The reality behind human beings and their actions can seldom be portrayed accurately in either/or terms. However, I have repeatedly observed that a lot of people don’t really want to deal with complex realities. These people are mostly interested in stories where protagonists are sorted into tidy definable categories, such as moral or immoral, right or wrong, good or bad, heroes or villains, and infamy or glory. Due to this, individuals that can’t fit nicely into these groupings are often mythologized by writers ranging from those who are practical and create a story in order to get a point across, to those who create a story to manipulate public opinion and shape current or future events, or reinterpret the past. In this way, the special nature of the human condition with all of its intricacies and contradictions is altered to serve purposes other than the truth.
Today we are going to get a glimpse of the complexity lurking behind some personalities in the fields of medicine and science.
Marion Sims was a 19th century American physician who pioneered surgical techniques and built medical devices that greatly advanced medicine. He is considered the father of modern gynecology and has had statues erected in his honor, and hospitals, universities, and schools named after him. Without a doubt Sims has benefited the lives of countless women. However there are significant blemishes in his record. For example, one of Sims’ claims to fame is the development of a surgical technique to correct a condition called vesico-vaginal fistula, where a tear in the bladder during childbirth results in a connection with the vagina leading to incontinence. Sims came up with a surgical procedure that corrected this condition, but to develop the procedure he performed many operations on slave women, and he did not use anesthesia. While he has been both attacked and defended, there is evidence that even his contemporaries were critical of his methods and deemed them unethical.
William McBride was an Australian obstetrician who in 1961 was told by a nurse that a new drug he was prescribing for nausea and vomiting during pregnancy, thalidomide, was causing birth defects in newborn babies. McBride sounded the alarm in a short letter published in the medical journal, The Lancet. Other researchers and clinicians confirmed his concern. By the time thalidomide was withdrawn from the market, it had caused limb malformations in thousands of newborn children. McBride became a hero receiving multiple awards. Thalidomide became an infamous symbol of industrial greed and recklessness, and triggered the implementation of tougher drug approval laws throughout the world.
Now fast forward several decades. McBride sounded another alarm, this time about a drug called Debendox (also prescribed for nausea and vomiting during pregnancy) that he found in his lab to cause birth defects in rabbits. The drug was withdrawn amid lawsuits, and McBride was a willing witness for the claimants. However, an investigation revealed that McBride falsified the data on which he based his claims. Extensive studies of Debendox found it to be safe and it was reintroduced under the brand name Diclegis . Meanwhile more research on thalidomide revealed that it is an effective drug against various cancers and other conditions, and its use has saved and improved many lives.
Fritz Haber was a German chemist who won the Nobel Prize in 1918 for his development of an industrial process to produce ammonia from nitrogen in the air. The ammonia thus produced could be used as a fertilizer, and this freed humanity from the dependence on natural sources of nitrogenous compounds, which increased the amount of crops that could be grown preventing famines and saving and improving the life of millions. But during World War-I, Haber had been enthusiastically involved in the German war effort that led to the manufacture and deployment of the infamous chlorine, phosgene, and mustard gases which caused hundreds of thousands of casualties and tens of thousands of deaths. Haber is recognized as the father of German chemical warfare, however being a Jew, he had to flee Germany in 1933 when the Nazis came to power. In the ultimate irony, Zyklon B, a chemical originally developed as a pesticide by a firm that Haber founded, was used to kill more than a million people during the holocaust including some of Haber’s relatives. The much feared mustard gas and several of its chemical derivatives were used decades after the war ended to treat cancer, a practice that gave rise to the field of chemotherapy which has saved the lives of millions of cancer patients.
Peter Duesberg, is an American scientist who in 1970 discovered the first in what would eventually turn out to be a long list of cancer causing genes (today called oncogenes). The discovery of oncogenes paved the way to the connection between these genes and viruses like the Human Papilloma Virus that causes cervical cancer for which a successful vaccine was developed in 2006. Duesberg’s career was on the rise and he received numerous awards. However, when the AIDS epidemic started in the 1980s and the HIV virus was discovered as its causative agent, Duesberg questioned this fact and became very vocal. Despite being shunned by most scientists, Duesgerg’s ideas convinced the then president of South Africa, Thabo Mbeki, that HIV did not cause AIDS. As a result of this Mbeki refused international help to treat the disease with drugs against the virus leading to hundreds of thousands of preventable deaths.
