Just over a year ago, I had a long talk with an immunologist in the US about the prospects of more effective ways of dealing with HIV infection. She had just come back from a meeting to talk about the likelihood of an effective vaccine being developed. She said that on the evening of the second day, she had gone back to her room and wept, so bleak was the outlook.
Now the mood is changing. For the first time in a dozen years, there is talk of the possibility of a cure for Aids. But there is great caution this time round. People are all too used to disappointment.
New hope stems not from a vaccine, but from the development of new drugs called protease inhibitors, the first of which was licensed by the US food and drug administration last December. Now there are half a dozen alternatives on or near the market. Since these materials were first in clinical trials, physicians have been reporting almost dramatic improvements in the condition of Aids patients on their books: the loss of debilitating symptoms, weight gain and, even more significantly, the return of the "feel-good factor." There is some evidence that the HIV virus can no longer be detected in the blood of some of those previously infected.
Where have these wonder drugs come from? They spring directly from what has been learned in the past decade of the molecular structure of HIV, which shares with all other viruses the property that it can replicate itself only by subverting the machinery of an infected cell to its own ends.
HIV has evolved an especially economical way of doing this. The virus has evolved a long protein molecule, normally wrapped round its own genetic material-a package of subverting enzymes that functions as a kind of molecular Trojan horse. Once inside a white blood cell, the package is cut into its component pieces by the protease it also carries. As much as five years ago, Dr Samuel Broder, then the director of the National Cancer Institute in the US, drew attention to the vulnerability of HIV to drugs that inhibit the protease enzyme.
By January last year, the first protease inhibitors were used in studies that will eventually be recognised as the turning point in Aids research. Previously, it had been thought that the first result of HIV infection was that the virus lay dormant in the white blood-cells until stimulated to activity, perhaps after an interval of several years. Then, last year, two separate groups were able to prove the opposite.
From first infection, several billions of fresh virus particles are generated each day, and are killed off by white blood cells called T-cells, which must themselves be renewed from the bone marrow between 50 and 100 times faster than in normal life. Eventually the virus gets the upper hand over the immune system, and overt Aids ensues. The unexpected dynamics of HIV infection came to light only because the researchers were able to use early versions of protease inhibitors to interfere with the replication of the virus. They found that the drugs became ineffective after a couple of weeks; HIV then became resistant to the drugs.
That observation dictates the new therapeutic regime. The new drugs are given together with AZT (which inhibits the conversion of HIV's genetic blueprint into human form) and an analogue thereof, in the belief that the virus will not be able successfully to change its spots. The cost of the treatment is reckoned to be $10,000 a year; too much to make a dent in the problem of Aids in Africa, for example.
But these are early days. The disheartening feature of Aids in the past 12 years is that there seems to have been no point in the life cycle of the virus at which physicians could exert benign leverage. Whatever happens next, it seems a fair bet that the drugs now being introduced will be the first of many.
Meanwhile, hope is tinged with caution. There is already evidence that HIV can lie dormant in lymph nodes, raising the prospect that even successful drug treatment may have to continue for the rest of a person's life. More worrying, there are some suggestions that the invasion of the nervous system by HIV, which leads to dementia in many Aids patients, may proceed differently from the damage done to the immune system. But with all that said, the new drugs are an important step forward.
What are the lessons to be learned? First, throwing money at a novel problem in public health seems a sensible course to follow. Spending on Aids research in the US probably exceeds tenfold the $1 billion with which President Nixon promised to "cure cancer" in 1971, but it has created the detailed knowledge of HIV without which the new drugs would not have emerged.
Second, the optimism of the mid-1980s seems even more ludicrous today. Since HIV is unlikely to be the last new virus to afflict us, biologists had better learn what technologists in other fields now appreciate-that understanding is necessary for the successful development of technical innovations, but that the time lag between discovery and application is unpredictable.
Third, even if the new drugs are successful, there will remain a huge public health problem even in the US. The temptation to skimp on counselling and palliative care will have to be resisted. And what is to be done about Africa...?
