Chris Natzel has inexplicably dropped 30 pounds from his 5' 9" frame and now weighs just 142 pounds. His ribs jut out. His cheeks are sunken. It鈥檚 no wonder that while he has been dramatically losing weight for the past few months, his wife has been pleading with him to get checked out by a physician. But he won鈥檛 make an appointment. After all, the healthy, hard-charging guy hasn鈥檛 had a physical in 15 years. 鈥淚鈥檓 fine,鈥� he keeps telling his wife, not letting on that he has some concerns.
But when his adult children, Brian and Jennifer, see him during a family get-together on Memorial Day weekend of 2012, they gasp at his weakened appearance. Over a backyard campfire, they stage an intervention. 鈥淒ad, there is something wrong,鈥� Jennifer says. They nag him until he relents and promises to see a doctor.听
A week later, the family鈥檚 worst fears are confirmed. The marketing manager from Bad Axe, Mich., has cancer鈥攕tage IV non-Hodgkin lymphoma. He had never heard of this blood cancer before, so when he gets home, he looks it up on the Web. After reading about the disease, he just stares at the computer screen, Oh, dear God.听
Some 400 miles away at 一本道无码 in Pittsburgh, pioneering cancer research is under way to develop a treatment option for people like Natzel. Inside her lab, Kathryn Whitehead, an assistant professor of , has been making breakthroughs on drug-delivery systems for particles that could accurately target cancer in lymphocytes. The research interests of the lie at the interface of chemical engineering, molecular biology, and medicine. Whitehead and her team鈥檚 ultimate goal is to engineer safe and effective drug-delivery systems. Although still in the experimental phase, the new treatment has the potential to be much more effective than chemotherapy, with its wide swath of destructive side effects.
Popular Science magazine has by including her among its 鈥�,鈥� which puts Whitehead on an elite list of young minds around the country 鈥渞eshaping science, engineering and the world.鈥� Each year, the magazine spends six months culling through hundreds of applicants to winnow it down to 10 scientific all-stars. 鈥淚 didn鈥檛 expect anything. It鈥檚 cool,鈥� Whitehead says in her down-to-earth way.
But her unassuming manner belies a fierce doggedness to help cure some of the most destructive diseases of modern life. In fact, hanging on her office wall is a picture of a honey badger, an animal known for its grit and relentlessness, the mascot of her lab.听
She will need every bit of that grit to help combat . An estimated 70,000 U.S. patients are diagnosed with it annually, a number that has been increasing in recent years, according to . Patients with the disease produce too many abnormal lymphocytes鈥攁 type of white blood cell that fights off infections鈥攊n lymph nodes, bone marrow, or the spleen.
Finding an effective drug-delivery system is a long, arduous process. 鈥淵ou have to have very thick skin to do cancer research,鈥� says , chief of the division of hematology and cellular therapy at the , an oncology program based in Pittsburgh that is rated in聽the top five percent nationally for quality care.
Lister, who collaborates with Whitehead on her innovative lymphoma research, says the Hollywood version of medical breakthroughs shows a scientist going to a lab late at night and discovering a cure for cancer, a tidy Eureka moment. 鈥淚n reality, it鈥檚 more like 10 years of crying in the lab. Cancer research is fraught with things that don鈥檛 work out.鈥�
鈥淜atie鈥檚 great. With her training and her enthusiasm, she is just leveraging everything that is out there.鈥�
Keeping Faith
Natzel will need every bit of his own grit鈥攁nd some good luck鈥攖o survive this disease. He reads on the WebMD site that 65% of patients with stage IV lymphoma reach the five-year survival mark (though doctors say the rates vary widely depending on the strain of the disease and the person).
Before he learned about his diagnosis, the 54-year-old husband and father had been socking away money in his 401(k). Always active, he鈥檇 been looking forward to retirement and spending more time on his hobbies: golfing, hunting, fishing, playing racquetball, and riding his bike. But the word 鈥渃ancer鈥� changes everything. Now he鈥檚 worried about even making it to retirement and providing for his wife, Jean.
