Source: Wired
Date: September 2009

Fake meat: burgers grown in beakers

By Leo Hickman

The prototype is carried to the table by a lab assistant in starch-stiff whites. "What we're making here is basically wasted muscle," says Mark Post, as he picks up the clear plastic dish containing a pinkish liquid and holds it up to the strip lighting for closer inspection. "Right now, it probably has the texture of an undercooked egg."

In a lab at the biomedical-engineering faculty at the University of Technology in Eindhoven, Post is holding an early example of what he hopes will be the food of the future: in vitro meat. Post, the university's professor of angiogenesis (growth of new blood vessels), is a specialist in tissue engineering. He is also part of a small team of Dutch scientists racing to develop the ability to grow muscle independent of a living animal so that it can be produced in commercial quantities and sold as meat.

He walks over to what looks like a large oven in the centre of the lab. Think of this Flexercell Strain Unit, he says, as an exercise machine for the microscopic skeletal muscle cells - in vitro meat, in other words - that he and his team are cultivating. To move on from that undercooked-egg texture, muscles need pumping.

"We're developing a very simplified version of what we know as meat," he explains. "The cells are grown in this dish within a growing medium and this unit is where they receive the electrical stimulation. These electrodes ensure there is an electrical current - about 1Hz - passing through the cells. To make these skeletal cells develop into muscle, they need to be constantly exercised, just like in the body." This, he explains, is one of the scientific hurdles for in vitro meat that has not yet been fully addressed. "We can convert stem cells into skeletal muscle cells; however, turning them into trained skeletal muscle appears to be a little harder."

But overcoming that challenge would bring vast rewards. The red-meat market was worth $61 billion last year in the US alone, according to Mintel. Carve out even a pastrami-thin slice and the in vitro pioneers will be wealthy beyond imagination. The rewards are not only financial. Livestock's Long Shadow, an influential 2006 report by the UN's Food and Agriculture Organization, calculated that the global livestock industry is responsible for about 18 per cent of mankind's greenhouse-gas emissions - more than all of our cars, trains, shipping and planes combined. The FAO said it also accounts for more than eight per cent of our freshwater use, largely to grow crops fed to animals. Meat production now uses up 70 per cent of the world's agricultural land. And then, of course, there is the animal suffering attributed to the industry and intensive animal-farming.

Last year, the animal-rights group People for the Ethical Treatment of Animals (Peta) announced a $1 million prize for the first team to develop and market in vitro meat. There were, admittedly, some pretty exacting clauses: it set the rather optimistic deadline of June 30, 2012. It also insisted that the winning entrant must "produce an in vitro chicken-meat product that has a taste and texture indistinguishable from real chicken flesh to non-meat-eaters and meat-eaters alike; and manufacture the approved product in large enough quantities to be sold commercially... at a competitive price". Lastly, it said a panel of ten Peta judges would assess the taste and texture of the in vitro chicken, prepared using a classic Southern fried-chicken recipe. No pressure, then.

Yet the science remains stubborn. To date, only a handful of scientists has attempted to tackle the considerable technical obstacles to cultivating meat. At the vanguard is the Dutch consortium that includes Mark Post. Post - who also specialises in "growing" new blood vessels for heart-attack victims - says either mechanical or electrical stimulation can be used to exercise the cells, but electricity is more energy-efficient than placing cells in, say, tubes that are then pulsated using vacuums. The reasoning is simple: once you scale up the technology for commercial use, minimising energy use will be key to making the manufacturing process viable.

This energy use is why Post sees neither of these methods as a longer-term way to exercise the muscle cells. Instead, he hopes to develop an alternative method by observing the cellular changes that occur under current techniques.

"We want to look at how the cells change, as well as their genetic programme," he says. "Which protein-manufacturing programs do they turn on to train them? Then we can use other ways to replicate that. For example, we might be able to use growth factors such as hormones. Inside us we have many natural proteins, such as bone morphogenetic protein and other transforming growth-factor proteins, which affect the differentiation of skeletal muscles. In real life, in the mammalian system, this is achieved with a cocktail of these hormones in a time-dependent and location-dependent manner. But we could manufacture them quite easily by using modified E. coli bacteria. We could then add them to the muscle as required."

