Monthly Archives: February 2014

Smallpox in the New World: Vignettes featuring Hernan Cortes, Francisco Pizarro, and Lord Jeffrey Amherst

Smallpox was one of the greatest scourges in human history. Before it was pronounced to be officially eradicated in 1977, smallpox was estimated to have killed, crippled, or maimed nearly 1/10 of all individuals who ever lived. During the 18th century in Europe, smallpox killed, on average, about 400,000 persons per year. In fact, even during the 20th century, before worldwide vaccination led its eradication, smallpox is believed to have killed more than 300 million people! [The last documented smallpox case worldwide occurred in Somalia in 1977. The last case in the United States was reported in 1949.]

 Notwithstanding the decimation smallpox wrought in European populations, which had several thousand years to adapt to it, smallpox was even more devastating to Native Americans, who were exposed to it only after European explorers, conquerors, and colonizers brought it to the New World. The Europeans also brought other diseases to the New World; most significantly, measles, influenza, typhus, and bubonic plague. Yet smallpox was the most devastating of the European infectious diseases to the indigenous people of the New World. Importantly, smallpox readily spread throughout the Americas, decimating Native American populations, before most had ever actually made contact with the Europeans themselves.

Estimates of how many Native Americans were living in the Americas when Columbus arrived, and how many may have succumbed to smallpox and other Old World diseases, vary considerably. Some estimates claim that 95 percent of the pre-Columbian Native American population succumbed to these Old World diseases. At any rate, the ruin caused by these diseases among the Native American populations was unquestionably enormous. Moreover, this devastation continued into the 20th Century, particularly among the Alaskan Inuit peoples, as well as the native populations of Australia, New Guinea, and Africa.

Bearing the above in mind, we now consider that Hernan Cortes and Francisco Pizarro each came to the New World, in the early 16th century, with an entourage numbering a mere several hundred or less. Yet each conquered a fierce warrior empire numbering in the millions. Cortes conquered the Aztecs and Pizarro, the Incas. How were the Spanish conquistadores able to vanquish these empires, in the face of such overwhelming numerical odds?

Some historians attribute the Spanish conquests of the Aztecs and Incas to their steel weapons and armor and, even more so, to their horses. Others attribute the Spanish victories to the devastating effect of smallpox on those Native American civilizations. Thus, a key purpose of this posting is to sort through these differing points of view, to give each standpoint its proper due. Then, noting that smallpox was an inadvertent factor in the conquests of the Aztecs and Inca empires by the Spanish conquistadores, we recount how British forces in colonial North America, led by Lord Jeffrey Amherst, deliberately used smallpox as a bio-weapon against rebelling Native Americans, in the first documented instance of biological warfare in the New World. [To place these events in time, recall that Columbus first landed in the New World in 1492. Cortes’ encounter with the Aztecs happened a mere 27 years later, in 1519. Pizarro’s encounter with the Incas happened only 13 years after that, in 1532. Amherst’s episode happened in what is now western Pennsylvania, more than 200 years later, in 1763.]

John Keegan, a well known writer on military history, believes that the Spaniards’ horses were the foremost factor in their conquests of the Aztecs and Incas. These Native Americans had never seen horses before they confronted the horses ridden into battle by the conquistadores. Thus, we might very well appreciate how shocking it must have been to Aztec and Inca foot soldiers, when facing a charging horse for the first time. Moreover, horses gave the Spaniards tremendous advantages of speed and maneuverability on the battlefield. Hence, Keegan states, “…in a contest of hundreds against thousands, it was their horses that gave the invaders the decisive (my emphasis) advantage.”

Yet Cortez started out with only 17 horses and Pizarro with only 27. Thus, could so few horses have actually been the factor that enabled several hundred Spanish conquistadors to defeat warrior empires of several millions? In support of this premise, there were numerous battles, in which a mere few dozen or less Spanish horsemen routed thousands of Aztec and Inca warriors, while slaughtering many of them in the process.

Keegan also credits another factor with regard to the defeat of the Aztecs; the extraordinary limitations the Aztecs imposed on their own war-making ability; at least by European standards. Although Aztec armies were very well trained, organized, and supplied, the objective of Aztec warfare was the taking of large numbers (many thousands in some instances) of live prisoners for their ritual sacrifices. Consequently, Aztec weapons and tactics were designed to wound and immobilize, rather than to kill. Thus, while the Aztecs had bows and arrows, their favored weapon was a wooden sword, studded along its sides with flakes of flint, which was designed just to wound. The warrior’s objective was to close with an opponent and strike a disabling blow to his legs, thereby crippling him and enabling his capture. And, since Aztec battles were fought for the purpose of taking prisoners, they were characterized by a high degree of ceremony and rituals. Moreover, the fighting effectiveness of their enemies was similarly limited by the same ceremony and rituals. Battles were prearranged, and the fate of the captives was known in advance. Remarkably, it was all part of a culture in which prisoners were expected to be voluntary participants in their own ritual murders. What’s more, the Aztecs could engage in such ritualized warfare because they were not challenged at their borders by any existential threat. Thus, Aztec weapons, strategy, and tactics were hardly suited for battle against the invading Europeans, whose sole purpose was to win a decisive crushing victory.

Nonetheless, while the Spanish had the advantages of horses, and superior weapons and tactics, could these factors alone have prevented the Aztecs from simply overwhelming them by weight of their sheer numbers alone. Indeed, the Aztecs nearly did just that in their first encounter with the conquistadores, in the Aztec capital, Tenochtitlan; at the time bigger and richer than any city in Spain. The conflict began when Cortes, famously and suddenly took the Aztec emperor, Montezuma, prisoner in his own palace. Despite the fact that the Aztecs were stunned by Cortes’ audacity, his assault on the now leaderless Aztecs nearly ended in disaster for him. Cortes lost two-thirds of his force, and was barely able to escape from Tenochtitlan, and then retreat back to the coast.

Cortes’ stroke of good fortune came after his failed attempt to capture Tenochtitlan. It was the chance introduction of variola (the smallpox virus), which spread rapidly through the densely populated Aztec empire, killing a third or more of its population in a mere few months. The smallpox victims included Cuitlahuac, the Aztec emperor who succeeded Montezuma. After that, in 1521, Cortes attempted to subdue Tenochtitlan a second time. In this instance, Cortes’ was reinforced with a large number of Indian auxiliaries (perhaps as many as 200,000). But, the defending Aztecs were no longer naïve regarding Spanish weapons and intentions, and they fought back tenaciously. Nevertheless, smallpox had been taking its inevitable toll, by then having killed nearly half of the Aztecs, and Cortes was able to capture the city.

