Curious Cook: Food, proteins and googly eyes on fish

My sister and her family recently came to stay in France, and one of their consistent comments was how good and “different” food tastes here – and were therefore curious about the “secret”.

September 23, 2018 

By CHRIS CHAN

Of course, there is no secret as such. For one, the food raised in France (and other parts of Europe) is different from food in Asia. By different, I mean the varieties of vegetables, fruits and animals here are distinct from other parts of the world. The preparation of the food is also often different, and I am also particularly fussy – for example, to get the right bangers for a barbecue, we made a return trip of around 100km to a butcher who sold sausages hand-crafted from pigs raised in the Cantal region.

There are, of course, several other items for which I would consider making such a long trip and top of the list would be good Malaysian durians – but sadly, there is no chance of that here as durians are still banned on flights.

This fussiness applies even to little things like salt. It is hard to believe but there are significant differences in the taste of salt. My personal preference is for Fleur De Sel De Guérande – if you are curious, try comparing a sample with ordinary salt side by side. The difference is usually due to the desiccants and/or flow-improvers in normal table salt.

French cheese Reblochon is made with raw, unpasteurised milk. Photo: The Star

France is largely agricultural and many regions are littered with remote farming communities where there is only one obscure road in and the same route out. Industrial farming is impossible and these communities mainly supply local markets with produce seldom contaminated by modern additives or processes used for mass production.

This is not always riskless – many fine French cheeses are made with “lait cru” or raw, unpasteurised milk and there was recently a recall of many tonnes of Reblochon de Savoie after some batches were found to be contaminated with E. coli. This outbreak had caused hemolytic-uremic syndrome in six out of seven affected children (though nobody died).

Statistically, this still makes eating Reblochon safer than crossing a road, so for that reason, such stories seldom bother me – though I would never offer young children cheese made with unpasteurised milk, just in case.

The right type of ingredients matter very significantly, especially in countries where there are few heavy spices to cover any deficiencies in food elements. For example, the closest to a French national dish might be boeuf bourguinon, a heady stew of beef, Provence herbs and red wine.

Boeuf bourguignon is made with few ingredients, unlike a Malaysian beef curry (see main image, top), which is often heavily spiced. Photos: The Star

In theory, it should be very easy to make (as it is mostly boiling lumps of beef for hours in wine and herbs) but it took a year before getting it right. The main problems were the cuts of meat used and the wine selection, according to a professional cook. So changing the meat for a fresher tougher cut and using a lighter Cote du Rhone (and adjusting the balance of herbs) now results in a pretty good stew every time.

I would probably not bother to make boeuf bourguinon in tropical Asian countries. This is because most “beef” in many South-East Asian countries is actually water buffalo imported from India. The other issue may also be the freshness of meat in tropical climates. Meat decomposes and changes its flavour very quickly, especially at warm temperatures – this rapid decomposition is mainly due to aerobic bacteria breaking down meat proteins and spoiling the flavour.

Hence in the Far East, it would make much more sense to cook food with strong spices or flavours to counteract any possible issues with meat protein decomposition. And of course, this is what most people do.

Check the eyes for freshness. Photo: The Star

Googly eyes

A funny story recently is the use of plastic googly eyes by a Kuwaiti fishmonger to cover the rotting eyes of old fish – a common way to test the freshness of fish is to check the decomposition of the eyes. The other is to check the redness underneath the gills. This indicates that consumers are acutely aware of the problems of protein decomposition.

Snack bars

This brings us round to the subject of proteins itself, especially in the modern diet. My daughter recently informed me that dietary protein is now such a fad that even confectionery manufacturers now offer protein-rich snack bars. This was a surprise to me, but a quick search proved she was right – you can get protein-rich Mars, Snickers and Bounty bars, for example. The Carnivore Diet is also an off-shoot of this protein fad. See “A modern food story – Part 1”.

Proteins

After ingestion, proteins are digested down into amino acids which are then released into the blood stream. Amino acids are extremely important as they are the building blocks of enzymes, antibodies, hormones, muscles and connective tissues such as collagen, without which the body simply cannot survive – and we cannot produce all the required amino acids so we require them in our diets. Humans need around 0.8g of protein per kilo of body weight.

One fact about proteins is they provide fewer digestible calories than carbohydrates and fat – as often stated before, not all calories from food are equal. This is because of the Thermic Effect of Food (TEF) which basically means that proteins take up five times more energy to digest compared to carbohydrates and fats. Hence, a piece of lean meat or soy protein delivers fewer calories than a fried doughnut of the same weight. This was reviewed in “The perils of dieting – Part 1”.

