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Tuesday, November 20, 2018

The definitions of SI units has been changed by BIPM: International Bureau of Weights and Measures.

Dear friends

The definitions of SI units has been changed by BIPM: International Bureau of Weights and Measures.
Some of the highlights of the changes are presented here from BIPM's Press KIT. For detail study of the changes syou can go to the original site. The link of original site is on your left hand side on this blog in link list.

About the BIPM 

The signing of the Metre Convention in 1875 created the BIPM and for the first time formalised international cooperation in metrology. In this way the foundations were laid for the worldwide uniformity of measurement in all aspects of our endeavours. Historically this focused on assisting industry and trade, but today it is just as vital as we tackle the grand challenges of the 21st century such as climate change, health and energy. The BIPM undertakes scientific work at the highest level on a selected set of physical and chemical quantities. The BIPM is the hub of a worldwide network of national metrology institutes (NMIs) which continue to realise and disseminate the chain of traceability to the SI into national accredited laboratories and industry. 

The Measurement Community 

The measurement community is made up of 250 institutes from 100 countries. The International Committee for Weights and Measures (CIPM) Mutual Recognition Agreement (MRA) has been signed by the representatives of 102 institutes – from 58 Member States, 42 Associates of the General Conference on Weights and Measures (CGPM), and 4 international organizations – and covers a further 157 institutes. The General Conference on Weights and Measures, established in 1875 under the terms of the Metre Convention, to represent the interests of member states. 

The Redefinition 

The International System of Units (SI) is structured around seven base units, with at least another 22 (such as volume) derived from these. It is expected that four of the seven base units (the kilogram, ampere, kelvin and the mole) will be redefined according to fixed values of natural constants. The new definitions will be based on fixed numerical values of the Planck constant (h), the elementary charge (e), the Boltzmann constant (k) and the Avogadro constant (NA), as well as on other three physical constants whose numerical values are already fixed in the present SI” or a similar formulation. Since the second, metre, and candela are already defined by physical constants such as the speed of light, this revision will make the definitions of all seven base units consistent. They will all be defined in terms of universal physical constants.
    Once the revision is implemented, the quantities for the physical constants will be fixed. The numerical values will be fixed by definition. For example, the value for the speed of light will remain the same, therefore the units defined by the speed of light – and other constants – will remain unchanged. Practically, little will change; water will still freeze at 0.00 °C, your smartphone will function as normal. But this redefinition of the SI lays strong foundations for the building blocks of future measurement and scientific research. The SI units form a foundation for measurement across the world that ensures consistency and reliability. Just like foundations are needed to keep a house from falling down, universal concepts of measurement are needed to support innovation now and into the future.

Mass 

Mass is measured in kilograms (kg). At the International Bureau of Weights and Measures in France, there is a platinum-iridium alloy cylinder called the International Prototype of the Kilogram (IPK). The mass of this artefact is what currently defines what we call a kilogram. The mass of this artefact may have changed since it was produced in 1884, but we have no way of knowing. Under the new definition, a kilogram will be defined instead by using the Planck and other constants. Using fixed, agreed upon values, these constants, as invariable features of nature, will not change; an improvement upon the IPK, an artefact, which could have changed in mass, been contaminated, or even lost. Another key benefit of the redefined kilogram will be improved scalability for measurements. When you use physical objects to measure things, accuracy decreases at sizes much smaller or larger than your standard. A pharmaceutical company, for example, may need to measure the mass of chemicals for research on new drugs in quantities that are a million times smaller than a standard kilogram. The mass of a litre bottle of soda, in contrast, is about a kilogram. So, if you used equally sophisticated equipment today, the soda could be measured more accurately than the tiny quantities in drug discovery. The new definition of the kilogram will allow much better measurements of milligram and microgram masses.
The SI unit, mass, will be defined by taking the fixed numerical value of the Planck constant h to be 6.626 070 15 × 10– 34 when expressed in the unit joules per second, which is equal to kg m2 s–1, where the metre (m) and the second (s) are defined in terms of the speed of light (c) and the hyperfine transition frequency of caesium (ΔνCs).

