2. 'Hand grenades' against cancer: Genspera
Even in this age of economic uncertainty, smart people are still developing new weapons against cancer, the second-most-common cause of death in the U.S., after heart disease. I sat down with one of those people recently: Craig Dionne, who headed up discovery research in biology at Cephalon (CEPH, news, msgs) for several years.
Dionne now leads a tiny biotech startup called Genspera (GNSZ, news, msgs), which is developing what he likes to call a "hand grenade" against cancer.
Researchers at Johns Hopkins University have figured out a way to put a chemical "pin" on a powerful anti-cancer drug called thapsigargin, extracted from a readily available weed.The pin deactivates the drug, allowing it to circulate in the body without causing damage to good cells.
Enzymes from tumors "pull the pin," activating the drug only near the tumors. The drug destroys blood vessels feeding tumors, with limited damage elsewhere in the body. Genspera, which bought this approach from the Johns Hopkins professors who developed it, thinks it could be effective against a range of cancers.
Why small-cap stocks can surge
The drug also causes cancer cells to flood with calcium, killing them. This approach is crucial against slow-dividing cells such as those in prostate-cancer tumors. Many chemotherapies take out cancer cells only when those cells divide; Genspera's compound doesn't wait.
Genspera is a risky investment, of course, as is any biotech startup. Its "hand grenade" approach looks effective in animals but may not work in humans. And it is still in early "phase one" testing, which checks for safety. However, I'm betting Dionne's two-decades-plus experience in drug development offsets these risks.
Buy below $2.30 a share.
Friday, February 26, 2010
Tuesday, February 23, 2010
After Long Fight, Drug Gives Sudden Reprieve
Target Cancer
After Long Fight, Drug Gives Sudden Reprieve
By AMY HARMON
Published: February 22, 2010
For the melanoma patients who signed on to try a drug known as PLX4032, the clinical trial was a last resort. Their bodies were riddled with tumors, leaving them almost certainly just months to live.
Neemah A. Esmaeilpour for The New York Times
ALWAYS WATCHING Randy Williams drove from Jonesboro, Ark., to Houston for treatment. Even after tumors disappeared, he says of his cancer, “I don’t think I’ll ever believe that it’s not coming back.”
Target Cancer
A Dose of Hope
Second of three articles.
Part One: A Doctor's Trial
Q & A with Amy Harmon
Sarah Phipps for The New York Times
FINGERS CROSSED Kerri Adams at home near Oklahoma City. After seeing an improvement from her treatment, she tried not to jinx it, declining to seek new information about the drug, the gene or the cancer.
Readers' Comments
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But a few weeks after taking their first dose, nearly all of them began to recover.
Lee Reyes, 30, of Fresno, Calif., who had begun using a feeding tube because of a growth pressing against his throat, bit into a cinnamon roll.
Nothing, he told his mother, had ever tasted as good.
Rita Quigley, who had been grateful just to find herself breathing each morning since learning she had the virulent skin cancer, went shopping for new clothes with her daughters at a mall in Huntsville, Ala.
Randy Williams, 46, who drove 600 miles from his home in Jonesboro, Ark., to the M.D. Anderson Cancer Center in Houston to get the experimental drug, rolled out of bed. “Something’s working,” he thought, “because nothing’s hurting.”
It was a sweet moment, in autumn 2008, for Dr. Keith Flaherty, the University of Pennsylvania oncologist leading the drug’s first clinical trial. A new kind of cancer therapy, it was tailored to a particular genetic mutation that was driving the disease, and after six years of disappointments his faith in the promise of such a “targeted” approach finally seemed borne out. His collaborators at five other major cancer centers, melanoma clinicians who had tested dozens of potential therapies for their patients with no success, were equally elated.
In a kind of “pinch me” exercise, the six doctors sent one another “before and after” CT scans of their patients.
One was of Mark Bunting, 52, an airline pilot in Sandy, Utah. His initial scan in early October showed the cancer in his bones, an incursion considered virtually impossible to reverse. After two months on the drug, it had all but disappeared.
“Holy Cow!” Dr. Flaherty typed in reply to the slide from Dr. Antoni Ribas at the University of California, Los Angeles, that Dec. 17.
“Are you sure it is the same patient??” added Dr. Jeffrey A. Sosman at the Vanderbilt-Ingram Cancer Center in Nashville.
From New York, Dr. Paul B. Chapman of Memorial Sloan-Kettering Cancer Center, perhaps the most determined skeptic of the group, acknowledged, “This looks impressive.”
The trial of PLX4032 offers a glimpse at how doctors, patients and drug developers navigate a medical frontier as more drugs tailored to the genetic profile of a cancer are being widely tested on humans for the first time.
Throughout the fall, the only two patients on the trial whose tumors continued to grow were the ones who did not have the particular gene mutation for which the drug had been designed. They were removed from the trial. By late December, tumors in the 11 patients who did have the mutation had shrunk. Those involved in the trial held their collective breath waiting to see how long the remissions would last.
It was a far cry from where they had been a year earlier, when a previous incarnation of the drug had no effect. Urged on by Dr. Flaherty and Dr. Chapman, the companies that owned it had spent months devising a new formulation that could be absorbed at higher doses.
But the new drug, still in the earliest phase of testing, had to pass several more hurdles before federal regulators would determine whether it was safe and effective enough for widespread use.
In December, as the doctors added more patients to the Phase 1 trial, looking for the highest dose they could give without intolerable side effects, they scrambled to prepare slides with graphs and statistics to convince the Food and Drug Administration that the drug should be tested in a larger Phase 2 trial. The agency required a summary of any and all side effects — there had been only a few — and any deaths of patients on the study; thankfully, there had been none since the drug was reformulated. In a matter of days they needed to submit their findings for a prestigious meeting of clinical oncologists in June.
First, though, Dr. Flaherty, 39, needed to respond to a desperate phone message from a patient named Christopher Nelson. It came the day after Christmas.
“Dr. Flaherty,” the message said, “I need to get onto your trial.”
Hoping for a Match
The doctor had expected the call.
Mr. Nelson, 42, and his wife, Sharlene, had come to see him just before Thanksgiving. They were planning to travel to Bethesda, Md., so Mr. Nelson could enroll in a trial for a different melanoma drug. But the couple, from Jackson, N.J., had learned of Dr. Flaherty’s trial, and wanted to cover all their bases.
He liked them: Sharlene, a real estate broker who peppered him with questions, and Chris, a furniture installer around his own age with a penchant for low-stakes poker and the Grateful Dead. Both were quick to make light of a grim situation.
“I’ve gained the 60 pounds he’s lost from the cancer,” Mrs. Nelson observed. “Stress eating.”
They had met after high school, at Levitz, the furniture store where they both worked. Like Dr. Flaherty, they had two children.
“He was never sick a day in his life,” Mrs. Nelson told Dr. Flaherty. “Never had a headache, never took a sick day. I mean, can’t you give me the common cold first? It had to be cancer?”
The trial in Bethesda, run by the National Cancer Institute, involved coaxing immune cells to grow in a test tube in a procedure that worked for only a small fraction of patients, Dr. Flaherty knew.
