Alan Rein and spouse Saraswati Sukumar (photo by Samuel Lopez)
In 1953, a teenaged Alan Rein read about what James Watson and Francis Crick famously called “the secret of life”—the double-helix structure of DNA, which had just been published in Nature. Captivated, Rein decided at that moment that he wanted to be a biochemist.
Rein’s biochemistry aspirations shifted to virology during college, leading him to a 60-year career in the field, the last 45 years of which were spent at NCI Frederick, studying how retroviruses like murine leukemia virus and HIV assemble themselves and infect host cells while somehow evading the immune response.
On November 1, 2024, friends and colleagues packed the Building 549 auditorium, with many more joining in remotely, to honor Rein, who is newly retired from his position as the head of the Retrovirus Assembly Section in the HIV Dynamics and Replication Program (HIV DRP).
Eric Freed, Ph.D., HIV DRP director, welcomed the crowd to “this celebration of Alan’s distinguished career,” a program featuring presentations from 10 virologists who worked with Rein over the years. Rein introduced each speaker personally.
Back to the Beginning
Rein said he began his graduate research training at the University of California, Berkeley, in a sea urchin embryology laboratory. “But there was this guy up the hill, Harry Rubin, who was studying these amazing viruses,” he said. “You just put the viruses on the cells, and a couple of days later, they are cancer cells. Isn’t that fantastic?”
The allure was irresistible, and Rein switched labs to study the Rous sarcoma virus, the first step on his career path in virology.
That was where he met Peter Vogt, Ph.D., now a professor emeritus at Scripps Research Institute and the senior virologist at the retirement symposium. Vogt was a postdoctoral fellow in Rubin’s lab when Rein arrived in the summer of 1962.
“Alan and I share early scientific roots,” Vogt said, speaking from his home in California. The two trained while working on the Rous sarcoma virus.
Vogt shared highlights of his own contributions to the field, including his discovery of some of the first oncogenes, and offered up advice for researchers just starting out on their scientific journeys: join an emerging, novel field; apply new concepts; generate new technologies; look at the work of other people in the field; ask for their reagents and share yours; and “Collaborate, collaborate, collaborate!”
Sharing Knowledge Builds Relationships
Perhaps fittingly, many of Vogt’s recommendations are characteristic of Rein’s career.
Françoise Barré-Sinoussi, Ph.D. emeritus professor at the Pasteur Institute, co-discoverer of HIV, and co-winner of the Nobel Prize for this achievement, nodded to that fact.
“[Alan] has always reminded us that science is not just about data, publications, and individual achievement, but about the people we work with and for, the relationships we build, about collaboration, and about sharing goals,” Barré-Sinoussi, joining the symposium virtually from her home in France, told the audience.
Barré-Sinoussi met Rein when she arrived at NCI Bethesda in the mid-1970s to do her postdoctoral studies on murine leukemia virus. Rein, who was working on tumor virus genetics there, mentored her.
After Barré-Sinoussi returned to France and isolated HIV in 1983, she and Rein continued to study retroviruses and remained friends and colleagues.
Mauricio Comas-Garcia, Ph.D., a virologist and professor at the Autonomous University of San Luis Potosi in Mexico, who also joined the symposium remotely, likewise thanked Rein for his mentorship and friendship. Comas-Garcia worked as a postdoctoral researcher in Rein’s lab from 2013 to 2018, studying how retroviral proteins interact with RNA in the process of retroviral packaging.
“Mauricio came from a community of physicists who had decided to study viruses,” said Rein by way of introduction, adding that Comas-Garcia “did beautiful work” in the lab.
“You taught me that words matter … that one should be very skeptical … and that it’s okay to say, ‘I don’t know,’” Garcia told Rein. “If I had to choose my career path again, I would for sure choose to work with you.”
Then there was Delphine Muriaux, Ph.D., director of the Montpelier Institute of Infectious Diseases in Montpelier, France, another former mentee who—clearly—remained friends with Rein.
