Many thought it was the poor hygiene and inadequate medicines that laid waste to the entire world -- particularly Europe -- as millions of lives were lost, although the death toll only subsided but it would be centuries before the population starts to show signs of recovery. I'll cut to the chase: today humanity took on Ebola and H5N1 and its variant head-on; both are often labeled as deadly but these epidemics never came close to Black Death during the middle ages. I need a powerful pandemic to cripple the entire world -- something that rivals the black death... by the way I already considered nuclear holocaust but not when only one leader is trigger happy about it, right Mr Kim?
You need a virus that starts to be contagious early, but give the full spectrum of symptoms late.
If your virus is fast to act, it will be caught in quarantines and studied. If you want pandemic scale event, you need it to spread "disguised" as common cold or something equally innocent, and only kick in when it's already too late and substantial portion of humanity either caught it, or was exposed. Then, after months, virus should kick in - but it should be already built into cells' DNA, or in some organ you can't cut.
That said, bioengineered herpes or retroviruses would be my best bet. Given that 5 to 8% of our genome is made of retrovirus DNA, it's not a far fetched idea that a virus infection may spread, and then only kill months, years or even generations later. Herpes can be reactivated by increased level of radiation. You don't have to have a nuclear war, some accidents may suffice.
Imagine the dread - black plague happened in your grandpa's generation, they was there to stop it... but they didn't, and now something triggered it and it'll kill you. With our level of medicine and sanitation, I think that's the only way for such disaster to happen. Sure, no single virus has all the traits I'm describing, and let's be thankful for that, but it's believable enough.
Humanity had a near-muss with the SARS virus. It had mortality approaching 40%. Fortunately its infectivity was low enough that mere changes to human behaviour were sufficient to convert it from an exponentially growing infection into one that died out. (Face masks, gloves, avoiding physical contact in business and social settings).
Next time we may be less lucky. What to be most afraid of is a virus which is endemic in some common non-human species, which mutates into a strain deadly to humans without losing its ability to be spread by the other species. It would also have to spread fast before we could develop any vaccine or effective antiviral drug.
The Spanish flu was the last time this happened. (Flu is spread by birds and/or livestock). It's possible that at least one of the mediaeval plagues and the Roman "plague of Justinian" were not plague (now curable) but some other viral epidemic. Flu or some emergent virus like SARS are candidates. Fragmentary records and the primitive medicine of those times make it hard to be certain.
Smallpox was also a virus that emerged in near-pre-historical times (and we have clear historical records of what it did in the Americas where the population had no historic immunity).
It's possible that we could inflict this or worse on ourselves, but it would take a team of lunatics to do it. Plagues do not discriminate between friend and foe. If some country or group had pre-vaccinated its population and somehow kept that secret in advance, it would rapidly become clear when the plague struck. Retribution would follow, probably nuclear.
You need very specific disease. Lethal, infectious, virulent and transmissive but with low visibility, long incubation period, slow acting, initially asymptomatic or at the least non-specific (hard to distinguish from more benign diseases) and hard to treat.
Disease which is too lethal runs the risk of killing or immunising (those who survive, do so because their immune system beat the pathogen, and thus, they become immune, they may or may not still be hosts, depends on disease, some stay forever, just suppressed) entire host population before it has a chance to spread, not to mention it's highly noticeable.
Infectivity is an ability to cause infections, to establish itself within the organism and evade latent immune response. There are a lot of bacteria and viruses around us and immune system is good at eliminating or suppressing them before they can cause trouble. To cause an infection, there needs to be enough of pathogens so that they either locally overwhelm immune system, or at least few successfully evade it, start multiplying and overwhelm immune system later. The more infectious the disease, the less pathogens are needed.
Virulence is ability to cause damage to the host. It's correlated with both infectivity and lethality. The most infectious virus or bacteria will be harmless if it doesn't actually do anything harmful. Ways how pathogen can cause damage are varied. Bacteria eat or poison tissues, viruses take over cells and literally overwork them to death, making more copies of the virus. There is one unusual way of which I will speak later.
Transmissivity (did I build the word correctly?)
Transmissivity is an ability to use different modes of transmission for horizontal transfer (from one host to another). The most obvious is through body fluids, for example blood. But that won't do for your purposes, those are easily contained. Water-borne pathogen won't do either, that's not enough. Droplet transmission (transmission through tiny droplets released during coughing/sneezing) is getting there, but what you need is truly airborne disease, capable of surviving in air for a long time and circulate through air conditioning.
