How Drug Companies Keep Medicine Out of Reach

The promise of delinking research and development from the actual manufacture of drugs, and why the pharmaceutical industry rejects an idea that could turn neglected diseases into profit


For almost a decade, the United States has been standing in the way of an idea that could lead to cures for some of the world's most devastating illnesses. The class of maladies is known as neglected diseases, and they almost exclusively affect those in the developing world. The same idea, if realized, might also be used in more affluent nations to goad the pharmaceutical industry into producing critical innovations that the free market has yet to produce - things like new antibiotics, which are likely to be used judiciously, and are unlikely to be wildly profitable.

But the idea, which advocates have outlined as a treaty, and which will have its fate decided next week at the World Health Organization (WHO) where it has languished for years amid bureaucratic tumult, is "good enough to be dangerous," in the words of one person close to the negotiations. It has thus drawn the fierce opposition of those who benefit most from the status quo, the pharmaceutical giants and the nations that claim them.

"It's a precedent. It's a competing paradigm," Jamie Love, 63, the director of Knowledge Ecology International, a progressive group agitating in favor of the idea, told me. "And the Obama administration, instead of wrapping its arms around it and trying to breathe some life into the future so we don't have $200,000 drugs, is killing it."

jamie_blue_tie_blue_jeans_DSC_0016_800x944.jpgjamiewithfish200.jpg James Love in Alaska, 1974, and at KEI's D.C. ofifces in 2010 [Dashiell Love]

When I met Love in February at his office in Washington, D.C., he had just returned from Geneva, where the WHO is based, and he planned to be on a return flight shortly. Coach class, he assured me. Love has a boyish face with pale blue eyes and an inscrutable energy about him. The energy, according to those who know him, is nothing new. As a young man, he dropped out of college in Washington and moved to Alaska, where he became a longshoreman and cannery worker and opened two small NGOs. The work drew the attention and support of Ralph Nader, and, in 1980, Love moved to Boston on a fellowship to Harvard's Kennedy School. He added a second Master's degree from Princeton, where he studied with Joseph Stiglitz.

"Part of the problem is that nobody understands what we're talking about," Love told me in his office, a small loft beneath a gabled roof on Connecticut Avenue. "There's really only twenty or thirty of us who understand what we're trying to do with this."

Bill Gates, speaking to the Royal Academy of Engineers in London last March, managed to capture the problem that Love's idea would be leveled against: "Our priorities are tilted by marketplace imperatives," Gates said. "The malaria vaccine, in humanist terms, is the biggest need, but it gets virtually no funding. If you are working on male baldness or the other things you get an order of magnitude more researching funding because of the voice in the marketplace."

This fact -- that research-based pharmaceutical companies focus on the most lucrative products, rather than the most needed -- is particularly damning for the global poor, whose diseases will never be profitable enough to attract the industry. The WHO has recognized 17 such diseases, known as either type III or neglected tropical diseases (NTDs). Almost all of them edge on biblical in both scope and horror.

"The needs are pervasive because these diseases have been so understudied," said Peter Hotez, the founding dean of the National School of Tropical Medicine at Baylor University. "Look at a disease like hook worm infection. Well we now know that single dose mebemindizole doesn't work against Nacator americanus, which is the major hookworm. Why is that? We really don't know," Hotez said. "The WHO I think did us a disservice a few years back when they coined the term 'tool ready' versus 'tool deficient' diseases. All neglected tropical diseases are tool ready, and those same diseases are tool deficient," Hotez said, meaning drugs exist to fight all of the conditions, but many are met by severe resistance and others are poorly adapted for low-resource settings.

The WHO list of NTDs includes Chagas disease, which has a burden of disease five times that of malaria in Latin America, and Dengue fever, which 40 percent of the world's population remains at risk of acquiring. It also includes river blindness, which affects 20 million people in sub-Saharan Africa and leads to infections that itch so severely -- as worms die in the flesh -- that sufferers turn to nails, scalding water, and other violent means to numb the sensation. The existing drug for the disease, Ivermectin, requires six doses over three years to be effective, a regiment that would be difficult to deliver in affluent countries with robust health systems, and is nearly impossible to accomplish in rural Africa.

Neglected diseases, even when coupled with type II diseases, things like malaria and tuberculosis that primarily affect the global poor, receive less than two percent of the $160 billion spent on medical research and development (R&D) each year.

