CANCER TREATMENT BREAKTHROUGH (WSJ)

 

 WALL STREET JOURNAL

Gene Breakthroughs Spark a Revolution in Cancer Treatment

A growing number of cancer practices are sequencing the DNA of tumors to uncover their genetic abnormalities. The aim: to pair a drug with the specific mutation fueling a patient’s disease. UC San Francisco’s Dr. Trever Bivona discusses.

Kellie Carey’s doctor finally stopped dodging questions about how long she had to live six weeks after he diagnosed her lung cancer.

“Maybe three months,” he told her in his office one sunny May morning in 2010, she recalls.

Yet she is still alive, a testament to the most extraordinary decade of progress ever in the long scientific struggle against lung cancer.

Tests found Ms. Carey’s lung cancer to be of a rare type that researchers had found just three years earlier by deciphering its genetic code. The 45-year-old businesswoman in 2010 went on a drug Pfizer Inc. PFE +0.27% was testing for that type. By pinpointing her cancer, the drug probably helped give her years more to live than chemotherapy would have, her doctors say.

Jesse Neider for The Wall Street JournalKellie Carey, who was given three months to live in 2010, discusses her lung-cancer treatment with her doctor, Roy Herbst, last month.

That is remarkable because lung cancer for decades defied efforts to find drugs that could extend an average patient’s life by even a few weeks.

But an explosion in knowledge about the genetic mutations that cause tumors is just now offering the first real promise of drugs that can control what is the most-common and most-deadly cancer.

Ms. Carey has one of at least 15 lung-cancer variations, almost all of which scientists didn’t know existed 10 years ago. Researchers have identified those variations, most of them in just the past four years, by decoding DNA in tumors—akin to how crime labs analyze DNA to genetically fingerprint suspects.

The newfound variants have led major cancer centers to revamp their approach to treating cancer and have spurred a rush among drug companies to find medicines that narrowly target each one.

The drugs don’t cure cancer and face significant hurdles. But doctors now talk of a “precision medicine” approach in which those pinpoint drugs can treat tumors far more effectively than catchall chemotherapy.

“What we’re seeing is the beginning of a revolution in therapeutics,” says Janet Woodcock, director of the Food and Drug Administration’s Center for Drug Evaluation and Research. “We can only hope that this gets us to where cancer is managed or curable.”

Among signs that revolution really is afoot: A June 2013 study found that lung-cancer patients who were treated with drugs targeted at their genetically identified varieties lived 1.4 years longer than patients on chemotherapy whose cancers weren’t genetically identified.

In effect, lung cancer is no longer a few common diagnoses. Instead, it is a growing list of rare cancers, each a target for its own drug regimen.

“It’s likely that more than half of tumors have some alteration we can target with a drug,” says John V. Heymach, a lung-cancer specialist at MD Anderson Cancer Center, Houston. “They may not all have the same success, but we know that in many cases, a targeted agent will work very well.”

The same goes for other malignancies: Scientists have decoded tumor DNA from breast, colon, kidney, skin and other cancers in recent years to discover scores of variations they didn’t know existed before.

Research hospitals like MD Anderson, Vanderbilt University and Massachusetts General Hospital are among a growing number of cancer practices that routinely decode the tumor DNA of most patients with advanced cancer.

The lists of newfound variations have invigorated the drug industry, with companies like Pfizer, Roche Holding AG ROG.VX +0.38% andMerck MRK -0.08% & Co. racing to develop drugs that target each one.

Last year, nearly 1,000 cancer drugs were in clinical development, up 52% from 2006, says the Pharmaceutical Research and Manufacturers of America, a trade group. The “vast majority” of that growth is from drugs targeted at genetic mutations, says Bill Chin, the group’s head of science and regulatory affairs.

Three drugs are on the market for newly discovered lung-cancer mutations. Dozens more are in clinical trials. Some approved for other cancers appear effective for specific lung cancers. And drug companies are targeting other mutations of all cancer types.

At least half the 27 medicines on Novartis AG’s NOVN.VX +0.74%current list of oncology drugs in clinical development target cancer mutations. Precision medicine is “fundamentally changing the way we think about cancer drug development,” says Hervé Hoppenot, president of the company’s Novartis Oncology unit.

Just last year, the FDA established a “breakthrough therapy designation” to hasten approval of experimental drugs that show striking benefits in early trials, including those targeted at cancer mutations.

Ms. Carey’s diagnosis in 2010 came just as that thinking was starting to change. Her roller-coaster ride of cancer remission and recurrence over the next three years shows the promise and shortcomings of precision medicine.

