In 1968, two recent U.S. medical school graduates working in Dhaka, Bangladesh, developed oral rehydration solution—a mixture of water, sugar, and salt—that the British medical journal the Lancet has hailed “potentially the most important medical advance of the twentieth century.” These two doctors, Richard Cash, senior lecturer in the Department of Global Health and Population at the Harvard T.H. Chan School of Public Health, and David Nalin, professor emeritus at the Center for Immunology and Microbial Diseases at Albany Medical College, discussed the fifty-year legacy of their invention and the lessons that legacy offers to the health challenges emerging in lower income nations today.
BOLLYKY: Thank you for coming on this busy news day right right before the Easter and Passover holidays. You’re in for a treat.
Think back to what you were doing when you were twenty-six years old. When these two gentlemen were twenty-six, they were in Dhaka, then known as East Pakistan, working on cholera treatments. It was 1968, and David Nalin had just completed his first year of medical residence. Richard Cash had just finished his internship in surgery and had become a U.S. public health service officer. They were based at the Pakistan Cholera Research Lab, which lab was established as part of a Cold War surge in U.S. aid to Pakistan. There, David and Richard tested an oral solution of glucose and salt with twenty-nine patients, based on some earlier scientific findings that sugar might help the gut absorb new fluid.
That simple solution has changed the world. During the late 1970s, the World Health Organization estimated that there were five hundred million episodes of diarrhea in children under the age of five each year, resulting in roughly five million deaths from diarrheal diseases, like cholera, annually. Part of the problem that you had was the standard of care for extreme dehydration was saline that needed to be provided intravenously. It was expensive. It required the help of a nurse or a physician. And it was difficult to provide in low-resource, low-infrastructure settings. Oral rehydration solution (ORS), which then became part of oral rehydration therapy (ORT), helped change all that. Today it is credited with saving more than fifty million lives in the twentieth century alone. And the Lancet has hailed it as potentially the most important medical advance of the twentieth century. Deaths from diarrheal diseases globally have declined more than 80 percent since 1980, in great part because of oral rehydration therapy.
Today’s roundtable is meant to mark the fifty years that have passed since David and Richard’s initial work. We will discuss what has transpired over those fifty years to disseminate that work and spread an idea that worked globally, which does not always happen. We will also discuss whether or not that approach can be applied to some of the health challenges that are facing Bangladesh and other lower-income countries today—like noncommunicable diseases.
And I’m thrilled to have this opportunity to host this event. It’s a great honor for me. I had the opportunity as part of a book I recently wrote to interview David and to talk to—or, correspond with Richard. I’m so pleased to have them here.
You have their biographies before you, so I’m not going to go over the distinguished career that they’ve had since they were twenty-six years old. I also realize I just revealed their ages. I hope they’re fine with that. (Laughter.) I will only note their current titles. Richard is the—to my immediate right—is the senior lecturer at the Department of Global Health and Population at the Harvard Chan School of Public Health. David is the—currently the professor emeritus at the Center for Immunology and Microbial Diseases at Albany Medical College.
As most of you know that have attended Council events in the past, we do not generally have slides. But when David asked to use some photos to support his initial remarks, I decided, particularly in this instance, this is something we can make an exception for. And I hope you’ll understand. They will both make ten minutes of initial remarks, and then I will ask a few questions to get us started, and then I’m looking forward to getting questions from all of you. Today’s event is on the record and for attribution. That means both the speaker and the ideas that are discussed today are welcomed to be used and quoted. If you haven’t already, I’d be grateful if you turned off your electronic devices. And, with that, allow me to turn it over to David.
