Dr. Flossie Wong-Staal: Cracking the Code

Unraveling a scientific mystery to save countless lives.

Dr. Flossie Wong-Staal by Weilu Shen

Since the discovery of viruses around a century ago, scientists have made remarkable progress in the development of medicines, treatments, and vaccines. But what happens when a new disease emerges and people start getting sick? As we’ve seen in the wake of the COVID-19 pandemic, scientists have to work quickly to understand the new virus and identify ways to fight it. Each new discovery is a step forward to saving countless lives. This was the case for the research of virologist Flossie Wong-Staal. In the 1980s, when a new virus called Human Immunodeficiency Virus, or HIV, started devastating communities, Dr. Wong-Staal’s pioneering work on genetic sequencing was the key to understanding the new threat. Flossie Wong-Staal was able to solve the mystery of this new virus, and lay the groundwork for life-saving treatments.

"Thankfully, ... HIV is no longer the death sentence that it once was. New treatments rest on discoveries made by Flossie Wong-Staal, and are thanks to her dedication, passion, and ingenuity. By carefully unraveling the genes of the disease, Dr. Wong-Staal was instrumental in saving a countless numbers of lives."

Watch the video or continue reading the transcript below!


 

Flossie's Early Life and Education


When Flossie was born in Guangzhou, China in the 1940s, her name was Wong Yee Ching. She grew up in Hong Kong, and was an excellent student. Even though no woman in her family had ever attended college or even had a job before her, Wong’s family encouraged her to continue her studies.

Flossie wears a striped coat and stands in front of an decorative garden with a fountain and bridge in Hong Kong.
Flossie as a young woman

When she decided to go to university in America, she chose to change her name and asked her family for help picking a new one. They picked Flossie, after a recent tropical storm.


Flossie wears a striped sleeveless shirt and is looking into a microscope in a crowded research lab.
Flossie as a graduate student at UCLA

Flossie moved to California to study molecular biology, and eventually earned her PhD. Throughout the course of her career in the United States, she would go on to work at the National Cancer Institute, start the Center for AIDS research at UC San Diego, and found a company to develop new treatments for diseases.


 

The Viral Lifecycle

Retroviruses are a rare type of virus which carry RNA in their nuclei..


In the late 1970s, when Flossie’s career was just beginning, she began to focus on a rare type of virus called retroviruses.


Viruses are tiny, infectious germs, so small that they can’t be seen with regular microscopes. They’re incredibly simple organisms, made out of just a shell of protein that protects the virus’s genetic material.


A simplified diagram of a virus showing some viral RNA surrounded by a shell of protein and protein spikes protruding.
Viruses are very simple: a shell of protein surrounding some genetic material.





These genes, long strands of DNA or RNA, encode directions for how to make more viruses. But viruses can’t reproduce on their own.


They have to infect a host cell and hijack it so the cell builds more and more viruses, which eventually spread and infect more cells.




The kind of viruses that Dr. Wong-Staal studied-- retroviruses-- had a special way of hijacking the infected cells. Retroviruses insert their own genetic material into the genes of the host cell, permanently altering the DNA!

A simplified diagram showing the life cycle of a retrovirus. First the virus attaches to a host cell, then injects its RNA into the cell through endocyosis. The RNA alters the host cell's DNA through integration, and the host cell goes through transcription and translation of the new DNA. Finally the virus' genetic material breaks off from the host cell and detaches as a new virus in a process called assembly and release.
The RNA a retrovirus carries is inserted into a host cell, altering that cell's DNA. The host cell's altered DNA then replicates the virus' genetic material and creates more retroviruses.

 

Cracking the Code

"In her research, she became the first person ever to clone the genetic material of HIV. ... Dr. Wong-Staal and her team had cracked the code of the virus."

As Flossie was working on understanding these types of viruses, a mysterious new disease began spreading in the United States. It was called Acquired Immunodeficiency Syndrome, or AIDS. This disease was particularly devastating to gay communities, and a huge number of people suffered from the terrible and deadly virus. At first, no one understood why people were getting sick, but Dr. Wong-Staal was one of the key figures who identified that this new disease was actually caused by a retrovirus called HIV. But it wasn’t enough to just know which virus caused the illness. We needed to know how to fight it.

The deadly virus, HIV, is shown here in green. The retroviruses will soon detach from the host cell once assembly of the virus is complete.

So Flossie Wong-Staal started working to learn as much as she could about this new virus. To do so, she wanted to isolate its blueprint- the genetic material that the virus uses to replicate itself. In her research, she became the first person ever to clone the genetic material of HIV, pinpointing the important strands of RNA from blood and tissue samples.


With the ability to clone the virus’s genes, it was now possible to make many copies of it and start probing different sections with experiments. Now we could start to understand how the virus works and, more importantly, look for its weaknesses. Dr. Wong-Staal and her team had cracked the code of the virus.


Dr. Wong-Staal wears a white lab coat and looks at the camera. Her lab is in the background of the photo.
Dr. Flossie Wong-Staal in her lab. Photo by Bill Branson and courtesy of the National Cancer Institute.

The work that Dr. Wong-Staal did to clone HIV revealed one of the reasons that the disease was so deadly- it was very genetically diverse, which made it hard for the body to identify it and fight it off. It also made treatments very difficult. If a virus always looks and acts the same way, we can more easily use vaccines to teach our bodies to fight them off. But when there are many different versions of the same virus, we have to use other methods to fight it.




To develop these methods, Flossie Wong-Staal was able to map out the full genetic sequence of HIV. With this map, scientists were able to understand the role of each part of the sequence and develop targeted treatments to disrupt the virus’s spread. This genetic map was also essential for the development of blood tests to identify the disease early, so we could stop spread and start treatment as soon as possible.

 

Saving Countless Lives


Since the start of the HIV epidemic, almost a million lives have been lost to the incurable disease. Those affected most by the terrible virus have disproportionately been gay, Black, and Latino communities. Thankfully, the tide is turning due to huge scientific progress, and HIV is no longer the death sentence that it once was. These new treatments rest on discoveries made by Flossie Wong-Staal, and are thanks to her dedication, passion, and ingenuity. By carefully unraveling the genes of the disease, Dr. Wong-Staal was instrumental in saving countless numbers of lives.

Dr. Flossie Wong-Staal in 2019

Credits:

Most images are courtesy of Dr. Flossie Wong-Staal's memorial website.

Written by Caroline Martin

Edited by Ella King

Illustrations and portrait by Weilu Shen


Primary sources and additional reading:

Flossie Wong-Staal, Who Unlocked Mystery of H.I.V., Dies at 73” from the New York Times

Dr. Flossie Wong-Staal Oral History 1997” from the National Institutes of Health

Introduction to Viruses from Let's Talk Science

DNA Sequencing from Khan Academy

 

Learn more about Dr. Flossie Wong-Staal's research with these activities!


Play (45-60 minutes): Create a larger-than-life, edible model of DNA.


Observe (45-60 minutes): DNA is the genetic blueprint for a cell. Extract a strawberry's DNA in your own kitchen!


Deepen (30 minutes): See if you can crack the code to understand how DNA leads to protein production.


Interact (30-45 minutes): How does a genetic sequence lead to proteins? Use the gene expression essentials simulator to find out.