“Will the speaker take her seat,” quipped Rein with a laugh as he introduced Muriaux, who was circulating through the audience, happily catching up with old friends.
Muriaux met Rein in 1995 when he served as a reviewer at her Ph.D. defense at the Pierre and Marie Curie University. A few years later, she came to NCI Frederick to complete her postdoctoral work with him, then stayed on as a researcher, learning to use many advanced imaging techniques to examine the interactions between viral proteins and host cell membranes.
Today, she runs a core imaging laboratory and studies HIV replication and assembly and how viruses interact with cell membranes. She told the audience that, before coming to Rein’s lab, she felt she knew “nothing of virology” so she was excited to work with Rein on murine leukemia virus, often taking advantage of late-evening scientific discussions.
“You’re the one who truly taught me virology,” Muriaux said to Rein.
Cold Spring Harbor Laboratory Connections
Jonathan Stoye, Ph.D., emeritus scientist at The Francis Crick Institute, was pleased to attend and congratulate Rein. “I haven’t been back to Frederick for some years,” said Stoye,” but it’s a place I remember with some pleasure.”
Stoye and Rein met at the Cold Spring Harbor Laboratory RNA Tumor Virus meeting (now called the Cold Spring Harbor Laboratory Retroviruses meeting) in 1979. Both were working on Fv1, a restriction factor protein that protects mice from infection by mouse retroviruses, hoping to use the information to develop ways to protect other hosts from retroviruses.
Rein told the audience that he eventually moved on to other projects, but Stoye “stuck with it,” going on to clone and characterize Fv1. Stoye presented some recent Fv1 findings to the audience in Frederick, including that Fv1 can protect against retrovirus types other than the mouse strains.
“It’s been a real privilege to be a part of this group who have tried to work out interesting biology,” Stoye said in closing. “Alan, it’s been a real pleasure!”
Karin Musier-Forsyth, Ph.D., Ohio Eminent Scholar in Biological Macromolecular Structure and professor of chemistry and biochemistry at The Ohio State University, also met Rein at the Cold Spring Harbor Laboratory Retroviruses meeting, in 1997.
A few years after meeting, “I decided I wanted to come [to NCI Frederick] and be immersed in retrovirology,” said Musier-Forsyth, who worked with Rein during a five-month sabbatical. “We’ve been talking ever since.”
Among her remarks, Musier-Forsyth shared some recent research with the audience on the preferential packaging of some types of RNA over others in HIV assembly, along with several anecdotes about Rein.
“Thank you, Alan, for being the center of our universe and of the retrovirus field, and congratulations!” she said.
Monica Roth, Ph.D., professor in the Robert Wood Johnson Medical School at Rutgers University, is “one of the few in our group who persisted in the study of murine leukemia virus,” said Rein, and “has made many seminal contributions to our understanding of murine leukemia virus biology.”
Roth is another faithful Retroviruses meeting attendee, and said she always looked forward to learning what Rein was working on every year.
But their collegiality wasn’t strictly business. The two corresponded frequently, and “a lot of our emails were about what movies we were watching,” said Roth, eliciting laughter from the audience. Rein’s 2015 recommendation, Ex Machina, stood out. “It’s a great movie. It’s AI before there was AI,” she said.
AI turned up for real in Roth’s life during the COVID-19 pandemic lockdowns a few years later. Since they could not work in the laboratory, her group started using an AI-based tool to predict different conformations of SLC proteins, which can play important roles in cells as drug transporters and viral receptors.
“Thank you to opening my eyes to AI with Ex Machina,” Roth said to Rein.
Rein’s Cold Spring Harbor Laboratory connections even came home to Frederick later in his career. John Coffin, Ph.D., American Cancer Society Research Professor and distinguished professor of molecular biology at Tufts Graduate School of Biomedical Sciences and former HIV DRP director, who studies the interactions between retroviruses and host cells, met Rein in the late 1970s at the Retroviruses meeting. The two forged a lasting friendship based on their mutual interest in retroviruses and Coffin’s “very smart ideas about HIV,” said Rein.