Never has the farmyard felt so distant.

And what, exactly, is in the liquid that harbours the invisible animal cells?

"This is the growing medium , " explains Post. "You need nutrients - basic amino acids, glucose and minerals. The medium also contains a serum we harvest from animals, usually calves. Within our consortium, a group headed by Professor Klaas Hellingwerf at the University of Amsterdam's Swammerdam Institute for Life Sciences is looking at how to develop the best growing medium. They need to work out how to get rid of the serum altogether. The problem is not just that it's of animal origin, but that it can vary from batch to batch.

"But an artificial serum has been produced already. It's not such a mystery. It's getting from the limp muscle to the exercised muscle; that's where we really have a knowledge gap. It's difficult to say how long this will take. It took us two to three years just to get to the limp muscle."

Natural muscle tissue is a relatively simple material. A series of long fibres, made up of contractile proteins called actin and myosin, are held together within a thin membrane of connective tissue. Think of a fibre-optic cable wrapped in plastic. Bar a few nerve endings and blood vessels, there's not much else to it other than a layer of fat to provide energy to the muscle. So just how easy would it be to replicate, say, a pork chop using in vitro technology?

"It is doable," says Post. "But in the end, the experience of eating meat comes down to the taste and texture. You would miss fat, but we can easily make that. You can even modify the feedstock to these fat cells so that they produce healthy fats. Just look at margarine.

"I don't think we will spend a whole lot of time trying to replicate the taste of meat, though - that will be artificially added later. The food industry is already expert at enhancing taste - creating the right texture is the Holy Grail."

Why complicate matters, adds Post, when you can nurture skeletal muscles to produce a simple, lean meat? Strip away the connective tissue, blood vessels and fat - as many of us do when we prepare a chicken breast prior to cooking it - and you're left with a lean fillet of meat which consists of, roughly, 75 per cent water, 20 per cent protein and three per cent fat. Post believes that we are not too far away from producing this kind of meat on a commercial scale - ten years, perhaps. Convincing in vitro steaks and chops are probably a few decades away.

Stem-cell technology could also help. Ideally, Post says, embryonic stem cells would be avoided, but undifferentiated stem cells found in muscles - "myoblasts" - are activated locally when the body is wounded to help with healing. They are even activated when a muscle is exercised hard. Harvest and grow these cells into muscle cells and, in theory, no animal would ever need die.

Post does see a problem, though: "Sure, in theory, you could have one cloned animal that was the source of all the meat in the world. It's a science-fiction dream, though. Additionally, we would not know the genetic stability of this tissue. This is a health risk and, therefore, a commercial risk. What happens if a tumour line suddenly develops?

"No, what I think will happen is that we learn to reprogram cells, rather than differentiate stem cells. Essentially, the cell in your fingertip is the same cell as the cell in the lens of your eye, or the cell in the lining of your stomach. At some point, they were programmed to become what they are. Some cells can still perform different functions if you put them in different conditions, like stem cells, whereas brain cells, for example, can be only brain cells. The idea now is to take stem cells that are not yet differentiated and coerce them into becoming some sort of organ or muscle. That organ cell is genetically the same as the stem cell - so why couldn't we make the same cell turn into a muscle cell?"

Researchers, he says, are gradually discovering the mechanisms for what steers the genetic material in our cells in one direction or another. "This research is being done by lots of people around the world, but it's probably decades away: after all, stem-cell technology has been around for three decades and we still don't know how to regenerate a tissue."

However, in vitro meat still risks being seen by its critics as a prime example of man "playing God" with nature.

"I'm still puzzled by this reaction," says Post, somewhat defensively. "I do see it as a challenge, but I don't see why it is any more problematic than, say, introducing a completely water-grown tomato. We have been domesticating grasses for thousands of years. This is pretty much artificial selection. You would just need one bad zoonosis, such as bird flu - where there is an HIV-type spread of infection from livestock into humans - to be the trigger for consumer acceptance for in vitro meat."

Over time, "real" meat might be labelled as being bad for the environment and our health. "Why not use the kind of warning messages we now have on cigarette packets?" suggests Post. "We could see these messages on the supermarket packaging for 'natural' steak."