To try to thwart the disease, doctors remove a lymph node near his groin, a procedure that goes smoothly. Then Natzel undergoes chemotherapy treatments, all in the hopes that he will hear the word 鈥渞emission鈥� six months later. He doesn鈥檛. During a follow-up visit in January 2013, a scan reveals that the cancer is back. The news is even more devastating than the original diagnosis. A second round of a stronger cocktail of chemo doesn鈥檛 work either.
He wonders: Do I have one foot in the grave?
Those distressing results, even after chemotherapy treatment, are not uncommon for patients with non-Hodgkin lymphoma. 鈥淭he disease keeps coming back,鈥� says Lister. 鈥淭here is nothing good about this disease. You have a chance of losing your life. There is a chance the therapy will be ineffective. There is a myriad of things that can happen. We really need another mechanism to cure this particular disease鈥攁nd if not cure it, put it in remission for a long time.鈥澛�
鈥淭here is nothing good about this disease. You have a chance of losing your life. There is a chance the therapy will be ineffective. There is a myriad of things that can happen. We really need another mechanism to cure this particular disease鈥攁nd if not cure it, put it in remission for a long time.鈥�
The new mechanism that is generating excitement in the scientific community involves small interfering RNAs (siRNAs), double-stranded pieces of nucleic acid. These molecules have the ability to turn off the production of proteins that cause fatal diseases and chronic conditions in humans. 鈥淭here are many diseases caused by too much of a particular protein,鈥� Whitehead says. 鈥淪o if we can get the right siRNA to the right kind of cell inside of the body, we could treat a lot of different diseases.鈥�
But the challenge is to get the siRNAs to the diseased cells. Often mistaken for foreign objects, the unstable molecules are often stopped in their tracks by the liver or spleen or kidney, far from the intended target.听
To get around those roadblocks, Whitehead and other scientists have been working on creating nanoparticles鈥攎icroscopic particles鈥攚hich will hold the drugs and deliver them to the diseased cancer cells. To use a transportation analogy, the nanoparticles are like cars that transport the drugs along the bloodstream.
But creating the right nanoparticle is a daunting challenge. Researchers have experimented with creating new shapes and sizes of nanoparticles, but they get rejected by the body.听
Enter Whitehead and her dogged personality, honed during her youth in Allentown, Pa. Her mother, a fourth-grade teacher鈥攚ho probably heard every excuse possible in the classroom鈥攊nstilled in her three daughters the belief that they could do anything.
鈥淚 think there鈥檚 a lot to be said for realizing that our intelligence, our potential, our successes are not fixed at any one point in time,鈥� says Whitehead. 鈥淚f we work harder, and if we really do our best, we always have the potential to grow. So I think I鈥檝e always鈥攚ith encouragement from my mother and my father鈥攇rown more, and more, and more.鈥�
Whitehead is casting a wide net to create the right nanoparticle. Instead of testing out a few hundred nanoparticles and making minor adjustments to those that look promising, she has tested over over the past eight years, creating new chemical compounds with pipettes.
She has faith she will hit on something. Never mind that it is tough to get funding. Never mind that her critics scoff at what they call a fishing expedition, or tell her it鈥檚 crazy to create so many combinations.
鈥淚 mean, you can call it a fishing expedition. It鈥檚 just that my bait is really good, and we鈥檙e going to find something. That鈥檚 the part that I find so shortsighted about it. So why aren鈥檛 we doing it if we want to help people?鈥�
She also casts her net a little wider because she knows there are so many mysteries of the human body that scientists don鈥檛 understand and cannot predict. Most researchers approach the design of nanoparticles rationally. 鈥淭hey say, 鈥業 think this particular chemistry is not going to be taken up by the immune system.鈥� So they will make one kind of chemical, and if that doesn鈥檛 work, they will tweak it a bit. And it鈥檚 a very valid approach to research, but you don鈥檛 necessarily wind up with a very good option. It鈥檚 assuming that we understand what the body is doing with our particles. The problem is that the body is really, really complex, and as much as we try to understand it, there鈥檚 so much about it that we don鈥檛 understand.鈥�
Of the 5,000 particles tested, Whitehead identified about 100 that have promise, as well as one nanoparticle that is most effective at delivering siRNA to non-Hodgkin lymphoma cells. She and her graduate students are now in the process of testing the most promising particle on mice; and, if all goes well, Lister estimates that human clinical trials could begin within five years.