The TEF is also known as dietary-induced thermogenesis and appears to be the rationale behind many of the protein diet fads. Unlike dietary carbohydrates, which are chains of glucose molecules easily freed by enzymes (eg. amylase, galactose, sucrase, etc) into energy-giving glucose molecules, proteins are digested via a completely different pathway.

Proteins are more difficult to convert into energy for two reasons: (i) proteins contain nitrogen; and (ii) the digestive system needs to break down the peptide bonds holding together polypeptides. A string of amino acids is a polypeptide and proteins are either polypeptides or chains of polypeptides. Degradation of proteins is known as proteolysis and the first stage is denaturation of proteins in the extremely acidic environment of the stomach, plus the introduction of a stomach enzyme called pepsin. The deconstruction of proteins is further enhanced by the enzymes trypsin, chymotrypsin, carboxypeptidase A and B and elastase produced by the pancreas while passing into the intestines via the duodenum (where bicarbonate is introduced to raise pH to the level needed for the pancreatic enzymes to function efficiently).

After reducing proteins into amino acids, the amino acids are then passed into the intestinal cell walls and released into the bloodstream to be absorbed by other tissues.

Excess amino acids produced after digestion cannot be stored, and can then be converted into energy. These excess amino acids are subjected to processes called transamination and deamination, which remove the nitrogen molecules in amino acids, thereby reducing amino acids to carbon-based structures (such as pyruvate) which can be converted into glucose (energy) or stored as fat. The nitrogen is freed as ammonia, extracted from the bloodstream by the liver and passed for excretion by the kidneys as urea.

Due to the increase in urea production, anyone with chronic kidney diseases may be negatively affected by high protein diets. Healthy people generally have no issues with any amount of protein.

Although a high-protein diet may help weight loss due to the TEF of proteins, in many ways it is not significantly better than eating raw vegetables, which also have a high TEF. Also, a recent cohort study published in The Lancet (based on 432,179 participants) found that high-protein diets involving mainly animal proteins shortened lifespans (the reasons were not investigated). The study also suggested getting 50% to 55% of daily energy requirements from carbohydrates extended lifespans.

In summary, there is no compelling reason to pursue a high-protein diet but if you must do so, then consider a diet with a much higher proportion of non-animal proteins. There is even less sense in eating expensive sugary confections with added protein – if you investigate the protein content, much of it are by-products from other food processing. Examples are hydrolysed collagen, soy protein isolate, milk protein isolate, skimmed milk powder, whey protein, egg albumen, etc, all mixed with sugars and fats.

https://www.star2.com/food/2018/09/23/curious-cook-food-proteins-googly-eyes-on-fish/

Theranos: Scandal hit blood-testing firm to shut

Scandal-hit US blood-testing start-up Theranos is to formally dissolve, the firm's chief executive David Taylor has told shareholders in an email.

BBC NEWS   5 September 2018

Mr Taylor said Theranos had run "out of time" to secure further investment or secure a buyer for its assets.

Theranos founder Elizabeth Holmes and former president Ramesh Balwani are facing criminal charges of wire fraud.

Prosecutors say they engaged in a multi-million dollar scheme to defraud investors, doctors and patients.

Mr Taylor, who also serves as general counsel to the firm, said that Theranos had engaged the services of investment bank Jeffries to try to "maximise the value of the company" for shareholders.

• Theranos founder hit with criminal charges
• Bad blood: The rise and fall of Theranos

In the email obtained by the Wall Street Journal, he said the investment bank had "reached out" to over 80 potential buyers, but to no avail.

"Unfortunately, none of those leads has materialized into a transaction. We are now out of time," he wrote.

Mr Taylor said the firm had breached the terms of its loan agreement with investor Fortress Investment Group, meaning the firm was now entitled to sell or take ownership of Theranos' intellectual property and assets.

Shareholders are expected to receive nothing after the firm's collapse.

Criminal charges

Theranos, founded in 2003 when Ms Holmes was 19, had claimed its Edison devices could test for conditions such as cancer and cholesterol with only a few drops of blood from a finger-prick, rather than taking full blood samples by needle from a vein.

Ms Holmes raised over $700m in funding for Theranos, but when she tried to pitch the technology to the US Department of Defense in 2012, her pitch was rejected due to the devices' unpredictable results.

The Wall Street Journal began investigating and published a series of exposes starting from October 2015.

Theranos denounced these articles, but by June 2016 it was facing legal challenges from investors, medical authorities and five federal agencies.

