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FTR #1168 This program was recorded in one, 60-minute segment.
Introduction: Significant to the issue of vaccination against Covid-19 is the consideration of whether available vaccines will prevent illness in the recipients, but still leave them capable of spreading the disease.
The first major portion of the program consists of analytical review of the capital interests behind BioNTech–the German corporate partner producing a Covid vaccine with Pfizer.
Headed by a German MD couple whose parents were “gastarbeiter” (guest workers), BioNTech has soared exponentially in value since the approval of the vaccine by a number of countries.
A dominant consideration in power politics remains the advisory to “Follow the Money.”
Against the background of I.G. Farben and its successor companies’ dominant position in both the global pharmaceutical and chemical market, as well as its major position within the remarkable and deadly Bormann capital network, the program explores the capitalization of Uğur Şahin and Özlem Türeci’s Ganymed firm and BioNTech.
Of paramount significance in both Ganymed (the couple’s initial commercial venture) and BioNtech are twin brothers Thomas and Andreas Struengmann.
Key points of analysis:
- The brothers are major players in the pharmaceutical and biotech market.
- They keep a purposefully low professional profile–a professional behavior characteristic of the deadly Bormann network.
- Thomas was an important member of the board of Wacker Chemie, a major successor to two I.G. Farben subsidiary companies.
- Wacker Chemie has apparently obfuscated its Nazi past.
- Andreas initiated his medical career in apartheid South Africa, and the brothers’ Hexal firm began its significant international expansion in that country. (The apartheid regime was an offshoot of the Third Reich.)
- Firms that evolved from I.G. Farben figure prominently in the dealings of Hexal, Wacker Chemie and BioNTech (Novartis, the Hoechst division of Sanofi-Aventis.)
The balance of the program presents analysis of the profound relationship between the Bormann capital network and I.G. Farben.
Forged during the closing days of the war, the close cooperation between corporate “masker” Hermann Schmitz and Bormann, the relationship built on the dominant position of I.G. Farben in the Third Reich and its interrelated military and industrial/commercial campaigns.
” . . . . If there is any doubt in Europe who in the long run won the peace, there is none whatsoever among the former German leaders dwelling in South America. It is a good bet that if Hermann Schmitz were alive today, he would bear witness as to who really won. Schmitz died contented, having witnessed the resurgence of I.G. Farben, albeit in altered corporate forms, a money machine that continues to generate profits for all the old I.G. shareholders and enormous international power for the German cadre directing the workings of the successor firms. . . . He was the master manipulator, the corporate and financial wizard, the magician, who could make money appear and disappear, and reappear again. His whole existence was legerdemain, played out on the gameboard of I.G. Farben and his beloved Germany. . . Their [Schmitz and Bormann] association was close and trusting over the years, and it is the considered opinion of those in their circle that the wealth possessed by Hermann Schmitz was shifted to Switzerland and South America, and placed in trust with Bormann, the legal heir to Hitler. [Hermann] Schmitz’s wealth—largely I.G. Farben bearer bonds converted to the Big Three successor firms, shares in Standard Oil of New Jersey (equal to those held by the Rockefellers), as well as shares in the 750 corporations he helped Bormann establish during the last year of World War II—has increased in all segments of the modern industrial world. The Bormann organization in South America utilizes the voting power of the Schmitz trust along with their own assets to guide the multinationals they control, as they keep steady the economic course of the Fatherland. . . . ”
After the war, the three main successor firms to I.G.–Hoechst (now a division of Sanofi-Aventis), Bayer and BASF rose to a pinnacle of sales and R & D dominance.
Review of Dorothy Thompson’s 1940 analysis of the Third Reich blueprint for world political domination, predicated on world economic domination (including the exploitation of decisive cartel relationships with the Wall Street elite; an account of Bertelsmann’s forthcoming purchase of Simon & Schuster, making this “former” publishing house for the SS a “Titan” in English-language publishing; a synoptic review of the scenario presented in the Nazi tract Serpent’s Walk.
1a. Significant to the issue of vaccination against Covid-19 is the consideration of whether available vaccines will prevent illness in the recipients, but still leave them capable of spreading the disease.
The new Covid-19 vaccines from Pfizer and Moderna seem to be remarkably good at preventing serious illness. But it’s unclear how well they will curb the spread of the coronavirus.
Thats’s because the Pfizer and Moderna trials tracked only how many vaccinated people became sick with Covid-19. That leaves open the possibility that some vaccinated people get infected without developing symptoms, and could then silently transmit the virus—especially if they come in close contact with others or stop wearing masks.
If vaccinated people are silent spreaders of the virus, they may keep it circulating in their communities, putting unvaccinated people at risk.
“A lot of people are thinking that once they get vaccinated, they’re not going to have to wear masks anymore,” said Michal Tal, an immunologist at Stanford University, “It’s really going to be critical for them to know if they have to keep wearing masks, because they could still be contagious.”
In most respiratory infections, including the new coronavirus, the nose is the main port of entry. The virus rapidly multiplies there, jolting the immune system to produce a type of antibodies that are specific to mucosa, the moist tissue lining the nose, mouth, lungs and stomach. If the same person is exposed to the virus a second time, those antibodies, as well as immune cells that remember the virus, rapidly shut down the virus in the nose before it gets a chance to take hold elsewhere in the body.
The coronavirus vaccines, in contrast, are injected deep into the muscles and quickly absorbed into the blood, where they stimulate the immune system to produce antibodies. This appears to be enough protection to keep the vaccinated person from getting ill.
Some of these antibodies will circulate to the nasal mucosa and stand guard there, but it’s not clear how much of the antibody pool can be mobilized, or how quickly. If the answer is not much, then viruses could bloom in the nose—and be sneezed or breathed out to infect others.
“It’s a race: It depends whether the virus can replicate faster, or the immune system can control it faster,” said Marion Pepper, an immunologist at the University of Washington in Seattle. “It’s a really important question.” . . . .
. . . . “Preventing severe disease is easiest, preventing mild disease is harder, and preventing all infections is the hardest,” said Deepta Battacharya, an immunologist at the University of Arizona. “It’s going to be something less than that in preventing all infections, for sure,” Still, he and other experts said they were optimistic that the vaccines would suppress the virus enough even in the nose and throat to prevent immunized people from spreading it to others. . . .
. . . . But some studies have suggested that even people with no symptoms can have high amounts of coronavirus in their nose, noted Dr. Yvonne Maldonado, who represents the American Academy of Pediatrics at meetings of the federal Advisory Committee on Immunization Practices. The first person confirmed to be reinfected with the coronavirus, a 33-year-old man in Hong Kong, also did not have symptoms, but harbored enough virus to infect others.
Vaccinated people who have a high viral load but don’t have symptoms “would actually, be in some ways, even worse spreaders because they may be under a false sense of security,” Dr. Maldonado said. . . .
1b. The first major section of the program consists of analytical review of the capital interests behind BioNTech–the German corporate partner producing a Covid vaccine with Pfizer.
Headed by a German MD couple whose parents were “gastarbeiter” (guest workers), BioNTech has soared exponentially in value since the approval of the vaccine by a number of countries.
A dominant consideration in power politics remains the advisory to “Follow the Money.”
Against the background of I.G. Farben and its successor companies’ dominant position in both the global pharmaceutical and chemical market, as well as its major position within the remarkable and deadly Bormann capital network, the program explores the capitalization of Uğur Şahin and Özlem Türeci’s Ganymed firm and BioNTech.
Of paramount significance in both Ganymed (the couple’s initial commercial venture) and BioNtech are twin brothers Thomas and Andreas Struengmann.
Key points of analysis:
- The brothers are major players in the pharmaceutical and biotech market.
- They keep a purposefully low professional profile–a professional behavior characteristic of the deadly Bormann network.
- Thomas was an important member of the board of Wacker Chemie, a major successor to two I.G. Farben subsidiary companies.
- Wacker Chemie has apparently obfuscated its Nazi past.
- Andreas initiated his medical career in apartheid South Africa, and the brothers’ Hexal firm began its significant international expansion in that country. (The apartheid regime was an offshoot of the Third Reich.)
- Firms that evolved from I.G. Farben figure prominently in the dealings of Hexal, Wacker Chemie and BioNTech (Novartis, the Hoechst division of Sanofi-Aventis.)
1c. The I.G. Farben company, a core element of the Third Reich, was central to Bormann’s plans to secret Germany’s wealth abroad. Note, also, I.G. Farben’s dominance of the European chemical industry, and the opinion of Dr. von Schnitzler that technical dependence on I.G. facilities would continue after the war. (To learn more about I.G. Farben, see—among other programs–FTR#’s 305, 411, 506, 552. Serious students should also read Treason’s Peace and The Devil’s Chemists, available for download.)
. . . I.G. Farben was a formidable ally for Reichsleiter Bormann in his plans for the postwar economic rebirth of Germany. In a telephone conversation with Dr. von Schnitzler, Bormann asked what would the loss of factories in France and the other occupied countries mean to German industry in general and to I.G. in particular. Dr. von Schnitzler said he believed the technical dependence of these countries on I.G. would be so great that despite German defeat I.G., in one way or another, could regain its position of control of the European chemical business. “They will need the constant technical help of I.G.’s scientific laboratories as they do not own appropriate installations within themselves.” . . . .
2. Bormann and Herrmann Schmitz then discussed I.G.’s prospects for the postwar period. The cozy relationship with powerful elements within the power elites of the Western allies was foreseen by Schmitz as boding well for the company’s future. Schmitz’s predictions were relatively accurate. Neither Schmitz nor any of the I.G. Farben executives were severely punished and the firm’s three successor firms carried on effectively in the postwar period.
. . . . The Reichsleiter asked Schmitz his views of the future. Schmitz replied, ‘The occupation armies will be understanding in the West, but certainly not in the East. I have instructed all Farben administrators and technicians to come to the West, where they can be of use in resuming our operations once the disturbances of 1945 come to a halt.’ Schmitz added that, while general bomb damage to the I.G. plants was about 25 percent of capacity, some were untouched. He mentioned speaking with Field Marshal Model, who was commanding the defenses of the Ruhr. ‘Model had planned to turn our Bayer-Leberkusen pharmaceutical factory into an artillery base, but he agreed to make it an open, undefended factory. Hopefully, we will get it back untouched.’ ‘What about your board of directors and the essential executives? If they are held by the occupation authorities, can I.G. continue?’ Bormann asked. ‘We can continue. We have an operational plan for such a contingency, which everyone understands. However, I don’t believe our board members will be detained too long. Nor will I. But we must go through a procedure of investigation before release, so I have been told by our N.W. 7 people who have excellent contacts in Washington.” . . . .
3. The broadcast details the profound relationship between I.G. Farben and the government of the Third Reich. Of particular utility to the Bormann flight capital program was I.G. Farben’s elaborate infrastructure in foreign countries. Note that, as is seen here, I.G. Farben was inextricably linked with both the government of the Third Reich and with the Nazi party itself.
. . . This, too, reported to Martin Bormann.I.G. Farben’s N.W.7 office in Berlin compiled military and economic data on all countries for the Wehrmacht. This department was staffed with men of recognized ability in all branches of business and science. It was under the direction of Dr. Max Ilgner, nephew of Hermann Schmitz, I.G.’s president, who was known throughout the industrial world as ‘the master of financial camouflage.’ [Emphasis added.] Farben had offices and representatives in 93 countries, and no social gathering of businessmen was too small to be covered by an N.W.7 representative, whose reports on market conditions, factory installations, raw-material supplies, and research were transmitted immediately to Berlin and Dr. Ilgner. In the United States, N.W.7 operated through the firm of Chemnyco, Inc., an American-formed subsidiary. Chemnyco sent tremendous amounts of information ranging from photographs and blue prints to detailed descriptions of entire industrial complexes and secret processes. . . .
4. Of particular importance for this discussion is the fact that I.G. used German military conquest to gain effective functional control of the chemical industry of the continent. In paragraph 13, we noted Georg von Scnitzler’s prediction that I.G.’s technical dominance would result in the postwar perpetuation of this control. As we will see, this control was maintained. It is against the background of I.G. Farben’s continued dominance of the European chemical industry as well as the postwar perpetuation of the Nazi party apparatus that the BioNTech capitalization relationship must be viewed!
. . . This huge organization functioned as a manufacturing and research arm of the German government, with the responsibility of discovering all possible means of increasing the military power of Germany. More than RM 4.25 billion was invested in new plants, mines, and power installations, with other millions going into new research facilities. . . . So close had Farben become to the government that I.G. always knew in advance all invasions planned by Hitler. It was to supply the materials necessary to each conquest, and when a land had been overrun and subjugated, the Farben experts would handle the consolidation and organization of the industrial facilities as additional supply sources for the German armed forces. As German troops swept across Europe and Hitler proclaimed his vision of a thousand-year Third Reich, I.G. Farben also dreamed of world empire. This was outlined with clarity in a document called Neuordnung, or ‘New Order,’ that was accompanied by a letter of transmittal to the Ministry of Economics. It declared that a new order for the chemical industry of the world should supplement Hitler’s New Order. Therefore, the document stated, Farben was fitting future industrial plans into such a framework. . . . I.G. Farben was the major chemical firm on the Continent, and as each country fell to Germany its acquisitions of chemical and dyestuff companies were enormous. I.G. also increased its investments in these by RM 7 billion. [Emphasis added.] . . . .
5. More about I.G. Farben, the Third Reich and the development of the remarkable and deadly Bormann organization.
. . . .The close relationship of Farben to the Third Reich leadership was underscored in other ways. I.G.’s leading officials assisted in formulation and execution of economic policies of government; its president was a member of the Reichstag; its leading scientist was a chief assistant to Hermann Goering under the Four-Year Plan; its statisticians and economists prepared intelligence for the Nazi High Command; scores of its technicians were at any given time on loan to the air and war ministries. . . . The contact men of N.W.7 throughout the world were called the I.G. Verbindungsmanner, the liaison officers between Farben back in Germany and the branches elsewhere. These I.G. Verbindungsmanner, as well as all other key Farben representatives working beyond the borders of the Third Reich, were members of the National Socialist German Workers Party. . . . So now Martin Bormann had at his command not only the Auslands-Organisation but also the I.G. Verbindungsmanner of Farben, which could be counted on to heed his orders when it was time to disperse the commercial assets of the Third Reich. . . .
6. The vast international operations of the I.G. Farben firm and its various subsidiary operations was a principal element of the Bormann organization. I.G. Farben chief Hermann Schmitz discussed I.G.’s involvement with the Bormann program.
. . . . In testimony later given to Nuremberg investigators, Schmitz praised Bormann for the way he had directed the distribution of German assets around the world. His own Farben organization had, of course, contributed to the success of the operation. Every regional representative working for Hermann Schmitz was an exceptional businessman, or he would not have been with I.G. All had contributed sound advice in their areas of competence, the regions of the world where they represented Farben while keeping an eye on the subsidiaries of the parent concern and the 700 hidden corporations they controlled. They had provided assistance and continuing guidance in establishing the 750 new companies created on order of Bormann, who wanted more than hidden assets; Bormann wanted the money and patents and technicians put to work to create even greater assets that would bolster Germany in the postwar years. In their meeting in the chancellery, both men checked over the figures of sums disbursed, and they were accurate to the pfennig. . . .
7. As forecast by Dr. Scheid in the August 10, 1944 meeting, the corporate allies of the major German corporations, including and especially those of I.G. Farben, proved to be of great value to the success of the Bormann flight capital program.
. . . . Powerful friends of the Bormann organization in all Western countries, including those sprinkled in control points throughout the administration in Washington and in the financial and brokerage businesses of Wall Street, the City of London, and the Paris establishment, did not wish a coordinated drive to get at these external German assets. They had understandable reasons, if you overlook morality: the financial benefits for cooperation (collaboration had become an old-hat term with the war winding down) were very enticing, depending on one’s importance and ability to be of service to the organization and the 750 corporations they were secretly manipulating, to say nothing of the known multinationals such as I.G. Farben, Thyssen A.G., and Siemens; and, as a second reason, the philosophy of free enterprise and preservation of private property. . . .
8. Note the postwar resuscitation of I.G. Farben, in the form of the “Big Three” successor firms that grew out Farben. Although officially broken up at the end of World War II, I.G. Farben continued functioning in new form. Recent mergers (such as the 1996 merger of I.G. cartel affiliates Ciba-Geigy and Sandoz to form Novartis) indicate a new coming together of the old components of I.G. Again, pay close attention to the relationship between these companies and the Bormann capital network.
. . . . By 1956, the three major multinationals (Hoechst, BASF, and Bayer) reshaped from the 159 companies within Germany that had comprised I.G. Farben were generating record profits for the original 450 major Farben stockholders, who had organized themselves into the I.G. Farben Stockholders Protective committee in Bonn. The Big Three went on expanding, tripling capitalization in 1956 from investment funds that poured in from the interlocking companies established in safe haven countries by Martin Bormann and Hermann Schmitz. There was a return, more vigorous than ever, of the huge, monolithic industrial multinationals that dominated the German economy before and during World War II. . . .
9. The enormous corporate wealth and power of the three successor firms is at the disposal of the Bormann capital network and Underground Reich.
. . . . Each of these three spinoffs from I.G. Farben today does more business individually than did Farben at its zenith, when its corporate structure covered 93 countries. BASF and Bayer individually boast worldwide sales of nearly $10 billion annually, while Hoechst, now the world’s largest chemical company, generated $16.01 billion in worldwide sales in 1980. Each does more business than E.I. du Pont de Nemours, with sales of $9.4 billion. The United States is, of course, the major market, one into which these German corporations continue to pour investment money for both new capital construction and corporate takeovers. Together, these three multinationals assure permanent prosperity for the original 450 Farben stockholders, their banks, and the shadowy shareholders of the Bormann organization in South America who guard and vote the Hermann Schmitz trust fund through intermediaries at the annual meetings of BASF, Bayer and Hoechst. [Emphasis added.] . . . .
10. A significant part of the I.G. Farben legacy, the Hermann Schmitz Trust is also at the disposal of the Bormann capital network and the Underground Reich.
. . . . If there is any doubt in Europe who in the long run won the peace, there is none whatsoever among the former German leaders dwelling in South America. It is a good bet that if Hermann Schmitz were alive today, he would bear witness as to who really won. Schmitz died contented, having witnessed the resurgence of I.G. Farben, albeit in altered corporate forms, a money machine that continues to generate profits for all the old I.G. shareholders and enormous international power for the German cadre directing the workings of the successor firms. . . . He was the master manipulator, the corporate and financial wizard, the magician, who could make money appear and disappear, and reappear again. His whole existence was legerdemain, played out on the gameboard of I.G. Farben and his beloved Germany. . . Their [Schmitz and Bormann] association was close and trusting over the years, and it is the considered opinion of those in their circle that the wealth possessed by Hermann Schmitz was shifted to Switzerland and South America, and placed in trust with Bormann, the legal heir to Hitler. [Hermann] Schmitz’s wealth—largely I.G. Farben bearer bonds converted to the Big Three successor firms, shares in Standard Oil of New Jersey (equal to those held by the Rockefellers), as well as shares in the 750 corporations he helped Bormann establish during the last year of World War II—has increased in all segments of the modern industrial world. The Bormann organization in South America utilizes the voting power of the Schmitz trust along with their own assets to guide the multinationals they control, as they keep steady the economic course of the Fatherland. . . .
11. In closing, the program notes the economic and political significance of the Bormann network:
. . . . Atop an organizational pyramid that dominates the industry of West Germany through banks, voting rights enjoyed by majority shareholders in significant cartels, and the professional input of a relatively young leadership group of lawyers, investment specialists, bankers, and industrialists, he is satisfied that he achieved his aim of helping the Fatherland back on its feet. To ensure continuity of purpose and direction, a close watch is maintained on the profit statements and management reports of corporations under its control elsewhere. This leadership group of twenty, which is in fact a board of directors, is chaired by Bormann, but power has shifted to the younger men who will carry on the initiative that grew from that historic meeting in Strasbourg on August 10, 1944. Old Heinrich Mueller, chief of security for the NSDAP in South America, is the most feared of all, having the power of life and death over those deemed not to be acting in the best interests of the organization. Some still envision a Fourth Reich. . .What will not pass is the economic influences of the Bormann organization, whose commercial directives are obeyed almost without question by the highest echelons of West German finance and industry. ‘All orders come from the shareholders in South America,’ I have been told by a spokesman for Martin Bormann. . . .
12a. We close with Dorothy Thompson’s analysis of Germany’s plans for world dominance by a centralized European economic union, utilizing dominant corporate relationships with American corporations to effect control of the United States.
Ms. Thompson was writing in The New York Herald Tribune on May 31, 1940! Her comments are reproduced by Tetens on page 92.
Germany Plots with the Kremlin; T.H. Tetens; Henry Schuman [HC]; 1953; p. 92.
. . . . The Germans have a clear plan of what they intend to do in case of victory. I believe that I know the essential details of that plan. I have heard it from a sufficient number of important Germans to credit its authenticity . . . Germany’s plan is to make a customs union of Europe, with complete financial and economic control centered in Berlin. This will create at once the largest free trade area and the largest planned economy in the world. In Western Europe alone . . . there will be an economic unity of 400 million persons . . . To these will be added the resources of the British, French, Dutch and Belgian empires. These will be pooled in the name of Europa Germanica . . .
“The Germans count upon political power following economic power, and not vice versa. Territorial changes do not concern them, because there will be no ‘France’ or ‘England,’ except as language groups. Little immediate concern is felt regarding political organizations . . . . No nation will have the control of its own financial or economic system or of its customs. [Italics are mine–D.E.] The Nazification of all countries will be accomplished by economic pressure. In all countries, contacts have been established long ago with sympathetic businessmen and industrialists . . . . As far as the United States is concerned, the planners of the World Germanica laugh off the idea of any armed invasion. They say that it will be completely unnecessary to take military action against the United States to force it to play ball with this system. . . . Here, as in every other country, they have established relations with numerous industries and commercial organizations, to whom they will offer advantages in co-operation with Germany. . . .
13. We have discussed the Nazi tract Serpent’s Walk in many programs and posts. Bertelsmann appears to be cementing Underground Reich control of English language publishing.
The biggest book publisher in the United States is about to get bigger. ViacomCBS has agreed to sell Simon & Schuster to Penguin Random House for more than $2 billion in a deal that will create the first megapublisher.
Penguin Random House, the largest book publisher in the United States, is owned by the German media conglomerate Bertelsmann. Adding Simon & Schuster, the third largest publisher, would create a book behemoth, a combination that could trigger antitrust concerns.
The deal announced on Wednesday includes provisions that would protect ViacomCBS in the event that a sale is squashed by authorities. Bertelsmann would pay what is known as a termination fee if the deal does not go through.
The sale of the company will profoundly reshape the publishing industry, increasingly a winner-take-all business in which the largest companies compete for brand-name authors and guaranteed best-sellers. . . .
Even MORE Fun With Science: Earthquake Weaponry
The following 64 page book was published by British Intelligence in 1942 and reveals IG Farben’s long term plans for world domination. It is relatively easy reading:
https://www.merriam-press.com/sequeltotheapocalypsehowyouhelpedpayforhitlerswar.aspx
Here’s a quick update on the relative status of Moderna’s and BioNTech in the eyes of the investment community:
BioNTech also reported stronger-than-expected quarterly results, posting $6.24 billion in second quarter sales compared to analysts expectations of $3.83 billion. The company alone is now projected to add 0.5% to Germany’s GDP this year. That is a HUGE contribution to the Germany economy from a single company. It’s an example of the kind of news coming out of these companies that’s triggered the 422 percent rising BioNTech’s stock since the beginning of 2021, while Moderna stock is up 333 percent. Again, that’s just since the beginning of 2021, which doesn’t factor in their enormous 2020 growth:
“In a note shared with The Post, Jefferies managing director Michael Yee said Moderna “continues to trade like the ‘Tesla of Biotech’” — meaning the stock has a massive valuation based on high investor expectations about its future.”
Moderna is trading like the ‘Tesla of Biotech’. In other words, investors are betting Moderna owns the keys to the future of medicine.
At the same BioNTech is already exceeding those lofty expectations, reporting second quarter sales at $6.24billion compared to analyst expectations of $3.82. These are the kinds of numbers that triggered 3 and 4‑fold increases in these stocks since the start of 2021 alone (so not even counting 2020’s massive gains):
To put BioNTech’s wild over-performance in perspective, it’s now projected that the company’s alone could lift the Germany economy by 0.5% this year. That is a HUGE impact for a single company to have on an economy as large as Germany’s, made even more remarkable by the fact that BioNTech is basically a startup. And this is just the start of this little startup. So while BioNTech has clearly made a big impact in the global biotech sector, that impact could end up being dwarfed by the impact BioNTech has on the German economy in the long-run
“His calculations are based on BioNTech’s latest earnings released on Monday which showed the start-up now expects to accrue 15.9 billion euros ($18.63 billion) in revenue from the vaccine this year, up from an earlier estimate of 12.4 billion euros.”
BioNTech’s revenue estimates just keep rising and that’s just for this year alone. Future revenue growth is almost impossible to meaningfully project given that we’re potentially looking at decades of biomedical revolutions emerging from this technology. It’s the kind of situation that’s perfect for generating stratospheric stock valuations.
So that’s the update on BioNTech and Moderna: they’re now valued by investors like companies with the potential to redefine the biotech sector in the future. And in the case of BioNTech, eventually redefine Germany’s economy.
Here’s one of those articles that serves as a reminder of the incredible scope of what’s theoretically possible using the mRNA lipid nanoparticle delivery system the Moderna and Pfizer/BioNTech mRNA vaccines are based on:
Newly published work in the New England Journal of Medicine demonstrated the effectiveness of a CRISPR-based mRNA drug therapy. And that means this was mRNA that permanently modified the patients DNA. At least the DNA of the liver cells that had the special CRISPR mRNA delivered via the drug. Specifically, a team at the U.K.’s Royal Free Hospital, used CRISPR mRNA to deliver shut down the gene responsible for producing a toxic protein in patients with transthyretin amyloidosis. Three of the six people in the trial saw an almost complete drop-off in protein production. That’s a remarkable proof-of-concept result for a trial like this.
So while the mRNA vaccines may not be modifying people’s DNA as many fear, that doesn’t mean the same underlying mRNA technology couldn’t be retooled for exactly those purposes in the future. Recall earlier work investigating the use of genetically modifying skeletal muscles to produce desired antibodies as an alternative to traditional vaccines. Because skeletal muscle cells can live for decades, by strategically injecting the DNA for these antibodies into just those cells the body could producing the antibody for decades to come, making it effectively a one-time life-long treatment. It sounds like this approach of using CRISPR mRNA with the mRNA lipid nanoparticle delivery mechanism could achieve a similar result. Targeted tissues could have their DNA permanently altered.
One technical obstacle that still remains is delivering the mRNA to the desired tissues. Thus far, researches have figured out how to do it with liver cells. But the researchers believe it could be applied near-term for bone-marrow, nervous-system, and muscle diseases. So we might end up seeing long-term target DNA modification medical therapies much sooner than many expect:
“In theory, the same general technology could be used to treat conditions beyond transthyretin amyloidosis. “There are a host of diseases in the liver where this might work in an analogous manner,” says Dr. Kenneth Chien, a senior professor of cardiology research at Sweden’s Karolinska Institutet and a co-founder of Moderna Therapeutics, who was not involved in the research. “The most important aspect of this is the implications that the technology can be repurposed.””
Yes, while the treament for transthyretin amyloidosis is indeed exciting, by far the most important aspect of this research are the implications for what’s possible. Combing CRISPR mRNA with the lipid nanoparticle delivery system used in the Moderna and Pfizer vaccines, an entire new modality of medical applications are possible. The transient nature of delivered mRNA can be made permanent. It’s huge. Half the subjects in the trial saw an almost complete drop off in the gene targeted for silencing after a singe injection. That’s the kind of study result that will reverberate through the next few decades of medical research:
Finally, note the rather curious twist this promising research creates for Moderna’s and Pfizer’s mRNA business model. As we’ve seen, the creation of mRNA vaccines was never the original plan. That was a backup plan Moderna fell back on after it became clear that repeated doses of the mRNA therapies was creating too many side-effects. Vaccines were seen as a way around this because they only require one or two doses. The original plan was to create therapies that involved regular repeated doses. A business model based on selling the treatment, not the cure. So as we’ve watched the world embrace mRNA vaccines and celebrate the promise this technology holds, it’s been looking like we’re heading towards a scenario where Moderna and Pfizer would finally have the momentum to overcome saftey concerns and start delivering mRNA therepeutics that involve regular dosing. But with the CRISPR option now demonstrably available, that business model faces some interesting competition. Selling the cure is now an option. In other words, while this study is great news for patients, it might not actually be the best news for Moderna’s and Pfizer’s bottom lines:
Imagine if drug makers had the option of creating one-shot drugs. You take one pill and that’s it. You’re cured. Exciting, right? But how about the executives making the decisions of which drugs to invest in next. How excited would they be about these new wonder drugs? It’s a question the pharmaceutical industry is probably asking itself these days. In particular Moderna and Pfizer.
Here’s a series of articles related to the questions that have remained unanswered so far about whether or not the legal immunity granted by the US to vaccine manufacturers during an emergency will extend to other countries. First, recall how the US Congress passed the Public Readiness and Emergency Preparedness Act in 2005 during a bird flu outbreak that conferred legal immunity, and just such a emergency was declared by then-HHS Secretary Alex Azar in March of 2020, lasting until 2024. As a result, the vaccine manufacturers have a four year liability-free window to develop and assess new COVID vaccine technologies. And while some COVID vaccines rely on traditional vaccine technology, like the Johnson & Johnson vaccine, there’s no denying that the liability waiver was particularly convenient for the liability-free development of new mRNA technology from Moderna and Pfizer. It’s like a four-year liability-free mass safety trial of the mRNA therapeutic platform.
A platform that goes far beyond vaccines. Recall the 2016 STAT News article describing how Moderna started off trying to design therapeutic mRNA applications involving the regular introduction of mRNA to create the proper versions of proteins but the repeated administration of the mRNA nanolipid particles caused too many side-effects for the company to continue with that line of research. Moderna instead jumped to mRNA vaccines due to the fact that vaccines hopefully don’t require too many shots. More recently, we’ve learned about lans to use mRNA nanolipid technology to deliver CRISPR mRNA that can permanently alter the DNA of an individual’s cells.
Which is all, again, why the four year liability-free waiver for Moderna and Pfizer are like commercial manna from heaven. Because it’s not like the safety information developed over the next four years are only going to apply to vaccines. The whole industry is going to be pointing back to the found safety of mRNA vaccine to justify the initial use of all sorts of other mRNA applications for years to come. At least assuming there any major safety issues discovered during this period which, again, is why we really shouldn’t be blindly trusting these vaccine manufacturers to conduct the bulk of the safety assessments for the vaccines. The stakes go far beyond the future of these vaccines. It’s not an exaggeration to say this kind of technology represents a major new chapter in medicine. Possibly a new chapter in the human species if we go bonkers with the DNA modification. New public and private commercial biomedical empires are going to be built in the coming decades by those who most effectively exploit this new technology and the stakes almost couldn’t be higher.
But, again, it was never really clear the liability waiver passed by the US congress was going to apply to the rest of the world. So here’s an update on that front out ot India last week:
So far, India has been reliant on the AstraZeneca vaccine, which is being produced without a liability waiver. After months of questions over whether or not the Indian government would grant US vaccine manufacturers liability waivers, we appear to have an answer. It’s an answer delivered by anonymous government sources talking to reporters, so it’s not a definitive answer. But according to these anonymous sources, there will be NO liability waivers, although Pfizer’s spokesperson assures us negotiations are ongoing. And part of what made this report notable is that it came one day after we got reports that the Indian government expects to receive millions of doses of the Johnson & Johnson vaccine some time in November. So it appears that J&J, with its traditional vaccine technology, has tentatively arrived at an agreement to proceed without a liability shield, while Moderna and Pfizer are continuing to hold out and wait for the situation to get worse so they can extract a better deal:
“The Indian government has also declined to meet the U.S. companies’ requests for legal protection over any side-effects from the use of their shots, which are currently made only in the United States or Europe, two of the sources said.”
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Sorry, there will be no liability shields for side-effects. Not for Moderna, Pfizer, or any company in India. According to one anonymous government source, “sovereign indemnity is clearly something we can’t give.” At the same time, Pfizer is telling sources the discussion were ongoing. At a minimum, there’s an impasse for now:
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So what about the Johnson & Johnson shot? Did it get a liability shield? It didn’t sound like it, based on that report. But as we learned the day before, Indian government sources were telling reporters that India could receive as man as 43.5 million doses of the J&J shot in October. No deal had been signed, but those were the reports were were getting a day before reports from anonymous Indian officials indicated no company ever would receive a sovereign immunity agreement. Taken together, it would seem that J&J is going ahead with a supply agreement without a liability shield:
“It could receive as many as 43.5 million doses of the single-shot vaccine in October, said the source — a big step towards helping India meet its target of producing more than 300 million doses in the month. read more”
It’s not a hard confirmation, but reports like this are typically what precedes hard confirmations. On the one hand, considering that the J&J shot is based on traditional vaccine technology, it wouldn’t be a huge surprise if the company agreed to supply India with the vaccine without a liability shield.
But Moderna an Pfizer, that liability shield is looking to be an absolute prerequisite. That’s the situation described in the following article from early August about the Indian government giving its approval for the J&J shot, which points out that the government approved the Moderna shot back in June but legal wrangling over the liability protection is holding up deliveries:
“Indian health authorities have so far approved the use of vaccines developed by AstraZeneca (AZN.L), Bharat Biotech, Russia’s Gamaleya Institute and Moderna (MRNA.O).”
Moderna’s shot got approved. It just didn’t get liability-free approval, which Moderna is continuing to demand. And until that waiver is provided, no Moderna shots for India. And note how Pfizer hadn’t even sought permission to get its vaccine approved in India:
Will the Indian government find any sort of agreement with the mRNA vaccine manufacturers given the apparent hard opposition to liability protections? Well, as the following article from late July described, the Indian government appeared to be open to some sort of creative agreement involving having Moderna’s Indian partner, Cipla, assume some of the liabilities on Moderna’s behalf. Moderna rejected the idea:
“SII has already told the government that any indemnity for foreign vaccine companies should also apply to Indian producers.”
Calls for fair treatment by domestic suppliers is one obvious reason granting liability waivers to foreign vaccine producers is a touchy topic, but even when unfair treatment that sounds like a partial liability waiver was proposed, Moderna rejected the offer. Full liability waivers are an absolute demand from the company:
So if the vaccine manufacturers are demanding liability protections at the same time the Indian government is repeatedly insisting it’s not going to be granting such protections to anyone, what are the realistic paths out of this impasse? Well, as the following article from back in June describes, there appeared to be a real expectation at the time that this impasse could be overcome...with the Indian government capitulating and granting the liability protections. At least those were the predictions we were hearing from observers, based in part on the fact that these protections have already been granted by the US, UK, and EU. It was just assumed that India would follow suit and submit to those manufacturer demands too. And yet, as the article also notes, these liability waivers that have become pro forma during the pandemic are historically unusual moves. As Amir Ullah Khan, an economist and former policy adviser for the Bill and Melinda Gates Foundation, put it, it would be fair for India to haggle over indemnity in normal circumstances, but not now. “People are dying right now, and we don’t have space to bury them. In such a situation, where there is such a supply problem, it makes no sense to insist on negotiating over indemnity,” Khan said. It was a sentiment perhaps put more succinctly by K. Srinath Reddy, president of the Public Health Foundation of India, who predicted the government would eventually grant indemnity because the risk of missing out on vaccines is too high. “It is a seller’s market,” says Reddy. And that gives us a snapshot of how this liability battle was looking back in June: the expectation was that India was acquiesce to the industry demands in part because other countries were already leading the way in submitting to the demands but, more importantly, because of the urgency of the situation. It really is a seller’s market, and the sellers are behaving like they know it:
“Naushad Forbes, past president of the Confederation of Indian Industry, is confident India will eventually grant manufacturers indemnity, “but we will do it at a leisurely pace,” he says. “I am unable to understand why there are these delays.””
Someone had to blink, and the vaccine manufacturers were openly expressing confidence that it would be the Indian government who did the blinking. People are dying, after all, who can the government justify any such delays? That was the narrative we got from the industry. A narrative that conveniently ignores the moral liability of the manufacturers during an emergency. And a narrative that conveniently ignores the genuinely novel nature of the vaccine technology in the case of mRNA vaccines. As we’ve subsequently seen, J&J seems to be moving forward with its traditional vaccine technology without the liability protections. And AstraZeneca must have come to some sort of arrangement. It’s Moderna and Pfizer where we’re seeing the intense industry resistance:
And note the particular sticking point: concern over whether or not lawsuits could be brought in Indian courts vs international courts. It’s the kind of sticking point that should be raising questions about the closeness between international courts and multinational companies:
Will India grant vaccine manufacturers a more limited liability? Or perhaps adopt a strategy similar to the US where the government provides compensation in the event of an adverse side effect? We’ll see. Those confident predictions of a liability waiver still haven’t panned out and it sure sounded like the anonymous Indian government sources were adamant that no company would end up being granted immunity. It’s a seller’s market, after all. And a lot can change in a situation like this. Especially the virus.
If there’s been one area of unambiguous good news on the Coronavirus front of late it’s been in the area of therapeutics, with not just one but two new drugs on the cusp of emergency approval that appear to demonstrate significant efficacy against the virus. Merck’s new drug, molnupiravir, reduced hospitalizations by 50% and prevented deaths entirely. Pfizer’s Paxlovid also prevented deaths entirely and reduced hospitalizations by a stunning 89%. That’s a blockbuster drug. The kind of blockbuster drug the world has been clamoring for ever since the outbreak of the pandemic.
And that brings us back to a question that has lingered over the global response to the pandemic from the very beginning: to what extent is Big Pharma influencing the global quest for emergency therapeutics? Are cheaper options being passed over for expensive novel therapeutics? It’s been a question raised repeatedly in the story of Gilead’s Remdesivir and the persistent pushing of the drug by the US government despite highly limited positive results. As we’ve seen, Gilead has already made billions of dollars in sales to governments for a drug that costs over $3000/patient with questionable benefits.
But then there’s the enduring mystery of the “Thai cocktail”. Namely, the mystery of why those seemingly miraculous reports of incredible recoveries for severly ill patients given large doses of oseltamivir (Tamiflu) combined with an anti-HIV protease inhibitor mix of lopinavir and ritonavir were largely just ignored by the global health community. Why has there be almost no reports on any investigations into this treatment option? We’ve never received an answer to this day.
So when we learn that Pfizer’s not Paxlovid drug (actually Paxlovid + ritonavir) works in a manner highly similar to lopinavir, we again have to ask the question: what has there been basically no interest in using this existing well-understood drug? Lopinavir is a protease inhibitor targeting HIV. Plaxlovid targets SARS-CoV‑2. What are the differences in efficacy when taken early on in the infection? You’d think this would have been asked by now. But as we’ll see, nope that basic question of how lopinavir works early on in a COVID infection has yet to be asked. There was basically a single study on severely ill patients that didn’t pan out (note, this study did NOT include Tamiflu) and that’s been it. The world really has continued to ignore the “Thai Cocktail” mystery even as we’re now learning the new Pfizer’s blockbuster drug is a “Thai cocktail” biochemical-cousin. Why is that? It’s one of the many questions still lingering over this story:
“Though the topline results are similar, the medicines could have different risks and benefits. The companies have only issued data in press releases, not scientific articles, and doctors need to know a lot more about both. Here is an overview of what we still don’t know about the Covid pills and when we might learn it.”
We don’t know very much about these drugs, and what we do know has come in the form of corporate press releases. But those press releases were exciting enough that emergency authorization is expected sooner rather than later. There’s just one catch: both drugs are more effective when given earlier in the infection. In other words, these two drugs do NOT appear to be the silver-bullet for severe infections after they’ve developed, but they may be silver-bullets at preventing those severe infections from developing in the first place. It really is legitimately good news even if it’s not the best possible news:
It’s worth noting that, as these drugs haven’t been seen as effective for already severely ill patients, they won’t be replacing Gilead’s Remdesivir, which is still used for severely ill patients despite the questionable results. So it’s worth comparing the expected costs of these two new drugs to Remdesivir’s $3000+ cost: It’s looking like around $700 both both drugs for a five day course. So these aren’t incredibly affordable drugs, but still a fraction of the cost of Remdesivir:
And what about the possibility of combining these two drugs? Well, that’s very possibly even more effective, but we’ll probably never find out. Why? Because Pfizer and Merck don’t have an incentive to do so. Keep in mind that this kind of behavior only encourages the development of drug-resistant strains. That’s one of the big advantages of multi-drug therapies. But nope, maximum profits are the primary motive here:
So how confident should we be in the safety of these drugs given that they’re new and bound for emergency approval? Well, on the one hand, we are told that the side effects were no worse than for the placebo group in their trials. That’s what that the companies are telling us. But when we look at the actual mechanism for how Merck’s molupiravir works, it’s harder to take those assurances at face value. Because it turns out monupiravir works by inducing mutations. Yes, ideally those mutations will only be impacting viruses attempting to replicate. But there’s no guarantee the drug isn’t inducing mutations in cellular DNA too, something that could take 10 to 20 years to really test. Long-term tests that obviously haven’t happened yet. But Merck’s confident assessment o the long-term safety of the drug is more or less being accepted. It’s good to be a pharma giant:
But it’s the mechanism for Paxlovid that is of particular interest here in relation to the question of whether or not other cheaper and more readily available treatments were effectively ignored in favor of novel proprietary (and therefore more extensive, but less safety-tested) alternatives: It turns out Paxlovid is a protease inhibitor. Specifically, a protease inhibitor designed with a SARS-CoV‑2 specific protease in mind. So, in theory, this could be a highly effective treatment and it turns out that, yes, it is a highly effective treatment if given within the first few days of an infection:
And that brings to back to the mystery of the “Thai cocktail” therapy from early on in the pandemic. Recall the reports of sick elderly patients showing a remarkable recovery when given the “thai cocktail” mix of oseltamivir (Tamiflu) combined with an anti-HIV protease inhibitor mix of lopinavir and ritonavir. Part of the mystery was whether or not this cocktail really did have the ability to clear the infection as these miraculous-sounding reports suggested. But there was a second, much larger mystery: why is the the global health community showing so little interest in these reports, but a near uniform focus on Remdesivir as the therapeutic almost all of the official hopes were being placed on. This was the state of affairs back in February of 2020, when the world barely seemed to know what it was dealing with and before remdesivir proved to be a disappointment. It implicitly raised a pair of questions at the time:
1. Would the “Thai cocktail” approach ever be meaningfully tested?
2. Would any of the eventually discovered effective therapeutics work using a similar drug mechanism?
So the question of just how big of an opportunity did the world pass up when it more or less ignored the “Thai cocktail” reports in favor of un unproven Remdesivir remains an open question to this day. For example, take a look at the follow NY Times piece that is constantly tracking the range of COVID therapies and what the overall scientific establishment has assessed on their effectiveness. It’s a constantly update piece that’s presumably giving us a reasonably up-to-date summary of what studies have actually been conducted on these therapies. And as we can see, while the full “Thai Cocktail” doesn’t appear to have been tested, the lopinavir + ritonavir combination alone has indeed been tested. With not very promising results. But as we’ll also see, these not very promising results were found in studies conducted on severly ill patients and the studies themselves stated they could not rule out the possibility of the drug combo working on patients not yet sick enough to be hospitalized or newly exposed to the virus. In other words, the question of whether or not a lopinavir + ritonavir combo could work in a manner similar to the Paxlovid + ritonavir combo has never actually been asked.
Paxlovid is turning out to be wildly effective. And yes, it was designed specifically for SAR-CoV‑2, which presumably explains in part its effectiveness. But considering those early miracle reports on the “Thai cocktail”, it seems rather absurd that this obvious possibility of lopinavir + ritonavir early in the infection was never actually taken to trial. And at this point it remains unclear if that trial will indeed take place:
“Twenty years ago, the F.D.A. approved this combination of drugs to treat H.I.V. Researchers found that they also stop the coronavirus from replicating in cultures of cells. But subsequent clinical trials in patients proved disappointing. In early July, the World Health Organization suspended trials on patients hospitalized for Covid-19. They didn’t rule out studies to see if the drugs could help patients not sick enough to be hospitalized, or to prevent people exposed to the new coronavirus from falling ill. The N.I.H. Covid treatment guidelines recommend against using lopinavir and ritonavir in both hospitalized and nonhospitalized patients. The drug could also still have a role to play in certain combination treatments.”
What will those eventual studies on moderately ill patients reveal? Or will those studies now never take place as a result of the discovery of Paxlovid? We’ll eventually, belated, find out. But just to underscore how it’s openly recognized that the lopinavir + ritonavir treatment has potential yet to be explored, here’s an excerpt of a review article on exactly that topic from February 2021. The conclusion of the reviewers? That while no clear evidence of the drug combo’s effectiveness against SARS-CoV‑2 exists yet, it deserves further evaluation in particular during the early stages of the disease:
“In consideration of the actual biphasic models of the pathogenesis of COVID-19, which hypothesize a virologic-driven damage in the first days of disease and a second phase of inflammation-driven pathology [80], studies of LPV/r efficacy focused on patients during very early phase of disease may help to discern the usefulness of this drug in the actual emergency context.”
First we had the miracle reports of the “Thai cocktail” in February of 2020, followed by nothing other than a long-term study on lopinavir + ritonavir alone on severely ill patients and endless recommendations that it be tried out on the newly infected. And then, a year and a half after those “Thai cocktail” reports, we learn that the biochemically-related Paxlovid — which operates on the same underlying principle of lopinavir, but is more specifically targeted to SARS-CoV‑2 — has indeed been run through those exact same types of trials and found to be wildly effective. So what’s the actual story here? Did the globe pass over what could have been a wildly effective treatment? Again, we don’t know but those trials never actually happened, still to this day.
But on the plus side, at least if Merck’s molnupiravir ends up inducing all sorts of dangerous mutations, the consequences probably won’t be felt for another couple of decades.
Here’s a pair of updates on the hunt for effective covid therapeutics. First, it turns out Merck’s new ‘blockbuster’ drug, molnupiravir, doesn’t have quite the efficacy against protecting against death as first advertised. Instead of the initially reported 50 percent reduction in hospitalizations and deaths, Merck provided updated information on its clinical trial, revealing just a 30 percent reduction. It’s a pretty big drop, especially in comparison to Pfizer’s new Paxlovid drug that can apparently cause an 89% reduction. It’s also the kind of update that could and should weigh the costs and benefits of approving the drug for emergency authorization.
It sounds like the plan for the US FDA is to have a committee of outside experts review the materials on molnupiravir and make a judgement. The FDA is asking the panel to review safety concerns involving the potential for birth defects and other issues that could arise should the drug end up introducing mutations in human DNA too. Recall how molnupiravir works by inducing mutations into the viral replication process, so concerns over whether or not the drug could induce mutations in human cells are grounded in that fact.
Disturbingly, Merck is taking the stance that the drug is not capable of inducing genetic changes in human cells. And yet, as the article notes, Merck had the men in the trial had to abstain for heterosexual intercourse or agree to use contraception and women of child-bearing age also had to use birth control. So the company clearly had internal concerns about the potential for the drug triggering mutations in the DNA of these volunteers, and yet the company is telling the world that the drug isn’t capable of any of that. It’s a pretty big red flag about Merck’s good faith here.
But the FDA asked the panel to not just review the issue of inducing mutations in humans but also weigh in on concerns over whether the drug could encourage the virus to mutate. Again, the drug literally works by inducing mutations in the virus, so this seems like a very reasonable concern. We’ll see what conclusions this panel arrives on on that matter, but the fact that this panel is meeting right as a new global panic over a new highly mutated strain is getting underway should make this a pretty pressing issue for the panel to investigate. Because as we’re going to see in the second article below, this new strain emerging out of South Africa is loaded with a large number of mutations, especially in the spike protein. And at least some of these mutations are known to enhance the innate immunity of the virus and could potentially lead to strains that both escape vaccines but also escape existing immune built up on people’s bodies. It’s potentially a very big deal. The kind of big deal that prompted multiple countries to shut travel from not just South Africa but a number of its neighbors.
Ok, first, here’s a report on Merck’s disappointing molnupiravir update, prompting next week’s review. A review that will cover not just the drug’s safety but whether or not the drug is inducing mutations in both humans and the virus itself:
“The drugmaker said its pill showed a 30% reduction in hospitalizations and deaths, based on data from 1,433 patients. In October, its data showed a roughly 50% efficacy, based on data from 775 patients. The drug, molnupiravir, was developed with partner Ridgeback Biotherapeutics.”
What role might molnupiravir play with just a 30% reduction in hospitalizations and deaths? That depends, in part on all the costs that come with that protection. Costs like the potential to induce mutations in the patients themselves. It’s an obvious concern based on the mechanism for the drug. And yet Merck insists there’s no danger while taking steps during its trial that clearly point towards concerns about the risk of mutations causing birth defects. The company is giving us an implausible blanket denial. That’s ominous:
But perhaps more ominous is the potential for molnupiravir to induce mutations in the virus itself, potentially creating highly mutated new variants:
Don’t forget, if molnupiravir doesn’t kill the virus all it managed to do is create a viable highly mutated version. It’s like turning each patient on the drug into a human version of those viral passage experiments on ferrets shown to create powerful new strains of viruses capable of jumping species. And that brings us to the disturbing new reports out of South Africa about the latest potential nightmare variant. A variant with an unusual number of mutations concentrated in the spike protein, including mutations known to enhance the virus’s innate immunity and escape the immune system. While the number of cases is tiny so far, they’re in such a tight cluster that fears are we’re seeing the start of the new global wave. As a result, countries like the UK and Israel have already cut off travel from South Africa and some of its neighbors. But, again, we’re just in the initial stages of this so we really don’t yet have a good idea of what this new variant is capable of and how effective current vaccines will be. It’s a game of wait and see. Wait and see and cut off travel in the mean time:
“Within hours, Britain, Israel and Singapore had restricted travel from South Africa and some neighboring countries, citing the threat of the new variant. By Friday, markets were down in Japan in response to the discovery, and officials in Australia and in New Zealand said that they were monitoring the new variant closely.”
It’s a dark reminder that we’re still in a situation where a single bad report about a nasty new strain can end up leading to a country effectively getting quarantined by the rest of the world over night. To some extent it’s a reflection of the ongoing dangers of this virus. But it’s also a reflection of just how much we are still forced to rely emergency ad hoc policy based largely on fears of what might happen because we still don’t really know what this virus is fully capable of. This is still only SARS-CoV‑2 version 1.0 or 2.0. We don’t know what version 10.0 of the virus is going to be capable of and whether or not any existing vaccines or drugs will work at all. But what we do know is that when a new version of the virus shows up, the more mutated it is the more potential it has to be a nightmare strain. That’s what’s driving a lot of this response: the combination of not yet understanding what this virus is capable of but recognize the signs that it could be a particularly nasty strain, with over 30 mutations on the spike protein alone. It’s an ominous mutant:
What kind of new nightmare mutant will molnupiravir end up creating once it gets thrown at a patient with this already-mutated strain? Let’s hope we never find out. But we’re probably going find out anyway, especially if that review panel ends up approving the drug for emergency use next week.
It’s also worth recalling one of the primary tools we have at our disposal for potentially preventing the development of mutant strains: drug combinations. As the world learned in its battle with HIV — a virus highly prone to mutations — you really need a combination of two or three drugs at once if you want to avoid the development of drug-resistant strains of HIV. A similar principle is going to apply for SARS-CoV‑2, which means the world really does need to be scrambling for as many different therapeutics as possible to be used in as many combinations as we can safely discover. Recall the concerns about actually seeing clinical trials on drug combinations take place because it would involve rival Pharma giants teaming up and potentially reducing their profits.
And that’s all part of what’s going to make the story of molnupiravir so interesting to watch play out: it’s a drug that, when used on its own, might actually end up creating more devastating versions of the virus. And yet those dangers might be mitigated significantly if the drug is taken in combination with other therapeutics like Paxlovid that are simultaneously attacking the virus in other ways. At least the dangers of creating a new viral strain. The dangers of inducing mutations in the patients will still potentially be there, but those may be relatively small dangers in comparison when faced with the prospect of a deadly coronavirus infection. There’s a number of red flags warning us about molnupiravir, and a number of other red flags telling us we’re going to maybe need it anyway.
Following up on Merck’s new covid drug currently under review for emergency authorization by the US FDA, molnupiravir, and concerns that the drug could be inducing mutations — mutations in both the patients’ DNA but also the virus itself, potentially driving the creation of new mutant variants — here’s a set of articles about those concerns about the risks posed by this drug. The first two articles were written by Harvard virologist William A. Haseltine about his concerns about both the risks posed to patients but also the risk posed to everyone through the creation of new variants.
The third article is a piece in Science summarizing Haseltine’s concerns in light of molnupiravir’s pending approval. And in this third piece we learn about some rather interesting research that was published in November of 2019, right when the virus was simmering in Wuhan and weeks before official detection. The research was published by Mark Denison, one of the virologists interviewed for the piece to share their take on the risks associated with molnupiravir. It turns out Denison’s lab at Vanderbilt University has actually conducted experiments with molnupiravir on coronaviruses. That was the research published in November 2019.
In that publications, the researchers subjected two different coronaviruses — Middle East respiratory syndrome CoV (MERS-CoV) and murine hepatitis virus (MHV) to repeated exposure to the drug. After 30 passages, they catalogued over 162 different observed mutations. These mutations did not kill the virus. It almost sounds like a ‘gain-of-function’ experiment, but technically it wasn’t because they weren’t actually setting out to identify new function, and if you read the paper there’s no reference to ‘gain-of-function’ at all. It’s an example of how routine the kind of research that involves the creation of new viruses really is in today’s modern medical research environment.
Oh, and if you look at the second-to-last author of the paper, it’s Ralph Baric, indicating that while this research was conducted by Denison’s lab at Vanderbilt it was part of a collaboration with Baric’s team. Which, again, is exactly as we should expect and there’s nothing scandalous about it. This is totally routine. That’s the story here. This research that literally involved generating new coronaviruses by passaging them through repeated exposure to a mutagenic compound and seeing what new variants emerge is absolutely routine. And routinely taking place in the immediate timeframe leading up to the SARS-CoV‑2 outbreak.
But while this kind of research is routine, that doesn’t mean there’s universal agreement on its safety or the implications of the use of these drugs. As we’ll see, Haseltine’s warnings aren’t entirely shared by his fellow virologists. As we’ll see, in the first excerpt below, Haseltine explicitly cites that November 2019 research as an example of how robust coronoviruses can be in the face of these kind of mutagenic drugs. But in the third excerpt, Denison had a very different take on the potential risks of the use of molnupiravir, suggesting that his research points towards the drug creating deleterious (harmful to the virus) mutations. There’s a real point of disagreement in the virology community here. That’s the other side of the story here.
Ok, first, here’s Part 1 of Haseltine’s piece from earlier this month in Forbes where he’s basically warning the world that the FDA could be on the precipice of a global catastrophe should it approve the use of molnupiravir. A catastrophe in the form of powerful new variants artificially created by the use of this drug:
“We are potentially headed towards a world class disaster. If the FDA does grant approval for the drug — and there is an argument to be made that better and safer antivirals are already on the way — it should be on a very narrow basis and include a black box warning to emphasize the potential danger of using the drug at suboptimal doses or for large numbers of people for preventive purposes. What we know with certainty is that his drug is far from the magic bullet we might hope for with an antiviral for Covid-19. The next article in this two part series will explore the potential risks and dangers of the drug for patients themselves.”
A world class disaster of our own making. That’s what Haseltine warned about early this month. And he went on to specifically cite the Denison Lab’s November 2019 research where they found coronaviruses were indeed heavily mutated by the drug and yet capable of surviving:
And note the important point Haseltine makes here, because it’s a kind of preemptive rebuttal to Denison’s dismissal of these concerns because they’ll inevitably lead to ‘deleterious’ mutations upon repeated exposure to the drug. Haseltine points out that while the observed mutated viruses did appear to demonstrated a slight replicative disadvantage from the original variants, that shouldn’t really be taken as a sign that this drug will ultimately generate weaker variants because once these viable mutate variants escape a lab, evolutionary dynamics immediately go to work. And viable variants are going to be escaping patients on these drugs with each breath:
Ok, next, here’s Haseltine’s Part II piece, that focuses more on the potential risks to the patients’ own DNA. As Haseltine points out, while it’s true molnupiravir has indeed been tested for mutagenicity in humans, those studies haven’t been large enough to catch rare mutations. The kind of mutations that have consequences that only show up years later.
Haseltine also points out another study published earlier this years that points to the potential risks posed by the drug. The study examined the muatgenicity of a molnupiravir metabolite along with the mutagencity of another drug, favipirivir, which works in a similar manner inducing mutations. Favipirivir also happens to be a drug with widely known dangers linked to teratogenicity and birth defects. Guess which drug was the most potent mutagen. Yep! Molnipiravir was found to be a far more potent mutagen.
Keep in mind that studying these kinds of long-term effects of drugs on DNA is Haseltine’s area of expertise. So these are warnings we should probably be heeding right now:
“Molnupiravir has been tested for mutagenicity in animals before being moved to human trials, where it is being tested for safety. But that doesn’t mean the drug is fully in the clear. The pool of participants in the clinical trial — around 1,500 patients — is too small to pick up on rare mutagenic events and the early nature of the trial is too short-term to provide a proper view of issues that may occur months, if not years, down the road. Merck would do well to remember their experience with Vioxx, a painkiller that was deemed safe based on initial studies, but later proved deadly. The FDA originally approved Vioxx based on a safety database that included around 5000 people. Five years later, the drug was recalled after a broader and longer term study found a definitive link between the drug and rare cardiac events. There is evidence that during the time the drug was on the market it may have killed up to 56,000 people and left up to 140,000 with heart disease.”
The problem isn’t a lack of testing. It’s a lack of long-term testing at the scale needed to truly assess the long-term risks of a drug known to induce the kind of mutations known to manifest years later.
But beyond that, it’s a problem with the actual test results we’ve already received. If molnupiravir is generating metabolites far more mutagenic than drugs like favipiravir, that alone should be a red flag:
And yet that red flag has been largely ignored it seems. It’s another bigger red flag. Although, to some extent, it’s also just a reflection of disagreement in the expert community. But that’s part of the story here. How is it that a prominent virologist like William Haseltine can be sounding the alarm like a major mistake is being made, at the same time so many others are taking a more sanguine approach to the risk of these drugs. It’s an alarming lack of shared alarm:
“Now, William Haseltine, a virologist formerly at Harvard University known for his work on HIV and the human genome project, suggests that by inducing viral mutations, molnupiravir could spur the rise of new viral variants more dangerous than today’s. “You are putting a drug into circulation that is a potent mutagen at a time when we are deeply concerned about new variants,” says Haseltine, who outlined his concern Monday in a Forbes blog post. “I can’t imagine doing anything more dangerous.””
So Haseltine’s position is: “I can’t imagine doing anything more dangerous,” which is about as alarmed as one can get. But then we find all these other experts, including Denison himself who generated the research Haseltine specifically cited as demonstrating the potential risks of this drug. As Denison put it, “If I take away anything from our work, it is that if the virus tries to adapt, say through resistance [to molnupiravir], it continuously develops deleterious mutations.” Of course, that would assume the same patient is being repeated exposed to the drug through the entire course of the treatment, something that doesn’t always happen. Denison goes on to predict that it’s more likely that the virus will develop a resistance to the drug. Isn’t that more or less the same thing and exactly what Haseltine predicted, but arguably worse?
Finally, note the truly disturbing language coming from Merck: the company hasn’t seen any evidence of people who take the virus developing dangerous new mutations. It sounds all soothing, but when you parse the language, it’s basically an admission that, yes, patients on the drug on generating new mutant variants but Merck hasn’t seen evidence that these mutations anything but random. Now, on the one hand, yes, not finding evidence of non-random mutations is a good sign because that would be evidence of evolutionary selection already in action. But on the other hand, whether or not signatures of evolutionary effects could already be detected in these trials is entirely beside the point. We know evolution will eventually take it from here. It’s like a corporate non-denial denial answer, which is scary news in this context:
Again, don’t forget that Ralph Baric is the second-to-last author on the November 2019 Denison Lab paper that Haseltine cited as a source for his alarm. So Denison’s relatively low sense of alarm over the risks posed by this drug is probably fairly widely shared in the virology community. But there’s clearly some major points of contention as Haseltine’s pieces make clear. That’s part of what makes this story so fascinating. This is like a serious scientific dispute inside the virology community. In this case, serious dispute centered around the interpretation of 2019 coronavirus passaging experiments involving the creation of new mutant coronavirus strains. Routine experiments, which are technically not ‘gain-of-function’ experiments but share a number of parallels, taking place in labs all over the world right now.
Well that was odd, albeit not too surprising: The FDA just issued another advisory warning the public against taking the Johnson & Johnson COVID vaccine. The vaccine is still technically available in the US, but under the FDA’s new guidance it should only be taken by individuals who can’t take the mRNA vaccines for whatever reason or who refuse to take the mRNA vaccines and won’t otherwise get vaccination. In other words, the FDA is telling the public that the J&J vaccine is better than no vaccine at all, but not as good as the mRNA vaccines.
Or course, while the new guidance doesn’t officially ban the J&J vaccine in the US, it will likely have that effect in many locations as demand for the vaccine plummets and the few vaccination sites that still offer it decide it’s no longer worth it. So the US is shifting into a COVID vaccine paradigm that where mRNA vaccines are effectively the only option. At last until new non-mRNA vaccines are approved.
So what prompted this new warning? Well, it sounds like the FDA was reviewing the vaccine safety data and found a single additional death tied to a rare blood clotting disorder, bringing the total number of deaths tied to the vaccine to 9. With 18 million doses of the vaccine distributed in the US that put the J&J vaccine’s death rate as one in 2 million. That’s what prompted the FDA’s warning that will effectively end the J&J vaccine in the US.
It’s worth recalling at this point how the long-term safety of mRNA vaccines remains an open question, with just a little over two years of large scale data. Also recall how Moderna appeared to shift its mRNA therapy ambitions for routine therapeutics to vaccines only after it became apparent that the lipid nanoparticle delivery vehicles used to deliver the mRNA were inducing too many side effects. Side effects that were effectively a bonus in the context of vaccines where an immune response to the injection is desired. So the question of the long-term impact of repeated doses with mRNA vaccines should be a massive area of inquiry at this point. And few things could be more valuable in that inquiry than having a comparable non-mRNA vaccine that was also being delivered to the same population. The invaluable long-term longitudinal study comparing the side effects and health impact of regular mRNA vs non-mRNA vaccines is now basically over in the US because of this FDA decision.
But there’s another angle to this story that should really be raising eyebrows in the public health community: this decision comes less than two months after reports that the J&J vaccine was actually performing better than the mRNA vaccines, with more durable protection against new variants including the Omicron variant. Yep, that was reported back in March in the NY Times. The research even indicated that people who were originally vaccinated with an mRNA vaccine might be better served against new variants by taking a J&J booster.
A few weeks later, the FDA issued another warning about the J&J vaccine about another rare side effect. That warning was lifted 10 days later, but it had an impact. The demand for the vaccine was crushed. And then a month later we get this latest FDA warning that effectively kills access to the vaccine in the US. So shortly after research started showing that the US might be better served with the J&J vaccine, the FDA took steps to effectively knock the J&J vaccine out of the market:
““We’re not saying that it’s a bad vaccine. We’re just saying that for our population, where there’s an alternative, we feel that the alternative should be used.””
It’s a rather bizarre public health advisory: We’re not saying the J&J Vaccine is bad. We’re just telling the US public not to take it.
And, of course, don’t forget that while this FDA ruling is still technically leaving open the option of taking the J&J vaccine for individuals, this advisory is obviously going to result in a dramatic reduction in the availability of the vaccine for everyone as more and more vaccination sites just stop offering it as demand plummets.
So what is the basis for the FDA’s warnings? A single new death associated with a rare blood clotting reaction to the vaccine was found after reviewing the data, bring it to 9 deaths in total. Out of ~18 million doses. So the rate of one death for every 2 million doses was deemed to be high enough to trigger an advisory that’s probably going to effectively force the J&J vaccine out of the US market:
But note how the impact of this ruling isn’t just going to be felt in the US, where individuals averse to taking still-experimental mRNA vaccines are going to be more inclined to go unvaccinated. It’s also potentially going to be derailing the ongoing efforts by J&J to role out its vaccine for the developing world. A vaccine that had major advantages for poorer countries, like no need to ultra-cold temperatures for storage. Peter Marks, the FDA’s vaccines lead, acknowledged that, while the move likely won’t affect vaccination patterns in the US all that much because so few vaccination sites still even offer the J&J vaccine, the implications could be felt in developing countries where J&J’s vaccine is still seen as a much-needed tool. It’s part of what makes this decision so puzzling:
Finally, note how this decision is justified, in part, based on the assessment that the J&J vaccine doesn’t have the same level of protection as the mRNA vaccines. First, keep in mind that utter absurdity of this routine comparison. It’s a comparison of a single-shot J&J vaccine vs a double-shot of these mRNA vaccines. Of course the J&J vaccine doesn’t elicit as strong an immune response! And this flawed comparison was used to justify the advisory recommending that people who initially got the J&J vaccine get an mRNA booster:
Now, regarding the warning issued in mid-April over the rare clotting side-effect, which was lifted 10 days later but still crushed the demand for the J&J vaccine, it turns out that warning came at a rather remarkable time. As we’re going to see in the following NY Times article from back in March, recent studies have found the J&J vaccine actually seems to offer better and more durable protection against COVID, in particular against the Omicron variant.
Yep, that’s what was reported back in March. Beyond that, the study even suggested that the J&J vaccine might make for an excellent booster for people who originally got the mRNA vaccines. And then a few weeks later the warning was issued that crushed the demand for the J&J vaccine. A few weeks after that and we get this latest FDA warning that appears to be an attempt to put the final nail in the coffin in this seemingly promising vaccine. So what’s going on here with these hyper-alarmist warnings directed at the one non-mRNA vaccine available in the US? If patient health is a priority, what about all the patients who could use the extra protection against variants these studies were finding?:
“But the notion that the vaccine is inferior has grown outdated, some experts said: More recent data suggest that it has more than held its own against its competitors.”
It was just two months ago that we were getting these reports about the surprising effectiveness of the J&J vaccine. A report that’s all the more remarkable given that the J&J vaccine regiment was a single-shot while the mRNA vaccines are given in two doses. How much better would the J&J vaccine’s protection be if people got a second shot 30 days later? Conversely, how much worse would the mRNA vaccines have performed with just a single dose? Somehow these very basic observations got lost as the coverage of the performance of these vaccines consistently portrayed the J&J vaccine is grossly inferior:
And as we probably should have expected given the one-dose vs two-dose comparisons, the J&J vaccine didn’t elicit as strong an immune response initially. But over time, the J&J vaccine has been coming out on top. It even appears that the immune system learns how to response against newer variants more effectively when exposed to the J&J vaccine. Which is exactly what we want, right?
And then there’s the question of whether or not all of the people who originally got an mRNA vaccine would be better served getting a J&J booster. A question the FDA apparently doesn’t actually want answered:
Yeah, it sure would have been nice to see how different combination of vaccines performed. Oh well.
Also keep in mind that there’s still a number of COVID vaccines still in development or already in use around the world. It’s just the US where only mRNA vaccines are available. Novavax, for example, has a COVID vaccine based on traditional vaccine technologies that’s still awaiting approval, potentially as soon as next month. And it’s already approved in the European Union, Canada, South Korea, Australia, New Zealand and Indonesia. So it’s possible the US’s de facto mRNA-only vaccine status won’t last long. There’s obviously no real excuse not to approve it if all of these other countries have already deemed it safe. Time will tell. But time won’t be telling us how the J&J vaccine would have actually performed vs the mRNA vaccines in the long run. That experiment is already over...right when it was getting really interesting.