The anti-minor-party Nevada Senate Bill 292 has advanced out of the Senate Committee on Legislative Operations and Elections on a party-line vote (3 Democrats in favor, 2 Republicans opposed). An amendment from the bill sponsor was included in the bill; Amendment No. 230 is an incremental improvement but maintains essentially insurmountable barriers for minor political parties. While the amended bill no longer raises the petition-signature threshold from 1% to 2% of the Nevada voters who voted in the last election, it does still seek to impose an impossible “equal distribution” requirement for the petition signatures and also moves the deadline for submitting petition signatures from the current third Friday in June to June 1.
Section 2 of SB292 is the most onerous for minor political parties. The provisions further limiting ballot access, relative to the already significant requirements, are found in the new language that the bill sponsor, Nevada Senator and former Nevada Democratic Party Chair Roberta Lange, wishes to insert in NRS 293.1715(2)(c), stating that to qualify for ballot access, a minor political party must:
(New proposed wording above is in bold blue italics, wording proposed to be deleted is in red strikethrough.)
While various other problems exist with SB292, particularly with the concept of straight-ticket, party-line voting – which aims to absolve voters of the essential responsibility to study individual candidates and their stances on the issues – the present commentary will focus on the most egregious flaws with Section 2 of the bill: requiring that the petition signatures be “apportioned equally among the petition districts” and moving the deadline for submitting petition signatures to June 1 preceding the general election.
The bill sponsor appears to be of the impression that removing the previously proposed doubling of the number of petition signatures required would alleviate the most visible added burden on minor political parties. Yet the remaining requirement of equal apportionment is actually far more burdensome and more insidiously so. It requires several more steps in one’s thought process to discern the burden – hence, the bill proponents may believe it to be a viable option to insert such a provision without significant portions of the public noticing or voicing their objections. Therefore, it is important to elucidate the immense problems with the “equal apportionment” criterion.
Nevada has four petition districts, corresponding to the U.S. Congressional Districts. The 3rd Congressional District is the most populous, with a population of 857,197 as of 2019. All three of the other Congressional Districts have populations below 800,000. Suppose that a minor political party were spectacularly successful in gathering petition signatures and managed to collect them from the entire population of registered voters in the 3rd Congressional District. (For this example, we will assume that the proportion of registered voters to the general population is the same in each Congressional District.) The very fact that this minor political party could accomplish such a feat would render it impossible for that party to qualify for ballot access, because the other petition districts simply do not have enough registered voters to match the number of signatures gathered from the 3rd Congressional District in that case.
Moreover, the “equal apportionment” requirement renders it almost effortless for a major party to challenge petitions submitted by minor parties, simply by counting the signatures from each district and noting any difference whatsoever in the numbers of signatures, even if the difference is literally one signature! Even if the total number of signatures is well above 1 percent of the registered voters statewide, if the number of signatures gathered in one petition district were 10,000, and the number of signatures gathered in another petition district were 10,001, that also, by itself, would be sufficient to technically fall out of compliance with the requirement of “equal apportionment”. Note that the text of the amended NRS 293.1715(2)(c) would not allow any room for deviation from a strictly “equal” apportionment. There is no mention of a possibility for the apportionment to be made “approximately equal” or “reasonably equal” or “equal within a tolerance of X%”; the text would mandate strict equality of petition signatures by district, and it appears to me that the Democratic Party proponents of the bill did this intentionally to be able to disqualify any minor party’s petition on a technicality. Given that different circulators of petitions are likely to operate in different petition districts, it is virtually certain that different numbers of signatures will be gathered by each team of circulators. This is so because precise coordination at the level that would be needed to achieve exactly equal numbers of signatures among all four districts and to stop gathering signatures in a perfectly choreographed fashion once such equal numbers were attained, would be essentially impossible to achieve.
Moreover, suppose a minor political party represented a set of positions that resonated to a greater extent with a particular segment of the Nevada population – for instance, young urban professionals, ranchers, miners, university students, residents of rural areas. Each petition district has considerably different proportions of these demographics than the other. For instance, the 1st Congressional District is 99.90% urban, so a hypothetical party that focused on representing the interests of ranchers or rural residents would find quite limited support there. Some city dwellers might, of course, sign a petition for such a party’s ballot access on principle, because they support inclusion of all political parties on the ballot; however, from a sheer probabilistic standpoint, the number of such people would be fewer than the number of people in rural areas who would be willing to sign that party’s petition. Even if the hypothetical party representing rural interests only intended to run candidates in rural areas, it would still need to receive an equal number of signatures from each urban-heavy petition district in order to qualify for the ballot. Therefore, regional parties or parties representing specific constituencies would essentially be permanently barred from ballot access by the “equal apportionment” requirement.
Because of the additional coordination required to even attempt to gather petition signatures “equally” by petition district, as contrasted with simply trying to gather as many signatures as possible, one would expect that the petitioning effort would be more time-consuming than previously. However, Section 2 of SB292 reduces the available time for a minor party to comply with the added burdens, thereby further lowering the probability of successfully meeting all of the requirements.
Moreover, the United States District Court for the District of Nevada already struck down an even less burdensome deadline of June 10; this occurred when the Judge in the case of Lenora B. Fulani et al. v. Cheryl A. Lau, Secretary of State (“Fulani v. Lau” – Case CV-N-92-535-ECR) issued a preliminary injunction on October 1, 1992, to require the State of Nevada to include Lenora Fulani and other independent and minor-party candidates on the ballot despite those candidates not having been able to gather the required number of signatures by June 10 of that year. In issuing the preliminary injunction (which effectively decided the case, since the election took place in November of the same year), the Judge wrote “that plaintiffs have shown likely success on the merits, that the balance of hardships tips in their favor and that they will suffer irreparable injury if their names are not put on the 1992 ballot” (Fulani v. Lau, p. 14). The Judge explained that
The character and magnitude of plaintiffs[‘] injury caused by the June 10 filing deadline shows a burden on their First and Fourteenth Amendment rights. The deadline burdens the rights of nonmajor parties[‘] candidates by excluding late[-]forming parties and forcing candidates to circulate petitions before most of the voting population has thought about the elections. Although this date is not as early as others which have been struck down as unconstitutional, most other states require the petitions be submitted several months later. Also, no evidence suggests that candidates who lack an established national affiliation are easily able to access the ballot. (Fulani v. Lau, p. 11)
If the United States District Court found that a June 10 petition-filing deadline is burdensome to non-major parties’ First and Fourteenth Amendment rights, then, logically, a June 1 deadline would be even more burdensome. Such a deadline would indeed serve to thwart any but the most amply funded minor political parties, if those parties choose to begin gathering the signatures extremely early in the year, whereas new minor parties, as well as minor parties that rely largely or exclusively on volunteer efforts and grass-roots organizing, would find themselves hobbled by lack of time. SB292 is seeking to institute in Nevada law a deadline more stringent than the one which the District Court has already overturned.
There is still time to express opposition to Senate Bill 292, particularly to the requirement that petition signatures be equally apportioned and the earlier June 1 deadline for submitting such signatures. SB292 is already one of the most actively commented on and least popular bills of the 2021 Legislative Session, with 209 public opinions expressed in opposition and only 4 in favor. You can submit your opinion in opposition to SB292 here and also e-mail the Senate Committee on Finance, where SB292 will be headed next, at SenFIN@sen.state.nv.us, as well as e-mail the Assembly Committee on Legislative Operations and Elections at AsmLOE@asm.state.nv.us. The Assembly Committee on Legislative Operations and Elections would be the committee where SB292 would be heard if it were to pass in the Senate. Please express your concerns civilly and politely but make it clear that you do not agree with any attempts to further limit minor-party ballot access. Also, please spread this article to as many constituencies as possible! People of nearly all political persuasions should be able to agree on the importance of voter choice and to abhor the injustice of intentionally restricting candidates and parties from even being available for voters to consider.
Even the current ballot-access thresholds in Nevada are unduly stringent; the last time a minor political party qualified for the ballot through petitioning in Nevada was in 2011, when the Americans Elect organization was able to submit the required number of signatures. It is time to pursue reforms in the opposite direction from Section 2 of SB292; it is time to repeal all petitioning requirements for ballot access and allow voters the choice of any candidate or party whom they wish to support. At minimum, it is essential to oppose the placement of any further obstacles along the path to ballot access. All provisions of SB292 related to minor political parties should be amended out of the bill upon further revision. Please add your voice to this important effort to preserve electoral choice and to oppose one major party’s efforts to monopolize Nevada elections.
The U.S. Transhumanist Party livestreams special Enlightenment Salon events every Sunday at 4 p.m. on YouTube. Two weeks ago, on April 4. 2021, the USTP organized a special Enlightenment Salon panel event on FDA reform. In addition to myself, the following people participated on the panel, which was moderated by USTP Chairman Gennady Stolyarov II:
Prof. Alex Tabarrok, Bartley J. Madden Chair in Economics, George Mason University
Dr. Max More, President Emeritus, Alcor Life Extension Foundation
Jim O’Neill, CEO, SENS Research Foundation
Dr. Edward Hudgins, Founder, Human Achievement Alliance
Prof. Garett Jones, Mercatus Center, George Mason University
Will C. , Medical Student and Blogger
The entire panel was probably the most information-dense event the USTP has done. I kicked things off by giving a short presentation, which I managed to blaze through in 15 minutes. (The slides can be viewed here.) The presentation set the stage for a very informative and productive discussion.
My only regret was that we didn’t have any women on the panel. However, during the course of researching my presentation, I found out about the work of Dr. Mary J. Ruwart. Dr. Ruwart estimated the number of people who die every year from FDA delays to be around 150,000 per year in her book Death by Regulation. So, I am happy to announce that Sunday, April 25th, from 4 – 6 p.m. Eastern Time, 1-3 p.m. Pacific Time, the USTP will be doing a special Virtual Enlightenment Salon with her.
Here is the recording of the FDA reform event. At 00:05:00 my presentation kicks off:
I’ve written a summary of the major points each of the panelists (and two others) made during approximately the first hour of the session. These are heavily paraphrased. (Instead of providing direct quotes, I shortened what was said in most cases while maintaining the core meaning of what was communicated.) I have put my own comments in italics.
Prof. Alex Tabarrok:
The FDA can approve a bad drug (Type I) or fail to approve a good drug (Type II). If they approve a bad drug, people who were affected will go on Oprah, and there will be huge backlash. If they don’t approve a good drug, there is no backlash. The invisible graveyard is a statistical reality, but it’s hard to see. This can be seen easily by asking people to name a time when the FDA approved a bad drug (or a drug with unexpected side effects). Lots of people can think of something. Many point to Thalidomide, which is actually a drug that was approved in Europe and caused birth defects. Thalidomide, incidentally, has many important applications but was not approved by the FDA until 1998.
When you have a Type I error, you learn something — we learn about the harms of a drug, and we change our behavior. With a Type II error we never learn anything. We can’t see the consequences of a failure to approve, and even worse, we can’t see the many drugs that never even made it to FDA-mandated trials in the first place because they were deemed too risky to justify the cost.
Reciprocity is a sensible reform that is one of the most feasible.
The FDA likes to think they are the “gold standard” for drug approval. Yet, people in other countries don’t worry about whether drugs are FDA-approved. For food safety we already have reciprocity with Canada.
