Straightforward tenacity.
Text: Irène Dietschi
In summer 2020, Scott McNeil assumed the first of two endowed professorships in nanopharmacy. Moving to Switzerland in the middle of the pandemic was an adventure, but the American scientist has lots of experience with new beginnings.
Toward the end of our meeting, Scott McNeil pulls his phone out of his pocket and shows me a photo. “This was me three years ago.” he says. “I was a bit of an adrenaline junkie.” The image on the screen shows a motorcyclist kitted out from head to toe, his powerful motorcycle leaning so deep into the curve that his heel is within a hair’s breadth of grazing the asphalt. McNeil laughs. “I’ve given all of that up now,” he says. After all, some of his friends have seriously injured themselves in motorcycle races, and he’ll be 60 in a couple of years. “I have a grandchild and responsibilities. I need to live a quieter life.”
Sitting in his office, McNeil is the picture of tranquility. In measured Midwestern tones, the tall and athletic 57-year-old explains why he wanted the job in Basel so badly: because the professorship would give him considerable freedom in his research; because it would allow him to compile basic data and hence to create something new in a “pioneering area of medicine”; and because he and his wife were incredibly excited at the prospect of living in Switzerland.
Tiny particels, great effect
A year ago, the University of Basel appointed McNeil to the first of two endowed professorships in nanopharmacy that are funded by the Vifor Pharma Group. Is that setup a problem? McNeil shakes his head. “I’m glad you asked that,” he says. Apparently, the university established a “firewall” to ensure that Vifor can’t interfere with his research.
McNeil has been working in the field of nanomedicine for almost 20 years and led a team of over 30 researchers in his most recent position in the USA. “A lot of nanomedicine is about drug delivery,” he explains. “In other words, tiny biological particles known as nanoparticles are used to smuggle specific active substances into the body in a targeted manner.”
Nanomedicine can do a lot more, however, than “just” transport things. By packing a molecule of an active substance into a nanoparticle, it’s possible to improve the pharmacokinetics. In other words, “a drug delivers its effects for longer and in a more targeted manner,” says McNeil. “At the same time, it’s possible to reduce unwanted side effects.”
Outsmart the system
McNeil explains this by referring to a group of diseases that he is particularly interested in, namely the lysosomal storage diseases (LSDs). These include some 45 inherited metabolic disorders in which a specific enzyme is missing, so that the cells fail to break down metabolic substances such as macromolecules, lipids or nucleic acids that are no longer needed. As a result, these substances accumulate and cause damage to organs, tissues and even the brain over time.
The standard treatment is to supply affected individuals with the missing enzyme by intravenous infusion, which may or may not be successful. “Our body is very good at recognizing foreign substances,” says McNeil, “and in many cases it identifies the supplied enzyme as ‘foreign.’ In other words, antibodies develop.” If that happens, the immune cells “remember” the enzyme and neutralize it. “Fifty to 90 percent of patients develop antibodies against this drug, which is actually meant to save their lives.” The treatment is therefore ineffective in most patients, and those people will ultimately die.
McNeil’s approach is now to equip the enzyme with a type of invisibility cloak made of a lipid called polyethylene glycol. “Although the immune cells circulating in the blood vessels are very good at identifying proteins and enzymes, they’re nowhere near as good at identifying lipids. You can imagine these as being like wet noodles thrashing around — the immune system can’t get a hold of them,” says the researcher.
By tweaking the properties of the nanolipid shell, the researchers can target the particles to different tissues of the body, causing them to accumulate in that environment and fuse with the membranes of cells they encounter there. In the process, they release the enzymes into the cell interior — that is, into the location where they are intended to act.
Starting from scratch again
McNeil has big plans for his work in Basel — both for LSDs and for the cancer treatments that he’s spent the last 15 years researching. After moving to Switzerland, however, the American researcher had to start “from scratch.”
The laboratory at the Pharmazentrum has only officially existed since the start of August 2021, and his research group currently consists of just two people: a postdoc and himself.
“It was a bit of an adventure for us in the early days,” says McNeil. He smiles as he recalls how he and his wife arrived in Switzerland in July 2020 with nowhere to stay, with their furniture stranded in Bremerhaven, with no knowledge of German, and in the middle of a pandemic. After three months, they found a house to rent in Aarau. They’re very happy there, he says, and the commuting time of just under 40 minutes to Basel is no problem at all.
Having grown up in a working-class family in Oregon, USA, McNeil is no stranger to the idea of working your way up from scratch. “I got into a lot of fights as a kid,” he says, adding that he made a lot of mistakes in those days — and learned from them. At the age of 20, he enlisted in the armed forces as a private, the lowest rank in the US Army. That’s also how he obtained a scholarship to go to college.
Gulf War and the laboratory
After studying chemistry in Oregon and earning a doctorate in cellular biology and anatomy, McNeil went on to work as a postdoc in Hawaii for three years. Alongside his studies, he pursued a career in the armed forces. Private McNeil soon rose to the rank of officer. He clocked up a total of 20 years’ service in the US Army, including a deployment to the Gulf War in 1991.
As an officer, he not only fought his way through rough, unfamiliar terrain and jumped out of countless planes with a parachute on his back for training purposes — “and for fun!” — but also gained experience of close combat. “The military, being in a leadership role — it’s characterbuilding,” he says. “My soldiers knew they could rely on me 100 percent.”
Although he left military life behind almost 20 years ago, he has retained the straightforwardness and tenacity he learned during his time in the army. Indeed, he’s brought these qualities with him to the world of academia and to his new role in Basel. “My main objective is to make my expertise in nanomedicine available to the next generation,” he says. “I want to ensure that basic research gains momentum and enjoys greater application in clinical practice.” For Scott McNeil, nanomedicine is the next big thing — and he believes that the time has come for it to be used in patients.
Scott McNeil ist seit has been Professor of Nanopharmaceutical and Regulatory Sciences at the University of Basel since 1 July, 2020. Prior to that, he led the Nanotechnology Characterization Laboratory in Frederick, Maryland (USA), a joint institution of the National Cancer Institute and the US Food and Drug Administration (FDA). McNeil is married and is not only a father of six children between the ages of 20 and 28 but also a grandfather of one.
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