NALIN: Thank you, Tom. I’m going to start with a capsule description of what oral therapy is in terms of patients, and how it benefits them. The series of slides I’m going to show you were based on photographs I took in Lahore, Pakistan around 1980, when I was called to a patient in a field area that we were working in. And if I can have the first slide? The patient was this little girl who was on the verge of death. Now, you can see the signs of severe dehydration—the deeply sunken eyes. She’s obtunded but still conscious. Next slide. We taught the parents—who recognized the deeply sunken eyes better than doctors do when their child is dehydrated to this extent—we taught the parents to pinch the skin and see if it tented. As you can see, due to dehydration, when you pinch the skin it remains up, doesn’t come back. These are basic clinical signs which we use to transform oral rehydration from hospital laboratory testing facilities to the home, where the mother would be treating her child, hopefully early in the course of disease. Next slide, please.
So having begun feeding the child the oral solution—and this was the original WHO oralyte, containing ninety millimoles of sodium, a very good solution. So she’s taking some given by her father. Next slide. Now she’s getting a little more alert, and she’s holding onto her father’s hand to make sure that it keeps coming. Next slide, please. Now, she’s waking up to her environment. Next slide. And here we see her at the beginning and then after treatment. Unfortunately, she still has that nib in her mouth, which probably gave her the infection in the first place, especially when the kids drop them in a highly contaminated environment. So next slide please. This is the ultimate goal. Not—to give oral therapy at the very onset of diarrhea, before dehydration, when children are taking it, in this case by spoonfuls, and prevent the type of dehydration we saw in the earlier slides.
And this approach is what has literally, as of the latest UNICEF figures, decimated—that is, reduced to 10 percent of the original five million deaths per year. The latest figures, last year it was seven hundred twenty thousand and this year it’s targeted to reach five hundred thousand, which would be a true decimated. Next slide. In this final slide, I summarize the benefits of ORT. First of all, it reduces severe malnutrition, called marasmus, because the previous treatments, including at Johns Hopkins and Bangladesh, was when a child had diarrhea, you practice what was taught at medical colleges at that time, starvation therapy. They thought that if you gave anything by mouth it made the diarrhea worse. And they didn’t know that in the presence of glucose, or some amino acids or other sugars, you could—even during diarrhea, they could absorb it.
So that reduced malnutrition to such an extent that in countries I visited, including notably Jordan and Costa Rica, where the malnutrition ward was right next to the diarrhea ward, after several years the malnutrition wards in those two countries were closed. Next. It bypassed the problems that were alluded to by Tom of cost and non-availability of intravenous fluids in many of the endemic areas affected by diarrhea. And those issues are obviated. Then it reduced the harm induced by IV. I have a series of photographs, we’re not clinical here today so I don’t show them, but in many countries I visited as a WHO or PAHO consultant, I would go in the ward and the little children were in straightjackets. Literally they couldn’t move their arms, because they’d pull out the IVs. And in these straightjackets, sometimes they would vomit and aspirate and die of aspirational pneumonia. And very often the IVs would become dislodged. And I have photographs with dozens of wounds from IVs. And the kids look like they have post-traumatic stress syndrome. So a lot of this IV harm can be also obviated.
In addition, by giving oral therapy an effective treatment, one helps to prevent use of inappropriate and ineffective other therapies. For example, in Jamaica, tincture of marijuana is a favorite for diarrhea. It doesn’t help. The most important thing is we give a tool to enhance the maternal repertoire. We enable the mother to take power over the condition, treat the child earlier, as you saw in that slide with the teaspoon, prevent dehydration. And this was particularly true in the days when I would go to the emergency rooms in developing countries and there would be a line of two hundred mothers holding infants with diarrhea in the waiting room. And it took eight hours for a doctor see them. During that eight hours, if they weren’t dehydrated at the beginning, they were dehydrated, sometimes severely, by the end. So by the simple maneuver of introducing oral therapy to be handed out by nursing assistants to that long line of mothers, we prevented a lot of severe dehydration.
I mentioned the decrease in mortality which Tom referred to as of 2000. But as of this year, as I say, it’s even more. And then at a presentation at the International Congress of Nephrology a few years ago in Hong Kong, the subject was—I was wondering why they invited me—but they said that the kidney specialists have observed a sharp decrease in acute renal failure induced by dehydration since the introduction of oral therapy. So that’s oral therapy in a nutshell.
