimer’s diseases – his enthusiasm comes through.

“I find it to be probably the most exciting time ever in my career right now,” he says.

From a Few Cells, a World of Knowledge

Dr. Lemischka, who holds a B.A. from Johns Hopkins and a Ph.D. from M.I.T., is a specialist in induced pluripotent stem cell (iPSC) research, which uses stem cells taken from adult patients to study the causes of genetics-rooted disease.

The research technique, derived from what is known as the Yamanaka technology (named for Dr. Shinya Yamanaka of Kyoto University, who first developed it) begins with the removal of skin cells from adult patients. Then three or four genes are introduced into the cells. The genes’ DNA “reprograms” the cells into pluripotence – meaning that they have the potential to turn into any of the 220 cell types in the human body. And because the iPS cells are genetically identical to those of the patient, they will contain the same genetic mutation that caused that person’s particular disease.

The significance of this is profound. “We now have a way to develop tools that allow us to understand the ideology of complex, genetics-based diseases,” says Dr. Lemischka, “and from there, to build a platform for better diagnostics for these diseases – and the discovery of drugs to treat them.”

In addition, Dr. Lemischka foresees a day when iPSC technology could be used to create healthy cells that could then be transplanted into patients, replacing diseased tissue in organs such as the heart.

“If you were to derive, say, some transplantable cells from a patient’s iPS cells and then try to put them back into the patient, because of the shared genetic identity there’s no problem of immune system rejection,” he observes. “For example, even if you were lucky enough as a researcher to get a biopsy sample of human heart tissue, you can’t grow human cardiac cells; but with iPS cells, we can make as many cardiac muscle cells as we want.”

An Early Breakthrough

Not long after arriving at Mount Sinai, Dr. Lemischka had his first opportunity to put his expertise to use.

Pediatric cardiologist Bruce Gelb, MD, the director of Mount Sinai’s Child Health and Development Institute, and his research team had discovered the first gene ever associated with two common genetic diseases, Noonan and LEOPARD syndromes (“LEOPARD” isan acronym for the first letters of seven symptoms associated with the disease). But Dr. Gelb wanted to learn more about LEOPARD’s deadliest symptom, hypertrophic cardiomyopathy (HCM) – a cardiac condition in which heart cells become enlarged and the heart muscle thickens and grows too stiff to function properly.

So the two researchers joined forces. Using skin cell samples from two LEOPARD patients, they used the iPS protocols to produce a limitless supply of heart cells – exact copies of those in the patients. And they found that the copied cells were enlarged in the same manner as the originals.

This was a major research achievement: through iPSC technology, Drs. Lemischka and Gelb had produced one of the world’s first in vitro (often referred to as “disease in a dish”) models of cardiovascular disease – an important advance in tackling one of the greatest challenges to global health.

“By getting a defective heart cell in a dish that recapitulates to a large extent – or even identically – a disease such as HCM,”  Dr. Lemischka explains,  “you can track the development of these heart cells and ask, ‘Where do you see the first example of something going amiss?’  Having pinpointed that, you can say, ‘Okay, let’s see if we can find small molecules that delay, or reverse, or block this first thing that’s gone wrong.’  And it’s not possible to do this in any other way.”

The work of Drs. Lemischka and Gelb was widely praised after they published their findings as the cover story in the June 10, 2010 issue of Nature, the world’s preeminent scientific journal.

Since that time, Dr. Lemischka and his staff at the Black Family Stem Cell Institute – which includes his wife, Dr. Kateri Moore, who came with him from Princeton – have moved ahead with research involving a wide range of afflictions, including cancer, diabetes, liver disease and spinal cord injury, in collaboration with specialists in other disciplines at Mount Sinai.

“It’s very exciting to work clinicians and translational researchers using human iPSC,” he says. “Bringing together different groups with different sets of complementary expertise makes for a synergistic effort that is much greater than the sum of excellent parts.”

Dr. Lemischka believes that even diseases affecting the brain are within the realm of possibility.

“I could imagine developing ways of treating Parkinson’s disease,” he says, “because we know quite a lot about it – we know which neurons are missing or damaged and we could make those neurons in a dish filled with stem cells. And with Alzheimer’s, to be able to study how the neurons might degenerate – in vitro, in a dish – allows you again to develop platforms for drug discoveries.”

“Education is the Key”

Still, Dr. Lemischka makes it clear that iPSC research is not yet “as far advanced” as embryonic stem cell studies, which remains the most fully developed form of stem cell research. “We know that in many ways, iPS cells closely resemble embryonic stem cells,” he notes, “but we don’t know how exact that similarity is. Before we can say, ‘These cells can replace embryonic stem cells,’ we’ll need to do in-depth comparative studies for quite a long time. We’re all very excited about iPS cells, but to jump to the conclusion and say they’re the same, and can already replace embryonic stem cell research, is way premature.”