Ms. Carey, who worked for a business selling private jets, suffered an apparent seizure at her gym. Doctors discovered a nodule in her lung of cancer that had spread to her brain. Surgery and radiation treated the brain tumor.

But when the New York City resident’s doctor said she probably had three months left, “I definitely felt like there were no options,” she says.

It wasn’t an unusual prognosis for lung cancer in 2010. Three decades of research starting in the 1970s into hundreds of potential lung-cancer drugs had produced dismal results, says MD Anderson’s Dr. Heymach: Over that time, a lung-cancer patient’s median survival improved by just one month, to eight months.

Ms. Carey found hope in news accounts of a drug Pfizer was testing against a cancer type researchers had identified in 2007. The type was caused by a mutation in the so-called ALK gene—it normally plays a role in brain development—and Ms. Carey wanted to know if that was her cancer.

In 2010, precision medicine was still so nascent that Ms. Carey had to show unusual persistence. Few doctors even considered testing tumors for mutations.

She says she had to demand the test. “Are you helping to save my life,” she recalls asking her doctor at the time, “or just waiting for me to die?”

That ALK-gene mutation was only the second mutation researchers had identified using advanced DNA-sequencing technology on lung-cancer tumors. The first was in 2004, a mutation in the so-called EGFR gene that responded well to an existing drug, Tarceva, now sold by Roche. (Another mutation, KRAS was discovered previously, with earlier technology.)

The discovery of the role of the EGFR mutation in 2004 sparked the search for more cancer-causing mutations.

Before that, a pathologist would identify a patient’s lung-cancer tumors through a microscope to see if they were of the “small-cell” or “non-small-cell” variety. The difference helped determine which regimen of chemotherapy to prescribe.

After finding the ALK-gene mutation, researchers in 2007 found another mutation. By 2010, for a few lucky patients whose tumors proved to be of the newly discovered varieties, there were a few drugs on the market or in trials.

Ms. Carey was among the fortunate: Her mutation proved to be of the ALK gene, which represents about 5% of lung-cancer cases.

The discovery of the ALK-gene mutation had prompted Pfizer to test a drug already in its portfolio, brand-named Xalkori and generically called crizotinib, to see if it worked on the mutation. Pfizer’s study of the first patients showed dramatic results, which Ms. Carey read about.

Again, Ms. Carey needed persistence, this time to get the drug. She visited different sites participating in Pfizer’s trials before finding a slot at the University of Chicago.

Within six weeks, two of three cancerous nodules in her lungs had disappeared, and the third had shrunk significantly.

The FDA approved the Pfizer drug in 2011 based on 250 patients, four years after the ALK-mutation link was discovered. That is lightning speed in an industry accustomed to spending a decade with thousands of test subjects to get drug approval.

Ms. Carey in 2011 began buying the Pfizer drug by prescription. It was expensive—today Pfizer charges $10,800 a month for it—but her insurance covered it.

Prices like that raise questions about the affordability of precision medicine. But those prices, and the speed at which genetically targeted drugs can come to market, had begun changing the economics of drug development.

The “precision medicine approach requires people to change the way they look at opportunities,” says Mace Rothenberg, a senior vice president who heads cancer clinical development for Pfizer. Instead of trying to apply a drug to the largest number of patients possible, it is possible to “demonstrate very significant value of the drug to the patient, the physician, the payers and the company.”

Discovery of new mutations accelerated. A 2011 report linked a mutation of a gene called RET to lung cancer, prompting researchers at Memorial Sloan-Kettering Cancer in New York to approach ExelixisInc. EXEL -0.61% The South San Francisco biotechnology company was developing a drug called cabozantinib to treat a rare form of thyroid cancer linked to the RET mutation.

That mutation is found in only about 1% of lung-cancer patients, but Sloan-Kettering launched a drug trial. The first few patients tested had striking benefits. “These were patients who had nothing six months earlier,” says Mark Kris, a lung-cancer specialist at Sloan-Kettering.

Discovery of still-more lung cancer mutations continued in rapid fire. The count is 15 today, accounting for about 60% of all lung cancers, according to some estimates, and researchers expect to find more.

Precision medicine is no cure. A tumor with a pinpointed mutation doesn’t always respond to a drug targeted at it. The drug often shrinks tumors within weeks. But the tumors can develop resistance and come roaring back.