The FDA has been working for 40 years on new standards for approving sunscreens. So Europeans have much more advanced sunscreen than the US.
If aspirin were invented today, it probably wouldn’t be approved.
One thing U.S. policymakers have done already, which is probably the smartest thing they have done in a while, is PEDUFA (Prescription Drug User Fee Act). The drug developers pay an extra tax as long as approvals are sped up. The FDA was happy because they got to expand their bureaucracy, and drug companies were happy because they could get to market faster.
In the EU the EMA “farms out” reviews to private companies. (So the EMA is more like “an approver of approvers”). Private companies can do a good job – for instance, look at Underwriters Laboratories in the realm of electrical devices. (If you look at many electrical devices, you may see a “UL” seal.) Many major companies like Amazon won’t carry devices unless they are UL-approved.
There is no formal process whereby where if a disease is more deadly, then the standards should be lowered to speed approvals. For instance, for pancreatic cancer, which often kills within 6 months, the standards should be lower (and more risk should be tolerated), since patients have less to lose. For something like acne treatment, the standards can be much higher. The FDA recognizes this to some extent in practice, but it’s totally informal – technically it’s not supposed to happen. However they could do this formally and adjust the required statistical significance levels. They could use Bayesian statistical techniques as well.
There’s no route to approve a drug for anti-aging. If a company wants to do R&D on anti-aging therapeutics, there is not a clear route for approval.
Dr. Max More:
We should keep in mind full abolition of the agency as a long-term goal. [My response: I am against full abolition, but I agree with this. Everyone should at least consider abolition, and if they are against it, explain in some detail why the government needs to be involved versus using private-sector companies and tort law. Going back to first principles regarding the role of government is healthy, especially in places like Washington, D.C., where government institutions are taken for granted and not questioned as much as they could be.]
We should keep in mind Milton Friedman’s statement that expecting the FDA to behave differently than it does is like expecting a cat to bark (Note: He said this in a 1973 Newsweek column.) We can’t just say, “We want the FDA to do X”; we have to make sure incentives are in place so people actually do the things we want. Legal mandates can help, but it’s easy for people to skirt around them if the proper incentives don’t exist.
We are facing an enormous cultural barrier when it comes to reforming the FDA and CDC. We don’t have a proactionary culture anymore; we have a very fear-based culture, and a simple solution to it does not exist. However, we have a good opportunity right now just like the AIDS activists had a good opportunity in the 1980s.
The proactionary principle is a “grab-bag” of tools based on a certain value perspective which basically says that progress is fundamentally good. We aren’t omniscient, so we have to learn by doing. As Alex Tabarrok said, you can’t really learn things without making mistakes. It’s impossible to make progress, like some rationalists believed, by just sitting in chairs and thinking carefully. We have to become empirical. You can “look before leaping”, but you also have “look while leaping” and adjust how you land, to use a crude metaphor.
Cost-benefit analysis is a basic approach that is used in many organizations but doesn’t seem to be used as much in government agencies. It shouldn’t be controversial. Mandating cost-benefit analyses would be a step towards using ideas from the proactionary principle.
We should institutionalize the Devil’s Advocate procedure and institutionalize respectful disagreement. Instead of having the most powerful person in the room getting what they want railroaded through, we should require debate and motivate decision makers to ponder both sides. Other approaches could help, such as reference class forecasting, structured argumentation techniques, auditing procedures, and auditing review panels.
Reciprocity seems like a no-brainer that is relatively easy to achieve, and would greatly reduce costs.
Besides getting out these great ideas, we need to figure out how to get people to follow those ideas. Laws can help, but people can choose to not follow them. How do we put “bite” into laws? I think an annual audit on the FDA’s decision making would be a good idea. Importantly, the auditor’s report should be made public. The auditors should come from a variety of institutions, for instance a variety of think tanks from different sides of the political spectrum.
Gennady Stolyarov II:
The USTP agrees that abolishing the FDA should not be out of the question. In our Platform, Section CXVIII states:
Section CXVIII [Adopted by a vote of the members during March 25-28, 2020]: Given the extreme delays, bottlenecks, and expenses created by the mandatory approval processes on the Food and Drug Administration (FDA), the United States Transhumanist Party supports abolishing the FDA and replacing it with a Radical Life Extension Administration (RLEA), whose mandate would be to prioritize the rapid development of potential disease cures, treatments, and vaccines – including any possible cures or vaccines for COVID-19, as well as treatments to mitigate and reverse the disease of biological aging, the major risk factor for COVID-19. The RLEA would allow the marketing and collection of patient data on any potential cure, treatment, or vaccine which has passed affordable safety testing at a reasonably acceptable threshold.
I’ve had the pleasure of working with the FDA quite a bit, and in my experience most of the people there are very smart, and they actually believe in approving things, contrary to what it may look like from the outside.
The problem is that incentives matter, and the FDA is a central point of failure.
When someone has a severe side effect from a drug, the FDA Commissioner gets hauled in front of several Congressional Committees and is interrogated. When someone dies because something wasn’t approved, there’s total silence in Washington. We should blame Congress, not the FDA, for that incentive being in place.
Individuals respond to the institutional incentives, but they also have personal incentives. A lot of people want to be the next whistle-blower who finds the next thalidomide and calls a halt to it. Both of these are pretty severe and would affect even the most principled person in ways they couldn’t even detect.
I disagree with Alex that “FDA not recognizing aging as a disease is a major problem.” In order for the FDA to reasonably measure success of any therapy, there must be metrics and biomarkers. It’s not the FDA’s job to do all the scientific work to develop biomarkers for aging. That’s the job of the science community and the NIH to some extent. There are epigenetic clocks, but we need a lot more work on those. Those clocks can then be run through the FDA’s biomarker approval program.
The second thing I disagree with is Dan’s idea of making the FDA independent from HHS. I think that would make things worse.
My favorite approval ideas fall under the category of “progressive approval” or what Dan calls “tiered approval”. Contrary to what the FDA often thinks, doctors and patients are capable of processing information and making risk-benefit calculations using their knowledge about the specific situation they are in. The more information provided and the more transparency, the better. The FDA should focus back on their original mission of safety and purity. I absolutely support repealing the 1962 Kefauver-Harris Amendments.
Prof. Garett Jones:
I come at this as an macroeconomist. I think we can learn from what economists have learned about central banks around the world. The FDA should be as independent of congress and the president as central banks are or as judges are.
The Federal Reserve is a panel. That’s how we run the SEC, the FEC, the Federal Reserve, and the Supreme Court. There seems to be some magic to having a panel — it’s probably giving us a bit of the Law of Large Numbers in decision-making.
Another aspect of these panels is they have long terms. They are probably going to be serving under a few different Presidents. As I say in my book 10% Less Democracy, “short terms make short-term thinking”. Political independence can lead to decision-making independence, and we have evidence that’s a good thing.
Discussions in institutional reform have “high marginal product” right now, as an economist would say. Congress moves slowly, but Congresspersons tend to look for big opportunities for reform a couple years after a crisis. The Federal Reserve was established in 1913 but was born out of the Panic of 1907. Six years was how long it took between a huge financial crisis and Congress getting around to making some reforms. We saw something similar after the global financial crisis – it took about 2-3 years. The ideas that people are discussing now will be part of the information ecology of the next few years in Washington, D.C.
These ideas of long terms, independence, and panels are a good path for decision making. I am an unreformed Tabarrokian, so I agree with everything Alex Tabarrok has written about FDA reform (chuckle). What I want to push here is institutional reforms that seem to work in a wide variety of settings. A little more financial and legal independence will lead to a situation where Congress is less of a source of fear for FDA officials.
A lot of people on social media have told me that the President is in charge of the FDA. These people have never actually talked to anyone who worked on Capitol Hill — agencies live in fear of their Congressional overlords. They live in fear of the Senate Majority Leader and the Speaker of the House, who have power over their budgets. They also know that if they make a mistake, they can be hauled up before Congress and fired ignominiously.
There is a risk that a more independent agency may misuse its freedom. However, in practice, if we look at the data, independent agencies with long terms have high benefits and low costs.
It’s fun to complain about the FDA, but it’s wise to complain about Congress.
Dr. Ed Hudgins
We’ve been talking about how FDA regulators are always in fear of Congress. What I want to see are FDA regulators in fear of patients who want to get access to medications at less cost and quicker.
One of the most egregious examples of defining efficacy was when the FDA decided that 23andme could not offer advice on whether someone was prone to breast cancer. Essentially they thought that women were too stupid to understand the information and would rush out to get a double mastectomy without getting a second opinion.
Another example is in 1989-1990 when they wanted to classify a urine sample cup as a “class A medical device”, in the same category as a heart valve.
In April 2019, the FDA stated that it wants to regulate artificial intelligence as a medical device.
There are many consultants now, whose entire job is to help companies get through the FDA bureaucracy. So there’s a whole industry now just to help people get through the FDA — and that’s part of the problem now, too.
The “Free to Choose Medicine” idea should be at the top. Something like this was created around 1992 during AIDS crisis. Congress stepped in and put pressure on the FDA to do something. What they did was create a parallel track where sufferers could access a particular medication for AIDS during the three years it was being tested. 12,000 people took advantage of that, so there are 12,000 people who are not in the invisible graveyard as a result.
The idea of a parallel track has been put forward by Bart Madden. Data from people on that track would be put into a public real-world database.
There are alternatives to randomized controlled trials (RCTs). If observational data is put into a public database, then doctors can look at that data and make informed recommendations. Drugs would be able to fail quicker, too.
In the case of AIDS, it was patient groups that besieged the FDA’s buildings. In light of COVID-19, and people seeing that the system isn’t working for them, we have an opportunity now to push for change.
There’s momentum for FDA reform building off of the right-to-try legislation that has been passed in many states. In Texas and North Carolina there are strong pushes to broaden right-to-try to people like patients with Alzheimer’s Disease.
The AIDS-FDA story is a little more nuanced than was described by Ed Hudgins and Max More. We all know about the militant groups like ACT-UP which pressured the FDA in the 1980s. However in the mid-1990s there developed a few counter-movements against that. One group was called Treatment Action Group, and they pressured the FDA to move slower because they felt the FDA was approving HIV/AIDS treatments that didn’t actually have much benefit.
A good book is Malignant by Vinay Prasad. It documents how, over the last twenty years or so, the FDA has lowered the standards for many cancer drugs. They often are approving drugs based on surrogate endpoints and biomarkers, and then the drugs don’t go through follow-up studies to show if they have actual clinical benefit. So there has been a natural experiment where we tried to lower the standards for cancer drugs, and it doesn’t seem to have worked very well. Of course, I’m not an economist, so there might be a way of adding up the costs and benefits where the marginal benefits have outweighed the costs.
The FDA had many failures during COVID-19. The first big one was with testing, both with the FDA and the CDC. Others were the decision to delay the approval of Pfizer and Moderna vaccines (by about 4-6 weeks), and the decision not to approve the AstraZeneca vaccine, which hasn’t had any transparency. Finally, there was a complete lack of experimentation with human challenge trials. What all of these share is there has been very little transparency and not much good reporting on these issues. There have not been any thorough investigations from journalists, and we don’t really know what’s going on. Before attempting reform we need to first go and find out what went wrong during COVID-19. We need a non-partisan investigation of all of these issues. We need to utilize Freedom of Information Act requests. We need to find out how Trump was involved, why approvals took the amount of time they did, etc.
