The Ongoing Fight to Publish an HIV Cure

Introduction.

In the following pages, I relate the history of the successful development of a genetic cure for the Human Immunodeficiency Virus (1). I’m writing this in the hopes that you will find the information I present interesting enough to scientifically verify. Later on in the article, I explain exactly how the gene therapy might be recovered from persons who have received the therapeutic genes. I will also elaborate some of the implications – economic and social – of a successful cure for HIV.  

Origins of the HIV cure.

In September 1988, I was beginning a PhD program in Developmental Biology at SUNY Stony Brook just after completing my Bachelor’s in Biology at Columbia University. The HIV pandemic was raging: a diagnosis of HIV-positive was an almost certain death sentence. That semester, as I was studying the lambda repressor for a molecular biology class, it occurred to me that it might be possible to introduce genetic material into HIV-infected cells that would code for a molecule that would shut down the virus.  

In September of the following year, I was recruited into the Central Intelligence Agency. My idea was brought to the attention of a senior member of the State Department, and I was subsequently invited to explain this idea to the science advisors of then-President George H.W. Bush, who was also present (and who, parenthetically, is no slouch in Biology). During our conference, it was conceded that the HIV virus had likely been engineered; despite extensive investigation, however, the CIA was unaware of who might have done so. It was further explained that for purposes of national security, the source did not so much matter: we needed to move ahead with the development of the cure. 

Dick Cheney, who was the Defense Department Secretary at the time, raised forcible objections to the proposal. The implications of a genetic therapy were immediately obvious, long before the actual cure was developed. Chief among those considerations for Mr. Cheney were economic in nature. A gene therapy that would provide long term protection after a single dose would render the pharmaceutical treatments unnecessary. Although the pharmacopeia for HIV was in its infancy at the time, it would eventually grow into a never-ending cash crop that only became more lucrative when the “drug cocktail” for HIV was developed in 1995, making it possible to survive an HIV-positive diagnosis indefinitely (2). Since the medications would never totally eradicate the disease, HIV-infected persons would thus be dependent on the medications for the rest of their now-extended lives.  

The AIDS epidemic – early stages

In the early stages of the AIDS epidemic, scientists held out hope that the disease would eventually mutate out of pathogenicity, as is common in many epidemics. The Black Death, for example, killed a third of Europe, but raged only for about seven years. This hope was founded on the fact that microorganisms, especially viruses, mutate much faster than human eukaryotic cells, meaning that they accumulate genetic “mistakes” faster. Also, they lack the DNA correcting mechanisms that are native to the cells of more complicated organisms (3).  

Paradoxically, this was the argument presented to explain the longevity of the HIV epidemic. We were told that because it mutated quickly, it rapidly developed into strains that were resistant to the available pharmaceutical treatments for HIV infection. The problem is that HIV has an extremely small genome, which codes for approximately nine primary proteins, which are subsequently processed into about 19 smaller gene products (4). There isn’t a lot of room for variation here. Proteins are extremely sequence-specific, and it is this specificity that enables them to carry out their extremely specific functions. A protein can only be modified so much before it loses its function entirely. The fact that HIV was still evolving dangerous pathological strains more than 30 years after being first identified needs to be regarded as extremely suspicious, and suggests strongly that the virus was being “upgraded” periodically. 

For exactly the same reason, the lackluster results of numerous HIV vaccine trials need to be examined carefully. The main goal of vaccine research is to raise broadly neutralizing antibodies that take out as much of the virus population as possible. There is some controversy surrounding the development of broadly-neutralizing antibodies for enhancing innate immunity against HIV. The argument presented to explain the minimal performance of the vaccine trials is that the surface of HIV is covered with glycosyl residues that vary too much to make successful targets. (5) In this way, HIV is not different from Hepatitis B Virus, or Influenza virus, or really any other virus. (6,7) Alternative studies suggest that antibodies can target the glycosyl residues that bind membrane gp120 or gp41, but not soluble Env. (8) Again, because HIV proteins (e.g. gp120 – the molecule by which HIV gains entry into a cell) can only vary so much before they become non-functional, it will be worthwhile to carefully review the conditions under which the vaccine trials were conducted to confirm that they were deliberately sabotaged.  

Also: in retrospect, the story that HIV had arisen in African Green Monkeys should have been regarded more critically. Viruses tend to be very host-specific, and jump species only rarely. (9)  While it is in fact plausible that a simian virus might have been transmitted to humans, it does not invalidate the possibility that the virus was deliberately engineered. Looking back on the history of the development of HIV with this in mind, the occurrence of Green Monkeys with an HIV-like pathology makes perfect sense if the Green Monkeys are seen as animal models for what would ultimately emerge as HIV.  

Who did it?