Exactly how smallpox came to Mexico is not entirely clear. Some sources state that an infected slave, who arrived in Mexico in 1520 from Spanish Cuba, transmitted the infection to the Aztecs. Other accounts suggest that smallpox was carried by Cuban Indians, who the Spaniards brought along as auxiliaries. Regardless, since the Aztecs had no prior exposure to variola, most of them and their leaders were killed by the Old World germ, leaving the survivors bewildered and demoralized. It is estimated that 3.5 million Aztecs succumbed to smallpox in a mere two years, vastly exceeding the number that possibly could have been killed by Spanish guns and swords!

Shortly after Cortes’ conquest of the Aztecs in Mexico, Francisco Pizarro, in 1532, with a mere 168 Spanish soldiers, and only 12 guns, which were the slow-to- load, inaccurate harquebuses of the day, conquered the Inca Empire of millions. The first encounter between Pizarro and the Incas was at Cajamarca, a town in what is now the Peruvian highlands. At Cajamarca, Pizarro’s force of 168 men faced, and soundly routed an Inca army of 80,000, without losing a single man! As in the case of Cortes at Tenochtitlan, Pizarro, at Cajamarca, enjoyed the advantage of his horses (27 in this instance) and superior weaponry. What’s more, following the example set by Cortes’ capture of Montezuma, Pizarro captured the Inca emperor, Atahualpa, moments after he unleashed his surprise attack on the shocked Inca warriors.

To wholly grasp the audacity of Pizarro’s achievement at Cajamarca, reconsider that Atahualpa was surrounded by his army of 80,000 soldiers, in the middle of his own empire of millions, while Pizarro’s force was comprised of a mere 168 men. What’s more, Pizarro was isolated from any other Spaniards, the nearest of whom were 1,000 miles to the north, in Panama.

Jared Diamond, in his marvelous book, Guns, Germs, and Steel, provides gripping first-hand Spanish accounts of the confrontation at Cajamarca. One of the conquistadores relates that many of the Spanish soldiers, when first seeing the enormous numerical advantage of the Incas, were terrified to the point of incontinence. He continues: “All of us were full of fear, because we were so few in number and we had penetrated into a land where we could not hope to receive reinforcements…The Governor’s brother Hernando Pizarro estimated the number of Indian soldiers there at 40,000, but he was telling us a lie just to encourage us, for there were more than 80,000 Indians…At noon Atahualpa began to draw up his men and approach. Soon we saw the entire plain full of Indians, halting periodically to wait for more Indians who kept filing out of the camp behind them. They kept filing out in separate detachments into the afternoon. The front detachments were now close to our camp, and still more troops kept issuing from the camp of Indians. In front of Atahualpa went 2,000 Indians who swept the road ahead of him, and these were followed by the warriors, half of whom were marching in the fields on one side of him and half on the other side.”

Another eyewitness describes Pizarro’s actual attack on the Inca force: “We had placed rattles on the horses to terrify the Indians. The booming of the guns, the blowing of the trumpets, and the rattles on the horses threw the Indians into panicked confusion…The Governor (Pizarro) himself took his sword and dagger, entered the thick of the Indians with the Spaniards who were with him, and with great bravery reached Atahualpa’s litter. He fearlessly grabbed Atahualpa’s left arm…The Indians carrying the litter, and those escorting Atahualpa never abandoned him: all died around him…Atahualpa himself admitted that we had killed 7,000 of his men in that battle…It was extraordinary to see so powerful a ruler captured in so short a time, when he had come with such a mighty army.”

Our eyewitness continues: “The panic-stricken Indians remaining in the square, terrified at the firing of the guns and at the horses-something they had never seen-tried to flee from the square by knocking down a stretch of wall and running out onto the plain outside. Our cavalry jumped the broken wall and charged into the plain… It was an astonishing sight, for the whole valley for 15 or 20 miles was completely filled with Indians. Night had fallen, and our cavalry were continuing to spear Indians in the field, when we heard a trumpet calling for us to reassemble at camp.”

From the above eyewitness accounts, and others as well, we know that horses indeed played an important role in the Spanish conquests of the Aztecs and Incas. Apropos that, David Diamond notes that the only instances where Native Americans were able to stave off being subdued by European invaders and settlers for any length of time were when they were able to acquire horses of their own and guns as well, and master their use (e.g., the Sioux warriors who annihilated Custer’s forces at the Little Big Horn in 1876).  The Aztecs and Incas, like all other foot soldiers, were never able to defeat cavalry in the open.

Actually, we’ve said only little regarding guns in the conquest of the Aztecs and Incas. That is so because the guns of that day were difficult to load and fire, and were inaccurate as well, as noted above. Thus, aside from their ability to induce panic, guns played only a minor role in those conflicts. Instead, Spanish steel swords, lances, body armor, and helmets, were more important than their guns, when pitted against the Indian’s blunt wooden clubs and thin quilted armor. [The Sioux warriors at the Little Big Horn had accurate, easy to load, repeating rifles that, in point of fact, were superior to the single-shot rifles carried by Custer’s cavalry.]

We’ve said nothing thus far regarding smallpox in the downfall of the Incas. To redress that point, note that while some of the details of the encounter between Atahualpa and Pizarro at Cajamarca, as recounted above, may be familiar to many readers, less well known is the reason Atahualpa was at Cajamarca, rather than at Cuzco, the capital of the Inca Empire. The reason is a follows. In 1526, a smallpox epidemic, which was brought to the New World by Spanish settlers in Panama and Columbia, spread overland to the Inca Empire, killing the then emperor Huayna Capac and his son and heir, Ninan Cuyuchi. Many other Incas were killed as well. But, for the moment, the gap in Inca leadership, caused by the deaths of Huayna Capac and Ninan Cuyuchi, gave rise to a contest for power between Huayna Capac’s two other sons, Atahualpa and Huascar. Atahualpa, and his army, was at Cajamarca because he had just won a decisive battle against Huascar’s forces.

From the time of the battle at Cajamarca, when Pizarro captured Atahualpa, at until eight months later when the Spaniards executed him, the Incas would not take any offensive action against the Spaniards; for fear that doing so might place their revered sun-god emperor in jeopardy. Pizarro used this respite to arrange for reinforcements from Panama. Then, when hostilities resumed after Atahualpa’s execution, the Spaniards were in a much stronger position militarily against the Incas, who were by then decimated by smallpox, as well as by their civil war. What’s more, because Inca society was very much connected to its emperor, Atahualpa’s death further hastened its disintegration and, thus, the ultimate defeat of the empire by the conquistadores.