The idea, which has gained the support of a range of academics and economists from around the world, as well as Doctors Without Borders/Médecins Sans Frontières (MSF), Oxfam, Health Action International (HAI), and DNDi, aims to develop new cures for those diseases, and to manufacture the drugs and vaccines at prices affordable to the global poor.

It hinges on the incredible discrepancy between the cost of developing a drug or vaccine -- an expensive and risky enterprise -- and the actual cost of manufacturing a drug, which is often astoundingly cheap.

"So there is the idea that there are gaps in research," Love told me in February, "and the second idea is that linking the cost of R&D to the price of the drug through the grant of a monopoly is inherently problematic, and the problems are diverse." The existing system relies on the promise of drug sales under patent to incentivize innovation -- an effective monopoly on production, typically lasting more than a decade. That system leads drug makers to set prices at whatever level they think the market can bear, regardless of the cost of manufacture or even the cost of development. The point was driven home last year, when Memorial Sloan-Kettering Cancer Center, in New York, refused a new colorectal cancer drug priced at over $130,000 per year. The drug maker, Sanofi, promptly cut the price in half.

The point is also particularly egregious in the case of lifesaving antiretroviral drugs (ARVs) for those suffering from HIV/AIDS. The fight to make those medications accessible to the global poor was another battle in which Jamie Love was intimately involved.

"If you're looking for sort of the intellectual driver for the idea, it's undoubtedly Jamie," said Robert Weissman, who now runs the storied advocacy group Public Citizen. Weissman was alongside Love in 2001 when Love made the most important play of his career: He asked Yusef Hamied, a chemist and the director of the Indian pharmaceutical manufacturer Cipla, for a rock-bottom price to produce a cocktail of ARVs. At the time, the pill regiments were selling for over $10,000 per year under patent-protected prices. Hamied said that Cipla could produce the drugs for a dollar a day per person.

"Jamie got that it had to be a dollar a day, that it wasn't $400 a year, that the price of a dollar a day would move the whole debate," Weissman said.

Hamied's offer made headlines around the world. It set a floor in the market and lead the prices for name brand drugs to fall precipitously.

"Before all this, we had a meeting with the U.S. Trade Representative and we were talking about how keeping these prices and patents in place was costing millions and millions of lives in Africa," Weissman recalled, referring to Love and himself. "And the Trade Rep. said to us -- I'll never forget this -- 'I don't work for millions of people in Africa.'"

The $10,000 that pharmaceutical companies were willing to charge for ARVs -- and that their US government was willing to defend as reasonable at the WTO -- was egregious in part because the drugs can be produced so cheaply, as Cipla proved. But the prices were also impossible to justify because the development cost for the first generation of ARVs was close to nothing for private industry. The drugs, known as dideoxynucleotides, were almost all developed in the 1960s at Wayne State University under National Institutes for Health (NIH) grants to research cancer therapies. And, in the 1980s, it was again NIH researchers who thought to test the compounds against the AIDS virus.

Love traces the genesis of the idea to a similar situation, this one involving cancer drugs. In the early 1990's, Love began investigating Taxol for Senator Ron Wyden of Oregon. The drug is used to treat breast and ovarian cancer, and was developed by the NIH and produced for less than a dollar per milligram for clinical trials. Bristol-Meyers Squibb, once effectively given the patent, sold the drug for $4.87 per milligram, roughly moving the price from $100 per dose to $850 per dose.

"I do a lot of historical research on the things I do. I like to go back and look at earlier disputes and case studies on particular drugs or legislation or just try to figure out how we got where we are," Love said. One of the cases Love climbed into involved Cisplatin, the drug that saved Lance Armstrong's life. The drug was also developed within NIH and effectively handed to Bristol-Meyers.

"In the old days, the government would grant five year monopolies on government-funded inventions that were done by NIH or universities or something, but if you wanted more than five years, you could ask the government to extend the monopoly," Love said.

In the Cisplatin case, when Bristol-Meyers wanted to extend the patent, the government negotiated a 30 percent drop in the drug's price, and for Bristol-Meyers to contribute $40 million in grants to research of the NIH's choosing.

The case fundamentally changed how Love thought about intellectual property.

"Once you sort of turn that corner and you realize that intellectual property rights are really man made policies and they're designed to do something, and there's other ways to induce that same thing that can compete those ideas, then it just opens your mind up."

