Frontlines

CuresNow, a coalition of scientists, patient groups, and entertainment executives recently launched an ad campaign to rally opposition to the Brownback-Landrieu bill that would criminalize all forms of research cloning ("Popular ad couple Harry and Louise are back, opposing Bush cloning ban," Wall Street Journal, April 24, 2002). The characters were featured in commercials that helped sink Bill Clinton's health care reform plan. In the current effort, the fictitious Louise refers to a bill that "puts scientists in jail for working to cure our niece's diabetes." Ben Goddard, partner at Goddard Claussen Porter Novelli, who wrote and directed the commercials, predicts the series will be as successful as its predecessor: "We have the advantage of repetition, where the essence of a complicated issue can be communicated in 30 seconds." The campaign also attempts to soften the terminology surrounding so-called therapeutic cloning to distinguish it from unpopular reproductive cloning. US Sen. Sam Brownback (R-Kan.), who sided with the characters in 1993, calls this misinformation. "Cloning is cloning is cloning," he says in a written statement. The first commercials aired April 24 in Washington DC, and will follow in other markets if all goes well, according to Goddard. Already, rival anti-cloning group Stop Human Cloning has started to run parodying ads entitled "Harriet and Louis."

When enemy forces threaten to attack, the military sends in the troops. Now medical researchers at the University of Florida hope a similar tactic will help ward off America's top killer: the heart attack. They foresee a tiny biological machine that could one day navigate the bloodstream of a heart attack-prone patient and sense when the heart is about to give out. Armed with a combination of genes from human and yeast cells, the university team, led by professor Ian Phillips, created a cardio-protective gene "switch" expressed specifically in the heart. They used the adeno-associated virus to deliver the gene switch to animal tissue cultures and live rats. When the virus sensed a reduction of oxygen, or hypoxia, in the heart tissue, it instantly switched on the accompanying protective genes. The genes thwarted the damage and scarring associated with low oxygen levels and ischemia (M.I. Phillips et al., "Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection," Hypertension, 39:651-5, February 2002.). "We give an IV injection, and although [it] goes everywhere in the body, it only works in the heart or other target," explains Phillips. "It just waits there until the right moment arrives to help the person." The "vigilant vector" technique is still years away from being administered to humans, but Phillips says he imagines it being used for a host of other disorders as well, such as diabetes and stroke.

Trauma such as a cut or comparable injury has been identified as a required element in kick-starting Kaposi sarcoma (KS), the most common cancer found in patients progressing from HIV to AIDS (J. Webster-Cyriaque, "Development of Kaposi's sarcoma in a surgical wound", New England Journal of Medicine, 346:1207-9, April 18, 2002). After a biopsy of the labial minor salivary gland of an HIV patient, Jennifer Webster-Cyriaque, assistant professor of dental ecology and microbiology at the University of North Carolina, Chapel Hill, says an angiogenic lesion formed at the biopsy site several days later. Studies of the biopsied tumor tissue revealed macrophages expressing viral genes in both epithelial cells around the wounds and lymphocytes. This suggests that macrophages recruited for healing process are already infected with human herpes virus 8 (HHV8). When they are introduced to the damaged tissue they induce KS. "This work appears to explain why some patients develop KS at their suture sites," says Webster-Cyriaque. She says the abundance of blood vessels at these angiogenic lesions are the perfect area for development of malignancy, where endothelial cells develop into spindle cells commonly seen in KS. She says that targeting anti-viral agents specifically at HHV8 may be useful in preventing KS.

The Brookhaven National Laboratory in Upton, NY, recently produced the first-ever images of in vivo effects of toluene, a solvent commonly associated with inhalation abuse (M.R. Gerasimov et al., "Study of brain uptake and biodistrbution of [¹¹C]toluene in non-human primates and mice," Life Sciences, 70:2811-28, April 26, 2002.). Madina Gerasimov, a Brookhaven associate scientist, says that because of inhalants' lipophilic nature, it is cleared more slowly from certain regions in the brain. It wreaks serious neurological consequences by disintegrating white matter, primarily in the lipid-rich cerebellum, chiefly responsible for motor skills. Gerasimov says labeling and purifying the toluene for imaging was a difficult task because it is a gas at room temperature with limited water solubility. After injecting the labeled toluene into baboons and mice, Gerasimov noticed similarities to other addictive substances. "It gets into the brain fairly fast, and provides a brain scan similar to that of cocaine, by predominantly affecting the reward/pleasure regions," she says. Among the prominent repercussions of inhalant abuse are sudden death and irreversible cognitive and motor effects. These effects, detrimental after one month of abuse, make long-term inhalation abuse more harmful than heroin or cocaine, says Gerasimov.

Neurons grafted into the human brain not only survive but appear to offer an effective, safe method for reversing neurological damage that can impair muscle control and cognitive function (P.T. Nelson et al., "Clonal human (hNT) neuron grafts for stroke therapy: Neuropathology in a patient 27 months after implantation," American Journal of Pathology, 160:1201-6, April 2002.). The research was derived from the first brain autopsy of a stroke victim treated with such grafts. The implanted neurons—cloned adult human cells called NT2N (hNT), which are derived from the Ntera2 (NT2) teratocarcinoma cell line—survived for more than two years without harming the patient, says John Q. Trojanowski, University of Pennsylvania neuroscientist and senior investigator. "We were gratified by the presence of remaining neurons and no tumor, which is what the animal studies predicted, but you never know for sure until you can show that things work the same in humans," Trojanowski says. He said that he was disappointed that the person did not clinically improve, unlike six of the other 11 individuals enrolled in a Phase I trial to test the implants' effects. The lack of clinical improvement may be linked to white matter damage, he says, speculating that those individuals who have improved clinically from the treatment might have smaller infarcts and more residual grafted neurons. When these patients die, autopsies will be performed to show for sure.

Federal agencies should be provided adequate budgets for developing international science and engineering collaborations, a US National Science Board task force recommended late last month. The NSB report, "Toward a More Effective Role for the US Government in International Science and Engineering," encourages agencies to evaluate whether new immigration and intellectual property policies and regulations will affect international science cooperation, for example. Agencies should also ensure that young US scientists collaborate with their developing-world peers, the report says. "The future of the developing countries rests on their ability to adapt to a culture of science and technology in the 21st century," says Eamon Kelly, chairman of the NSB, who adds that advances reducing information technology infrastructure costs will enable developing-world scientists to more easily access discoveries. "This is an important step, and intellectual capital is going to be as important as financial capital." But boosting international science development could be a challenge in the current US political climate. "NSF programs can have an impact; this needs help from other agencies and perhaps more coordination with the Office of Science and Technology Policy," says Richard W. Getzinger, director of international programs for the American Association for the Advancement of Science. "It's not clear that it will happen, but I encourage it very strongly."