Ms. Carey’s cancer found a way around the treatment, in early 2012. An analysis of her tumor found the ALK-gene mutation still active. She took to calling her mutation the “Darth Vader of cells.”

Doctors think most patients will need a series of precision drugs, sometimes with chemotherapy. “The tumor will keep evading our best therapies,” says Trever Bivona, a lung-cancer researcher at University of California San Francisco. “Ultimately we’re going to have to get to combination approaches.” exdiscovery of new

Ms. Carey in the spring of 2012 went off crizotinib for another regimen of brain radiation, then went back on the drug.

By that year, interest was surging among drug companies in targeted drugs. At least three “next-generation crizotinibs” against the ALK-gene mutation were now in trials. Ms. Carey entered a trial for one of them, being developed by Ariad Pharmaceuticals Inc. ARIA +0.27%

Not all patients can find a trial. Precision drugs are approved for only two lung-cancer mutations, the ALK and the EGFR-gene mutations. A patient with a different mutation must look for a drug in development and try to join its trial.

Dr. Bivona of University of California San Francisco says he treated a patient this year who died a month before the launch of a clinical trial for a drug that matched the patient’s mutation. “We were in a black hole,” he says. “Getting drugs to the patients who need them will take an entire remodeling of the drug-development system.”

While there are drugs approved for other cancers that appear effective for some newfound lung cancers, insurers generally feel data don’t yet justify coverage of such “off-label” drugs. And for several of the 15 known lung-cancer variants, an especially promising drug has yet to emerge.

Tests for mutations are less likely to be available in smaller doctors’ offices. Even many large centers are just putting in place systems to act on the information. “A lot of places can tell you they do this now, but few really have the people in place who know what to do,” says Roy Herbst, chief of medical oncology at Yale Cancer Center, New Haven, Conn., who is Ms. Carey’s current oncologist.

But rapid diagnostic advances are making it easier for any doctor to test for the newfound cancers. Tests now can hunt for more than 200 mutations—of lung and other cancers—in one biopsy.

Evidence that precision medicine works will likely broaden its use quickly. A June 2013 report on 1,007 patients with advanced lung cancer whose tumors were sequenced by a group of researchers called the Lung Cancer Mutation Consortium found that 62% had alterations suspected of being driver mutations.

The researchers reported that the 265 patients on the study treated with a targeted drug had a median survival of 3.5 years from diagnosis, compared with 2.1 years for the 361 patients for whom a mutation wasn’t identified.

“It opens up so many more doors for patients if you can find their target,” says Alice Shaw, an oncologist at Mass General in Boston.

At Ms. Carey’s checkup late this July, her doctor said her new drug regimen is keeping her lung tumor from progressing.

She is also considering a new class of drugs called PD-1 inhibitors that enlist the immune system. Such agents from Merck, Roche andBristol-Myers Squibb Co. BMY +0.51% are creating a buzz among oncologists for use in parallel with the genomic strategy.

“Now when I look back, I’m astonished at the timing of everything,” she says.

“My quality of life is extraordinary,” she says. “The science in this and the positive response I’ve had—I wouldn’t be alive without that.”

GET KIDS BED ON TIME

New Study Shows Why You Should Get the Kids to Bed on Time

Going to bed at a regular time every night could give your child’s brain a boost, recent research shows.

Columnist's name

A large study published in June found that young children with an irregular bed time fared worse on cognitive tests several years later. Sumathi Reddy explains on Lunch Break. Photo: Getty Images.

Going to bed at the same time every night could give your child’s brain a boost, a recent study found.

Researchers at University College London found that when 3-year-olds have a regular bedtime they perform better on cognitive tests administered at age 7 than children whose bedtimes weren’t consistent. The findings represent a new twist on an expanding body of research showing that inadequate sleep in children and adolescents hurts academic performance and overall health.

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Izhar Cohen

The latest study considered other factors that can influence bedtime and cognitive development, such as kids skipping breakfast or having a television in their bedroom. After accounting for these, the study found that going to bed very early or very late didn’t affect cognitive performance, so long as the bedtime was consistent.

“The surprising thing was the later bedtimes weren’t significantly affecting children’s test scores once we took other factors into account,” said Amanda Sacker, director of the International Center for Lifecourse Studies in Society and Health at University College London and a co-author of the study. “I think the message for parents is…maybe a regular bedtime even slightly later is advisable.”

The researchers suggested that having inconsistent bedtimes may hurt a child’s cognitive development by disrupting circadian rhythms. It also might result in sleep deprivation and therefore affect brain plasticity—changes in the synapses and neural pathways—at critical ages of brain development.

