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p214 One flu over p216 Bugs vs. drugs: p219 German genius:
Asia: Small steps Can GM insects Otmar Wiestler
toward a human succeed where promises to transform
vaccine for the conventional drugs translational cancer
avian flu. have failed? research.

Contraceptive research pregnant with anticipation

© 2004 Nature Publishing Group

In 1964, a woman had three choices for con- variations on steroid manipulation. “It’s sort scriptome’ can be a powerful tool, says John
traception: she could take a hormone-based of the ‘same-old, same-old’ approach,” says Herr of the University of Virginia. But because
pill, insert a barrier device or convince her John Eppig, a senior staff scientist at The there is more diversity at the protein level, pro-
partner to wear a condom. A woman in 2004 Jackson Laboratory in Bar Harbor, Maine. “I teomics is a more useful approach, Herr says.
has the same choices—and they leave much to think [the companies] want to change that.” Herr and his colleagues have created
be desired: pills affect the whole body, barrier In some laboratories, recent advances in ‘sperm-check’—the male equivalent of the
devices can fail and condoms are not an mass spectrometry, two-dimensional gel pro- ovulation kit—to detect and quantify sperm.
option for many women, particularly in the teomics and other techniques are helping scien- The device, which can be used to check sperm
developing world. tists zero in on molecules responsible for sperm levels in the weeks after a vasectomy or as a
The dearth of choices is not for lack of and egg development, fertilization and implan- companion to male contraceptives, will be
demand. Between 1995 and 2000, there were tation of fertilized eggs in the uterine lining. submitted for FDA approval in a few months.
300 million unplanned pregnancies world- “Like the rest of biomedical science, the Herr has also identified sperm-specific mem-
wide, according to the Global Health Council. field of reproductive science is really in its brane proteins required for sperm-egg fusion.
The demand will only increase: within the golden age,” Eppig says. “I’m 60-something— A recombinant sperm vaccine created from
next decade, an unprecedented 600 million and I’ve never been more excited about the five such proteins is being tested in monkeys.
women are expected to enter reproductive age. research going on in my lab and elsewhere.” David Garbers’ team at the University of
“If you look at where contraception is now, Texas Southwestern Medical Center at Dallas
it’s really not much further along than in the is also interested in proteins on the sperm’s
1960s, when the first hormone pills came out,” outer surface, as those proteins are more likely
says Gregory S. Kopf, assistant vice president to be involved in important signaling cas-
of Wyeth’s Women’s Health Research Institute. cades. The researchers have already found sev-
In male contraceptives, there has not been a eral candidates, including an unusual
breakthrough since the condom, which was voltage-gated calcium channel crucial for
first seen in ancient Egypt, Kopf notes. sperm hyperactivation.
“There’s not a whole lot out there.” As scientists come up with possible new
That could soon change. In January, a US contraceptives, “one has to be thinking almost
Institute of Medicine (IOM) panel called for simultaneously about the method of delivery
scientists to use the powerful tools of and the likelihood of acceptance in the target
genomics and proteomics to create compre- community,” says Jerome Strauss III, director
hensive lists of the genes, proteins, fats and of the Center for Research on Reproduction
sugars expressed in sperm and eggs. The goal, and Women’s Health at the University of
the panel said, is to sift through those that are Eppig’s team is trying to decipher how eggs Pennsylvania. People don’t like to take pills
uniquely expressed in those tissues and create talk to the nonreproductive cells surrounding every day, notes Strauss, who chaired the IOM
a new generation of contraceptives. them. “We believe this two-way communica- panel. But, for instance, a ‘smart material’ that
Because of the many obstacles—economic, tion will ultimately yield interesting contra- is liquid at room temperature and forms a gel
regulatory, political and legal—to contracep- ceptive targets,” Eppig says. Using microarrays inside the body could reversibly block fallop-
tive research, only a handful of companies, and techniques such as subtractive hybridiza- ian tubes, he says.
including Wyeth, are still invested in the field. tion and a signal-sequence trap to detect To promote interdisciplinary research on
Germany-based Schering, along with secreted proteins, the team has already found a such smart materials and maintain a dialogue
Organon, recently began clinical trials on a few egg-specific signals. “We’re using just between basic biologists, product developers,
male contraceptive combining testosterone about everything we can think of,” says Eppig. behavioral scientists and funding agencies, the
and progestin, which temporarily turns off the “We’re throwing the kitchen sink at it.” panel recommended the creation of an inter-
brain signals that stimulate sperm production. Eppig also heads a mutagenesis program national alliance for contraceptive research,
The US Food and Drug Administration (FDA) where researchers are screening hundreds of which would monitor progress in the field.
recently approved Seasonale, a new birth con- mouse families for infertility mutations.“This, “We’ve made more progress in the last two
trol pill that suppresses periods for months at I believe, is the most interesting approach to years than we’d made in all the decades
a time. Australian researchers are beginning contraception you could have,” he says. before,” says Garbers, who also served on the
trials on a spray that transfers Nestorone, a Some researchers are using DNA microar- panel. “I think it’s going to explode around us
synthetic progestin, across the skin. rays to identify genes selectively expressed in in the next 5 or 10 years.”
Still, most new products continue to be the testis or oocytes. The sperm or egg ‘tran- Apoorva Mandavilli, New York