Conquering Pandemics


 The Race to Conquer Pandemics 

Viruses are neither unambiguously alive nor dead; they exist in a dubious state less than alive (they cannot replicate without hijacking the machinery to reproduce from within a living cell) yet once activated within a host cell they replicate rapidly and pass their genetic material to future generations. 

There is one characteristic of viruses that is indisputable: they evolve faster than almost anything on the planet (HIV, the human immunodeficiency virus, holds the record as the highest recorded mutation rate known). This century produced more new viruses of a global concern than ever before. Viruses are multiplying faster than in the past. Add the explosive globalization of economic and social activity and future pandemics could overwhelm civilization. With the unprecedented response to COVID-19, the world's virologists have the opportunity to forestall, even block, future potential pandemics. 

COVID-19 highlighted how important rapid real-time responses are to combat pandemics as new viruses appear and mutate. At the outset of the pandemic, the United States was ill-prepared to control COVID-19. Research and biomanufacturing were constrained by single-purpose equipment designed and built with mass production rather than adaptability in mind (compare a 3D printer with a room full of equipment made for producing a single part). 

It took the novel virus COVID-19 to initiate the most aggressive global vaccination research ever undertaken. The Pfizer vaccine took just one year to develop compared to the previous record of four years set by the mumps vaccine. Scientists had a head start compared to mumps. Coronaviruses were well known, there are hundreds of them including some that cause common colds. In addition, the technology to create man-made viruses has existed for two decades: a poliovirus was synthesized in 2002 using research focused on biowarfare countermeasures. In November of 2003, a team of scientists in Maryland built a virus strain that was 100% identical to a natural virus. Synthetic vaccines would inevitably follow.

Despite all the scientific advancements, the primary defense against a pandemic was to disengage people from one another. Most of the world chose to impose lockdowns of varying degrees and take the usual precautions to avoid spreading viruses. People were told to stay home except for essential purposes. Educational classes were conducted remotely, social and religious gatherings were prohibited or restricted. Economic and social life was suppressed. 

Lockdowns Evoked Both Proponents and Opponents   

The World Health Organization (WHO) chose not to recommend lockdown fearing it would have a disproportionately detrimental impact on the most disadvantaged segments of society. WHO envoy David Nabarro stated WHO’s position, “The only time we believe a lockdown is justified is to buy you time to reorganize, regroup, rebalance your resources, protect your health workers who are exhausted, but by and large, we’d rather not do it.” The US had no cohesive national plan to combat the pandemic. Unlike many other countries mitigation measures were left to state and local governments. A number of countries reacted quickly and effectively.

New Zealand locked down “hard” early in the pandemic and reopened with virtually no restrictions in early June 2020, just four months after the pandemic was widely recognized. Twelve countries (including New Zealand) currently have no COVID-19 cases. In those countries,  lockdowns were limited to buying time to do what WHO advocated. Other countries were able to open economic and social life early without extended lockdowns and few COVID-19 cases and deaths by restricting travel in and out of "quarantined" countries or regions.  

Nevertheless, most of the developed world relied on lockdowns in an attempt to isolate infected people and otherwise minimize the opportunities for the virus to spread. Whether justified or not lockdowns did save lives but precipitated significant economic and social catastrophes which are certain to outlast the pandemic. There are better ways to manage pandemics.

Combating Future Pandemics Without Lockdowns

Real viruses need to reproduce to be harmful but they can't reproduce alone; they must hijack the manufacturing machinery of host cells. The virus breaks into the host cell and deposits the instructions for the cell to make clones of the virus. A synthetic virus must go through a similar process to fool the host's body into thinking has been invaded by a pathogen. Both synthetic real viruses trigger the same immune response in our bodies. 

The breakthrough that enabled the Moderna and Pfizer synthetic vaccines to work without stripping parts from real viruses was the ability to synthesize the messenger RNA (mRNA) of the SARS-CoV-2 and embed it into the host cell. The mRNA is the set of instructions that tells a cell how to manufacture the protein that triggers an immune response. An immune response is triggered by antigens which in turn causes your immune system to produce antibodies that block or destroy the target pathogen.