But there would be no point in Mr. Nelson taking PLX4032 if his tumor did not carry the right mutation. For now, the doctor had a slot for only one more patient on the trial, and he and his collaborators had agreed it was almost unethical to give the drug to people without that mutation.
Peter MacCallum Cancer Centre
BEFORE AND AFTER Within weeks of starting a clinical trial of a cancer drug, nearly all of the patients began to recover. Doctors, impressed by the results, began trading scans like this one, which shows how a patient's tumors shrank in 15 days.
Target Cancer
A Dose of Hope
Second of three articles.
Part One: A Doctor's Trial
Q & A with Amy Harmon
Ángel Franco/The New York Times
LEADING THE PACK Mark Bunting in Sandy, Utah, with his wife, Trish, and children, Koda, Kylee and Kaila. He had cancer in his bones, seen as irreversible. After two months of treatment, it had nearly vanished.
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Amy Harmon is answering readers’ questions about experimental drug trials on the Well blog. Please post yours here.
He wished, not for the first time, that he could snap his fingers and know the genetic profile of his patient’s cancer cells. But getting a hospital that had operated on a patient months earlier to retrieve a tumor sample from storage could take days or weeks; the test for the gene mutation could take even longer. To speed the process, Mr. Nelson drove his tumor sample himself from Robert Wood Johnson University Hospital in New Brunswick, N.J., where it had been removed from his lymph nodes, to the laboratory at the University of Pennsylvania.
Dr. Flaherty agreed that while they waited, Mr. Nelson should proceed with the trial in Bethesda, which first required the removal of his tumor-laden spleen. Either way, that needed to go.
Mrs. Nelson thought her husband had died when she saw the stricken look on the face of the surgeon after the operation. Normally 2 pounds, the spleen had weighed 10. Mr. Nelson’s liver was so enlarged that maneuvering around it had been almost impossible. And then, on Dec. 23, Mr. Nelson learned that the doctors running the trial had been unable to grow his immune cells.
On the phone, Dr. Flaherty assured him he would let them know his genetic status as soon as he found out. “If it’s positive,” Dr. Flaherty told him, “the spot is yours.”
Checking, Checking
No one knows just what causes the single change in a single gene in a single cell that fuels a malignant melanoma.
Randy Williams, now in recovery, had gone over in his mind a million times the day he fell asleep in the sun at the lake when he was 16. His feet were so badly burned, he could not walk for a week. Twenty years later, a mole inside the arch of his left foot turned cancerous.
Was that it? Was that the moment his fate was set? Because melanoma has been linked to sunburn, especially in childhood, many of the trial’s participants relived such memories. Almost certainly, each had accumulated mutations in many other genes, at other moments, over the course of their lives. Some may have inherited a gene that was already damaged.
Once unleashed, however, any cancer seemed to rely on the protein made by a particular mutated gene to fuel its wild growth. In all of the PLX patients, that gene was B-RAF. And whatever the cause, they came to consider themselves, so far as it was possible with what has always been a virtually untreatable cancer, charmed.
At least they had a chance. The patients took pills the size of large vitamins, twice a day. Some gulped them down with water. Others spooned them up with applesauce.
To get to the mandatory doctor’s appointments where patients were given precisely one month’s supply, Mr. Williams, a contractor with two teenage children, drove all night with his brother in a pickup truck. One young woman hopped “corporate angel” flights on private jets whose owners donated empty seats.
Mark Bunting used his pilot privileges to commute to Los Angeles to see his oncologist. “He says,” Mr. Bunting told friends as his tumors melted away last fall, “that I’m the leader of the pack.”
For some patients and their family members, though, the sudden reprieve was almost as disorienting as the diagnosis.
Mr. Bunting, for one, could not convince his wife, Trish, that it was for real.
A former flight attendant, she had coped with her husband’s cancer by confronting it head-on. She organized a family trip to Disney World, so their young children would have the memory. She entered nursing school, so she would have a means of supporting herself.
As if to drive home the point, on her first day, a teacher had illustrated a lesson on cell growth with a picture of melanoma that had metastasized. “Here’s when I think of one of my favorite Carole King songs: ‘It’s Too Late,’ ” the teacher said.
Now, even as Ms. Bunting watched the color seep back into her husband’s gray skin, even as they celebrated a Christmas she never thought he would live to see, she found herself unable to shake the need to prepare for his death. “You need to sit and write down stuff for me,” she told her husband. “I need to know who I call for this, I need to know where things are.”
“But I’m doing better!” he pleaded. “Can’t you see?”
In Oklahoma City, Kerri Adams, 30, just tried not to jinx it. She did not look up anything about the drug, the gene or the cancer on the Internet or anywhere else. Single and employed as an analyst at a local utility company, she attended church with her mother and ate dinner with friends. But when they coaxed her to meet new people, she demurred. The future seemed too uncertain.
Mr. Williams, back full time at his contracting business with his brother, climbed ladders, lifted weights and fixed up his Corvette.
The tumors on his legs that had constantly oozed blood dried up and then disappeared. Yet every day, he ran his fingers over the spots where they used to be, checking, checking, checking.
“I don’t think I’ll ever believe,” he said, “that it’s not coming back.”
After Long Fight, Drug Gives Sudden Reprieve
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(Page 3 of 3)
Still waiting to hear if he would be eligible for Dr. Flaherty’s trial, Mr. Nelson managed to get to a Portuguese restaurant with the rest of the family for his son’s 16th birthday in January 2009, but he could not eat.
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Courtesy of the Nelson Family
NEW APPETITE Christopher Nelson of Jackson, N.J., could barely eat or walk when he began a drug trial. Soon, he was out enjoying meals with his wife, Sharlene, and children, Julia and Dylan.
Target Cancer
A Dose of Hope
Second of three articles.
Part One: A Doctor's Trial
Q & A with Amy Harmon
Related Series: Forty Years' War Readers' Comments
Amy Harmon is answering readers’ questions about experimental drug trials on the Well blog. Please post yours here.
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Read All Comments (75) »
One morning a few weeks later, the pain in his stomach was so overwhelming that he told his wife they needed to go to the emergency room, where he was admitted and hooked up to intravenous morphine for the pain.
“There’s nothing we can do for him,” the doctor told her. “You should think about getting hospice.”
Frantically, Mrs. Nelson left a message for Dr. Flaherty. She wanted to order an ambulance, an airlift, whatever it took to get her husband to Philadelphia.
He called back immediately. The test had finally come back, he said.
Mr. Nelson had the mutation.
“Is my husband going to be able to get on this drug?” she demanded. “I need to know because there’s no waiting.”
First, she would need to wean him from the auto-drip morphine, Dr. Flaherty told her gently. To qualify for the trial, he needed to be able to walk in. And the last spot on the trial had to be filled within a week.
Mr. Nelson, who had not eaten in days, threw up the morphine pills the first several times he tried to get them down. But he went home the day before Valentine’s Day.
“Honey,” his wife told him, “you don’t have to get me anything.”
At home, Mr. Nelson called her on her cellphone as she waited in a long pharmacy line to pick up the morphine. The pain was breaking through.
