Dirty shots in the dark

Unsterile injections, which may have led to the emergence of Aids, show the risks of using new, poorly understood technologies inmedicine, argues Ernest Drucker.

Darwin taught us that although evolution is governed by random variation, it is regulated by rigid bureaucrats: rules are rules. These rules never change, but the world and its biological actors do. So individual and species survival has a lot to do with serendipity.

I have always been impressed by the power of serendipity. In science, invention often turns on recognising the significance of a chance observation - an insight that precedes more systematic study. The classic example is Sir Alexander Fleming, who first noticed the antibiotic properties of penicillin in a laboratory Petri dish accidentally contaminated with bread mould.

So I was not totally surprised when I found myself on a flight to New Orleans seated next to a couple reading the same page as I in The New York Times - an article about an ethically controversial study on Aids in Africa.

It turned out that my seat mates were Preston Marx and his wife, Mary Francis. Preston is a well-known virologist and a leading researcher on the simian immune viruses (SIVs) now known to be the progenitors of the human Aids viruses that first emerged in Africa. Aids vaccine development is a focus of his work, and simian models are the gold standard for determining any vaccine's safety and efficacy before human trials can begin. So we had plenty to talk about.

I am a public health programme director and researcher who has studied the role of unsterile injections in spreading Aids among drug addicts in the Bronx and elsewhere since the early 1980s. I was only remotely concerned with simian viruses. But I understood that somehow SIV had crossed the species boundaries, launching the global pandemic that has already taken more lives than the medieval plague. The origins of Aids were of interest but, like most frontline public health workers, I felt there were more pressing problems - such as preventing new infections and slowing the epidemics' spread until a vaccine could be developed.

As we swapped stories about our work, I explained that the meeting I was attending in New Orleans was to promote syringe exchange programmes in the United States, where we have faced implacable hostility from federal health authorities despite abundant evidence that providing clean needles to addicts helps to prevent Aids and saves lives. They argue that such schemes "give the wrong message" about drugs and have prohibited the use of federal funds to support such harm-reduction programmes.

Hearing my tale, Preston commented: "Yes, I've always thought that dirty needles were responsible for the Aids epidemic."

"Sure," I said. "We've got scores of studies showing that sharing needles spreads HIV."

"No, no," he said. "I mean responsible for Aids. I believe that HIV exists because of unsterile medical injections in Africa."

He went on to explain two critical pieces of information that I had been unaware of. First, there are several different HIVs that are descended from different SIVs, and they all emerged, in a very short period of time, from different simian species living in different parts of Africa. Since all the SIVs are ancient and people have been exposed to them for thousands of years - in the course of hunting and butchering simians for meat - the key question of Aids origins becomes "why did this occur in several places at the same time and what was the mechanism that caused it?"

Around the middle of the 20th century, multiple crossovers of SIVs occurred in different parts of Africa in areas where humans have lived with, hunted and been exposed to the blood of simian species for aeons without the emergence of HIV. What happened?

The second new idea for me was that unsterile injecting does not just move blood-borne viruses around from person to person - it can also help viruses to mutate. The mechanism is called serial passage. The brief sojourn of these normally weak pathogens in humans exposed to SIV does not normally allow sufficient time for them to fully adapt to their new hosts (us) and to fully mutate into HIV. That is why it never happened before the 20th century. Preston sketched out this story of mutation - an evolutionary tree of genomes and DNA - on a barf bag, which I have saved as humbling evidence of the complexity of nature and the power of serendipity.

Animal viruses may move from one person to another via contaminated syringes. This allows them the time to fully adapt and evolve into a new virus compatible with the new host. It looks as if even a small number of serial passages of SIV, through contaminated needles, could help SIV along this path and create a fully adapted HIV that can survive and reproduce in humans, be transmitted sexually and, in a few decades, become a global epidemic.

My chance encounter has led to four years of work as we have tried jointly to document the levels and circumstances of unsterile injections in the time and place of Aids' first appearances in central Africa in the late 1950s and to discover if such a mechanism still operates. We have conducted historical research to link the emergence of several HIVs in Africa to the dramatic increases in medical injections after the second world war. In this period, the production of injection equipment increased greatly and the cost fell rapidly as penicillin was introduced as a public-health tool. The first mass injecting campaigns to eradicate Yaws - a painful parasitic disease that is cured by a single shot of antibiotics - took place in central Africa in the 1950s. These campaigns resulted in millions of unsterile injections that, we now believe, helped to produce the first and oldest Aids virus (HIV1) and, later in West Africa, HIV2. Today, there are many other partially mutated dead-end SIVs across Africa, suggesting that the processes that produced the HIVs are still operating.

Following a similar line, the journalist and naturalist Edward Hooper spent ten years exploring the origins of Aids in Africa. In his 1999 book, The River , he proposes that the origin of Aids is linked to the early trials of oral polio vaccine (OPV) in central Africa. Hooper contends that early batches of OPV were contaminated with chimpanzee viruses. This theory has not been confirmed by subsequent tests for chimp DNA or by traces of HIV in archived OPV samples from the time of the original trials 50 years ago. But Hooper was the first to think seriously about an iatrogenic origin of HIV, seeing it as a product of well-intentioned (but poorly controlled) medical efforts using new technologies that we never took the time to understand fully.

There is now more awareness of the problems of unsterile injections, but billions of such injections still take place outside formal healthcare. In poor countries, the driving force is the demand for injectable drugs and for their real and imagined therapeutic effects in the face of continuing disparities in access to modern medical care. And, of course, the growth of heroin and cocaine injecting in developing countries is part of the global market in drugs of all sorts and the dangerous technology we use to inject them.

Unsterile injections have created the conditions for a new ecology of infectious diseases - in which old and new pathogens (including drug-resistant strains of bacteria and viruses) may move with unprecedented ease across geographic and species boundaries. As with diseases associated with new mass-feeding methods in agribusiness and its movement to humans (such as variant Creutzfeldt-Jakob disease), the serial passage effects of massive unsterile injecting appear to be an unintended consequence of large-scale technological innovation.

These newly emerging diseases are clear testimony to our continued insensitivity to our own species' precarious place in the biological order. They also show us the dangers of our failure to understand the important links to our closest animal ancestors. Ironically, as many of these species are threatened with extinction, their ancient viruses jump ship and board our own.

But serendipity is meant to have a positive meaning. So let's hope we can use the case of Aids' origin as an opportunity for some insight into who we are and the rules of the biological world in which we live.

Ernest Drucker is professor of epidemiology and social medicine at Montefiore Medical Center/Albert Einstein College of Medicine, New York. On March 20, he will give a seminar on unsterile injections as part of the London School of Hygiene and Tropical Medicine's series on drugs and alcohol research.