I think that this question, perhaps, most closely gets at the heart of the matter under consideration……what is the most appropriate (most rational) balance to strike between (1) the safety of vaccine candidates under testing versus (2) the burden of human disease that is being caused because we lack an effective vaccine? If the USA was a competitive market to rapidly and efficiently bring live HSV vaccines to market, it would be my first choice. But, it’s really pathetically bad to the point where I anticipate it will take the USA a decade to get the FDA to back off their uber-authoritarian stance and become as competitive as many other countries in the world who have already, TODAY, streamlined their paths to advance safe and effective biologics & vaccines to market.
Great question from Terri, but there is a lot more to consider here than meets the eye.
- Bill H.
Do you think the 21st Century Cures bill that has been passed by the Senate and is expected to be signed by the President will help move your vaccine along in the US? Even if you plan to do work in other countries, the evidence that you collect as to the efficacy of your product should count as evidence to help progress the approval of the product in the US.
This is a great question, but like many great questions, the answer is complicated. I try my best to answer it, as follows.
Am I optimistic that the 21st Century Cures bill or the Trump Presidency (i.e., let’s challenge the assumptions of every gov’t agency) will change the regulatory landscape for HSV-2 vaccine development in my lifetime? My answer is an unequivocal “No.” However, this does not mean that I don’t agree with your general sentiment, it’s just that I have cancer that most likely reduces my remaining lifetime to something less than five years. And both my parents were attorneys, and so I know the other reality that whenever you are talking about either changing or interpreting laws, the devil is in the details and it takes time. The Clintons pushed for broader medical coverage in the U.S. in the 1990s, and ObamaCare has only been around for a few years (i.e. post-2010).
So, does anything happening in the U.S. change Halford’s personal calculus? No. Do the things happening in the U.S. affect RVx’s calculus…..absolutely. My business partners in RVx are my successors, as are the members of RVx’s Scientific Advisory Board with whom we just met on Saturday December 10. So, the possibility that the U.S. FDA will likely undergo reform over the next decade does change the timeline by which RVx may advance its live HSV-1 and HSV-2 vaccines into routine clinical practice by the USA.
So, I come to Part 2. Before I shuffle off this mortal coil, I want to see herpes sufferers provided with access to potentially life-changing (hope-restoring) medicine so that they do not feel like they are slaves to the whims of their herpes symptoms. That is something we can start doing in 2017 if we simply expand the jurisdictions where we offer the vaccine to all 190-odd countries around the world. The science I have done with HSV ICP0- mutant viruses for 20 years now establishes the idea of injecting a person in the skin of the calf with a live HSV-2 ICP0- virus as something that is clearly safe. If the approach is safe and creates a new opportunity to (1) prevent herpes in vulnerable HSV-seronegative persons and (2) better treat herpes patients who are not well treated with acylovir-based antiviral drugs, then that is something that we should do ASAP. Period. End of sentence.
I have been listening to scientists tell me for a decade…..”Whoa Halford, we have to slow down, and you have to convince me that (1) not only is a live HSV-2 ICP0- virus vaccine safe, but I also want to know (2) that a live HSV-2 ICP0- virus works better than a gD subunit vaccine, and then (3) you need to prove to me why it works better, and then (4) you need prove this is not only true in mice, but you also need to prove this is true in guinea pigs, rabbits, monkeys, cats, dogs, squirrels, llamas, etc.