CASH: OK. Thanks. I’m going to look at the whole notion of how do you take this observation and scale it up, both locally and globally, or from one to many. It seems obvious that people would want to take this on, but discovery does not equal implementation. In the early days, we tried to actually—we were very enthusiastic to get pharma or Coca-Cola distributors, or people who made matches, or sandals, or what have you, to distribute this. But we couldn’t find much enthusiasm. Maybe they thought that there wasn’t enough profit to be made, because we were talking about something worth a few cents. And there was resistance, especially from doctors who thought maybe this is too simple, too inexpensive and, by the way, were selling other things, many of them, rehydration units in their little—in their little cabins anyway.
But then a series of things took place, not to our making but internationally. There was a conference called the Alma Ata Conference in 1978 which called for Health for All by the year 2000. And they were looking for low-cost, accessible, effective treatments to prevent or lead to a reduction in the common event, and oral therapy was, like, the poster child for that. So they were really enthusiastic. This was then picked up by Jim Grant, who was head of UNICEF, who developed a program. And his colleagues developed something called GOBI—growth monitoring, G; O, oral rehydration therapy; B, breastfeeding; and, I, immunization. And so there were these international movements that saw this as a very positive thing—including USAID, who sponsored a number of major meetings and so on that brought people together.
And after all the experience in the agricultural community was that it takes about fifteen years for an innovation to become widely accepted. Now, one of the problems, of course, with any international organization is they kind of want to do it their way. And so WHO wanted everybody to use their method. They were having packets. They said, we want these packets to be for one thousand ccs, and so on. Here’s one of these kind of packets. This is for five hundred, and I’ll get into that. But ultimately, the acceptance of this is—really has to be done nationally or locally. You can have all of the global movements you want, but the actual implementation has to come where the problem is.
One of these that I was very involved in is with an NGO in Bangladesh, now actually the world’s largest NGO. It’s called BRAC, B-R-A-C, and it’s actually also been rated number. Now, I’m a little biased. I’m on the board of BRAC USA. But, you know, we’ll consider that. And it’s a pro-poor, pro-women NGO. The favorite quote of the director, Sir Fazle Abed, is: “Small is beautiful but big is necessary.” So the were into scaling up. And they developed this method where they would use a three-finger pinch of salt and a handful of sugar and five hundred ccs, which they showed women how to reach five hundred ccs. And over a ten-year period, they literally trained women in their home, not in the clinic, twelve million mothers. And Bangladesh today has the lowest—one of the lowest death rates from diarrhea, and the highest use rate of ORT.
Actually, we wrote those in a book called The Simple Solution, which sort of documents this whole issue. And the method of teaching the mothers was very, very effective, from a management point of view, so that 98 percent of the women learned how to make this. And it became almost part of the folk culture. So you can go to—you can go to villages in Bangladesh ten years, fifteen years after the mother was taught, and the children will know how to do this. They’ll know this method. So once—you know, one could say, well, where did the folk wisdom for chicken soup and colds come from? Probably a similar approach was used.
Finding the right actors and programs to implement is as important as the technology itself. And WHO did get involved in training programs for doctors to convince them that this was important. But there are, I think, very important lessons from the BRAC program. You have to have an institutional vision. You got to—you got to decide: I want to scale this up. And in scaling up, you got to keep things as simple as possible. You got to take that Mercedes Benz and make a Volkswagen out of it, because that’s the way you’re going to increase use. You have to train people. And you have to get mothers and people in the community involved. As I say, finding the right actors is really important.