Distance 

Distance is measured in metres (m) In 1791, a metre was defined as one ten-millionth of the distance from the equator to the North Pole. You can probably guess how difficult this would have been to check things against. In 1875, a bar made of a platinum/iridium alloy was designated as the international prototype of the metre. While more practical, this was still not as accurate as we can now achieve. One of the issues with a prototype like this is that, over time, the length can potentially change. Since 1983, we have precisely defined a metre as the length of the path travelled by light in a vacuum in 1/299792458 of a second. This accurate definition of the metre helps us measure the size and shape of things that are large, like bridges and buildings, as well as tiny things, like proteins and viruses. The SI unit, metre, will be defined by taking the fixed numerical value of the speed of light in vacuum c to be 299 792 458 when expressed in the unit m s–1, where the second is defined in terms of the caesium frequency ΔνCs.

Time 

The unit for measuring time is seconds (s) Since 1967, the second has been defined by a number of cycles of the radiation from a particular caesium-133 transition – 9 192 631 770 to be precise. Before this, it was defined by the movement of the earth around the sun, which was recognised as not predictable enough for highly accurate timekeeping. Accurate timekeeping underpins the functioning of important technologies, like GPS or the internet, as well as having an important role timestamping trades in the financial sector.
Ancient Egyptians used sundials and the Chinese used water clocks to tell the time, which was not very precise. Now, a caesium-beam atomic clock is accurate to within 30 billionths of a second per year (and it works in all weather). The SI unit, second, is defined by taking the fixed numerical value of the caesium frequency ΔνCs, the unperturbed ground-state hyperfine transition frequency of the caesium-133 atom, to be 9 192 631 770 when expressed in the unit Hz, which is equal to s–1.

Electric current 

Electric current is measured in amperes (A) Amperes, or ‘amps’ for short, measure electric current, which is a flow of electric charge. Charge is commonly carried by electrons moving inside a wire, or, as in batteries, by ions in an electrolyte. Accurate measurement of current is important for electrical devices like smartphones and laptops, as well as for developing sustainable batteries with longer lives. Today’s SI definition of the ampere is impractical and is rarely implemented because there are alternative approaches for measuring electrical currents that are easier and more accurate. The current SI definition of the ampere describes the amount of current within two infinitely parallel wires that would produce a specific force between the wires. For over 30 years, this has meant that the best electrical measurements have been tied to quantum-based voltage standards and quantum resistance standards instead of to the official SI approach. Nature-based approaches to precision electrical measurements have been common practice since the latter part of the 20th century, and the redefinition of the SI ampere in terms of natural constants is effectively catching the definitions up to reality in the lab. The new definition of the ampere is expected to be more intuitive and easier to realise. It is tied to natural quantum phenomena that has been used to create highly accurate voltage and resistance standards since the latter part of the 20th century. The SI unit, ampere, will be defined by taking the fixed numerical value of the elementary charge e to be 1.602 176 634 × 10–19 when expressed in the unit C, which is equal to A s, where the second is defined in terms of ΔνCs. 

Temperature 

Temperature is measured in kelvin (K) It is possible for water to exist as a solid (ice), liquid and as a gas (water vapour). These three states coexist in stable equilibrium at a certain temperature, +0.01 °C, or 273.16 K. One kelvin is currently defined as 1/273.16 of this temperature. However, this definition is unsuitable for scaling measurements and accurately measuring very cold temperatures (below 20 K) and extremely hot ones (over 1300 K). When you use physical objects to measure things, accuracy decreases at sizes much smaller or larger than your standard. It is expected that the kelvin will soon be defined using the Boltzmann constant, a constant of nature. This will link the kelvin to the other SI units in a stable manner, independent of any particular substance. Accurate temperature measurements are important in a wide range of areas, including manufacturing materials with specific desired qualities. The Si unit, kelvin, will be defined by taking the fixed numerical value of the Boltzmann constant k to be 1.380 649 × 10–23 when expressed in the unit J K–1, which is equal to kg m2 s–2 K–1, where the kilogram, metre and second are defined in terms of h, c and ΔνCs. 

