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Revolution in the Labs

Efforts to cure herpes and asthma advance, while geneticists delve back in time

By Laurence H. M. holland, Crimson Staff Writer

When the history of our time is written 250 years from now, there’s not going to be a great deal that people are going to remember of what happened in this quarter century,” University President Lawrence H. Summers said at the inauguration of the Harvard Stem Cell Institute in April 2004. “But I’m convinced that one thing they will remember is the revolution that took place in the life sciences, that this was a period when we went from a crude empirical set of notions to a real understanding of life processes, with profound implications for disease.”

Long after the Summers-Faculty fight is forgotten, these five advances in the life sciences from the past academic year will continue to wield an impact.



A BLOOD TEST ON YOUR BLACKBERRY?

Last September, Charles M. Lieber, the Hyman professor of chemistry, put the finishing touches on an invention that could revolutionize the process of detecting and monitoring diseases such as cancer.

Lieber explains in an e-mail that his device consists of several hundred silicon wires, each measuring only around 10 nanometers in diameter, each containing a receptor for a specific protein—for instance, a cancer marker.

The new detector allows for real-time monitoring of blood, saliva, and urine using as little as one drop, whereas current detection involves sending several milliliter samples to a lab and waiting several days for results, Lieber says.

Lieber says he believes the device is ready for production and is waiting for the stars to align.

“It will depend on getting the right group of people together who are motivated to make that happen and not simply interested in money,” Lieber writes.

Lieber envisions a hand-held device for use at home or at doctors’ offices.

“There is great advantage to getting answers about disease when you want it and not going through the painful procedure of having blood drawn and then waiting days to weeks for an answer,” Lieber says.

And although he says the innovation may be far off, Lieber even imagines that the technology could be used in a transdermal patch, giving patients real-time updates on their health as they go about their daily lives.

BREATHING EASY

In findings published in the March 16 issue of The New England Journal of Medicine, a team of Harvard Medical School (HMS) researchers discovered the cause of asthma, paving the way for better treatment and possibly a cure for the respiratory disease suffered by 20 million Americans.

Harvard professors Dale T. Umetsu and Omid Akbari, researchers at Children’s Hospital Boston, found that the immune response that triggers asthma symptoms is caused not by Helper T (Th2) cells as was previously thought but by Natural Killer T (NKT) cells in the lungs.

“It’s very new. No one else has seen this before,” Umetsu says. “The biology of these cells is very different from Th2 cells.”

Umetsu first discovered the power of NKT cells when he was at Stanford University, working with specially engineered mice.

“In the absence of NKT cells, we couldn’t induce asthma. We thought it had to be looked at in humans. We found that there are a large number of these NKT cells in the lungs of patients with severe asthma.”

Umetsu and Akbari credit new technologies—such as monoclonal antibodies that can identify specific types of cells—for enabling their discovery.

“The tools were not really available until a couple of years ago,” Akbari says.

Umetsu says that a better understanding of the cause of asthma might lead to an improvement on the current steroid-based treatments.

“The current treatments are effective in most people with asthma, but they don’t cure people. They’re mostly aimed at symptom relief,” Umetsu says. “If we target NKT cells, better therapies are available.”

Umetsu hesitates, however, to predict that an asthma cure is imminent.

“I suppose if we figure out a way to eliminate NKT cells in the lungs, that might be a potential way of curing this disease,” Umetsu says, “but that’s just speculation.”

SORE WINNERS

In December, HMS researchers at the CBR Institute for Biomedical Research found they could harness RNA interference (RNAi), an important gene-expression mechanism, to suppress the virus that causes genital herpes.

Judy Lieberman, David Knipe, and Deborah Palliser discovered that a 22-base-long strand of RNA, when absorbed by genital cells in mice, can destroy the messenger RNA responsible for expressing the HSV-2 virus, which is carried by over 20 percent of American adults.

Lieberman says she hopes that this process can become the basis for a convenient, inexpensive drug that can prevent the transmission of genital herpes.