The one area where Post can't yet foresee any technological advance is the speed it takes to grow meat. "We are limited by the multiplication time of cells, typically about 18 hours," he says. "This is called the 'doubling time'. After 18 hours you have two cells, after another 18 hours you have four cells, and so on. It continues exponentially, and it takes time, but this still allows you to turn one pig into a million pigs in 14 days, which is not bad going.

"I know that in the Old Testament it only took a couple of seconds, but that was in a book," he adds with a wry smile.

Before leaving, I ask Post if I can taste his cultured meat cells. "No, that's not possible," he says firmly. And has curiosity ever led him to taste them? "No. Why would I?"

Next door to a multicoloured, Lego-like prefabricated block of student accommodation in the heart of the University of Utrecht's sprawling campus stands the faculty of veterinary medicine. In the department of the science of food of animal origin, Henk Haagsman's office is brightened by his children's paintings of farm animals. His window looks on to a pastoral idyll - cows lazily pacing grassland below - but these animals are, in fact, the source of much of his research. Haagsman is professor of meat science here at Utrecht and, like Mark Post, is a key member of the in vitro-meat consortium that is currently coming to the end of a five-year €2 million research grant. The faculty's on-campus farm gives him access to hundreds of cows, sheep and pigs to study.

Haagsman's role in the consortium has largely been to research stem cells' role in developing in vitro meat. But he also specialises in infectious diseases, and he says that if in vitro meat is to be produced on a commercial scale, hygiene controls will be paramount to its success.

"If you make a mass of muscle in a fomenter, you really don't want an infection," he says. "We're working on natural antibiotics to combat this threat. In tissue cultures in the lab we use antibiotics in the medium. It's convenient in a lab, but you can't do this in a big commercial fomenter. Quorn [a meat-substitute made from mycoprotein, a nutritious fungi] has the same issue with fungi and we have to do the same. We have to find antibiotics that are derived from animals. For example, small peptides are found in animals, such as chickens and pigs, which prevent the infection. Maybe they can be used, but it all needs to be sterile from the beginning."

Proving to consumers that in vitro meat is safe to eat will be crucial, he says. This is why so much effort is being made to avoid relying on the "easy street" of genetic modification. "If we were to use GM we could quickly make stem cells that fulfil the properties we require," he says. Because embryonic stem cells haven't yet been harvested from pigs ("the embryology in a pig is different from a human and a mouse"), his team has been exploring the possible short cut of trying to retrieve "clonal cells" - myoblasts - from pig muscle. But public acceptance of in vitro meat could prove a hurdle equal to the science.

The name chosen for the new product will determine its destiny, says Haagsman: "We don't want the words 'lab meat' to be used. 'Test-tube meat' does not have good connotations. Maybe we should not talk about meat at all. It is muscle - but maybe it's not meat? I would hesitate to call it meat. It's about perception. Meat is associated with killing animals. I was on television once, talking about it, and they held a contest asking viewers to send in suggestions. My favourite was 'krea', the Greek word for meat."

Dr Bernard Roelen, an assistant professor at the faculty, greets us as we enter the "cell culture" laboratory. He washes his hands in ethanol to sterilise them and turns on the lab's air filter to restrict the flow of airborne bacteria. "These are cells from a pig muscle," he says, pointing inside a dish. There seems to be nothing there.

"The cells are in the medium, invisible to the naked eye," he explains. "The medium contains water, a little bit of salt, glucose, amino acids, a red-colour pH indicator and an antibiotic. The cells were isolated from the pigs on our farm and then frozen."

Most of the cells were taken from a stillborn pig foetus. "There are always some dead ones around," Roelen says. "The cells are taken from the semitendinosus - the pig's hamstring. We freeze them in liquid nitrogen and we can keep them for years. We then thaw them out and put them in this culture plate. The capacity of the cells of young animals is larger than that of full-grown animals. They have a better potential to differentiate into a variety of cell types and to proliferate."

How, though, will in vitro meat taste? My own request to taste the sample is once again blankly rebuffed.

