Spotlight on

Dr. Stephen Hughes

Spotlight Archive

"In science, there is the magic of the epiphany, and that is wonderful."

So explains Dr. Stephen Hughes, chief of the Retroviral Replication Laboratory and Vector Design and Replication Section in the HIV Drug Resistance Program. As head of one of the 20 research groups within the National Cancer Institute studying HIV, Dr. Hughes describes the urgency in the research that he and his collaborators are doing. There is hope, fueled by statistics that show research has led to the development of AIDS therapies that work in many cases. But the hunt goes on as he and his colleagues work to stem additional deaths caused by the virus.

At present about three and half million deaths worldwide occur per year as a result of HIV/AIDS. This translates to about seven deaths per minute. Dr. Hughes notes that although newly developed therapies have improved the life expectancy of people who have access to therapy, the problem is still growing, particularly in developing countries where there is little access to drugs or therapy.  It's not just a problem of quality of care, he says, but it's because the HIV virus develops resistance to the drugs. "We need to make therapy better and less expensive, and that means we need to develop better drugs and a better health care infrastructure that will deliver therapy in a more cost-effective manner," Dr. Hughes states.

Effective therapy in the fight against HIV has been developed through use of combinations of antiviral drugs. If a combination of three drugs is given, many patients can be kept alive. Although there are side effects, patients live who would otherwise die. So far, many of the problems have stemmed from development of resistance to the available drug therapies. Researchers have found that giving a patient high doses of a combination of drugs can succeed if the patient carefully follows a strict schedule for taking the drugs. 

"You can't give a patient one drug. Resistance will occur, and the usefulness of that drug will be lost.  If three drugs are given, this is often enough to prevent viral replication and the emergence of drug resistance. What we want is for the drugs to completely block the replication of virus. So the patient is given as much of the drugs as he or she can reasonably tolerate and the drugs must be taken faithfully in compliance with dosage instructions. We want drugs that are long acting and strong. In the United States, about 60% of those newly infected with HIV will succeed when put on the three-drug therapy," concludes Dr. Hughes.

"But, we are not in the business of developing drugs," explains Dr. Hughes. "What we are doing, is trying to come to grips with the mechanisms of resistance to the drugs we have. And, we want to come up with strategies on how to build better drugs. We work in collaboration with other labs in an effort to get our information [both chemical and structural data] out into the public domain just as quickly as we can. As of now, though, we're not able to tell people exactly what drugs they should build. What we are able to do is to tell people what drugs not to build."

In explaining why HIV research is an integral part of the National Cancer Institute, Dr. Hughes points to similarities in the research performed in cancer and HIV labs. "In both instances," he says, "we are trying to get rid of a disease, without the disease developing resistance to the drugs we are using. That's one reason it is hard to treat cancer, and why it is hard to defeat the HIV virus. We are trying to develop better methods that will lead to the discovery of more effective drugs to fight HIV and we hope what we learn will apply to other diseases, like cancer.  Working on HIV gives us an advantage in testing drugs and drug therapies. In HIV, resistance develops rapidly. You get told right away if an experimental system is going to work or if resistance will develop, and it keeps you from wasting precious time. This should lead to useful information in developing better therapies for other diseases, including cancer," he continues.

"There is a need for new and better drugs. And there is a need for the development of the  next generation of drugs as quickly as possible," Dr. Hughes explains. "Modern science is collaborative. I don't work on this alone. There is an extensive list of people who work together, both here in the lab and in a number of other laboratories. For example, our collaboration with the laboratory of Dr. Edward Arnold has been an essential part of this work. Because no one individual has the expertise to do all the work well, each shares his or her expertise and out of that good things can come," he said.

When one meets Dr. Stephen Hughes for the first time, one thinks of a football or basketball player, noting immediately the impressive 6'5" frame. However, says the scientist, he has always been interested in biology and can't remember a time he wanted to do something else. "My mother was a scientist," he explains. "She went back to school for her Ph.D. when she was 41 or 42 years old. I remember talking science with her and I know she was the major influence in my life. When I went to college and grad school [he received his Ph.D. from Harvard], I just never found anything as interesting as biology," he said.

Dr. Hughes suggests that although science is his profession, and the major focus in his life, "people should seek balance in their lives.  I like to spend time with my family. I have a farm and like to work in the garden. I enjoy the outdoors and fly fishing. Those things tend to make me feel connected to the larger, living world," he said.

"If the marvel of the universe amazes you, and you like to learn new things, then science could be for you," Dr. Hughes advises students who are making a career choice. "In science, the rules are always changing. Experiments you could not do 20 years ago, even 10 years ago, you can do now. You can keep growing with science, and it's something you won't grow old on too quickly. Science lasts a lifetime, and scientists can be productive for very long periods of time."

"To me, science is like a game," says Dr. Hughes, who in 1996 was named one of the most frequently cited AIDS researchers by Science Watch. "It's a game in which we get to ask interesting questions, and sometimes, if we work long enough and hard enough, we find an answer. I can't think of anything that someone would pay me to do that I'd rather be doing than science," he said.

To read more about Dr. Hughes's research, visit http://home.ncifcrf.gov/hivdrp/Hughes.html or the mirror website http://www.retrovirus.info/Hughes.html.  Two additional websites provide detailed information about Dr. Hughes's projects on HIV reverse transcriptase (http://home.ncifcrf.gov/hivdrp/rt) and the RCAS system of retroviral vectors (http://home.ncifcrf.gov/hivdrp/RCAS).

Marg Mills, writer
Gene Regulation and Chromosome Biology Laboratory
National Cancer Institute at Frederick

Maritta Grau, editor
Scientific Publications, Graphics & Media
SAIC-Frederick, Inc.
National Cancer Institute at Frederick

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Scientific Publications, Graphics & Media
SAIC-Frederick, Inc.
National Cancer Institute at Frederick

Jim Miller, Web Graphics and Development
Computer & Statistical Services
Data Management Services, Inc.
National Cancer Institute at Frederick