James Swartz at Stanford University wants to speed up the process between identifying a pathogen and annihilating it. He imagines building an inventory of bioparticles (empty antigen containers) waiting to be loaded with the specific antigens needed to target the dangerous virus.   As soon as the effective antigens are identified they would be loaded into the bioparticles and the synthetic vaccine could be ready to deliver billions of injections within weeks. In essence, Swartz imagines a biological equivalent of a 3D printer that sits waiting for the right materials and instructions to produce the final product.

Swartz's most formidable obstacle is acquiring the $40 million to develop the concept and test it in humans and another $250 million to create the supp[y chain that would put it into practice. However, this is a trivial amount compared to the U.S. federal government spending over $5 trillion to manage the COVID-19 pandemic and mitigate its collateral problems. That amount of money would fund 20,000 research projects of the magnitude equal to the one proposed by Swartz.

The current pandemic underscored the need to shift from high volume specialized manufacturing processes to more flexible and adaptable production of vaccines; potential pandemics must be stopped before large segments of the population are infected. The mRNA-based Pfizer and Moderna vaccines set records in time-to-market by using recently developed single-use technologies. The next step is to accelerate the processes needed to go from discovering a virus to obliterating it. 

A number of fundraising efforts to promote rapid effective responses to future pandemics are in progress. For example, the Coalition for Epidemic Preparedness Innovations (CEPI) is seeking $3.5 billion to create a platform to have a vaccine ready to combat the next potential pandemic within 100 days of its discovery. The Bill and Melinda Gates Foundation has contributed to CEPI.

Hunting for Novel Viruses

Novel viruses appear regularly yet remain relatively harmless. Most novel viruses originate in other animals and adapt to the ability to reproduce in human cells. For example, novel influenza viruses included avian flu and swine flu. The SARS-CoV-2 and SARS-CoV are coronaviruses that originated in bats and MERS appears to have originated in bats and passed through camels to humans (80% of reported cases in humans occurred in Saudi Arabia). We could prevent or stall the next pandemic by discovering viruses in animals that might jump to humans. This requires large-scale capabilities to find and monitor viruses that have the potential to jump to and proliferate in humans. The knowledge and technology to do so are developing rapidly.

Edward Holmes at Sydney University sampled urine, saliva, and feces of bats in a small area and found 24 new coronaviruses, four of which were closely related to COVID-19. The challenge, then, is to better understand “spillover” (a term scientists use to describe viruses jumping from animals to humans) and respond to the next pandemic before humans begin to spread the disease on a large scale. This underscores the need to expand our ability to use 
genomic surveillance in both animal and human sources of contagious viruses. 

Genomic surveillance scans genomes to find sequences of interest. The virus (SARS-CoV-2) that causes the disease COVID-19 existed in nature in the form of virus “assembly instructions,” a genome that contains about 30,000 letters each representing one of four chemical compounds (labeled c, u, g, a). The sequence of letters encodes all the information needed to build a virus coronavirus. The SARS-CoV-2 contains a small sequence of just 12 ominous letters (ccu cgg cgg gca) that cost the lives of nearly 3 million people to date. Hunting viruses requires finding such harmful segments in virus genomes. Had those letters been discovered when the COVID-19 first appeared and had a real-time mitigation technology existed, there likely would have been no pandemic. Our challenge is to create those real-time capabilities before the next pandemic strikes.

Virus hunters scan sequences of genomes by identifying the 30,000 letters inique to each suspect virus. So far, 700,000 genomes have been sequenced and 
more are added every day. Virus hunts identified the UK, South African, and Brazilian variants of the coronavirus. 

The UK and South Africa virus hunterswere able to identify the more deadly variants more quickly because of their systematic genomic surveillance. Genome browsers like the one at the University of California, Santa Cruz is providing access to extensive genome data segments of which can be searched with a click similar to Google Chrome. The technology for rapid real-time mutant identification and research exists and is paying dividends today. A "double mutant" variant (two mutations on the same virus) of COVID-19 was just discovered a few days ago in India. This discovery will allow scientists to determine if a double mutation allows the variant to evade one's immune system. These and advancements in virology give us reason to be optimistic that we might never again suffer the magnitude of virus-induced illness,  deaths and social disruption of the past year.