If we accept the possibility that HIV had been deliberately engineered, and occasionally modified in order to develop resistant strains and maintain its pathogenicity, the obvious question becomes: who would do such a thing? The answer would have to take into account three main factors: 1) idealogy, 2) technological capacity, and 3) financial means. At the time of my conference with Mr. Bush, the CIA had been keeping an eye on some unusual activity at a port in Namibia. It seemed an odd place for Chinese nationals to be conducting research. This particular party seemed to fit the bill. Ideologically, these were scientists whose morality was shaped by Malthusian considerations. Their socio-demographic was characterized as strongly homophobic. And they had the requisite technical capacity and financial resources to conduct the experimentation needed to develop a bio-weapon such as HIV. Many years later (2002) suspicions were heightened still further when an epidemiology team visited Beijing to provide tactical assistance with the bird flu outbreak. In the course of their investigation of the epidemic, they ran into intractable obfuscation in the vicinity of a large laboratory in Beijing with official ties to the researchers being followed in Namibia.    

Early Clinical Trials. 

It was estimated that the genetic approach to an HIV cure would take years to develop. By 1990, however, the first safety trials were underway. HIV-infected persons with full-blown AIDS who were nearly at death’s door were inoculated with a prototypical adeno-associated virus (AAV) carrying genes that encoded segments of HIV proteins designed to boost their immune response to the HIV virus. All of them perished, most likely due to the demands placed on an already over-stressed and critically impaired immune system. The AAV likely contributed to that stress. It became clear that a suitable vector would have to be engineered to safely deliver a genetic cure. [Addendum: in retrospect, it is entirely possible that the test patients had been inoculated against the AAV vector. AAV is not entirely non-immunogenic (unlike FIV), and vaccinating already-immunocompromised individuals against the AAV may have been what killed them.]

Despite this initial setback, the idea of a gene therapy for HIV did not perish. It was realized early on that medications costing upwards of $14,000 to $20,000 per person per year (pppy) (10) posed a completely unsustainable economic burden, especially considering that the patients with full-blown AIDS requiring a medication regimen this expensive might be unable to contribute to the cost of end-of-life care. In Africa, where treatment cost up to $3000 pppy, (11) the HIV epidemic was estimated to slow the economic growth of Sub-Saharan nations by 3 to 4 percent per year.  

Progress continued on HIV cure research throughout the 1990s. The HIV genome was sequenced early on, and bio-researchers expanded their understanding of the functions of the various HIV genes. There are approximately 10 steps in the life cycle of the HIV virus that are vulnerable to disruption (12) – these were successfully targeted in vitro with drugs; singly at first, and then someone had the bright idea of administering several drugs at once, thereby creating the Highly Aggressive Anti-Retroviral Therapy (HAART), or “drug cocktail.” (13) With the advent of the HAART therapy, HIV changed from a lethal disease to a manageable chronic infection. But it was universally conceded in the bioresearch community that because HIV could harbor in the genome of literally any cell type in the body, there would never be a pharmacological “silver-bullet” that could knock it out entirely.  

As a general rule, anything that is susceptible to small-drugs will be vulnerable to genetic intervention. But the real stumbling-block was the delivery system (i.e. the vector). We needed a vector that could transduce human cells in vivo, safely and effectively, and on a long-term basis. In practice, this means delivering the genetic payload in such a way that it integrates into the genome of the patient, without setting off an oncogene or a potentially fatal reaction to the delivery system itself. (14) The failure of the early AAV clinical trials pointed up the need for suitable animal models. HIV does not normally infect mice, so “humanized” mice had to be genetically engineered to carry T-cells with human T-cell receptors. (15, 16)  

In 1999, I went back to school at New York University to get a Master’s degree in Recombinant DNA Technology. In March of 2000, the night before an interview for admission to a doctoral program at Mt. Sinai School of Medicine, as I was falling asleep, I had a vision of how a delivery vector might be rigged to turn off its own replication once the target virus was gone. I described this to Dr. AR at Mt. Sinai’s Department of Gene Therapy, who gave it the title: “A Replication-Competent, Auto-Inhibiting Vector.” I also explained it to Dr. PP, a prominent influenza researcher at Mt. Sinai, who compared it favorably to a Rube Goldberg machine (PP, personal communication, January 2001). I had a conference with Dr. MK, Chief of Infectious Diseases at Mt. Sinai, in which we talked about the clinical implications for a virus that was capable of hiding in the genome of any cell in the body (MK, personal communication, January, 2001). What came out of this particular conference is what I like to call “The Ugly Compromise.” Simply put, even if a long-lasting, safe, and effective HIV cure that functioned after a single administration could be developed, the pharmaceutical industry would suffer unimaginable economic consequences. However, if an effective genetic cure was delivered using HIV itself as the delivery system, nobody would really be any the wiser; HIV-positive persons would be non-symptomatic and non-infectious, but still HIV-positive, and would therefore still serve as a market for HIV drugs.  

If so, why develop a cure at all? 

By this time, there were three convergent forces at work. First, there was the looming economic apocalypse presented by the prospect of funding HIV medications for HIV-infected people who, even if they were healthy enough to work for the rest of their lives, would probably never earn enough to repay the cost of their medications and treatment. The staggering remunerative rewards of the HIV pharmacopeia were available only to a very select few. The prospect of rounding up and gassing the HIV-infected does not play well in America, although it was certainly not off the table in certain circles. Second, there were the profound psycho-social ramifications of a lethal sexually-transmitted virus. Sex is perhaps the most powerful biological drive there is. Bottling up a biological drive leads to unimaginable violence. Third, in an effort to contain the HIV epidemic, the CIA had officially sanctioned the killing of sex-workers: as an unintended by-product, America developed a popular media culture which deified serial killers. The AIDS epidemic was handed to the Clinton administration as a problem which, if not fixed, would destroy the world.  

Research on the cure progresses.

For strategic reasons (explained later), it was sagaciously decided that work on an HIV cure was going to have to be performed under conditions known to the Intelligence Community as “black.” While the world indulged in salacious gossip about Bill Clinton’s sex-life, work on a delivery system for the HIV cure continued. By 1998, scientists were using an HIV-based vector with a modified surface molecule (i.e. “pseudo-typed”) allowing them to target the vector to human T-cells. (17) Researchers had successfully knocked HIV out of the T-cells of a humanized mouse. The trouble was, HIV needed to be knocked out of every type of cell that could harbor HIV. The mouse’s T-cells could be cleared of HIV, but T-cells have a defined lifespan and once the original population of transduced T-cells was replaced, the infection rebounded. (18) In order to create a bigger pool of immune cells that were resistant to HIV infection, we needed to know more about stem cells – the precursors that give rise to the various types of immune cells.   

In 2001, George W. Bush took office. The high regard I have for his father is exactly mirrored by my disregard for “Shrub.” Obscured by the smokescreen generated by two unnecessary wars, he created a multi-billion dollar slush-fund called “President’s Emergency Plan for AIDS Relief” (PEPFAR) (19) - the unstated agenda was essentially to ensure that HIV-infected persons in Africa were taking their medications. Another aspect of this project was to hobble the vaccine trials being conducted in Africa and Southeast Asia. After all, HIV drugs that had taken several years and billions of dollars to develop had to produce some return on investment, and it was proving difficult to market the drugs in the Third World without taking a haircut on the cost of the treatments. (20) Not coincidentally, one of the earliest actions of George W Bush’s administration was to pass legislation that would make experiments with stem cell technology harder to do. (21) This would hinder efforts to test a genetic HIV cure that needed to be introduced into hematopoietic stem cells, not to mention crippling the American biotechnology sector in general. The development of the HIV cure continued in secret, however, and by 2002, clandestine trials on human subjects had begun in Africa. And here is where the story of the HIV cure develops an ethical kink.  

The ethical kink.

As previously mentioned, although it is commonly understood that HIV primarily attacks immune cells, it is not as commonly known that HIV can linger in the genome of literally every cell and tissue in the body. (22) The only way a gene therapy could triumph over HIV completely would be if it were universally tropic (i.e. capable of being expressed in every cell that might harbor HIV). One implication of this is that such a vector could potentially be “horizontally transmitted”- in other words, transmitted through bodily fluids, in exactly the same way the HIV virus is transmitted. (23) The chances of a regulatory agency such as the Food and Drug Administration (FDA) approving such a technology are diminishingly small. Another implication is that the vector might be “vertically transmitted” (i.e. passed down to genetic offspring). The chances of the FDA approving such a technology are absolutely zero. (24) Furthermore, in light of the popular public perception that genetically modified organisms are evil, it was supposed that getting any regulatory agency’s permission to permanently alter the human genetic lineage (no matter how benevolent the intent), would be completely impossible. It was decided to not ask.  

Clinical trials.

In 2002, clinical trials began using an FIV-based vector to deliver a gene to prohibit the proliferation of HIV. By this time, it had been clearly established that FIV – the feline version of HIV – could adequately transduce cells in vivo. (25) FIV had been found to be completely non-immunogenic in humans – despite any number of exposures, FIV had never been shown to produce any sort of human pathology. (26) This made it the ideal virus for a viral-based delivery system. The first in vivo clinical trials were conducted clandestinely in Africa by U.S. Naval Intelligence. The results were immediate and very gratifying. In persons who had been exposed to the vector, viral load dropped to undetectable levels and stayed there, whether or not the person was taking anti-retroviral drugs. Subsequent research showed that the vector was indeed transmitted both horizontally and vertically, as expected.  