No matter how many scientific questions you answer for Dr. Studies-Widgets-Dude #1, the answer you provide that person will beget 10 more questions from Dr. Studies-light flares, Dr. Studies-MHC, Dr. Studies-Lymphocytes, Dr. Studies-gD epitopes, etc. And while academic scientists sit around in their little closed circles talking to themselves (e.g., NIH study sections; scientific talks), all of their little conversations (and little is a deliberate word choice) have no impact on the 1,000,000-fold BIGGER PROBLEM THAT 4 BILLION PEOPLE ARE INFECTED WITH HSV-1 OR HSV-2, AND 100,000,000 OF THOSE PEOPLE PERIODICALLY FEEL LIKE BATTERY ACID IS BEING POURED ON THEIR CLITORIS, LABIA, SHAFT, GLANS, ANUS, BUTTOCKS, EYES, MOUTH, FACE, ETC. Academic scientists treat the problem, well, academically. It is not an academic problem for the MILLIONS AND MILLIONS of people who live with a disease that destroys their lives.
Call me crazy, but I don’t think that the established community of herpes researchers has taken a particularly noble or enlightened path to alleviate the human suffering caused by the human herpesviruses that they allegedly study. All of the scientists who take the approach I describe above (which is easily >95%) sit in their ivory towers for decades studying aspects of “herpes virus molecular genetics, or immunology, or latency, or vaccines, or novel antiviral therapies,” but rarely do they ever talk to an actual patient suffering with recurrent genital herpes; the most common human disease that any of the 8 human herpesviruses inflicts upon patients. The T-shirt at the top of the post…..yeah, that’s for you guys.
I have a news flash for all my pointy-headed science colleagues (of which I consider myself one)……..pick a nice restaurant or bar and meet 4 people who have genital herpes and let them unload………it’s a lot more entertaining than most scientific activities, you might actually make some new friends, and most importantly YOU WILL learn something new that rocks you to the core in terms of understanding how this topic you have studied for decades intersects with and torments people’s live. ACTUAL PATIENTS are the natural system that counts, and in the case of genital herpes, scientists missed a LOT in the 1970s and noone double-checked their work. I would recommend to my fellow scientists that you seriously reconsider studying herpes patients in a one-on-one conversational fashion as (1) I don’t think the medical textbooks do the topic justice and (2) there is ample room for improvement in how we diagnose, prevent, and treat recurrent genital herpes.
During the last decade I have been answering a myriad of scientific questions to UNEQUIVOCALLY PROVE that the live HSV-2 0deltaNLS virus vaccine is head and shoulders better than the HSV-2 subunit vaccine approach, which is all we have tested in the USA for the past 30 years. Scientifically, this is a slam dunk. We put all of our eggs in the HSV-2 subunit vaccine approach and it did not pan out. NEVER ONCE did anyone push to seriously test the logical alternative; a live HSV-2 vaccine, which works about 100 times better. Regarding the zero US trials of live HSV vaccines, I generally find that it is difficult to make new discoveries in areas that one systematically avoids exploring.
Herpes sufferers (all 100 million of them) should be at the center of the equation. What do they want? They want a treatment, ANY TREATMENT, that better controls their herpes symptoms and allows them to protect their loved ones from the risk of transmission by virtue of a preventative HSV vaccine. The new treatments that HERPES SUFFERERS want to see tested, those should be the ones that advance to Phase I Clinical Trials first. And, it should not be one treatment, but 10 treatments that simultaneously advance to small Phase I trials on a timeline of less than one year.
Aside from getting more trials of live HSV vaccines going ASAP, a second issue is building scientific consensus that this is a reasonable approach that deserves the scientific community’s full attention. So, this requires that I engage scientists year-in and year-out in talks and papers that generally sound like this……”There are a lot of good reasons that a live HSV-2 ICP0- virus vaccine should actually solve the herpes problem.” The established group of herpes vaccine scientists in the room either (1) don’t let me give a talk (bury the body) or if I manage to get some public air time, (2) well let’s just say the leaders who have been failing at this task for 30 years don’t applaud and cheer that I am claiming to have a live HSV-2 vaccine that works 100 times better than their lame HSV subunit vaccine approach.