“Hurry,” he said.
Mrs. Nelson drove to Philadelphia a few days later, her husband sprawled in the back seat. At the cancer center, she pushed him in a wheelchair into the waiting room of the melanoma clinic. When the nurse called his name, he struggled to his feet and walked in to see the doctor.
Dr. Flaherty looked at him. He did not need the required blood test to tell that his numbers were off the charts. Mr. Nelson’s eyes were yellow, a sign that his liver was at the edge of failure. He had, at the most, the doctor thought, a month to live.
Maryann Redlinger, the clinical trial nurse, was not one to mince words.
“Are you out of your mind?” she asked Dr. Flaherty when he told her he wanted to put Mr. Nelson on the trial. A death on a trial was a black mark. No matter how good the other numbers were, it would count against them.
If his decision delayed by even a few months the approval of a drug that could help tens of thousands of patients, surely it would be unethical. But there might be a benefit in seeing what the drug could do for a patient like Mr. Nelson. This was the kind of patient who came to him all the time.
And how could he deny Chris Nelson a drug that, he knew in his gut, would give him extra time?
“He has two kids at home, Maryann,” he said. “Do you want to tell him he can’t get it? Go ahead, you call him up and tell him no.”
Dialing Back
The side effects struck at the 1,120-milligram dose.
Many patients had been taking the reformulated drug for five months with no signs of relapsing. The doctors had hoped that by pushing up the dose they could shut down the cancer more effectively. Some patients were taking as many as 28 pills a day.
Ms. Adams, in Oklahoma City, woke up one morning covered in a rash. Frightened that she would be dropped from the trial, she tried to ignore it. But at work, her boss was horrified and insisted that she call the doctor. Another woman’s hand swelled up, and she could not make a fist. A Philadelphia patient had horrible nausea and diarrhea, and Mr. Bunting’s joints grew so stiff that he had to hand jars to his wife to remove the lids, even when they had already been opened.
Maybe the drug, designed to turn off only the defective B-RAF protein, was, at high doses, also affecting its role in healthy cells. Or perhaps it was interfering with other proteins the body needed to function properly. On their next conference call, the doctors agreed that they had to dial back the dose.
As the side effects began to subside, many of the patients began to believe they had beaten their cancer. One evening, Mr. Bunting performed what had become his pill-taking ritual as his wife puttered around the kitchen.
He liked the water to be room temperature, so he heated it in the microwave and added cold from the tap. He burped, and some powder from the pills came out of his mouth just as she turned to look.
They both laughed.
One Step Forward ...
When Mr. Nelson strolled into the University of Pennsylvania for a scheduled day of blood work and monitoring in mid-March, Ms. Redlinger greeted him as if he had risen from the dead.
Gazing out the window of the clinic room, he spied a hot dog stand.
“Dirty water dogs,” he exclaimed.
“Can you get me one?” he asked his wife’s sister. “Actually, two?”
“Chris is feeling better,” the nurse told Dr. Flaherty casually when she saw him.
“What do you mean?” he pressed.
“Well, he’s off pain meds,” she said.
Dr. Flaherty was not scheduled to see Mr. Nelson until three weeks later. But between appointments that day, the doctor found time to visit his patient. In Mr. Nelson’s room, he broke into a wide smile, a tension he had not realized he was holding seeping out of him.
He had never seen a melanoma patient who had been that sick improve that much. He was not sure he had ever seen a melanoma patient that sick who improved at all.
Mrs. Nelson hugged him. In the weeks that followed, Mr. Nelson gained 17 pounds. One morning a friend drove him to Atlantic City, where for a $35 buy-in, they played his favorite game, Texas hold ’em, all day. The drug had made him sensitive to the sun, and he burned his skin cleaning the pool one afternoon, even with strong sunblock. Mrs. Nelson bought an umbrella, and he spent much of the spring sitting underneath it.
“Today’s a nice day,” he said over the phone to a friend in early May. “There’s a cloud, and the sun is behind it.”
In mid-May, right before he was to fly to Orlando, Fla., to present the trial’s data, Dr. Flaherty received a message on his BlackBerry as he was walking on campus.
The first patient to respond in the trial, Elmer Bucksbaum, had been admitted to the hospital. The cancer had spread to his brain.
Dr. Flaherty stopped walking.
The drug, Dr. Flaherty knew, was powerless in the brain. But had the drug held off the cancer elsewhere in Mr. Bucksbaum’s body? Or would other patients, too, begin to relapse?
Mr. Bucksbaum died a few days later.
Dr. Flaherty called his family and offered his condolences. It had been not quite eight months.
Comments
My husband, possibly the best human to walk the planet, died of malignant melanoma at 51, a short six months after diagnosis. Although there was talk of targeted therapy in 2004, it was one of several generally ineffectual treatments for this juggurnaut of a disease. While I struggle with the thought that this promising treatment came too late for my husband, it is wonderfully affirming to think that, at last, there may be hope. Thank you to Dr. Flaherty for his dedication to fighting an implacable foe. Go get 'em.
Recommend Recommended by 28 Readers 31.HIGHLIGHT (what's this?) GoGoMedia, PAFebruary 23rd, 20109:29 am
My sister was diagnosed with melanoma earlier this year. I don't think the general population realizes how devastating melanoma can be.
It took us some time to truly grasp (1) how virulent the disease could be and (2) the reality that the arsenal of therapies to fight it were very small.
Thankfully, Philadelphia has two amazing institutions with laser-like focus and expertise on this horrendous cancer: Penn and Jefferson. We are so grateful for Dr. Flaherty, Dr. Mastrangelo and the nurses, researchers, scientists and assistants who keep fighting for patients with this horrible disease.
Fortunately, my sister's melanoma had not yet spread internally. But she will be under close scrutiny for the rest of her life. It's a great relief to know that new therapies are being developed should she require further treament in the future.
Recommend Recommended by 8 Readers 39.HIGHLIGHT (what's this?) markprovidence, riFebruary 23rd, 20109:30 am
Some of the comments on this article reveal how much this type of journalism help to excite people's hopes about the wonders that modern medicine is or will be able to do. Regrettably this kind of excitement is premature, and so this type of journalism helps to further our addiction to what inevitably will be hugely expensive treatments which we all hope and pray will be payed for by someone else, but not by ourselves. I am certain I will be viewed as a spoilsport in saying that this data, while certainly encouraging, is only preliminary. The miraculous responses of these patients with melanoma are reminiscent of the patients who received L-Dopa when it first was introduced, as catalogued in Oliver Sacks book, Awakenings. Stunning though the initial improvements were, they proved transitory. Similarly, Penicillin was viewed at the outset as the beginning of the end of germ warfare. History has proven otherwise. We still do not know about the long term side effects of PLX4032, and we do not know about the ability of this drug to prevent remissions. More research will reveal this in time. We do know several things for sure though. This drug is likely to be extremely expensive, if found to be safe and effective, and the cost will be born by insurance companies, who will then pass it along to all of us. Next, it does not change the underlying genetic make-up of the individual. This might make us worry about the potential for relapse, and the resulting need for extended, perhaps life-long treatment, with all the attendant risks that go along with prolonged exposure to a highly potent medication. Third, while sometimes cures are acheived in cancer, very often, particularly with solid tumors, these cures are more difficult to acheive.