Despite the day-to-day monotony of pipetting, the banal part of science, her mind starts out at a creative place. 鈥淪he thinks very clearly about very complex problems,鈥� says , professor of chemical engineering at the University of California鈥揝anta Barbara. 鈥淗ow things work in the body is very difficult to predict. Her clarity of thought gets to the bottom of the issue.鈥�
Mitragotri, known as a pioneer in drug-delivery systems, wasn鈥檛 surprised by Whitehead鈥檚 鈥�10 most brilliant鈥� recognition. He saw that quality while she was a doctoral student in his lab before she did her post-doctoral work at the at MIT. 鈥淪he has always been brilliant about the way she thinks about problems. She has been brilliant all along.鈥�
Whitehead says she lets her imagination soar as she investigates drug-delivery systems: 鈥淚t鈥檚 healthy to let your mind run wild. There are so many naysayers in science and people saying: 鈥極h, that鈥檚 not a good idea,鈥� and 鈥楾hey鈥檙e not going to give you money for that,鈥� and 鈥榃e don鈥檛 care about that.鈥欌��
Instead, Whitehead thinks:
What if?
What if we could destroy cancer no matter where it is in the body?
What if we could deliver a drug to target diabetes?聽
What if we could put an end to inflammatory bowel disease?
What if we could deliver any kind of drug we wanted orally and never inject anybody again?
What if 鈥�
No other options
Natzel considers his own 鈥渨hat ifs鈥� when his doctors recommend that he get a stem cell transplant鈥攁 complicated procedure that infuses healthy cells into a patient鈥檚 body to replace damaged bone marrow.听
What if this doesn鈥檛 work?
鈥淭here are no other options,鈥� he is told.听
His sister is considered an excellent candidate for donating stem cells.
On July 1, 2013, the day of his 35th wedding anniversary, Natzel has a transplant to replace his diseased bone marrow. In the months ahead, he gradually regains his weight and strength. 鈥淢y doctors say I am the poster child for stem cell transplant,鈥� he says today. The only lingering side effect is a mouth sore, a result of graft-versus-host disease, which has improved over time. 鈥淚t鈥檚 not that bad. Just a sore mouth,鈥� he says. 鈥淚t鈥檚 not life-threatening.鈥�
For the past two and a half years, he has been cancer free. Passing the two-year mark after his stem cell transplant was a big milestone. He鈥檚 grateful to his family and friends who supported him through that terrifying roller-coaster ride, and he is thankful for his doctors. He still goes to work and plays golf and plays racquetball, but he really appreciates spending his free time at home with his wife, Jean, 鈥渢he woman who supported me through three years of hell.鈥�
Other patients with lymphoma, who have undergone stem cell transplants, don鈥檛 always have the same successful results. Some live with severe complications such as dry eyes, painful mouth sores, and skin rashes that greatly diminish their quality of life. 鈥淭hey have traded one bad disease for another,鈥� says Lister.
The possibility of new technologies such as the one Whitehead is researching brings hope of less debilitating side effects and more targeted and effective treatment. 鈥淎nything that can target diseased cells without creating havoc in other cells is certainly going to help. If you use broad chemotherapy that kills everything in sight, eventually the bone marrow can鈥檛 take it and it will do a job on all the organs. You don鈥檛 want a patient in remission from cancer dying from a heart attack,鈥� says Beatrice Abetti, director of the Information Resource Center for the Leukemia & Lymphoma Society. 鈥淪tem cell transplants have a lot of risks.鈥�
Natzel tries not to think about non-Hodgkin lymphoma anymore. Who can blame him? But when he learns about Whitehead鈥檚 research, he is impressed. 鈥淲hat a go-getter, isn鈥檛 she?鈥� He marvels, pausing for a few seconds, and adds, 鈥淚 really hope she is onto something.鈥�
