The World Journal, a Chinese-language newspaper with worldwide circulation, recently named Hopkins biology professor Ru-Chih C. Huang as one of "The Most Notable 100 North American Chinese of the Century."
Also included on the list, which was subdivided into categories like politics, architecture, law and business, were AIDS researcher and 1996 Time Man of the Year David Ho, author Amy Tan, newscaster Connie Chung, architect I.M. Pei and five Nobel laureates in physics and chemistry.
"When they called me and asked me for a picture, I was in the middle of something, and I asked them, 'Can you call back later?'" Huang admits with an embarrassed laugh. The Journal ran her profile without a picture.
Even if she weren't in the middle of a busy day in the lab, fame has never one of Huang's primary objectives as a scientist. For years, she combined her career in science with "devoted and successful" efforts to raise her children, Suber and Suzanne, with School of Public Health Professor Pien-Chien Huang.
Over the decades, though, Huang has been the gradual recipient of growing acknowledgment for doing something outstanding: helping to redirect genetic and biochemical research to a new and very productive angle of attack that is still in use.
Huang set a revolution in motion in 1962, just a few months after her move to the United States from China, when she joined the laboratory of the late James Bonner, a professor at Caltech. Huang and Bonner developed a new way to study how cells manage genetic information and convert selected gene signals to instructions for the synthesis of proteins required to build specialized tissues.
Genes contain instructions for building the proteins that make up cells and tissues, and the plan for the whole body. To make proteins based on the instructions embodied in the DNA in the chromosomes, the cell reads chromosome-encoded information into RNA, a compound used as a messenger that begins the process of producing specific proteins. This process of reading information is called transcription.
Scientists had determined the structure of DNA, the material that contains genes, little more than a decade earlier. They knew that almost every cell contained copies of all the genes typical of that organism; however, they also knew that a given cell type never used all of those genes in its lifetime. So how did the cell pick and choose which genes to transcribe at a given period in its life?
"Before Ru-Chih's work, scientists were looking at the question of gene transcription at the level of the whole cell," says Hopkins biology professor E.N. Moudrianakis. "Ru-Chih defined the process of studying transcription in a test tube in a way that would let us more directly and more effectively link the process of regulation of gene transcription with specific effectors, compounds that help initiate or halt transcription."
Huang and Bonner developed methods to purify rapidly and efficiently large quantities of the genetic material that make up chromosomes, a complex of DNA with special proteins called histones.
"This DNA-protein complex is known as chromatin, and it represents a native or faithful soluble state of the substance of chromosomes," Moudriankis says. "Huang and Bonner's highly efficient yet simple methods of purifying and isolating large amounts of chromatin from a variety of plant and animal sources opened this field to many and made this area of research popular."
Next, they placed this chromatin material in a test tube with RNA polymerase, the "reader" protein that takes information from DNA. In this system they could now measure the RNA produced and also examine how specific compounds, partnered with DNA in chromatin, effected transcription. Histones, they found, inhibited transcription.
"Being ahead of time ought to give you an advantage," Huang says. "What I learned was that it can sometimes give you a disadvantage--you have to wait a while to see the fruits of your work."
At least one person caught a hint of the start of something great. Prolific science writer and science-fiction author Isaac Asimov described the work of Huang and Bonner in a book called The Genetic Code. Huang and Bonner appear on page 180, the next-to-last page of the book, in a chapter called "The Future." The original publication date for The Genetic Code was 1962, the same year as Huang and Bonner's groundbreaking paper. Huang keeps a well-preserved copy.
"Dr. Huang was a true pioneer in what is now an ever-growing field," says Victor Corces, chairman of the Hopkins Biology Department. "She made it possible for many scientists later to refine our understanding of the central process of transcription."
In 1978, Huang and Bonner's 1962 paper was selected for "Citation Classics," a series of descriptions of influential papers often cited by scientists.
Huang became in 1965 the first female tenure-track professor in the Biology Department at Hopkins. Her research experience and expertise inspired a young Moudrianakis, then finishing up his graduate work at Hopkins, to begin a career studying histones and chromatin. Corces also studies aspects of chromatin. Together, the three researchers and their labs make Hopkins a leader in chromatin research.
Do all histones inhibit transcription? Are some histones more effective inhibitors than others? What, if any, other molecules have modulating effects on transcription? These pioneering questions were the first focus of Huang's research after arriving at Hopkins and are still central in the quest to understand tissue-specific gene expression.
Corces notes that Huang's contributions to the field of transcription picked up even greater pace at Hopkins. With the aid of many gifted graduate students, the Huang lab was the first to transcribe, purify and then translate in vitro the genetic message for the protein immunoglobin, a critical molecule of the immune system.
"That paper, published in Nature, represented a landmark event in the area of in vitro expression of genetic activity," Corces says.
In the 1980s, Huang began to examine the potential for direct impact of her research on clinical treatment. She found the problem of viral infection particularly interesting. To reproduce, retroviruses have to insert their genetic material into a cell's chromatin and trick the cell to transcribe the viral genetic material as if it were theirs. This leads to the production of new copies of the virus, which spread out, seek new host cells and start the process all over again.
Four years ago, Huang and postdoctoral fellow John Gnabre were in the news for identifying a potential antiviral drug from extracts of the creosote bush, a plant used as a remedy by native people in the Southwest.
They discovered a compound that could block a key stage in the transcription of the human immunodeficiency virus, which causes AIDS. Other viruses under study are the herpes simplex virus and the human papilloma virus, which has been linked to oral and uterine cancers.
Currently, several new related compounds have been chemically synthesized and are being used in experiments aimed at blocking transcription and reproduction of several viruses and of cancer cells. Clinical trials are planned in this country with some of these compounds.
"In what has been a brilliant scientific career with no sign of slowing down after almost 40 years, Dr Huang has many times crossed the line of innovation and has successfully tackled many obstacles," Corces says. "She is admired not only as a successful researcher but as a warm and caring human being who has served as an inspiration and a role model to many young women in science."