Before moving on, note that smallpox was a non- premeditated, chance factor in the conquests of the Aztec and Inca Empires by the Spanish conquistadores. In contrast, smallpox was used deliberately against Native Americans by the British military in colonial North America, in what was the first known example of biological warfare in the New World. But, before we begin that story per se, note that biological warfare was not a new concept. Indeed, there is evidence that it was practiced as early as the 6th Century B.C., when the Assyrians were said to have poisoned enemy wells with a fungus that was supposed to make the enemy delusional. Irrespective of whether this particular tactic might actually have worked, the concept was nevertheless in existence. Later, in medieval Europe, bubonic plague victims and their excrement were catapulted over castle walls. The last known use of plague corpses being used as a bio-weapon occurred in 1710, when Russian forces flung plague-infected corpses over the city walls of Reval, the capital city of Estonia. Incidentally, despite the devastation wreaked by natural smallpox infections over the course of several millennia, the earliest example that I found of smallpox actually being used as a bio-weapon is that which follows.

Our current tale features Lord Jeffrey Amherst, for whom my home-town in Massachusetts is named. Amherst was the commanding general of British forces in North America during the final battles of the so-called French and Indian war (1754-1763). The French and Indian War was the American theater of a much larger conflict playing out in Europe, known as the Seven Years War. In the New World, the British and French vied for domination over North America. The British were victorious, but at great cost to them. Their heavy taxes on the colonies, to recover the costs of the war, ultimately led to the American war of independence only 13 years later.

Amherst led military victories over the French forces that were critical to the British winning control over all of North America. Nevertheless, Amherst’s reputation is tarnished by the belief that he deliberately gave smallpox-infected blankets to North American Indians, thereby starting a deadly epidemic among them.

These events happened just after the French and Indian war, when relations between the British and Native Americans in the Ohio and Great Lakes region began to deteriorate, leading to the 1763 Indian uprising known as Pontiac’s Rebellion. The conflict is named for the Ottawa chief, Pontiac, who led a coalition of tribes in an attempt to drive British forces from the region. The Ohio and Great Lakes region was previously occupied by the French, who had been courting the Native Americans’ favor. However, when British forces took control, they treated the Native Americans as a conquered people.

Amherst believed that the Native Americans should have to unconditionally accept British rule. But, as Pontiac’s forces seized the military initiative in the Ohio and Great Lakes region, Pennsylvanian colonists sought refuge at Fort Pitt (located at what is now Pittsburgh). Next, after warriors of the Delaware tribe laid siege to the fort, Amherst wrote the following to the British colonel who was about to lead an expedition to relieve it: “Could it not be contrived to send the small pox among the disaffected tribes of Indians? We must on this occasion use every stratagem in our power to reduce them.” The colonel wrote back to Amherst in agreement, suggesting blankets as the vector by which to transmit the contagion. Amherst replied: “You will do well to inoculate the Indians by means of blankets, as well as every other method that can serve to extirpate this execrable race.”

While Amherst is generally regarded as the villain of this episode, there is evidence that the British commander at Fort Pitt (the Swiss-born captain, Simeon Ecuyer) had already, and independently of Amherst, attempted this very tactic, by giving representatives of the besieging Indians blankets and a handkerchief that were deliberately exposed to smallpox at the fort’s hospital. This is not meant to exonerate Amherst, whose intentions and hatred of Native Americans are clear from his own correspondences. Nevertheless, in fairness to Amherst, we need to view his attitudes and actions in the context of his own times.  While eighteenth century European rules of warfare indeed had strictures against the use of “poison” weapons and the “poisoning” of streams, springs, and wells, they nevertheless allowed for excessive brutality when putting down rebellions or against populations or groups regarded as heathens or savages. That was the code of warfare of the day, to which Amherst adhered. Apropos that, Amherst never showed any obsessive desire to “extirpate” his other enemy, the French. Yet irrespective of who may have initiated the attempt to spread smallpox among the Native Americans besieging Fort Pitt, this was the first documented example of deliberate germ warfare in North America.

We might ask whether this tactic on the part of the British at Fort Pitt actually worked. But, historians writing on this issue have not come to a consensus for several reasons; most importantly because smallpox was already present among the Native Americans in the region, before the start of their rebellion. At any rate, in the spring and summer of 1763, the Indians around Fort Pitt were stricken with smallpox.

Some final points on bio-weapons:

First, whereas bio-weapons have been used throughout the past three millennia, many contemporary military experts believe that infectious agents would be of little use on a modern battlefield. One reason is that unlike nuclear, chemical, and conventional weapons, they would not immediately stop an advancing army. Another reason is that once released, the spread of a bio-agent would be virtually impossible to control. Finally, use of bio-weapons would invite retaliation in kind. Thus, in the contemporary world, bio-weapons are feared mainly for their potential use by terrorist groups. In this regard, when used as a terror agent, an infectious bio-weapon does not need to cause an epidemic to cause widespread panic and disruption. This was shown by the 2001 episode in the United States, in which B. Anthracis was sent through the postal system.

Second, of the many pathogenic microorganisms that might be used by terrorists, most biological warfare experts believe that smallpox and Bacillus anthracis pose the major threats. Bacillus anthracis offers the advantage of being highly stable in the environment. The advantages of smallpox are that it can spread very rapidly from person-to-person, it is difficult to diagnose until the variola infection is well underway in an individual, it is highly virulent (killing about 30% of infected humans), and there is no effective treatment.

Third, until recently, any incentive to use smallpox as a bio-weapon was greatly diminished by the success of worldwide vaccination. However, this state of affairs began to change in 1980, three years after smallpox was declared to be eradicated. At that time,the World Health Assembly recommended an end to routine vaccination, and most countries complied. Thus, most individuals living today have never been vaccinated against smallpox, and it is not known for certain whether those who received vaccinations 25 or more years ago are still protected.

Fourth, and finally; because of the success of the 20th century’s smallpox eradication program, all reference stocks of variola virus in laboratories worldwide were destroyed, with the exceptions of those at the U.S. Centers for Disease Control and Prevention (CDC), and at Russia’ State Research Center of Virology and Biotechnology (VECTOR). What’s more, the former Soviet Union weaponized variola virus, in contradiction of the 1972 Biological and Toxin Weapons Convention. Because of concern that any of this remaining virus might somehow fall into the hands of terrorists, or inadvertently escape from these laboratories, and since rogue nations or terrorist groups may also be able to develop it as a bio-weapon, many have argued that these last remaining variola stocks should be destroyed. Yet a case can also be made for maintaining them (e.g., for continuing research on the virus). Perhaps this issue might be the topic of a future posting.