Democracy v. Human Nature


Democracy v. Human Nature

Note: The recent violence in our Capitol is being addressed by government authorities charged with doing their jobs according to their constitutional and legal obligations. I have neither the expertise nor the influence to help quell the seditious attitudes of Trump's more violent supporters. Instead, I will address how we can better align human nature with our democracy knowing there always will be ambitious people obsessed with power who would exploit weaknesses in human nature to become autocrats.
The Framers of the Constitution Were Wary of Human Nature

The framers of the Constitution took a strong position that the foundation of a durable democracy must accept human nature as it is, imperfections and all, and not attempt to change it. Thus, they accepted that a politician's self-interest could not be disregarded and we must assume decisions will be influenced by that self-interest. After all, the primary duty of our representatives in Congress is to serve the constituents who elect and re-elect them. 

The task of creating a constitution was to design a government that matched self-interest to the politician's job with external controls in the form of checks and balances. The framers of the Constitution assumed politicians may or may not be ethical and would need external judicial oversight or discipline. To accomplish this, the framers carefully balanced the conflict between an individual's need for freedom against society's need for order and equality.

If you are elected to the house of representatives to represent farmers in a rural solidly red district in Georgia, you will have very different public positions and attitudes than if you were elected to represent a solidly blue congressional district in the bay area of California. The election of representatives depends on how well they align with their constituent's basic needs and partisan positions. That is an essential component of a democracy. However, all of us need to heed the power of an unethical manipulator to ensure our representatives are acting in our collective interests, not their personal ambitions.

The framers respected the need for flexibility to bend our democratic principles to fit unknown future conditions. As the Constitution was being formalized and amended, compromises would be needed to preserve the essence of our democracy. For instance, the northern and southern states disagreed on how slaves should be counted to apportion seats in the House of Representatives. The compromise to count each slave as 3/5ths of a whole person solved the problem at the time and remained in place for almost a century.

Many other parochial compromises altered the framer's original design of our democracy. For example, the electoral college was in part a compromise between allowing Congress to elect a president and a presidential election by popular vote. We live with these "temporary" compromises to the present day because partisan self-interests were served by exploiting them. This is not a flaw in democracy, it is embedded in human nature. To compensate we can either change the aberrant rules or fortify ourselves to protect our democracy from abuse by overcoming some basic flaws in human nature that were useful as we evolved but mislead us in today's world.   

 Beware Your Biases

I had not seriously considered the prospect of influencing human nature to protect our democracy until I met with a psychologist friend I had not seen in 40 years.

After the conversation with my friend, I wrote a blog post entitled "Is Your Doctor Making Poor Diagnostic Decisions

Our conversation was about his research on confirmation bias (specifically, information distortion). Here are two pertinent excerpts from that blog post.

Last night, Helen and I met with a friend we haven't seen for 40 years. Jay Russo and I were colleagues on the UCSD faculty, he in the psychology department and I in the economics department. We both studied decision making as viewed from the perspectives of our respective disciplines. Jay has studied decisions made by physicians and the heuristics and biases that can lead to poor medical treatment. 

Heuristics are useful instinctive reactions, "rules of thumb", common sense, intuitive judgments, or any other expedient way of making decisions with less than complete information. Unfortunately, without adequate information our cognitive biases can result in a poor decision. Much of the time, the consequences of a poor decision are minor. When decisions are critical, such as diagnosing a medical condition, the consequences can be devastating or even fatal.

During our conversation, Jay mentioned that he had recently completed a study of 101 medical diagnoses; 86 of those decisions likely were influenced by cognitive biases. In another study in which 26 doctors verbalized the diagnostic process, only 6 clearly avoided the pitfalls that can lead to misdiagnoses. 
Hearing about these studies helped me reconsider a particular cognitive bias of my own. I had incorrectly assumed highly educated intelligent people typically make better more informed decisions than do uneducated or ignorant people (my academic arrogance, I suppose). During my conversation with Jay, I learned that doctors, some of the most educated and intelligent professionals in our society, vulnerable to misleading cognitive biases just as are those of my gardener or a homeless person on the street. This lesson and has crept into many of my blog posts and given me a more compassionate view of aberrant behavior. 