Dr. Natasha Vita-More
Cosmetics does not need FDA approval pre-marketing. It only needs post-market approval if the company says something in their marketing materials that could be misleading. There are many doctors pushing crack cosmetic treatments and behaving in a very “loosey goose-y”. I have a hard time understanding how they get away with these things, unless there are big-monied interests behind them.
We all know about Theranos. In 2015 they got FDA approval for one of their tests. There’s clearly an imbalance here – many life-saving treatments struggle to get approval, but a company which is completely fraudulent like Theranos was able to get approval. [My response: This is a great point! Theranos did receive approval, but only for their Herpes test. If I recall correctly, this test was done with conventional laboratory equipment rather then their special “minilab” device, a fact which Theranos hid from investors. Theranos also utilized a loophole to sell tests without FDA approval.]
Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party. You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack.
U.S. Transhumanist Party Vote on the Question of Endorsing Jennifer A. Huse for Mayor of Camden, New Jersey
The U.S. Transhumanist Party will hold an electronic vote of the membership for a seven-day period ending on 6:01 p.m. U.S. Pacific Time on Friday, April 30, 2020, on the question of whether to endorse Jennifer A. Huse, who is running as an independent candidate for Mayor of Camden, New Jersey, in 2021.
Registered U.S. Transhumanist Party members as of 12:01 a.m. U.S. Pacific Time on Friday, April 23, 2020, would be able to cast their ballots on this question and will be sent their ballots via e-mail.
Watch the U.S. Transhumanist Party Officers’ interview of Jennifer A. Huse, conducted on February 15, 2021, by U.S. Transhumanist Party Chairman Gennady Stolyarov II, Director of Applied Innovation David Shumaker, and Director of Energy Issues John Kerecz.
Highlights from Ms. Huse’s campaign website include the following (see additional issues here):
Healthy Life Extension Initiatives for All
We aim through a variety of initiatives, combined with human health services and biological sciences, to bring Camden to the top quality of health known to us at this time and to continue to progress in every possible endeavor to bring our citizens the highest and longest length of life in the world. We will explore every possible avenue through collaboration with leaders in health industries from around the country and world together with all of our valued Camden health professionals and researchers to work on this as a top priority.
We seek to provide the people of Camden with access to information, medicines, technology, and research as each develops. This includes offering transparency in health-related and all of our initiatives through new communication technologies and expansion of existing communication technologies for all people.
We aim to provide the community of Camden with the highest quality of water in the world. We firmly believe that water is life and essential to all persons’ quality of life and the quality of life of the planet itself. We will immediately undertake every possible opportunity to deliver top-quality water to all people of Camden.
We aim to collaborate with the small business owners of Camden to deliver an abundance of nutritious food to the community of Camden through Vertical Farming and other initiatives.
We aim to provide quality, nutritious food for the people of Camden through any initiatives we can possibly secure and in collaboration with experts from around the country and world. We aim to provide opportunities to our valuable industrial partners to participate in these efforts in order to bring them to the forefront of their industries and enhance all of our health and wellbeing.
Our administration values the health, wellbeing, and abundance for all of the people of Camden above all other things. We consider quality of life to be an essential and equal part of life extension.
One of our most immediate concerns has to do with Housing for All.
Every day that someone is without safe and secure housing, they are at risk of unnecessary sickness and death. We feel that without this basic need, the people of Camden are placed under unnecessary suffering and stress. We wish to explore every avenue to solve this issue entirely and permanently for all the people of Camden.
We aim to help all households feel secure by having all of their utilities consistently connected so fear and stress do not cause detriment to their quality of life. We will explore all possible aid and programs throughout the entirety of our administration to make sure none of the households in Camden go without basic needs such as working utilities.
Parallel in U.S. Transhumanist Party Values and Platform: The United States Transhumanist Party supports concerted research in effort to eradicate disease and illness that wreak havoc upon and cause death of sapient beings. We strongly advocate the increase and redirection of research funds to conduct research and experiments and to explore life, science, technology, medicine, and extraterrestrial realms to improve all sentient entities. [Article VI, Section V]
Ending The War on Drugs
The War on Drugs has repeatedly been proven to be detrimental to the health and wellbeing of people around the world. Our administration aims to work together with our local law enforcement to continue ending The War on Drugs locally in Camden, NJ. For years, our police have worked to help make Camden safer and more prosperous. We look to encourage and promote this loving, respectful, and effective way of policing throughout our beautiful city.
We look to continue exploring every possible avenue in regard to full decriminalization and legalization of all drugs found to be beneficial to human systems. We support the right to try any medication that may be able to improve the pain and suffering a person is experiencing within their own body.
We no longer want anyone to live in fear of arrest, detention, hefty legal and other fees, loss of time with loved ones, lowered quality of life, etc., simply for the choice of medicine they wish to put into their own bodies.
We no longer want persons that wish to work in industries that supply medicines to live in fear of arrest, detention, hefty legal and other fees, loss of time with loved ones, lowered quality of life, etc., or have to risk inferior medicines because of restricted access.
We wish all persons that may have been hurt by the war on drugs to be able to work in the legal industries through training incentives and employment opportunities.
We wish to expunge as many nonviolent drug charges as possible and will seek to help to the extent of our local powers in all areas. This is already being done in cities all over the country, and we will pursue all possible avenues to accomplish this. We aim to work together with others by looking into any other cases where persons from Camden may need assistance in regard to legal matters.
Parallel in U.S. Transhumanist Party Values and Platform: Section XIV [Adopted by a vote of the members during March 26 – April 1, 2017]: The United States Transhumanist Party supports an end to the costly drug war, which is often an infringement upon the lives and liberties of innocent citizens who do not use drugs but fall victim to militant enforcement of drug prohibitions. The United States Transhumanist Party supports legalization of mild recreational drugs such as marijuana.
Our administration works for you! We would like for each and every one of the people of Camden to present us with any issues that you would like to see strategic solutions applied to. Upon being elected, we will put in as many avenues as possible for our valued residents to be able to present and possibly work on solving issues together along with our administration.
We aim to be as accessible as possible to all of the people of Camden, viewing each and every one of you and the quality of your health and life as our most important priority. We look to make sure that everyone has internet capabilities. We will seek to provide each person with online access through their home or by ensuring they have smartphone technologies available to them. Through new newsletter and paperless electronic alert systems, we will be able to inform all of the people of Camden of new grants, employment opportunities, health advances, and more. This will enable all people to be informed of our continued progress in our city.
We aim to achieve competence in all decision making together with maximum courtesy and empathy to ALL persons. We intend to initiate systems to allow for all of the people of Camden to be able to speak their concerns about the issues they and the city are facing. This will be set up through a variety of options including new contact methods in many departments, appointment scheduling, and problem-solving-related events. We are also interested in any persons who wish to help work on the issues themselves or may have ideas on how to improve the issues important to them.
Parallel in U.S. Transhumanist Party Values and Platform: Section XIII [Adopted by a vote of the members during March 26 – April 1, 2017]: The United States Transhumanist Party supports the involvement of intelligent laypersons in the political process to counteract and neutralize the influence of politically connected special interests and their paid representatives. The United States Transhumanist Party supports all electronic and other technologies that can inform and empower intelligent laypersons to monitor and contribute to political discussions and decisions.
Education for All
Our administration seeks to develop, together with our existing educational systems and the Center for Scientific Solutions, a path for all interested people of Camden to obtain education for as long as they wish to pursue it.
We also look to bring in the most progressive education system reforms and support for students and educators possible.
Our administration looks to work together with our valued Department of Education and educators to develop all of Camden’s educational systems together with experts from around the country and allies from around the world in every subject and field.
For more information on our Center for Scientific Solutions, click here.
Parallel in U.S. Transhumanist Party Values and Platform: Section XII [Adopted by a vote of the members during March 26 – April 1, 2017]: The United States Transhumanist Party holds that present and future societies should provide education systems accessible and available to all in pursuit of factual knowledge to increase intellectual acuity; promote critical thinking and logic; foster creativity; form an enlightened collective; attain health; secure the bounty of liberty for all sentient entities for our posterity; and forge new ideas, meanings, and values.The United States Transhumanist Party supports efforts to reduce the cost of education while improving its access. In particular, the United States Transhumanist Party supports freely available, open-source, methods of learning, teaching, credentialing, and cultural creation that integrate emerging technologies into every facet of the learning process. The United States Transhumanist Party primarily advocates private innovation to deliver such educational improvements, but also advocates the application of these improvements to all publicly funded educational institutions. The United States Transhumanist Party holds that every person should aspire toward intellectual, moral, and esthetic enlightenment and sophistication and should contribute toward bringing about a new Age of Reason, where the highest reaches of intellectual activity are attainable and eagerly pursued by the majority of the population.
The Center for Scientific Solutions
The future of Camden…The future of the World!
We aim for collaboration in this endeavor with award-winning city and community designers. It is one of our goals to offer new disaster-resistant residences and other designs to protect against extreme weather conditions. We will obtain opportunities by reaching out to every grant provider and organization available to develop the most advanced technological systems worldwide.
We aim to become prime examples of accessible displays of water, sewer, and electrical systems. We look to advance Camden’s air, soil, and water to optimal levels. Furthermore, we aim to create advanced school curriculum designs.
In collaboration with partners from around the world, we will test and advance solutions for improving our current social systems and introducing new technological solutions. The Center for Scientific Solutions will create an evolving social blueprint upon which we will work on all feasible and beneficial scientific solutions to the issues our city faces, while developing technologies that can also be used for other parts of the Nation and World. Our administration will work hand in hand together with the Center for Scientific Solutions to bring the highest quality of life to all residents of Camden and to serve as an example and innovator of progress throughout the nation and the world.
Parallel in U.S. Transhumanist Party Values and Platform: Section IX [Adopted by a vote of the members during February 16-22, 2017]: The United States Transhumanist Party supports all emerging technologies that have the potential to improve the human condition – including but not limited to autonomous vehicles, electric vehicles, economical solar power, safe nuclear power, hydroelectricity, geothermal power, applications for the sharing of durable goods, artificial intelligence, biotechnology, nanotechnology, robotics, rapid transit, 3D printing, vertical farming, electronic devices to detect and respond to trauma, and beneficial genetic modification of plants, animals, and human beings.
Review of Rykon Volta’s “Arondite” – A Fascinating Exploration of a Hypothetical Future History, With Relevance to Our World – by Gennady Stolyarov II
Arondite by Rykon Volta offers a fascinating exploration of a hypothetical trajectory of humankind’s future history, in which Hugo de Garis’s dire predictions of an “Artilect War” had come to pass. As in de Garis’s narrative, so in Volta’s, the anti-technological reactionary Terran faction initiates that war to assail emergent sentient artificial general intelligences and their philosophical allies, the pro-innovation Cosmists. Rather than allow such artificial general intelligences to develop, the Terran General Vantus destroys the entirety of the Earth in the year 2071 and binds the remnants of humanity to an Artilect Protocol, which imposes the harshest punishments on any humans who experiment with genetic modification, cybernetic implants, or artificial intelligence.