Sleep experts often focus largely on how much sleep children get. While that is important, “we tend to not pay as much attention to this issue of circadian disruption,” said Judith Owens, director of sleep medicine at Children’s National Medical Center in Washington, D.C., who wasn’t involved with the study.

Insufficient sleep and irregular bedtimes may each affect cognitive development through different mechanisms, Dr. Owens said. “The kid who has both [problems] may beat even higher risk for these cognitive impairments,” she said.

The study, published online in July in the Journal of Epidemiology & Community Health, examined data on bedtimes and cognitive scores for 11,178 children.

The children were participants in the U.K.’s Millennium Cohort Study, a nationally representative longterm study of infants born between 2000 and 2002.

Mothers were asked about their children’s bedtimes at 3, 5 and 7 years of age. Nearly 20% of the 3-year-olds didn’t have a regular bedtime. That figure dropped to 9.1% at age 5 and 8.2% at age 7. Mothers were also asked about socioeconomic and demographic characteristics and family routines.

When the children were 7 years old, they received cognitive assessments in reading, math and spatial abilities. The poorest test scores were recorded by children who went to bed very early or very late, and by those who had inconsistent bedtimes, said Dr. Sacker. But once other factors in the home were taken into account only the inconsistent bedtime was associated with lower scores, she said.

A consistent pattern of sleep behavior mattered. “Those who had irregular bedtimes at all three ages had significantly poorer scores than those who had regular bedtimes,” Dr. Sacker said. This was especially true for girls who didn’t establish consistent bedtimes between 3 and 7 years old.

Yvonne Kelly, a co-author of the study and a professor in the department of epidemiology and public health at University College London, said the researchers aren’t sure why girls seemed to be more affected. She noted that the difference in scores between these groups of girls and boys wasn’t statistically significant for the reading and spatial tests, but it was for the math test.

“I don’t think for one moment that boys are immune to these things and girls are more affected,” Dr. Kelly said.

The researchers didn’t have data on the total number of hours children slept overnight because mothers weren’t asked about what time the children woke up.

In general school-age kids—kindergarten through eighth-grade—should be getting about 10 hours of sleep, while 3- and 4-year-olds might need 11 to 13 hours, including day-time naps, said Shalini Paruthi, director of the pediatric sleep and research center at SSM Cardinal Glennon Children’s Medical Center at Saint Louis University.

Dr. Paruthi said the good news from the study is that the majority of the children went to bed at a consistent time, reinforcing advice from sleep specialists. “The younger the child is, the better it is to get into the habit of a regular bedtime,” said Dr. Paruthi, who wasn’t affiliated with the study. She recommends a 15-minute, pre-bedtime routine to help the brain transition from a more alert to a quiet state.

And in order to keep the body’s internal clock in sync with the brain, bedtimes on weekends and in the summer should only stray from the normal time by an hour or less, Dr. Paruthi said. “The internal clock in the brain and the body like to have consistency every day,” she said.

 

INTELLIGENCE AND BREASTFEEDING

Links Tighten Between IQ, Breast-Feeding

    By

  • AVERY JOHNSON
  • PICASSO

           MOTHER AND CHILD BY PABLO PICASSO

 

Breast-feeding longer can make children smarter. That’s the conclusion of a study published Monday in JAMA Pediatrics, a journal of the American Medical Association.

In many ways, the study won’t surprise proponents of breast-feeding, who have long posited a connection between nursing and cognition and now have an additional piece of research to back up their argument. Skeptics could likely stick to the view that what matters most is how smart a baby’s mom is, or that social pressure to breast-feed can have its own problems for children’s development by creating stressed-out parents. However, the findings are likely to add muscle to public-health advocates’ push to increase breast-feeding rates, which start out around 75% but slump to an average of 25% at a baby’s first birthday, according to the Centers for Disease Control and Prevention.

The JAMA study isn’t the first to study a link between nursing and intelligence, but researchers say it is more conclusive because of its size and how it has isolated variables such as the mother’s IQ and the child’s upbringing. Previous studies have had difficulty adjusting for other factors that might influence a child’s IQ, were limited by their small size or didn’t account for length of nursing, said Mandy Belfort, the JAMA study’s lead author and assistant professor of pediatrics at Harvard Medical School.

The latest study examined and rated each child’s environment based on factors such as how many books are available, and gave each mother an IQ test. They also asked detailed questions about factors that might influence IQ, such as child care, income and parental education. They then subtracted those factors using a statistical model. Dr. Belfort said she hopes that “what we have left is the true connection” with nursing and IQ.