In April 2017, the Centers for Medicare and Medicaid Services (CMS) sanctioned Theranos and revoked its clinical laboratory testing certificate, which caused the pharmacy chain Walgreens to terminate its partnership with the start-up and sue Theranos for $140m.

In March, Ms Holmes settled charges with the Securities and Exchange Commission, a top US financial regulator.

The regulator alleged that Theranos, Ms Holmes and Mr Balwani made a series of false and misleading statements in investor presentations, product demonstrations and interviews.

As part of the settlement, Ms Holmes had to return millions of shares to the privately held company and pay a $500,000 fine. She was also banned from serving as an officer or director of a public company for 10 years.

https://www.bbc.co.uk/news/business-45418615

List of Theranos postings on this blog :

1. Theranos: Scandal hit blood-testing firm to shut
2. Theranos founder Elizabeth Holmes indicted for alleged fraud, out as CEO
3. The rise and fall of Elizabeth Holmes ...
4. Lesson of Theranos: Fact-Checking Alone Isn't Enough
5. A 31-year-old's fight to disrupt a $75 billion industry
6. TEDMED: Elizabeth Holmes Lab testing reinvented
7. Blood, Simpler: One Woman's Drive to Revolutionize Medical Testing

This post is on Healthwise

Curious Cook: A modern food story – Part 3

Closer to home, France recently legislated against vegetarian foods being sold as “burgers” or “sausages”, even if they are shaped like burgers and sausages.

August 26, 2018 Food, Food News

By CHRIS CHAN

The writer’s daughter’s UMF burger dinner. Photo: Chris Chan

READ:   Part 1    Part 2

Airline food

New Zealand’s Deputy Prime Minister (then Acting PM) complained recently about a burger on his national airline. The burger is the Impossible Burger, a moist, meaty-tasting burger made entirely from vegetarian products and has the ability to “bleed” like real ground beef – in blind tastings, several professional cooks have confirmed it tastes better than real burgers.

Closer to home, France recently legislated against vegetarian foods being sold as “burgers” or “sausages”, even if they are shaped like burgers and sausages.

These are examples of governments pandering to their huge livestock industries, and they are blowing against the wind. New vegetarian foods which simulate meat, packed with flavour and nutrition, produced with technology unheard of even 15 years ago, are the future of food. It is certain we will see supermarkets selling these ultra-modern foods (UMF) in huge quantities once the food industry manages to reduce cost of production.

Cost

A good UMF burger currently costs around 50% to 100% more than a comparable premium beef burger. This sounds expensive but the original gluten-free loaves used to cost three times (300%) the price of normal bread, and they tasted like flip-flops.

However, the real cost of the beef burger is much higher – and you do not get charged money for it because this cost is not counted in terms of money, and everybody in the world is forced to pay for meat. More on this later.

Technology

The production of UMFs uses some of the latest food technologies available, including genetic engineering, to recreate the textures, flavours and characteristics of real meat. Although most of these techniques are proprietary, researching around the subject indicates that UMFs use plant proteins from grains, root vegetables, beans, fungi and other non-meat sources to simulate the textures and taste of meat.

The curious red juice or “blood” which oozes from some UMFs can be modified beetroot or other vegetable juices, or in at least one case, made from genetically-modified (GMO) yeast which synthesises a close relative of myoglobin (the red juice of meat) called leghemoglobin which is normally found in the roots of soy plants.

GMO

Although some might recoil at eating GMO food, there is one important difference between genetically synthesising taste compounds and synthesising compounds used for pest control. For example, the anthrax-related insect-killing Bt-toxin found in GMO corn is introduced by splicing bacterial genes from bacillus thuringiensis into corn DNA so that corn plants themselves produce Bt-toxin even more efficiently than bacillus thuringiensis. If you are curious, please read “The verdict’s still out on genetically modified food”.

For UMFs, genetic engineering is applied to prolific organisms such as yeast to induce the production of isomers of non-toxic taste compounds. This is much the same technology used in the manufacture of medical insulin. As there is no replication of toxic compounds involved, no health concerns are presented. These GMO compounds are then used to add flavours/textures to UMFs.

Taste

Taste is probably the most critical factor in the acceptability of UMFs, and technology may have solved this complicated issue. Standard vegetarian ingredients are treated using non-standard techniques (eg. enzymatic reactions, fermentation, dessication and reconstitution, etc) to alter textures, taste profiles – and in some cases even chemical compositions. The results are new ingredients which taste remarkably like animal proteins, with nutrition profiles roughly comparable to meats.