Love's idea suggests the use of cash prizes -- rather than patents -- to incentivize research; say, $2 billion for an effective therapeutic drug for Chagas disease. A cure, once developed, proven, and awarded a prize, would then exist as open-access intellectual property, with manufacturers around the world competing to produce the drug in the most cost effective manner. Implementing the idea, Love said, "is effectively leveraging the power of the free market twice, once to produce the thing you want and then again to manufacture it as economically as possible." The concept is known as delinking.

The prospect also has interesting second-order effects. "The numbers have to be big enough," Love said. "You can't replace monopolies that involve billions of dollars with prizes that involve thousands of dollars, but it's financially easy to do that because the savings from delinking are so big." Because drug makers are no longer dependent on sales, delinking would relieve huge strains on budgets beyond research and development; the industry only spends about 16 cents on the dollar for R&D. Massive ad campaigns, for instance, would become obsolete in such a system, because the innovator's profits are no longer tethered to sales, the same for gifts and meals to woo physicians.

Love's concept of delinking is outlined in a proposal for an R&D treaty, which remains in limbo at the WHO in Geneva. It will have its fate decided in late May, at the annual World Health Assembly (WHA), the democratic forum of members states that governs the WHO.

The proposal adds a second, equally powerful idea to Love's, one inspired by open-source software models.

Historically, basic research and drug innovation has been done in silos, with little communication across companies and labs. That isolation guarantees that researchers repeat failures that have already occurred elsewhere, a problem that becomes glaring in the case of neglected diseases, where the total research investment is a fraction of what it is for profitable diseases. The lack of information sharing also guarantees that some labs remain stymied by problems that researchers in other places may know how to solve.

"The existing funding structures are competitive, national grant based," said John Wilbanks, who works at the non-profit Sage Bionetworks and is a fellow at the Kauffman Foundation. "So, for most people, the rational economic decision is not to share, not to collaborate, in order to obtain additional taxpayer grants to continue the research and to keep employment."

Wilbanks's background is largely in tech, and the group he works for is building a platform for computational biology akin to GitHub, a system that lets computer programmers track their contributions to open-source code.

"The fear is that by spending my time working on your project, for which I don't have a system to get credit that the existing system recognizes, I will be less competitive over time than someone who participates in the traditional system of information hoarding and publication," Wilbanks said. "We're trying to fix that problem through openness, similar to the R&D treaty."

To combat the problem, the R&D treaty would create an observatory, an open platform for researchers in disparate corners of the globe to pool data and coordinate their work. Grants given to fund their studies would come with provisions requiring that the research exist on that public, cloud-based observatory.

Such an open system also means that help can come from unexpected places. Mathew Todd, a chemistry professor and researcher in Sydney, is currently running an open-source malaria project. He explained how a post-doctoral student in Edinburgh, Scotland, who had been tracking the project's open lab books online, produced a compound that his own lab couldn't figure out how to synthesize.

"The chemistry wasn't working out, and we were being open with this," Todd said. "And he looked at it and said, 'Well I can make that.' And so he went off and made it, and we were interacting with him by Twitter, sort of following his progress and he was posting his experimental data to our lab books online, and he made it."

"It's that kind of example where you think, 'Well if everything's open and it's clear what needs to be done and anybody can chip in, then that means you're going to attract the expertise you need without actually knowing who those people are," Todd said.

Todd told me he's put forward a proposal to host a panel focused on the future of intellectual property and drug development at the February meeting of the American Association for the Advancements of the Sciences. "I think the time is right to have that discussion about whether the patents are working, and whether they're necessary for drug discovery," Todd said. "I want to hear from people on both sides. I think we just have to have that conversation."


Last November, the Obama administration made its most strident effort to date to stall the idea. Because successive U.S. administrations have stonewalled the process so effectively, negotiations on actual language for an R&D treaty have never begun. That hasn't prevented the intellectual scaffolding beneath the idea from developing, though.

To fund the system -- research grants and an observatory to produce and coordinate the foundational science, and prizes to incentivize the pharmaceutical industry to spring off of that basic research -- the treaty would commit member states to spending 0.01 percent of GDP on neglected diseases each year. The U.S. already spends at that level, and would have no further financial obligations. No other country comes close.

Nonetheless, the idea of binding financial commitments by way of treaty has been a centerpiece of US opposition.