Amount of a substance 

The amount of a substance is measured in moles (mol) Currently, the definition of the mole is the amount of substance of a system which contains as many elementary entities as there are atoms in 0.012 kilogram of carbon 12. The new definition will remove the present link between the mole and the kilogram. The word ‘mole’ comes from the word ‘molecule’. Accurate measurements of moles are used to calculate how much of a drug goes into your body, and for producing solutions of a precise concentration. 
The SI unit, mole, will be defined as exactly 6.022 140 76 × 1023 elementary entities. This number is the fixed numerical value of the Avogadro constant, NA, when expressed in the unit mol-1 and is called the Avogadro number. The amount of substance, symbol n, of a system is a measure of the number of specified elementary entities. An elementary entity may be an atom, a molecule, an ion, an electron, any other particle or specified group of particles. 

Luminous intensity 

Luminous intensity is measured in candelas (cd) A candela was once based on the brightness of a ‘standard’ candle. However, this ‘standard’ candle varied from country to country, and from candle to candle, so this definition was not sufficiently accurate In 1948 the 'new candle' became the candela and was adopted worldwide. It was defined as: “The magnitude of the candela is such that the luminance of a full radiator at the temperature of solidification of platinum is 60 candelas per square centimetre”. In 1979 the candela was redefined in terms of the watt at only one wavelength of light. It measures luminous intensity, and can be used to calculate the brightness of lightbulbs or lasers. The candela is defined by taking the fixed numerical value of the luminous efficacy of monochromatic radiation of frequency 540 × 1012 Hz, Kcd, to be 683 when expressed in the unit lm W–1, which is equal to cd sr W–1, or cd sr kg–1 m–2 s3, where the kilogram, metre and second are defined in terms of h, c and ΔνCs. For technical or scientific press you can include the Information for users about the proposed revision of the SI from the Brand Book V2. 
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• Since 1884, the kilogram has been defined by an artefact – from 2019, it will be defined by fundamental constants of nature: URL #SIredefinition 
• Constants like the speed of light are not going to change, but a physical artefact might. We’re redefining the definition of SI units to enable future #measurement research: URL #SIredefinition 
• Water will still freeze below 273.2 K, but the way we define the kelvin is changing – learn how: URL #SIredefinition 
• #ThrowbackThursday - In 1324, an inch was defined as the length of three barleycorns. In 1983, the metre was redefined by the distance light travels in vacuum in a tiny fraction of a second. : URL #SIredefinition 
• The definition of the ampere, the unit of electric current, is becoming more intuitive and easier to realise: URL #SIredefinition 
• Under the new SI definition, if you have 6.022 140 76 ×1023 entities of a substance, you have one mole of it. Learn more: URL #SIredefinition 
• As a National Measurement Institute, we are proud to be part of the redefinition of SI units. Read more about the future of #metrology: URL #SIredefinition 
• Today is #WorldMetrologyDay – you can read more about the constant evolution of measurement: URL #SIredefinition 
• Being a fraction of a second off doesn’t make much difference when you’re boiling pasta, but it would to someone like @UsainBolt. Learn how scientists are enhancing measurement: URL #SIredefinition
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Frequently asked questions                                                         

* What are measurements for?     

Measurements are the quantitative way to compare one thing with another. The International System of Units, also known as the SI, is the most widely used system of measurement in the world. It is a coherent system of seven base units (kilogram, metre, second, ampere, kelvin, mole, candela) which allows science, industry and trade to measure all physical objects and phenomena in the same way, using the same units and get the same number. 

*How are the units of measurement defined? 

Originally measurement units were defined by physical objects or properties of materials. For example, the metre was originally defined by a metal bar exactly one metre in length and subsequently in terms of the wavelength of light. However, these physical representations can change over time or in different environments, and are no longer accurate enough for today’s research and technological applications. Over the last century scientists measured natural constants of nature, such as the speed of light and the Planck constant, with increasing accuracy. They discovered that these were more stable than physical objects, and fixed numerical values to these constants. Therefore, the SI base measurement units are being redefined so that they are rely on these natural constants, the most stable things known in the physical world. These natural constants do not vary, so are at least one million more times more stable.

*Why do we need more accurate definitions? 

As science advances, ever more accurate measurements are both required and achievable. The standard and definition must reflect this increasing accuracy. The kilogram has been based on a physical object certified in 1889, consisting of a cylinder of platinum-iridium and it is the last unit to be based on an actual object. Its stability has been a matter of significant concern, resulting in recent proposals to change the definition to one derived from constants of nature. Page | 24 By defining measurement units in terms of constants means that the definitions of the units do not need to be changed over time. If we develop more accurate ways of measuring these constants, the definitions still apply, they can just be realised with greater accuracy. 