As an aside, a reason raw meat “bleeds” is because of the heme in myoglobin, the red liquid in meats people often confuse with blood. This iron-based compound makes myoglobin reddish and this colour is often taken as a sign of tenderness and freshness. Cooking changes the colour of myoglobin to beige. However, the taste of meat is the summation of several hundred different compounds – and oxidation/spoilage of some of these compounds leads to a loss of taste in meat. Hence, although vegetarian substitutes of myoglobin such as leghemoglobin may lead to a better visual perception, the actual reason why many UMFs taste great is simply because they contain complex compounds carefully engineered to simulate the taste of meat. These compounds, being plant-based, are less likely to spoil easily – therefore UMFs can stay fresh and tastier for longer as they do not oxidise as quickly as meat.

Why?

There are several good reasons UMFs should be adopted to replace animal-based proteins.

For a start, the production of meat is appallingly inefficient. For every 1,000 calories fed to a cow, we get back only 30 calories of meat, a loss of 97% of the original energy provided. This is comparable to using a 100W bulb and getting the output of an imperceptible 3W toy light.

Another reason is environmental. The Commonwealth Scientific and Industrial Research Organisation estimated in 2013 each kilo of beef generates up to 1,000kg of greenhouse gases (GHG). But according to the UN’s Food and Agriculture Organization, each kilo of beef produces 295kg of GHG – so let us take the lower number. In the US where on average everyone eats 26kg of beef a year, almost 2.5 billion tonnes of greenhouse gases are caused by 325 million Americans alone. Over 55% of all agricultural land is now used for producing animal feed. As demand for meat presently still seems to be growing globally, the environmental toll can only increase. This is the hidden cost of meat mentioned earlier – we do not pay for this cost in monetary terms, but eventually our descendants will pay for our meat today. More at “Vegetarianism and other dietary tales – Part 5”.

The Impossible Burger. Could meatless burgers be better for us than packaged meats? Photo: impossiblefoods.com

Why not?

If we can accept that sausages, burgers and packaged meats are not actually real meat, and in some cases mostly animal by-products, it is only a small step to recognising that if something tastes just as good, then it may be safer and healthier to eat the alternative option. You will also avoid eating additives such as antibiotics, growth hormones, artificial conditioners, colours and preservatives. I would also add pesticides as food grown for animal consumption do not meet the same standards as for humans.

So for people on the Carnivore Diet, it actually makes more sense to follow a diet based on UMFs, especially as research indicates excessive eating of animal protein significantly reduces lifespans.

Shrimp eyes

We all know about the appalling conditions of most animals reared for meat, but it seems we still do not know enough. Some cattle are injected with papain (a powerful papaya-based enzyme for tenderising meat) prior to being slaughtered. Female shrimp have their eyes physically cut out to encourage them to breed faster, in a process called eyestalk ablation – and then they are thrown back into (usually) filthy pools. Hens have their beaks burnt off to stop them hurting each other in (extremely) crowded farms. All this is done to sell more animal protein, when new modern food technologies are available to eliminate such incredible cruelty.

Maillard reaction

Since UMFs are also proteins (ie, chains of amino acids), cooking them can utilise the same techniques as with meats. Include some simple sugars, heat above 135°C on a pan and UMF proteins will brown and create Maillard compounds just as for meats. In fairness, the taste is often different but this can be mitigated by using small quantities of meat at the browning stage of cooking. A simple trick is to brown a little organic minced meat in a hot pan before adding UMF proteins when making a stew – the taste difference is negligible, even to a fussy meat-lover such as myself.

For details, please read “The Maillard reaction”.

Nutrition

It is often suggested that plant protein is somehow inferior to animal protein. There is absolutely no basis for this claim in modern society – in fact there are no known incidents in the EU for protein-deficiency diseases such as marasmus and kwashiorkor despite several countries having 9% (or more) of the population as vegetarians.

Having a wholly non-meat diet may raise only one major issue: Vitamin B12.

A normal human body requires 2.4 micrograms of vitamin B12 every day, which is an important nutrient used in red blood cells, DNA, repairing nerve cells and other functions. Vegetables do not have this vitamin, and the body cannot manufacture it – hence it must come from the diet. Although commonly found in meats, vitamin B12 can also be found in fortified breads and cereals, along with cheeses and eggs.

Health, anyone?

