WHAT IF YOU COULD CATCH OBESITY as easily as you can catch a cold? Just one unlucky sneeze in a crowded railway carriage or lift, and that鈥檚 it. Bang! Never mind that you鈥檝e been a string bean all your life. Never mind that you鈥檝e always taken plenty of exercise and watched what you eat. Pick up the wrong virus, and you鈥檙e almost certain to get fat.
It sounds preposterous, but remember that only a few years ago the idea that a bacterium could give you ulcers or heart disease sounded crazy. Those theories are now well accepted 鈥 and the 鈥渙besity virus鈥 could be the next one to become respectable. Traces of the virus show up in enough overweight people to suggest that the 鈥渆pidemic of obesity鈥 in today鈥檚 world may be more than a mere metaphor. But don鈥檛 sidle away from that extra-large person on the train just yet. Your greatest risk of catching obesity might come from someone you least expect.
BOMBAY, INDIA, 1988 鈥 Nikhil Dhurandhar鈥檚 life was turning out just as he鈥檇 always imagined. Like his father before him, Dhurandhar was a doctor specialising in obesity. His practice was thriving and he saw a thousand patients a year. Until, one day, a casual remark changed his life forever.
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A family friend, veterinary pathologist Sharad Ajinkya, mentioned that he鈥檇 been studying a viral epidemic that was sweeping through poultry flocks, killing hundreds of thousands of chickens. And oddly enough, when he examined the dead birds he鈥檇 been surprised by the large amount of body fat they were carrying. Dhurandhar was amazed. How could birds ill enough to die of a virus be overweight? 鈥淭here should be little or no fat,鈥 said Dhurandhar. 鈥淭hey should be wasting away.鈥
The two men decided to investigate. They injected the virus, known as SMAM-1, into some chickens in the lab. Six weeks later the infected ones had almost 50 per cent more fat in their body cavity than chickens that had not been exposed to the virus. Oddly enough, the fatter group also had less cholesterol and triglycerides in their blood. This was surprising because fat animals usually have high levels of these two molecules, which transport fat round the body in the bloodstream. Intrigued, Dhurandhar took blood samples from 52 of his obese patients and tested them for SMAM-1 antibodies. He found them in 10 of the 52, and those 10 were heavier than the other patients. They also had lower cholesterol levels 鈥 the same unusual signature he had found in the chickens. 鈥淲hen I got that, I thought this was something which was very important to pursue,鈥 says Dhurandhar.
But he knew, too, that he didn鈥檛 have the lab space or funding to study this at his clinics in India. He started writing and phoning obesity researchers in the US, and soon realised that no one was going to take a chance on an unknown Indian scientist with an offbeat idea. He hoped there鈥檇 be a better chance of convincing someone if he went there. 鈥淪o I closed my clinics 鈥 I had three at that time 鈥 got permission from my wife and my son, and we all came to the States,鈥 he recalls. 鈥淚t was a big, big leap of faith.鈥
THE WORLD has become dramatically fatter in the past few decades. Since 1980, obesity rates have risen more than 30 per cent in the US. Today, fully 23 per cent of adult Americans and about 20 per cent of adult Britons are obese, as defined by a body mass index (weight in kilograms divided by the square of height in metres) over 30, which works out to 97 kilograms for a person 1.8 metres tall. The problem is even worse in countries like Samoa, where more than half the adults are obese.
This sudden billowing of fat in rich and poor countries alike puzzles obesity experts. The usual suspects 鈥 notably poor diet and inadequate exercise 鈥 haven鈥檛 worsened as rapidly as obesity has burgeoned, which has left experts with the feeling that they must be overlooking some important factor. 鈥淭he fat content of the diet is too high and the level of physical activity has declined, but still we feel we cannot explain all of this obesity problem,鈥 says Arne Astrup of the University of Copenhagen.
What if the problem was, quite literally, an epidemic 鈥 a pathogen sweeping through the population, leaving obesity in its wake? The idea had always intrigued Richard Atkinson, an obesity researcher at the University of Wisconsin in Madison. Atkinson was aware that three other viruses 鈥 including canine distemper virus and Borna disease virus 鈥 had been shown to cause obesity in animals, usually by destroying the part of the brain that regulates appetite. In his lectures, he鈥檇 often joked about the possibility that fat could be contagious in humans, too. 鈥淚鈥檇 say, well, it鈥檚 possible you get on an elevator, somebody sneezes on you, and you catch obesity. It got a good laugh,鈥 says Atkinson. But he鈥檇 never seriously tried to follow up on the idea.