 

References:

Guns, Germs, and Steel, by Jared Diamond, (W. W. Norton & Company, 1999)

1493, by Charles C. Mann, (Alfred A. Knopf, 2011)

 A History of Warfare, by John Keegan, (Alfred A. Knopf, 1993).

                The first two of these books were my principal sources for matters concerning the conquests of the Aztecs and Incas. Diamond’s book offers fascinating insights into human history in general and, apropos this posting, eyewitness accounts of the battle at Cajamarca. Mann’s book tells of human life in the Americas before the arrival of Columbus. It contains a detailed, spine-tingling description of Cortes’ capture of Tenochtitlan. Each of these books is very strongly recommended. Keegan’s book, which is a general history of warfare, gives an intriguing depiction of warfare in Aztec culture.

 Fenn, E.A., (2000) Biological Warfare in Eighteenth Century North America: Beyond Jeffrey Amherst, American Journal of History 86:1552-1581.

 This paper contains a detailed account of the events at Fort Pitt in 1763. It also notes other possible, but not as well documented examples of biological warfare in colonial North America.

Cotton Mather, Onesimus, George Washington, and Variolation, on the blog.

See this posting for more on smallpox in colonial North America.

 

 

 

 

 

 

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Carlo Urbani: A 21st Century Hero and Martyr

Carlo Urbani was the first to recognize that the severe acute respiratory syndrome (SARS) epidemic of 2003 signified a new, not seen before, life-threatening, infectious disease. Sadly, Urbani succumbed to SARS while organizing the most effective containment response to a major epidemic in history. Several weeks afterward, the SARS agent was found to be a previously unknown coronavirus, and then aptly named the SARS coronavirus.

Carlo Urbani’s actions during the severe acute respiratory syndrome (SARS) epidemic of 2003 are remarkable on several counts and need to be much better known. But first, we begin with some relevant background

The first known reference to the SARS epidemic dates to February 2003, when the Chinese Ministry of Health announced the mysterious outbreak of an atypical pneumonia in the Guangdong Province of southern China. Chinese authorities reported a total of 305 cases, including five deaths, during the preceding three months. However, these figures were almost certainly an underestimate of the scope of the Chinese epidemic, as discussed below.

A Chinese doctor, who had been treating SARS patients in Guangdong, is believed to have brought the disease to Hong Kong that same February. He developed symptoms during his first day in Hong Kong, where he stayed at the Hotel Metropole. The next day he was transferred to a hospital, and succumbed the day after. However, during his brief stay at the Hotel Metropole, he somehow infected at least 10 other guests. Eight of those infected guests were on the same floor as the doctor, and the two others were two and five flights up from him. Those infected individuals subsequently boarded airplanes that took them to Singapore, Vietnam, Canada, and the United States, thereby spreading an epidemic that lasted more than 100 days.

The World Health Organization (WHO) estimated that there were 8,422 SARS cases worldwide during that 100-day period, resulting in 908 deaths. In all, 29 countries were affected. In the United States there were a total of eight confirmed SARS cases, none of which was fatal. Each of the infected individuals in the United States had shortly before traveled to an area where SARS transmission was occurring. Thus, the SARS outbreak of early 2003 was truly an epidemic of our modern global era, spread by air travel to at least three continents in a period of just a few weeks. Importantly, its consequences might well have been vastly more devastating and, perhaps, less so as well, as described below.

Our story of Carlo Urbani begins in Vietnam, where on February 28, 2003 (a still early time in the epidemic), the Vietnam French Hospital of Hanoi contacted the Hanoi office of the World Health Organization concerning a patient, an American businessman, who seemed to be showing signs of what the Vietnamese doctors feared might be an unusually severe case of the flu. Believing that they might be facing a potentially deadly avian influenza outbreak, hospital officials called on the WHO for help. Urbani, who was an infectious disease specialist, answered the call and quickly determined that the hospital was not facing influenza but, instead, something unusual; a new, previously unknown contagious respiratory disease.

Interestingly, Urbani might not seem to have been the obvious choice to consult on this case, since he was best known as an expert on parasitic infections. Nevertheless, the WHO staff still recommended him to the Vietnamese because of his reputation as a superb clinical diagnostician. Urbani lived up to his reputation, recognizing that SARS was a new and extremely dangerous infectious disease. Moreover, and crucially, he immediately notified the WHO of his findings, thereby without delay setting in motion the most effective global response to a major epidemic in history. His decisive and timely action may have saved millions of lives worldwide!

 urbani

Carlo Urbani, at the Vietnam French Hospital of Hanoi

Disregarding his own safety, Urbani spent the next several days continually at the Vietnam French Hospital of Hanoi, where he organized infection control procedures, while also taking patient samples for analysis. And, as it became clear that the infection was highly contagious and deadly, Urbani worked closely with the hospital staff to maintain morale. Moreover, Urbani, as well as others on the hospital staff, decided not to leave the hospital, so as not to place their families or the community at risk. In doing so, they knowingly placed themselves in jeopardy.

Acutely aware of the danger that the new disease posed to the Vietnamese, Urbani undertook the difficult task of arranging a meeting between WHO officials and the Vietnamese Vice Minister of Health. Urbani was able to bring these parties together largely because of the strong trust he had been building with Vietnamese authorities. At the meeting, Urbani explained the steps that needed to be taken to contain the Vietnamese outbreak. The Vietnamese government responded to Urbani’s recommendations by quarantining the Vietnam French Hospital of Hanoi, and establishing infection control procedures at other hospitals as well. Moreover, the Vietnamese government took the extraordinary step on its part of issuing a public international appeal for expert assistance, despite the possibility of hurting the Vietnamese economy or image by doing so. Specialists who answered the Vietnamese appeal came from the WHO, the CDC of the United States, and Médecins sans Frontières (Doctors without Borders). [Urbani was in fact president of the Italian chapter of Médecins Sans Frontières and was one of the individuals who accepted the 1999 Nobel Peace Prize on its behalf. 1 Speaking at the 1999 Nobel ceremony, Urbani stated that it was the doctors’ duty “to stay close to the victims.”]

Sadly, Urbani began to develop symptoms of SARS during a March 11 flight from Hanoi to Bangkok, where he had planned to attend a conference. He succumbed in a Bangkok hospital on 29 March 2003, not knowing that within several weeks’ time researchers working worldwide would isolate the SARS agent, sequence its genome, and identify it as a newly discovered coronavirus. 2 He was 49 years old. The following is from his obituary in the Guardian, written by Lorenzo Savioli: “His wife Giuliana told me that a few days before falling ill he had argued with her. She was concerned to see him working with patients with such a deadly disease. He said: ‘If I cannot work in such situations, what am I here for – answering emails, going to cocktail parties and pushing paper?’”