Critical Thinking

Heuristics and cognitive biases will always be with us but we can make better decisions for ourselves and others if we practice critical thinking as discussed in Jonathon Haber's book with that title. Haber argues that the most important critical thinking issue today is that not enough people are doing enough of it. He goes on to say, " might even be said that critical thinking is vital to the survival of a democratic society." 

As the term suggests, critical thinking is critically evaluating your own thinking and beliefs. Shakespeare understood this, "The fool doth think he is wise, but the wise man knows himself to be a fool."

Here are some examples of critical thinking.

1. Look beyond the obvious. The best doctors consider alternatives to their initial diagnosis and ask what would disprove rather than confirm their diagnosis. [An excellent summary of the five most common heuristic pitfalls leading to an incorrect medical diagnosis is here.]

2. My Opthamologist's daughter is just entering grammar school. When she shares suspicious information with her dad, he asks, "is that fact or opinion?" They work together to verify the information. She and her friends are becoming quite proficient at critical thinking at a very young age. Educators are beginning to build the concept into the early school curriculum (here). Programs like this can have a lifelong positive influence on young people growing up.

3. I draft my blog posts as if my facts and opinions are sound. Then I fact-check all the important information in sources that are reasonably unbiased such as the eight sites listed by the Berkeley Library (here). Finally, I examine the intentions and interests behind the sources of information. On average, I modify about 10 - 15% of what I write today because I am initially misled by my preconceived positions, incomplete knowledge, and veiled personal biases.  I am much less often misled now than when I started this blog five years ago. I have become sensitized to the problem and try to stay alert to critical thinking.

4. The following exercise was performed by a classroom of high school students studying critical thinking.
“For the assignment, which featured both group discussion and individual writing, students watched political ads released by both Hillary Clinton and Donald Trump. The class watched each ad multiple times, with equal exposure, and had a discussion on a handful of close reading topics: what the ad said, what the ad might have left unsaid, and how the ad was constructed in terms of tone and direction. Afterward, students used the ads and what they learned during class to provide evidence to support their claims and write an argumentative essay…”
Critical thinking sensitizes us to both the benefits and abuses of our cognitive biases. Emphasis on abuses has exacerbated our present partisan divide. The nation's two major political factions (pro- versus anti-Trump) have become increasingly violent and hostile since the 2016 election. Research blames much of our partisan hostility on three deepening changes in our political environment: 

1) the self-sealed information bubbles enabled by the internet and partisan channels -- anyone who desires fake news can get fake news, and more or less exactly the fake news that they prefer; 
2) intensified in-group bias towards one's chosen political party and increasingly fierce hostility towards others; and 
3) Trump's exceptional ability to manipulate his loyal supporters and to appeal to pervasive human biases.

We have increasingly replaced reason with emotion-driven heuristics to make political decisions. At the same time, our political proclivities are reinforced by confirmation bias, the Dunning- Kruger effect (overconfidence), and in-group bias, rather than knowledge about a subject and logical judgments. 

We Can Moderate Our Political Hostilities

Aberrant human behavior is the fuel waiting for the flame. Our Constitution and all of its amendments, judicial interpretations, and layers of large and small governments are today barely adequate fire suppressants. We need to turn our attention to diluting the fuel with critical thinking  Here are a few ways critical thinking is being integrated into our educational institutions and businesses.  

1. There is a growing number of school programs building critical thinking into the grammar school curriculum. There are organizations today doing the same and they need support and opportunities to expand. Here is an excellent summary of some of the programs being used in K-12 education. And here is a list of 25 of the best resources to share with teachers at all levels of education.

2. A Master of Arts in Business Education at Rider University emphasizes critical thinking in its program.

3. Six benefits of critical thinking in daily life will motivate you to make it your own practice.

4. Training in critical thinking gives you the skills to avoid reinforcing biases perpetuated by the pervasive slanting of information on the Internet. Try using Google to find, "reasons to drink coffee" on the website Healthline. You will get a long list of nutrients, praise for its antioxidants, and how it improves brain function. Next, do the same search with one word added, "reasons not to drink coffee" and you will see reasons never to drink coffee. The two conflicting answers are in the same article but the search takes you to areas of the article that confirm your inferred bias for or against drinking coffee depending on how you phrase your search. 

The more people who become aware of their biases and the uncountable ways they are reinforced through critical thinking, the more stable will be our political processes and the more durable will be our democracy.