The story of Arondite takes place 500 years later, in 2571-2572. Humanity has, over the course of five centuries, risen slowly from the ashes of the Artilect War, and multiple competing societies and governments have taken hold in the Solar System – particularly the Martian Republic and the Jovian Empire, who are now on the edge of major war. The historical narratives at the beginning of each chapter are among the most intriguing aspects of Arondite and serve to add great depth to the world in which the events of the plot transpire. Indeed, the historical scenario presented by Volta is reminiscent of two epochs already experienced by humankind: the emergence of Classical Antiquity after a gradual recovery from the Late Bronze Age Collapse, and the rise of Medieval and then Renaissance societies after the Dark Ages following the fall of the Roman Empire. Every such recovery of civilization is a testament to human ingenuity in the face of immense adversity, and in the world depicted by Volta, the hardships of outer space certainly magnify those constraints for the remnants of humanity. Yet by developing extensive settlements both on multiple planets and in space, as well as advanced spacefaring vessels on which much of the book’s plot takes place, humans demonstrate irrepressible innovation by advancing in practically the only directions available to them. Still, the harsh boundaries imposed by the Artilect Protocol are beginning to fray, and indeed, would need to be overcome in order for further progress in the Solar System to be possible.
The protagonists of Arondite are a group of space pirates – Peron, Ashlyn, and Carlile, as well as their various and situationally shifting allies – who are quickly drawn into matters far weightier and more perilous than they could have expected, as they unwittingly find themselves at the epicenter of the struggle by multiple major powers for the Arondite Chip – a map to one of the few artilects rumored to remain. Without revealing the specific details, the plot features numerous rapid developments in this struggle – filled with shifting allegiances, sudden changes of fortune, and revelations of hidden motives which diverge from surface appearances. The reader is kept wondering throughout as to who will gain possession of the Arondite Chip – the pro-artilect Acliate Brotherhood, the Martian Republic, the Jovian Empire, the tense and ever-precarious alliance of the protagonists who must resist pressures from each of these forces, or perhaps someone else entirely. Characters from every faction, however, are united in their recognition of the vast transformational power of an artificial general intelligence; some fear it and wish to destroy it, whereas others wish to harness it for their own objectives. But will the protagonists be not only capable enough to locate this artilect, but wise enough to truly understand its capabilities and nature – and respect its autonomy?
The events of Arondite are driven strongly by all-too-familiar flaws of human character – from irrational fear to the desire for the subjugation of others to the perception of existence as a zero-sum struggle of all against all. Because of the prohibitions of the Artilect Protocol, these flaws have persisted and become endemic within the societies of 2571; after all, no fundamental improvements upon human nature had been made available via technological pathways. Thus, for all of humankind’s spacefaring progress, the aforementioned deleterious vestiges of the suboptimal evolution of the human mind had not been corrected; another major war looms on the horizon and threatens to undo centuries of hard-earned advancement. However, the rediscovery of the artilects might just open an entirely different and more hopeful set of possibilities for the future of civilization. One can only hope that, in our own civilization, that set of possibilities can be opened much sooner and with major conflicts averted.
Through the plot of Arondite, Volta illustrates the futility of attempting to impose restrictions on technological progress – restrictions which only serve to mire humankind in an escalating war of all against all. The protagonists are thrust into such an all-encompassing struggle, but because of their relative naiveté (despite being space pirates) are able to keep their minds open to alternative possibilities and thus have a chance to bypass the numerous hostile forces and machinations standing in their way. There is a broader message contained in this kind of narrative – the ability of an earnest individual, who is not altogether experienced with “the way things are done” in a given field, to significantly influence that field and overcome institutional barriers that had hitherto prevented progress past a certain point. Both in the world of Arondite and in our world, Volta shows that the philosophy of transhumanism, with its openness to technologies that can radically transform the human condition to remedy age-old flaws, is the way forward, transcending the destructive power struggles which needlessly stunted the advancement of humanity in the past.
I have compiled a list of some of today’s most exciting, cutting-edge biotechnologies! Some of these technologies are emerging, and some of them are already prevalent in a translational context.
1. CRISPR-Cas systems: revolutionary for gene editing, gene therapy, fundamental biology, diagnostics, and more.
2. Gene therapy: enables cures for genetic diseases and powerful treatments for many cancers, may eventually treat polygenic disorders, ameliorate aging, and even enhance human biology (e.g., provide radiation resistance to astronauts). Synergy with CRISPR-Cas technologies will greatly aid gene therapy.
3. DNA origami: paves the way for new nanomedicines, biocatalysts, biosensors, imaging probes, diagnostics, data storage methods, biocomputing, and more.
4. Computational protein engineering: paves the way for new nanomedicines, biocatalysts, biosensors, diagnostics, biomaterials, imaging probes, and more.
5. Immunotherapy: enables cures for many cancers, treatments for autoimmune diseases, and more.
6. Computational protein structure prediction: revolutionizes drug discovery and basic biology, synergizes with computational protein engineering.
7. Spatial transcriptomics: method for interrogation of cell and tissue biology in a holistic and multidimensional fashion to deeply understand health and disease, may lead to dramatic insights on aging, cognition, and pathology.
8. Optogenetics: powerful tool for understanding cellular physiology and neural circuits, may greatly enhance brain-machine interfacing (with the help of gene therapy).
9. Expansion microscopy: physically enlarges biological samples to multiply resolution. Making major strides in connectomics, vastly enhancing study of spatial organization of cells and tissues in general, synergizing with spatial transcriptomics.
10. Longevity medicines: pharmacological, gene therapy, and other methods of treating aging may extend human lifespan and dramatically reduce the prevalence of most aging-related diseases.
11. Bioprinting: produces replacement tissue and may enable manufacturing of replacement organs. Also greatly aids study of tissue biology and provides platforms for drug testing.
12. Organ-on-a-chip systems: may greatly reduce the need for animal models in research, helping to understand organ microenvironments and organ physiology in general, serving as platform for drug testing and discovery.
13. Organoids: may greatly reduce the need for animal models in research, helping to understand organ physiology (especially in context to 3D structure and function), serving as platforms for drug testing and discovery, contributing to understanding of cognition, aiding understanding of developmental biology.
14. Cryo-EM and cryo-ET: rivaling x-ray crystallography for solving high-resolution protein structures and is much easier than x-ray crystallography (especially for certain problematic samples), giving 3D images of cellular environments at sufficient resolution to see some macromolecular structural details, preserves sample integrity better than other methods.
15. Phage therapy: enables versatile and potent treatment of bacterial infections, may save the world from antibiotic resistance.
16. Synchrotron x-ray nanotomography: rapid 3D imaging in one or two colors, may help map brain structure much more rapidly than other methods. This could lead to superior brain-inspired AI and robotics, treatments for brain disease, and whole-brain simulations.
17. Tissue clearing with light-sheet microscopy: facilitates 3D imaging of tissues and even whole organs, leading to much better understanding of biological function, aids connectomics.
18. Predictive systems biology models: transforming vast biological datasets into parameters for large-scale simulations which give valuable insights. Some key examples are kinetic signaling network simulations, molecular dynamics simulations, and biophysical neuronal network simulations.
19. Injectable electronics: minimally invasive method of delivering brain-machine interface hardware, may lead to widespread biomedical and nonmedical adoption of brain-machine interfaces.
20. Minimal cells: may transform understanding of cellular physiology, may act as a superior biomanufacturing platform, may act as a superior platform for cell therapy, and more.
Logan Thrasher Collins is a U.S. Transhumanist Party member, futurist, synthetic biologist, author, and innovator. When he was 16, he invented a new antimicrobial protein, OpaL (Overexpressed protein aggregator Lipophilic). He next developed a bacterial conjugation delivery system for the gene encoding OpaL. His synthetic biology research has been published as a first-author journal article in ACS Biochemistry: “Design of a De Novo Aggregating Antimicrobial Peptide and a Bacterial Conjugation-Based Delivery System.” In addition, his synthetic biology research has been recognized at numerous venues including TEDxMileHigh, the Intel International Science and Engineering Fair (ISEF), the International BioGENEius Challenge at the BIO International Convention, and at the American Society for Microbiology General Meeting. At Intel ISEF 2014, his synthetic biology research won 1st place in microbiology and best of category in microbiology ($8,000) as well as the Dudley R. Herschbach award. The latter included a trip to take part in the Nobel Prize ceremonies via the Stockholm International Youth Science Seminar (SIYSS). As part of the honors at Intel ISEF, a minor planet was officially named Logancollins.
As the Chief Technology Officer (CTO) at Conduit Computing, Mr. Collins is leading a supercomputing project which has allowed visualization of how the constituent proteins of SARS-CoV-2 interact inside of cells to build whole viruses.
Editor’s Note: The U.S. Transhumanist Party publishes this article by Michael Herschman to illuminate his creative idea for the development of skyships that would act as permanent human habitats and transitional platforms between Earth and space, benefiting the infrastructures and development of both of these realms. The skyship concept echoes the floating structures observed above the Earth and other worlds in the paintings of Robert McCall, and it would be an impressive feat of human progress for them to be brought into concrete reality.
~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, April 17, 2021
Physics evolves, and we can soon expect our advances in engineering. They rarely come, but they never leave. Voices can evolve from turmoil or from excess: People do not often think about science in terms of moral progress… However, there is no holiness of the mind that does not seek happiness. If we choose to look into the sky rather than at the ground, we will find more area for expansion. To a degree, our economy has developed an association with buoyancy. Self-reflection will take you far, but aviation can take you further.
Individuals try to want what is right. Most people never consider human-governed celestial action. NASA, Blue Origin, and SpaceX are influences toward limitless human engineering capacity. To not engage is to hold on… We face gravity as a creative people: Skyscrapers are natural, airplanes are natural, space rockets are natural. Skyships are natural. We need to defy current electronic constraints. It is the natural imperative of every individual to understand according to their capacity the truth of climate change. We see our Earth becoming more and more deceased from carbon. And we use carbon-dioxide-emitting rockets as we leave Earth. By our current standards, the safety and integrity of life on Mars is absurd.
Rendering a sustainable life in the sky is a real and true objective. It is a necessary structure for our next aeronautic epoch. Having a structure between skyscrapers and a space station will bring both closer. Common flying vehicles will proceed from skyship systems and intellectual scaffolding. Its existence will temper its surroundings. And its inhabitants will contribute to society. Everyone on the ship will have the goal of improving life on terrestrial Earth. It is Earth that got them there. They will serve Earth.
Skyships will come about naturally. They are a platform for energy freedoms and personal flight vehicles: so we are guided toward their construction. During the ship’s existence it will help society. Nothing onboard will languish from lack of attention or ability. The ship will be composed of givers that learn and share and provide examples for human structure. The ship will be bound by holistic healthy associations. Craft inhabitants will cure diseases.
We already have airships. A skyship is an airship that can be lived on indefinitely. They will be buoyant and provide protection and can be lived on indefinitely. They will be assisted by fuels and electricity but have no carbon footprint. They are bound to give to society.
Note from the Editor: In a conversation on Clubhouse that I hosted, entitled “Is the FDA moving too slowly with vaccine approvals?”, Will C. articulated a number of nuanced points about the FDA. He had recently finished reading Reputation and Power, an 856-page book on the history of the FDA. I asked Willy to organize his notes on the book so that the USTP membership could learn his key takeaways from the book and learn more about the history and role of the FDA. Willy graciously accepted my request. I have edited his notes somewhat for length and made some minor copyedits. A few key takeaways are bolded.