"There are two types of muscle fibre," explains Haagsman. "If a pig has more movement they have more Type 1 muscle fibre, less movement they have more Type 2 muscle fibre. Wild fowl such as pheasants have a lot of Type 1 dark meat because they use their wings, but if you look at the Type 2 breast of chicken it is completely white. Type 1 has a lot of mitochondria to break down fatty acids and then oxidise. Mitochondria have a lot of cytochromes which means it has more colour. Type 1 is easier to make, because Type 2 requires fatty acids that are metabolised.

"We like the sirloin in beef, a piece of muscle that doesn't do too much exercise," he continues. "That taste is determined by the sugar that makes connections with the proteins. This is what gives you the general meat taste. And then you get extra taste from the particular metabolism of the animal, which is why, say, mutton tastes like mutton. If you have more Type 1 muscle, you will have meat with a richer, more liver-type taste."

But will you the consumer swallow it? Professor Edmund Rolls, an Oxford-based neuroscientist who has studied how the brain processes signals when we place food in our mouths, had questions about the palatability of in vitro meat. Still, presentation could be all. "Cognitive inputs, such as packaging and marketing, can have a large effect on the flavour," he says. "Emphasising the excellent nutritional and environmental benefits, for example, might enhance the 'reward value' and therefore the perception of the taste."

Science's obsession with growing meat in the lab goes back at least to 1912, when Alexis Carrel placed a small piece of heart muscle cut from a chicken embryo into a stoppered flask, filled it with a mysterious culture, and waited to see how long the muscle would survive. Carrel - a French Nobel Prize-winning surgeon better remembered now for his writings on eugenics - died waiting. Every day until his death 32 years later, Carrel kept the muscle "alive" by refreshing the culture. To date, no one repeating the experiment has achieved such results over such a long period - fuelling the theory that Carrel's culture contained supplementary living cells rather than only simple nutrients.

Indeed, if Carrel's experiment were ever to be repeated, it would defy one of biology's central tenets - the Hayflick limit, which states that the vast majority of living cells (undifferentiated stem cells being a significant exception) cannot divide and multiply infinitely. For example, human cells will divide only 70 times inside the body before the telomere, the region of DNA at the end of the chromosome, starts to self-destruct. Biologists believe this occurs to minimise the risk of cancerous cells developing and then rapidly multiplying. Learn to control this process and you might even hold the key to eternal life - something Carrel, by his own admission, was very interested in.

It wasn't until 1931 that the concept of in vitro meat entered popular discourse. A future-gazing essay by Winston Churchill in a monthly magazine called The Strand alerted the general public to its possibility. Entitled "Fifty Years Hence", Churchill's article hypothesised about the potential of technologies ranging from nuclear energy to robots. "Up till recent times the production of food has been the prime struggle of man," he wrote. "That war is won. There is no doubt that the civilised races can produce or procure all the food they require...We shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under a suitable medium."

Nine years after Churchill (an avowed fan of roast beef followed by a plate of Stilton) wrote these words, a 17-year-old Dutch soldier called Willem van Eelen was captured by the Japanese during the first months of the Second World War. For the next five years van Eelen narrowly avoided starvation in a prisoner-of-war camp, in part because he was given the task of handing out the pitiful rations of rice. Here he soon realised that he held the very life of some of these frail men in his hands simply by choosing how many grains of rice he placed in their bowls, either by design or accident. Van Eelen spent much of his time musing about when, or even if, he and his fellow prisoners would ever again see plentiful food supplies. Specifically, he wondered how the post-war world could build an equitable and sustainable system of food production. The experience would lead him to become the self-proclaimed "godfather of in vitro meat".

Now 86, Willem van Eelen pours himself a cup of black coffee and takes a seat in the study of his modest ground-floor flat in Amsterdam. He starts to rummage through a perilously tall pile of papers on his desk.