"They are using a process argument, saying we are against the form, but in fact what they are opposing is the content of the negotiations," said Judit Rius, the U.S. manager of Doctors Without Borders/Médecins Sans Frontières Essential Medicines Campaign. "When governments get serious about an issue, they agree to binding global norms and they agree to be held accountable. And that's what we want," Rius said. "What the U.S. is really opposing is a conversation about the how this funding should be spent. They are protecting the current business model, the status quo innovation models."

At the November meeting, the U.S. hammered through a resolution effectively neutering the idea in a late night vote. It was held four hours after simultaneous translation of the debate ceased, with only 25 of the original 194 member state representatives remaining in the negotiating hall.

"I've never seen something like that happen in an international negotiation," Carlos Correa, the representative from Argentina, told me. "The meeting should have been terminated, because clearly some of the delegations were not able to follow the debate. In these cases, the governments generally say, 'Well this is not possible to go on, so we'll finish and inform the assembly there was no conclusion.'"

According to delegates present at the meeting, which took place behind closed doors, it was clear from the outset that the U.S. had no intention of negotiating in good faith. "The U.S. was delaying the issue and opposing it totally," one negotiator said. "Very little real negotiation, they were very radical. They were even insisting on some ideas that were not totally correct."

The resolution that emerged from the November session will be taken up in late May, at the annual meeting of the World Health Assembly. If the measure is adopted, further consideration of the idea will be pushed until at least 2016. The resolution also includes the unusual provision of being sealed, barring any further discussion at the WHA.

The document also suggests the creation of a pilot program and an observatory to monitor research, but does so without allocating funds, and with such vague language as to render the resolution moot.

The U.S. has promised to bury the resolution altogether if other countries try to reopen negotiations in May.

"We saw in January that the U.S. negotiator said publically what we had been told he was saying in November behind closed doors, which is that, 'If you change even one comma, we'll kill it altogether," Rius said.

Early in the November meeting, the U.S. moved to quiet a Colombian negotiator. Nils Daulaire, the lead U.S. representative in Geneva, has made a habit of using backchannels to sideline other delegates voicing positions he does not share.

The negotiator in question declined several requests for comment for this piece.

"She was very well prepared, and she was taking the floor several times during the first day," another delegate told me. "And I saw that the U.S. delegation was a little bit nervous, because usually Colombia -- in the last years -- they never take the floor on these issues and they always support the U.S. position. Around four o'clock on the afternoon of the first day, she was called outside the room, and one hour after she came back to the room and she never took the floor again in the next two and a half days. She stayed until two o'clock in the morning the last day, but she never took the floor again."

512px-Dr._Nils_Daulaire_at_May_17_Press_Conference_cropped.jpgNils Daulaire [Wikimedia Commons]

In March, when I spoke with Daulaire, an assistant secretary for global affairs at the Department of Health and Human Services (HHS), I asked what had provoked his complaint. His response took the kind of emphatic tone that conveys both displeasure and the desire to say a great deal more: "I'm not familiar with any formal diplomatic complaint against the Colombian representative," he said. "I don't know where that comes from." Daulaire struck the same tone later in our conversation, when I asked at what level within the Obama administration the U.S. position had been crafted. "I do not discuss internal administration processes," he said.

Daulaire has a round nose and soft chestnut hair with a beard and glasses, lending the overall affect of a college dean. He is -- according to his official biography -- the speaker of seven languages, and a graduate of both Harvard College and Harvard Medical School. He is known as exceedingly ambitious, and is rumored to have put himself forward to replace Eric Goosby as U.S. AIDS Coordinator. The position is one of the most vaulted in the field of global health.

"He is very trenchant in his views, and I'm not sure whether that is because he's hearing that from the industry or whether he's hearing that from the administration, but he's looking at where the political wind is going," one source with intimate knowledge of the debate said.

Daulaire's efforts to derail the November meeting started more than a month before he and his staff arrived in Geneva. His office sent representatives to a WHO regional meeting in Angola to discourage support for the treaty amongst African states, and Daulaire himself made bilateral calls to number of negotiators and ministers of health. On the calls, he asked whether the officials were prepared, at the November meeting, to commit their governments to financing the treaty. None of the officials Daulaire called have the power to make such a commitment, nor does Daulaire himself. Moreover, the treaty he asked them to commit to financing has not yet been written, largely because of Daulaire's own intransigence.