Breast-feeding is hard to study in a randomized trial because it is unethical to put some children in the non- group, Dr. Belfort said, which leaves researchers with observational studies such as the one she conducted. Researchers at Boston Children’s hospital followed 1,312 babies and mothers from 1999 to 2010. They found out how many of those children were still consuming their mothers’ milk at their first birthday, and then tested the children’s intelligence at ages 3 and 7.

Intelligence is a strange brew of nature and nurture and isolating one factor is challenging. Breast-feeding in the first place has a lot to do with class and wealth, with richer, better educated women typically opting to make the effort to nurse their babies.

Children who were still nursing after a year had higher receptive language scores at age 3, which means they understood what was being said to them better than their formula-fed peers. At age 7, the breast-fed children scored higher on verbal and nonverbal intelligence tests.

In 3 year olds, every month of breast-feeding raised cognition scores by an average of .21 point. Each month of breast-feeding was associated with a .35 more verbal IQ point and a .29 more nonverbal point in the 7 year olds. A full year of nursing would boost a child’s IQ by about 4 points over a child who didn’t nurse, said Dr. Belfort, a significant bump considering that IQs average around 100. That is for children getting some breast milk in their diets; those consuming only breast milk before starting to eat solid foods around six months of age saw even greater advantages.

“For an individual person, it would be hard to tell a two or three point difference in IQ, but it would matter a lot for society,” said Dr. Belfort. “If we can shift the IQ up, we would have to invest less resources at the low end.” Meaning that with improved IQ scores across the board, less funding would have to be spent on remedial education programs.

Dr. Amy Tuteur, an obstetrician who writes a blog called skepticalob.com, is unconvinced by a four-point increase in IQ, saying the bump needs to be bigger to prove that it isn’t just random variation. “Intelligence is multifactoral and the idea that any one thing can make a big difference right away makes me skeptical,” she said. “American IQ has been increasing steadily, it rose when breast-feeding rates were going down and it rose when breast-feeding rates were going up.”

The possible link between breast milk and brain development is only starting to be teased out. Some theories suggest that it isn’t the content of the milk but the bond between mother and child developed while nursing that accounts for some of the boost. Other ideas hinge on nutrients found in breast milk such as DHA and ARA, which are fatty acids linked to brain development. Some formula companies put DHA and ARA in their offerings.

“There are nutrients in breast milk that don’t really exist anywhere else, and we don’t fully know why,” says Dimitri Christakis, a pediatrician at Seattle Children’s Hospital Research Institute and wasn’t involved in the research.

He wrote an editorial in JAMA pediatrics on the study and leads an advocacy group called the Global Breast-feeding Initiative. In the editorial he contends the JAMA study should put skepticism to rest about whether breast-feeding is best for brain development and that society should make it easier and more acceptable for moms to nurse.

For Amra Chudleigh-Neal of Thousand Oaks, Calif., intelligence is just one more reason for her to breast-feed her 6-week old daughter. She said her older child, now 7, has above average IQ, which Ms. Chudleigh-Neal said could be in part because she exclusively breast-fed until her daughter was 6- months old.

“It tends to be a little more of a sacrifice to nurse the second child, you think ‘oh my gosh is it really worth it’ but looking back with my older child I believe it did make a difference,” she said. Ms. Chudleigh-Neal receives extensive support from The Pump Station, a Los Angeles-area nursing resource center that helps with things like connecting moms to lactation professionals.

Not everyone can breast-feed successfully, and that needn’t make parents worry. “Talk to your baby, hold your baby and read to your baby,” Dr. Belfort said. “There are so many different factors in a child’s development.”

One difficulty in studying breast milk is that every feeding can vary based on the mother and what she has eaten. So the Boston researchers also examined a component in mothers’ diets that might be responsible for children’s brain development: fish, which contains DHA.

The authors found that more than two or more servings of fish per week seemed to confer IQ benefits, but that boost in children’s cognition wasn’t statistically significant.

Write to Avery Johnson at avery.johnson@WSJ.com

PHILADELPHIA CHROMOSOME

A Battle Against Wayward Genes

The story of how ingenious medical researchers and big pharma teamed up to defeat a rare form of leukemia.