Now what?

At this point, one might reasonably anticipate a happy ending. Hooray, HIV is cured, it is now safe to make love again. However, “The Ugly Compromise” was still in play. The public has to be made aware of the fact of the cure. Until the cure for HIV is publically acknowledged and explicitly verified, sexual security will be forever unattainable. On the other hand, the CIA was not prepared to divulge all the details of the vector that had already been developed: in particular, the fact that it is universally tropic, with the potential for vertical transmission. To be fair, this is extremely sensitive information. The mere fact that it can be done means that someone might try it, but with less benevolent intentions.    

Early development, civilian science.

As I mentioned above, the first clinical trials were conducted under strict secrecy, due to the fact that the vector was capable of transducing literally every type of human cell. This further implied that the delivery system, having been successfully validated, would need to be re-developed independently under civilian auspices, but modified in such a way as to only affect immune cells. Deployment of a vector that could transduce literally every type of cell is a huge ethical leap that would have to be taken in stages, while the human race adjusted to the idea that the human genetic lineage could be altered. 

Additionally, during the development of the original vector, our research group became aware of the magnitude of the opposition the pharmaceutical industry (which, at the time, had deep connections with the CIA and the NSA) was apparently willing to raise against an HIV cure. By the time the clinical trials were successfully concluded, it was apparent that the entire civilian US Biotechnology sector had been essentially paralyzed. Any basic research which did not favor the pharmaceutical interests would essentially be doomed, with almost no chance whatever for getting funded through the usual channels. The job of re-developing the HIV cure under civilian auspices now involved a “cat-and-mouse” game with malfeasant elements of the US government (and other interests), which by then had the means (financial), motive (self-preservation), and opportunity (technological hegemony) both to prevent the cure from being re-developed, and to prevent the public from ever learning about it. It would become necessary to identify and isolate the entities that were disrupting both scientific research and the grant-funding process. As I was the original author of the delivery system, this project (along with all of its implications) landed back in my lap, 20 years after I’d first conceived of a gene therapy.  

In 2008, I met Dr. WS (formerly a Senior Principal at a major biotechnology company) at a job fair. I related to him the technical details of the vector’s delivery system: recognizing it as an idea with merit, he encouraged me to form a Biotechnology startup. I enlisted a trusted friend as CEO, and formed VectorGen, LLC, as a funding entity for grant applications. Mr. McH, a successful business developer, gave the company its name, and lent professional credibility to the entire endeavor, leading to the inclusion of VectorGen in a business incubator at New Jersey City University, and fostering an early collaboration with researchers at NJCU.  

In 2009, I was researching monovalent antibodies – pieces of an antibody molecule that recognize very specific targets. I was intending to make use of these to target the vector specifically to cells that were HIV infected. I made a phone call to a researcher, and was told in discouraging terms that this particular avenue had been thoroughly explored, and found not to work. Although I didn’t suspect this at the time, it is likely that an intercept order had been placed on my cell phone (later on this became a certainty). This may have been one of the first “interdicted” conversations. Although I don’t know exactly who I was speaking to, it was likely not the bio-researcher I was trying to reach. A more recent literature search turned up several papers on the use of monovalent antibodies for successfully targeting phage delivery systems. (27, 28) There is no reason to suppose that this approach would not have worked for targeting HIV-based vectors. 

By the mid-1990’s, the NSA had developed the capacity for comprehensively monitoring internet traffic and cell phone transmissions, using a program titled “Echelon.” (29, 30) With Echelon and the surveillance technology that succeeded it (PRISM), it became possible to quarantine very specific information on the internet, at least on a temporary basis, and only on machines available to a specific researcher. This capacity adds an intractable complication to the conduct of bioresearch, which depends critically on being able to review previous published experiments, develop new research tools, and make the results of one’s research available to other scientists. Obviously it would be somewhat problematic to eradicate widely known information (such as this year’s winner of the Superbowl) off the internet. But highly technical information that is vital for the conduct of a research program might be hidden in this manner.  

In writing this article, I tried to recapitulate the results of a search I had done a few years ago for information about an HIV molecule called “p6”. If I plug “HIV” into a browser, I get 171,000,000,000 hits. Searching for “p6” in Google gets a lot of hits, but doesn’t turn up anything relevant to the HIV protein. I put “HIV” and “p6” into a browser, and I get 401,000 results. So I am at a loss to explain how it is that when I was searching for information on p6 (at the time I was doing the search, the information I sought was critical to the composition of a time-sensitive grant application), plugging both “HIV” and “p6” into a browser turned up absolutely no results at all. Zero. 

Applications for funding.