So it is too early to be sure if this drug will prove to be the wonder drug the preliminary trials suggest it might be. But it is certainly not too soon to fan people's excitement. It does sell newspapers.
Recommend Recommended by 19 Readers 40.HIGHLIGHT (what's this?) CheciSafety Harbor, OppenheimFebruary 23rd, 20109:30 am
I remember an interview of Arlo Guthrie I read many years ago where he spoke about his father's illness and death. A genetic carrier, Arlo commented, "Well, I'm probably gonna get it." I feel like Arlo when I consider melanoma. My father died of melanoma in 2006 and my oldest brother had a malignant tumor removed from his leg when in his 30's. I grew up on the Long Island shore roasting on Jones Beach during the summers and continued to let myself burn in the sun till my mid 20's. I frequently think, "I'm gonna get it." So I read this article with a tremendous empathy for the trial patients. You know how so many people annoyingly chant about how our soldiers are paying for the freedoms we enjoy? That's how I feel about these trial patients. I don't believe they are being given false hope by participating in pharmaceutical trials. They are the pioneers along with the doctors and geneticists and chemists. I think they know that. Someday, I may be in their shoes after a visit to my dermatologist. If so, I will think of those who lost the battle, those who won, and I will thank them for their sacrifice and for their courage. Some of them, a lot of them, will have spent their last days pushing for a cure that someday I may need.
Recommend Recommended by 24 Readers 58.HIGHLIGHT (what's this?) Bob KoelleWilmington, DelawareFebruary 23rd, 201010:00 am
The avenues that are open to Dr Flaherty and big pharma are also open to all: peer reviewed research, using a standard beyond anecdotes and inspirational stories of people spontaneously in remission after drinking green tea and cannabinoids or whatever. A poster from the previous story linked to a website concerning low dose naltrexone being the obvious cure. Have they published? Run any actual controlled trials?
Disclaimer: Yep, I'm big pharma. We make lots of money launching the fifth or sixth identical cholesterol or diabetes drug, to my chagrin and embarrassment, so at least we can blow lots more on research for cancer therapies that fail far more often than these other drugs. The rigors of documentation and science we use for something like Dr Flaherty's research are real and intense and expensive. And I've seen my colleagues, so-called greedy money-grabbing big pharma employees, collapse and sob when a therapy is discontinued from trials because it didn't work, despite its theoretical promise. Because the patients really exist for them, for me. My brother was saved by Jefferson oncologists, and Dr Flaherty's work may lead to a great compound or not, but will definitely add to the knowledge we have about treatment, so we can start again.
To answer a previous question, yes we spend lots on ads, but it generates its own revenue, or else we wouldn't do it. That spending doesn't take a dime away from research budgets. That's the purpose of all advertising, to generate revenue beyond the cost of the advertising itself. Why isn't that obvious?
After Long Fight, Drug Gives Sudden Reprieve
By AMY HARMON
Published: February 22, 2010
For the melanoma patients who signed on to try a drug known as PLX4032, the clinical trial was a last resort. Their bodies were riddled with tumors, leaving them almost certainly just months to live.
Neemah A. Esmaeilpour for The New York Times
ALWAYS WATCHING Randy Williams drove from Jonesboro, Ark., to Houston for treatment. Even after tumors disappeared, he says of his cancer, “I don’t think I’ll ever believe that it’s not coming back.”
Target Cancer
A Dose of Hope
Second of three articles.
Part One: A Doctor's Trial
Q & A with Amy Harmon
Sarah Phipps for The New York Times
FINGERS CROSSED Kerri Adams at home near Oklahoma City. After seeing an improvement from her treatment, she tried not to jinx it, declining to seek new information about the drug, the gene or the cancer.
Readers' Comments
Amy Harmon is answering readers’ questions about experimental drug trials on the Well blog. Please post yours here.
Post a Comment »
Read All Comments (75) »
But a few weeks after taking their first dose, nearly all of them began to recover.
Lee Reyes, 30, of Fresno, Calif., who had begun using a feeding tube because of a growth pressing against his throat, bit into a cinnamon roll.
Nothing, he told his mother, had ever tasted as good.
Rita Quigley, who had been grateful just to find herself breathing each morning since learning she had the virulent skin cancer, went shopping for new clothes with her daughters at a mall in Huntsville, Ala.
Randy Williams, 46, who drove 600 miles from his home in Jonesboro, Ark., to the M.D. Anderson Cancer Center in Houston to get the experimental drug, rolled out of bed. “Something’s working,” he thought, “because nothing’s hurting.”
It was a sweet moment, in autumn 2008, for Dr. Keith Flaherty, the University of Pennsylvania oncologist leading the drug’s first clinical trial. A new kind of cancer therapy, it was tailored to a particular genetic mutation that was driving the disease, and after six years of disappointments his faith in the promise of such a “targeted” approach finally seemed borne out. His collaborators at five other major cancer centers, melanoma clinicians who had tested dozens of potential therapies for their patients with no success, were equally elated.
In a kind of “pinch me” exercise, the six doctors sent one another “before and after” CT scans of their patients.
One was of Mark Bunting, 52, an airline pilot in Sandy, Utah. His initial scan in early October showed the cancer in his bones, an incursion considered virtually impossible to reverse. After two months on the drug, it had all but disappeared.
“Holy Cow!” Dr. Flaherty typed in reply to the slide from Dr. Antoni Ribas at the University of California, Los Angeles, that Dec. 17.
“Are you sure it is the same patient??” added Dr. Jeffrey A. Sosman at the Vanderbilt-Ingram Cancer Center in Nashville.
From New York, Dr. Paul B. Chapman of Memorial Sloan-Kettering Cancer Center, perhaps the most determined skeptic of the group, acknowledged, “This looks impressive.”
The trial of PLX4032 offers a glimpse at how doctors, patients and drug developers navigate a medical frontier as more drugs tailored to the genetic profile of a cancer are being widely tested on humans for the first time.
Throughout the fall, the only two patients on the trial whose tumors continued to grow were the ones who did not have the particular gene mutation for which the drug had been designed. They were removed from the trial. By late December, tumors in the 11 patients who did have the mutation had shrunk. Those involved in the trial held their collective breath waiting to see how long the remissions would last.
It was a far cry from where they had been a year earlier, when a previous incarnation of the drug had no effect. Urged on by Dr. Flaherty and Dr. Chapman, the companies that owned it had spent months devising a new formulation that could be absorbed at higher doses.
But the new drug, still in the earliest phase of testing, had to pass several more hurdles before federal regulators would determine whether it was safe and effective enough for widespread use.
In December, as the doctors added more patients to the Phase 1 trial, looking for the highest dose they could give without intolerable side effects, they scrambled to prepare slides with graphs and statistics to convince the Food and Drug Administration that the drug should be tested in a larger Phase 2 trial. The agency required a summary of any and all side effects — there had been only a few — and any deaths of patients on the study; thankfully, there had been none since the drug was reformulated. In a matter of days they needed to submit their findings for a prestigious meeting of clinical oncologists in June.
