Vaccines Are the Safest Medical Procedure We Have. Make Your Wager Wisely.
In the late 1650's the French polymath and renowned scientist Blaise Pascal, having undergone a religious experience that transformed him into something of a zealot, suggested the following logical strategy regarding belief in God: If there is a God, then believing in him will ensure you an eternity of bliss, while not believing in him could earn you an eternal sentence to misery.
On the other hand, if there is no God, believing in him anyway will cost you very little, and not believing in him will mean nothing in the non-existent after life. Therefore, the only sensible bet is to believe in God. This has come to be known as Pascal's wager.
It has a surprising number of applications beyond concerns for a comfortable afterlife. There are many things for which the value of believing something or not can be seen as a cost vs. likely benefit wager, often without regard to the actual truth of the matter. Since science does not profess to have a final truth, and in many areas freely admits its incomplete knowledge, Pascal's wager can provide a useful method of deciding between two alternatives.
For example, it seems that a significant percentage of the population is suspicious of science, or so we are told. We often hear that some large number, approaching or exceeding half of Americans, do not believe in evolution. This seems remarkable on the face of it because there is no viable scientific opposition to evolution and it is widely accepted by biologists and other life-scientists as being fundamental to understanding biology – from genetics to medicine.
What we are not often told is that most of those who answer negatively about believing in evolution nonetheless understand evolution – or at least the basics of it. They are not stupid, ignorant or uninformed. They have simply made a Pascalian wager. What benefit we might ask is derived from believing in evolution rather than a divine creation? Unless you are a professional biologist it is hard to see how this would affect your everyday life. On the other hand professing a belief in Darwinian evolution over the biblical narrative will likely ostracize you from family, friends, co-workers, your church community - in short most of your social infrastructure. Place your bets.
Can we apply any of this to decisions over the current controversy surrounding vaccination – and in particular the newly arrived Covid-19 vaccine?
While it is true that for entirely economic reasons, this is the first vaccine to be produced in this way, the method is not really new and the science that makes it possible has been developing over the last 40 years.
Common Concerns
There are certainly reasons to be concerned about being vaccinated and it would be a gross over-simplification to consider anyone who expresses reticence about taking a vaccine, this new vaccine in particular, as being just plain dumb or scientifically illiterate or gullible. They need be none of these things and still may be suspicious of the vaccine.
One issue is safety. The vaccine, any vaccine, is designed to mobilize your immune system, essentially to fool it into believing that there is an invading virus present and to mount an immune response. That way it will be ready when the real invasion comes, if it comes. This seems pretty sensible and preferable to going to war with an opponent you know nothing about. But still, it is fooling around with Mother Nature and some people are uneasy about that. Although it must be pointed out that the virus is not at all shy about fooling around with your immune system and many other parts of you, so letting it have its way is not good policy either.
What about a vaccine made of genes? This vaccine is being produced by what is being touted as a new method using RNA – genes. While it is true that for entirely economic reasons, this is the first vaccine to be produced in this way, the method is not really new and the science that makes it possible has been developing over the last 40 years. So it's not so radical as the press makes it seem.
But it is true that this method uses RNA, genetic material, to make the vaccine. We hear a lot about gene modification and the potential dangers associated with it. Why then am I going to allow RNA, genes, to be injected into me? The first thing to realize is that this is exactly what the virus does – so whether you get a vaccine or an infection, you are getting genes injected into you. The virus RNA encodes around 12 functional genes (by comparison humans and other mammals have around 25,000 genes). The virus only contains the genes to make a new virus – it does not have any of the capabilities of a normal cell to actually turn those genes into the proteins that make up the complete virus. It hijacks your cells to do this – and that's how it sickens you, by forcing your cells to make new viruses instead of what they should be doing.
Now the new vaccines have taken just one of those genes – the one that directs the production of the now infamous spike protein that appears on the surface of a normal virus – and injects just that one gene into your muscle cells, which then make that one single protein. Your immune system comes along and sees that weird protein and makes antibodies to it. These same antibodies will now recognize the spike protein on the surface of any viral particles that invade your body. We have effectively turned the virus into its own enemy.