MEANWHILE, Dhurandhar鈥檚 big gamble had not paid off. He had landed a job as a researcher at North Dakota State University in Fargo. But as he neared the end of his second bitterly cold winter, he still had found no one willing to support his work on the chicken virus. Discouraged, he decided he鈥檇 pack up and move back to Bombay. But just before he gave up, one of his letters ended up on Atkinson鈥檚 desk. A few months later Dhurandhar moved to Madison to take a research position in Atkinson鈥檚 new lab.
The collaboration almost ended before it ever began. 鈥淭he plan was that we would import SMAM-1 and start working on it,鈥 recalls Dhurandhar. 鈥淥f course, you need permission from the US Department of Agriculture to import a virus. We applied for a permit, and they very promptly refused it.鈥 Not all that surprising since the virus would devastate chicken flocks if it got out and maybe even make people fat.
Unable to do the research they had planned, the researchers decided to try their experiments with a different virus. Since SMAM-1 belonged to a group of viruses called adenoviruses, they scanned a list of the 50 or so commercially available human adenoviruses, which cause colds, diarrhoea and conjunctivitis. They decided to start with one called Ad-36, mostly because it was different enough from other adenoviruses to make antibodies formed against it easy to recognise. 杏吧原创s knew almost nothing about Ad-36 except that it had originally been isolated from a German girl with diarrhoea.
It turned out to be a lucky choice. After just three weeks, chickens inoculated with Ad-36 had two-thirds more abdominal fat than chickens without the infection 鈥 and once again, they had unusually low cholesterol. The new virus they had picked out of a catalogue, in other words, had exactly the same effect as their banned Indian virus. 鈥淲e should have bought a lottery ticket on that day,鈥 says Dhurandhar, who suspects that their good fortune must mean that at least a few other viruses have similar effects.
When the researchers gave Ad-36 to mice, the effect was the same: two-thirds more abdominal fat than controls, and lower cholesterol levels. In a pilot experiment with marmosets, three animals infected with the virus put on three times as much weight over a six-month span as monkeys not exposed to the virus, Dhurandhar and Atkinson reported in May at the European Obesity Congress in Antwerp. And, as with the chickens and mice, their cholesterol went down. The monkey experiment should go a long way towards convincing sceptics that the animal experiments are relevant to people, says Atkinson. 鈥淧eople can dismiss chickens, and they have. They can dismiss mice, and they have. It鈥檚 a lot harder to dismiss monkeys,鈥 he says.
But even if Ad-36 can make chickens, mice and monkeys pile on the fat, could it really do the same thing to people? To find out, Dhurandhar and Atkinson collected blood samples from 313 obese people and 92 lean ones in Wisconsin, Florida and New York. They found antibodies to Ad-36 in just four of the lean people but in 100- 鈥 that鈥檚 32 per cent 鈥 of the fat ones. Once again, the obese people exposed to Ad-36 had unusually low cholesterol levels.
What those numbers suggest is frightening: should you be unlucky enough to get the virus, you鈥檙e overwhelmingly likely to end up fat. 鈥淭hat鈥檚 pretty scary,鈥 says John Foreyt, an obesity researcher at Baylor College of Medicine in Houston, Texas.
Could it be that fat people are just more likely to get the virus than skinny folks? After all, obesity often leads to a depressed immune system. To test this, Dhurandhar and Atkinson also looked for antibodies to three other adenoviruses 鈥 Ad-2, Ad-31 and Ad-37. All three turned up equally often in lean and obese people, and none was associated with the telltale signature of lower cholesterol.
And Dhurandhar keeps accumulating more evidence. Recently, he looked for antibodies in blood samples drawn from 86 pairs of identical or fraternal twins. In the 26 pairs where one twin had antibodies to Ad-36 and the other didn鈥檛, the one who had been exposed to Ad-36 proved to be significantly heavier, with a body mass index 1.5 points higher, on average. Once again, there was no such pattern with the other three adenoviruses.
Even with this growing weight of evidence, though, Dhurandhar and Atkinson have had trouble convincing their colleagues to accept their theory. 鈥淲e鈥檝e had people laugh at us,鈥 says Atkinson. 鈥淥ne of the most frustrating things I鈥檝e ever done in my life is trying to get this stuff published. We鈥檙e getting nit-picked to death.鈥
That鈥檚 not too surprising, says Frank Greenway, an obesity expert at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. 鈥淚 think that鈥檚 typical in the scientific community,鈥 he says. 鈥淧eople aren鈥檛 comfortable with taking quantum leaps. The guy who decided that Helicobacter pyloriwas responsible for ulcers had a terrible time.鈥
But their persistence may finally be paying off. Dhurandhar and Atkinson鈥檚 first peer-reviewed paper, on their animal experiments, appeared this month in the International Journal of Obesity (vol 24, p 989). And none of the obesity experts contacted by New 杏吧原创 thinks the idea that a virus might cause some cases of obesity ridiculous, though most still say the idea is 鈥渘ot proven鈥 in humans. 鈥淚 think we can say for the moment that this virus induces obesity in some animals, but that this is not yet found to be true in humans,鈥 says Luc Van Gaal of the University of Antwerp. Even Dhurandhar agrees. 鈥淓verybody wants me to say this virus causes obesity in humans for sure. I鈥檓 not prepared to do that yet,鈥 he says.