"Ah, here it is," he says, holding up a sheet of A4 paper. "This shows that I am the godfather." Every part the self-styled maverick amateur scientist, van Eelen hands over a patent certificate from the Nederlandsch Octrooibureau - one of the Netherland's leading patent agencies - dated March 3, 1995. With a confusing combination of pidgin English and bureaucratic doublespeak, it describes the patent's purpose: "The industrial production, with new techniques using elements of laboratory tissue cell culture method, of all 100 per cent pure meat and fish sorts with complete maintenance of exterior, taste facets and character, thereby rendering the keeping of cattle (fish) and the slaughtering (catching) thereof - ie as economically too costly - superfluous."

As a result of this omelette of words, rubber-stamped by Dutch officialdom, van Eelen is now the world's only patent-holder for in vitro meat - in terms of its basic concept, scientific technicalities and commercialisation. Since 1995, he has gone on to secure patents in the US, Europe, Japan and most other major commercial territories. Every player in the development of in vitro meat must now channel their efforts through him at some stage, whether they like it or not.

Van Eelen corralled and initiated the Dutch consortium of scientists, pushed for the grant, and acts as the technology's commercial gatekeeper. But his eccentricities may be a hindrance to investors' taking the technology seriously. His shadow looms large over in vitro meat - as well it might, considering he has spent almost six decades trying to develop it.

Following his liberation from the prisoner-of-war camp, van Eelen returned to his education. After a brief stint working as a ledger clerk for the Dutch finance ministry, he enrolled for a psychology degree at the University of Amsterdam.

"It was there that I attended a lecture where a professor - inspired by Carrel's experiment - took a big piece of meat and kept it alive by feeding it," he recalls. "It even grew a little bit. At that moment I got the idea that you could eat this meat. I also thought that it would be possible to produce it without killing animals. I talked to the professor and read papers. I was very enthusiastic. They said it was a dream, impossible. But I continued."

For the next 30 years, van Eelen undertook a wide range of jobs and academic courses to give him the time and know-how to develop his idea. By day he ran a series of art galleries, restaurants and cafés with his artist wife (now deceased). When time allowed, he studied medicine and nurtured connections with various Dutch companies focused on cellular biology. But it wasn't until 1981 - the year stem cells were discovered in mice - that van Eelen began to see that his idea could become a reality: "I knew much earlier on that they [stem cells] must be there, but I just called them something else. When they found them I was very excited as I knew my idea was now possible. But since then, the whole world has been looking for human stem cells. I needed cow stem cells. If the funding came through to find cow stem cells, we could develop in vitro meat in one year. All the rest of the technology to make this happen is in already in place."

Frustration is never far from the surface when van Eelen paces through his story. It has been only in the past few years that, after forming the Dutch consortium, his in vitro meat project has received serious funding. But the money runs out soon.

"It took five years to persuade the Dutch government to give us €2 million," he says. "I had to write bibles for them. Food companies are very interested, but they want to see the finished product. They say they will wait for it. It is too innovative for them. Some don't believe me and think I'm crazy. People are jealous about my brilliant idea. My patents are worth millions, but I can't eat. I need more money to continue my research and pay off my debts. The only solution is, unfortunately, to sell my patents. It's stupid, but I have to do it."

If it were left to him, van Eelen says, he would just bypass the need for conventional research and instead speed the process up by playing a lucky-dip-style alternative: "Einstein was an artist. You have to be creative to find a new way. The best inventions are from accidents. For example, the [contraceptive] pill was discovered by accident. To find the perfect growth medium for in vitro meat, you could just take, say, 100 bottles of serum [the clear liquid that can be separated from clotted blood] each containing different proportions of nutrients. Then you put in the stem cells and wait. Just play. If you are lucky, in one of the bottles they will grow. Other scientists make the mistake of wanting to know exactly how everything has happened. But I say, if you see it work you should just get on with it. This is how cheese was made."

But will anybody want to eat the stuff?

"True, it will be a problem to convince people to eat it," says van Eelen. "If I tell you it is not from a living animal, it might be a problem. At first, people will be suspicious, but after they taste it they will be 'wow'. I like to go to McDonald's, but I don't like to think what's in the burgers. When they eat my burger they will say it's nice and notice it is cheaper and healthier, too."

And has he himself ever tasted in vitro meat? He smiles like a mischievous child: "I once put a few cells on the tip of my tongue. I couldn't resist it. It tasted a little like chicken." But playing the tease, he refuses to elaborate about the source of his experimental in vitro meat cells.

