Thick bands wrap around your ribs, tightening and squeezing the air from your lungs. Cords coil around your neck and arms, gripping, suffocating. Nausea and dizziness wash over you. Cold beads of sweat wet your forehead. Your vision narrows, then everything goes black.
You have just had a heart attack.
Although more people survive heart attacks today than did years ago, coronary heart disease is still the number-one killer in the United States. Addressing heart disease is also a research focus for Omolola ("Lola") Eniola-Adefeso, a chemical engineer at the University of Michigan in Ann Arbor.
Eniola-Adefeso (pronounced ah-DAYfeh- so), 32, is developing a way to deliver heart disease medicines right to the places they're needed-the blood vessels near the heart-and to do so without surgery.
Her strategy relies on an understanding of white blood cells, one of the body's first lines of defense against illness and infection.
"I am trying to create artificial white blood cells to deliver medicines," says Eniola-Adefeso. "These drug-filled carriers would navigate through the bloodstream and move into diseased tissues just like white cells do. Then they'd slowly release their drugs."
Growing Up Early
Eniola-Adefeso's special interest in heart disease stems in part from the death of her father five years ago from the condition. For as far back as Eniola-Adefeso can remember, he inspired and nurtured her interest in science through storytelling, especially about geography, his favorite topic. He also encouraged what Eniola-Adefeso calls her "profound, sometimes bizarre" questions about the world around her.
Eniola-Adefeso spent her childhood and early teen years with her family in Nigeria, where she describes the educational system as "fabulous, but only through high school." So, like her two older siblings, she traveled to the United States at the age of 16 to go to college.
The three siblings lived together in Maryland while their parents and two younger siblings remained in Nigeria.
"We grew up early," she remembers. "We were working, going to school and renting an apartment-it was an adventure!"
The experience shaped not only her own life path, but also the advice she gives to others.
Eniola-Adefeso says she took a "non-glamorous route" with her education. She started out in a community college before attending a four-year college, the University of Maryland, Baltimore County (UMBC).
"By taking a small school path, I learned you can find your way to anything if you have the desire for it and stay focused," she says.
Always intensely curious about the human body and driven by a desire to help people, Eniola-Adefeso was drawn to a career in medicine. That was until she took college biology, which drove her nuts.
"[College biology] didn't have enough numbers [for me]," she remembers.
Soon afterward, Eniola-Adefeso switched her major to chemical engineering. The move satisfied her desire for numerical explanations and harmonized her dual loves of chemistry and math.
"Chemical engineering gave me the tools to answer some of the questions I had growing up-things like 'Why does heat transfer?' and 'How do fluids move?'" she says.
Eniola-Adefeso got hooked on research when she was a junior in college. She was a member of the first class of students at UMBC to participate in the Minority Access to Research Careers (MARC) program (see "Making a MARC").
For Eniola-Adefeso, research had an instant appeal. "Being one of the very first people to observe something-it's very addictive," she says.
She enjoyed research so much that she decided to apply to graduate school. Knowing she could join a program that would pay her tuition and other expenses only made the choice more appealing.
"When you're 19 or 20, that's like, 'Wow! How cool!'" she says.
Right now, there are more than 200 different medicines for treating heart disease, and most of them are pills that need to be swallowed. But medicines that enter through the mouth have to navigate the digestive system to get into the bloodstream. Then they have to be ferried throughout the body. During this process, the drugs can leak into the liver, kidneys, fat, muscles and other organs.
Eventually, only a portion of the original dose makes it to the target tissue.
There are two major problems with this, Eniola-Adefeso says.
"Being one of the very first people to observe something-it's very addictive."
First, it's inefficient.
Second, it sometimes causes side effects. When drugs saturate the body, rather than just the problem area, they can have unintended consequences. For example, a notorious side effect of chemotherapy is hair loss. This occurs because cancer drugs affect not only the fast-dividing cancer cells, but also the fast-dividing cells in hair follicles.
In her quest to deliver the right amount of drug to the right place, Eniola-Adefeso is developing hollow, biodegradable plastic beads that can be filled with medicine. The beads, each about the size of a white blood cell and visible only under a microscope, are designed to be loaded into a syringe and injected into a vein.
"It would be just as easy as a blood draw," she says. The same strategy is already used by others to treat some cancers.
Eniola-Adefeso is working on customizing the beads so that they travel directly to their destination and release their contents in a controlled way over a specified length of time. The trick is to engineer the drug-filled particles to have the same navigational abilities as white blood cells, specifically the type called neutrophils.
"The beauty of the particles is that, just like white cells, they can find their way from anywhere we inject them to the diseased [blood] vessels," Eniola-Adefeso says.
Once at their destination, the beads latch onto the vessel wall. Then they slowly wear away, releasing medicine that helps heal the vessel.
Because neutrophils are generic defenders-they protect the body from all sorts of threats, including bacterial and viral infections, foreign particles and cancerous cells- Eniola-Adefeso's approach has applications far beyond heart disease. In theory, the method could help treat virtually any injury, infection or disease that neutrophils confront.
"Neutrophils are like the Coast Guard of the body," Eniola-Adefeso says.
"They always move around, defending our tissues just like the U.S. Coast Guard patrols the nation's shorelines."
When there is an infection or disease in the body, nearby blood vessels send out chemical distress signals. Like superheroes, neutrophils sense the signal and spring into action. They exchange their normal, spherical appearance for an aggressive, action-oriented shape. They manufacture sticky proteins and thrust them through their outer membrane as grappling hooks to connect with specialized molecules on the blood vessel surface.