The viral RNA that you are getting will decompose over a few days because RNA is not a stable molecule (that, by the way, is why the vaccine needs to be kept frozen) and it will no longer exist in your body. It could only become a permanent part of your genome if it were a DNA molecule instead of an RNA molecule – and even the chances of that happening would be chemically remote. So regardless of how it sounds, this may actually be the safest sort of vaccine to use. In the future it is likely that all vaccines will be made this way.
Then, of course, there is the issue of who is running this whole vaccine program – the government and the pharmaceutical industry. These are the guys who brought you opioid addiction, death by Vioxx, soaring drug prices, the worst health care system in the developed world, regulations where you don't need them and none where you do – am I really going to trust this cast of so-called "inept villains," as some believe, to dictate my personal health choices? Do we know for sure that the claims of efficacy are real or just made up to sell some worthless procedure? It would not be the first time. (I would not, on the other hand, worry about Bill Gates having a chip inserted into you along with the vaccine – if you use any social media, navigational tools, or purchase anything online, then Bill Gates already knows more about you than he will get from any injectable chip. So that train has left the station.)
The main upside to vaccines is that because they use your already existing defense system, they are surprisingly safe.
The Vaccine Wager
All this and a few lesser issues are worth a pause for sure. But we must also look on the positive side of the ledger. Why trust science? Modern medicine and the science behind it has eliminated or dramatically lessened such scourges as smallpox, polio, cholera, chicken pox, measles, rabies and dozens of other killer pathogens that had previously wiped out enormous numbers of people, in some cases significant parts of entire generations. Don't we depend on science for much of the comfort and safety of our everyday lives? Isn't science the way we heat our homes, drive to work, fly around the world, have dependable food? Yes, there is the bomb – but there is also anesthesia.
When it comes to viruses, the only tool we have to fight them is vaccination. The only tool. Antibiotics are for bacteria, a completely different sort of creature. Sanitation beyond personal hand washing is ineffective. Vaccines trick the immune system into recognizing the virus earlier than it would otherwise and protect normal cells from invasion by the virus. Tricking the immune system is understandably problematic for people who believe that their body knows best if it's just kept healthy. This virus, as we have seen from the array of infected people that includes apparently healthy folks, unfortunately does not subscribe to that belief.
By a similar sort of reasoning, some people make the plausible error of calculating that the vaccine is 95% effective but the survival rate is 99%, so why not just let my natural resistance take care of this? Indeed, that might not be unreasonable thinking if we were talking about the common cold, but this virus has shown itself to be a tricky character and we are not yet able to predict who gets a serious case and who a mild one. With those sorts of stakes, you shouldn't wager on either of those numbers because they have nothing to do with you as an individual. Like flipping a coin, there is only a 1% chance of it coming up heads 6 times in a row. But if it has come up heads 5 times in a row the probability of it coming up heads on the next flip is … still 50/50.
An even larger unknown is whether there may be long-term effects associated with SARS-Cov-2, as is the case for many viruses. The 1918 influenza virus has been linked to a subsequent 2-3 fold increase in Parkinson's disease by a mechanism we still don't understand. The virus that gives children chicken pox will hide out in a person's body for 40 years or more and then emerge as a painful, sometimes debilitating, case of shingles. The 99% survivability rate of this virus is meaningless if 20 years from now it causes some devastating pulmonary or brain disease.
The main upside to vaccines is that because they use your already existing defense system, they are surprisingly safe. Safer than antibiotics which have numerous side effects because they are not part of our normal make up and are cell killers – mostly bacterial cells, but they are not so perfectly targeted that they don't leave some collateral damage in their wake. All drugs and treatments have side effects, but vaccines in general have the fewest. This vaccine in particular has undergone many more than the usual safety measures - multiple independent review boards, massive press and public attention, governmental and non-governmental oversight, the most diverse trial cohorts ever assembled. Nothing here was rushed, no shortcuts were taken.
So here's the vaccine wager. Vaccines are the safest medical procedure we have. They are also among the most effective, but that's curiously not important for the bet. My claim about their safety is because vaccines are in a special class of medical tools. They are the only medical procedure or drug that is given to healthy people. Every other treatment we use medically is aimed at some existing pathology - from a cold to cancer.
Vaccines therefore have to reach a higher standard of safety than any other medical treatment. You can't take healthy people and make them sick. Vaccines have fewer side effects than virtually any other drug you wouldn't even think twice about taking – aspirin, for instance, which can cause internal bleeding, gastric ulcers, stroke. But since you are sick when you take those drugs you are willing to make the bet that the benefits will outweigh the possible side effects.
With vaccines the wager is much simpler – it is indeed more like Pascal's original wager. It may or may not be highly effective (some vaccines are only 60% effective) but they are so safe that taking them poses little risk, whereas not taking them subjects you (and others) to considerable risk, i.e., getting the virus. Like believing or not in an afterlife, the smart money is with Pascal, who I think would have reasoned himself right to the head of the vaccination line.
In May 2022, Californian biotech Ultima Genomics announced that its UG 100 platform was capable of sequencing an entire human genome for just $100, a landmark moment in the history of the field. The announcement was particularly remarkable because few had previously heard of the company, a relative unknown in an industry long dominated by global giant Illumina which controls about 80 percent of the world’s sequencing market.
Ultima’s secret was to completely revamp many technical aspects of the way Illumina have traditionally deciphered DNA. The process usually involves first splitting the double helix DNA structure into single strands, then breaking these strands into short fragments which are laid out on a glass surface called a flow cell. When this flow cell is loaded into the sequencing machine, color-coded tags are attached to each individual base letter. A laser scans the bases individually while a camera simultaneously records the color associated with them, a process which is repeated until every single fragment has been sequenced.
Instead, Ultima has found a series of shortcuts to slash the cost and boost efficiency. “Ultima Genomics has developed a fundamentally new sequencing architecture designed to scale beyond conventional approaches,” says Josh Lauer, Ultima’s chief commercial officer.
This ‘new architecture’ is a series of subtle but highly impactful tweaks to the sequencing process ranging from replacing the costly flow cell with a silicon wafer which is both cheaper and allows more DNA to be read at once, to utilizing machine learning to convert optical data into usable information.
To put $100 genome in perspective, back in 2012 the cost of sequencing a single genome was around $10,000, a price tag which dropped to $1,000 a few years later. Before Ultima’s announcement, the cost of sequencing an individual genome was around $600.
Several studies have found that nearly 12 percent of healthy people who have their genome sequenced, then discover they have a variant pointing to a heightened risk of developing a disease that can be monitored, treated or prevented.
While Ultima’s new machine is not widely available yet, Illumina’s response has been rapid. In September 2022, the company unveiled the NovaSeq X series, which it describes as its fastest most cost-efficient sequencing platform yet, capable of sequencing genomes at $200, with further price cuts likely to follow.
But what will the rapidly tumbling cost of sequencing actually mean for medicine? “Well to start with, obviously it’s going to mean more people getting their genome sequenced,” says Michael Snyder, professor of genetics at Stanford University. “It'll be a lot more accessible to people.”
At the moment sequencing is mainly limited to certain cancer patients where it is used to inform treatment options, and individuals with undiagnosed illnesses. In the past, initiatives such as SeqFirst have attempted further widen access to genome sequencing based on growing amounts of research illustrating the potential benefits of the technology in healthcare. Several studies have found that nearly 12 percent of healthy people who have their genome sequenced, then discover they have a variant pointing to a heightened risk of developing a disease that can be monitored, treated or prevented.
“While whole genome sequencing is not yet widely used in the U.S., it has started to come into pediatric critical care settings such as newborn intensive care units,” says Professor Michael Bamshad, who heads the genetic medicine division in the University of Washington’s pediatrics department. “It is also being used more often in outpatient clinical genetics services, particularly when conventional testing fails to identify explanatory variants.”
But the cost of sequencing itself is only one part of the price tag. The subsequent clinical interpretation and genetic counselling services often come to several thousand dollars, a cost which insurers are not always willing to pay.
As a result, while Bamshad and others hope that the arrival of the $100 genome will create new opportunities to use genetic testing in innovative ways, the most immediate benefits are likely to come in the realm of research.
Bigger Data
There are numerous ways in which cheaper sequencing is likely to advance scientific research, for example the ability to collect data on much larger patient groups. This will be a major boon to scientists working on complex heterogeneous diseases such as schizophrenia or depression where there are many genes involved which all exert subtle effects, as well as substantial variance across the patient population. Bigger studies could help scientists identify subgroups of patients where the disease appears to be driven by similar gene variants, who can then be more precisely targeted with specific drugs.
If insurers can figure out the economics, Snyder even foresees a future where at a certain age, all of us can qualify for annual sequencing of our blood cells to search for early signs of cancer or the potential onset of other diseases like type 2 diabetes.
David Curtis, a genetics professor at University College London, says that scientists studying these illnesses have previously been forced to rely on genome-wide association studies which are limited because they only identify common gene variants. “We might see a significant increase in the number of large association studies using sequence data,” he says. “It would be far preferable to use this because it provides information about rare, potentially functional variants.”
Cheaper sequencing will also aid researchers working on diseases which have traditionally been underfunded. Bamshad cites cystic fibrosis, a condition which affects around 40,000 children and adults in the U.S., as one particularly pertinent example.
“Funds for gene discovery for rare diseases are very limited,” he says. “We’re one of three sites that did whole genome sequencing on 5,500 people with cystic fibrosis, but our statistical power is limited. A $100 genome would make it much more feasible to sequence everyone in the U.S. with cystic fibrosis and make it more likely that we discover novel risk factors and pathways influencing clinical outcomes.”
For progressive diseases that are more common like cancer and type 2 diabetes, as well as neurodegenerative conditions like multiple sclerosis and ALS, geneticists will be able to go even further and afford to sequence individual tumor cells or neurons at different time points. This will enable them to analyze how individual DNA modifications like methylation, change as the disease develops.
In the case of cancer, this could help scientists understand how tumors evolve to evade treatments. Within in a clinical setting, the ability to sequence not just one, but many different cells across a patient’s tumor could point to the combination of treatments which offer the best chance of eradicating the entire cancer.
“What happens at the moment with a solid tumor is you treat with one drug, and maybe 80 percent of that tumor is susceptible to that drug,” says Neil Ward, vice president and general manager in the EMEA region for genomics company PacBio. “But the other 20 percent of the tumor has already got mutations that make it resistant, which is probably why a lot of modern therapies extend life for sadly only a matter of months rather than curing, because they treat a big percentage of the tumor, but not the whole thing. So going forwards, I think that we will see genomics play a huge role in cancer treatments, through using multiple modalities to treat someone's cancer.”
If insurers can figure out the economics, Snyder even foresees a future where at a certain age, all of us can qualify for annual sequencing of our blood cells to search for early signs of cancer or the potential onset of other diseases like type 2 diabetes.
“There are companies already working on looking for cancer signatures in methylated DNA,” he says. “If it was determined that you had early stage cancer, pre-symptomatically, that could then be validated with targeted MRI, followed by surgery or chemotherapy. It makes a big difference catching cancer early. If there were signs of type 2 diabetes, you could start taking steps to mitigate your glucose rise, and possibly prevent it or at least delay the onset.”
This would already revolutionize the way we seek to prevent a whole range of illnesses, but others feel that the $100 genome could also usher in even more powerful and controversial preventative medicine schemes.
Newborn screening
In the eyes of Kári Stefánsson, the Icelandic neurologist who been a visionary for so many advances in the field of human genetics over the last 25 years, the falling cost of sequencing means it will be feasible to sequence the genomes of every baby born.
“We have recently done an analysis of genomes in Iceland and the UK Biobank, and in 4 percent of people you find mutations that lead to serious disease, that can be prevented or dealt with,” says Stefansson, CEO of deCODE genetics, a subsidiary of the pharmaceutical company Amgen. “This could transform our healthcare systems.”
As well as identifying newborns with rare diseases, this kind of genomic information could be used to compute a person’s risk score for developing chronic illnesses later in life. If for example, they have a higher than average risk of colon or breast cancer, they could be pre-emptively scheduled for annual colonoscopies or mammograms as soon as they hit adulthood.
To a limited extent, this is already happening. In the UK, Genomics England has launched the Newborn Genomes Programme, which plans to undertake whole-genome sequencing of up to 200,000 newborn babies, with the aim of enabling the early identification of rare genetic diseases.
"I have not had my own genome sequenced and I would not have wanted my parents to have agreed to this," Curtis says. "I don’t see that sequencing children for the sake of some vague, ill-defined benefits could ever be justifiable.”
However, some scientists feel that it is tricky to justify sequencing the genomes of apparently healthy babies, given the data privacy issues involved. They point out that we still know too little about the links which can be drawn between genetic information at birth, and risk of chronic illness later in life.
“I think there are very difficult ethical issues involved in sequencing children if there are no clear and immediate clinical benefits,” says Curtis. “They cannot consent to this process. I have not had my own genome sequenced and I would not have wanted my parents to have agreed to this. I don’t see that sequencing children for the sake of some vague, ill-defined benefits could ever be justifiable.”
Curtis points out that there are many inherent risks about this data being available. It may fall into the hands of insurance companies, and it could even be used by governments for surveillance purposes.
“Genetic sequence data is very useful indeed for forensic purposes. Its full potential has yet to be realized but identifying rare variants could provide a quick and easy way to find relatives of a perpetrator,” he says. “If large numbers of people had been sequenced in a healthcare system then it could be difficult for a future government to resist the temptation to use this as a resource to investigate serious crimes.”
While sequencing becoming more widely available will present difficult ethical and moral challenges, it will offer many benefits for society as a whole. Cheaper sequencing will help boost the diversity of genomic datasets which have traditionally been skewed towards individuals of white, European descent, meaning that much of the actionable medical information which has come out of these studies is not relevant to people of other ethnicities.
Ward predicts that in the coming years, the growing amount of genetic information will ultimately change the outcomes for many with rare, previously incurable illnesses.
“If you're the parent of a child that has a susceptible or a suspected rare genetic disease, their genome will get sequenced, and while sadly that doesn’t always lead to treatments, it’s building up a knowledge base so companies can spring up and target that niche of a disease,” he says. “As a result there’s a whole tidal wave of new therapies that are going to come to market over the next five years, as the genetic tools we have, mature and evolve.”
This article was first published by Leaps.org in October 2022.
The livestock trucks arrived all night. One after the other they backed up to the wood chute leading to a dusty corral and loosed their cargo — 580 head of cattle by the time the last truck pulled away at 3pm the next afternoon. Dan Probert, astride his horse, guided the cows to paddocks of pristine grassland stretching alongside the snow-peaked Wallowa Mountains. They’d spend the summer here grazing bunchgrass and clovers and biscuitroot. The scuffle of their hooves and nibbles of their teeth would mimic the elk, antelope and bison that are thought to have historically roamed this portion of northeastern Oregon’s Zumwalt Prairie, helping grasses grow and restoring health to the soil.
The cows weren’t Probert’s, although the fifth-generation rancher and one other member of the Carman Ranch Direct grass-fed beef collective also raise their own herds here for part of every year. But in spring, when the prairie is in bloom, Probert receives cattle from several other ranchers. As the grasses wither in October, the cows move on to graze fertile pastures throughout the Columbia Basin, which stretches across several Pacific Northwest states; some overwinter on a vegetable farm in central Washington, feeding on corn leaves and pea vines left behind after harvest.
Sharing land and other resources among farmers isn’t new. But research shows it may be increasingly relevant in a time of climatic upheaval, potentially influencing “farmers to adopt environmentally friendly practices and agricultural innovation,” according to a 2021 paper in the Journal of Economic Surveys. Farmers might share knowledge about reducing pesticide use, says Heather Frambach, a supply chain consultant who works with farmers in California and elsewhere. As a group they may better qualify for grants to monitor soil and water quality.
Most research around such practices applies to cooperatives, whose owner-members equally share governance and profits. But a collective like Carman Ranch’s — spearheaded by fourth-generation rancher Cory Carman, who purchases beef from eight other ranchers to sell under one “regeneratively” certified brand — shows when producers band together, they can achieve eco-benefits that would be elusive if they worked alone.
Vitamins and minerals in soil pass into plants through their roots, then into cattle as they graze, then back around as the cows walk around pooping.
Carman knows from experience. Taking over her family's land in 2003, she started selling grass-fed beef “because I really wanted to figure out how to not participate in the feedlot world, to have a healthier product. I didn't know how we were going to survive,” she says. Part of her land sits on a degraded portion of Zumwalt Prairie replete with invasive grasses; working to restore it, she thought, “What good does it do to kill myself trying to make this ranch more functional? If you want to make a difference, change has to be more than single entrepreneurs on single pieces of land. It has to happen at a community level.” The seeds of her collective were sown.
Raising 100 percent grass-fed beef requires land that’s got something for cows to graze in every season — which most collective members can’t access individually. So, they move cattle around their various parcels. It’s practical, but it also restores nutrient flows “to the way they used to move, from lowlands and canyons during the winter to higher-up places as the weather gets hot,” Carman says. Meaning, vitamins and minerals in soil pass into plants through their roots, then into cattle as they graze, then back around as the cows walk around pooping.
Cory Carman sells grass-fed beef, which requires land that’s got something for cows to graze in every season.
Courtesy Cory Carman
Each collective member has individual ecological goals: Carman brought in pigs to root out invasive grasses and help natives flourish. Probert also heads a more conventional grain-finished beef collective with 100 members, and their combined 6.5 million ranchland acres were eligible for a grant supporting climate-friendly practices, which compels them to improve soil and water health and biodiversity and make their product “as environmentally friendly as possible,” Probert says. The Washington veg farmer reduced tilling and pesticide use thanks to the ecoservices of visiting cows. Similarly, a conventional hay farmer near Carman has reduced his reliance on fertilizer by letting cattle graze the cover crops he plants on 80 acres.
Additionally, the collective must meet the regenerative standards promised on their label — another way in which they work together to achieve ecological goals. Says David LeZaks, formerly a senior fellow at finance-focused ecology nonprofit Croatan Institute, it’s hard for individual farmers to access monetary assistance. “But it's easier to get financing flowing when you increase the scale with cooperatives or collectives,” he says. “This supports producers in ways that can lead to better outcomes on the landscape.”
New, smaller scale farmers might gain the most from collective and cooperative models.
For example, it can help them minimize waste by using more of an animal, something our frugal ancestors excelled at. Small-scale beef producers normally throw out hides; Thousand Hills’ 50 regenerative beef producers together have enough to sell to Timberland to make carbon-neutral leather. In another example, working collectively resulted in the support of more diverse farms: Meadowlark Community Mill in Wisconsin went from working with one wheat grower, to sourcing from several organic wheat growers marketing flour under one premium brand.
Another example shows how these collaborations can foster greater equity, among other benefits: The Federation of Southern Cooperatives has a mission to support Black farmers as they build community health. It owns several hundred forest acres in Alabama, where it teaches members to steward their own forest land and use it to grow food — one member coop raises goats to graze forest debris and produce milk. Adding the combined acres of member forest land to the Federation’s, the group qualified for a federal conservation grant that will keep this resource available for food production, and community environmental and mental health benefits. “That's the value-add of the collective land-owner structure,” says Dãnia Davy, director of land retention and advocacy.
New, smaller scale farmers might gain the most from collective and cooperative models, says Jordan Treakle, national program coordinator of the National Family Farm Coalition (NFFC). Many of them enter farming specifically to raise healthy food in healthy ways — with organic production, or livestock for soil fertility. With land, equipment and labor prohibitively expensive, farming collectively allows shared costs and risk that buy farmers the time necessary to “build soil fertility and become competitive” in the marketplace, Treakle says. Just keeping them in business is an eco-win; when small farms fail, they tend to get sold for development or absorbed into less-diversified operations, so the effects of their success can “reverberate through the entire local economy.”
Frambach, the supply chain consultant, has been experimenting with what she calls “collaborative crop planning,” where she helps farmers strategize what they’ll plant as a group. “A lot of them grow based on what they hear their neighbor is going to do, and that causes really poor outcomes,” she says. “Nobody replanted cauliflower after the [atmospheric rivers in California] this year and now there's a huge shortage of cauliflower.” A group plan can avoid the under-planting that causes farmers to lose out on revenue.
It helps avoid overplanted crops, too, which small farmers might have to plow under or compost. Larger farmers, conversely, can sell surplus produce into the upcycling market — to Matriark Foods, for example, which turns it into value-add products like pasta sauce for companies like Sysco that supply institutional kitchens at colleges and hospitals. Frambach and Anna Hammond, Matriark’s CEO, want to collectivize smaller farmers so that they can sell to the likes of Matriark and “not lose an incredible amount of income,” Hammond says.
Ultimately, farming is fraught with challenges and even collectivizing doesn’t guarantee that farms will stay in business. But with agriculture accounting for almost 30 percent of greenhouse gas emissions globally, there's an “urgent” need to shift farming practices to more environmentally sustainable models, as well as a “demand in the marketplace for it,” says NFFC’s Treakle. “The growth of cooperative and collective farming can be a huge, huge boon for the ecological integrity of the system.”