"Nils says, 'The U.S. is the biggest funder of R&D, and we don't think anyone else is going to put up the money,'" one civil society member said. "But the bizarre thing about that is when developing countries said, 'We will put some money up, whether we will reach sort of figure that the experts came up with, we might not but we're prepared to do it incrementally,' he just said, 'No I don't believe you, let's just take the whole thing off the table.' It's very strange to me that the U.S., being the largest funder, is actively undermining putting pressure on other countries to step up to the plate."

"I was sort of looking forward to working with the guy," Jamie Love said of Daulaire. "Everybody knew that he was close to the industry, but that's not necessarily a bad thing. But he really changed when he got the job [at HHS]. At least with the Bush guys you could have a conversation with them about this kind of stuff."

Daulaire's deputy at HHS, Holly Wong, previously worked for the drug industry's main lobby group, PhRMA, and as director of public affairs at Schering-Plough Pharmaceuticals. The company was acquired by Merck in 2009.

Before his appointment to HHS, Daulaire ran a nonprofit called the Global Health Council (GHC) for close to a decade. The group was based in White River Junction, Vermont, where Daulaire lived. The organization had an annual budget of close to $7 million, although it didn't actually provide any health services. After Daulaire left, the organization was handed off to Jeff Sturchio, a former Vice President at Merck. Sturchio drove the group into the ground in less than three years. "It was really a lobby group," one observer said, speaking of the GHC. "At the World Health Assembly meetings they would rent huge halls in the Intercontinental with very expensive food and drinks," another recalled.

The GHC's main function appears to have been providing briefings for incoming members of Congress and new presidential administrations. "I don't think anyone has filled that role," Jonathan Quick, who is trying to revive the GHC, told me. Quick spent eight years working at the WHO as the Director of Essential Drugs and Medicines Policy.

Quick and several others in the global health space pushed back against questions about GHC's lobbying, arguing that the organization served as a kind of hub for advocates of greater U.S. involvement in global health. I asked Quick about his thoughts on the U.S. opposition to the R&D treaty, and whether he, having worked at the WHO, had misgivings about U.S. negotiators having such strong ties to the pharmaceutical industry.

"The U.S. is interesting, having seen it from the WHO side," Quick said. "Most countries when they come to the World Health Assembly lead with their health policies. And they bring to the WHA the values and policies they have at home. There are a few countries where that's difficult, because there are such strong commercial interests that there's a tension. That's always been a very difficult challenge for people representing the U.S. in the international health sphere."

The battle for the idea has peaked at a time when the pharmaceutical industry finds itself under extraordinary duress. Despite significant advances in drug development technology, the number of new drugs per billion dollars spent on R&D has halved every decade since 1950. And the industry, over the course of the current decade, is watching many of its most profitable drugs come off of patent. In November 2011, Pfizer lost exclusivity on the most lucrative drug ever made, Lipitor. The statin grossed more than $130 billion for the company. The patent on GlaxSmithKline's Advair also went dry in 2011. The drug made $7.8 billion in 2009 alone. Eli Lilly, which has been hit hardest by the patent cliff, lost its patent on Zyprexa in 2011. The antipsychotic made them close to $5 billion per year. The firm is projected to lose half of its total sales across the decade.

"We're public companies, and sometimes the CEOs are kind of stuck," said Derek Lowe, a chemist who has worked in the industry since 1989. "Every one of our drugs is a wasting asset, they're all wasting away in front of you." Lowe also runs a blog about the industry, called In the Pipeline. The site manages to couple reverence for the complexity of drug development with sharp critiques of the industry. Last year, for instance, when it became clear that the industry's largest players had put unprecedented sums into buybacks of their own stock in 2011 -- a total of $76 billion across the largest 15 companies, which is $14 billion more than the entire NIH budget -- Lowe wrote a long post. "It gets me because companies are in effect saying, 'you know what? We are better off spending this money to make the shareholders happy than spending it doing what we are allegedly supposed to be doing, which is discovering drugs,'" Lowe said.

AP05051602420.jpgBill Gates at the 2005 World Health Assembly [Anja Niedringhaus/AP]

I asked Lowe about the state of the industry. "It's tough right now because the drug industry is at this adolescent stage, we're at that awkward stage. We've gone through a lot of the easy targets, and there's a lot of real big opportunities out there, but the reason they're big opportunities is because nobody's been able to do anything with them," Lowe said. "We keep spending tons of money on these things and missing."