– Daniel C. Elton, Director of Scholarship, United States Transhumanist Party, April 2, 2021
Reputation and Power Organizational Image and Pharmaceutical Regulation at the FDA by Daniel P. Carpenter 856 pgs. Princeton University Press, 2010
Reputation and Power is a very deep dive into the history of the FDA and the reputational universe that it inhabits and creates. The gist of the book is that reputation management is the best lens to understand the FDA, not “public interest” versus “regulatory capture”. The political and regulatory power of the FDA is bound up inextricably with how Congress, the pharmaceutical industry, academic medicine, and consumer-protection groups view it. By virtue of the size of the market it regulates and its pre-market approval power, the FDA is likely the most powerful regulatory agency in the world.
Because of the length of the book and the variety of topics it covers, I’ve split this book summary into two parts. The first half covers the history of the FDA and the second half covers the themes and lessons I learned from the book. Though Carpenter covers up to about 2010, time constraints meant that this summary only covers up to 1992. Hopefully future posts will cover the remaining material.
The origin story of the FDA in popular political mythology begins with thalidomide, but Carpenter does an excellent job showing how the FDA started as an obscure branch of the USDA, originating with the Pure Food and Drug Act of 1906. In the early 1900’s the FDA had nothing but the ability to confiscate dangerous drugs or compounds from the market. Later, in a pattern that will repeat itself, forces within and without the FDA made good use of the dictum “Never let a crisis go to waste.”
The context is that the early 1900s were a stupendous time to be a patent medicine salesman– a synonym for charlatan. Apart from aspirin, it’s not clear that any patent medicine of that time ever turned out to be effective. Medicines to lull your baby to sleep relied on opium or alcohol, and sulfonamide antibiotics were not invented until the 1930s, and even then their manufacturing process was initially unreliable . Yet the patent medicine trade was booming. In an interesting historical irony, John D Rockefeller, through his foundation’s funding of the Flexner Report, which birthed medical education as we know it, ended the traveling medicine salesman/huckster-doctor profession – which his own father had been in.
The Pure Food and Drug Act of 1908 required accurate labeling of products and also gave the FDA the power to seize and destroy products that violated the law. Importantly, this did not give the FDA the power of pre-market approval, which is its most important power today. Though the FDA was prohibited from directly lobbying for more authority, many in the agency and their Progressive congressional allies believed the FDA was weak and underfunded relative to the growing pharmaceutical industry it was supposed to regulate. In 1935, New York Senator Copeland had tried to pass legislation that would strengthen the FDA, aided by women’s political organizations and the Consumers Research group, but his attempt had failed in the House.
There had been previous small-scale pharmaceutical disasters, but the Sulfonamide Elixir stood out for scale and the media attention that it garnered. The leading role that the FDA eventually took in handling the disaster, as well as the relationship with the media that it cultivated, also made this disaster special. This is the beginning of the sidelining of the American Medical Association (AMA), which had previously been one of the centers of organized medical power.
People became seriously ill from its consumption, and by late October 1937, at least seventy-three of these had died. The FDA, assisted by state and local health officials and the American Medical Association, commenced an effort to secure as much of the compound as possible before any more was consumed.
The media ran stories of heroic FDA officials working late into the night trying to confiscate a dangerous drug, and the story re-surfaced whenever another death was reported. The cherry on top of this story was a report released by the Secretary of Agriculture, the Campbell-Wallace Report:
‘A few simple and inexpensive tests,’ the sort that would be performed by the company before marketing and analyzed in a pre-market review process by the FDA, would quickly have evinced the elixir’s “toxic properties.” Translation: with a pre-market review process, none of this would have happened.
In February 1938, Copeland’s S.3073 was again considered in the Senate. Women’s groups and public-health leagues now lobbied intensively for its passage, and their rhetoric made clear the centrality of the Wallace report in the new deliberations.
Contrary to the theory of regulatory capture, large pharmaceutical firms, who might have expected to benefit from a regulatory moat, did not advocate for the 1938 Food, Drug, and Cosmetic Act. Instead, it was Progressive politicians pressured by consumer protection groups, women’s groups, and forces within the FDA that advocated for it.
The 1938 Food, Drug, and Cosmetic Act gave birth to modern pharmaceutical regulation: The four enumerated powers—(1) pre-market review and notification, (2) prohibition (or withdrawal authority), (3) labeling regulation, and (4) compulsory disclosure of all drug contents (active and inactive)—have become assumed and core legal features of pharmaceutical markets
While the 1938 act did not contain an efficacy provision, Carpenter shows how this was effectively smuggled into drug regulation anyways, with officials saying:
It has been emphasized that there is no arbitrary standard of safety; it is a relative matter in which the toxicity of the drug must be weighed against the therapeutic benefits which its use will bring about.
In the 1940’s and 1950’s the FDA gradually raised the standards for drug approval, and its Division of Pharmacology drew many talented pharmacologists from academia. Throughout the FDA-cultivated “reputational ambiguity”.
The simultaneous ambiguity and fear-provoking stance of investigational regulation was, in part, FDA officials’ manner of expressing and maintaining the agency’s gatekeeping role, even as they did not fully comprehend…
Though a Randomized Controlled Trial was not yet an explicit requirement for drug approval, the FDA gradually raised the bar on the required toxicity, stability, and drug metabolism studies. As pharmacology refined its methodology, the FDA required more and more from drug companies, viewed amateur physician-directed trials with more suspicion, and by being the central gatekeeper of pharma, made the whole field more rigorous and scientific.
The FDA used a variety of carrots in addition to the “stick” of gatekeeper:
From the beginnings of the Eisenhower administration and probably earlier, FDA officials acted intentionally, strategically, and with foresight to establish numerous committees of liaison to the professions. Agency officials established not just medically specialized “advisory committees” of the sort that became institutionalized in the late twentieth and twenty-first centuries, but also more temporary committees that helped the FDA recruit and retain allies and consultants.
The Administration cultivated relationships with academic luminaries in pharmacology, and many of their promising students became part of it. Dr. Frances Kelsey, a Professor of Pharmacology at South Dakota State University who had done important research on the teratogenic effects of drugs on animal fetuses, was an archetypical example. She had come highly recommended to the agency, and though she developed a reputation as being a more exacting drug reviewer than most, the agency as a whole had become more cautious over the decades.
Thalidomide, marketed as Contergan in Europe, was being widely used there as a sedative, and the company (Merrell) submitted a drug application to the FDA. Kelsey held up the application due to safety concerns, even in the face of vigorous company complaint, and was vindicated when it was later tied to an outbreak of birth defects in Europe.
This might have remained the stuff of obscure industry history if the antitrust subcommittee led by Senator Estes Kefauver had not leaked the details of the story to the reporter Morton Mintz. Kefauver, who had been leading high-profile hearings on the “drug industry” and had been trying to shorten their drug patent periods as well as incentivize generic drug prescription, gave Morton Mintz key data about the Thalidomide saga as well as Frances Kelsey’s role in it.
1962 Amendments and After…
The Drug Amendments of 1962 were opposed by the Pharmaceutical Manufacturers Association, but the FDA’s star was ascendant with the Thalidomide crisis having shown its worth.
At their core, the Amendments contained three provisions governing pharmaceutical regulation (table 4.1). They first required affirmative evidence of “effectiveness” and “safety,” evidence in the form of “adequate and well-controlled investigations,” before any “new drug” could enter into interstate commerce. Second, they required designation of a medicine as an Investigational New Drug during its period of experimentation (and submission of the IND to the agency), and empowered the Administration to nullify this status (and hence development of the drug) if research protections for patients were not being observed, if the clinical trial protocol was not sufficiently rigorous, if pregnant women were being exposed to teratogens, or if any evidence of research as commercialization emerged. Third, they required the Administration to lay out and enforce new procedures to protect the interests and rights of patients in medical research.
The impact of the law was significant: Before 1960, there are no references to phased trials in the American and European medical literature, and there is no reference to a “Phase 3” study in Western medical literature before 1964. In the early 1960s, reports of “Phase 1” and “Phase 2” experiments appear haltingly, then rapidly near the end of the decade (table 4.2). What is more, American researchers and doctors began to reflect systematically on the relationship between earlier phases and later phases.
In the 1960’s, as the FDA continued to gain in power, it met with some moderate resistance from organized medicine. These incidents illustrate the reputational politics that the FDA is sensitive to: when comments by Frances Kelsey at a medical conference were taken to indicate that patients always had to be informed that they might receive a placebo, a leading clinical trialist at Harvard, Henry Beecher, wrote to the FDA Commissioner. In another incident, the FDA’s General Counsel William Goodrich implied that medical journals might be liable for misleading advertisements, which prompted a prominent Cornell pharmacologist Walter Modell, who had previously been an ally of the FDA, to publicly rebuke them.
In both cases, to varying degrees, those statements were publicly walked back by the FDA.
Sometimes public dissent against the FDA could damage one’s career, even for the most credentialed academic, as Louis Lasagna’s advocacy for combination antibiotics demonstrated:
Lasagna’s advocacy for Panalba was risky and vocal, and it marked the beginning of a steady decline in his status among medical academicians. Lasagna’s name was golden in the 1950s, when he had authored pathbreaking papers on the placebo response and clinical trial design, when he had founded the nation’s first clinical pharmacology department at Johns Hopkins, and when he had testified in support of efficacy standards at the Kefauver hearings in 1960.
…The diverging paths of Louis Goodman and Louis Lasagna marked the splintering audiences of the Food and Drug Administration as well as the agency’s enduring scientific legitimacy. In the status-conscious world of academic medicine, Louis Lasagna never fully recovered from the Panalba battle.
An important feature of FDA history in the 60’s and 70’s was the congressional hearing. Because of changes in how congressional committee chairs were chosen, congressional hearings became more important in this period. The obligation of FDA officials to appear before Congress when requested and to testify was an important check on its power and a venue where its public reputation was maintained.
Criticism from an industry-friendly senator could strengthen the FDA’s image as pharma policeman while an FDA whistleblower like John Nestor testifying to its regulatory inadequacy could force less accommodation with the drug industry by effectively shaming the FDA into more stringency.
Congressional hearings seemed, at least in the 1970s, to be the strongest check on FDA behavior. When Senator Gaylord Nelson read The Doctor’s Case Against the Pill, and started hearings into the FDA’s approval of it, and its widespread use, the end result was, after much criticism from prestigious physicians, scientists, and consumer safety advocates, the creation of the patient-package-insert. (see chapter 9)
An illustration of how the FDA sought to collaborate with other scientific institutions can be seen in how it dealt with medications that had been approved before 1962 and the formal recognition of an efficacy standard. Thousands of drugs had been approved in the 1940s and 1950s on the basis of evidence that were wholly inadequate by 1962 FDA standards. These drugs had now been incorporated into clinical practice for many years, and so any FDA action on them would be seen as doubly intrusive by physicians. To strengthen their position and reduce their workload, the FDA collaborated with the National Academy of Sciences to evaluate these old drugs.
The 1970s probably marks the peak of the FDA’s power, as a series of court decisions endowed the Administration with the authority to issue rules with “the force of law” and creating “a presumption in favor of agencies that claimed legislative rulemaking authority”. When the FDA does not want to create formal rules, which require an elaborate process, it also uses “nonbinding” guidance documents which are, in reality, quite binding:
Because the Administration has the ultimate say over whether and when a new drug will be marketed, its mere suggestions and intimations induce compliance even where they are not backed by legal authority. The agency’s use of Federal Register policy statements and “guidance documents” (nonbinding statements of policy that are not customarily published in the Federal Register but are published under the auspices of the FDA itself) permits its officials to avoid the more costly and elaborate process of formal rulemaking, while still gaining acquiescence with its regulatory wishes.