I once heard a scientist state, “You know, scientists would much rather wear each other’s underwear than use each other’s nomenclature.” The negative reaction is far stronger when you lead with, “Hi, my name is Bill, I grew up in Louisiana, and all of you Ivy-League trained scientists are very, very smart, but I think you missed the line where God was handing out the common sense. You should check it out….I find it to be extraordinarily helpful.” Generally, the words I choose are softer, but the meaning is similar, and all of the scientists who have worked on, studied, and published on HSV subunit vaccines that have a long history of failure do not appreciate it when I pile on with words like “inferior,” “garbage,” and “waste of time and money.” These are the only final conclusions that I may offer, because they are the only truth (explanation) that remains after a decade of studying this topic. Sometimes in science, you have to choose between pleasing the group or telling the truth. I opted for the latter.
The reaction that comes from the scientific establishment in these situations is generally not pretty. The phenomenon is called “Scientific Suppression” and is nothing new. Rumor has it, the Catholic Church and the thought-establishment of the middle ages were not fans of the idea that the Earth was not the dead-center of the universe. Thus, several “heretics” were burned at the stake for claiming the Earth was rotating around the sun (https://en.wikipedia.org/wiki/Giordano_Bruno). Similar story for a German physician who was laughed out of the profession when he suggested to his colleagues at a hospital that they should consider washing their hands with soap and water in between perforrming autopsies and delivering babies (https://en.wikipedia.org/wiki/Ignaz_Semmelweis).
So, Terri, returning to your original question, “Yes RVx is very interested in seeing the FDA become less regressive and more interested in eradicating herpes by advancing live HSV-1 and HSV-2 vaccines that actually work to American clinics and citizens.”
However, my experience informs me that the key to success is to (1) hope for the best (and exploit new opportunities as they arise), but (2) plan for the worst so that the project advances regardless of whether or not the ideal situation arises. Nearly all of the NIH grants I have submitted over the past 15 years were not funded, and yet I am one of the more influential thinkers in HSV vaccine development today. How can this be the case? Because my research always moved forward with the MODEST MONEY I HAD IN HAND rather than going on hold while I waited for the ideal situation when I reached the pot of gold at the end of the rainbow of a NIH-funded grant. If I had lived in fantasy and waited for the NIH to fund my science, I would not have gotten far. However, I did keep applying and received a single 2-year NIH R21 grant (by accident), and that helped.
Likewise, I take a similar view to advancing RVx’s live HSV-1 and HSV-2 vaccines in the USA to the FDA. Fortunately, it’s not the middle ages, and so a good Halford-burning-at-the-stake seems unlikely. But that same emotional vitreol does, and will always, exist in science, when (1) the established group of scientist made miscalculations that led them to a conclusion that was diametrically opposed to the truth, and (2) then 20 to 200 years later the Established Group is forced to react to the one newcomer who has the audacity to wear the shirt at the top of this post and say, “You fellas are real smart, but did you ever hear of common sense and double-checking your work to figure out what you missed during the first few passes?” That takes balls (courage and self-assuredness), and that is what a lot of the scientists we remember today had….. because they dared to think and say something different.
So, I would love to move things forward in the USA tomorrow. However, in my experience, 95% of academic scientists suffer from the conditions of arrogance, ignorance, and often a profound disconnect / inability to differentiate bullshit from reality. The USA just isn’t all that. Adolf Hitler made the USA a scientific powerhouse between 1950 and 1980…because a LOT of German scientists fled war-time Germany en masse, and post WWII the USA wisely (at that point in time) invested a truckload of money into infrastructure. German was the international language of science at the dawn of the 20th century, and English became the international language of science in the wake of WWI and WWII. In 2017, I see science moving to China and India or other countries who actually understand how to use logic, reason, and mathematics to figure out how natural systems work. The American people (and my fellow New Orleans natives) have many wonderful attributes, but I am definitely the freak in the group who thought it was worthwhile to seriously study science and mathematics. It’s lonely being a freak, and I think I am not alone in that regard. So other freaks like me often choose to go to countries where a higher percentage of the group understand what a cell is, or who perhaps invested a year of their lives studying chemistry, physics, and biology so they could spend the rest of their lives understanding the basic rules that describe how the natural systems (in which they live) work.