What is the SI?               

The International System of Units (SI) is a globally agreed system of measurements. The SI has seven base units and a number of derived units defined in terms of the base units. The SI units express measurements of any quantity like physical size, temperature or time. This International System of Units is necessary to ensure that our everyday units of measurement, whether of a metre, or a second, remain comparable and consistent worldwide. Being inaccurate by a fraction of a second might not matter for cooking pasta, but it becomes very important for determining who won the 100 metres at the Olympics or in high frequency stock market trading. Standardising such measurements, not only helps to keep them consistent and accurate, but also helps society to build confidence. For instance, the kilogram is used every day, and defining this unit helps to outline how much food a shop is selling, and means that consumers can trust that the shop is really providing the amount they say they are. This consistency is also relied on to ensure the correct dosage of medicine is taken even when measurements are very small. In 1889 the international prototypes for the metre and the kilogram, together with the astronomical second as the unit of time, were units constituted as the base units metre, kilogram, and second, the original MKS system. In 1946 the scope of this was extended to adopt the ampere giving the four-dimensional system based on the metre, kilogram, second, and ampere, the MKSA system. Following an international inquiry by the BIPM, in 1954 the introduction of the ampere, the kelvin and the candela as base units was approved joining the original MKSA system. The name International System of Units, with the abbreviation SI, was given to the system in 1960. The creation of the decimal metric system, the ancestor to the SI, was considered to be on 22 June 1799, when two platinum standards representing the metre and the kilogram were deposited in the Archives de la République in Paris. 

What are the seven base units? 

• The kilogram (kg) – the SI base unit of mass 
• The metre (m) – the SI base unit of length 
• The second (s) – the SI base unit of time 
• The ampere (A) – the SI base unit of electrical current 
• The kelvin (K) – the SI base unit of thermodynamic temperature 
• The mole (mol) – the SI base unit of an amount of substance 
• The candela (cd) – the SI base unit of luminous intensity 
For further information on how to use SI units, please visit: www.bipm.org/en/measurement-units/base-units.html 

Why is the SI important? 

The SI units form a foundation for measurement across the world to ensure consistency and reliability. Just like foundations are needed to keep a house from falling down, universal concepts of measurement are needed to support innovation now and in the future. SI units can provide new opportunities for innovation. Some examples where greater accuracy is supporting better methods and understanding with a positive impact on society include: 
• The accurate measurement of temperature. This will support the ability to identify and measure reliably very small changes across large time periods with greater accuracy. Therefore, it will allow for more precise monitoring and better predictions for climate change. 
• The more accurate administration of drugs. The pharmaceutical industry needs to use a standard for very small amounts of mass in order to make dosages of medication even more appropriate for patients. SI units can help us support innovation into the future. As our ability to measure properties improves, the standards we have for measurement will need to keep up. SI units based on physical constants are important for developments to come:
• The accuracy of services like Global Positioning System (GPS) are limited by our ability to use standard units, in this case, the second to measure time We can track our locations effectively because we can establish time using the SI definition of a second, which can be realised by an atomic clock. This advancement was made possible because society had defined the second more accurately well before we had even discovered what it could be used for. The atomic clock was made before computing really took off. Now accurate timing is a fundamental part of the industry; without it the internet, mobile phones and other technologies could not work reliably. 

What is the SI redefinition? 

The global metrology community anticipates that a revision to the SI units will be agreed in 2018, when the General Conference on Weights and Measures (CGPM) meets from the 13-16 November. This decision is expected to mean a more practical definition of the SI. All of the units would be expressed in terms of constants that can be observed in the natural world (for example, the speed of light, the Planck constant and the Avogadro constant). Using these unchanging standards as the basis for measurement will mean that the definitions of the units will remain reliable and unchanging into the future. The new definitions will be based on fixed numerical values of the Planck constant (h), the elementary charge (e), the Boltzmann constant (k) and the Avogadro constant (NA), as well as on other three physical constants whose numerical values are already fixed in the present SI” or a similar formulation.. 
You can find more information on the constants the SI units will be based on here: www.bipm.org/en/measurement-units/rev-si/ 

Why do we need this change? 