“A problem with most microbicides is that most people have to use them before they have sex, and application is an issue,” Lieberman says. Since RNAi can suppress gene expression for long periods of time, Lieberman says, “a woman might only have to administer it every week or every couple of weeks, which is feasible.”

Lieberman says that since the amount of material necessary for effectiveness is miniscule—a few picomoles in mice—the drug has the potential to cost only around $8 per application.

The findings also have the potential to have an impact on the transmission of HIV.

“Herpes infection is the leading risk factor for sexual transmission of HIV worldwide,” says Lieberman, who adds that reducing the occurrence of genital herpes would make HIV much less transmissible.

In addition, Lieberman says, RNAi could, “in principle,” be used to repress HIV—a hypothesis her laboratory will soon begin to test in a macaque-monkey model.

LIKE THEY DO ON

THE DISCOVERY CHANNEL

In ancient times, humans and chimpanzees might have known each other—in the biblical sense, that is.

Last month, a team of geneticists at HMS and MIT compared the human genome to that of chimpanzees and two more distant primates and found that early humans and chimpanzees may have interbred to form a more successful hybrid species.

Scientists had previously believed that humans and chimpanzees split into separate species 7 million years ago. But “on the X chromosome, we’re more closely related to chimpanzees by 1.5 million years,” says David E. Reich, an HMS assistant professor of genetics.

Reich says the data suggests that rather than following the traditional view of speciation, in which populations split and are isolated for long periods of time, the human-chimp split involved a “long, drawn-out period of genetic exchange between populations.”

The next step for the team is to test whether the human-chimpanzee relationship is an exception or part of a larger pattern.

While this sort of hybridization is not an accepted mainstream process, it may have evolutionary benefits­—since they combine traits of different populations, hybrids may be more adaptable, Reich says.

Hybridization, he adds, “might be fundamental to the creative process of evolution.”

UNANSWERED PRAYERS

A seminal 1988 article in the Southern Medical Journal found that heart patients performed better when Christian groups outside the hospital prayed for their well-being.

But HMS researchers Jeffrey A. Dusek and Herbert Benson were unwilling to take those findings on faith.

In a study published in the Apr. 4 issue of the American Heart Journal, Dusek and Benson found that patients who had undergone Coronary Artery Bypass Grafting surgery did not recover faster when they were prayed for by strangers.

In the nationwide study, 604 patients were prayed for without their knowledge, 601 patients knew they were being prayed for, and 597 were not prayed for at all.

Dusek and Benson, who performed the study in conjunction with investigators at medical centers in Florida, Minnesota, Oklahoma, Tennessee, and Washington, D.C., found that patients who were prayed for without their knowledge fared no better than patients who were not prayed for, and patients who were aware of being prayed for actually experienced more complications.

While on the surface the study may seem to deal a blow to religions that believe in the power of prayer, in a Mar. 30 teleconference, the researchers stressed that they were not reading too much into the conclusions of the study.

“It’s not unusual to have unanticipated results in such studies,” said Charles F. Bethea, chief medical officer at the INTEGRIS Baptist Medical Center in Oklahoma City and a member of the study’s research team, in the teleconference. “And when they occur, it’s really better to consider possible causes of the unexpected finding, redesign the inquiry, and perform it again rather than try to overgeneralize from the results that you have in front of you.”

“I think at this point, any scientific endeavor, a single study does not answer the question,” Dusek said in the teleconference. “I’m hoping that family and friends will continue doing what they’ve done for years and pray for whomever they want to and loved ones before surgery.”

Benson said that results, especially the high percentage of complications when the patients were aware of being prayed for, were particularly interesting from a psychological perspective.

“[One] feature that future studies should look at are mind-body interactions that came about in this case from awareness,” said Benson, the founder and president of the Mind/Body Medical Institute. “This study might be opening doors to show us the power of mind-body interventions—both positive and negatively.”

—Staff writer Laurence H. M. Holland can be reached at lholland@fas.harvard.edu.

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