And because of the continued value of embryonic research, Dr. Lemischka does not shy away from addressing its main point of controversy: the extraction of cells from frozen embryos which are destroyed in the process.

“I do not object to somebody’s personal moral, ethical or theological beliefs, such as the belief that a fertilized egg, an embryo, is the same as a human being – I’m respectful of that,” he says. “But when a minority of people influences the government to dictate policy for the whole country, I feel that borders on a violation of church-state separation – which is one of the things this country was founded on.”

Ultimately, says Dr. Lemischka, “education is the key” to changing minds. “I’ve seen it work,” he adds. “I’ve had experiences where I would give a half-hour talk to a group of non-scientists – a retirement community, for example – and people have come up to me afterwards and said, ‘I came here very anti-embryonic stem cell research, and now I have a different opinion. You’ve changed my mind.’”

And he is certain that concrete results will also help influence public opinion: “Once there’s some cure – let’s say, a child with diabetes is cured by stem cell transplants – it then becomes a very different ballgame, because then the outcry from the public of ‘How can you possibly deny my child this?’ would become huge.”

The Next Leap Forward

For all his enthusiasm, Dr. Lemischka cautions against predicting quick benefits from any form of stem cell research.

“We all believe that there will be stem cell-related cures,” he says, “but we can’t with any certainty say how soon. So it’s important – and again, this is where education comes in – to create a realistic set of milestones which you can take the time to explain to the public. You don’t say something like ‘next year, we’re going to be able to cure your father’s Parkinson’s.’ Because then, inevitably, there’s a public backlash – and it’s the public that largely pays the bills, since we run in large part on federal or state money.”

However, Dr. Lemischka acknowledges “that we see amazing advances happening every day. Keep in mind that there are already stem cell cures, such as cord blood transplantation” – a stem cell therapy widely used for leukemia, sickle-cell anemia and other diseases – “where you transplant a blood-forming stem cell from a donor to a recipient.

“It’s one of the best things about being in this area, the fact that you don’t know what’s next. It’s incremental, by and large – 99.9 percent of it. But every once in a while, you get something that moves the whole field forward with a leap. You can’t anticipate these things, but you have to be open to them.”

Originally published in Mount Sinai Science & Medicine magazine, 2011.

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Every other week, Laura Hoskins, PsyD, leaves her practice at North Shore University Hospital and flies to upstate New York, where she immerses herself in the treatment of wounded Iraq and Afghanistan war veterans at the U.S. Army base Fort Drum. The work of Dr. Hoskins, a neuropsychologist, is part of an initiative under North Shore-LIJ’s Welcome Back Veterans program, a fund of the McCormick Foundation, in partnership with Major League Baseball. Dr. Hoskins spoke with Philip Berroll about her experiences:

Describe your work in your own words. As a neuropsychologist, studying brain-behavior relationships, I’ve specialized in traumatic brain injury (TBI). The conflicts in Iraq and Afghanistan have produced a large increase in TBIs – it’s a signature injury of these wars. The closest parallel would be a severe concussion in football; like football players, many of these soldiers have repeated concussive events – often as many as three to six – because they’re exposed to a lot of blasts from improvised explosive devices (IEDs). And they need proper treatment should there be any long-term negative sequelae – pathological conditions.  I focus on mild TBI; the more severe injuries go to a place like Walter Reed Army Medical Center (in Washington, DC).

What is a typical day at Fort Drum like for you? I see one patient a day, with whom I meet at 8:00 a.m. for about an hour – going through their medical and psychological history, and focusing on the details of the concussive event(s) as they recall them. Then we have a three- to four-hour series of tests to assess cognitive status, memory, attention… get a good sense of how they’re functioning. If they’ve had a TBI, my job is to find out if there’s cognitive impairment as a result – and if so, is it related to the TBI and/or post-traumatic stress disorder (PTSD) or other factors. The good news is that with mild TBI, the vast majority of individuals recover within hours and days, with only about three percent having long-term, protracted sequelae post-injury.

How do you approach this other three percent? I have to look at all the variables that may be playing a role – which can include PTSD, orthopedic injuries or an overuse of pain medication. Then there are the “social” factors: the vast majority of these soldiers have been deployed multiple times; they have years of being away from their families and then coming back and re-integrating, which is often very difficult and is complicated by the strong possibility that they’ll be redeployed – why fully re-engage when you know you may have to disengage again?