With its arsenal of new authorities and the powers that flowed from them, the Administration began in the 1960s and 1970s to exercise vast sway over the medical marketplace. Familiar over-the-counter remedies and doctor-prescribed pills vanished. The place of the general practitioner in drug development waned to the point of disappearance, as companies could no longer rely upon doctors’ casual observations or observations of patient histories to buttress claims of safety and effectiveness.
Though there were occasional media critiques of the FDA in the late 1960s, the 1970s and 1980s were really the beginning of a sustained critique of the FDA from the right. This came from many quarters: business-friendly publications like the Wall Street Journal, prominent economists like Sam Peltzman who were quantitatively assessing regulatory impact on innovation in various industries, and industry organizations. In 1974, the American Enterprise Institute played a key role by launching the AEI Center for Health Policy Research, which brought together pharmacologists, industry officials, and economists. The “drug lag”, coined in 1972, was the time between a drug being introduced in Europe vs the US, and along with the cost-benefit analysis of regulation, was a key critique of the administration. A sign of the success of these critiques was that while top FDA officials publicly rejected the premise of the drug lag, inside the administration, increased attention was paid to the drugs that had already been approved in peer countries.
Even as libertarian-aligned think tanks, academics, and newspapers criticized the FDA for being too cautious, the opposite critique was sustained by consumer-protection groups throughout this period.
No voice more cogently or passionately articulated the case for rigorous drug safety standards than that of physician-activist Sidney Wolfe, and no arrangement better amplified the concerns of Wolfe and his allies than the committee systems of the U.S. House and Senate. Wolfe helped to found the Health Research Group, a subsidiary of Ralph Nader’s Public Citizen, in 1971.
Wolfe had no formal role in the Administration, but by careful use of administrative procedures like FOIA requests and citizen petitions, combined with journalist connections, he could push the FDA into action when it was reluctant. The whole section on him is worth excerpting:
Wolfe’s principal weapon was his threat to the Administration’s consumer protection image. The credibility of this threat depended on a set of strategies by which Wolfe and his organization could embarrass the agency, extract data from it, influence the FDA’s decision agenda, or (less commonly) induce courts to force the agency to take a given action.
First, he was adept at using administrative procedures refined in the 1970s, including Freedom of Information Act (FOIA) requests and citizens’ petitions, to pry important drug safety and procedural information out of the agency, or to place contentious and uncomfortable items on the Administration’s agenda. Second, Wolfe exploited the public comment period of the FDA’s advisory committee meetings on drugs, an opportunity that offered a public venue albeit with brief appearances. Third, Wolfe appeared regularly at congressional committee hearings as an invited guest, and his ties to committee chairs and their staff gave him indirect access to committee powers (replete with tools for discovery). In the 1970s and 1980s, Wolfe worked partially in tandem with subcommittee chairmen ranging from Lawrence Fountain, Henry Waxman, and Ted Weiss in the House to Senators Edward Kennedy and Abraham Ribicoff.
Fourth, Wolfe maintained ties to journalists over a period of several decades (Morton Mintz, Christine Russell, Philip Hilts, and others). He used these journalists to publicize actions (such as the taking of surveys of FDA medical officers) that would otherwise not have received much public attention. Finally, Wolfe and his organization shrewdly used lawsuits and the threat of legal action to induce rulemaking and jar the agency into action. The strategies of administrative maneuvering, advisory committee testimony, appearances at congressional hearings, and media access became much more pivotal to Wolfe’s leverage over the FDA after 1979, when a federal judge limited the right of Nader’s group to sue agencies on behalf of the general public.
A clear demonstration of the conservative sentiment of the times was the backlash against the FDA when it attempted to regulate supplements more stringently:
In August 1973, the Administration published fourteen final regulations and five proposed rules that governed the labeling of foods and food supplements.
Led by Wisconsin Senator William Proxmire, Congress in 1976 passed an amendment to the 1938 Act which extended the “generally recognized as safe” (GRAS) exemption for vitamins and minerals to dietary supplements. The “Proxmire Amendment” prevents the Administration from restricting the potency of a vitamin or mineral supplement based on either of two criteria: (1) food misbranding charges or (2) on the premise that the supplement would qualify as a drug if it surpassed the agency’s desired level of potency. For almost two decades, FDA officials largely backed off from rule-making on supplements.
In the late 1990s, the FDA again attempted to regulate supplements and faced a similar legislative rebuke.
Overall, though the FDA faced some setbacks when it attempted to regulate supplements, it survived the conservative turn in the 1980s with its power and reputation mostly intact, an impressive achievement for such a powerful regulatory agency. In some ways, the criticism from the libertarian perspective may have strengthened the FDA’s reputational position:
[I]t would be wrong to conclude that the persistence of criticism and scrutiny has undermined the agency’s reputation and power. It is certainly plausible that criticism has depleted morale, and on occasion publicity and hearings have weakened its leadership.
For those who have paid attention to the increasing polarization of US politics over the last 20 years, this may sound familiar – criticism from your enemies can be a reliable signal to your allies that you’re on their side. In a similar way, pharma and libertarian criticism of the FDA may strengthen its reputational position in the views of consumer-protection groups and allied groups.
AIDS and Cancer
The “drug lag” criticism was a long-lasting and effective critique of the FDA, but Carpenter seems to argue that the most significant reforms of the FDA were really brought about by inter-agency squabbles over cancer drugs and the moral outcry of the HIV epidemic. The interactions of AIDS activists and the FDA are probably more well-known than the turf battle between the National Cancer Institute (NCI) and the FDA, but it appears that the latter may have been more influential.
NCI-supported investigators were developing combination chemotherapies that were very promising, modeled after the lucky discovery of platinum’s anticancer potential by physicist Barnett Rosenberg. From 1975 to 1977 Robert S. K. Young, an FDA medical reviewer, repeatedly took issue with the study protocols of combination chemotherapy trials and halted several trials. A prominent MD Anderson oncologist, Emil Freireich, retaliated by reading out a list of complaints about FDA interference into NCI-funded trials at an important meeting of President Ford’s Cancer panel. Benno Schmidt, the chairman of the panel and a prominent official in Ford’s Administration, agreed with him. Young’s supervisor William Gyarfas stuck by his subordinate.
Young overreached when in a 1977 Advisory Committee he attempted to more aggressively regulate the clinical trials of combination chemotherapy and effectively eliminate dosage variation in chemotherapy without preclinical studies. The Committee voted against his proposal, and this caught the attention of Richard Crout, then-head of the Bureau of Drugs. Crout met with the head of NCI and basically admitted his subordinate had overreached, and they worked on a series of protocols to relax FDA restrictions for terminally ill patients.
While this might have been the end of the bureaucratic conflict, the NCI had decided to escalate:
House Health Subcommittee chairman Paul Grant Rogers (D-FL) released a December 3, 1976 letter from the American Cancer Society calling for full “NCI control over the testing of new anticancer drugs, instead of FDA control” for nonprofit research sponsors. This transfer of power would be accomplished, as ACS representative Nathaniel Polster hoped, by amendments to the National Cancer Act. While NCI officials were largely silent about the ACS proposal, M. D. Anderson’s Freireich was not. He openly called for deep “structural changes” so that the “FDA can never again shut [down cancer research].”
This would be a huge escalation. If the NCI succeeded in wresting control over regulation of a specific disease, it would set a precedent for continued piecemeal diminishment of FDA authority:
And to Administration officials concerned about the maintenance of their authority over clinical trials, the ACS-NCI proposal raised the specter of debilitation by precedent. Once an exception for one category of illness was carved out of the FDA’s power over clinical research, it was feared, demands from representatives of other diseases would soon follow. As if to confirm the FDA’s premonitions, Solomon Garb of the Citizens’ Committee for the Conquest of Cancer seized upon the NCI-FDA dispute and called for ending FDA power over any clinical trial in which patients have “poor prognoses.” Garb’s remarks introduced a different and more formidable voice to the growing chorus of criticism, in part because the Citizens’ Committee was an amalgam of union, scientific, corporate, scientific, and civic leaders…
This proposal didn’t come from a fringe libertarian or anti-government organization but from respected sources. The NCI and the FDA eventually came to agreement:
DeVita and Crout settled on a new procedure whereby “stop orders” for NCI-sponsored trials for terminally ill patients could be issued only by the Bureau of Drugs chief (Crout himself at the time) or the deputy chief (Marion Finkel, at the time). The two groups later agreed to use the nation’s forty comprehensive cancer centers to mediate the surveillance of research protocols. The new arrangement embedded meaningful victories for both sides. For the Institute, the new procedures effectively bypassed Robert Young and, more notably, William Gyarfas, Director of the Oncology Drugs Division. NCI officials and their grantees would now deal more directly with Crout and Finkel, who were more trusted within oncology networks. And the Institute’s détente with the FDA helped it to buttress claims that it was being “dominated”…
The Administration would retain full control over cancer trials. The NCI would now officially acknowledge and defer to the IND regulations, and in so doing it would develop a “Master Plan” of drug development…
By January 1979, the dispute had issued in a document with odd legal status but firm organizational commitments (figure 6.1). An informal procedure for resolving FDA-NCI disputes appears to have been worked out in April 1979. The procedure entailed four steps: (1) first devolving disputes to the lowest managerial level deemed suitable for negotiation—the Associate Director of the Bureau of Drugs (at that time, Finkel) and the Director of the NCI’s Cancer Treatment Division (DeVita), then (2) to negotiations between the Bureau of Drugs head (Crout) and the NCI Director, then (3) to negotiations between the FDA Commissioner and NIH head, and (4) finally, determination by FDA Commissioner himself if none of these previous options produced a resolution. The memorandum bound neither agency legally. It was rather an informal institution founded in a political equilibrium, a mutual wish to avoid the spectacle of open, public conflict among two agencies whose reputations generally benefited from being out of the public eye.
While the NCI and FDA struggle would lead to a durable compromise between the two agencies, the Laetrile saga would come closest to threatening FDA power, and yet ultimately affirm it. From a libertarian perspective it is darkly amusing that the drug that came closest to breaking the FDA’s stranglehold was the charismatic but ultimately useless drug Laetrile.
Laetrile had been developed by an Ernst Krebs (of no relation to the Krebs cycle) who had failed out of medical school and whose father, incidentally, was also a conman physician. At various times its supporters described it as vitamin B17, as a relative of cyanide, and as amygdalin. NCI scientist Dean Burk had developed a molecular model that was supposed to demonstrate Laetrile’s anti-tumor activity and a San Francisco foundation applied to the FDA for an IND for experimentation.
Their IND was ultimately rejected by the FDA, which cited problems with the sponsors and monitors of the trial and its design. The key difference between the FDA’s rejection of Laetrile and its previous policing of quack medicines was the FDA exerting its power on the IND stage. This was a rhetorically powerful difference.