Grabbing onto vessels slows neutrophils down, enabling them to pull out of the bloodstream. Then the cells slip through tiny holes in the vessel wall and enter the damaged tissue. They confront the threat by surrounding it, spraying it with poison and digesting it.
Eniola-Adefeso is designing her beads to accomplish the same job.
To understand the journey her drug carriers will take, Eniola-Adefeso is carefully studying the human circulatory system.
"Your blood vessels are like rivers," she says. "Some flow smoothly and slowly. Others are fast and turbulent."
In vessels exiting the heart, blood churns rapidly and pulses to the beat of the heart. As vessels get smaller and further from the heart, blood flow becomes smooth and constant, she explains.
Naturally, plastic beads that deliver medicine through a tranquil river blood supply require different properties than those heading for churning rapids.
Also, she adds, targeting different diseases means targeting different vessels.
"If we're going after cancer, we need to look at the sort of vessels that are affected by [cancer] rather than those affected by atherosclerosis," she says. Atherosclerosis, or thickening of the arteries, can begin in early adolescence and is a common cause of heart attacks and sudden death later in life.
In addition to designing drug carriers with particular vessels in mind, Eniola-Adefeso must correctly mimic the chemical connections between neutrophils and a blood vessel wall. To encourage the drug carriers to behave just like neutrophils, Eniola- Adefeso is trying to figure out how to cover them with the same sticky proteins that the white cells display during their superhero stunts.
It's not easy, she says, because the types and combinations of proteins on blood cells and vessel walls differ depending on the medical condition and location in the body.
If Eniola-Adefeso puts the wrong proteins onto these beads, they will misbehave-they could stick too tightly to a vessel wall and never migrate into damaged tissue. Or they might not stick well enough to resist being pulled off by the rush of passing blood.
Eniola-Adefeso is also focused on the material she uses to construct her beads. She aims to combine the properties of plastic and paper.
"Think about plastic grocery bags. They can live in a landfill for decades before they break down," she says. "In contrast, paper towels start breaking down as soon as they are exposed to water."
"Our bodies are mostly water," she continues, "so we need a material that does not dissolve in water, but that will slowly fall apart to let out the medicine inside."
It's the same theory as timed-release cold capsules. But instead of delivering drugs over a period of 12 or 24 hours, Eniola-Adefeso wants to deliver them at a desired rate for much longer.
"Based on the type of material we use, we can design particles to degrade in days, months or even years," she says.
This would greatly enhance the treatment of long-term conditions like heart disease, cancer or AIDS, to name just a few.
There are lots of materials to choose from, Eniola-Adefeso says. Her favorite is called PLGA, an abbreviation for a long chain made up of repeated units of two chemical building blocks. By altering the relative quantities of each chemical unit, she can control how slowly the material degrades.
Because PLGA is compatible with living tissue and its properties can be tailored, it is already used in a variety of biomedical devices including sutures, skin grafts and bone implants.
Eniola-Adefeso feels lucky that she found a job that allows her to use engineering principles to solve medical questions.
"Engineering is not limited to building pumps, bridges and equipment, but it's applicable to biology," she says, "When I finally realized that, I found my own way to be a doctor without being a medical doctor."
When she's not working in the lab or spending time with her husband and infant son, Eniola-Adefeso loves to cook.
"I do all sorts of cooking," she says, adding that she is partial to ethnic cuisines, especially Thai.
She is also particularly fond of seafood.
"Any which way I can make seafood, I go after it," she says. "I'm a pescetarian-a vegetarian who eats fish."
Eniola-Adefeso is known for her mackerel stew. "I didn't realize how good it was until my college roommates showed up with cans of fish and asked me to make it," she laughs.
She also collects Nancy Drew books and has about 250 of them, including the entire original series.
"I really identify with Nancy," Eniola- Adefeso says. "She is a smart, powerful character who does good things-solves crimes and brings the bad guys to justice-and has fun."
She also sees the books as a fictional reflection of her work.
"What I like best about research is that it allows me to solve mysteries," she says. "I'm a Nancy Drew at heart. In the lab, I'm always trying to solve mysteries."
"And the ultimate mystery," she says, pointing to herself, "is the human body."
Making a MARC
What's the best way to solve a complicated problem? Get a bunch of different people to work on it together.
Research has shown that the diverse ideas, approaches and experiences of a group produce a creative energy and breadth exceeding even that of an expert working on his or her own.
That concept is key to the National Institute of General Medical Sciences' Minority Access to Research Careers (MARC) program. The goal of this program is to increase the number of scientists from groups that are underrepresented in research careers and help the scientific workforce reflect the diversity of the U.S. population.
Lola Eniola-Adefeso launched her scientific career as a MARC student at the University of Maryland, Baltimore County. The program there provides two years of research experience, special courses and seminars and lots of academic coaching and career guidance. The program also gives funds for tuition, stipends for living expenses and travel to scientific meetings where students can present their research and meet other scientists.
A number of MARC students go on to Ph.D. programs where tuition, stipends and other fees are also paid by the government.
What made the biggest impression on Eniola-Adefeso was the required MARC course in bioethics. It dealt with issues like whether and when it is acceptable to conduct research on humans or animals.
"It was very useful," she says. "I would not have taken it if it wasn't required for the MARC program, but now it really shapes the way I think about research." —A.Z.M.