In 2018, the Nobel Prizes in Physiology or Medicine and Chemistry were all related to the field of biomedical research, especially research on cancer treatment. The field of biomedicine has become the most anticipated frontier for the future generation.
In the MRC Laboratory of Molecular Biology in Cambridge, in just one laboratory, a total of 12 researchers have become Nobel Prize laureates. It is quite clear that breakthroughs in the right field of research will result in major contributions to mankind. Most of today’s advanced cancer therapies are based on newly developed antibody drugs from great scientists.
Altruism has always been in our blood. Recently, Hermes-Epitek has been thinking about how we can use some of our resources for altruistic purposes, and about choosing some longer-lasting and meaningful endeavors that can contribute to the well-being of human life. Therefore, we have begun investing in life science research in hopes of bringing together partners and peers with the same goal.
Introduction to the 2018 Nobel Prize in Chemistry
At the announcement of the 2018 Nobel Prize recipients, the Chemistry Prize was awarded to British scientist Sir Gregory P. Winter and two American scientists Frances H. Arnold and George P. Smith. The research of the three prize recipients encompassed simulating the evolution of nature, which ultimately promoted the development of new fuels and drugs, as well as further advances in medicine and the environment.
▲ Poster of the prize recipients published by the Royal Swedish Academy of Sciences in recognition of their work “for the directed evolution of enzymes” and “for the phage display of peptides and antibodies”.
Arnold, from the California Institute of Technology, was the fifth female laureate of the Nobel Prize in Chemistry, and also one of the pioneers in directed evolution.
Directed evolution is a method used in protein engineering to simulate the process of natural selection in order to develop proteins of interest or technically useful to researchers. The process involves inducing gene mutations through repeated rounds of engineering （mutagenesis）, followed by screening of proteins with the desired characteristics （selection）, then finally undergoing amplification.
▲ Random mutations are introduced into the genes of enzymes to simulate the process of natural selection.
In short, Arnold introduced random genetic mutations into the enzyme to see how these mutations can affect the enzyme. Next, specific mutations that are effective are selected, such as mutations that enable the enzyme to catalyze in a solvent that was previously ineffective. She further repeated the process and re-introduced the mutant gene into these selected enzymes.
Arnold’s research provides suitable enzymes applicable to various fields, including biofuel development and pharmaceutical production, and effectively reduces the use of many toxic catalysts.
“After Arnold put forward her research, enzymes can be effectively adjusted to achieve better results in an industrial environment. Its ultimate result is to reduce the evolutionary progress that would otherwise take billions or millions of years in nature down to less than a week.”
The co-recipients of the Chemistry Prize were Winter and Smith for their research on “the phage display of peptides and antibodies”. A bacteriophage (phage) is a virus that infects bacteria and induces bacteria to multiply. Smith, from the University of Missouri, discovered that modifying the genetic material of the phage can change the molecules attached to it.
▲ Using phage display technology, scientists can genetically engineer phage to carry specific proteins in order to explore how these proteins interact with specific targets.
Smith realized that this feature might be very useful, for example: if it is not known what protein a particular gene will make, then the gene can be inserted into the DNA of the phage; this unknown protein will then appear on the surface of the phage and can be identified. This also means that scientists can implant a large number of unknown gene fragments into the phage to see if they can produce any known proteins and in turn determine which genes correspond to which protein.
The approach has also opened a new door for scientists, that is, using phage display technology to genetically engineer phage to carry specific proteins in order to explore how these proteins interact with specific targets.
Today, phage display has produced antibodies that can neutralize toxins, fight autoimmune diseases, and cure metastatic cancer.
Winter’s research direction is to implant DNA from various antibody binding sites into phage, allowing phage to present the antibodies on the surface. This means that it goes through phage selection to find antibodies that have the best response to specific molecules.
Winter can use this phage display method to produce new drugs that provide treatment for cancer and autoimmune diseases. One of the new drugs that has already been developed is adalimumab, an antibody drug that can treat rheumatoid arthritis, psoriasis, and inflammatory bowel disease.
“Almost all modern therapies today are antibody drugs, and they all use phage display technology. This is a completely groundbreaking study; if Smith didn’t develop phage display first, these outcomes might never have happened.”