Perhaps the best aspect of UMFs (apart from tasting good) is that they are also inherently healthier and more convenient than meat. There is often no need to add greens to UMF-based meals as fibre is usually automatically included. They reduce the dispersal of pathogens (toxic bacteria) around the kitchen, stay fresh longer and retain nutrition better. It is also important to acknowledge that meat has also changed its profiles over the decades – for example, modern battery chickens would be considered freakish mutants less than 75 years ago: “The story of a superchicken”.

Flexitarian

However, there is no need to drop meat completely, as people can elect to be flexitarians, and enjoy the widest range of foods available via the latest technologies while reducing our ecological footprint by cutting unnecessary meat consumption. If Americans can cut beef consumption to 15kg annually instead of 26kg, that alone can eliminate over one billion tonnes of greenhouse gases.

https://www.star2.com/food/2018/08/26/curious-cook-a-modern-food-story-part-3/

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Curious Cook: A modern food story – Part 2

Curious Cook: A modern food story - Part 1

Curious Cook: A modern food story – Part 2

When thinking of home modern foods, many would probably think of ready-to-eat meals, available for dining after a spell in the microwave, oven or pan of boiling water. 

August 12, 2018 Food, Food News

By CHRIS CHAN

Read Part 1

At home with food 

There are many other foods which are used at home which are not available only a hundred years ago. Examples are frozen vegetables, fancy tinned/bottled sauces, special seasonings, coffee pods, vacuum-sealed products, etc. Even tins of food have not been around more than two centuries – the can opener was only invented in 1866 and this then spurred the adoption of tinned foods for use by armies and travellers before making their way into homes. There are now also packs of controlled nutrition meals available from diet management companies which help people manage their calories and nutrients – these are usually home-delivered or sold in large supermarkets. There are even more modern foods which will be reviewed in the next part.

Modern foods offer convenience and much richer eating experiences at home, though there is normally a requirement to suspend belief. By this I mean people have to be conditioned to think that a tube of intestine-wrapped gunk (aka a hot dog or frankfurter) has anything to do with real meat, a mound of sludge from a packet is a casserole, a soggy brown crusted slab was once a fish, etc. But we are so used to this repackaging and reassembly of food into convenient formats that we hardly notice it. An issue though are the processes and additives needed to repackage foods for convenience. If you are curious about additives, read this six-part series, “How to count on food“.

Fresh herbs can be frozen in ice cube trays.

Despite qualms about additives and loss of nutrition after processing, modern foods for the home are generally safe. They are a boon for people who want to save time making home meals – and it is not all only about ready dinners. For people aspiring to cook from raw ingredients, various modern formats are extremely handy– for example, frozen herbs are useful for adding quick flavours, frozen vegetable pureé cubes or greens save time when making soups, vacuum-sealed ingredients bring fresh tastes from foreign lands, etc. Many varieties of prepared sauces also provide countless options for interesting home-cooked meals.

An observation

It is not uncommon to see packaging highlighting a product as “Made WITH 100% Organic Chicken” or something like that. This is not as healthy as it sounds because these labels do not indicate the amount of the organic meat. It may be 80% or it may be 1% – we cannot tell from the label. It would therefore be better if a label stated that something is “Made OF 100% Organic Chicken”.

Similarly, be a little wary of products that claim to consist of 100% natural ingredients. While the ingredients may all be from natural sources, it is not natural to have, for example, a preservative such as sodium lactate injected into chicken meat. The self-evident fact is chicken meat by itself will never have sodium lactate included in its natural configuration, even if the compound is derived from other natural sources.

Food at restaurants

It would be tempting to think restaurants cook food like at home, only in larger volumes – and in rare cases it is possibly true. However, many modern restaurants rely heavily on pre-packaged commercial foods and seasonings, even if they do some form of cooking on site. A few of the worst examples may be some British pubs where you can find the kitchen area by following the “ding!” sounds of microwave ovens sitting next to deep-fat chip fryers.

The simplest indication that restaurants are nothing like home cooking is the menu – the larger the number of offerings, the greater the likelihood that pre-processed foods would be involved in some manner. Also the requirement to deliver the same dishes over and over every day usually leads to some form of standardisation on commercially-prepared ingredients to promote consistency, efficiency and reduce time/effort for cooking.

Restaurants have ways to promote consistency, efficiency and reduce time/effort for cooking.

Another pressure on restaurants is cost. As commercial enterprises, restaurants need to keep costs low to maximise profit. While being economical may apply for many homes, people are usually unaware of the very dubious quality of ingredients available at wholesalers, in particular cheap commercial cooking oils which often contain trans-fats to extend shelf life. Oils with trans-fats are banned for home sales in almost all developed countries, but curiously are still available for use in commercial kitchens in many countries, including Britain.