 
 
      By

LAURA LANDRO

    More than 50 years ago, scientists working in the City of Brotherly Love discovered a genetic mutation that they called “the Philadelphia chromosome” in patients with chronic myelogenous leukemia, a fatal, spontaneously arising cancer of the blood.In her book of the same title, Jessica Wapner chronicles the ensuing decades of laborious scientific inquiry and industrial ingenuity that led to the discovery of Gleevec, the first drug designed to attack cancer at the genetic level. Its success in beating CML into remission and making the errant chromosome disappear has helped to revolutionize cancer research, unleashing a hunt for the genetic basis of other cancers and opening the door to comparable targeted treatments.

    While the money came from drug maker Novartis,NOVN.VX -0.07% the hero of the story is Brian Druker, an oncologist and researcher at Oregon Health & Science University. His unwavering determination kept the development of Gleevec on track against formidable odds, not least of which was the fact that CML, a rare disease with fewer than 6,000 new cases annually in the U.S., seemed to hold little potential for the blockbuster sales that typically attract pharmaceutical-company investment.

    Ms. Wapner tracks decades of work by scientists who often had little knowledge of one another but eventually proved that the Philadelphia chromosome was the sole cause of CML. The mutation causes separate genes to fuse and become one, producing an abnormal protein, tyrosine kinase, which causes white blood cells to proliferate uncontrollably. The resulting cascade becomes a “killing machine,” in Ms. Wapner’s phrase. Blood turns into “viscous sludge” as red cells plummet. Meanwhile, platelets become too few to make the blood clot, and severe bleeding precedes death.

    Having myself received the diagnosis for CML in 1992, I can testify that it is a fairly terrifying experience. At the time there was no Gleevec in sight. Patients were prescribed the drug hydroxyurea to slow things down, but it didn’t work for long, and another common treatment, interferon, was tough to tolerate and wasn’t a long-term solution in any case. The only possible cure was a bone-marrow transplant, which carried risks—including rejection—and required a suitable donor, preferably a matched sibling. (I was fortunate to have two.)

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    The Philadelphia Chromosome

    By Jessica Wapner 
    (The Experiment, 303 pages, $25.95)

    Surprisingly, Ms. Wapner gives short shrift to bone-marrow transplantation, portraying it as the worst possible option when in fact it has saved the lives of many CML patients, including my own. She also dismisses the side effects of Gleevec as minimal. Having taken the drug as part of treatment for recurrences more than a decade after my transplant, I can attest to its unpleasantness, a reason that some patients have stopped using the drug. Resistance also develops, leading some patients to seek transplants after all.

    In “The Philadelphia Chromosome,” Ms. Wapner routinely translates the complexities of science for the lay reader, notably the role of tyrosine kinase and the quest to inhibit its deadly activity. Whenever the details get to be tough slogging, she offers up straight talk to explain what it all means: “In the hunt for cancer’s underlying mechanism, finding tyrosine was like a tracker finding an animal print or a broken branch. They knew they had caught the right trail.”

    The narrative picks up steam when Dr. Druker moves from the Dana-Farber Cancer Institute in Boston to a new research job at Oregon Health & Sciences University. He secures several compounds from Ciba-Geigy, the pharmaceutical company, which is also pursuing a drug. He ultimately uses the compounds to find the Holy Grail: an antibody that is able to bind to the errant protein and block its effects.

    Dr. Druker found supporters among Ciba-Geigy’s scientists, but it was hardly clear coasting from there, and Ms. Wapner’s tale shifts to the often-frustrating struggle to clear the regulatory, political and financial hurdles that kept popping up. Though the lead compound of the drug that would become Gleevec was synthesized by 1990, seven years later the first phase of human trials had yet to begin.

    The turning point came in 1996, after the merger of Ciba-Geigy and Sandoz created Novartis, whose new chief executive, Dr. Dan Vasella, allowed the evidence to prevail over business hesitations within the company. Once human trials were under way, the results were breathtaking: Abnormal white blood cells disappeared, and normal blood cells were not affected.

    Soon the Web was abuzz with news of the drug. For patient Bud Romine, it was a miracle. “The sword that had been hanging over his neck, waiting to fall, was now gone,” Ms. Wapner writes. “He’d been waiting to die, and now he knew he was going to live.” After being fast-tracked at the Food and Drug Administration, Gleevec set a record for swift approval in 2001. Gleevec must be taken daily for life and costs about $6,500 a month, though there are programs for those who can’t afford it. From 2001 to 2011, Ms. Wapner reports, world-wide sales were close to $28 billion, and Novartis and others now offer second-generation drugs that may be more tolerable and effective.