For the first time we will see all base units in the SI dictated by constants of physical science we observe in nature. Using the constants we have found in nature as our universal basis for measurement allows not only scientists, but also industry and society, to have a measurement system that is more reliable, consistent, and scalable across quantities, from very Page | 27 large to very small. This change is needed to ensure that the definitions will not need to be modified to accommodate innovation and even more accurate measurement techniques in future. 
There are two key ways the SI will change to create a more stable and future-proof basis for measurement: It will take physical artefacts out of the equation:
• Many of the SI units began life based on a physical artefact. Previously, in order to ensure that quantities like the metre remained consistent, there was a physical representation of the measure (such as a metre stick) that was used as a basis for all of the other metres globally. The kilogram is still defined by a physical object– equal to the mass of the International Prototype of the Kilogram (IPK), a physical artefact stored at the International Bureau of Weights and Measures in France. 
• This technique has the limitation that the properties of the artefact may change over time and it could be damaged. There can also be changes to size due to the process of translating measurements from one artefact to another. As a replica is created from the original kilogram, small differences could occur that may not be noticed immediately, but in time, and with improvements in technology and science, may become significant. 
• It can also be extremely difficult to check measurements this way. Not only because the physical artefact will need to undergo a process of cleaning to ensure nothing is affecting the measurement (apparently chamois leather will do the trick for the IPK) but if we want a universal standard for measurements we need a definition that can be realised anywhere. As such, a change is necessary to democratise this process, so that definitions can be checked anywhere in the world. Separating the realisation of the unit from its definition for the first time ever: 
• For the first time all the definitions will be separate from their realisations. Instead of definitions becoming outdated as we find better ways to realise units, definitions will remain constant and future proof. 
• For example, the ampere is currently defined as the magnetic force between two wires at a certain distance apart, which means that it uses the realisation of measurement to define it. However, advancements like the development of digital voltmeters and the advent of the Josephson Effect, have revealed better ways of realising the ampere, making the original approach obsolete. 

What does this mean in practice? 

On the surface, it will appear not much has changed. In the same way that if you replaced the decaying foundations of a house with new shiny ones, it may not be possible to identify the difference from the surface, but some substantial changes have taken place to ensure the longevity of the property. These changes will ensure that the SI definitions will never become outdated by advancements in technology, but will continue to remain robust. 

When will the proposed change come into effect? 

Redefinition, if agreed, will come into practice on World Metrology Day, 20 May 2019.

What is World Metrology Day? 

World Metrology Day is an annual event on 20 May during which more than 80 countries celebrate the impact measurement has on our daily lives. On this day, the international metrology community, which works to ensure that accurate measurements can be made across the world, raises awareness of the impact and importance of having reliable measurements. The theme for World Metrology Day 2018 is Constant Evolution of the International System of Units (SI). This year’s theme was chosen due to the proposed SI redefinition, expected to be agreed in November 2018, when the General Conference on Weights and Measures meets. This will be one of the largest changes to the International System of Units (the SI) since its inception. The date marks the beginning of a formal international collaboration in metrology in 1875, when the first international measurement treaty, the Metre Convention, was signed by representatives from 17 nations to agree on the coordination of measurement. 
This treaty saw the creation of organisations to oversee the running of the institute, including the General Conference on Weights and Measures, CGPM. In 1921, at the 6th meeting of the CGPM, the mandate of the body was extended from mass and length to all physical measurements. In 1960, at the 11th meeting, the ‘International System of Units’ was established.

Who agrees to the SI? 

The signing of the Metre Convention in 1875 saw the creation of the BIPM. It operates under the supervision of the CIPM which is itself set under the authority of the CGPM. The CGPM is the General Conference on Weights and Measures that meets every four to six years. With delegates from all of the 59 member states, this body discusses and chooses to endorse changes to the SI, after taking on board advice from the CIPM. The CIPM is the International Committee for Weights and Measures. It is a committee made up of eighteen individuals, each of a different nationality, nominated by the CGPM for their high level of understanding in the field. The CIPM is still to this day responsible for decisions about the SI with the goal of creating a reliable basis for measurements that can be used now and into the future. The international community now includes 59 Member States, and 42 Associate States and Economies. The BIPM is the International Bureau of Weights and Measures based in Sèvres where it has laboratories that provide metrology services for the member states. It also carries out coordination and liaison activities and houses the secretariat for the CIPM and its consultative committees. The BIPM’s original purpose was to house the international prototypes defining units of the SI, as such it is where the international prototype of the kilogram resides.