To save on transport, fresh food is stored for lengthy periods in fridges, leading to food critic Anthony Bourdain’s advice against ordering fish on Mondays at restaurants because that is when leftover fish from the weekend is sold. Some restaurants do source and prepare fresh seasonal ingredients on a daily basis but they are the exception rather than the rule, at least in the West.

Making food look pretty (or “classy”) and delicious also involves using items seldom found at home, such as maltodextrin and food colourings. If you are curious why maltodextrin features in many top-end restaurants, please read “How to count on food – Part 6“.

But this does not mean avoiding dining out, because restaurants offer a meal experience that differs significantly from home dining. Apart from the variety of good dishes, there is also the ambience, service, wide selection of wines/drinks, lack of washing up, and no requirement to shop and do the cooking. Also some top kitchens have specialised equipment which cooks in a manner impossible at home, such as industrial smokers. Another is the Josper charcoal oven (a favourite of Ferran Adrià), which can sear, grill and roast meats at up to 500°C – my oven can only stretch to 280°C. The difference is sensational flavours which simply cannot be reproduced at home.

There is also the cost of dining out, which is usually higher than home dining. However, I had visited food courts in Kepong, Kuala Lumpur, where cooked meals are considerably cheaper than what I could have prepared at home. I sometimes still shudder when thinking of the ingredients used there. It is the starkest reminder that convenience does not necessarily mean quality.

Downsides of modern food

Apart from some dubious ingredients in modern foods, there is another downside: modern food has conditioned many people to prefer robust flavours, making it difficult to appreciate the natural taste of food unadulterated by hearty seasonings. Why this is problematic is because many people have lost the ability to discern good produce from poor-quality substitutes. This is a huge benefit to the food industry because they only need to manage cheap seasonings and texture compounds to sell vast quantities of inexpensive food that people would not normally choose to eat. A case in point is sausage rolls, which can contain less than 8% meat. To know more, please read “How to count on food“.

Infusing intense flavours via modern sauces or blends of herbs is simply an easier form of cooking compared to teasing subtle tastes from ingredients. It is also difficult to retain original flavours over time, especially in commercial packaging.

A preference for robust flavours can make dietary changes difficult (eg. for losing weight or health improvement). Most modern foods contain added salt, sugars and fats combined with seasonings for taste stimulation. It is known that sugars induce cravings while removing fats causes anxiety – therefore both items can encourage addictive behaviours (again helpful for the food industry). This is because such additives have an insidious effect on the mesolimbic pathway in the brain – for more about addiction, please read “Symbols of addiction– Part 2“.

It is feasible to re-capture an unbiased sense of taste – though studies have suggested it may take around 30 days of avoiding modern flavoured foods. It may be worth the effort (and pain) if you genuinely need dietary changes.

As an aside, if you wish to eat less, try drinking 500ml of water just before eating. Before distension, a human stomach is one litre in volume, expanding to four litres when fully stuffed. So drinking water before food will reduce how much you can eat. It also cleanses the palate.

The next part deals with some very modern foods, which may also provide unexpected benefits apart from tasting pretty good.

Curious Cook appears on the second and fourth Sunday of the month.

https://www.star2.com/food/2018/08/12/curious-cook-a-modern-food-story-part-2/

Boosting our immune system to treat tumours

The immune system is our body’s armed forces, designed to defend our body against all intruders that seek to harm us.

SEPTEMBER 5, 2018

A doctor examines a chest x-ray. One of the cancers immunotherapy has been successful in treating is non-small cell lung cancer. — Photos: AFP

So, why doesn’t it seem to work when it comes to cancer?

Well, the answer is that cancer cells can be really crafty, employing a number of strategies to avoid being sought out and destroyed by our body’s soldiers.

That is why we humans had to get even craftier.

Immunotherapy is a form of cancer treatment that helps our immune system in its fight against cancer.

According to consultant clinical oncologist Dr Tho Lye Mun: “Immunotherapy is probably the biggest, most exciting breakthrough we’ve had in cancer for a long, long time.”

He adds: “The success story of immunotherapy is in melanoma, but we don’t get a lot of that in Malaysia.

“But we get a lot of lung cancer. It is the number one cancer killer of men in Malaysia, and the third for women after breast and cervical cancer.

“And that’s where immunotherapy has had the greatest impact (in Malaysia).”

He explains that immunotherapy was initially used as second-line treatment after non-small cell lung cancer (NSCLC) patients had failed to improve after chemotherapy or targeted therapy.