First, though, Dr. Flaherty, 39, needed to respond to a desperate phone message from a patient named Christopher Nelson. It came the day after Christmas.
“Dr. Flaherty,” the message said, “I need to get onto your trial.”
Hoping for a Match
The doctor had expected the call.
Mr. Nelson, 42, and his wife, Sharlene, had come to see him just before Thanksgiving. They were planning to travel to Bethesda, Md., so Mr. Nelson could enroll in a trial for a different melanoma drug. But the couple, from Jackson, N.J., had learned of Dr. Flaherty’s trial, and wanted to cover all their bases.
He liked them: Sharlene, a real estate broker who peppered him with questions, and Chris, a furniture installer around his own age with a penchant for low-stakes poker and the Grateful Dead. Both were quick to make light of a grim situation.
“I’ve gained the 60 pounds he’s lost from the cancer,” Mrs. Nelson observed. “Stress eating.”
They had met after high school, at Levitz, the furniture store where they both worked. Like Dr. Flaherty, they had two children.
“He was never sick a day in his life,” Mrs. Nelson told Dr. Flaherty. “Never had a headache, never took a sick day. I mean, can’t you give me the common cold first? It had to be cancer?”
The trial in Bethesda, run by the National Cancer Institute, involved coaxing immune cells to grow in a test tube in a procedure that worked for only a small fraction of patients, Dr. Flaherty knew.
But there would be no point in Mr. Nelson taking PLX4032 if his tumor did not carry the right mutation. For now, the doctor had a slot for only one more patient on the trial, and he and his collaborators had agreed it was almost unethical to give the drug to people without that mutation.
Peter MacCallum Cancer Centre
BEFORE AND AFTER Within weeks of starting a clinical trial of a cancer drug, nearly all of the patients began to recover. Doctors, impressed by the results, began trading scans like this one, which shows how a patient's tumors shrank in 15 days.
Target Cancer
A Dose of Hope
Second of three articles.
Part One: A Doctor's Trial
Q & A with Amy Harmon
Ángel Franco/The New York Times
LEADING THE PACK Mark Bunting in Sandy, Utah, with his wife, Trish, and children, Koda, Kylee and Kaila. He had cancer in his bones, seen as irreversible. After two months of treatment, it had nearly vanished.
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Amy Harmon is answering readers’ questions about experimental drug trials on the Well blog. Please post yours here.
He wished, not for the first time, that he could snap his fingers and know the genetic profile of his patient’s cancer cells. But getting a hospital that had operated on a patient months earlier to retrieve a tumor sample from storage could take days or weeks; the test for the gene mutation could take even longer. To speed the process, Mr. Nelson drove his tumor sample himself from Robert Wood Johnson University Hospital in New Brunswick, N.J., where it had been removed from his lymph nodes, to the laboratory at the University of Pennsylvania.
Dr. Flaherty agreed that while they waited, Mr. Nelson should proceed with the trial in Bethesda, which first required the removal of his tumor-laden spleen. Either way, that needed to go.
Mrs. Nelson thought her husband had died when she saw the stricken look on the face of the surgeon after the operation. Normally 2 pounds, the spleen had weighed 10. Mr. Nelson’s liver was so enlarged that maneuvering around it had been almost impossible. And then, on Dec. 23, Mr. Nelson learned that the doctors running the trial had been unable to grow his immune cells.
On the phone, Dr. Flaherty assured him he would let them know his genetic status as soon as he found out. “If it’s positive,” Dr. Flaherty told him, “the spot is yours.”
Checking, Checking
No one knows just what causes the single change in a single gene in a single cell that fuels a malignant melanoma.
Randy Williams, now in recovery, had gone over in his mind a million times the day he fell asleep in the sun at the lake when he was 16. His feet were so badly burned, he could not walk for a week. Twenty years later, a mole inside the arch of his left foot turned cancerous.
Was that it? Was that the moment his fate was set? Because melanoma has been linked to sunburn, especially in childhood, many of the trial’s participants relived such memories. Almost certainly, each had accumulated mutations in many other genes, at other moments, over the course of their lives. Some may have inherited a gene that was already damaged.
Once unleashed, however, any cancer seemed to rely on the protein made by a particular mutated gene to fuel its wild growth. In all of the PLX patients, that gene was B-RAF. And whatever the cause, they came to consider themselves, so far as it was possible with what has always been a virtually untreatable cancer, charmed.
At least they had a chance. The patients took pills the size of large vitamins, twice a day. Some gulped them down with water. Others spooned them up with applesauce.
To get to the mandatory doctor’s appointments where patients were given precisely one month’s supply, Mr. Williams, a contractor with two teenage children, drove all night with his brother in a pickup truck. One young woman hopped “corporate angel” flights on private jets whose owners donated empty seats.
Mark Bunting used his pilot privileges to commute to Los Angeles to see his oncologist. “He says,” Mr. Bunting told friends as his tumors melted away last fall, “that I’m the leader of the pack.”
For some patients and their family members, though, the sudden reprieve was almost as disorienting as the diagnosis.
Mr. Bunting, for one, could not convince his wife, Trish, that it was for real.
A former flight attendant, she had coped with her husband’s cancer by confronting it head-on. She organized a family trip to Disney World, so their young children would have the memory. She entered nursing school, so she would have a means of supporting herself.
As if to drive home the point, on her first day, a teacher had illustrated a lesson on cell growth with a picture of melanoma that had metastasized. “Here’s when I think of one of my favorite Carole King songs: ‘It’s Too Late,’ ” the teacher said.
Now, even as Ms. Bunting watched the color seep back into her husband’s gray skin, even as they celebrated a Christmas she never thought he would live to see, she found herself unable to shake the need to prepare for his death. “You need to sit and write down stuff for me,” she told her husband. “I need to know who I call for this, I need to know where things are.”
“But I’m doing better!” he pleaded. “Can’t you see?”
In Oklahoma City, Kerri Adams, 30, just tried not to jinx it. She did not look up anything about the drug, the gene or the cancer on the Internet or anywhere else. Single and employed as an analyst at a local utility company, she attended church with her mother and ate dinner with friends. But when they coaxed her to meet new people, she demurred. The future seemed too uncertain.
Mr. Williams, back full time at his contracting business with his brother, climbed ladders, lifted weights and fixed up his Corvette.
The tumors on his legs that had constantly oozed blood dried up and then disappeared. Yet every day, he ran his fingers over the spots where they used to be, checking, checking, checking.
“I don’t think I’ll ever believe,” he said, “that it’s not coming back.”
After Long Fight, Drug Gives Sudden Reprieve
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Still waiting to hear if he would be eligible for Dr. Flaherty’s trial, Mr. Nelson managed to get to a Portuguese restaurant with the rest of the family for his son’s 16th birthday in January 2009, but he could not eat.