Here is another important aspect of the 2003 SARS epidemic to consider; the response of the Vietnamese authorities to the outbreak in their country, versus that of the Chinese authorities to the Chinese outbreak. The Vietnamese responded to their SARS outbreak by taking the unexpected step on their part of promptly issuing an international appeal for expert assistance, which it accepted from U.S. Centers for Disease Control, the WHO, and Médecins sans Frontières. And, by following Urbani’s recommendations, the Vietnamese quickly brought the outbreak in their country under control. In contrast, the Chinese initially tried to cover up their SARS outbreak, and then misrepresented the number of their cases. Indeed, there are reports that they had their SARS patients driven around in taxis to avoid being detected by WHO officials who came to visit their hospitals. News of the Chinese epidemic surfaced in the outside world largely because scientists, who were working in neighboring countries, become aware of what the Chinese authorities knew about, but tried to conceal.

Bearing in mind that the 2003 SARS epidemic may have initially emerged in China, if the Chinese authorities had been more forthcoming, and if they had taken appropriate containment measures at the start of their epidemic, many lives might have been saved worldwide. Moreover, the quarantines that needed to be instituted globally in response to the SARS epidemic, the disruption of international travel, and the worldwide economic consequences, all might have been much less severe. Reacting to international pressure, China finally established strong containment measures in April 2003. [In April 2004, the Chinese Ministry of Health reported several new SARS cases. And, in contrast to its actions of the preceding year, this time China responded aggressively, quickly isolating patients who developed SARS, identifying their nearly 1,000 recent contacts, and sharing information with outside groups such as the WHO.]

 On July 5, 2003, the WHO announced that the cycle of human-to-human transmission of the initial SARS outbreak was broken and that the epidemic had come to an end. The fact that containment of the 2003 outbreak was achieved within 4 months of the first global alert is a tribute to effective public health policy and, what’s more, to the united effort of the international community. As noted above, the global response to the SARS outbreak, first initiated by Urbani in Vietnam, was indeed the most effective response to a major epidemic in history. It also is noteworthy that containment was achieved without the benefit of a vaccine or critical diagnostic reagents; further evidence of the efficacy of good public health policy.

While the public health community well deserves praise for containing the SARS epidemic, the scientific community also merits praise for isolating and identifying the SARS agent within weeks of the initial 2003 outbreak. It happened as follows.

The symptoms of SARS did not suggest any one cause in particular. Thus, researchers tested patient specimens for a broad range of bacterial, chlamydial, rickettsial, and viral agents that were known to target the lower respiratory tract. Viral agents under suspicion included influenza viruses, paramyxoviruses, herpesviruses, and picornaviruses.

In order to amplify potential viral agents, patient samples were inoculated into cell cultures. Then, by means of electron microscopy, a virus, which originated in the respiratory secretions of a SARS patient, was seen which displayed characteristic coronavirus structural features. Then, using electron microscopy in some instances, and serological procedures in others, this virus was detected in additional SARS patients. Subsequent molecular biological and immunologic studies confirmed that the isolated agent was, in fact, a novel coronavirus. Next, the SARS virus isolates that had been grown in cell cultures were found to cause lower respiratory tract disease when inoculated into monkeys.

It is noteworthy, that in the modern genomics era of PCR primers and so forth; the SARS virus was first identified by means of classic tissue-culture amplification and electron microscopy. As noted by the authors, “…electron microscopy proved to be a rapid technique that did not require specific reagents for or prior knowledge of a particular agent but that could nevertheless categorize a pathogen on the basis of its appearance and morphogenesis.” 3

Although the SARS virus was identified using classic virological procedures, the SARS epidemic was the first infectious disease outbreak in which virus researchers took full advantage of the powerful new techniques of the genomics era to analyze the new pathogen. Using these techniques, the SARS virus genome was sequenced less than one month after the virus was first isolated. Within the next three months, genome sequences of 20 independent clinical isolates of the SARS virus were available in the GenBank database for comparison.

Interestingly, the SARS virus’ genealogy initially took researchers in the field by surprise. That was so because coronaviruses were previously known for the mild upper respiratory tract infections they cause in humans; infections which are similar clinically to the innocuous common colds caused by the human rhinoviruses.  In contrast, as many as 40% of individuals infected with the SARS coronavirus required mechanical breathing assistance, and the overall mortality rate for infected individuals was about 10%, rising to as high as 50% in the elderly.

Urbani succumbed to SARS just weeks before the SARS coronavirus was isolated and identified as the cause of the epidemic. So, Urbani never knew of the discovery. But, in tribute to the singular importance of Urbani’s deeds during the epidemic, and his personal sacrifice, the authors of the paper, which reported the identification of the SARS virus, dedicated the paper to Urbani. 3

Urbani also was not forgotten by the Vietnamese government, which conferred upon him two of their highest honorary titles: the medal of Friendship and the medal for People’s Health. What’s more, outside of Hanoi, a hospital has been built in his name. And, in Taiwan, a foundation has been named after him.

Footnotes:

1. The following is excerpted from the “Doctors Without Borders/Médecins Sans Frontières (MSF)” website:

“ Doctors Without Borders/Médecins Sans Frontières (MSF) is an international medical humanitarian organization created by doctors and journalists in France in 1971.Today, MSF provides independent, impartial assistance in more than 60 countries to people whose survival is threatened by violence, neglect, or catastrophe, primarily due to armed conflict, epidemics, malnutrition, exclusion from health care, or natural disasters. MSF provides independent, impartial assistance to those most in need…MSF medical teams often witness violence, atrocities, and neglect in the course of their work, much of which occurs in places that rarely receive international attention…. At times, MSF may speak out publicly in an effort to bring a forgotten crisis into view….For example, in 1985, MSF spoke out against the Ethiopian government’s forced displacement of hundreds of thousands of members of its own population. In 1994, the organization took the unprecedented step of calling for an international military response to the 1994 Rwandan genocide. The following year, MSF condemned the Serbian massacre of civilians at Srebrenica, and four years after that, denounced the Russian military bombardment of the Grozny, the capital of Chechnya. In 2004 and 2005, MSF called on the United Nations Security Council to pay greater attention to the crisis in Darfur. And in 2007, MSF denounced the targeting of civilians in conflict—something that was occurring with greater frequency in the Democratic Republic of Congo, Central African Republic, Chad, and Somalia—and the governments of Thailand and Laos, which were threatening to forcibly return nearly 8,000 Hmong refugees to Laos….”

