Philip Felgner almost chose Spanish classical guitar over science. The world should be glad he didn’t
By Teri Sforza
Back when Philip Felgner was a kid — in a Michigan farming town in the 1950s — science was cool. Walt Disney TV specials focused on the wonders of space exploration, “Watch Mr. Wizard” featured fun experiments, Henry Ford’s Greenfield Village celebrated American resourcefulness and ingenuity, and Sputnik spurred a nation to action.
The conviction that science can and should make lives better always ran deep in Felgner, and his painstaking work over the past 35 years laid the groundwork for the mRNA vaccines that are so startlingly effective against COVID-19. The UC Irvine professor has seen his work take off in ways he never quite expected, and soon he’ll be rubbing elbows with Spain’s King Felipe and Queen Letizia as they honor him — alongside the German creators of the Pfizer/BioNTech vaccine and four others — for outstanding advances in technical and scientific research.
Felgner, director of UCI’s Vaccine Research and Development Center and Protein Microarray Laboratory and Training Facility, has won Spain’s Princess of Asturias Award in recognition of his contributions. The award includes a $60,000 prize and a grand reception in Oviedo in October, where the whole town comes out to celebrate.
While not quite as well-known as the Nobels — Felgner had to do a bit of research himself — the Asturias prizes are awarded in eight categories each year, including for the arts, social sciences, literature and sports as well as science. They were created in 1980 and are bestowed by the Princess of Asturias Foundation, a private nonprofit.
“It’s just going to be a real thrill,” said Felgner, also a professor in residence of physiology and biophysics at UCI. “What a gift. I don’t have to keep telling the lab members what a great job they’re doing — the Spanish are telling them, too. It’s fantastic.”
Those who marvel at how fast COVID-19 vaccines were developed don’t understand that it all really began 35 years ago. Felgner’s work paved the way.
After getting his Ph.D. in biochemistry from Michigan State University in 1978, he did postdoctoral work at a biophysics lab at the University of Virginia and delved into the study of liposomes — tiny round membranes made of fat that could encase a drug, and then carry that drug into cells.
“It was the biotechnology heyday and entrepreneurs were so interested in these liposomes for pharmaceutical applications,” he said. “That was a beginning for scientists understanding what they actually were and how they could be used.”
Soon he joined Syntex Research as a staff scientist. There, on a beautiful campus next to Stanford University, he developed lipofection technology — using a lipid nanoparticle to deliver DNA to cells. It was a tremendous breakthrough — and a surprisingly simple matter of attraction.
“We could improve the delivery of all kinds of drugs with these positively charged liposomes because they’re like magnets, and they attach themselves to cells because all of our cells are negatively charged,” he said. “So if you want to deliver a drug to a cell, put it in a positively charged liposome. We did a lot of experiments like that.”
It was the 1980s, and the promise of gene therapy — using genetic material to treat or cure disease — had become a holy grail. If liposomes were so good at carrying drugs into cells, might they also be good at carrying genes into cells?
Yes. Felgner put DNA inside those liposomes and, sure enough, the cells began to produce the protein that was encoded by the gene. He was eager to take the next step — gene therapy experiments in animals — and he’ll never forget what his bosses said: “Gene therapy will be something for the year 2020.” It was only 1987, and the company had to work on products that would help the bottom line in some foreseeable future.
He soon left for San Diego and became director of product development and founder of Vical Inc. Working with former researchers from UC San Diego, they were able to deliver DNA into mice, and the mice made the new proteins. “The gene was expressed,” he said with some wonder. “All these things, they worked the first time.”
Then came another big surprise. “Naked DNA,” without nanoparticle, could also be expressed in mouse muscle tissue. “That was so wacky,” he said. “If you put DNA on cultured cells nothing happens. But in an animal, you could inject DNA in and get expression. That’s because, when you inject into muscle, it makes transient breaks in the membrane that allow the DNA to get in.”
Felgner’s findings led to the development of DNA vaccines, and Vical became “the naked DNA vaccine company.” It was in business for about 30 years when it merged with Brickell Biotech in 2019. Companies like BioNTec and Moderna built on this work to create the COVID-19 vaccines, using single-stranded RNA rather than double-stranded DNA.
“Our Awards give us hope, because they constitute a recognition of those who, with dedication, work tirelessly to jointly achieve the advancement and well-being of the whole of society,” said The Princess of Asturias in a statement.
Felgner came to Irvine in 2002. Here he has studied the proteome — the entire complement of proteins that is, or can be, expressed by a cell, tissue, or infectious microorganism — and has begun to manufacture the first microarray of the human proteome. That’s a lab tool used to detect antibodies against thousands of individual proteins at the same time.
Growing up in a farming community made him a very practical scientist, he said. “In farming, you have to make things other people can use right away, so I think that came through in a lot of what we do in the lab. We learn things, but we want to use the products of what we learn,” he said.
He has authored more than 250 articles that have been cited more than 38,000 times, and holds 50 U.S. patents. He loves playing Spanish classical guitar, and was torn in his youth about whether to pursue music or science. The world may be grateful that he chose the latter.
Today’s COVID-19 vaccines are the culmination of decades of work by hundreds of scientists and numerous biotechnology companies, fueled by the investment of billions of public and private dollars.
“For 35 years we prepared the science to react and have a successful outcome,” Felgner said. “We’ll continue to work on vaccines here — it’s great to see the vaccine science developing and there’s plenty to do. More targets, more work to be done to understand how they’re working as well as they are, to understand and reduce side effects and make them even safer than they are right now. We’re going to learn a lot more about the immune system and be even better prepared for the next time.”