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Courtesy of the Nelson Family
NEW APPETITE Christopher Nelson of Jackson, N.J., could barely eat or walk when he began a drug trial. Soon, he was out enjoying meals with his wife, Sharlene, and children, Julia and Dylan.
Target Cancer
A Dose of Hope
Second of three articles.
Part One: A Doctor's Trial
Q & A with Amy Harmon
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One morning a few weeks later, the pain in his stomach was so overwhelming that he told his wife they needed to go to the emergency room, where he was admitted and hooked up to intravenous morphine for the pain.
“There’s nothing we can do for him,” the doctor told her. “You should think about getting hospice.”
Frantically, Mrs. Nelson left a message for Dr. Flaherty. She wanted to order an ambulance, an airlift, whatever it took to get her husband to Philadelphia.
He called back immediately. The test had finally come back, he said.
Mr. Nelson had the mutation.
“Is my husband going to be able to get on this drug?” she demanded. “I need to know because there’s no waiting.”
First, she would need to wean him from the auto-drip morphine, Dr. Flaherty told her gently. To qualify for the trial, he needed to be able to walk in. And the last spot on the trial had to be filled within a week.
Mr. Nelson, who had not eaten in days, threw up the morphine pills the first several times he tried to get them down. But he went home the day before Valentine’s Day.
“Honey,” his wife told him, “you don’t have to get me anything.”
At home, Mr. Nelson called her on her cellphone as she waited in a long pharmacy line to pick up the morphine. The pain was breaking through.
“Hurry,” he said.
Mrs. Nelson drove to Philadelphia a few days later, her husband sprawled in the back seat. At the cancer center, she pushed him in a wheelchair into the waiting room of the melanoma clinic. When the nurse called his name, he struggled to his feet and walked in to see the doctor.
Dr. Flaherty looked at him. He did not need the required blood test to tell that his numbers were off the charts. Mr. Nelson’s eyes were yellow, a sign that his liver was at the edge of failure. He had, at the most, the doctor thought, a month to live.
Maryann Redlinger, the clinical trial nurse, was not one to mince words.
“Are you out of your mind?” she asked Dr. Flaherty when he told her he wanted to put Mr. Nelson on the trial. A death on a trial was a black mark. No matter how good the other numbers were, it would count against them.
If his decision delayed by even a few months the approval of a drug that could help tens of thousands of patients, surely it would be unethical. But there might be a benefit in seeing what the drug could do for a patient like Mr. Nelson. This was the kind of patient who came to him all the time.
And how could he deny Chris Nelson a drug that, he knew in his gut, would give him extra time?
“He has two kids at home, Maryann,” he said. “Do you want to tell him he can’t get it? Go ahead, you call him up and tell him no.”
Dialing Back
The side effects struck at the 1,120-milligram dose.
Many patients had been taking the reformulated drug for five months with no signs of relapsing. The doctors had hoped that by pushing up the dose they could shut down the cancer more effectively. Some patients were taking as many as 28 pills a day.
Ms. Adams, in Oklahoma City, woke up one morning covered in a rash. Frightened that she would be dropped from the trial, she tried to ignore it. But at work, her boss was horrified and insisted that she call the doctor. Another woman’s hand swelled up, and she could not make a fist. A Philadelphia patient had horrible nausea and diarrhea, and Mr. Bunting’s joints grew so stiff that he had to hand jars to his wife to remove the lids, even when they had already been opened.
Maybe the drug, designed to turn off only the defective B-RAF protein, was, at high doses, also affecting its role in healthy cells. Or perhaps it was interfering with other proteins the body needed to function properly. On their next conference call, the doctors agreed that they had to dial back the dose.
As the side effects began to subside, many of the patients began to believe they had beaten their cancer. One evening, Mr. Bunting performed what had become his pill-taking ritual as his wife puttered around the kitchen.
He liked the water to be room temperature, so he heated it in the microwave and added cold from the tap. He burped, and some powder from the pills came out of his mouth just as she turned to look.
They both laughed.
One Step Forward ...
When Mr. Nelson strolled into the University of Pennsylvania for a scheduled day of blood work and monitoring in mid-March, Ms. Redlinger greeted him as if he had risen from the dead.
Gazing out the window of the clinic room, he spied a hot dog stand.
“Dirty water dogs,” he exclaimed.
“Can you get me one?” he asked his wife’s sister. “Actually, two?”
“Chris is feeling better,” the nurse told Dr. Flaherty casually when she saw him.
“What do you mean?” he pressed.
“Well, he’s off pain meds,” she said.
Dr. Flaherty was not scheduled to see Mr. Nelson until three weeks later. But between appointments that day, the doctor found time to visit his patient. In Mr. Nelson’s room, he broke into a wide smile, a tension he had not realized he was holding seeping out of him.
He had never seen a melanoma patient who had been that sick improve that much. He was not sure he had ever seen a melanoma patient that sick who improved at all.
Mrs. Nelson hugged him. In the weeks that followed, Mr. Nelson gained 17 pounds. One morning a friend drove him to Atlantic City, where for a $35 buy-in, they played his favorite game, Texas hold ’em, all day. The drug had made him sensitive to the sun, and he burned his skin cleaning the pool one afternoon, even with strong sunblock. Mrs. Nelson bought an umbrella, and he spent much of the spring sitting underneath it.
“Today’s a nice day,” he said over the phone to a friend in early May. “There’s a cloud, and the sun is behind it.”
In mid-May, right before he was to fly to Orlando, Fla., to present the trial’s data, Dr. Flaherty received a message on his BlackBerry as he was walking on campus.
The first patient to respond in the trial, Elmer Bucksbaum, had been admitted to the hospital. The cancer had spread to his brain.
Dr. Flaherty stopped walking.
The drug, Dr. Flaherty knew, was powerless in the brain. But had the drug held off the cancer elsewhere in Mr. Bucksbaum’s body? Or would other patients, too, begin to relapse?
Mr. Bucksbaum died a few days later.
Dr. Flaherty called his family and offered his condolences. It had been not quite eight months.
Comments
My husband, possibly the best human to walk the planet, died of malignant melanoma at 51, a short six months after diagnosis. Although there was talk of targeted therapy in 2004, it was one of several generally ineffectual treatments for this juggurnaut of a disease. While I struggle with the thought that this promising treatment came too late for my husband, it is wonderfully affirming to think that, at last, there may be hope. Thank you to Dr. Flaherty for his dedication to fighting an implacable foe. Go get 'em.
Recommend Recommended by 28 Readers 31.HIGHLIGHT (what's this?) GoGoMedia, PAFebruary 23rd, 20109:29 am
My sister was diagnosed with melanoma earlier this year. I don't think the general population realizes how devastating melanoma can be.
It took us some time to truly grasp (1) how virulent the disease could be and (2) the reality that the arsenal of therapies to fight it were very small.
Thankfully, Philadelphia has two amazing institutions with laser-like focus and expertise on this horrendous cancer: Penn and Jefferson. We are so grateful for Dr. Flaherty, Dr. Mastrangelo and the nurses, researchers, scientists and assistants who keep fighting for patients with this horrible disease.