As David had noted, and others have noted, diarrhea deaths have fallen, of which ORT I’m sure has played a role—as has immunization, and a number of different things. But it’s now finding other uses. In nursing homes, the elderly often get dehydrated because they lose their ability to feel dehydration. ORT is effective. ORT, it turns out, is very important in the Ebola outbreak, because diarrhea is a major killer. In 2007, there was a cholera outbreak in Dhaka, and about forty-three thousand people were admitted to the institution that we were at. And using a combination of treatments, not one person of that forty-three thousand died of diarrheal disease. But I can tell you, that if the same thing happened in the Mecca, in Boston, or in Washington, D.C., and so on, it would implode the system because in Dhaka the parents were involved in the treatment. Nobody can treat patients coming in at a thousand today. So you’ve got to—you’ve got to transmit that knowledge and get them involved in treatment. We don’t do that. We separate the parents from children, and so on. We professionalize. But in the process of doing it, I believe, we don’t achieve what we could achieve.
I was very heartened the other day. I was talking to a recent doctoral student. And he said, ORT, that’s really big in the economics community. I said, oh, yeah? Really? Evidently—I’m no economist—but Paul Romer, who was the co-winner of the Nobel Prize for Economics in 2018, uses ORT as a model for pointing out how new ideas and the transmission of new ideas can influence economic growth. That is, ideas are non-rival. They’re not limited in distribution. And ORT, once you know how to do it, it’s not limited by cost. It’s not limited by availability. And so he uses this as a model for how to transmit ideas. And lastly, I’ll finish with a well-known quote from Albert Einstein, who said, “Everything should be as simple as possible, but not one bit simpler.” (Laughter.)
So those are my thoughts on scaling up. And it’s—you know, we’ve been very privileged to be able to get in on the ground floor of development, and to see something through a fifty-year lens is a rare privilege. And so I think we’re both fortunate that we’ve been able to do that. So those are my thoughts.
NALIN: I just want to add one thing.
NALIN: In case Richard’s remarks about cholera in Washington, D.C. have made any of you queasy—(laughter)—the good news is that in developing countries where people have a good diet, stomach acid is normal. And individuals with normal stomach acid, cannot—almost never get cholera, unless they take the cholera germs in a glass of bicarbonate of soda or Alka-Seltzer to neutralize the stomach acid. The problem in the developing world is that almost 40 percent of individuals in the developing world have no stomach acid, for reasons that have yet to be discovered.
BOLLYKY: All right. Hopefully that gave everyone some comfort. (Laughter.) I am going to ask two very hopefully relatively brief questions to get the conversation started. But I had my chance to interview both of these gentlemen before and focus on it in the book, so I will turn it over soon to you. So I want you to think about what questions you might ask, because I will then turn to you. I will call on you in the order that I see your placard. So for those of you that would like to raise that placard now, you’re welcome to do so.
So you mentioned the spread of ORT. And what I wanted to ask about are some of the limits to that spread and the reasons why you think that’s so. You mentioned that in high-income countries the use of oral rehydration therapy is relatively low. But it’s also true that use is low in a lot of sub-Saharan Africa nations. What do you see needing to happen to change that? Is it the lack of a supporting institution? BRAC was obviously initially Bangladesh based. It has now spread more globally. But is it because of that lack of an institution to do the hard work of connecting this remedy to parents? What do you see as limiting the reach of ORT in both high-income countries and some of the poorest?
CASH: Well, I think in the poor countries, you know, all of these things require multiple entry points. You’ve got to, A, convince the hierarchy of the medical profession, the health profession, that this is a good thing. You have to do training of the kind that David did for a number of years in a number of different countries. You have to have international organizations that say: Hey, this is good. This is not second-class medicine. This is first-class medicine. And all of those things, I think, need to take place. And also you need to—teaching people—you know, I read papers. They say: one thousand people were taught. But how were they taught? Folks in Bangladesh were taught in the home by people who came to the house, not in a large auditorium, not in the outpatient department of a hospital where the children are running around, and so on. So I think that was important.
Now, this country? I am not a student of U.S. health systems and so on. But as an outside observer, I would say there are a lot of things that go against it. One is you’re having the mothers involved in the treatment. Is the profession willing to turn over therapy to mothers? Secondly, the reimbursement of putting an IV in so far exceeds an oral solution, they’re on different planets in terms of—I don’t know what the cost of putting an IV in, but I bet you it’s at least two hundred bucks—$150 to $200. So the economics of it is not very strong.
