RALEIGH, N.C. — Last summer, a young, unheralded scientist named Zhen Gu unveiled a “smart” insulin patch, yet another in a string of biomedical creations that could be traced back to his early childhood. This one stood out: Headlines hailed it as the beginning of the end of painful injections for diabetes.
The biomedical engineer’s inbox was flooded with emails from patients eager to try out the thumbnail-sized device, covered with more than 100 tiny needles like a miniature bed of nails. “Thanks so much for your interest and encouragement!” Gu would patiently respond to each, trying to let them down easy. “We are currently planning to do large animal tests … if successful, we will move to clinical trials. We will update you!”
Shortly thereafter, MIT Technology Review recognized Gu as one of the world’s top 35 innovators under 35, putting him in the company of previous winners Mark Zuckerberg, Sergey Brin, and Larry Page. “I would not hesitate to say that Zhen is one of the most creative people with whom I have ever worked,” said renowned MIT inventor Bob Langer, who nominated his protégé for the honor. “Zhen never seems to run out of ideas.”
The range of Gu’s intellectual curiosity was clear from the moment I walked into his office on North Carolina State University’s sprawling campus in Raleigh. Neat stacks of papers covered his desk and were crammed into every vertical inch of the bookcase in the corner. Framed journal covers adorned another wall, displaying the most impressive of his 75 or so scientific publications.
Gu pointed to one picture that — to my untrained eye — evoked a ream of wax paper dotted with old-fashioned, rainbow-colored candy buttons. He explained that the illustration depicted his graduate work at the University of California, Los Angeles, on a technique for printing molecules into orderly arrays for sensors or diagnostic tools. He moved on to another frame, this one showing the tip of a hypodermic needle squirting tiny green and red droplets: microscopic particles Gu created during his postdoctoral fellowship at the Massachusetts Institute of Technology to treat diabetics for days at a time.
“People often ask why I don’t find one approach and stick with it. But I think it is better to keep trying new strategies, to develop new ways of solving problems. Why focus on one when you could do many?” said Gu, a solidly built man with an easy smile, closely cropped jet black hair, and rectangular, semi-rimless glasses.
Later, he told me that relieving the suffering of diabetics — though admirable — was never his aim; rather, he has always been drawn to cancer, tugged along by the marionette strings of the father he wished he knew.
“I saw him, but I don’t remember him,” said Gu. “I heard stories, but they aren’t my memories. Still, he affected me a lot.”
Great expectations from birth
Months before Zhen Gu was born, his father, a chemist just starting his career at a metallurgical plant, was diagnosed with an aggressive form of leukemia. The cancer took hold in his marrow and quickly spread throughout his bloodstream.
Family urged Gu’s mother to get an abortion, arguing that they were too poor and it would be too hard for her to raise a child on her own. But she adamantly refused because she believed her child might one day grow up to cure the disease that killed his father. She named the baby Zhen, Chinese for “achieve the aim.”
Gu’s English is usually pretty easy to follow, but when he talks about his father’s passing, his sentences suddenly lose nouns and verbs. Gu explained that because of his father, he has consciously avoided anything having to do with death or dying; the words obituary, headstone, cemetery never became part of his lexicon.
Even though he can’t say the word obituary, he has heard the story enough times that he can tell me what his father’s said. In it, his father declared his wishes to donate his remains to a local research facility, though traditional Chinese beliefs hold that the dead must be buried intact to be reincarnated. It was the final act of a man who had been stripped of his chance to make any other contribution to society.
Despite its tragic start, Gu’s childhood was happy. He entertained himself with a chemistry set in his mother’s apartment behind the grocery store where she worked. In the summers, he stayed with his grandmother in the country, where he picked locust casings off tree trunks and snatched fireflies at dusk. His grandmother had diabetes, and he often played with her syringes, shooting sprays of water out of the tips like water guns, or disassembling them to create newfangled contraptions.
One time, Gu fashioned an old syringe into a toothpaste dispenser that could deposit the perfect amount of toothpaste onto his toothbrush, without any goopy residue. He wishes he had patented the invention, several versions of which are now on the internet. “I learned my lesson,” he said. He has since filed 29 other patents.
Before Gu took the National College Entrance Exam — a high-stakes test that determines the fate of youth in China — he recalled everyone telling him how gifted his father had been in chemistry. Gu performed poorly on the test. Then he entered a science competition and his invention for a safer IV drip device won first prize, adding 20 points to his score. That changed everything, allowing him to attend Nanjing University (the Yale of China), then UCLA and MIT, where he landed a coveted position under Langer.