Monday, October 8, 2018

The Nobel Peace Prize 2018



The Nobel Peace Prize 2018





Prize share: 1/2

Prize share: 1/2
The Nobel Peace Prize 2018 was awarded jointly to Denis Mukwege and Nadia Murad "for their efforts to end the use of sexual violence as a weapon of war and armed conflict."

2018 Nobel Prize in Physiology or Medicine


Press release 2018-10-01
Nobel Assembly logo
has today decided to award
the 2018 Nobel Prize in Physiology or Medicine
jointly to

James P. Allison and Tasuku Honjo

for their discovery of cancer therapy by inhibition of negative immune regulation

SUMMARY

Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy.

James P. Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors. He then developed this concept into a brand new approach for treating patients.

In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer.

Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer.

Can our immune defense be engaged for cancer treatment?

Cancer comprises many different diseases, all characterized by uncontrolled proliferation of abnormal cells with capacity for spread to healthy organs and tissues. A number of therapeutic approaches are available for cancer treatment, including surgery, radiation, and other strategies, some of which have been awarded previous Nobel Prizes. These include methods for hormone treatment for prostate cancer (Huggins, 1966), chemotherapy (Elion and Hitchins, 1988), and bone marrow transplantation for leukemia (Thomas 1990). However, advanced cancer remains immensely difficult to treat, and novel therapeutic strategies are desperately needed.
In the late 19th century and beginning of the 20th century the concept emerged that activation of the immune system might be a strategy for attacking tumor cells. Attempts were made to infect patients with bacteria to activate the defense. These efforts only had modest effects, but a variant of this strategy is used today in the treatment of bladder cancer. It was realized that more knowledge was needed. Many scientists engaged in intense basic research and uncovered fundamental mechanisms regulating immunity and also showed how the immune system can recognize cancer cells. Despite remarkable scientific progress, attempts to develop generalizable new strategies against cancer proved difficult.

Accelerators and brakes in our immune system

The fundamental property of our immune system is the ability to discriminate “self” from “non-self” so that invading bacteria, viruses and other dangers can be attacked and eliminated. T cells, a type of white blood cell, are key players in this defense. T cells were shown to have receptors that bind to structures recognized as non-self and such interactions trigger the immune system to engage in defense. But additional proteins acting as T-cell accelerators are also required to trigger a full-blown immune response (see Figure). Many scientists contributed to this important basic research and identified other proteins that function as brakes on the T cells, inhibiting immune activation. This intricate balance between accelerators and brakes is essential for tight control. It ensures that the immune system is sufficiently engaged in attack against foreign microorganisms while avoiding the excessive activation that can lead to autoimmune destruction of healthy cells and tissues.

A new principle for immune therapy

During the 1990s, in his laboratory at the University of California, Berkeley, James P. Allison studied the T-cell protein CTLA-4. He was one of several scientists who had made the observation that CTLA-4 functions as a brake on T cells. Other research teams exploited the mechanism as a target in the treatment of autoimmune disease. Allison, however, had an entirely different idea. He had already developed an antibody that could bind to CTLA-4 and block its function (see Figure). He now set out to investigate if CTLA-4 blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells. Allison and co-workers performed a first experiment at the end of 1994, and in their excitement it was immediately repeated over the Christmas break. The results were spectacular. Mice with cancer had been cured by treatment with the antibodies that inhibit the brake and unlock antitumor T-cell activity. Despite little interest from the pharmaceutical industry, Allison continued his intense efforts to develop the strategy into a therapy for humans. Promising results soon emerged from several groups, and in 2010 an important clinical study showed striking effects in patients with advanced melanoma, a type of skin cancer. In several patients signs of remaining cancer disappeared. Such remarkable results had never been seen before in this patient group.