2. Norkin, L. C., 2010. Virology: Molecular Biology and Pathogenesis, ASM Press, Washington, DC.

3. Ksiazek T. G., D Erdman, C. S. Goldsmith, S.R. Zaki, T. Peret, S. Emery, S. Tong, C. Urbani, J.A. Comer, W. Lim, P.E. Rollin, S. F. Dowell, A.E. Ling, C. D. Humphrey, W. J. Shieh, J. Guarner, C. D. Paddock, P. Rota, B. Fields, J. DeRisi, J. Y. Yang, N. Cox, J. M. Hughes, J. W. LeDuc, W. J. Bellini, L. J. Anderson; SARS Working Group. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348:1953-1966.

How the Human Immunodeficiency Deficiency Virus (HIV) Got Its Name

This story began with the clash between Luc Montagnier and Robert Gallo over priority of discovery and, with it, the right to name the virus. In the midst of this controversy, Harold Varmus seized the initiative to find a universally accepted name for the virus that causes AIDS.

Our previous posting (Who Discovered HIV?) told how Robert Gallo, at the U.S. National Institutes of Health (NIH), and Luc Montagnier, at the Pasteur Institute in Paris, vied to be recognized as the sole discoverer of the AIDS virus. Montagnier named his isolate of the virus “lymphadenopathy associated virus” or LAV, because it came from a patient presenting with lymphadenopthy. 1 Gallo, in contrast, named the virus “human T-cell lymphotropic virus III” or HTLV-III, based on his belief that it was a variant of the human T-cell leukemia viruses-I and –II, which were isolated earlier in his laboratory.

It soon became clear that LAV was quite distinct from HTLV-I and –II. 2 Moreover, and improbably, HTLV-III was found to be identical to another LAV isolated in Montagnier’s laboratory. What’s more, Montagnier had sent a sample of his virus to Gallo before Gallo reported isolating HTLV-III. These events led to recriminations flying back and forth between Montagnier and Gallo, and, not surprisingly, to a bitter rivalry between them, as each held fast to his claim for priority of the discovery.

For the sake of completeness, Jay Levy, at the University of California, San Francisco (UCSF), was also among the first to isolate the AIDS virus, which he named the “AIDS-associated retrovirus” or ARV. Levy did not take part in the dispute between Gallo and Montagnier and, consequently, did not receive the publicity that they did. And, while Levy did not contend for recognition with the fervor of Gallo and Montagnier, his designation for the AIDS virus, and other proposals as well, also had to be considered in the deliberations described below.

The discoverer of a new virus is generally accorded the privilege of naming it. Consequently, the name that the scientific community might ultimately adopt for the AIDS virus could have implications beyond merely providing an appropriate designation for it. Specifically, if the scientific community were to acknowledge LAV or HTLV-III as the name for the virus, it would have been tantamount to recognizing Montagnier or Gallo, respectively, as its discoverer. Thus, any individuals entrusted with resolving the naming issue had to be wary of inadvertently advancing the claims of one, or the other, of the two main protagonists. There was even more at stake for Gallo, since his integrity was being called into question and, consequently, his reputation as well. Moreover, the national pride of both the United States and France were also at issue, as well patent rights to the blood test for the virus.

Although it was clear to all that HTLV-III (or LAV) is distinct from HTLV-I and –II, and that HTLV-III and LAV are one and the same virus, Gallo still went all-out to preserve HTLV-III as the designation for the virus. So, for a time, the awkward solution of the scientific community was to call the virus LAV/HTLV-III, as was recommended by the World Health Organization, or HTLV-III/LAV, as preferred by the U.S. government.

Harold Varmus now steps up to become the key player in the resolution of the naming dispute. But first, here is his bio in brief. Varmus, born in 1939, shared a 1989 Nobel Prize with Michael Bishop for demonstrating that retroviral oncogenes (e.g., v-src) have their counterparts (proto-oncogenes; e.g., c-src) in normal cells. 3 In turn, this led to the realization that mutations in particular host genes, or the inappropriate expression of those genes, might be the underlying basis for human cancers.

varmusHarold Varmus (1981)

To appreciate the huge significance of Varmus’ and Bishop’s 1976 findings, bear in mind that most of the scientific community of the day were skeptical of the notion that cancer had a genetic basis, until Varmus and Bishop provided direct evidence in its support.  Moreover, as Varmus later stated: “In recent years, after our prize was awarded, mutant proto-oncogenes and the proteins they encode have become critical tools for the classification of cancers and promising targets for drugs and antibodies-treatments that have, in some cases, proven to be effective for a significant and growing number of cancers, including leukemias and lymphomas, lung, gastrointestinal, and kidney cancers: and cancers of the breast.” 4

Varmus was a professor at UCSF during the happenings recounted here. Later, between 1993 through 1999, he served as Director of the U.S. National Institutes of Health, and from 2000 through 2010, as President of the Memorial Sloan Kettering Cancer Center. He is currently Director of the National Cancer Institute. On a personal note; I got the idea for this posting from Varmus’ brief account in his book, The Art and Politics of Science (2009). This is a marvelous book that I strongly recommend to all readers of this blog.

At the time of our story, Varmus also was serving as chairman of the Retrovirus Study Group of the International Committee on Taxonomy of Viruses (ICTV). [The ICTV, through its various study groups, has the task of developing and maintaining the commonly accepted virus taxonomy.] As chairman of his study group, Varmus assumed responsibility for resolving the AIDS virus naming dispute. To advise him in that effort, he created an international panel of eminent retrovirologists, which included Howard Temin, 5 Peter Vogt, Myron Essex, Ashley Haase, Steven Oroszlan, Natalie Teich, Kumao Toyoshima, Robin Weiss, John Coffin, and Jay Levy, as well as Gallo and Montagnier. Moreover, Varmus solicited written opinions from more than fifty additional prominent scientists and clinicians, not on his panel.

The panel was soon considering more than a dozen names. Some of these were suggested within the panel, while others were suggested by Varmus’ outside correspondents.

After the panel invested more than a year deliberating these proposed names, which included the two that Montagnier and Gallo originally adopted, it finally settled on “human immunodeficiency virus,” or HIV, as the AIDS virus is now universally known. In reaching its conclusion, the panel considered many issues, including the controversy over priority of discovery, the phylogentic relationship between the AIDS virus and HTLV-I and -II, 2 the immunosuppressive properties of the virus, and the desirability of including the term “AIDS” in its designation. Finally, the panel considered how its preferences squared with established naming conventions and precedent. Varmus, of course, mediated all discussions within his panel.