    Novartis took much of the credit for Gleevec’s success, and Dr. Vasella wrote his own 2003 book about its development, “Magic Cancer Bullet.” Dr. Druker, who did not profit from the drug, did not seem to get the credit he deserved. Thanks to Ms. Wapner, he gets it now. Dr. Druker and Dr. Vasella, since retired from Novartis, strike a conciliatory note at the end of Ms. Wapner’s account, stressing the importance of collaboration between academia and industry, especially when research funding is limited. “The drug companies aren’t evil,” Dr. Druker says from his vantage as a university scientist. “They make drugs, and we should help them.”

    Ms. Landro, a Journal editor and columnist, is the author of “Survivor: Taking Control of Your Fight Against Cancer.”

    SON DERS: Prof. Dr.Ufuk Cığızoğlu Beyazova’dan

     Sevgili sınıf arkadaşım Prof. Dr. Ufuk Cığızoğlu Beyazova’dan ogrencilerine emeklilik öncesi “SON DERS” konuşması       

    “SON DERS  

    UFUK

    Değerli arkadaşlarım

    Bu son dersi anlatma görevinin bana verilmiş olmasından son derece mutluyum, onur duydum.gurur duydum. Teşekkür ederim.

    Bir öğretmen, hekim olmak üzere olan arkadaşlarından ayrılırken onlara son olarak ne söylemek ister. Belki biraz öğüt vermek. “İyi bir hekim olmak” üzerine öğütler. Ancak ben tüm meslek yaşamımda öğüt vermekten çok örnek olmaya çalıştım. Kendimce iyi hekim olmak neyse öyle bir hekim olmaya çalıştım. En sık gördüğü hastalıkların tanı ve tedavisini, bu hastalıklardan korunmayı iyi bilmek, her gün yeni bir şey öğrenmeye çalışmak, öğrendiği her şeyi başkaları ile paylaşmaya çaba göstermek yardım isteyen bir şeyler danışan herkese yardımcı olmaya çalışmak, insanları sevmek, insanlar arasında ayrım gözetmemek, yurdunu sevmek, dilini sevmek, infant yerine bebek, prenatal, natal, postnatal yerine doğum öncesi, doğum, doğum sonrası demek, marker yerine belirteç sözcüğünü kullanmak, mesleğimiz çok yoğun çalışma gerektirse de yaşamda sanata, spora, yurdu ve dünyayı tanımaya zaman ayırmak, çocuklara, insanlara, mesleğe yararlı olabilmek için sivil toplum örgütlerinde çalışmalar yapmak, bu günü anlayabilmek için geçmişi bilmeye çalışmak iyi hekim olmaktı benim için, bunlarla örnek olmaya çalıştım.

    Sizlere dersleri anlatırken konu ile ilgili küçük öyküler de anlattım. Aşıları anlatırken Türkiye’nin Pasteur’u Muammer Tunçman’ın Kurtuluş savaşı sırasında aşılanmış tavşanları İstanbul’daki telkihhaneden kaçırabilmek için İngiliz işgalini nasıl yararak İneboluya geldiğini. Orada bir laboratuar kurarak nasıl kuvayı milliye için aşı ürettiğini anlattım.

    Cumhuriyetin kurulmasından sonra Dr. Refik Saydam’ın savaşın yoksul ve yorgun Ankara’sında herkesin hayal diye nitelediği Hıfzıssıhha enstitüsünü nasıl kurduğunu, o yıllarda dünyada aşı üretebilen 5 merkezden biri haline getirdiğini bir  çok Orta doğu ülkesi ve Çin’in aşılarını Türkiyenin ürettiğinin öyküsünü anlattım.

    Bu gün son dersimizde de bir kısa öykü daha anlatmak istiyorum. Fatma Müfide hanım’ın öyküsü.

    Sonradan Küley soyadını alan Fatma Müfide hanım 1900 lerin başında doğmuştu. Şimdiki lise eğitimine karşılık gelen idadiyi bitirdikten sonra 1919 da Tıp Fakültesine girip hekim olmak istemişti. Ancak 1900 lerin başında İstanbul’da bu o kadar kolay değildi. Osmanlı Sıhhiye Meclisi kadınların hekim olamayacaklarına dair bir mazbata çıkarmıştı. Bu mazbatada Kadınların evlenip aile kurduktan sonra mesleklerine devam etmeyecekleri, fakülteye girmenin “iffet ve ahlak” değerlerini zedeleyeceği, erkek hastaları muayene etmemeleri ve anatomi diseksiyonlarına da katılmamaları gerektiği belirtilmişti. İstanbul Darülfünunu Tıp fakültesine kız öğrenci almıyordu. Bu nedenle başvurusu reddedildi.