What is the next step in the process? I provide my diagnostic conclusions and treatment recommendations, in collaboration with my rehab team. We use a very integrated, individualized treatment approach because no two cases are alike. One soldier may have cognitive issues such as a decline in attention or memory; another may have more behavioral issues – sleep changes, changes in mood; some may have both, as mild TBI often has both neurological and psychological symptoms. After that, the soldier may be referred to a three-week TBI treatment program, or to the Warrior in Transition Unit (WTU). Usually he or she will be considered on active duty, but may be put on a Temporary Duty Profile in which his or her responsibilities may be limited given their medical condition.

What if you feel a soldier isn’t ready to return to duty? I speak to the commander or someone in their unit. Because sometimes soldiers are reluctant to report a problem – they want to be “a good soldier,” they don’t want to let their unit down – and often with a mild TBI, they may look okay on the surface, but something may not be right with their thinking; they may have a slower response time, etc. And the commanders may not have prior training or experience in this area, so you have to explain it to them and say, “This guy should sit out for another week or two weeks or whatever.”

You’ve been working at Fort Drum since November 2009, when the Welcome Back Veterans Initiative started? Yes, I came on as a result of the program. They had received the funding to be able to hire me and cover my trips to Fort Drum and my services there.

Prior to that, were you doing any kind of work with soldiers? I was doing my fellowship at Dartmouth Medical School, and I was in the clinical service. I’d see the occasional veteran, but it was not specific to my job.

So what got you interested in doing this? I specialized in TBI during my fellowship and my clinical research work had focused on that area. So I felt I had a unique service that I could provide; and while I think it’s important to help these soldiers who have served our country, we can also learn a lot from their experiences.  

Has dealing with these men and women affected you personally? All my patients impact me – but especially this group. It’s overwhelming to hear their stories, and to realize that at such a young age – the vast majority of them are between 18 and 25 years old – they’ve left their families to enter this extremely high-stress situation. To me, that level of sacrifice and dedication is awe-inspiring.

Originally written for the newsletter of North Shore-LIJ Medical Center, 2010.

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Dr. Janice Gabrilove, daughter of a Mount Sinai legend, has forged a distinguished career of her own.

By P.H.I.Berroll

As a child, Janice Gabrilove did not dream of a career in medicine – “I was thinking more of going into the performing arts,” she recalls. This is surprising, considering her family background: her father is Dr. J. Lester Gabrilove, a pioneering endocrinologist and a longtime leader of Mount Sinai’s Division of Endocrinology, Diabetes, and Bone Disease (which is named for him and his late wife Hilda).

But Janice later changed her mind – and has had a distinguished medical career in her own right as a researcher, educator and clinician.

Dr. Gabrilove is James F. Holland Professor of Medicine, Hematology and Medical Oncology and Professor of Oncological Sciences at Mount Sinai School of Medicine, from which she earned her medical degree. She also directs the school’s Clinical Research Training, M.S. and Ph.D. in Clinical Research programs, where trainees learn how to apply the observations gained from clinical practice to medical research. Those programs, now renamed the Center for Patient-Oriented Research, Education, Training and Development (CPORETD), recently had a major boost when Mount Sinai received a Clinical and Translational Science Award (CTSA) – a $34.6 million, five-year grant – from the National Institute of Health (NIH).  Dr. Gabrilove hopes to make Mount Sinai’s clinical research training “the centerpiece of the CTSA.”

The CTSA award is the culmination of years of work by Dr. Gabrilove to establish Mount Sinai as a world-renowned leader in clinical research – starting in 1998, the year she was appointed Chief of Medical Oncology and Deputy Director of the Cancer Center.

That year, the NIH created the Clinical Research Curriculum Awards to help medical institutions train a greater number of researchers; the Institute was concerned, Dr. Gabrilove says, “that clinical investigation was becoming a dying art and a dying science…  something that was kind of learned on the sly” due to a lack of funding.  The newly hired Dr. Gabrilove was assigned by then-Dean of Mount Sinai Medical School Dr. Arthur Rubinstein and then-Department of Medicine Chair Dr. Barry Coller to apply for an award. The application was successful, enabling Mount Sinai to establish a certificate program which was later expanded to include Master’s and Ph.D. degrees. “We recruited our first Ph.D. cohort last fall,” she says proudly. “Seven students were accepted.”

From One Small Cell, Dramatic Breakthroughs

Dr. Gabrilove decribes herself as “passionate about clinical research,” and it was such research that produced her crowning achievement to date:  the development of human granulocyte colony stimulating factor (G-CSF),a major breakthrough in both chemotherapy and bone marrow transplantation.

Dr. Gabrilove and her research team studied the neutrophil granulocyte, a white blood cell that plays a crucial role in preventing bacterial infection. In chemotherapy, these rapidly growing cells are injured or killed, resulting in a condition known as febrile neutropenia where the body’s defenses against infection are greatly reduced – “a significant cause of mortality,” she notes.