In 2010, I moved to upstate New York, to accept a position as a Senior Research Technician at Albany Medical College. I moved VectorGen’s headquarters to Albany in 2012, and sought out researchers who could help with grant applications. I developed collaborative relationships with researchers at Albany Medical College, and Rensselaer Polytechnic Institute (RPI). VectorGen was accepted for inclusion in a business incubator at R.P.I. I secured an agreement to allow me the use of a laboratory space in Rensselaer. We consulted with a patent attorney, and filed a provisional patent application. Over the next several years, I wrote two Small Business Innovative Research (SBIR) grants, an R21 grant, a Letter of Intent submitted to the Gates Foundation, an application for funding through Breakout Labs, a proposal to Rho Ventures, a crowd-funding proposal on Experiment.com, and an application for the Jeff Lawrence Innovation Fund through Fuzehub.  

As I mentioned earlier, getting money for research from the NIH is difficult, even under the best of circumstances. The National Institute for Allergies and Infectious Diseases is only funding about (24) percent of the grant applications they receive. In order to present a meaningful application, several elements are absolutely necessary. (31) One needs a suitable Principal Investigator, with a doctoral degree, expertise in the specific field of research, experience directing a research project, and ideally, a proven track record getting successfully funded. Also, since SBIR money cannot be used to outfit and provision a laboratory, it is necessary to have an already fully-equipped laboratory, which, for our purposes, meant BioSafety Level 2. And most critically, one needs what’s known as “prior data” – experimentation that validates some elemental aspect of the design - even if the particular funding mechanism claims it not required. 

Getting prior data is a famous chicken-and-egg problem. To get funding, one needs prior data. To get data, one needs funding. Most researchers start their careers as post-doctoral workers after finishing a PhD program. Post-doctoral work usually involves spinning off one’s own project from an already-established Principal Investigator’s laboratory, which serves as a springboard for future research. Unfortunately, this wasn’t an available option for me. In the role of a civilian researcher with an MS, I was qualified to be a Research Technician performing experiments in someone else’s lab, with minimal input into the research strategy. I had no laboratory facilities of my own, no publications, no experience writing grant applications, and no prior data.  

The first couple of grants I submitted to the National Institute of Allergies and Infectious Diseases at the National Institutes of Health were SBIR grants on behalf of VectorGen. SBIR money may not be used for laboratory equipment such as centrifuges or laminar flow hoods. Lacking an already fully-outfitted laboratory space and a suitable Principal Investigator, I recruited Dr. KD, formerly at Albany Medical College (AMC), who agreed to allow me the use of her laboratory space and assisted with the composition of an R21 grant application, submitted under the auspices of Albany Medical College. Dr. CD, also of Albany Medical College, also materially contributed to the design of the auto-regulatory mechanism and assisted with the grant application. Dr. Wilfredo Colon at Renssalaer Polytechnic Institute (RPI) offered to perform stability testing on our therapeutic molecule. In an effort to acquire funding for the proof-of-concept experiments, we recruited business students at the Lally School of RPI to do outreach to organizations who might be funding HIV research. I recruited Mr. Eric Shannon, a brilliant young graduate of RPI’s Lally School, to be VectorGen’s Chief Operating Officer. Mr. Shannon provided invaluable assistance with the development of our website, and our provisional patent application, in addition to countless other tasks. We reached out to angel investors and venture capitalists in the Capital District who might consider funding our experiments.

In 2012, we met Mr. Stephen Petti, a successful serial entrepreneur, who agreed to present our work to a group of investors at RPI. We quickly learned that investors like to see an return-on-investment in five years or less, but we did not anticipate having anything marketable within that time-frame. We also learned that investors want to see that members of a corporation are confident enough to invest some of their own resources into a project. For his own reasons, Mr. Petti was not prepared to invest at that level, although the business plan he wrote was quite valuable, and formed the basis for a very comprehensive business plan ultimately completed by Eric Shannon. It was Mr. Petti who used the term “pharmaco-economic argument” to characterize the extremely forceful economic motivations for developing it. Given the potential magnitude of the cure’s economic impact, I thought to reach out to economists, in order to develop economic arguments for carrying out the research. In essence, since the cure threatened to obliterate a billion dollar pharmaceutical sector, I wanted reasoned, mathematically well-grounded counter-arguments to support our contention that the HIV cure had to be developed.

Frustration.