Truly convincing proof in people may be hard to come by, though. 鈥淚n the theoretically ideal world, you鈥檇 take a bunch of people and infect half of them and see what happens,鈥 says Greenway. 鈥淭hat鈥檚 clearly unethical, so the next best thing is to understand the mechanism.鈥 Once scientists know what molecular triggers the virus trips to make animals fat, they can look to see if the same triggers are active in humans.
Dhurandhar is beginning to see the first hints of how the virus might make people fat. In test-tube experiments, he added Ad-36 to cultures of immature fat cells of mice. The infected cells were three times as likely as uninfected ones to mature into fully fledged fat cells, he found. Sure enough, he also found that Ad-36-infected animals have more fat cells in their bodies. Once formed, these still-slender fat cells begin doing their job, sending out the hormonal signals to gather and store fat. Which means that you鈥檙e more likely to put on weight.
This summer, Dhurandhar 鈥 who moved last autumn to take up a professorship at Wayne State University in Detroit 鈥 is beginning a new set of experiments to try to understand how the virus lowers cholesterol even as it increases obesity. He鈥檚 now testing to see whether hamsters 鈥 the lab animal of choice for cholesterol researchers 鈥 respond to Ad-36 in the same way as chickens, mice and monkeys. If researchers can figure out how the virus lowers cholesterol, they will know whether this reduction benefits the individual or not. 鈥淲here does it go? If it鈥檚 going into arterial walls, that鈥檚 not good,鈥 says Dhurandhar. On the other hand, if the liver breaks it down and excretes it 鈥 or if the liver simply produces less 鈥 scientists may eventually be able to treat high cholesterol with drugs that mimic the virus鈥檚 action.
IF DHURANDHAR and Atkinson鈥檚 work eventually proves that the Ad-36 virus is responsible for some proportion of the obese people we see today, what happens then? To begin with, Dhurandhar has seen some hints that obese people with antibodies to the virus may respond better to anti-obesity drugs. Perhaps, he guesses, such people lack any genetic predisposition to obesity 鈥 they simply had the bad luck to catch the virus, so their obesity is easier to reverse. And antiviral drugs or, eventually, a vaccine might prevent the disease altogether in such people. Dhurandhar is already working with a company 鈥 which he won鈥檛 name 鈥 to develop an antiviral drug which is effective against Ad-36.
Governments should also begin screening blood donors for the virus, suggests Dhurandhar. His experiments show that the virus remains infectious in human blood even after long storage, meaning that someone could become infected after a blood transfusion.
If obesity does prove to be infectious, the researchers hope this knowledge may help erase some of the stigma that surrounds fat people. 鈥淥bese people suffer huge discrimination, and it鈥檚 because of this moralistic Judaeo-Christian ethic that you must be greedy, you must not have any self-discipline, and so therefore you must be a bad person,鈥 says Atkinson. 鈥淚f people understood that there but for the grace of God go they 鈥 because somebody didn鈥檛 sneeze on them in an elevator 鈥 they might have a bit more compassion.鈥
But might obese people just be trading one stigma for another? After all, most human adenoviruses are highly contagious. And Ad-36 clearly spreads easily in animals. For example, Dhurandhar can detect viral DNA in the blood of previously uninfected chickens just 12 hours after housing them in the same room as chickens carrying the virus. And birds that catch the virus in this way get fatter, just like ones that Dhurandhar inoculates directly with the virus. 鈥淭hey caught obesity just from being in the same room,鈥 says Dhurandhar.
So what does this mean for people who must share buses, offices and theatres with potential carriers? Should people play it safe and shun fat people even more than they do already? Dhurandhar thinks not. 鈥淭he virus is highly infectious, for sure,鈥 he says. But so far he has only found antibodies to the virus in obese people, not the live virus itself. 鈥淭he million-dollar question is, does the person carry the virus intact for many years or not, and are obese people carrying the virus more than lean people?鈥 The marmosets, for example, stopped releasing live virus in their faeces after 60 days. If that鈥檚 typical, people who have become fat because of the virus are likely to be long past the infectious stage, even though their blood still carries antibodies as evidence of their past infection.
As Atkinson says: 鈥淎 fat person who鈥檚 gotten fat because of this virus isn鈥檛 going to hurt you. It鈥檚 that skinny guy with a cold who鈥檚 sneezing on you. Watch that guy. Discriminate against him.鈥