    Fatma Müfide hanım 1921 de yeniden tıp fakültesine başvurdu, kaydını yaptırdıysa da kız öğrenci kabulüne karşı olan hocalardan birisinin tıp eğitiminin zor ve uzun olması, laboratuar çalışmalarının fazlalığı üstelik tek bir kız öğrencinin o kadar erkek arasında eğitim almasının uygun olmayacağı nedeniyle Saray’a ve o zamanki hükümet yetkililerine şikâyeti ile yine derslere kabul edilmedi. Ertesi yıl 1922 ders yılında, Anadolu’daki başarıların artışı, Sarayın ve İstanbul Hükümeti’nin güçsüz kalmasından cesaretlenip 2 kız arkadaşını daha ikna etti. Yeniden başvurdu. Üniversite onları kabul etmek zorunda kaldı.

    Kurtuluş savaşının ardından Fatma Müfide hanımı 7 kız öğrenci daha örnek aldı ve Tıp Fakültesine alındılar. Fatma Müfide Küley fakülteyi bitirdikten sonra 1933 de öğretim üyesi oldu. 1973 yılına dek üniversitede çalıştı. Öğretim üyeliği dışında Çeşitli derneklerde etkin olarak görev alan Dr.Küley, üniversiteli kadınlar derneğinin kurucu üyelerindendi,  Türk Tıp Cemiyeti genel sekreterliği, ve başkanlığını yaptı. 

    Dr. Müfide Küley bana örnek oldu. Ben ondan çok daha kolay olarak Tıp Fakültesine girmiştim. Kimse bana kadınlar evlenip aile kurduktan sonra mesleklerine devam edemezler demedi, fakülteye girmenin “iffet ve ahlak” değerlerini zedeleyeceği ne benim ne ailemin aklına geldi. Kaydımı yaptırmak için başvurduğumda kimse git birkaç kız öğrenci daha bul erkek öğrencilerin arasında yalnız kalırsın demedi. Zaten bizim sınıfın yarısı kızdı. Hiçbir hocam erkek hastaları muayene etmemem ve anatomi derslerine katılmamam gerektiğini söylemediler. Bunların hiç birini kimse düşünmedi bile. Çünkü cumhuriyet döneminin söylemi bu değildi.

    1923 de Atatürk “Daha esenlikle, daha dürüst olarak yürüteceğimiz yol vardır. Bu yol,Türk kadınını çalışmamıza ortak yapmak, ilmî, ahlâkî, sosyal, ekonomik yaşamda erkeğin ortağı, arkadaşı, yardımcısı ve destekleyicisi yapmak yoludur.” demişti.

    Cumhuriyet, kadınların düşünebileceklerine inandı, kadınların okuyup yazabileceklerine inandı, kadınların da öğretmen, bilim insanı, hakim, hekim olabileceklerine inandı. Cumhuriyet bana inandı. Sizlere inandı. Gençliğe inandı.

    Çünkü Cumhuriyeti gençler kurmuşlardı. Atatürk samsuna çıktığında 38 yaşındaydı. Fikir arkadaşları Rauf Orbay ve Refet Bele, Kazım Karabekir, Ali Fuat Cebesoy hep 37-38 yaşında gençlerdi. Lozan antlaşmasını imzaladığında ismet İnönü onlardan da gençti. Kurtuluş savaşının komutanları 30 lu yaşlardaydılar. Milli Mücadeleyi destekleyen sanatçıların çoğu, Ruşen Eşref, Falih Rıfkı, Yakup Kadri 25-30 yaşlarındaydılar. Cumhuriyeti o yılların gençleri kurdu.  “Biz kurduk onu yücelterek yaşatacak olan sizsiniz”. diyerek sonraki kuşaklara emanet ettiler. 

    Gençlerin hem yurtta hem cihanda barışı koruyacağına, ülkenin bağımsızlığını ve cumhuriyeti muhafaza ve müdafaa edeceğine  ve bilimi en büyük yol gösterici olarak kabul edeceğine inandılar. 

    Onların bu inancını boşa çıkarmayacağınıza bizler de inanıyoruz. Cumhuriyetin hiçbir kazanımından geri adım atmayın. Sizlere yeni yaşamınızda başarı ve mutluluklar diliyorum. Yolunuz açık olsun.