Henry Heimlich was an American surgeon who is famous for inventing the “Heimlich Maneuver” in 1974. This procedure to rescue people from choking has saved many lives and is taught as part of first aid courses throughout the United States. However, the Heimlich Maneuver was not accepted after a rigorous scientific evaluation of the proposed procedure, but rather because of Heimlich’s promotional talents. Despite the acceptance of the maneuver, the scientific community thought Heimlich went too far when he advocated its use for treating people having asthma attacks, expelling the mucus clogging the airwaves of patients with cystic fibrosis, and clearing water from the lungs of persons who nearly drowned. However, what thrust Heimlich into infamy was his proposal to cure Lyme disease, AIDS, and cancer by infecting patients with malaria (malariotherapy). As Heimlich was unable to find support among scientists in the United States for his idea, he raised funds from Hollywood celebrities, skirted around US regulatory agencies, and sponsored and funded several controversial and dubious clinical trials in other countries where AIDS patients were infected with malaria. In these trials a few patients died under ill-defined circumstances. No therapeutic advances resulted from this research.
Nevertheless, Malariotherapy was not an invention of Heimlich. It was originally conceived by Austrian physician, Julius Wagner-Jauregg who used it successfully in the era before antibiotics to treat patients with neurosyphilis. The infection with malaria would produce a fever that killed the syphilis bacterium (this is why it was also called pyrotherapy), and later the malaria would be treated with quinine. For the development of this treatment, Wagner-Jauregg received the Nobel Prize in 1927. He is considered one of the leading psychiatrists of his time and in his native Austria there are streets and hospitals named after him. Unfortunately, Wagner-Jauregg was also an anti-Semite who supported the concept of racial hygiene and advocated the forced sterilization of people who were mentally ill, criminal, or considered genetically inferior. He was an early supporter of the Nazi party and applied to join, but ironically was turned down because his first wife was Jewish.
The foregoing are but a small sample of complex individuals whose actions have had a substantial impact on our world. It is easy to box these individuals exclusively in the categories of heroes or villains, but doing so is a disservice to those whom their actions directly or indirectly helped or hurt. Give these individuals their fair share of infamy and glory, but do not let their narratives become just another story.
Photo of engraving by R. O'Brien of Marion Sims is by William Kurtz and is in the public domain. Photograph of Fritz Haber from the German Federal Archive (Bundesarchiv, Bild 183-S13651) is used here under an Attribution-ShareAlike 3.0 Germany (CC BY-SA 3.0 DE) license. Photograph of Henry Heimlich by Nieznany is used here under an Attribution-Share-Alike 4.0 International (CC BY-SA 4.0) license. The photograph of Julius Wagner-Jauregg from Universität Graz is in the public domain.
I had an exchange on Twitter with people alleging that doctors are finding that the drug hydroxychloroquine is 100% effective against COVID-19 and posting videos of patients claiming they had been cured by this drug. I tried to explain that this evidence is not valid and provided a link to one of my previous posts that addressed these claims. Then I stated that we need to wait for the results of the clinical trials. The response I got was that if doctors and their patients have tried it and are convinced it works, then that’s all the evidence we need.
Unfortunately, this is simply not true. Even before hydroxychloroquine came along, the majority of patients hospitalized with COVID-19 would survive. If all patients are treated with hydroxychloroquine, then how do we know which patients got better because of the drug and which got better because they were going to get better anyway, or because of other treatments? In an uncontrolled clinical environment in the middle of a pandemic, patients are not randomized into matched groups and their treatments controlled and blinded to exclude placebo effects and other biases. Patient testimonials and doctor’s opinions are valuable to design clinical trials, but they have many shortcomings and should never be used to establish whether a drug works or not. All doctors know (or should know) this.
However, the main point of this post is not to address the claim that hydroxychloroquine is 100% effective against COVID-19, but rather the attitude of scientists towards such claims, especially when they are reported using the media instead of the regular scientific channels.
Scientists know that products or therapies that are 100% effective are rare, and this is even more so in the case of major diseases like COVID-19. Some vaccines, hormones like insulin, or a few antibiotics have approached this level of effectiveness, but this is not very common for most other compounds or drugs. About 86% of the drugs tested in clinical trials are found not to be effective and are not approved. Claims of 100% efficacy for a drug or therapy will trigger a strong (and warranted) skeptical response from most scientists.
I have been around a while, and I have read many investigations into multiple bogus claims regarding miracle cures or procedures promoted by quacks. One of the characteristics of these individuals is that they inflate the claims they make regarding the efficacy of their products or therapies beyond the bounds of credibility. If these fraudsters wanted to be believable, they would probably look up the percentage cure rate of the best science-sanctioned therapy and then inflate the claims for their products or therapies by a few percentage points to make them look significantly better but not impossibly so. However, the target audience of these individuals is not scientists but the general public, which has no experience with scientific research or clinical trials and their nuances.
As I have explained before, the best way to promote a bogus product or therapy is to make your audience assimilate your product as part of their identity. If you can achieve this, your audience will be impervious to evidence that the product does not work. This is because any attack on your product will be viewed by the members of your audience as a personal attack on themselves. From this vantage point, it is unfortunate that the president of the United States has promoted the use of hydroxychloroquine. In the current politically charged atmosphere, I am concerned that this identity-forming process seems to be coalescing around the notion that if you don’t accept that hydroxychloroquine works, then you are against the president and thus part of a left-wing conspiracy. It is then all too easy for unscrupulous individuals to exploit this situation by linking themselves to the “pro-president” audience and peddle hydroxychloroquine or other as yet unproven drugs or therapies for COVID-19. If their claims are questioned, all they have to do is argue they are being attacked by the same system that their audience believes is against them and the president.
I was skeptical about hydroxychloroquine from the beginning, not because the president promoted it, but because the data for its effectiveness was weak. Thus when I hear these claims for 100% effectiveness of hydroxychloroquine (or any other drug or therapy for that matter), this immediately raises a red flag, and I close my mind to them. This may not seem the scientific thing to do, but remember that keeping your mind too open can be dangerous. As far as I’m concerned, like the late astronomer Carl Sagan said, “Extraordinary claims require extraordinary evidence.”, and the burden of proof is on those individuals who make these claims. It is up to them to produce high-quality evidence to support that what they claim is true, and, seriously, with a 100% success rate this should not prove too difficult, right?
At this point you may argue that even if the effectiveness of hydroxychloroquine is less than 100%, but something like 80%, or 50% or 30%, that would still be significant and important. My answer to this is, yes, but this HAS to be established by well-designed clinical trials. At the moment, many clinical trials of hydroxychloroquine are ongoing, and several of these trials are sufficiently well-designed to yield unambiguous results. As I write this, among the best trials completed so far, one has indicated that hydroxychloroquine does not work as a prophylactic against COVID-19, and another has indicated that hydroxychloroquine does not reduce the risk of death among patients hospitalized with COVID-19. The FDA recently revoked its emergency use authorization of hydroxychloroquine, because based on the available evidence it’s unlikely to be effective in treating COVID-19 and any potential benefit from its use outweighs the potential risks.
Many of these trials were designed to address the initial claims for hydroxychloroquine being very effective when administered alone or with certain antibiotics. A new claim has been made that hydroxychloroquine is only effective when it is administered with zinc, and new clinical trials are being performed to evaluate this possibility. As I stated above, I am skeptical about hydroxychloroquine, but I don’t want to be right, I want to save lives, and I hope the combination of hydroxychloroquine with zinc works. However, the public has to understand and accept the need to perform clinical trials and stop relying on testimonials and other anecdotal evidence.
Image of a quack doctor selling remedies from his caravan; satirizing Gladstone's advocacy of the Home Rule Bill in Parliament is a Chromolithograph by T. Merry, 1889, and comes from the Welcome Collection. The image was modified and used here under an Attribution 4.0 International (CC BY 4.0) license, and no endorsement by the licensor is implied.
Every activity performed by groups of human beings interacting with each other tends to have some drama, and science is no exception. The quest of scientists to discover, be recognized and respected, and remain relevant has produced amazing stories that form a permanent part of the lore of scientific research. And these stories have it all: triumph and tragedy, the clash of strong willed characters, and the fireworks displays stemming from the mixing of the most honorable and dishonorable aspects of human nature. But these stories seldom make it to the end product of scientific research in which scientists report the results of their work: the scientific article. Scientific articles tend to be highly technical, full of jargon, and are mostly read by specialists. However, many scientific articles have subtle and not so subtle hints of what’s going on behind the science.
Today we will take a look at two scientific articles related to two such stories.
The first one is the famous article entitled, A structure for deoxyribose nucleic acid, published in the Journal Nature in 1953 by James Watson and Francis Crick. In this article, these two scientists propose a structure for the chemical molecule that contains the blueprint of life: DNA. This article ushered a revolution that changed science and the word forever.
The most mentioned passage in this article is the one below:
It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
This whopper of a sentence, which has been described as anything from “coy” to “one of the greatest understatements in the history of science”, makes a reference to the fact that the model of the structure of DNA that Watson and Crick proposed explained a phenomenon which at the time was the holy grail of the biological sciences (how genetic information is copied). However, the passage that reveals some of the human drama behind the science is found in the previous paragraph.
The previously published X-ray data on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications. We were not aware of the details of the results presented there when we devised our structure, which rests mainly though not entirely on published experimental data and stereochemical arguments.
Watson and Crick never worked with DNA themselves. As they wrote, they relied on work already published by others and on their own theorizing. However, they claim their model agrees with “more exact results” in the following communications. This makes an allusion to two additional articles published simultaneously with theirs by other researchers. Among them was Rosalyn Franklin. Watson and Crick claim they were not aware of the “details” of these results when they put their model together, but this carefully worded statement is misleading. Franklin’s work with DNA was made available to Watson and Crick without her knowledge, and whether detailed or not, it was a crucial part of the puzzle that allowed them to solve the structure of DNA.
Watson and Crick would go on to be corecipients of the Nobel Prize for the discovery of the structure of DNA in 1962. Rosalyn Franklin continued her work and went on to make several important discoveries, but died from Cancer in 1958 at the age of 38 never having known that it was her uncredited work that allowed Watson and Crick to figure out the structure of the molecule of life.
The second article we will consider today is famous because of its infamy. It is entitled: Warburg Effect Revisited: Merger of Biochemistry and Molecular Biology, and was published in the journal Science in 1981 by Efraim Racker and Mark Spector.
In the late 1970s, Efraim Racker was one of the surviving elder scientists of biochemistry. He had won numerous awards for his work but not the Nobel Prize. When the 1978 Nobel Prize was awarded to Peter Mitchel for his theory regarding how cells obtain their energy, there was consternation in the scientific world as it had been Racker who had performed the experiments that had conclusively demonstrated Mitchel’s theory to be true.
Undeterred by this, at the beginning of the 1980s, Racker took up researching an unexplained phenomenon that he had addressed off and on throughout his career called the Warburg Effect. Normal cells use oxygen as part of the normal mechanism of producing the energy they need. However, when cells become cancerous, they switch their energy producing mechanisms, in large part, to one that does not require oxygen even if oxygen is present. Many scientists think that this switch holds the key to explain what causes cancer and how it can be treated.
At the same time a bright Ph.D. student named Mark Spector joined Racker’s lab and began researching the Warburg Effect. Spector proved to be a talented researcher making discoveries in a few months that would take others years. By 1981 he had put together a wonderful story linking cancer-causing genes to signaling pathways that led to changes in the bioenergetics of the cells which explained the Warburg Effect. This result was really big, and probably Nobel Prize material. The Warburg effect’s relation to cancer had not been explained for decades. Racker was elated. The passage in the article that best describes the sense of fulfilment, optimism, and aspirations that Racker had is the first sentence which is not even a scientific statement but a quote from the English writer Gilbert K. Chesterton.
There are no rules of architecture for a castle in the clouds.
And herein lies the brutal irony of this story. Spector tuned out to be a con-man. He had falsified the data! Racker retracted the article and dismissed Spector from his lab. Racker would still perform important research for the next decade, but the Nobel Prize would elude him. He died from a stroke in 1991. The Warburg Effect remains unexplained, and is still an active area of investigation in cancer.
These are but two of the thousands of stories lurking behind the technical jargon, the graphs, and the tables in the pages of the scientific literature.
Photos of Rosalind Franklin by Silver Screen and of James Watson by the National Cancer Institute are in the public domain. Photo of Francis Crick by Marc Lieberman used here under an Attribution 2.5 Generic (CC BY 2.5) license. I do not own the copyright to the articles mentioned here from which the text is quoted or the image of Efrain Racker and Mark Spector from the journal Science (Vol. 214, No. 4518 (Oct. 16, 1981), pp. 316-318), Copyright Cornell University. These are used here under the doctrine of Fair Use.
There is a tsunami of misinformation being circulated about COVID-19, and many science communicators are trying to counter this with facts. I have already explained, for example, that COVID-19 is not like the flu, and the perils of ignoring this have already been exposed by the situation of Brazil whose president, Jair Bolsonaro, considers COVID-19 to be “a little flu”, and has done his best to undermine the efforts at mitigation by cities and states in his country. As a result of this, Brazil's COVID-19 cases have jumped to second place in the world after the United States.
Another misinformation that is being circulated in social media is the notion that all the mitigation measures against COVID-19, from masks and social distancing to the stay at home orders, did not work to contain the spread of COVID-19. This can be demonstrated not to be true. There is abundant evidence that mitigation against COVID-19 reduced its spread both in the United States (for example: 1, 2, 3, 4, 5, 6, 7, and 8) and in other countries (1, 2, 3). There also is evidence from the past that these measures work. Even if you are not a scientist, it’s not difficult to figure out that a virus will spread more slowly in a population whose members interact less with each other compared to a population whose members interact more. This is really a no-brainer. Mitigation measures have prevented the health care system from being swamped with hospitalizations (what is known as “flattening the curve” of viral spread) as happened in populous localities that did not implement these measures soon enough. You have all read the stories and seen the pictures and videos of what uncontrolled spread of COVID-19 can do. I don’t need to belabor this point.
But there are other important things that we have gained with mitigation that are not often mentioned.
There is a vast world-wide network of hundreds of thousands of scientists that has been working around the clock during the pandemic in hospitals, universities, companies, and other organizations investigating the virus, how it spreads, and meticulously analyzing the symptoms of the patients presenting with the disease. These scientists share findings, information, ideas, and experience, and test old and new treatments on cultured cells, animals, and humans.
It is thanks to the action of these scientists that we now have a more accurate picture of the symptoms of COVID-19 and effective strategies to minimize the spread of the virus as we rescind stay-at-home orders and begin reopening our society. These scientists are also developing vaccines against COVID-19 and dealing with some unique problems in vaccine development pertinent to coronaviruses, and they are conducting studies to evaluate the benefit of other potential treatments for COVID-19. All in all, there are currently more than a thousand clinical trials all over the world investigating treatments for COVID-19. In these studies, some treatments that were initially touted as game changers such as hydroxychloroquine have so far not lived up to their initial promise. But other studies have shown more promise, such as that of the antiviral compound remdesivir, which is part of a remarkable story involving two decades of research into coronaviruses.
One of the greatest achievements of scientists studying COVID-19 is a reevaluation of what the disease really is. The virus that causes COVID-19 is called “SARS-Cov-2”. This stands for “severe acute respiratory syndrome coronavirus 2”. This is because it was thought that the virus would predominantly infect the airways. But early in the pandemic, doctors in China treating COVID-19 patients made the observation that hospitalized patients were experiencing blood clots. Bloodwork analysis indicated that the patients with the most severe illness were strongly positive for some of the most common indicators of risk of increased clotting. Doctors in other countries also found the same thing. A study with almost 3,000 patients found that indeed, those patients administered anticoagulants survived longer: an effect that was even more striking in the sickest patients. The International Society on Thrombosis and Haemostasis issued a document where they provided an interim guidance to treat patients with COVID-19 based on their coagulation parameters. This and other evidence ranging from the molecular to the clinical, has contributed to shape an emerging theory regarding COVID-19 which proposes that, although the disease starts in the lungs, the virus then proceeds to attack the blood vessels. This theory would explain many of the observations made regarding the particular symptoms of COVID-19, and suggests many new lines of treatment.
Apart from flattening the curve and other considerations, by delaying the spread of the virus through mitigation we have gained time and knowledge, and during a pandemic these two things are invaluable.
Image from pixabay by Queven is used under a pixabay license.