So, the real question is, “Do I hate Americans?” No I do not. But, I do believe that, as a group, Americans suffer from an overly high opinion of themselves and they are demonstrably less educated than about 30 other countries in the world. From a business viewpoint, 95% of herpes sufferers do not live in the USA, many of them live in far-better educated countries who are doing better financially, and many of them are not run by the 800-pound gorilla of the FDA that passionately hates live virus vaccines. The FDA folks won’t admit that, but the last live virus vaccine developed in the USA with the FDA’s blessing, well, that happened before I was born. So in my lifetime, the jokers at the FDA have offered no demonstrable support for a live virus vaccine to be developed.
Does this annoy me in the arena of live HSV vaccines. To quote Sarah Palin, “You betcha.”
But where it really deeply upsets me is in the realm of live-attenuated HIV vaccines that could save over 1 million lives per year in Africa alone. The FDA would never allow a live HIV vaccine to be tested in 10 people because it could be dangerous. But, it’s OK that >30 million people have died of AIDS, and >10,000 people will die of AIDS this weekend.
I am from New Orleans originally, and I met a gentleman from the Northeast who had lived in New Orleans for 8 years. One night over drinks (which rarely happens in that city), we were discussing why most people who hail from the Northeastern U.S. do not care for New Orleans in the long term, and often choose to leave. When I asked him his thoughts on why this was the case, he responded very simply and in a very matter-of-fact tone; “It’s not the heat. It’s the stupidity.”
So, why do I believe that RVx’s mission to eradicate herpes should start outside the USA? Well, I will give you a hint…it’s not the heat.
Black, white, brown, tan, Japanese, Chinese, Indian, Brazilian, Belgian, Turkish, Iranian, Egyptian, Chilean, Christian, Muslim, Buddhist…..it really makes no difference to me. Herpes affects every nationality, race, and creed on Earth. I don’t think anyone should have to suffer with this needless affliction. If the American establishment want to cling to HSV subunit vaccines and lame antiviral drugs as the only biotechnologies they will throw at the herpes problem, then I say, “Good luck fellas. Maybe you will find something new in the next 30 years that you missed in the first 30 years you were testing those same approaches.”
RVx is a company with a global perspective. Our website is available in English and Spanish, and will soon be available in Russian. We don’t need the USA’s inward-looking stupidity, which is most obviously manifest in the FDA….the very agency charged with protecting the health of Americans that will be the last to consider a live HSV vaccine capable of eradicating herpes.
RVx believe that it is time to put patients (and their treating physicians) first! No more needless infections, and let’s see if therapeutic HSV vaccines dial back herpes sufferers symptoms. So far, the results have been pretty impressive. Down with the pure academic scientists who have been talking about “curing herpes” since 1983, and who have delivered jack. Over the time I was in high school, college, grad school, a postdoc, and three University professor jobs, and started my own company, these bozos offered failed herpes subunit vaccine concepts from 1985 – 2000, and have been doing little more than CYA science for the past 15 years to save face and not admit that their approach is diametrically opposed to the truth….a live HSV-2 vaccine was always the most viable option from the start, and the subunit vaccines just proved to be hopelessly ineffective.
Let’s do something real and eradicate herpes once for all. Outside of the USA mostly (where 95% of the Earth’s population lives), but if Americans want to eradicate herpes in their own country, well I am all for that too. To my fellow Americans, I offer you a simple message if you want to see viable HSV vaccines at home……..get your so-called leaders to get their shit together and create a landscape where an American company with live HSV-1 and HSV-2 vaccines has a real path forward in this decade. It should take a year of trials and science to figure this out if these vaccines works……not 30 years.
For myself, I am going to go where my passion takes me, which is wherever I can best use my science to help improve people’s lives.
– Bill H.