Notwithstanding all the arguments and compromises that the panel considered, Gallo was not satisfied when all was said and done, nor did the outcome end his dispute with Montagnier. 6 Although the panel’s end result essentially nullified the right of Montagnier and his group to name the virus which they believed they had discovered, Montagnier was already prepared to accept an alternative name, although not HTLV-III. In contrast, since the panel rejected Gallo’s claim that the virus was a variant of HTLV, he, unlike Montagnier, would not sign-off on the May 1986 letter the panel sent to Nature, which proposed that the AIDS virus be called human immunodeficiency virus, or HIV. [The panel also recommended subcategories of HIV. HIV-1 designates the more common type of HIV, which Gallo and Montagnier each claimed to have discovered. HIV-2 designates the less common variety seen in West Africa, which Montagnier is acknowledged to have discovered. 6]

As Varmus later related, “However difficult this process was-with leaks to the press by Montagnier, belligerent letters to me from Gallo that were copied to most of our nation’s leaders, surly and aggressive behavior by the two rivals, and refusals to sign the final statement by Gallo and his close colleague Max Essex, a virologist at Harvard’s School of Public Health-it was interesting intellectually and socially.” 4 [It’s been said that the diplomatic skills, which Varmus acquired while leading the effort to solve the AIDS virus naming dispute, served him well later in his role as Director of the NIH. For much more on Varmus in that later role see: Varmus, H. 2009. The Art and Politics of Science. Norton Books, New York, NY.]

Some of the thorny issues that Varmus’ panel had to come to grips with with were enumerated above. Those issues and additional others, were also discussed in Varmus’s written correspondences with members of his panel, as well as with the outside experts whom he consulted. 7 We now draw on those communications to glimpse the multiple points of view that Varmus and his panel had to wrestle with.

We begin by considering why the term “AIDS” was not included in the panel’s designation for the virus. This is particularly interesting, especially in view of the naming precedent for viruses such as poliovirus, hepatitis A virus, hepatitis B virus, and the influenza viruses; all cases where the virus is designated by the clinical syndrome that it is associated with. Moreover, that naming convention is generally accepted, despite the fact that in these and other such instances, only a small minority of infected individuals ever manifest the disease. What is more, taking the cases of Hepatitis A and B viruses as an example; these are two phylogenetically unrelated viruses that have nothing whatsoever in common, other than that each causes liver disease. And, as Varmus, himself, noted: “Traditional retroviral nomenclature has worked well in this regard. The convention has been to name viruses according to the host species and the prominent pathology associated with the prototypic isolate of a single type; two examples of such names are ‘feline leukemia virus’ and ‘mouse mammary tumor virus.’” 8 And, even more to the point, there are the examples of the human T-cell leukemia viruses, which have already featured prominently in this tale, and in our previous one (Who Discovered HIV?). So, why then did the panel not choose to simply call the etiologic agent of AIDS “the AIDS virus”?

Michael Gottlieb was one of Varmus’ correspondents who spoke out strongly on this issue. He, and his colleagues at UCLA, command our attention, since, in 1981, they were the first to realize that individuals suffering from persistent infections with the protozoan Pneumocystis carinini, and those with the rare cancer, Kaposi’s sarcoma, were all afflicted with the same underlying disease that specifically targeted their CD4 T cells for destruction. That is, they were the first to recognize and report the existence of the disease that subsequently was named AIDS. Here, then, is an excerpt from Gottlieb’s April 25, 1985 letter to Varmus.

“I am writing to convey my concerns as a clinician about sentiment for nomenclature which would identify the agent as the ‘AIDS virus.’ I believe that this nomenclature would be unfortunate. It is estimated that over one million persons in the U.S. alone have serum antibodies. The fully expressed AIDS syndrome is well publicized to be a lethal intractable illness associated with considerable suffering. In my view the term ‘AIDS virus’ would create considerable distress among all individuals found to have previous exposure…I am hopeful that your Study Group will also wish to avoid creating widespread social distress…”  [My note: Gottlieb’s comments, as well as others quoted below, reflect that it was not yet appreciated that virtually all HIV-infected individuals would eventually succumb to AIDS. That disheartening state of affairs would begin to change dramatically with the development of antiretroviral therapy. 6]

Mark Kaplan (North Shore University Hospital), Jerome Groopman (New England Deaconess Hospital), and several other clinicians spoke on the same issue in their April 29, 1985 letter to Varmus:

“The last major aspect to consider in determining the nomenclature of this virus must be the emotions of the patient who is infected with this agent. Patients told that they have infection with the AIDS virus develop devastating psychological symptoms that have been witnessed by all clinicians dealing with these patients and their families. It is a cruel name for the virus for it leaves no hope for the patient, implying that the patient will inevitably develop and die from AIDS. If we were to have called the EB virus by the disease it was first felt to produce, it would have been called the Burkitts Lymphoma virus. By analogy, one can imagine the distress caused to a patient with EBV if told that he had the Burkitts lymphoma virus…”  [My note: EBV, for the Epstein-Barr virus, is a ubiquitous herpesvirus that occasionally causes the non-fatal illness, infectious mononucleosis. It also is associated with Burkitt’s lymphoma, a malignant B-cell lymphoma seen in children living in equatorial Africa and New Guinea.]

Addressing the same issue in her April 22, 1985 letter to Varmus, panel member Natalie Teich, at the Imperial Cancer Research Fund Laboratories, wrote the following :

“Poliovirus was acceptable even though the vast majority of infected persons remained asymptomatic. However, with AIDS, the social and economic implications and stigma may be too overriding.”

Yet in the case of this issue, and others as well, there was no immediate consensus among those contributing to the discussion. Here is what Jay Levy, also a panel member, wrote in his May 10, 1985 letter to Varmus:

“The concern about frightening individuals with the term ‘AIDS’ virus should not be a consideration…no matter what term is given to the AIDS retrovirus, individuals will easily recognize its connotation.”

Levy adds the following: “I favor classifying the AIDS virus in a category by itself. It is most likely the prototype of a human lentivirus and should not be confused with other human retroviruses. My group prefers to maintain our initial nomenclature, that of AIDS-associated retrovirus (ARV) as it best defines the agent linked to this distinct clinical disease.”

Irrespective of whatever scientific merits Levy’s proposal may have brought to the table, it was not seriously considered by the discussants. For example, Natalie Teich dismissed it as follows: “With due regard for Jay, this was clearly a ‘johnny-come-lately’ claim.”

And, William Haseltine, at the Dana-Farber Cancer Institute, wrote the following in his August 7, 1985 letter to Varmus. “…Dr. Jay Levy’s proposed name has no merit as his report merely repeated the original isolations using previously published methods.”