Jack Scannell is one of the people trying to usher in a new era of drug discovery. "In very broad terms, I'm pretty pessimistic about the industry," Scannell said. "I don't think at a sort of aggregate, macro level classical R&D as it's been done for the last forty or fifty years has a particularly bright future." Scannell is British, and dropped out of medical school in favor of a PhD in computational neuroscience from Newcastle University. He met Malcolm Young there, and the pair worked a together on systems for analyzing networks, specifically for mapping neuronal activity.

Scannell worked as a consultant in the drug industry and then as an equity analyst, but quit last year to team up with Young once more at small biotech firm Scannell described as "heretical." The company is called e-Therapeutics, and its approaching drug design via the pair's background in networks. "Go back to how the drug industry says it discovers drugs. It looks for individual targets and then it optimizes drugs for high affinity binding on that target," Scannell said. The strategy, to Scannell's and Young's eyes, fails to take into account the complexity of biological systems.

"If you look at the structure of protein-protein interaction networks in cells, or the metabolic networks, these have been designed by evolution to be robust. You've got feedback loops, you've got parallel pathways, you've got redundancies. And what that says is, if you start your search process looking for an individual molecular component you want to perturb to influence a disease, probably evolution has designed your cell that, if you perturb that component, nothing is going to happen." Given the approach, Scannell said, "Maybe it shouldn't be surprising that 95 percent of drugs going into clinical trials fail."

"Historically, you can make a very strong case that the way drugs were discovered when it was cheap and easy -- you can't do all this now because of the regulators, but some of this you might be able to do -- was essentially through broad phenotypic screening, very often in man," Scannell said. "Drugs were regarded as potential tools that might do something useful, and then people essentially searched for uses for the tool. And today we do the exact opposite. Which is we say, we want something that cures Alzheimer's disease, let's design something that cures Alzheimer's disease, and frankly that just doesn't work."

I asked Derek Lowe, the chemist and blogger, for his thoughts on the principle of delinking R&D from the actual manufacture of drugs, and why he thought the industry, facing such a daunting outlook, would reject an idea that could turn fallow fields of research on neglected diseases into profitable ones. "I really think it could be viable," he said. "I would like to see it given a real trial, and neglected diseases might be the place to do it. As it is, we really already kind of have a prize model in the developed countries, market exclusivity. But, at the same time, you could look at it and it will say, 'You will only make this amount of money and not one penny more by curing this tropical disease.' Their fear probably is that if that model works great, then we'll move on to all the other diseases."


In January, at the final WHO meeting before the World Health Assembly in late May, a number of countries began agitating over the circumstances of the November meeting. China, in particularly, argued loudly for the democratic ideals of the WHO, and every state's right to be heard. The meeting grew so contentious that the Director-General, Margaret Chan, began to sing "Getting to Know You," from the musical The King and I to try to calm the negotiators.

The tactic failed, and Nils Daulaire made it clear that the U.S. would kill what remained of the idea if any country moved to reopen negotiations at the World Health Assembly.

I spoke with Daulaire in February, and asked him to clarify the U.S. position. "I'm not sure that I understand that the treaty is the sole way or the preferred way to get to the aim that we have, which is to make more products available at affordable or no cost to the people who need it most," Daulaire said. "I think the idea of the treaty is ill-considered, and is not going to lead us in the direction we want to go."

Daulaire argued that the process of drafting a treaty is long and expensive, and that it would be better to model something on the Global Fund to Fight AIDS, Tuberculosis and Malaria or the GAVI alliance. "If we had started that process [of designing GAVI ] in 2000 by proposing that we would have a binding international treaty with required contributions, etc. we would still be negotiating the terms of that treaty," Daulaire said. "I just consider the amount of time we're spending debating what is essentially a dead idea to be not very well spent. It's simply a dumb idea."

Ideas, though, are powerful things, and last September, as it became clear that the developing world planned to fight for the treaty at the November meeting, Daulaire's office put out a quiet call for competing ideas. The request came via email from the Institute of Medicine, a wing of the National Academy of Science. The message was leaked to the blog Don't Trade Our Lives Away .

"HHS was hoping that an independent body such as IOM could suggest alternative ideas for consideration at the WHO," the email reads. "Given that these ideas need to be developed before the WHO Executive Board meeting in January, there is insufficient time (and insufficient money) to employ the usual IOM consensus committee study process." It concludes, "The IOM is committed to being of service to the country and this is one of the times when we can pull together and make a special contribution."

Daulaire arrived at the November meeting in Geneva without a competing idea to put forward.