Fortunately, my sister's melanoma had not yet spread internally. But she will be under close scrutiny for the rest of her life. It's a great relief to know that new therapies are being developed should she require further treament in the future.
Recommend Recommended by 8 Readers 39.HIGHLIGHT (what's this?) markprovidence, riFebruary 23rd, 20109:30 am
Some of the comments on this article reveal how much this type of journalism help to excite people's hopes about the wonders that modern medicine is or will be able to do. Regrettably this kind of excitement is premature, and so this type of journalism helps to further our addiction to what inevitably will be hugely expensive treatments which we all hope and pray will be payed for by someone else, but not by ourselves. I am certain I will be viewed as a spoilsport in saying that this data, while certainly encouraging, is only preliminary. The miraculous responses of these patients with melanoma are reminiscent of the patients who received L-Dopa when it first was introduced, as catalogued in Oliver Sacks book, Awakenings. Stunning though the initial improvements were, they proved transitory. Similarly, Penicillin was viewed at the outset as the beginning of the end of germ warfare. History has proven otherwise. We still do not know about the long term side effects of PLX4032, and we do not know about the ability of this drug to prevent remissions. More research will reveal this in time. We do know several things for sure though. This drug is likely to be extremely expensive, if found to be safe and effective, and the cost will be born by insurance companies, who will then pass it along to all of us. Next, it does not change the underlying genetic make-up of the individual. This might make us worry about the potential for relapse, and the resulting need for extended, perhaps life-long treatment, with all the attendant risks that go along with prolonged exposure to a highly potent medication. Third, while sometimes cures are acheived in cancer, very often, particularly with solid tumors, these cures are more difficult to acheive.
So it is too early to be sure if this drug will prove to be the wonder drug the preliminary trials suggest it might be. But it is certainly not too soon to fan people's excitement. It does sell newspapers.
Recommend Recommended by 19 Readers 40.HIGHLIGHT (what's this?) CheciSafety Harbor, OppenheimFebruary 23rd, 20109:30 am
I remember an interview of Arlo Guthrie I read many years ago where he spoke about his father's illness and death. A genetic carrier, Arlo commented, "Well, I'm probably gonna get it." I feel like Arlo when I consider melanoma. My father died of melanoma in 2006 and my oldest brother had a malignant tumor removed from his leg when in his 30's. I grew up on the Long Island shore roasting on Jones Beach during the summers and continued to let myself burn in the sun till my mid 20's. I frequently think, "I'm gonna get it." So I read this article with a tremendous empathy for the trial patients. You know how so many people annoyingly chant about how our soldiers are paying for the freedoms we enjoy? That's how I feel about these trial patients. I don't believe they are being given false hope by participating in pharmaceutical trials. They are the pioneers along with the doctors and geneticists and chemists. I think they know that. Someday, I may be in their shoes after a visit to my dermatologist. If so, I will think of those who lost the battle, those who won, and I will thank them for their sacrifice and for their courage. Some of them, a lot of them, will have spent their last days pushing for a cure that someday I may need.
Recommend Recommended by 24 Readers 58.HIGHLIGHT (what's this?) Bob KoelleWilmington, DelawareFebruary 23rd, 201010:00 am
The avenues that are open to Dr Flaherty and big pharma are also open to all: peer reviewed research, using a standard beyond anecdotes and inspirational stories of people spontaneously in remission after drinking green tea and cannabinoids or whatever. A poster from the previous story linked to a website concerning low dose naltrexone being the obvious cure. Have they published? Run any actual controlled trials?
Disclaimer: Yep, I'm big pharma. We make lots of money launching the fifth or sixth identical cholesterol or diabetes drug, to my chagrin and embarrassment, so at least we can blow lots more on research for cancer therapies that fail far more often than these other drugs. The rigors of documentation and science we use for something like Dr Flaherty's research are real and intense and expensive. And I've seen my colleagues, so-called greedy money-grabbing big pharma employees, collapse and sob when a therapy is discontinued from trials because it didn't work, despite its theoretical promise. Because the patients really exist for them, for me. My brother was saved by Jefferson oncologists, and Dr Flaherty's work may lead to a great compound or not, but will definitely add to the knowledge we have about treatment, so we can start again.
To answer a previous question, yes we spend lots on ads, but it generates its own revenue, or else we wouldn't do it. That spending doesn't take a dime away from research budgets. That's the purpose of all advertising, to generate revenue beyond the cost of the advertising itself. Why isn't that obvious?
Evidence That Little Touches Do Mean So Much
Evidence That Little Touches Do Mean So Much
By BENEDICT CAREY
Published: February 22, 2010
Psychologists have long studied the grunts and winks of nonverbal communication, the vocal tones and facial expressions that carry emotion. A warm tone of voice, a hostile stare — both have the same meaning in Terre Haute or Timbuktu, and are among dozens of signals that form a universal human vocabulary.
Clockwise from top left: Jed Jacobsohn/Getty Images; Mark Avery/Reuters; Vivek Prakash/Reuters Charles; Dharapak/Associated Press
YOU FEEL ME A quick hug, fist pound, high five or belly bump can communicate a wide range of emotions, sometimes more accurately than words.
But in recent years some researchers have begun to focus on a different, often more subtle kind of wordless communication: physical contact. Momentary touches, they say — whether an exuberant high five, a warm hand on the shoulder, or a creepy touch to the arm — can communicate an even wider range of emotion than gestures or expressions, and sometimes do so more quickly and accurately than words.
“It is the first language we learn,” said Dacher Keltner, a professor of psychology at the University of California, Berkeley, and the author of “Born to Be Good: The Science of a Meaningful Life” (Norton, 2009), and remains, he said, “our richest means of emotional expression” throughout life.
The evidence that such messages can lead to clear, almost immediate changes in how people think and behave is accumulating fast. Students who received a supportive touch on the back or arm from a teacher were nearly twice as likely to volunteer in class as those who did not, studies have found. A sympathetic touch from a doctor leaves people with the impression that the visit lasted twice as long, compared with estimates from people who were untouched. Research by Tiffany Field of the Touch Research Institute in Miami has found that a massage from a loved one can not only ease pain but also soothe depression and strengthen a relationship.
In a series of experiments led by Matthew Hertenstein, a psychologist at DePauw University in Indiana, volunteers tried to communicate a list of emotions by touching a blindfolded stranger. The participants were able to communicate eight distinct emotions, from gratitude to disgust to love, some with about 70 percent accuracy.
“We used to think that touch only served to intensify communicated emotions,” Dr. Hertenstein said. Now it turns out to be “a much more differentiated signaling system than we had imagined.”
To see whether a rich vocabulary of supportive touch is in fact related to performance, scientists at Berkeley recently analyzed interactions in one of the most physically expressive arenas on earth: professional basketball. Michael W. Kraus led a research team that coded every bump, hug and high five in a single game played by each team in the National Basketball Association early last season.
In a paper due out this year in the journal Emotion, Mr. Kraus and his co-authors, Cassy Huang and Dr. Keltner, report that with a few exceptions, good teams tended to be touchier than bad ones. The most touch-bonded teams were the Boston Celtics and the Los Angeles Lakers, currently two of the league’s top teams; at the bottom were the mediocre Sacramento Kings and Charlotte Bobcats.