However, immunotherapy has proved to work so well that it is now a first-line treatment.

According to Dr Tho, the majority of patients who are suitable for immunotherapy now receive it as their first treatment.

“And it’s been shown to be more effective than chemotherapy,” he says, adding that Malaysia actually took part in the international Keynote-042 clinical trial, which established that a particular immunotherapy drug, pembrolizumab, was more effective than chemotherapy for advanced NSCLC – the most common type of lung cancer.

Blocking proteins

Pembrolizumab, also known by the brand name Keytruda, is a type of immunotherapy known as a checkpoint inhibitor.

A checkpoint inhibitor is basically a monoclonal antibody that blocks proteins that stop the immune system from attacking the cancer cells.

A monoclonal antibody is a type of protein made in the laboratory that is produced by a single cell line and only binds to one substance, i.e. one particular antigen.

Dr Tho explains: “When tumour cells exist and when they die, they release antigens into the bloodstream, and these are picked up by antigen-presenting cells.

“These cells then travel to the lymph node where they ‘educate’ or prime T-cells (a type of immune cell) to recognise the antigens.

“These T-cells then exit the lymph nodes into the bloodstream and travel to the tumour, where they recognise it and kill it.”

However, some tumour cells have cleverly managed to incorporate a protein called programmed death-ligand 1 (PD-L1) into themselves.

According to Dr Tho, PD-L1 exists in nature to prevent T-cells from recognising our own cells as foreign and killing them.

T-cells have a receptor called programmed cell death protein 1 (PD-1) that fits specifically with PDL-1. This is the signal to the T-cells not to attack the cell with PDL-1.

So, cancer cells that express PD-L1 are actually disguising themselves – or putting on a mask, as Dr Tho says – as one of the body’s normal cells in order to avoid being killed by our T-cells.

Dr Tho explains how cancer cells trigger the immune system. According to him, the problem is not that cancer patients do not have a strong enough immune system, but that the immune cells are unable to recognise the cancer cells due to a number of reasons. — AZLINA ABDULLAH/The Star

Pembrolizumab and nivolumab are immunotherapies that block PD-1 from fitting with PD-L1, allowing the T-cells to go ahead and kill the cancer cells.

Pembrolizumab was recently approved in Malaysia as a first-line treatment for metastatic NSCLC where over 50% of the cancer cells express PD-L1.

It is also approved as both first- and second-line treatment for unresectable or metastatic melanoma, and recurrent or metastatic head and neck squamous cell carcinoma, which has progressed while either on or after receiving platinum-containing chemotherapy.

Meanwhile, atezolizumab, also known by the brand name Tencentriq, is an immunotherapy that works by blocking PD-L1 itself, effectively “unmasking” the cancer cells and allowing the T-cells to recognise them as “foreign” and kill them.

It was approved recently in Malaysia for the treatment of metastatic NSCLC, which has progressed while either on or after receiving platinum-containing chemotherapy.

Another checkpoint inhibitor, ipilimumab, blocks the action of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).

Explains Dr Tho: “This CTLA-4 inhibitor acts at the lymph node level. They basically cause the T-cells to be up-regulated.

“They are not specific (to the cancer), they turbocharge the T-cells, overwhelming the cancer with large forces.”

He adds that while ipilimumab, which is used to treat advanced melanoma, is not approved in Malaysia, it has been allowed to be used in certain cases.

Occasionally, our body’s T-cells do not even know that there is a cancer in the body as they cannot get to the tumour, due to various reasons.

In cases like this, Dr Tho says that radiotherapy comes in handy.

“Basically, you’re blasting it, you’re sending in a missile to kill the tumour cells, and in killing the tumour cells, the tumours release all these antigens, and these antigens are picked up by the T-cells, which now know who they are suppose to kill.

“This is why we now have a lot of studies combining radiotherapy with immunotherapy – this is the next wave.”

Caution needed

However, checkpoint inhibitors do not work in all situations.

For example, it does not work in NSCLC that have driver mutations like EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase) and ROS1.

Dr Tho explains that a driver mutation is an oncogene that produces a protein all the time – it has no off switch.

“The normal proteins in our body, if it’s done its job, the body can send a negative feedback signal to say, ‘Ok, right, you’ve done your job, you can stop now.’.

“But these overactive proteins just keep working and working and never stop, and this causes the cancer to develop.”

He adds: “In those situations, immunotherapy doesn’t work. What you need is a treatment for that particular gene, to tell them to stop working.”

This treatment is known as targeted therapy.