What most bothered many Laetrile supporters and their distant sympathizers was not the absence of Laetrile from the drug marketplace, but the absence of a permit for testing. Appropriating the juridical metaphor of a “fair trial,” they linked a populist ethic of self-medication to issues of justice and to more progressive norms of academic and intellectual freedom, the liberty of research and exploration of ideas. … By pressing the case for a total ban, by publicizing its seizures, and by assisting with state and federal prosecutions of Laetrile distributors, the Administration had resurrected a face that had been nearly invisible since the 1950s: the FDA as police.
Newspapers ran headlines criticizing the FDA for overreach. Organizations for therapeutic freedom sprung up across the country and a bill sponsored by Representative Steve Symms that would repeal the efficacy provisions of the 1962 amendments attracted over 100 sponsors. Several states passed laws legalizing Laetrile. The anti-FDA sentiment was nearly mainstream: Time Magazine, The Wall Street Journal, and the New York Times all ran editorials with some support for Laetrile proponents, or at least criticized the FDA’s overreach.
From the FDA’s perspective, several court cases were going in an unwelcome direction. Lower courts had issued an injunction against seizure of Laetrile, had decided that the FDA had the duty of showing lack of safety, not the sponsor affirmative proof of safety, and that the FDA had not exercised due process in its Laetrile ban. Since the regulatory power of the FDA was inextricably bound up with its flexible ability to issue rules and the affirmative requirement of drug sponsors to show safety and efficacy, these rulings were a threat to the FDA. In recognition of this enormous pressure, the FDA Commissioner did two contradictory things: one, he affirmed his agency’s judgement that Laetrile was ineffective and dangerous; two, he granted an IND to the NCI for Laetrile. In a PR coup for the Laetrile camp, they also testified before Congress to the Health and Scientific Research Subcommittee. The ability of the agency to offer different faces to different audiences is a recurring theme of Carpenter’s, who views it as key to the FDA’s long-term success.
In June 1979, in Rutherford vs United States, The Supreme Court reversed the Tenth Circuit, which had previously ruled that the FDA could not regulate drugs given to terminally ill patients. It was a powerful affirmation of the FDA’s regulatory authority. Though at this point the FDA could have likely dropped the Laetrile IND for any number of reasons, the FDA issued a conditional approval for Laetrile’s IND, which was set to be tested at rigorous NCI-affiliated institutions that the FDA trusted.
The Supreme Court decision, followed by the very public death of actor Steve McQueen, who had pursued a number of alternative medicine therapies including Laetrile after a mesothelioma diagnosis, led to the gradual decline of Laetrile’s political power. The FDA post-Laetrile had its legal power affirmed over every part of medicine: terminally ill patients, cancer patients, whether a given drug was even a legitimate experimental drug, etc.
Like the NCI and FDA power struggle, the AIDS crisis resulted in substantial concessions by the FDA. Unlike the former, the AIDS crisis played out much more publicly, and instead of bureaucratic warfare, the battle was a reputational one. The primary strategy of AIDS activists was to attack the FDA’s good name– instead of a public health agency and “protector of the American consumer” they sought to cast it as a villain who was killing AIDS patients through its slow and inflexible procedures. Until the 1990s AIDS was a slow death sentence, and in the early 1980s it was still poorly understood, with an official announcement by HHS Secretary Margaret Heckler that AIDS was caused by HIV occurring only in 1984. Retroviruses had only been discovered in 1970, and there were no targeted therapies for them until the HIV antiretrovirals.
An important advantage that AIDS activists had was that decades of organizing had left the gay community with many highly effective and experienced community activists. Many of them went on to form important groups: the most prominent of them were Gay Men’s Health Crisis, AIDS Foundation, Project Inform, and ACT-UP. Gay men were also highly concentrated in urban centers and in some places, like San Francisco, had achieved some degree of political power. Nancy Pelosi, a rising star in the Democratic Party, was sympathetic to many gay activist groups and a Congresswoman. All of these resources would eventually be mobilized against the FDA.
A key event was the story of HPA-23 and Rock Hudson. Rock Hudson, a movie star who had been diagnosed with AIDS in 1984, died of AIDS in 1985. Newsweek reported that before his death he had traveled to Paris to receive an experimental HIV treatment, HPA-23, which was being given there, though under poorly controlled conditions and with little good evidence. The FDA had banned even its experimental use in the US because of severe liver toxicity concerns; it then reversed course and allowed testing in 1985, likely due to the Newsweek story. Well-done trials in 1986 in the US later demonstrated severe toxicity and no efficacy, vindicating the FDA’s earlier caution.
The first effective treatment for HIV was azidothymidine (AZT), which was being developed by Wellcome, a reputable drug company that had substantial experience with the FDA. To the FDA’s credit, the AZT path to approval was remarkably quick: the company first started investigating AZT in June 1984 for possible HIV activity in-vitro; notified the FDA in April 1985, submitted an IND in June 1985, the FDA approved it in a week, and the first clinical trial (Phase 1) began in July 1985.
Phase 2 trials which had begun in February 1986 were halted early in September 1986 due to clear signs of treatment success, and AZT was officially submitted to the FDA for approval in December 1986. Eileen Cooper, a rising young star at the FDA, was in charge of reviewing it, and had been reviewing the AZT data for months before the official submission date. Even before the most militant AIDS activists had begun pressuring the FDA, she had been discussing with others on ways to speed and streamline the approval process.
She took two important steps. First, in September 1986 she had released AZT for compassionate use to 4000+ AIDS patients, which likely saved many lives. Second, she sought the support of the FDA’s Advisory Committee on Ineffective Drug Products in a January 1987 meeting, which would symbolically back up the FDA’s decision to approve AZT on the basis of a single prematurely ended clinical trial. This would achieve two contradictory goals: the rapid release of a likely effective drug to suffering patients; and satisfy the consumer-protection and public-health voices that generally urged caution.
Thus, even before much of the publicized anti-FDA activism, the FDA had demonstrated flexibility and speed in approving AZT. However Larry Kramer, a prominent playwright and activist in the gay community, viewed this as grossly inadequate, and penned a 1987 essay in the NYTimes attacking the FDA. Carpenter is skeptical of Kramer’s specific claims:
Kramer’s essay is shot through with inaccuracy and hyperbole. Of the therapies he mentions, only ddC (zalcitabine) emerged as a recognizably and broadly effective treatment for HIV/AIDS in the ensuing two decades—and its development had been accelerated by the Administration at the very time that AIDS activists were expressing strong doubts about it. Furthermore, many who perceived organizational problems at the agency—including journalists at the New York Times but also the George H. W. Bush administration—saw less a malady of bureaucracy and more a deficiency of resources. Like other AIDS activists, moreover, Kramer was equating the FDA with the Reagan administration when in fact much of Reagan’s and his administration’s ignorance of or indifference to AIDS was unrelated to FDA policy or regulations… Yet for all of its shortcomings and simplifications, and indeed because of them, Kramer’s essay was politically effective because it projected a simple, accessible, and forceful threat to the FDA’s reputation. Like much of the portraiture emerging from AIDS activists, it recast the Administration in terms and symbols diametrically opposed to those fashioned by Young, Cooper, and Tabor in the review and approval of AZT. In some ways, the FDA was being cast as a generalized but faceless bureaucracy, as an inefficient, an “intransigent,” “callous,” and inaccessible organization. In other ways, it was the Administration’s very gatekeeping power—over drugs themselves (the NDA process) and over clinical trials (IND approvals)—that was under attack. By serving as a “bottleneck,” a public health agency dedicated to consumer protection was lengthening the “roll-call of death.” Instead of raising genuine and substantive issues regarding clinical trial design with AIDS drugs, the Administration was in Kramer’s depiction imposing classic “red-tape” constraints upon medical research, nitpicking research protocols, shuffling words and sentences.
Beyond criticizing the FDA, local activists and physicians also directly subverted the traditional placebo-controlled trials:
Doctors would lie about their patients’ previous disease status to secure patient enrollment in a trial. Activist physicians and health-care workers would examine a pill to expose its placebo content. Once a placebo was identified, activists and patients would substitute the genuine treatment for the research subject, using supplies procured underground.
In California activist Martin Delaney ran an unofficial trial with “Compound Q”, distributing it to patients that had failed to respond to other drugs and bypassing the FDA entirely. Part of the project’s explicit aim was to push the FDA harder against its traditional approach to drug development.
Activists like Delaney and Kramer also personalized their criticism of the FDA by singling out Ellen Cooper, the medical reviewer for AZT (and the FDA’s unofficial point-person for HIV drugs), attacking her in the New York Times and in ACT-UP manuals. The peak of activist militancy was probably the October 1988 Rockville demonstration against the FDA. More than 1000 activists gathered in front of the FDA and displayed a banner that read, “Federal Death Administration”. Of note, these protests occurred after the AZT approval. Media coverage followed the protest, and the FDA responded by hosting a press release which effectively restated the new procedures that Ellen Cooper had developed for AZT. This announcement made newspaper headlines, though activists viewed it as a publicity stunt, not as a substantive change.
The most substantive change was probably the “Subpart E” regulation, which would allow for the possibility of a single expanded Phase 2 Trial sufficing to prove safety and efficacy for certain debilitating diseases. Again, this formalized the process that AZT had undergone, and this and other changes had actually been foreshadowed by the FDA’s behavior with cancer therapeutics. This is a recurring observation by Carpenter – phase shifts in FDA behavior are usually preceded by more subtle but similar behavior years or decades before. AZT had sped through the FDA approval process faster than any drug before – but it followed the template of cancer drugs before it. Continuity, not revolution, is the running theme of the FDA’s history.
ACT-UP was very strategic: some elements of conservative politics had long wished for a repeal of the 1962 Kefauver-Harris Amendments, but ACT-UP made sure to maintain “organizational and rhetorical distance” from those groups, which likely preserved their credibility with other forces. ACT-UP overplayed their hand in 1991. With the looming threat of another protest, ACT-UP demanded a 30-day review of DDI, which was undergoing the reformed approval process that incorporated surrogate endpoints (CD4 counts) and a historical controls of the patient’s previous history. Though they received a letter from the FDA Commissioner in response, the approval took more than 30 days, and so ACT-UP staged another protest. It was a dud in comparison to the 1988 protest, with many fewer protesters and little media attention.
This was likely because the FDA had neutralized much of the group’s criticisms by moving quite quickly with approvals and liberally allowing treatment INDs (which allow “compassionate use” of drugs outside of trial settings). The FDA had also begun reaching out to less militant AIDS groups and invited activists into Advisory Committee meetings. In a move reminiscent of how the FDA recruited prestigious academics in the 1950s and 1960s, the FDA waved the “carrot” of being a (partial) insider to neutralize opposition. Another factor may have been a changing media narrative that argued (apparently without evidence) that Reagan-era cuts were the reason for FDA slowness, which exonerated the FDA of blame.
The unofficial buyer’s clubs popularized in film were treated deferentially by the FDA in comparison to Laetrile sellers decades before. It tread lightly, likely in fear of invoking the “FDA as policeman” image.
Something inconvenient for the libertarian and AIDS activist critique of the FDA was the “medical reversal” on the DDC/DDI/AZT combination therapy. After DDC and DDI were approved in 1992 on the basis of surrogate endpoints showing boosted T-cell counts, follow-up studies failed to show benefit relative to AZT alone, and the combination was more toxic than AZT alone. This led to an internal debate in the AIDS-treatment-activist sphere. Here is one account, from Treatment Action Group, an organization that successfully pushed for stricter AIDS drug standards instead of continued loosening of regulatory standards. For a book-length treatment on the loosening of regulatory standards in the cancer world, and the consequences that followed, read “Malignant” by Vinay Prasad.