Daulaire's other suggestion has been criticized. "You cannot think that the R&D mess that we are currently in is going to be solved with the GAVI model," Judit Rius of MSF said. "GAVI is basically about taking vaccines that have been produced by Pfizer, GSK, and by other northern pharmaceutical companies, and giving those companies huge subsidies so that they will give time-limited price discounts and accelerate delivery to the developing world."

This R&D void was also acknowledged by John-Arne Røttingen, the Norwegian doctor who led the second expert working group for the WHO, known as the Consultative Expert Working Group (CEWG). The report of a first expert group was thrown out for issues of political malfeasance -- it became clear that proposals from developing countries were excluded from consideration, and that experts met with pharmaceutical industry representatives but not civil society members.

I spoke with Røttingen by phone, and asked if he thought the ideas within the R&D treaty could be implemented through some kind of global partnership. "To actually get agreement on something like this with wide member state involvement, you need some sort of platform to negotiate," he said, implying a treaty negotiation would provide such a forum. "GAVI and the Global Fund are first and foremost mechanisms for procurement for commodities that already exist. The R&D landscape is completely different. In addition to agreeing on financing and doing collective action here, you also need to agree on some principles and norms on how to structure the R&D system. That's a lot more complicated than just buying commodities in a market."

I first learned about the R&D treaty in December, in a speech Røttingen gave at conference at Mt. Sinai Medical School, in New York. In his talk, he specifically called on the Gates Foundation to take a position on the matter. The Foundation is the one of the WHO's largest funders, and its second largest funder of researcher for neglected diseases -- only the U.S. government contributes more each year.

"The Gates Foundation has unfortunately been very absent in the process," Røttingen said when we spoke. "They have not been willing to engage I would say, and have not come forward with any constructive ideas on how they could be a part of a more concerted action. They seem to be satisfied with the status quo where governments are in general not contributing their fair share to this area of R&D."

Their absence has been noted by others. "I think it's very interesting that Gates is not commentating on this," one longtime observer said. "He has been asked about it, and he either claims to not to know anything about it or says, 'Oh that might be interesting, we have to look into it.' But they are singularly failing to publicly engage in this despite Gates acknowledging the lack of funding. And I think that's a sign in itself."

The Foundation did not respond to multiple requests for comment for this piece.

I spoke with Jamie Love again in March as the WHA meeting approached. He was in Geneva once more, this time working to expand copyright exceptions for products that benefit the blind. I asked him for his thoughts on whether the idea could be brought to life through some agreement other than a treaty.

"You can argue about whether or not it should be through treaty or some other legal instrument, but that's a separate issue of whether the commitments should have a binding nature," Love said. "And if you look at what takes place at GAVI or these other PDPs or the Global fund, they've struggled to keep their funding levels up." He added by email: "It depends a lot on what you think you are doing -- creating a global system of finance, or just passing the hat for some odd donations."

I also asked Love about Gates's role in the process.

"Frankly, it's our perception that they're really, in their own channels, in opposition to it," Love said. "We'd like to be able to work with them once in a while, not always be the on the other side of the street," he added. "Nobody's really eager to make enemies of the biggest philanthropist there ever was, right? But we've kind of done it I guess, because you know sometimes you just gotta do what you gotta do. You can't ignore some issues, so we step up, which we often do when other people are looking for cover."

Love and others point to Gates's complicated history with Microsoft and his departure from Harvard as an undergraduate as coloring his view on the need for strong intellectual property law.

"He slowly, as Foundation and as a philanthropist, is being drawn into more open-source policies," Love said. "If you look at the licensing he does on his own government-funded research, he has experienced a little bit of frustration when he doesn't get sufficient openness in the research he's funded himself, so he's begin to put things that much very much like open-source provisions in his own licenses," Love said. "That has been progress, and people have noticed that. It used to be that if you applied to the program to fund libraries -- I know somebody that did this -- she was told you had to eliminate the words 'open-source' because they couldn't fund anything that had even the words."

In the current debate, documents submitted to WHO working groups attacking the idea were largely authored by individuals and groups that receive support from Gates.

The Gates Foundation was also the largest funder of Nils Dualaire's Global Health Council. They donated more than $30 million.

On May 19th, Jamie Love will again fly to Geneva, this time for the 66th World Health Assembly. It remains unclear whether the developing world states will challenge Nils Daulaire and his promise to kill what remains of the R&D treaty.