One hour north-east of Utrecht, near the town of Deventer, is Stegeman's giant processed-meat factory. Beyond a security hut and barrier stands an austere factory façade - windowless grey walls and a chugging smoke stack. Stegeman is the Netherlands' largest meat company, and main supplier of own-brand meat products to Dutch supermarkets. Inside the factory, the majority of the Netherlands' cooked meats - sausage, hams, pâtés - are systematically processed, shaped and packaged.

It is into this production system that in vitro meat could enter. Peter Verstrate, the operations director, is the only member of the in vitro meat consortium from within the meat industry. He says that as soon as he heard about it, he immediately spotted its commercial potential.

"Willem van Eelen contacted me in 2002 with this crazy idea that he had invented in vitro meat," says Verstrate. "My first thought was whether or not it could work, but I also thought we must be involved. We agreed to help van Eelen financially so he could continue to work on it. It's either going to be a huge success, or it will be nothing at all. In the short term, say the next five years, I see us producing fragments of meat or protein tissue, and then merging them into a larger pattern, like a Frankfurter-type product. This is very doable technically."

He even envisions thin layers of in vitro meat being "printed" using the technology found in an ink-jet printer. "At some point we will see steaks and chops, but that could take up to 30 years. In ten to 20 years, we will have the spaghetti meat sauce, the sausages and the meatballs. The consumer will choose to eat it to save the environment, save money and for animal welfare. It would be great to have a picture of, say, Paul McCartney eating one of these sausages. It won't be so important whether in vitro meat is actually called 'meat' or not. It might have a branded name, like Quorn does. In the end, the product should be the hero. It will have animal-welfare and environmental labelling. When the real effects of climate change start to become visible and tangible - the Arctic melting, etc - it will clear the path. As paradoxical as it sounds, it must be seen to be natural. It should be made clear that we don't do anything other than grow the in vitro muscle outside of the body."

Verstrate estimates that as "real" meat prices rise amid shortages and increased environmental regulation, the price of in vitro-meat products could be half that of conventional equivalents. But why, then, isn't every major meat company in the world now chasing this technology?

The global meat industry is a cut-throat business - on every level - but it is inherently risk averse, he explains. Frustratingly, it really wouldn't take that much investment to develop in vitro meat to the stage where it was ready to be stacked in our supermarket chiller cabinets: "To get it to market within a couple of years, it would take, say, only €10 million."

Another keen advocate is Peter Singer, the Ira W DeCamp professor of bioethics at Princeton and a founding father of the modern animal-rights movement. "I support the efforts of the scientists in Holland," he says over the phone. "It's a great idea. The potential is there, but whether anyone is going to eat this stuff seems to be a question of marketing it right."

So is it really meat? "I'm prepared to call it 'meat'," he says. "It's a broad term, etymologically, in English. There's this term 'sweetmeat', for example, used for sweets in Elizabethan England. We talk about the meat of the coconut. There is a question about the use of a word that's now moved from its original form."

But, on a philosophical level, is someone who places in vitro meat in their mouth actually eating meat? The original cells still had to come from an animal source, after all; so could a vegetarian eat this stuff without compromising their beliefs?

"If I ate it, I would consider myself to be eating meat," Singer responds. "I don't see anything wrong with eating a piece of meat, as such. It's the same with road kill. If I came across a freshly killed kangaroo and I felt like slicing it up and putting it on the barbie, I wouldn't have any problems. If they are only genetically modifying the meat at a cellular level, I don't have any problem. It's not something that is going to harm any animals. I hope the day will come that people won't want to eat meat from animals that have suffered for our benefit and have contributed to climate change."

As I set off to leave the Netherlands, I travel past mile after mile of erect, white polythene-sheeted greenhouses. Inside many of the fruit and vegetables that fill our supermarket shelves - tomatoes, melons, cucumbers, peppers - are grown through the use of hydroponics. The Netherlands is already an industrial-scale food-production factory. Within a decade or so - if the consortium achieves its goals - this giant operation could be joined by a town-sized patchwork of vats, brewing up tonnes of in vitro meat.

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