Notice that both Teich and Haseltine rebuff Levy’s preference solely on the basis of right-of-discovery. With that in mind, here is Haseltine’s take on the appropriateness of calling the virus HTLV-III:

“I strongly favor the name HTLV-III for the virus. I would not oppose the name HTLV-III/LAV or LAV/HTLV-III. My reasons are as follows:…Unless there is good reason to the contrary, the original discoverers of the virus should have the right to call the virus the name they chose. Both the laboratories of Drs. Gallo and Montagnier have valid claims to be original discoverers of the virus. Although the Paris laboratory published first, I am convinced that Gallo had, in fact, isolated the virus at or before late 1982 to very early 1983 as did the Paris Laboratory…Given what must be considered to be a lack of consensus of the committee on the appropriate nomenclature, there is no compelling reason not to abide by the choice of the discoverers themselves…HTLV-III is a far better name than LAV. LAV refers to a specific disease state. HTLV-III does not.” [My note: This passage underscores that the controversy between Montagnier and Gallo, over priority of discovery, was still very much alive at this time.]

Anthony Fauci, as Director of the National Institute of Allergy and Infectious Diseases, also commanded attention. In his May 3, 1985 letter to Varmus, Fauci noted that he typically refers to the virus as the “AIDS retrovirus.” However, he argues against adopting that name, not quite for the reasons expressed above, but seemingly because of the mistaken belief at the time that many infected individuals will not develop AIDS. Nevertheless, even if that belief were correct, the very vast majority of individuals infected with poliovirus, and the hepatitis A and B viruses, and other viruses likewise named for the pathology with which they are associated, do not develop those diseases, as was noted above.

Fauci’s most interesting comments may be those concerned with naming the virus either “LAV” or “HTLV-III.” Regarding “LAV,” he says: “…I do believe it would be inappropriate to call this the lymphadenopathy-associated virus (LAV). The reasons for this should be obvious. First, the virus causes more than lymphadenopathy…”

Regarding “HTLV-III,” he says: “Although there are accumulating data, of which you are aware or more aware than I am, that there are significant dissimilarities between this virus and HTLV-I and –II, I still believe that there is enough reason to maintain this virus within the HTLV nomenclature that this should be continued. The reasons for this are that it surely is a human virus (H), it is a T-lymphotropic virus (TL), and it is a virus (V). Therefore, I would think that HTLV itself is a reasonable abbreviation for the virus. For that reason I would suggest naming it either HTLV-III alone or HTLV-III/LAV. However, for reasons given above concerning the disadvantage of using the terminology LAV, I would elect to call it HTLV-III.”

Fauci does not neglect to point out: “I am well aware of all the difficulties and the emotional issues that are interjected into this vis-à-vis who will get more credit related to the name that is chosen. I will try to disassociate myself from any of that and give you as objective a viewpoint as I possibly can concerning the nomenclature….”

The above comments are from but a small subset of Varmus’ correspondences. And, the comments cited above are merely a subset of the positions and arguments stated in them. Yet they enable us to better appreciate Varmus’ accomplishment in arriving at an acceptable and appropriate name for the AIDS virus, and one which did not stir up further discord. As he succinctly stated in his January 17, 1986 memorandum to his panel: “I and several committee members have come to favor HIV: it is simple; it is novel (and hence does not inflame controversies); and it is based upon the name of the disease with which the virus is readily identified, without including the term AIDS.”

I end this posting with the text of a December 19, 1984 letter from Varmus to David Kingsbury at Oxford, in which Varmus informs Kingsbury of the progress of his ICTV Retrovirus Study Group towards revising the retrovirus phylogeny. Varmus’ letter is followed by a portion of Kingsbury’s January 4, 1985 response. [Kingsbury is best known for his research on influenza viruses. I presume that Varmus was corresponding with Kingsbury here, in part because of the latter’s stature within the ICTV, which put Kingsbury in a position to help Varmus gain approval from the ICTV’s higher leadership for his study group’s recommendations.]

“Dear David:

Thanks for your newsletter. As you probably know, we have updated the summary of Retroviridae for Intervirology (a minor task), and we are anticipating some difficulty with finding a suitable name for the AIDS virus. I am waiting for the dust to settle from the nucleotide sequencing (done or almost done in four labs at least) before convening a subcommittee. But it is clear that the AIDS virus is no more related to HTLV-I than to any other retrovirus on the basis of sequence comparison. Would you like to tell Bob Gallo it shouldn’t be called HTLV-III?

Best regards,

Harold E. Varmus, M.D.”

And Kingsbury’s  reply:

“Dear Harold:

….The news about the AIDS virus is startling! Another family of human retroviruses? When you have adequate data to take a firm position on this I will be happy to tell Bob Gallo the facts. I have no vested interest in the matter.

With best wishes,

David”

Footnotes:

1.  As noted in Who Discovered HIV?, before Montagnier began his search for the AIDS agent, a group of French physicians and scientists suggested to him that the best chance to find and isolate it might be at the start of the disease, before the patient’s T cells had severely declined.The reasoning was that if a virus were found at this early stage of the disease, then it would more likely be its cause, rather than merely a consequence of the immune depression. So Montagnier and co-workers looked for a retrovirus in a lymph-node biopsy from a patient with persistent lymphadenopathy (swollen lymph glands); an early sign in patients progressing towards AIDS, but with little sign yet of the impending severe immunodeficiency.

2.  The following statement appears in Harold Varmus’ draft report (Naming the AIDS Virus), which reviews the deliberations of his panel to find a suitable name for the retrovirus that causes AIDS.

 “If an evolutionary tree is established for retroviruses by comparing the order of amino acids in the protein most characteristic of retroviruses, the enzyme that converts RNA to DNA, it is apparent that the AIDS virus is most closely related to the sheep lentivirus, called visna, whereas the human T cell leukemia viruses are in another limb of the tree, more closely related to other oncogenic viruses, leukemia and sarcoma viruses of various animals, particularly the bovine leukemia virus.”

3.  Stehelin, D., H.E. Varmus, M. Bishop, and P.K. Vogt. 1976. DNA related to transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170-173.

4.  Varmus, H. 2009. The Art and Politics of Science. Norton Books, New York, NY.

5.   For more on Temin, see: Howard Temin: In From the Cold, on the blog.

 6.  Who Discovered HIV? On the blog.

7. The Harold Varmus Papers, AIDS and HIV: Science, Politics, and Controversy, 1981-1993: Documents

8.  Harold Varmus’ April 10,1986 draft of his report, Naming the AIDS Virus, which reviews the deliberations of his panel to find a suitable name for the retrovirus that causes AIDS.