Is the time since infection to appearance of first symptoms. Host may or may not become infectious before showing symptoms, depends on disease.
Is a visible effect of a disease. Asymptomatic means without symptoms, since death is the most severe symptom imaginable, your disease can't go entirely asymptomatic.
Taken together, analysis of some famous pathogens
Ebola is right out. Severe bleeding gives it its high virulence and infectivity and lethality (it's very easy to catch disease by contact with blood, and bleeding weaken the organism), but at the same time makes it very visible, and since it's not airborne and thus not very transmissive, it's easy to contain. Also, it kills too fast. Unless vaccine/treatment was discovered recently, best course of action is to quarantine the area and let the virus "starve" itself, it will run out of new bodies to infect and disappear quickly. Fruit bats apparently are the reservoir of Ebola (animals which can carry it without getting sick - it's benign and asymptomatic for them), which extremely limits Ebola's ability to stay dormant in animal population outside of Africa - continent of its origin (if it could infect rats, that would be completely different matter).
Smallpox is out too. Mortality of 30% is too low for your purposes, furthermore, effective vaccines were developed, used both as treatments (when given very early during infection) and pre-emptive measures, leading to its effective eradication. If it somehow came back, we know how to handle it. It would take some time to collect new viral samples, compare with retained ones and re-establish vaccine production, but we know how to do it and we did it once, we can do so again.
Bubonic plague is in. Mortality reaching 90% in some outbreaks, proven track record (killed 50% of European population in 14 century) and nearly 2 week incubation period sound promising, but while vaccines are not very effective against it, antibiotics are. It's transmitted and hosted by fleas (to which it's harmless), which ride around the world on ever present rats, making controlling and quarantining it tricky, but not impossible. If you make it antibiotic resistant (which is happening to many bacteria due to overuse of antibiotics), somehow increase the reservoir to house pet fleas, you might get quite a lot of mileage out of this one. It's still highly visible, so after extreme containment measures, including extermination of rats, mice and all the house pets in affected areas, the threat will fade, you need your fleas to somehow bite a lot of international flight passengers to spread it before it's discovered and containment begins, that's going to be tricky. In first world rats and fleas are exterminated, in third world, the disease might "tip off its hand" too early, by infecting some village or small city, I assure you that this one would be taken way more seriously than Ebola was (Ebola was known for nearly 40 years now, but it never was and never will be a serious global threat because of reasons I outlined earlier, unless it evolves to be airborne or something like that).
My personal favourite, but actually less plausible than Bubonic Plague. Thanks to being airborne, influenze has extremely high transmitivity and infectivity, it however has very short incubation period, which means that depending on where the outbreak starts, it might be very easy to contain. Even in worst case scenario, it should be easier to quarantine than less transmitive diseases with much longer incubation period, and stable animal reservoir. Furthermore, influenza mutates rapidly, this means that it can become highly lethal out of the blue, but also means that lethal strains will starve themselves out of the hosts (because virus NEEDS the host to survive, or live at all, since it's an ongoing debate if viruses are actually alive at all, they don't have all the organelles to qualify as truly alive), and eliminate themselves out of the flue gene pool, leaving less lethal ones. It's a debate as to the true cases of mortality of Spanish Flu, one of the proposed is triggering a positive feedback loop in immune system reaction, causing it to effectively kill the body (you know how in cartoons multiple characters start fighting in a ball of dust and then the one who cause the fight slowly crawls out leaving rest to beat each other senseless? That's similar thing), making healthy adults more susceptible due to the strong immune system, whereas people with weaker immune system just suffer it like normal flu. It is however possible that reason behind mortality of Spanish Flu was external, 1918 was the last year of the Great War, shortages were widespread, and conditions were bad, both at the front and in far behind them. It's possible that this particular strain merely hit at the right moment, when supposedly strong people and societies were weakened, and flu was merely able to pave the way for secondary infections which would be what claimed the lives. Either way, you can get some serious mileage out of this, but you need to pick the moment and place right, since it can't stay hidden for long. Deadly flu would have to rely on being mistaken for normal (mostly harmless) one during first week, while asymptomatic hosts spread around the world, but after people start dying, it has no way to hide.
It's as much modern attitudes to sickness that have changed as modern medicine. In most western countries it's considered unacceptable to spread it around.
Consider a normal person with a severe illness. Most people in such a situation would call in sick and not go to work. Those who do go in are frowned on by colleagues for risking other people's health. You don't "man up" and go in regardless because that's antisocial. This means that even though we live in a high density world, and theoretically diseases could spread very rapidly, our attitudes and behaviours while sick will make most diseases self limiting.
The most recent pandemic was H1N1, Spanish Flu in 1918-1920. Viruses are much harder to treat than bacteria since the dawn of antibiotics, mostly with a virus you treat the symptoms and wait it out. In the case of Spanish Flu it primarily killed the young fit and healthy, soldiers coming out of the war, killed effectively by immune overreaction. The spread can also be considered to be down to vast numbers of people on the move and living in close quarters who would not normally have done so (i.e. not during a war).
I'm not going to write out the various theories of how such an aggressive strain of the flu came into circulation, but given the existence of such a strain you'd have to find some way of spreading it rapidly before the dangers became known.
With current monitoring of causes of death for exactly the reason of preventing another pandemic, you'd have to have a war at least on the scale of the Korean War, with large numbers of troops manning front lines, coming from across the world to high density locations, with people flying in and out steadily. Otherwise it's going to be nasty but localised, covering no more than a few surrounding regions. See Ebola for reference.
At the end of the day, given modern medicine and behaviours, while you could still potentially manage a pandemic, it's unlikely something will get established the way the Black Death did.
Have you considered... influenza? The Flu is pretty good at killing people. Think that the deadliest one is still H1N1. So you would just need to engineer it to hide like helicobacter pyroli (so a virus that survive 36,6 temperature) so almost anyone would be carrier. And then design "starter" point in virus so it would start acting on a large amount of people at once (maybe something with temperature? with global warming the difference in temperature in Europe is much more rapidly than it was before).
The virus must defeat modern preventitive measures
There are a variety of modern protective measures against disease. These modern measures are first and foremost cultural. If you are sick, most people don't try to go to work and spread their diseases around. Either they loaf around at at home or go to the doctor. Since everyone knows how modern diseases spread (more or less), everyone can take simple sanitary actions. The Black Death today would be much less likely to spread, first and foremost due to the lack of rats, but secondly due to the natural instinct of the sick to self-quarantine.
To defeat our modern cultural anti-sickness measures, the disease would need to pick up some new tricks. The most potent would be to simulate a mild illness for a long period of time allowing it to spread.
Characteristics of this disease
The illness should cause symptoms of a mild runny nose and sneezing. People who had gotten ill would think that they had a common cold. It should not cause fevers at an early stage or many people will be alerted to its potential severity.
The illness must be contagious immediately. As soon as the sneezing starts, the disease should be able to spread.
The illness should be viable airborne. If the disease can make people sneeze, and can stay infectious in the air for some hours (or even days), it can spread the most other people.
The illness should take a long time to kill. Here is the key. Once a disease is known to have killed many people, it will be widely reported and cause a near panic. Just look at how many people are upset over Zika despite its relatively low fatality rate. The disease needs to take weeks or months to kill. That would allow it the time to spread around the world and infect as many people as possible before causing fatalities.
I already asked a question along these lines here: Is non-manmade pandemic a realistic threat to modern first world?
The general answer I got from all of them was no. The major plagues spread so well in the past due to a lack of understanding of basic sanitation, our modern understanding of sanitation, quarantine, etc have made us much better at isolating and stopping the spread of disease. Antibodies also prevent the spread due to germs and vaccines the spread of viruses. While antibiotic immunity is an issue that would help a disease spread it's unlikely a disease would grow immune to all brands of antibiotics which are available at once, so antibiotics could a least be used to slow and limit the spread of the disease.
However, my original question was for natural viruses. The is also the possibility of man mad disease. I would suggest using a disease which was modified by man to make it more dangerous if you wanted a black plague scenario. It could have been an intentional bio-weapon which got out of hand, or a disease which was released by accident. However, adding the tweaking of humans could justify such things as how a disease developed an immunity to all known anti-biotics at once and thus justify it being a more lethal threat to society.
Black Death level diseases can only exist with a dispersed population or with a non-human reservoir, otherwise they burn themselves out and go extinct.
Since we no longer have an adequately dispersed population and no such killers are known that means something new.
Unfortunately, new diseases are all too possible due to mutations or species jumps. Fortunately, such upstarts tend to start out not too infective as they haven't adapted to the human body well enough yet.
We had a close call with SARS which was no doubt such a scenario. It hit in a place with sufficiently high tech medicine that it got pounced on and quarantined fast enough that it never developed the easy spreading that is required for a pandemic. Fortunately, nobody who was infected flew to a place like Africa that lacks the ability to stomp on it. It would have burned hot through the millions of Africans infected with HIV and by then it would likely be spreading better.
However, the really nasty scenario is when something that does spread well picks up lethal genes from somewhere. The flu is notorious for exchanging genes and so it's a likely culprit for this. Of course the disease hunters would see it and try to stomp on it but it spreads well enough quarantine would likely fail and vaccines take months. Modern air travel is a nightmare for quarantine efforts.
If you want to take the threat up to 11 consider a madman who does this deliberately. Instead of one patient zero you could have thousands. Put dispensers in a bunch of airports and the chance of a quarantine is zero.
Edit: Covid-19 and SARS are closely related. This time it got the spreadability, very fortunately its nowhere near as lethal.
Yersinia Pestis, with a twist!
Considering the fact that this little germ has been responsible for many significant outbreaks throughout history (the black death among them), using this troublesome bacterium would be a good start. If you want it to cripple modern civilization, not much has to be adjusted.
One of the things that makes Y. Pestis so deadly is the fact that it compromises immune function. Combine that with a resistance to most (or all) antibiotics and faster transmission vectors(casual contact, airborne), and you have an essentially untreatable pathogen that will spread like wildfire. Vaccines have been developed but aren't very effective and have some pretty nasty side effects, so they've fallen out of use for the most part. So, even if they were to develop a vaccine, there simply wouldn't be enough time to manufacture and distribute before it's too late.
Depending on how you want to utilize this pandemic, you could easily create a scenario with some sort of nanobots which gain a collective conscious. Prey by Michael Crichton has a similar premise.
If you are incorporating this into a story, it could be some level of AI like nanobot or otherwise be customized.
From the organic perspective, Executive Orders by Tom Clancy is insightful. Ebola is basically made airborn with a slower incubation period and released via aerosol cans at many conferences, resulting in it being quickly carried on airplanes around the world. This avoids some of the "problems" with a disease as dangerous as Ebola being too effective at killing its hosts, though within the novel this ultimately saves the United States.
I suggest a viral pathogen, man-made, transmitted both thru bodily fluids and airborne (highly contagious). Then add a long incubation during which infected person APPEARS symptom-free but is contagious, then respiratory symptoms kick in, making patient more contagious. Make disease a retrovirus that can go dormant and reappear once treatment stops, make respiratory symptoms resemble a fatal pneumonia and Voila! Instant Catastrophe.
One interesting possibility to look at is the (possibly) coming Antibiotic Apocalypse. Basically, certain antibiotics only work for so long before bacteria adapt to survive them. The more an Antibiotic is used (say, on livestock, or when over prescribed), the faster it becomes obsolete. We haven't run out of backup medicines yet, but if Antibiotic use keeps rapidly rising, and science starts running into barriers with regards to inventing new antibiotics, we could have a major problem.
At that point, even simple infections could cause death, surgeries would always be life threatening, and cuts would have the potential to kill. Now, add in some new super-bacteria, and you may have a ballgame.
Virus have a good characteristic: antibiotics don't prevent those little bunch of atoms from spreading and doing their nasty thing.
Just make it easily transmissible (like airborne, not requiring blood and so on). With a death probability high enough (>60%) and that takes some time to fully develop (a month), while it's capable of transmission since day 0, and it'll spread a lot before being detected and producing deaths.
Also make the death occur from symptoms that are easily mistaken from something else, and you gain some weeks before someone thinks that a new kind of plague is happening. For example, creating nodulus like a pancreatic cancer will make many patients go to a oncologist first, consuming time and not generating alarms from the first few days, nor special warnings about avoiding some kinds of contact.
And make it appear first in a crowded city, with many travelers, so that is spreads out fast enough since the first day.
If you want something that truly rivals black death you could create a more unique disease. One thing that immediately comes to mind is the issue of quarantining a disease (i.e. if nobody knows of it then it cannot be quaruntined). One thing you could do is make a disease with the symptoms of a normal cold. However, the symptoms start one month after exposure. Perhaps the disease lies dormant for some time and spreads itself whilst keeping immune system triggering damage to a minimum? Ultimately we want this disease to not be about affecting a body but rather infecting as much of the populous as possible. Furthermore, make the disease like rabies but not quite. We don't want zombies so instead cause people after 2 or 3 weeks of infection to somehow develop a compulsion to do something that infects other people. Perhaps make the disease cause a large amount of sneezing. Sneezing is less associated with illness so it's not going to be assumed as disease based but rather as allergy-related. Also, during this stage perhaps create compulsions of a need to be in social environments or something. Anything that could maximize exposure. Also, this disease should be about as contagious as bubonic plague (black death). Then it's pretty much guarunteed to spread amongst the masses. My guess. Within a month 60% of the world populous will be showing symptoms with the other 30% being infected. If you want to really make people spread this thing, have the virus or bacteria release adrenaline or other chemicals that make people feel not as sick as they truly are. Then at the 6th week drop all of those things like a rock by ceasing production which will result in an extreme crash of energy and then finally an unavoidable death as the virus/disease has by then obliterated the immune system (whilst temporarily replacing it to prevent suspicion).
Let me boil all of this down in a nutshell:
We want a disease whose primary method of attack is not brute force but rather deception. Therefore, it's plan of attack should be as follows:
Week 1: Spread throughout the body and replace as much of the immune system as possible. Work with the immune system if possible and have no tolerance for external diseases. Essentially replace the immune system.
Week 2: Continue a breakdown of natural systems whilst preventing overall detriment to the body. Produce sneezing and/or coughing as ways to spread the disease contagiously
Week 3-4: Attempt to produce chemicals and hormones to induce an intense need to be in public social environments as much as possible without appearing as a mental disorder. Use this to infect as many others as possible.
Week 5: Begin to show symptoms of some kind whether it be infections or whatever. Essentially test at breaking down systems of the body whilst not killing it (yet). Start producing hormones to fake higher energy levels to make the person feel better than they are. Raise these levels over time.
Week 6: Switch gears completely and start ripping the body to shreds. Work backwards to plummet the hormone levels to near nothing. Essentially cripple the person overnight. Fear is a tactic here. Make it seem worse than it is. Make people believe it appeared overnight and essentially ravaged EVERYTHING. Kill the bones completely. Ravage tissue. Make holes in the skin everywhere. Completely devour the internal organs. You've had six weeks to grow unimpeded. You are the immune system. You OWN the body and can consume it entirely near to the bone.
How would this disease occur? I would imagine it would bio-engineered and I think this would be a disease that could render man extinct. You basically have two months that this disease goes on before it reveals itself for the first time. That's a large time to be infecting others. Plus, it kills your immune system on day one. At that point, it is virtually incurable. It's got the force of an immune system disorder with the savageness of a foreign disease. Put those together and everyone is dead for sure.
I believe the gold standard civilization-killer is a bioengineered pox virus with a common animal reservoir. Release it at a few big airports and in a week it's everywhere, just as the first victims start showing symptoms.
In an interesting twist, a killer mousepox (lethal to mice only) from 2001 was accidentally created during research on injectable contraceptives. http://www.cidrap.umn.edu/news-perspective/2003/11/scientists-research-antidotes-super-mousepox-virus
COVID-21 (SARS-NCoV-2 x RHDV2)
While humans were busily fighting COVID-19 precautions, a little known virus called RHDV2 (rabbit hemorrhagic disease virus 2) took root in the United States, spreading from Arizona to Oregon and most places between. It killed both rabbits and hares, and no one cared, though few have seen any coney lately that doesn't lay boiled chicken eggs in green plastic grass. The CDC said it was not a hazard to human health.
Meanwhile, COVID viruses continued to mutate, occasionally undergoing a process of recombination in which the RNA-dependent RNA polymerase would dissociate from one virus it was copying, and begin copying another. Mutations were combined from different strains. Additionally, COVID, which had travelled the whole world, was in an excellent position to take up permanent endemic status in many mammalian species - cats, ferrets, horses ... and especially, rabbits.
What came next should not have surprised anyone.