Around this time, I began to observe a tedious pattern in my efforts to develop relationships with collaborators. Generally, I would make contact with a scientist to introduce them to the company, and explain a little about our proposed research. After initial expressions of enthusiasm and encouragement, I would send them a more detailed explanation of how the vector worked. As a precaution, we generally took the measure of instating a Non-Disclosure Agreement (NDA) with researchers before divulging any proprietary information. And then a delay would set in. We would exchange emails; the researcher would be out of town, or down with the flu; and a few weeks would go by. There would be some phone-tagging. Then more phone-tagging, and some back-and-forth trying to arrange a conference about the research strategy or a meeting time for grant mentoring. After a prolonged silence, I would get a terse communication – sometimes as many as two sentences - saying the researcher would not be able to devote any more time to the project.  This happened with VectaLys, a French company that specialized in vector research. It happened with Dr. Marty Chalfie, a Nobelist at Columbia University, who taught me Genetics while I was a student there. It happened with Dr. Jeffrey Sachs, the head of the Earth Institute at Columbia – perhaps the most qualified person to pronounce on the likely economic implications of our research. It happened when I was looking for seed /money at the Biomedical Accelerator and Commercialization Center (BACC) at Albany Medical College. It happened when I submitted a Letter of Inquiry to the Bill and Melinda Gates Foundation. It happened when I sought to communicate with researchers at GE-Global Research about a possible collaboration. It happened when I tried to submit this article to numerous news outlets – most recently with Marshall Allen of ProPublica. 

Most disturbingly, this happened while I was developing a collaborative relationship with Dr. Daniel Pack, an HIV researcher at University of Kentucky at Lexington. Dr. Pack was a chaired professor with appointments in two departments who had agreed to assist with the composition of another grant application. We’d had a few phone conversations; he’d signed an NDA…and then he dropped out of sight entirely. He didn’t return calls to his cell phone. His office phone wouldn’t go to voicemail. I tried calling his secretary – the person on the other end said he was in the other department, but she didn’t know the number.

Interdiction, Part I: Misappropriated Grant Funds.

In 2013, I developed a mentoring relationship with Dr KD at Albany Medical College, who generously donated her time to helping me through the process of applying for an R21 grant through the NIH. Unlike the SBIR grant (approximately $50K for 6 months to a year), the R21 is substantially larger ($250K). The R21 grant, if I had received the money, would have provided an adequate salary for myself, and funded my research for approximately two years. Had I received the money in 2013, I might be well on my way into clinical trials as of this writing (2019). 

But I never received the money. 

Given the technical content of the R21 grant application, it would be reasonable to expect that it would be evaluated by scientists who were familiar with the gene delivery and knowledgeable about virology and molecular genetics generally. But when I took a really objective look at the reviews I got back from the R21 submission, I noticed several glaring discrepancies. One reviewer, displaying an unforgiveable ignorance of viral-based vectors, was apparently unaware that FIV had been successfully used for gene delivery both in vitro and in vivo. One reviewer wrote there was no published evidence suggesting that the approaches I presented would work, ignoring a comprehensive list of peer-reviewed sources I had provided to back up every single element of the design. Overall, the comments suggested that the reviews were written by persons with only the most minimal understanding of genetics.  In fact, it seemed the authors of the reviews I received were not only ignorant of current gene therapy technology – but intentionally devaluing the project. 

At this point, I started to suspect that the Summary Statements I had received were not, in fact, written by scientists recruited by the NIH to review grant applications. I concluded that the reviews had been written by people who were completely uninterested in understanding the proposed research, and instead putting forth a thinly veiled attempt to invalidate the project entirely.

Around the time I filed the R21 application, I noticed that someone had opened a “placeholder” website for a company called VectorGene. The website contained a single picture of an electron micrograph, and no contact information. 

I’m going to advance a hypothesis here, in the full understanding that it sounds a little sketchy. Anyone with adequate skills in coding would have the capability of putting up a placeholder webpage. But hacking the NIH systems would require more than adequate coding skills. It would require someone with the capability of hacking into the NIH grant submissions system, and hijacking the communications between the NIH and the reviewers they had retained to review the grant applications. 

Now, keep in mind the implications of an HIV cure. Not a treatment. Not a vaccine. An actual cure that threatens to obviate a trillion dollar pharmaceutical sector. Note carefully, a trillion dollar industry. I am directly alleging that elements of the pharmaceutical sector are sufficiently liquid, and could easily access resources to intercept VectorGen’s grant application; change the name of the company on the application to VectorGene, and add their own contact information; install a cutout between the NIH and the scientists selected to review VectorGen’s application; insert their own faux-science Summary Statements to be returned to me; and then live it up on the misappropriated funds, while making academic jokes about getting funded to study the interaction of lobster, caviar, and champagne. 

Interdiction, Part II: Is there anyone else there I could talk to?