In 1997, Coffin was part of the team that established the HIV DRP, where Rein has worked ever since. Rein and Coffin have collaborated to advance the understanding about how HIV replicates, integrates into host genomes, and develops resistance to antiretroviral drugs.
Generosity Fosters Discovery
Stephen Goff, Ph.D., Higgins Professor of Microbiology and Immunology and of Biochemistry and Molecular Biophysics at Columbia University Medical Center, was a postdoctoral fellow in David Baltimore’s lab in 1979 when it came time to prepare for an NIH site visit. It turned out that Rein was a member of the site visit committee. Goff was tasked with presenting some data and was “terrified,” Goff told the audience. “This was me just starting into retroviruses … and I had read all of Alan’s papers and … here he was to review us!”
After that auspicious first meeting, Goff went on to study retroviral replication and often turned to Rein for advice and reagents.
Goff noted that Rein’s generosity with materials and time impacted all in the retroviral research community. “He’s reviewed papers of most everyone in the room,” said Goff, adding, “He’s always there [to help], and always sends materials to anyone who needs them.”
Stephen Hughes, Ph.D., NIH scientist emeritus in the HIV DRP, has studied retroviruses at NCI Frederick for nearly as long as Rein. As the symposium approached its close, he remarked that Rein’s work on retrovirology brought “a lot of positives” to his own work to understand the subtle differences between what it takes for the virus to assemble itself into a mature virus and what it takes to make it infectious.
“Alan’s experiments helped me understand how elegantly and carefully simple viruses manage their maturation and interactions with the host cell and how exquisitely appropriate their interactions with the host cells are,” said Hughes.
'A Complete Surprise'
Rein offered up heartfelt thanks to everyone involved in making this event happen, calling it “a complete surprise.” He further thanked HIV DRP event coordinators Anna Norris, Ph.D., and Terri Burdette.
Rein also recognized his longtime technicians, Jane Mirro and Demetria “Meech” Harvin, as well as protein expert Sid Datta, Ph.D. “I want everyone to recognize the importance of Sid’s work to the accomplishments of the lab for the past 20-plus years,” said Rein.
Members of Rein’s family were present to support him. Saraswati Sukumar, Ph.D., Barbara B. Rubenstein Professor of Oncology and professor of pathology at Johns Hopkins University School of Medicine and Rein’s spouse, said, “This is my first time listening to his colleagues give their personal accounts of how they know him and how he has impacted their life,” adding that the experience was “wonderful!”
The Paradox
Thinking back to early days, Rein mused, “here we are, all these decades later, still talking about what we now call retroviruses.”
“I think I became a virologist because [viruses] epitomize this paradox, this contradiction: On the one hand, they’re just a handful of molecules, but on the other hand, [the molecules] sure seem to act with a purpose. It was the fascination with this paradox that has driven me all these years, and I still find it fascinating,” he said.
It’s no surprise that retirement won’t mean the end of Rein’s scientific journey. He becomes a scientist emeritus at NCI Frederick this year, and he plans to use some of his newfound free time to try his hand at teaching virology.
He’ll also have more time for birdwatching, a favorite pastime. “Alan loves birds,” Hughes told the audience. “Walking with him and having him tell you which bird it is based on birdsong is an education.”
Editor’s note: To read well wishes from Rein’s friends and colleagues, please visit his Kudoboard.
To read about his research and accolades, please visit: Alan Rein, Ph.D. | Center for Cancer Research
To view the video recording of the event, please visit: NIH VideoCast - HIV DRP Conference Honoring Alan Rein's Career
Lisa Simpson is a technical editor in Scientific Publications, Graphics & Media (SPGM), where she edits corporate reports, client projects, and scientific manuscripts, and writes for the Poster newsletter. SPGM is the creative services department and hub for editing, illustration, graphic design, formatting and multimedia training and support for NCI Frederick and Frederick National Laboratory.
