It's that time again. Maggie is back at the largest science convention in the Western Hemisphere for four days of wall-to-wall awesomeness. Each day, she'll tell you about some of the cool things she learned watching scientists from all over the world talk about their work. Check the bottom of each post to find links to earlier posts in this series!
Fifteen years ago, Dr. Harry Kestler got a call from a colleague in Florida who had inadvertently stumbled across a very unique family. An African-American woman had brought her sick child into the hospital only to discover that the child was HIV-positive and experiencing symptoms of AIDS. Further tests showed that she, herself, had HIV. As did four of her five children. It was a family tragedy. But in the midst of that, Kestler's colleague had noticed something odd.
The woman knew how she must have been infected—her ex-husband had been an intravenous drug user. But that had been more than 20 years ago. She, and her oldest child, had had HIV for over two decades without developing any symptoms. And her second-oldest child—who shared the same father—wasn't infected with HIV at all.
I've written here before about long-term non-progressors—a rare class of people who can be infected with HIV and live for decades without the virus ever developing into anything serious. Their secret: mutations in their genes that prevent HIV from binding to cells, which means it can't invade the cells or replicate.
Yesterday at the American Association for the Advancement of Science conference, I visited the student poster session, a place where undergraduate college students present research projects they're involved in and compete against one another to earn their poster a spot in an upcoming issue of the journal Science. There, among undergrads from MIT, Harvard, and other prestigious institutions, I met some surprising entrants. Eric McCallister—a student at Ohio's Lorain County Community College—and Megan Sheldon and Conner Anderson—two teenagers who go to high school at the same community college. All three of them are working with Harry Kestler to study the mutations that protect HIV non-progressors against an otherwise deadly virus. Unique researchers studying a unique family.
If you're not from the United States, you might not realize what a big deal this is. Research like this does not normally happen at community colleges. Instead, those schools are usually treated as a second-class system—a way for people to knock out two years' worth of college courses for less money, or just earn a two-year associates' degree. Lorain has partnerships with multiple traditional universities and allows students to take all but 30 credit hours of a four-year degree at the community college. They graduate with a full bachelor's degree from the four-year university. Because of that, the school offers more advanced classes than you can usually find at a community college, and it attracts highly-credentialed, research-oriented professors like Harry Kestler.
If you've heard about HIV non-progressors much at all, you've probably heard about one specific mutation called Delta 32. It's the most commonly talked about. "Basically, if you have this deletion mutation, there are 32 base pairs that should be in your gene sequence that just aren't there," Megan Sheldon told me. (Again, take a moment to process the fact that Megan is 17.) "When you loose those, it means you don't have this specific receptor on your cells and HIV can no longer bind to them."
Delta 32 mutations have been used to cure one man of HIV. In 2007, doctors killed off all the blood cells in the body of a man named Timothy Ray Brown, replacing them with a bone marrow transplant from a donor who carried the Delta 32 mutation.
If you're homozygous for Delta 32—that is, if you carry two copies of the gene that creates this mutation—you simply can't get HIV. About 1% of caucasians are homozygous, Sheldon said. If you're heterozygous, and have one copy of the gene, then you can contract HIV, but it will move very slowly, often taking 10 or even 20 years longer to progress into full-blown AIDS than would otherwise have happened.
Now that you know that, let's go back and talk about that anonymous family in Florida. They seem like they fit the patterns we're talking about here. But they didn't have the Delta 32 mutation. Their mutations were completely different. In fact, all three of the family members studied—the mother, and her two oldest children—had different mutations from one another. They represented three different paths to protection.
Eric McCallister, the college student who getting his bachelor's degree through that Lorain/university partnership, is doing research on blood samples from the second-oldest child—the one who never contracted HIV. Right now, he's trying to prove that this particular mutation—a shift in a single base, compared to the 32 base pair deletion you see with Delta 32—is, in fact, responsible for the child's ability to fend off HIV.
If he can prove that, though, it would be a big deal. I already mentioned that scientists have used Delta 32 mutations from one person to cure HIV in another person. This is not a cheap procedure, a safe procedure, nor a widely available one. The new mutation that McCallister is studying has the potential to remove one of the many roadblocks to curing HIV this way.
As with Delta 32-based treatments, doctors would still have to kill off all the blood cells in a patient's body. But, instead of needing to find a bone marrow donor who is both a match to patient and a carrier of Delta 32, McCallister says the single-point mutation could be induced in a sample of patient's own bone marrow. You'd remove some of their bone marrow, make the change, and then, after their blood cells had been killed off, transplant the altered version of their own marrow back into them.
As McCallister tries to prove he's found a better option for HIV treatment, his teenage colleagues are trying to document Delta 32 mutations in a more diverse swath of the population. Megan Sheldon, and her 16-year-old research partner Connor Anderson, got involved because they go to high school at Lorain County Community College. Every year, the school accepts 100 high school students through an application/lottery system. Those students attend class with college students through all four years of high school, graduating with both a high school diploma and an associates' degree. They'll have two years worth of college credits already knocked out.
Right now, Sheldon said, most of the research on Delta 32 mutations has been done in caucasian populations. When we say that the homozygous mutation is present in 1% of white people, that's not the same thing as saying that it's present in other populations. The truth is that we just don't know because those populations haven't been as well documented.
Sheldon and Anderson want to get a better idea of the rates of Delta 32 mutations within different racial and ethnic groups. Their current poster is basically a proof-of-concept, showing that they are capable of doing the research necessary to reach this goal. For their first study, the teenagers took blood samples from 50 students and teachers at a local high school. The data was completely anonymized. Although they want to study demographics of the mutation in the future, Sheldon and Anderson don't know anything about the people the current samples came from.
What they do know: Out of that 50 people, five were heterozygous for Delta 32. If any of those five contract HIV, they would be long-term non-progressors, going far longer without symptoms than other infected people.
A QUICK NOTE: Eric McCallister told me that the researchers have lost track of the anonymous family at the heart of his research. He knows that the mother eventually died from non-HIV causes, and that the third child—the one who was first brought to the hospital with symptoms of AIDS—died from the disease. But that's it. He doesn't know the family's real name. Or how the other members of the family are doing today. All he has are their blood samples. That's a big deal, because one of the unknowns here is whether the mutations were random or genetic. The fact that the mutations were only present in the children that shared both father and mother suggests a genetic link. But the fact that they all had completely different mutations suggests something more random. The child who didn't contract HIV—and whose mutation could represent a step forward in HIV treatment—might have inherited their protection, or they might have just gotten very, very lucky.
McCallister told me that he'd love to find this family, to let them know how they're contributing to the fight against AIDS, and to find out what's happened to them. I wanted to make a point of that here, on the off chance that this medical history sounds familiar to anyone.
Again: This is an African-American family from Florida—a mother and five children. The two oldest children share a father (now deceased) who had been an intravenous drug user and who was HIV positive. The three younger children share a different father. About 15 years ago, the third child became sick and was diagnosed with HIV, which led to diagnoses for the mother, the eldest child, and the two youngest. The second child never contracted HIV.
PREVIOUSLY FROM AAAS:
- Birth control is safer than pregnancy: Day 1 at AAAS 2012
- Highlights from AAAS: The sign language of science
- Highlights from AAAS: Plant-inspired robots
- Highlights from AAAS: When solar flares attack
- Highlights from AAAS: Microbial spit in the Gulf of Mexico
- Highlights from AAAS: More great stuff from around the Web
- Highlights from the AAAS: Food allergies, superheroes, electric cars and Opie
- Highlights from the AAAS: Science speed-dating
- Highlights from the AAAS: Batteries out of Paper, Order out of Chaos