A less visible but likely more important event in FDA history was the Lasagna Committee, which was announced in 1988, and gathered many of the FDA’s critics.
Rhetorically, Administration personnel claimed from the late 1980s onward (with great plausibility) that drug review delays were primarily a matter of staffing. Internally, FDA leaders looked at the oncology drug division as an exemplar of what quick NDA review could look like, as many of its reviews were completed in less than a year. Oncology drug reviewers were quietly transferred to the anti-viral division, and new medical reviewers were hired. In the late 1980s and early 1990s, drug review times for new molecular entities – perhaps the single most important quantitative measure on which the Administration was judged in pharmaceutical politics – began to decline appreciably
In 1992 FDA Commissioner David Kessler, patient advocates, pharma industry representatives, congressional committee chairs, and President Bush’s staff agreed to the Prescription Drug User Fee Act, which informally bound the FDA to review time goals and effectively taxed drug companies per drug application. To the degree that FDA staffing was the rate-limiting step on drug approval, this would speed approval, but critics said it eroded the FDA’s willingness to push back against shoddy drugs. I am not sure how to evaluate that claim, but I don’t understand the mechanistic claim – the user fees tied the FDA to a review timeline, but it didn’t mandate approval or penalize rejection. Carpenter writes that it might have eroded FDA culture by tying it financially to pharma, but this seems somewhat implausible, because it did not tie funding to any drug in particular, or any particular target of “X% of drugs must be approved”.
FDA in the 2000s
Briefly, the FDA in the 2000s has been described as becoming increasingly lax on drug approval, particularly in cancer. This is covered in-depth in Malignant by Vinay Prasad. The Vioxx scandal, in which Merck was viewed as having concealed the fact that patients taking Vioxx were experiencing higher rates of cardiovascular complications, and in which the FDA seemed to take quite a long time to remove Vioxx from the market, also damaged the FDA’s reputation. In 2004 the FDA was widely viewed as having ignored science for political reasons when it kept Plan B (emergency contraception) prescription-only instead of making it OTC. Here is one perspective on that.
Scott Gottlieb, who had been a high-level FDA official before being Commissioner but also worked for the AEI (the leading think tank criticizing the FDA), had been anticipated to be a highly de-regulatory FDA Commissioner. I can’t find sources for this claim, but my impression is that Gottlieb has generally acquired a good bipartisan reputation and did not oversee a radical shift in FDA direction. He also won praise for moving somewhat aggressively against flavored vapes, which are widely viewed (rightly or wrongly) as a growing public health threat.
Approval is Final
Because approval of a drug is so symbolically powerful, and effectively stakes the FDA’s reputation to a given drug, the FDA only does so very deliberately. It is a social technology that reduces the immense complexity of an IND application (consisting of clinical trials, endless manufacturing and absorption data, etc.) into a binary YES/NO that physicians and nurses can rely upon. Reversing a decision is reputationally damaging, and the FDA has occasionally faced criticism from consumer-protection groups and even internal FDA employees that it is too unwilling to withdraw unsafe drugs from the market. This is problematic when drugs are approved based on surrogate endpoints instead of clinical endpoints, or when safety problems emerge after approval, as with Vioxx.
Carpenter comments on this:
It is interesting in light of these conflicts that, in the wake of the Vioxx tragedy of October 2004, higher FDA officials (including many long-term careerists) engaged in an organizationally motivated embrace of the status quo by defending randomized controlled trials and by disparaging pharmacoepidemiology. For different reasons, Deputy Commissioner Scott Gottlieb, CDER officials Sandra Kweder, Robert Temple, and others did not want to cede more control of the pharmaceutical market to David Graham and his colleagues at ODS. Yet it was also an extension of the familiar, an area where the agency had already developed capacity. Clinical trials have advantages when they are randomized and placebo-controlled. They also have drawbacks. Often tests are done on homogeneous patient populations, among patients who differ in many ways from the patients who will utilize the drugs in clinical situations. Clinical trials usually have an endpoint, and can often be too brief to allow analysts to detect whether the drug is inducing adverse events, particularly for toxicity, hepatotoxicity (or liver damage), and cardiovascular outcomes.
On Pressuring the FDA through Reputation
The FDA is responsive to both reputational and political pressure. The former is best thought of as arguing with the FDA on its own ground, which can be done from multiple perspectives. Patient advocacy groups can push the FDA to approve cancer drugs on less evidence; “thought-leader” physicians can sing the praises of an innovative drug and call the FDA slow; FDA whistleblowers can testify before Congress that the FDA is too deferential to pharma; consumer-protection groups can call the FDA’s approval based on a surrogate endpoint “reckless”. All these approaches seek to push the FDA in one direction or another, but fundamentally accept the legitimacy of the FDA and especially in the case of those pushing for more regulatory caution, hearken back to some idealized version of the FDA as a rhetorical device. In the early 2000’s, as the FDA was perceived to have relaxed its regulatory standards, especially on cancer, this occurs more often, with long-time FDA critics like Sydney Wolfe unfavorably compared the current FDA to the old FDA.
A recent example of reputational pressure was Eric Topol’s open letter to the FDA in October 2020 that criticized the emergency approvals of convalescent plasma, hydroxychloroquine, and remdemisvir, and pressured the FDA Commissioner to delay approval of a Covid-19 vaccine. Though many have criticized his actions, its method is illustrative: Topol, who has immense reputational power in academic medicine through decades of leading large clinical trials, publicly attacking Merck during the Vioxx scandal, and having critiqued the FDA in the past for its lack of action on Vioxx, was well-positioned to push the FDA to be more cautious. In addition, the emergency approvals Topol criticized (with the possible exception of Remdemisvir, and maybe Convalescent Plasma if you play with subgroup analysis….) seemed to have been regulatory bets that did not pan out, which left the FDA in a weak position. The politicization of hydroxychloroquine in particular made Topol’s arguments extremely appealing among the reputational audience (large medical journals, elite media, etc.) that the FDA caters to, which all dislike Trump. The combination of a weakened FDA and a strong attacker were the likely reasons for Topol’s success (and in the view of Alex Tabarrok and many others, the rest of the US’s disaster, since any delay in vaccine approvals likely cost many lives). Here an in-depth read on this.
The pro-regulatory counter to the previous paragraph is that vaccine approval was only an obviously good idea in retrospect and that vaccine hesitancy would rise with a rushed process. I think both of those claims are wrong, and I think Ezra Klein argues this well in a recent piece.
Political pressure takes the form of more direct action: Congressional committees can ask FDA officials to justify their actions and have public hearings that embarrass an agency that prefers less public attention. They can threaten FDA funding and if they’re playing hardball, threaten legislative action that directly alters FDA authority.
The challenges to FDA practice which resulted in sustained reform are those that combine both approaches, along with policy solutions that can be proposed at the right political moment. Conservative think tanks had long wished to tie some FDA funding to drug approvals and hold the FDA to a deadline and when conservatives made sustained and substantial gains in the 1980s and 1990s, the FDA, first informally and then through legislative change, moved in that direction.
Sustained media attention also seems to be important for pushing the FDA, but is not essential. The NCI-FDA disputes were not as high-profile as the 1980s AIDS activism but effected reform that was just as important.
An important but vague “audience” that the FDA defers to is the medical community as a whole. This might be thought of as the “elite consensus” in medicine. By directly incorporating respected medical scientists and doctors onto Advisory Committees, the FDA accedes to this audience but also partially neutralizes it. Pharmaceutical companies seek to use this in their favor as well by recruiting big-name academic stars to head clinical trials or research divisions and thereby “borrow” some of their reputation. A sustained critique of the FDA from these directions would also likely be a powerful pressure. For instance, if Advisory Committees repeatedly disagreed with the FDA in one direction, they could likely shame it into changing course.
Theoretically this might be strengthened if a sitting Congressman/woman then called a hearing to directly ask FDA officials about controversial decisions or if sympathetic media ran pieces highlighting this discrepancy. This would be a direct reputational attack on the FDA and a veiled political threat because it would raise the specter of legislative reform of the FDA with enough political attention.
Regulatory Caution is Often Proven Right
As disappointing and non-contrarian as it is to agree with a large, slow-moving government bureaucracy, my impressionistic summary of Reputation and Power along with background knowledge from Ending Medical Reversal and Malignant is that the FDA has usually been proven right in its caution. Approvals based on surrogate endpoints sometimes work, but in Malignant Vinay Prasad makes a strong argument that this often doesn’t speed approvals and that a substantial number of drugs approved on surrogate endpoints are never properly followed up on. Low regulatory standards in cancer drugs have led to a proliferation of low-value treatments approved on the basis of surrogate endpoints that don’t predict clinical (a.k.a. useful) endpoints and that may not actually provide any benefit outside of carefully selected clinical-trial participants. (Editorial Note: For a counterargument, see this post and linked SSRN article on “Type II” errors at the FDA).
A full argument that strict regulation is required for medical innovation is too long for this paper, but Ending Medical Reversal is an excellent argument along these lines. Here is a summary of it. I fully agree with Cowen and Tabarrok that the FDA was far too slow during COVID-19, but I think the libertarian critique of the FDA (usually) goes too far.
The FDA is More Powerful Than You Think
– Apart from holding pre-market approval power over a drug, the FDA also intensely regulates drug experimentation in the first place. It also regulates drug labeling. By virtue of regulating a drug’s intended use (which has substantial effects on insurance coverage) it also informally regulates medical practice in general. And in a decentralized fashion, by being able to disqualify Institutional Review Boards (IRBs), it also regulates clinical research on a fine-grained level.
This IRB-mediated power means the FDA can effectively ban individual physicians or entire institutions from research.
To the degree that overly-cautious IRB’s (who are in turn fearful of FDA attention) constrained Human Challenge Trials, this seems like an under-appreciated cost of the FDA and one that has not previously faced any sustained challenge. The lack of a constituency that is visibly harmed by overly cautious IRBs makes developing political pressure on this more challenging, but this seems valuable.
The FDA and COVID-19 Vaccines
As a thought exercise, it is worth considering what a successful attack against Topol on the vaccine delay question might have entailed. Academic stars in medicine that argued for faster vaccine approval, in contradiction to Topol, would have been rhetorically effective. A less politically polarized COVID-19 response in general would have neutralized the specific anti-Trump claims that Topol made.
Not being in an election year and so proximal to November 2 would have removed the incentive for anti-Trump individuals and institutions to view an early vaccine approval as a Trump victory and likely alleviated some concerns that the vaccines were being “rushed through.” Elite media that favored faster approval and that continually raised vaccine approval salience would not have so favorably amplified Topol’s open letter.
There were some prestigious names contra Topol on vaccines like Walid Gellad but few or none with Topol’s star-power and connections. The prominent economists who pushed for faster approval were all, fairly or not, associated with a deregulatory perspective, which likely made their arguments less credible to the FDA. If the FDA had not burned their credibility on hydroxychloroquine early on, they would have been less vulnerable to Topol’s reputational attack. The somewhat Rationalist-aligned academics and institutions that consistently pushed for vaccine approval and human challenge trials have no cachet in the medical community, and so cannot effectively engage in this reputational battle as insiders.
Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party. You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack.