On the evening of 9 November, Beijing time, Pfizer and the German company BioNTech announced that their joint development of the new coronavirus vaccine candidate BNT162b2 has made significant progress in the interim analysis of the Phase III clinical trial study. In the double-blind trial, the vaccine's effectiveness exceeded 90% on the 7th day after the second injection, which means that the protective effect can be achieved on the 28th day after the first injection.

After that, the global stock market skyrocketed, and US President Trump also complained that Pfizer did not announce the good news before the election. It can be seen that everyone generally has high hopes for the effectiveness of this vaccine.

The U.S. Food and Drug Administration (FDA) will hold a meeting to evaluate the effectiveness of this vaccine on 10 December. If passed, the vaccine will be officially launched on 11 December. The following is the question of time for deployment on a global scale.

This is also the first transcriptional ribonucleic acid (mRNA) vaccine that humans may use. It uses a mechanism called "vaccine as code". Once it proves effective, the future vaccine development process may be completely changed, greatly shortening the research and development process. cycle. Of course, this vaccine is currently facing some transportation problems (requiring the storage temperature to be lower than minus 75 degrees Celsius, resulting in extremely high transportation and storage costs), and it has yet to be resolved.

This article will review how this vaccine was born. However, this needs to be traced back to the experience of two people: Şahin and Türeci.

Şahin's parents immigrated to Germany from Turkey in the 1960s. His father participated in a foreign employment project organized by the German government to promote the country's economy and worked in a Ford factory. Türeci's parents were also Turkish immigrants, who immigrated to Germany from Istanbul.

Şahin and Türeci both attended medical school and met while working in the hospital. They returned to the laboratory to continue working on the day of their wedding. Both were dedicated to research and teaching at the beginning, mainly teaching at the University of Zurich. Şahin once worked in the laboratory of Rolf Zinkernagel, the 1996 Nobel Prize winner in medicine.

Şahin & Türeci

They founded their first company Ganymed Pharmaceuticals in 2001, focusing on developing tumor drugs which is based on single-cell antibody.

The company was acquired by Japan-based Astellas Pharma for US$1.4 billion in 2008, and they have also become one of the richest people in Germany.

Their lives have not changed much after the company was sold. They still live in the original apartment, do not buy a car, and ride to work every day. Şahin doesn't even have a driver's license.

In 2008, the couple founded BioNTech to develop mRNA-based cancer treatment methods. Soon after, BioNTech raised hundreds of millions of dollars in funding and currently has more than 1,800 employees, mainly in Berlin, Germany and Cambridge, Massachusetts. As shown in the figure below, as a NASDAQ listed company and the largest pharmaceutical unicorn in Europe, BioNTech’s stock price has risen nearly four times this year.

In 2018, it began to cooperate with Pfizer, the world's largest pharmaceutical company. In 2019, Bill Gates’ Bill Melinda Foundation invested US$55 million to fund their research on AIDS and tuberculosis.

Compared with traditional vaccines, mRNA has more safety advantages. It will not insert gene mutations and can be degraded by normal cells. Its half-life can be changed by modifying the regulatory sequence and delivery vectors. More importantly, traditional vaccines are powerless against many new viruses, not to mention diseases such as cancer that seriously threaten human health. The mechanism of action of mRNA makes it like a meal book.  As long as you compile the RNA sequence, you can turn the cell into a small drug factory, and the mRNA guides the cell to produce specific proteins by itself to exert systemic effects.

mRNA vaccines currently have two major application areas, infectious diseases and cancer.

Introduction to mRNA

In mid-January 2020, Şahin heard about the infectious disease in Wuhan. At first he thought it was nothing, because infectious diseases appeared every six months in the world. But on 24 January, he read the analysis of an infection case in a Chinese family in The Lancet. He learned that this virus has a new form and a fast spread, and the key is that it can spread asymptomatic. He checked the traffic location in Wuhan again, and he realized that the virus may have spread around the world.

He immediately called the investor and said that he hoped the company could switch to vaccine research and development. The investor agreed.

On the weekend of 25-26 January, he drew 10 possible mRNA vaccines on the computer. The vaccines waiting to be approved that everyone sees in the news are drawn by him at that time.

On Monday, 27 January, he canceled weekends and holidays for company employees, and grouped company employees. If one group is infected, another group will continue. The employees of the company didn't feel the urgency of the matter at first, so Şahin called the employees one by one to talk.

Looking back now, their decision requires a lot of courage, because:

• At that time, everyone didn't know how serious the matter would be. Let alone Europe, China just realized the harm of this virus;

  
  

• BioNTech's mRNA technology is not mature in the field of vaccines, and has only been tried in clinical trials;

  
  

• The previous vaccine research and development record was four and a half years, and BioNTech's goal is one year.

As input costs increase, BioNTech needs to find partners with more funds and larger companies. On 1 March, Şahin contacted Pfizer, the world's largest pharmaceutical company, and both parties agreed to split the cost and revenue in half. BioNTech is responsible for vaccine development and Pfizer is responsible for vaccination trials around the world.

Regarding the issue of patents, Şahin said that patents themselves are not a bad thing (technological development requires millions and millions of investment from investors). But if some people cannot get the vaccine because of the patent, that is a bad thing and he cannot accept it.

The money earned from vaccine research and development will continue to be invested in the research and development of cancer treatments.

Şahin concluded in a recent interview that you should not close your eyes when you encounter a problem, and the sooner you can deal with the danger, the better.

Everyone knows the following story. From the development process of this product, I think we can learn at least one point:

Opportunities only favor those who are prepared. Without BioNTech’s long-term accumulation in the mRNA field, there would be no way to develop a symptomatic vaccine so quickly.

Richard W. Hamming (I wrote an article about Hamming before, this is Mr. Hamming) once in his book "The art of doing science and engineering" (the art of science and engineering), proposed a famous Equation of luck (Equation of luck):

Luck = preparation level * chance of winning

The former depends on everyone, the latter is decided by God.

Of course, there may be many other inspirations, including the role of immigrants (Şahin and Türeci are both descendants of immigrants) and so on.