I didn’t fare any better with the Gates Foundation. In 2014, I put a lot of effort into composing a Letter of Inquiry, which I then sent off to the Gates Foundation, including with it a request to speak to a representative who could knowledgeably converse about the distinction between a gene therapy and a vaccine. (I should add that at the time I wrote the LOI, the Foundation website stipulated that they were only funding vaccine research).  I waited the requisite 10 weeks for a reply but received nothing. I then began calling the Foundation on a daily basis. Each time I was told (by the same person, who generally answered on the first couple of rings), that because the Gates Foundation received tens of thousands of calls per day, that there was no way they could forward my calls. I politely explained that I had a scientific question that needed to be addressed by someone qualified to have a technical discussion. Occasionally, I would be allowed to leave a message on the Grants Information line; this too, failed to elicit any response. I was also told that because they were at a “secure campus” that I could not be transferred to anyone at the Foundation unless I had the name of the specific person I wanted to reach. I did not, nor was that information available from the Gates Foundation website. After several weeks I was told it was unlikely that the Gates Foundation would ever respond.  

Interdiction, Part III: Grant Funds Hijacked Again?

In 2017, I tried applying for funding through New York State Division of Science and Technology. I formed a partnership with one of New York State’s Centers for Advanced Technology at the University of Buffalo, and applied for about $75,000 for one year of research through Fuzehub, a networking organization for NY State manufacturers. 

Around the time the awards were supposed to be announced, I checked on the status of our application on the Fuzehub; I was ecstatic to observe that University of Buffalo had been awarded $75,000 – the same amount as our grant application. I eagerly dialed the official at UBuffalo responsible for grant management. The person at the other end of the line expressed regrets in disingenuous tones, reporting that UBuffalo had not received any funding. 

Dejected, I went to the Fuzehub office in person to inquire what had happened. Apparently UBuffalo had received a $75K grant, but no-one was quite sure what had happened to the money.

Further complications.

Meanwhile, I continued to work on finding ways to get prior data to support our grant applications. In collaboration with Dr. CD at AMC, we came up with a genetic sequence for the therapeutic molecule that we wanted to test. By this time, we’d successfully negotiated a relationship with a reputable Contract Research Organization (CRO) in Maryland [name redacted to protect the company] that had agreed to perform the necessary proof-of-contact research on a pro bono basis. According to the agreement we worked out, VectorGen would keep the Intellectual Property if we supplied the genetic material. Eric Shannon and I pooled our resources, and scraped about $1,500 together to purchase some genetic material for testing.

I was ecstatic when we signed the contract with the CRO, hoping that we might finally see some traction. And yet, months went by and no significant progress was made. It seemed the CRO was having minor technical difficulties – at first, a possible mycoplasma contamination…then the cells selected for transfection showed very little evidence of transfection…then the project got transferred to somebody else at the research facility…and then they tried a different type of cell line…and I started to get discouraged. The CRO was in Maryland, and I live in upstate New York, so I couldn’t oversee the experimentation in person. Several months after the CRO received our genetic material, with no measurable progress, they informed us that they could not continue the research on a pro-bono basis. 

Bioresearch takes a long time, and progress is frequently incremental. Experimental procedures are quite delicate, and a mistake at any point can ruin days or weeks worth of work. Consequently, biological experiments are quite easy to sabotage. If an experiment doesn’t yield the desired results, a great deal of troubleshooting has to be done. Did a reagent go bad from being left out of the incubator? Are the cells viable? Did the cell media get contaminated? Experiments can take months to bear fruit, even in the absence of any malfeasance. The problem becomes completely intractable when sabotage is suspected. How much misfortune does a scientist have to endure before it becomes reasonable to suspect interference? At what point should the scientist sound an alarm?  And who does one call? It’s one thing to suspect that a janitor with a grievance might be incapacitating experimental reagents. It’s an entirely different thing to suggest that an element of one’s own government might be deliberately sabotaging your experiments because your project is inconveniently expensive to the entrenched pharmaceutical interests.  

Worse, it has become apparent in the last eight years that it is now possible to sabotage research programs using bio-active electrodynamic waveforms (EDWFs)that can be designed in silico and broadcast through phone towers or drones. Although a complete explanation of how this is done is outside the scope of the present article, I’ve written on this subject elsewhere, outlining the design of EDWFs, and their potential uses.

Kafka-esque.

At this point I’d like you to put yourself in my shoes. How can I be certain that a sketchy email purporting to be from a scientific collaborator is really who it claims to be from? I had by then established that anything sent from my personal email account could be hacked, regardless of which computer I’ve sent it from. If there were an intercept order on my cell phone, I would have no way of establishing if I’d reached the person I was trying to call. I consulted with InfraGuard, a partnership organization between the FBI and the private sector to safeguard vital infrastructure in America. I was told I would need hard evidence that my communications were being disrupted. Producing this would far exceed my skill-level at information technology (I’m a biologist not a computer programmer). Around this time, Senator Elizabeth Warren courageously went on record and publically accused the CIA of monitoring her emails. (32) It isn’t much of a jump from simply monitoring email messages to disrupting communications entirely.  