Nanodaisies and DNA cocoons
Like Gu, Langer has a habit of displaying his accomplishments on the walls of his light-filled office at MIT. Only in his case, the shiny frames are arranged so tightly from wall to wall and floor to ceiling that it is difficult to tell if there is wallpaper or paint underneath. I told Langer how Gu had his own, albeit smaller, “wall of fame.” Langer, regarded by many as the most cited engineer in history, simply smiled and noted that he had “been at it” much longer than Gu.
Together, they designed the first injectable insulin-containing particles — each 1,000 times smaller than a grain of sand — that could control blood sugar levels for as long as 10 days.
The development laid the groundwork for Gu’s current research on the smart patch, which contains nano-sized bubbles of insulin and glucose-sensing enzymes that expel their contents whenever sugar levels rise dangerously high.
Gu draws inspiration from nature, building upon his memories of collecting flowers and insects in his grandmother’s yard as a child. The approach is known as biomimetics, an emerging field that adapts designs from the natural world to address modern problems. Researchers have created search-and-rescue robots that reflect the agility of cockroaches or the behavior of a flock of birds. They have also designed naturally air-conditioned buildings based on the remarkable temperature control of termite mounds.
“Nature indeed has the most elegant and effective design — always with the lowest energy to achieve the best performance,” said Gu.
He has turned to bio-inspired design to tackle the thorny issue of cancer-drug delivery. Cancer drugs traditionally are given to patients through the bloodstream, where they encounter healthy cells and tissues before a small portion of the original dose reaches the tumor. As a result, patients end up taking these toxic medicines in large doses, and the side effects can be deadly. Gu is engineering tiny machines that can precisely deliver medicines to tumor cells, leaving normal cells relatively unscathed.
One of his most evocative creations is the nanodaisy, a flower-shaped drug mule that is invisible to the naked eye, and even too small be captured by a conventional light microscope. Gu based his plan for building this nanocarrier on the way nature builds proteins. These chains of amino acids naturally arrange themselves into a variety of different shapes based on their chemical personalities — whether they have a positive or negative electrical charge, whether they like water or fear it.
To create his nanodaisy, Gu concocted a mixture of the anticancer drugs camptothecin and doxorubicin and a polymer called polyethylene glycol, or PEG, that is often used in medicines. The water-fearing cancer drugs assembled into a tight little core on the inside — much like the coalescing of oil droplets in water — surrounded by strands of water-loving PEG that looped in and out like an array of petals.
Gu has also wrapped drugs in cocoons made of DNA and encased them in orbs of liquid metal. He has even drawn inspiration from our own bodies by cloaking cancer drugs in the membranes of platelets, the cells that keep us from bleeding to death from a cut or scrape.
“Zhen Gu is one of the most innovative researchers in nanomedicine today,” said Kam Leong, a biomedical engineer at Columbia University who has been following Gu’s research for years.
With all the advances in Gu’s laboratory and others, cancer nanotechnology remains largely experimental. Researchers have manipulated materials smaller than a single cell to detect and treat cancer, in Petri dishes and animal models. Only a few of these inventions have made their way into patients, such as the Gliadel wafer, a treatment for brain tumors based on a technology that Langer spent almost 28 years developing.
Gu recently re-envisioned his smart insulin patch as a treatment for melanoma, the most dangerous form of skin cancer. Instead of insulin, each microneedle is packed with anti-PD-1 antibodies, the same kind of molecules used to treat President Jimmy Carter’s cancer. These immunotherapy drugs work by unleashing the immune system to kill cancer cells, but because they are usually injected into the bloodstream, they can trigger autoimmune disorders. The patch avoids that problem by delivering the therapy locally to skin tumors.
In early studies, more than 40 percent of rodents treated with the microneedle patch survived and had no detectable remaining melanoma, compared to no survival in those left untreated. Adding another immunotherapy molecule called anti-CTLA-4 bumped this survival rate up to 70 percent. Gu is now testing the approach in larger-animal models.
Gu is four years into his academic post and works 12-hour days, though now that he is a father himself he tries to get home earlier to be with his 17-month old son. In May, the joint department in biomedical engineering at N.C. State and the University of North Carolina at Chapel Hill awarded the 35-year-old Gu tenure, an achievement that takes most scientists six or seven years.
“Zhen has about a bazillion papers now, and he creates the coolest technologies,” said Nancy Allbritton, the department chair and Gu’s boss. “I don’t know how he does it.”
Last October, Gu launched a startup to commercialize the diabetes and cancer technologies he has developed in the laboratory. He calls the company Zenomics, a nod to his given name Zhen and the great expectations that come with it.