But the researchers were able to discover the normal growth factor for neutrophil granulocytes, which they tested after purifying the protein and then cloned in collaboration with the biotech company Amgen to produce G-CSF. Further tests and trials showed that G-CSF could reduce the incidence of febrile neutropenia by as much as 50 percent. Other researchers, building on Dr. Gabrilove’s work, subsequently used G-CSF to achieve greatly improved survival rates in diseases such as breast cancer and lymphoma.

Dr. Gabrilove and her team made another important discovery: G-CSF drives stem cells from the bone marrow out into the bloodstream, allowing doctors to collect the cells and use them in bone marrow transplants.  Previously, the cells had to be surgically removed; with a dosage of G-CSF, they can be obtained through a simple blood extraction. “It’s much less invasive,” says Dr. Gabrilove, “you get a better quality stem cell… and reconstitution is much faster.”

In talking about her Mount Sinai experience as a medical student and staff member, Dr. Gabrilove cites several doctors as inspiring teachers and colleagues.  Naturally, her father – whom she calls “just an unbelievable role model in the kind of person he was” – has been a particular influence. And she continues to benefit from his insights: Lester Gabrilove currently serves as Baumritter Professor of Medicine, Emeritus at Mount Sinai School of Medicine – while continuing his clinical practice – as he approaches his 93^rd birthday.

“My father drops in now and again for a visit,” she says. “He’s a great guy.”

Originally published in Mount Sinai Science & Medicine magazine 2010.

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From Mount Sinai to West Africa, Dr. Jeffrey Freed works to help people in need.

Jeffrey S. Freed, MD, began his medical residency at Mount Sinai after graduating from public institutions where he had paid little or no tuition. “I had the good fortune to leave medical school with absolutely no debt,” he says.

And Dr. Freed – a colorectal surgeon and Associate Clinical Professor of Surgery at Mount Sinai Medical School – has tried to aid students who are not so fortunate. As a member of the Mount Sinai Alumni Association, serving as Board President from 2001 to 2003, he has worked to make medical education affordable for those students “so that the onerous burden of debt does not impede their careers.”

This kind of activism is why Dr. Freed is a 2010 finalist for one of Mount Sinai’s most prestigious honors, the Jacobi Medallion. Created in 1952 to mark the 100th anniversary of Mount Sinai’s founding, and named for Dr. Abraham Jacobi, a pioneer in pediatrics and a past president of the Mount Sinai Hospital Medical Board, the award recognizes Mount Sinai physicians for medical achievements and/or service to the hospital, the Medical School or the Alumni Association.

The accomplishments of Dr. Freed, who says he would be “humbled” to receive the Medallion, are both local and international: Since 2008, he has led an annual Mount Sinai medical mission to the West African nation of Liberia – helping to rebuild that country’s healthcare system, which had been shattered by decades of civil war.

‘A Full-Court Press’ to Help Medical Students
As Alumni Association Board President, Dr. Freed and his predecessor, Dr. Avi Barbasch, partnered with Mount Sinai’s Development Office to create a fundraising network of alumni and other donors. Dr. Freed has also worked with the Association’s chapters in other parts of the country to encourage alumni involvement in fundraising, primarily to endow scholarships. In addition, an alumni scholarship was recently donated in Dr. Freed’s name – “for some student(s) in need, with exceptional credentials,” he explains, “who would receive $50,000 a year, for five years.”

The need for such scholarships, says Dr. Freed, is urgent. “In a survey, we found that debt is a tremendous factor in medical students’ choosing their specialty training upon graduation,” he notes, “and that for minority students, fear of debt is a major reason that they shy away from pursuing any medical education. This led me to believe that a full-court press for raising money for scholarships was really necessary.”

Rebuilding from the Ashes of War
Dr. Freed faced even greater challenges on his first mission to Liberia. “There were between 35 and 40 Liberian doctors left in the country,” he recalls. “That’s about one doctor for every 100,000 people.”

Working at two local hospitals, Dr. Freed and his team of 16 physicians and seven medical students treated close to 200 patients for conditions including cancer, hernias and cataracts, trained local health providers and set up a chemotherapy suite.

Dr. Freed subsequently led two more missions, in 2009 and 2010, and is currently planning another for early 2011. In that time, he has seen significant progress.

“Their X-ray and sonogram capabilities have increased remarkably,” he says. “Nursing protocols have been put in so women in labor are more closely monitored. These are relatively simple, basic programs – and they are sustainable by the people there.”

Whether at home or abroad, as physician, educator or fundraiser, Dr. Freed is motivated by the same sense of compassion that has inspired his medical career.

“We are physicians to really help people,” he says. “That is the primary goal.”

– Philip Berroll

Originally published in Mount Sinai Science & Medicine magazine, 2011.

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