Figure: 
Upper left: Activation of T cells requires that the T-cell receptor binds to structures on other immune cells recognized as ”non-self”. A protein functioning as a T-cell accelerator is also required for T cell activation. CTLA- 4 functions as a brake on T cells that inhibits the function of the accelerator. 
Lower left: Antibodies (green) against CTLA-4 block the function of the brake leading to activation of T cells and attack on cancer cells.
Upper right: PD-1 is another T-cell brake that inhibits T-cell activation. 
Lower right: Antibodies against PD-1 inhibit the function of the brake leading to activation of T cells and highly efficient attack on cancer cells.

Discovery of PD-1 and its importance for cancer therapy

In 1992, a few years before Allison’s discovery, Tasuku Honjo discovered PD-1, another protein expressed on the surface of T-cells. Determined to unravel its role, he meticulously explored its function in a series of elegant experiments performed over many years in his laboratory at Kyoto University. The results showed that PD-1, similar to CTLA-4, functions as a T-cell brake, but operates by a different mechanism (see Figure). In animal experiments, PD-1 blockade was also shown to be a promising strategy in the fight against cancer, as demonstrated by Honjo and other groups. This paved the way for utilizing PD-1 as a target in the treatment of patients. Clinical development ensued, and in 2012 a key study demonstrated clear efficacy in the treatment of patients with different types of cancer. Results were dramatic, leading to long-term remission and possible cure in several patients with metastatic cancer, a condition that had previously been considered essentially untreatable.

* Immune checkpoint therapy for cancer today and in the future


After the initial studies showing the effects of CTLA-4 and PD-1 blockade, the clinical development has been dramatic. We now know that the treatment, often referred to as “immune checkpoint therapy”, has fundamentally changed the outcome for certain groups of patients with advanced cancer. Similar to other cancer therapies, adverse side effects are seen, which can be serious and even life threatening. They are caused by an overactive immune response leading to autoimmune reactions, but are usually manageable. Intense continuing research is focused on elucidating mechanisms of action, with the aim of improving therapies and reducing side effects.

Of the two treatment strategies, checkpoint therapy against PD-1 has proven more effective and positive results are being observed in several types of cancer, including lung cancer, renal cancer, lymphoma and melanoma. New clinical studies indicate that combination therapy, targeting both CTLA-4 and PD-1, can be even more effective, as demonstrated in patients with melanoma. Thus, Allison and Honjo have inspired efforts to combine different strategies to release the brakes on the immune system with the aim of eliminating tumor cells even more efficiently. A large number of checkpoint therapy trials are currently underway against most types of cancer, and new checkpoint proteins are being tested as targets.

For more than 100 years scientists attempted to engage the immune system in the fight against cancer. Until the seminal discoveries by the two laureates, progress into clinical development was modest. Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed.

Key publications


Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992). Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 11(11), 3887–3895.



Leach, D. R., Krummel, M. F., & Allison, J. P. (1996). Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271(5256), 1734–1736.



Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C., Feldhaus, A. L., Greenberg, N. M., Burg, M.B. & Allison, J.P. (1997). Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci USA, 94(15), 8099–8103.



Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999). Development of Lupus-like Autoimmune Diseases by Disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 11, 141–151.

Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., Horton, H.F., Fouser, L., Carter, L., Ling, V., Bowman, M.R., Carreno, B.M., Collins, M., Wood, C.R. & Honjo, T. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med, 192(7), 1027–1034.

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James P. Allison was born 1948 in Alice, Texas, USA. He received his PhD in 1973 at the University of Texas, Austin. From 1974-1977 he was a postdoctoral fellow at the Scripps Clinic and Research Foundation, La Jolla, California. From 1977-1984 he was a faculty member at University of Texas System Cancer Center, Smithville, Texas; from 1985-2004 at University of California, Berkeley and from 2004-2012 at Memorial Sloan-Kettering Cancer Center, New York. From 1997-2012 he was an Investigator at the Howard Hughes Medical Institute. Since 2012 he has been Professor at University of Texas MD Anderson Cancer Center, Houston, Texas and is affiliated with the Parker Institute for Cancer Immunotherapy.
Tasuku Honjo was born in 1942 in Kyoto, Japan. In 1966 he became an MD, and from 1971-1974 he was a research fellow in USA at Carnegie Institution of Washington, Baltimore and at the National Institutes of Health, Bethesda, Maryland. He received his PhD in 1975 at Kyoto University. From 1974-1979 he was a faculty member at Tokyo University and from 1979-1984 at Osaka University. Since 1984 he has been Professor at Kyoto University. He was a Faculty Dean from 1996-2000 and from 2002-2004 at Kyoto University.