Immunotherapy is also not without its side effects.

“The side effects of immunotherapy are basically ‘-itis’, which means inflammation, and it can happen in any part of the body, so that is a scary thing.

“We’ve had patients die from immunotherapy due to autoimmune lung damage, autoimmune liver damage, autoimmune gut damage.

“So, immunotherapy is not something benign, you can overstimulate the immune system to such an extent that it basically destroys the own body, so that is the caveat,” he explains.

Due to this, Dr Tho recommends that any doctor wanting to prescribe immunotherapy needs to be aware of how to manage its toxicities, adding that there are many guidelines available on this.

“So, I would say, if a hospital wants to embark on an immunotherapy programme, they must have a structure in which all the other clinicians are involved, so it’s not just oncology.

“So when a patient develops lung problems, they need the lung specialist to be involved; if they develop a liver problem, the gastroenterologist must be involved; if they develop skin problems, a dermatologist needs to be involved.

“And the accident and emergency doctors need to be aware that the symptoms the patient gets may be due to immunotherapy,” he says.

He shares that there have been certain cases where a cancer patient on immunotherapy has come in with a cough to the emergency department and been prescribed antibiotics.

“Then they go home and they die. Because they didn’t have a chest infection, what they were having was an autoimmune reaction – the right treatment is steroids,” he says.

“So this has to be disseminated throughout the whole hospital, not just the oncologists. We give patients alert cards, so that they know what they are on and can present it to the physician that they see.”

Dr Tho also notes that because immunotherapy is quite new in Malaysia, there are two things patients should be aware of.

One, that there are some unscrupulous people offering what purports to be immunotherapy, but is not – “they’re just trying to make a fast buck”.

And two, that there are doctors prescribing immunotherapy, who might not be trained to do so, and this can be very dangerous for patients due to the side effects.

Other immunotherapies

The tuberculosis vaccine is now also used as a cancer vaccine to prevent the recurrence of
early-stage bladder cancer.

The tuberculosis vaccine is now also used as a cancer vaccine to prevent the recurrence of early-stage bladder cancer.

While checkpoint inhibitors have proven to be the most successful form of immunotherapy, there are also other types of immunotherapy being developed.

Cytokines are proteins that are important in cell signalling and can affect the behaviour of other cells.

Cytokines like interferon-alpha have been used to treat kidney cancer, melanoma, multiple myeloma and certain types of leukaemia, while interleukin-2 has been used for kidney cancer.

However, Dr Tho says: “In kidney cancer, cytokine therapy such as interferon-alpha has largely been superceded by newer and more effective targeted agents (such as VEGF inhibitors) and checkpoint inhibitors.

“Older therapies such as high dose interleukin-2, even though associated with very good responses in some patients, resulted in significant side effects, and sometimes even ICU (intensive care unit) admissions and fatalities.”

Cancer vaccines are another form of immunotherapy under development.

Similar to how normal vaccines for infectious diseases stimulate the immune system to recognise the germs that cause these diseases and attack them, cancer vaccines stimulate the immune system to recognise certain cancer cells and attack them.

In fact, one familiar vaccine – the BCG (Bacillus Calmette–Guérin) vaccine for tuberculosis – has been repurposed to prevent recurrence in early-stage bladder cancer.

Dr Tho adds: “Limited success has been achieved with the vaccine sipuleucel-T, which is prostate cancer- specific, and talimogene laherparepvec (T-VEC), an oncolytic virus therapy, and both therapies are now approved by the US FDA (Food and Drug Administration).”

However, various vaccines for lung cancer have failed at the clinical trial stage.

According to Dr Tho, the most innovative and exciting type of immunotherapy currently under development is adoptive cell therapy, specifically chimeric antigen receptor (CAR) T-cell therapy.

This therapy involves removing the body’s own T-cells and genetically-engineering them to express a CAR that only fits a certain protein on the cancer cell.

With this specific recognition ability, the CAR-T cells can zoom in and kill the cancer cells when infused back into the patient.

“CAR-T cells have seen dramatic successes in haematological malignancies, especially acute lymphoblastic leukaemia and lymphomas. It’s science fiction come true!” he says.

Dr Tho adds that certain Malaysian cancer centres have collaborated with Singapore’s National Cancer Centre to offer the first-ever CAR-T cell therapy for advanced nasopharyngeal cancer patients, which is a disease prevalent in this region.

“The trial has completed recruitment in Malaysia and we are all eagerly awaiting the final results,” he says.

https://www.star2.com/health/2018/09/05/boosting-immune-system-treat-tumours