In an interview in 2016, Winter admitted to his first cancer patient that he did not know if the antibody treatment would be effective. But in reality, the treatment results were quite successful, resulting in the disappearance of a gigantic tumor. This victory allowed researchers at the MRC Laboratory of Molecular Biology in Cambridge to be awarded a total of 12 Nobel Prizes.
The contributions of these three Nobel laureates will bring improvements to many areas of everyday life, including the pharmaceutical industry, biofuels, and green catalysts. They have been much lauded by scientists in all fields.
Introduction to the 2018 Nobel Prize in Physiology or Medicine
The 2018 Nobel Prize in Physiology or Medicine, which was announced on October 1, was awarded to the American immunologist James P. Allison and Japanese immunologist Tasuku Honjo, who have made significant contributions to anti-cancer immunotherapy.
As cancer cells have complex mechanisms that can evade the attack of the immune system, cancer treatment is always difficult. Nearly a century ago, scientists first proposed the idea of using the immune system to treat cancer, but without a corresponding breakthrough study, this concept has been put on hold until the discovery of Allison and Tasuku Honjo; now, it is possible to apply cancer immunotherapy in actual clinical treatments.
In studies conducted in the 1990s, Allison discovered an “immune checkpoint” mechanism that regulates T cell activity in the human immune system, and while other research teams explored enhancing the checkpoints for the treatment of autoimmune diseases, Allison also found in subsequent studies that the inhibition of checkpoints can have a significant effect on treating cancer in mice.
In 1992, Professor Tasuku Honjo of Kyoto University discovered the existence of a second checkpoint that operated through different mechanisms during independent research. The treatment based on this finding has now significantly improved the clinical therapeutic effect on patients.
▲ Research on CTLA-4 by Allison and PD-1 by Tasuku Honjo
have made many contributions to the study of immunological anticancer therapies.
Through this research, checkpoint inhibitors were developed, and despite the obvious side effects, treatments for lung cancer, kidney cancer, lymphoma, and melanoma have produced significant therapeutic effects.
There are currently many checkpoint treatment trials for cancers being undertaken around the world. These findings have transformed our understanding of the human immune system and uncovered the potential to control and even eradicate tumors and leukemia.
“A decade ago, metastatic melanoma was largely incurable, but thanks to the work of Allison and Tasuku Honjo, patients now have real hope: more than one-third of patients will gain long-term benefits and even have the opportunity to recover through treatment.”
Cancer is the greatest hazard to human health, with approximately 15 million people getting cancer every year worldwide and causing more than 8.2 million deaths (equivalent to 14.6% of total deaths in the world every year). However, according to US research surveys, there has been no significant progress in cancer treatment survival rate in the past 30 years, and treatment effects have not been as successful as we have expected. In was not until recently, with regard to immune checkpoint inhibitors and cellular immunotherapy, that there has been a breakthrough in the treatment of specific cancers. The immune checkpoint inhibitors have progressed from the previous five-year survival rate of about 15% to more than 50% against advanced metastatic melanoma. The derived CAR-T treatment has increased the former effective rate of less than 10% by more than 85% in children with acute leukemia, and both have become important methods for cancer treatment.
The 2018 Nobel Prize in Physiology or Medicine was awarded to two immunologists researching cancer immunotherapy, and the Nobel Prize in Chemistry was awarded to three scientists who invented and applied phage display technology and protein directed evolution technology. Today’s biomedical scientists use phage to direct the evolution of antibody proteins in conjunction with the methods invented by the above scientists. The antibody database established by means of phage display is used to link the antibody fragments attached to the surface molecules of the phage and its genetic information, thereby providing a selection method for high-efficiency monoclonal antibodies.
References
- Li Yi-xuan (2018/10/04 1:32). “Nobel Prize 2018” Promoting the development of biomass energy and new drugs, Chemistry Prize awarded to protein evolution research and genetic engineering tools. TechNews. 2018.11.16, retrieved from http://technews.tw/2018/10/04/nobel-chemistry-2018-for-protein-evolution-and-gentic-enginner-tools/
- Nana Ho (2018/10/02 14:21). “Nobel Prize 2018” Medicine Prize announced, two cancer immunotherapy scholars selected as award winners. TechNews. 2018.11.16, retrieved from https://technews.tw/2018/10/02/2018-nobel-prize-for-medicine/