Illustrations: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén
The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humankind.
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Nobel Prize in Chemistry 2018


Press release: The Nobel Prize in Chemistry 2018


English
English (pdf)
Swedish
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3 October 2018
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2018
with one half to
Frances H. ArnoldCalifornia Institute of Technology, Pasadena, USA
“for the directed evolution of enzymes”
and the other half jointly to
George P. Smith
University of Missouri, Columbia, USA
and
Sir Gregory P. Winter
MRC Laboratory of Molecular Biology, Cambridge, UK
“for the phage display of peptides and antibodies”

They harnessed the power of evolution

The power of evolution is revealed through the diversity of life. The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and in some cases cure metastatic cancer.
Since the first seeds of life arose around 3.7 billion years ago, almost every crevice on Earth has filled with different organisms. Life has spread to hot springs, deep oceans and dry deserts, all because evolution has solved a number of chemical problems. Life’s chemical tools – proteins – have been optimised, changed and renewed, creating incredible diversity.
This year’s Nobel Laureates in Chemistry have been inspired by the power of evolution and used the same principles – genetic change and selection – to develop proteins that solve mankind’s chemical problems.
One half of this year’s Nobel Prize in Chemistry is awarded to Frances H. Arnold. In 1993, she conducted the first directed evolution of enzymes, which are proteins that catalyse chemical reactions. Since then, she has refined the methods that are now routinely used to develop new catalysts. The uses of Frances Arnold’s enzymes include more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels for a greener transport sector.
The other half of this year’s Nobel Prize in Chemistry is shared by George P. Smith and Sir Gregory P. Winter. In 1985, George Smith developed an elegant method known as phage display, where a bacteriophage – a virus that infects bacteria – can be used to evolve new proteins. Gregory Winter used phage display for the directed evolution of antibodies, with the aim of producing new pharmaceuticals. The first one based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Since then, phage display has produced anti-bodies that can neutralise toxins, counteract autoimmune diseases and cure metastatic cancer.
We are in the early days of directed evolution’s revolution which, in many different ways, is bringing and will bring the greatest benefit to humankind.

Illustrations

The illustrations are free to use for non-commercial purposes. Attribute ”©Johan Jarnestad/The Royal Swedish Academy of Sciences”
(R)evolution (pdf)

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Frances H. Arnold, born 1956 in Pittsburgh, USA. Ph.D. 1985, University of California, Berkeley, USA. Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry, California Institute of Technology, Pasadena, USA.
http://fhalab.caltech.edu
George P. Smith, born 1941 in Norwalk, USA. Ph.D. 1970, Harvard University, Cambridge, USA. Curators’ Distinguished Professor Emeritus of Biological Sciences, University of Missouri, Columbia, USA.
http://biology.missouri.edu/people/?person=94
Sir Gregory P. Winter, born 1951 in Leicester, UK. Ph.D. 1976. University of Cambridge, UK. Research Leader Emeritus, MRC Laboratory of Molecular Biology, Cambridge, UK.
www2.mrc-lmb.cam.ac.uk/group-leaders/emeritus/greg-winter/
Prize amount: 9 million Swedish krona, with one half to Frances Arnold and the other half to be shared between George Smith and Gregory Winter.
Further information: www.kva.se and http://www.nobelprize.org
Press contact: Kajsa Waaghals, Press Officer, +46 70 878 67 63, kajsa.waaghals@kva.se
Expert:Sara Snogerup Linse, member of the Nobel Committee for Chemistry, +46 70 250 77 66, sara.linse@biochemistry.lu.se
The Royal Swedish Academy of Sciences, founded in 1739, is an independent organisation whose overall objective is to promote the sciences and strengthen their influence in society. The Academy takes special responsibility for the natural sciences and mathematics, but endeavours to promote the exchange of ideas between various disciplines.


Nobel Prize® is a registered trademark of the Nobel Foundation.