Commentary in 2002

Breast cancer is the most common malignancy in females in most western countries, with about 1 in 10 women at risk of developing the disease in the course of their lifetimes. Since its introduction over 30 years ago, tamoxifen has been the mainstay of the endocrine treatment of breast cancer. It has become the most widely used anticancer drug, and may be thought of as among the first targeted therapies. Yet the results of a major new trial of endocrine therapy after surgery for breast cancer using aromatase inhibitors cast into question tamoxifen's future role.

Assisted reproductive technologies (ART) are exceptional among clinical therapies, as unlike most medical procedures, ART have generational consequences. Further, human embryo research in the US has been sponsored solely by the private sector and, until recent biotechnology forays into human embryonic stem cell (hESC) and cloning research, exclusively by infertility clinics. Additionally, the relatively brief clinical history of ART has made it difficult for practitioners and researchers to agree on criteria for its safety and success. Against this backdrop, market pressure on biotechnology companies to create hESC lines and on clinical practices to occupy the innovative forefront has resulted in arguably risky experiments with human embryo cloning, as well as in unintentional germ-line genetic modifications during ART and perhaps during gene therapy. Reproduction, once governed largely by passions and instinct, now seems to need further governance. Some argue that it could now be time for the biomedical community, especially in the US, to take further steps to safeguard ART.

Unlike other countries that regulate assisted reproduction, the US has largely left this field to the domain of professional self-regulation and market preferences. The reason lies both in the confused jurisprudence of reproductive liberty and the paralysing effect of the abortion debate on US politics. The debate surrounding cloning, however, has galvanized both activists and the government to revisit the question of regulation, and recent cases in the US Supreme Court suggest that if the political will to regulate this field is found, governmental authority to intervene in areas such as pre-implantation diagnosis, gamete donation and surrogacy might well be upheld, even in the face of constitutional challenges.

Thousands of cycles of in vitro fertilization (IVF) are performed each year. In the US, multiple births occur after 39% of IVF cycles, whereas in Europe, the figure is 26%. Indeed, multiple births are a major factor in the costs attributable to IVF. Reducing the multiple birth rate may reduce the overall costs of IVF, and providing insurance coverage of IVF may contribute to lowering multiple birth rates. The use of IVF is likely to expand in response to increases in infertility and scientific advances.

By conventional assessments, in vitro fertilization (IVF) is one of the safest medical treatments. But producing new life brings immense responsibilities. Recently, there have been disquieting reports of foetal abnormality after these treatments and here we evaluate the potential risks associated with intracytoplasmic sperm injection (ICSI), embryo freezing and pre-implantation genetic diagnosis. In our opinion, before translating new techniques into practice, more research, particularly in animals, is desirable. In addition, better child follow-up and a fresh approach to regulation are also needed.

Pharmacological agents directed against the integrins α_vβ₃ and α_vβ₅ have been reported to inhibit angiogenesis. However, genetic ablations of the genes encoding these integrins fail to block angiogenesis and in some cases even enhance it. This apparent paradox suggests the hypotheses that these integrins are negative regulators of angiogenesis and that the drugs targeting them may be acting as agonists rather than antagonists.

The diversity in growth and morphological characteristics among endothelial cells in different normal tissues and tumors has been long recognized. Yet there has been no clear molecular explanation for such diversity at the level of vascular endothelial growth factor A (VEGF-A) and other established regulators of angiogenesis that are expressed widely and show little tissue selectivity in their angiogenic properties. Endocrine gland–derived VEGF represents the first example of a tissue-specific angiogenic factor, likely to be followed by others.

Pressure by AIDS activist groups, compassion by the pharmaceutical industry and action by the United Nations Secretary General have resulted in a global fund to enable developing countries to purchase cheaper AIDS drugs. Here, the authors describe the World Health Organization's first attempts to devise guidelines for their widespread use in these resource-poor nations.

Prior to the XIII^th World AIDS Conference in Durban, debate raged in the community over the practicalities, cost and ethics of delivering antiretroviral drugs to the developing world. Two years on, that discussion is history. Political and financial forces will now deliver these drugs to such nations. How then can we expect their arrival to alter the HIV landscape?

New uses warranted for cannabinoids? Recent data indicate that synthetic or endogenous substances activating the receptor for marijuana's psychotropic component might be used as templates for the development of new anti-cancer drugs.

It is widely anticipated that the sequencing of the human genome, the characterization of the human proteomic map and the underlying advance in technological know-how will give rise to an unprecedented leap in biomedical science over the next half century. It may be that the bottleneck in the equation is the availability of staff trained to understand the scientific data generated and transform it successfully into something with medical value. Such people must have detailed knowledge both of medicine and the practice of scientific investigation. Here, we present three commentaries that endeavor to explain how such hybrid researchers can be recruited, trained and retained.

Is CD4⁺ cell depletion due to rapid elimination by HIV and failure of the immune system to replace these cells at the required rate? Increasing evidence suggests that this is not the case, and that infection-induced immune activation drives both viral replication and CD4⁺ cell depletion.