The same was true, more or less, for players. The touchiest player was Kevin Garnett, the Celtics’ star big man, followed by star forwards Chris Bosh of the Toronto Raptors and Carlos Boozer of the Utah Jazz. “Within 600 milliseconds of shooting a free throw, Garnett has reached out and touched four guys,” Dr. Keltner said.
To correct for the possibility that the better teams touch more often simply because they are winning, the researchers rated performance based not on points or victories but on a sophisticated measure of how efficiently players and teams managed the ball — their ratio of assists to giveaways, for example. And even after the high expectations surrounding the more talented teams were taken into account, the correlation persisted. Players who made contact with teammates most consistently and longest tended to rate highest on measures of performance, and the teams with those players seemed to get the most out of their talent.
The study fell short of showing that touch caused the better performance, Dr. Kraus acknowledged. “We still have to test this in a controlled lab environment,” he said.
If a high five or an equivalent can in fact enhance performance, on the field or in the office, that may be because it reduces stress. A warm touch seems to set off the release of oxytocin, a hormone that helps create a sensation of trust, and to reduce levels of the stress hormone cortisol.
In the brain, prefrontal areas, which help regulate emotion, can relax, freeing them for another of their primary purposes: problem solving. In effect, the body interprets a supportive touch as “I’ll share the load.”
“We think that humans build relationships precisely for this reason, to distribute problem solving across brains,” said James A. Coan, a a psychologist at the University of Virginia. “We are wired to literally share the processing load, and this is the signal we’re getting when we receive support through touch.”
The same is certainly true of partnerships, and especially the romantic kind, psychologists say. In a recent experiment, researchers led by Christopher Oveis of Harvard conducted five-minute interviews with 69 couples, prompting each pair to discuss difficult periods in their relationship.
The investigators scored the frequency and length of touching that each couple, seated side by side, engaged in. In an interview, Dr. Oveis said that the results were preliminary.
“But it looks so far like the couples who touch more are reporting more satisfaction in the relationship,” he said.
Again, it’s not clear which came first, the touching or the satisfaction. But in romantic relationships, one has been known to lead to the other. Or at least, so the anecdotal evidence suggests.
By BENEDICT CAREY
Published: February 22, 2010
Psychologists have long studied the grunts and winks of nonverbal communication, the vocal tones and facial expressions that carry emotion. A warm tone of voice, a hostile stare — both have the same meaning in Terre Haute or Timbuktu, and are among dozens of signals that form a universal human vocabulary.
Clockwise from top left: Jed Jacobsohn/Getty Images; Mark Avery/Reuters; Vivek Prakash/Reuters Charles; Dharapak/Associated Press
YOU FEEL ME A quick hug, fist pound, high five or belly bump can communicate a wide range of emotions, sometimes more accurately than words.
But in recent years some researchers have begun to focus on a different, often more subtle kind of wordless communication: physical contact. Momentary touches, they say — whether an exuberant high five, a warm hand on the shoulder, or a creepy touch to the arm — can communicate an even wider range of emotion than gestures or expressions, and sometimes do so more quickly and accurately than words.
“It is the first language we learn,” said Dacher Keltner, a professor of psychology at the University of California, Berkeley, and the author of “Born to Be Good: The Science of a Meaningful Life” (Norton, 2009), and remains, he said, “our richest means of emotional expression” throughout life.
The evidence that such messages can lead to clear, almost immediate changes in how people think and behave is accumulating fast. Students who received a supportive touch on the back or arm from a teacher were nearly twice as likely to volunteer in class as those who did not, studies have found. A sympathetic touch from a doctor leaves people with the impression that the visit lasted twice as long, compared with estimates from people who were untouched. Research by Tiffany Field of the Touch Research Institute in Miami has found that a massage from a loved one can not only ease pain but also soothe depression and strengthen a relationship.
In a series of experiments led by Matthew Hertenstein, a psychologist at DePauw University in Indiana, volunteers tried to communicate a list of emotions by touching a blindfolded stranger. The participants were able to communicate eight distinct emotions, from gratitude to disgust to love, some with about 70 percent accuracy.
“We used to think that touch only served to intensify communicated emotions,” Dr. Hertenstein said. Now it turns out to be “a much more differentiated signaling system than we had imagined.”
To see whether a rich vocabulary of supportive touch is in fact related to performance, scientists at Berkeley recently analyzed interactions in one of the most physically expressive arenas on earth: professional basketball. Michael W. Kraus led a research team that coded every bump, hug and high five in a single game played by each team in the National Basketball Association early last season.
In a paper due out this year in the journal Emotion, Mr. Kraus and his co-authors, Cassy Huang and Dr. Keltner, report that with a few exceptions, good teams tended to be touchier than bad ones. The most touch-bonded teams were the Boston Celtics and the Los Angeles Lakers, currently two of the league’s top teams; at the bottom were the mediocre Sacramento Kings and Charlotte Bobcats.
The same was true, more or less, for players. The touchiest player was Kevin Garnett, the Celtics’ star big man, followed by star forwards Chris Bosh of the Toronto Raptors and Carlos Boozer of the Utah Jazz. “Within 600 milliseconds of shooting a free throw, Garnett has reached out and touched four guys,” Dr. Keltner said.
To correct for the possibility that the better teams touch more often simply because they are winning, the researchers rated performance based not on points or victories but on a sophisticated measure of how efficiently players and teams managed the ball — their ratio of assists to giveaways, for example. And even after the high expectations surrounding the more talented teams were taken into account, the correlation persisted. Players who made contact with teammates most consistently and longest tended to rate highest on measures of performance, and the teams with those players seemed to get the most out of their talent.
The study fell short of showing that touch caused the better performance, Dr. Kraus acknowledged. “We still have to test this in a controlled lab environment,” he said.
If a high five or an equivalent can in fact enhance performance, on the field or in the office, that may be because it reduces stress. A warm touch seems to set off the release of oxytocin, a hormone that helps create a sensation of trust, and to reduce levels of the stress hormone cortisol.
In the brain, prefrontal areas, which help regulate emotion, can relax, freeing them for another of their primary purposes: problem solving. In effect, the body interprets a supportive touch as “I’ll share the load.”
“We think that humans build relationships precisely for this reason, to distribute problem solving across brains,” said James A. Coan, a a psychologist at the University of Virginia. “We are wired to literally share the processing load, and this is the signal we’re getting when we receive support through touch.”
The same is certainly true of partnerships, and especially the romantic kind, psychologists say. In a recent experiment, researchers led by Christopher Oveis of Harvard conducted five-minute interviews with 69 couples, prompting each pair to discuss difficult periods in their relationship.
The investigators scored the frequency and length of touching that each couple, seated side by side, engaged in. In an interview, Dr. Oveis said that the results were preliminary.
“But it looks so far like the couples who touch more are reporting more satisfaction in the relationship,” he said.
Again, it’s not clear which came first, the touching or the satisfaction. But in romantic relationships, one has been known to lead to the other. Or at least, so the anecdotal evidence suggests.
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