However, under the best of circumstances, human nature will ensure a very large portion of today's voters will remain hostile and partisan differences will keep many of us separated into warring in-groups. Most nations will never be at peace with their enemies. Our nation will never be free of hostile in-groups. 

But we don't need a nation full of like-minded people to have a secure democracy. We need enough critical thinkers of every political persuasion for our democracy to function without fear of insurrections and the nearly certain future attempts to replace democracy with autocracy. 

Two Heuristics Dictators Love to Exploit

Unless you have a background in psychology or familiarity with the subject the label "affect heuristic" may seem odd. Think of it as your "gut feeling" about a person, an opportunity, a visceral reaction, an intuition, or feeling "vibes" knowing very little about the situation. 

This heuristic was a powerful weapon in Trump's political arsenal. Trump employed it to energize his base with optimistic promises and visions of a bright future. He also used it to repulse those who disagreed with him and make them fearful of criminals and rapists crossing our borders. In general, Trump used it to unite his loyal supporters and to vilify his chosen enemies. As a result, our gut feelings largely fell into two categories: you either hated Trump or loved him.

Con artists and effective salesmen refine their "affect appeal." There are training programs on how to use the affect heuristic to persuade people. And some people like Donald Trump have a talent for using the heuristic exceptionally effectively. People with this talent make good reality TV hosts, draw devoted enthusiastic crowds, attract large congregations, build cults, and sell lots of products at county fairs. Trump's most adamant supporters feel ecstatic at his rallies, are energized by his promises to remove restrictions on guns, or feel a loss of freedom when told to wear a mask in public. People believe Trump's lies just because he is, well, Trump; they are affected by their positive feelings about him. Others hate Trump and are repulsed by most everything he says or does. There are few if any feelings shared between the two groups.

Trump bonded together tens of millions of followers who believe his promises, lies, and delusions, using the affect heuristic bolstered by its amplifier, the availability heuristic which acquired its name from how readily a consequence of a decision comes to mind. Immediately following the 9/11 attack, air travel fell 20% due to the availability heuristic. The horrific image of the World Trade Center attack instantly came to mind for many people who considered taking a flight.

Trump is an expert practitioner of the art of creating images using the availability heuristic. From the beginning of Trump's presidency, immigrants were repeatedly referred to as"criminals" and "rapists" triggering fearful images of dangerous people entering the U.S. Hillary Clinton was taunted with the chant "lock her up" triggering images of her behind bars imprisoned to punish her criminal behavior. Trump, like the most feared dictators around the world, is a skilled user of this availability heuristic.

Trump used the availability heuristic to implant desirable outcomes in the minds of people he wanted to energize. He painted images of a white America becoming great again, building walls to secure our borders, and peaceful suburban neighborhoods free from the threat of racial integration. Much of Trump's appeal was his promise to recreate a peaceful America that existed in the past but was lost in the eyes of neglected workers who once had secure jobs and promising futures. 

Combined, the affect heuristic and the availability heuristics are not only powerful, they are particularly difficult to ignore; they are durably etched into one's mind triggering strong emotions that displace reason and knowledge.

You can help yourself avoid making bad decisions by understanding and practicing critical thinking. Remain alert to your biases and critically examine your political decisions. One effective technique to make critical thinking a habit is to dig deeper into your current attitudes and consider contrary opinions from the perspective of those who hold them.

For example, if you believe Democrats want socialism, rely on credible sources to dig into the technical definition of socialism and examine the various ways people use the term both correctly and incorrectly. What exactly are the problems with, and benefits of, socialism. Do the same with capitalism. It takes effort but examining one example thoroughly will be enlightening and alert you to the importance of critical thinking in general. 

In keeping with my own advice (and I am more liberal than conservative), I searched for information about how some of the most conservative people in our nation felt about Biden's inauguration. I found an article that portrayed the reactions of people in a Georgia community nearly 90% of whom voted for Trump over Biden in both elections. 

The article in the Atlanta Journal-Constitution provides an interesting perspective. I recommend reading it and putting yourself in the shoes of the people being interviewed. You likely will not change your own views but will see glimmers of hope that democracy can prevail as human nature meanders down its many diverse paths.