Keep in mind that the existence of an actual cure for HIV needs to be taken very seriously. Being publically represented as a nutcase would be the easiest way to invalidate any legitimate claims I might make to having developed an HIV cure. The history of the most momentous scientific developments is littered with the careers of scientists whose advances were economically inconvenient to powerful interests (think: cold-fusion, fuel cell, cloning technology). 

I once took hope in the notion that a development of this significance could not possibly be suppressed for very long. Eventually, I reasoned, people who had been exposed to the vector carrying the gene therapy would start to sero-reconvert (i.e. return to an HIV-negative state), whether or not they are taking ARVs. But whether or not a formerly HIV-positive person ever becomes aware of having sero-reconverted is another question entirely. 

How would we know?

In order to document a legitimate sero-reconversion (SRC) as the result of a genetic cure which hasn’t been published or publically acknowledged, two things need to happen. 

 First, an HIV-positive individual would have to actually cease taking their meds. And yet, from the earliest stages of the epidemic, HIV-infected persons taking prescribed ARVs have had it drilled into their heads that discontinuing their medications will cause the virus to rebound, evoking the spectre of a resistant HIV strain.  

Second, in order to be certain of an SRC, one would have to be re-tested for HIV antibodies. This isn’t logistically difficult – an HIV-positive person can get at-home HIV tests off the shelves of a pharmacy. Or go to a HIV-treatment center where they aren’t already known to be HIV-positive. But who does that? And even if an SRC were to be recorded, it would likely be written off as a false negative, and possibly never spoken about again. Seriously, who would you tell? Would you try to explain this to a potential sex-partner? If they were to doubt you, would you be willing to try and replicate the results, with such high emotional stakes? 

And finally, given the magnitude of the obstructionism I’ve already encountered, it is certain that any individual who went public with a personal account of an SRC would be discredited (at best) or ruthlessly suppressed. In other words, occasional reports of an SRC will not suffice to bring the existence of the cure to light.

What are my options?

The way I see it, the best possible outcome is full disclosure. I have specific and detailed knowledge of a working cure for a deadly, but very lucrative virus, and the capability to recapitulate every element – chapter and verse – of the research program that developed it. I’ve established by now that the pharmaceutical interests are willing to employ extreme measures and vast amounts of money to ensure that the public never learns of its existence. The only possible way the existence of a genetic HIV cure will come to light is if it is independently and scientifically verified. So I now outline what to look for to find it.  

Proof: Verifying the Existence of the Vector.

The delivery system for the HIV cure genetics made use of Feline Immunodeficiency Virus. FIV is sufficiently well known to the bioresearch community that isolating FIV virions from individuals who had received the vector would be quite simple. (34) Presence of FIV in serum, saliva, semen, or any cell or tissue can be established with an Enzyme Linked Immunosorbent Assay (ELISA) probing for antibodies to FIV virus coat proteins. Presence of FIV vector carrying HIV cure genes can be proved by isolating FIV from test subjects, and sequencing the genetic payload: the vector’s genetic material will be found to have an FIV packaging sequence, a known quantity to Molecular Biologists. Presence of the FIV packaging signal will make it possible to isolate the vector’s entire genome, which can then be sequenced and compared with normal FIV: the vector’s genetic material is vastly different from the wild-type FIV. I can, if necessary, provide the amino sequence of the specific therapeutic gene used in the mechanism of the HIV blocker.

Conclusion. 

I hope I’ve made the case that verifying the existence of a working genetic HIV cure needs to be done. Actually accomplishing this may be another matter. There are good and bad reasons for this.  

The bad reason is that considerable resources have been deployed to ensure the public does not become aware of the existence of a genetic HIV cure. Scientifically verifying the existence of the vector presents tremendous challenges. Every step of the process: collecting samples from subjects; transporting the samples to a research facility; and performing the necessary experimentation will have to be vigilantly supervised to ensure a tightly closed loop. 

One very good reason for not putting all this information in the public domain is that the technology I describe would be extremely dangerous in the wrong hands. Much of the information I’ve presented in this article is classified, and thus will be challenging to verify. I have left out certain proprietary details of the vector’s mechanism, but I would be happy to describe them to a qualified biologist for the purpose of verifying the existence of the working vector.  

The best reason I have for being cautious about public disclosure is that I would like to protect the people who generously and courageously offered to help with the development of the project. And I do not feel my concerns are at all frivolous. Dr. WS was very seriously injured when his bicycle was hit by a car; he subsequently decided to discontinue his involvement in the project. Dr. KD, disillusioned, underfunded, and undervalued at AMC, decided to move to a research institute in a different state after receiving the unfavorable reviews of questionable authorship on the R21 grant application. 

I am not sure about the fate of Dr. Daniel Pack.

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The definition of a "functional HIV cure" means:-undetectable viremia without ART;-no disease progression;-no CD4 loss;-lack of HIV transmission ? Eradication/Cure: complete eradication of HIV infected cells from the body. 

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