Alan Rein, Ph.D. (left), with his mentor, the former director of Cold Spring Harbor Laboratory, Dr. Arthur Chovnick (right). The laboratory, located in Long Island, New York, has shaped contemporary biomedical research and education with programs focused on a range of scientific and biological research topics. This picture was taken during Rein’s first time at the institute during the summer of 1961, which he spent studying Drosophila genetics.
Alan Rein, Ph.D., has been at the NCI for almost five decades researching viral assembly, particularly in human and murine (mouse) retroviruses. A known expert in the field, he studies molecular mechanisms of retroviral replication and pathogenesis, including the human immunodeficiency virus (HIV). Now, the senior investigator in the HIV Dynamics and Replication Program and the head of the Retrovirus Assembly Section has announced his retirement.
Rein earned his Ph.D. at the University of California, Berkeley in the lab of Dr. Harry Rubin. He was fascinated by the paradox that the behavior of molecules seemed to be governed by a sense of purpose, despite the fact that it was impossible for this to be the case.
He started his degree studying sea urchin embryology, but was intrigued by Rubin’s work studying chicken viruses that would come to be called retroviruses and switched to his lab. Rein continued studying retroviruses throughout the rest of his career.
After completing his Ph.D., Rein served as an American Cancer Society Postdoctoral Fellow at Massachusetts Institute of Technology under Dr. Sheldon Penman, where he studied RNA metabolism in mammalian cells. He then worked as a scientist with Litton Bionetics in Kensington, Maryland, where he studied the biology of mouse retroviruses under Dr. Robert Bassin — in particular, he studied how host cells defend themselves against infection using proteins called restriction factors.
In 1976, Rein joined the Laboratory of Tumor Virus Genetics at NCI. He then moved to the Molecular Biology of Retroviruses Section of the Laboratory of Molecular Virology and Carcinogenesis at NCI Frederick as a senior research scientist. Later, he worked as head of the Retroviral Genetics section in the program headed by Dr. George Vande Woude. Together with Dr. John Coffin, Vande Woude created the HIV Dynamics and Replication Program (DRP) at CCR, which is the program Rein has worked in since.
In the Q&A that follows, Rein reflects on his successful career and the future of the retroviral replication and pathogenesis field.
What advice do you have for future generations of cancer researchers?
Remember that the field is going to change. Research is now answering questions and, within the next few years, those questions will have been answered, and new questions will be being asked. So, you have to be ready to answer not only the questions that are being asked today, but the questions that will arise tomorrow. I have been doing this for 60 years, and the topics that we study today could not have been imagined decades ago.
For this reason, when I meet someone who is starting graduate school, I always tell them, pay attention to your coursework. Don't be in such a hurry to go into the lab where they're answering today's questions. You need the foundation of knowledge to understand the questions that are going to come up next year and the year after that.
What scientific achievements are you most proud of?
My career is a little unusual in that it spans both the biology of viruses and the molecular biology or biophysics of viruses. In the last 20-plus years, a lot of the research in the lab has been biophysical analysis of the building blocks of HIV virus particles, the Gag protein.
Here is a problem I have studied extensively: when HIV particles are assembled in the cell, the assembling viral proteins have to pick up the viral RNA to be their cargo, but they are swimming in a sea of thousands of other RNAs in the cell. How do they pick out the right RNA? This is a challenging problem. I still don't know the answer.
What do you see as some of the most important work NCI has done?
At the end of the 1970s and into the 1980s, people started basically losing their immune systems and dying of infections that are normally mild or harmless to most. These people were largely gay men, but also intravenous drug abusers and those who had had blood transfusions or who took blood products due to hemophilia.
It was terrifying. Was it caused by a virus? Was it caused by a bacterium? Was it caused by some kind of pollutant in the atmosphere? Nobody knew. In 1983, the French isolated the virus, and it was a retrovirus — HIV.
By 1995, highly active antiretroviral therapy (HAART) was introduced, and the death rate due to HIV/AIDS in the U.S. dropped like a stone because of the development of this therapy. It seemed like a miracle, only 12 years between isolating a virus and being able to treat it. I want to insist, above all, it was possible to develop that therapy so efficiently because of the prior work on mouse viruses and chicken viruses at the NIH and elsewhere. We knew what a retrovirus was; we knew a retrovirus was going to have enzymes called reverse transcriptase and protease. We could look for inhibitors of reverse transcriptase and inhibitors of this protease. That's how therapy was developed in only 12 years.
So, this is an argument for the importance of basic research. It was incredibly valuable that this prior work had been done on mouse and chicken viruses. Things come out of left field that you cannot anticipate, and science helps you to be prepared for the unexpected. And that is an important lesson.
What are you most looking forward to during your retirement?
I am hoping to do some teaching about viruses when I am no longer employed to do research. I have grandchildren within a couple of hours drive, although they’re flying the coop themselves. I also like to travel and read.
Dr. Alan Rein will retire from CCR on January 1, 2025, but will remain as an NCI Scientist Emeritus.