Thirdly, again, whether nurses and doctors want to control this, they say well, we haven’t got the time. But as I noted, much of the care can be given by family members. And the beauty of that is, that when the child gets sick at home, somebody already knows how to intervene. So I would say that there are a number of things. And we’re enamored by high technology. That’s what we’re all about. And we’re not in love with low tech. Low tech is always seen in our eyes as second-class. Why would you do this, when you could do that? And I would argue just the opposite.
NALIN: Yeah, critical to this in both developing and underdeveloped countries, as well as the developed world, is the flow of resources. In this country, Richard was very modest, actually once you put an IV in, it’s at least an eight hour stay in the ER, or often an overnight stay, running up a bill of $2,000 to $3,000, compared to a ten-cent packet. We talk in this country about reducing costs, but actually the medical system is totally oriented towards profits. So it’s not going to work. That’s the short and simple answer.
CASH: In fact, about six, seven years ago there were two students who were taking a class of mine. And both of them had come to the U.S. because their husbands or they were in a training program for years. So they didn’t have a pediatrician. Both of them went to, dare I say, Boston Children’s Hospital. One was in for twenty-four hours, the other was in for thirty-six hours. The bill of one was $8,000 to $10,000, and the other was $15,000, which I consider nothing short of a heist.
NALIN: Watch your terms. (Laughter.)
CASH: Watch—a watch heist. But that’s what the bills were, $10,000 and $15,000. One was covered by her country, the other she had to pay out of pocket.
NALIN: Even in the developing world, when we as consultants were sent by WHO or PAHO to—it was essential to start a national oral therapy training center where groups of doctors in the National Health Service could be sent in for a couple of weeks training. And that required a central children’s hospital seeing at least five dehydrated patients a day. If you had five a week, there wouldn’t be enough children to use for training the doctors. Now, when I went—some countries just loved it, like Nepal, I’m happy to say, where oral rehydration therapy is called, in Nepali jivanjol (ph), which means life water. It’s popular everywhere, everyone knows about it.
Whereas, in one country I went to, Jamaica, I was puzzled, even though I was working at that time for PAHO, that there was terrific opposition. It seemed that they wouldn’t cooperate with anything. Even they wouldn’t give my assistant a bed in the residence quarters. So I found out gradually—I was investigating this—and I found out several things. One is, the head of the hospital was so skeptical about this working that he had made a hundred dollar bet with his residents that it would fail. So obviously there was an incentive for it to fail. (Laughs.) Secondly, the head of hospital stores, I found out, was making a lot of money on kickbacks from the IV company. So he had no interest in terms of resource flow of substituting oral for IV. And so on, and so on. So it’s very complex, because you’re basically an agent of change, and change is going to threaten some people’s resource flow. So making those changes requires a very subtle and knowledgeable in-depth analysis.
BOLLYKY: Great. One more question then, again, I’m calling the group in the order I see your placards.
What strikes me about the ORT story is how unlike it is the models that we’re applying in global health today. It’s an idea that was extremely local in its generation. You developed it both by being embedded in the countryside, immersed in working on this issue. You did the clinical studies first. You worked the idea with local physicians and NGOs before going to international or philanthropic institutions. As was mentioned by Richard in the reference to Paul Romer, ORT is an idea. It’s not patented. It’s not commercializeable or at least wasn’t commercialized. Like other ideas, it can achieve that volume to scale. It was helped to be spread by U.N. agencies. And it’s extremely low tech. That is, on almost every metric, ORT is different from the higher-tech solutions we see for a lot of global health focus today. And I wonder whether, when you look at other challenges that we’re confronting today in global health, is there still a space for the model that the two of you pursued on oral rehydration therapy to be applied in addressing other pressing health challenges in low- and middle-income countries?
NALIN: I think there is. But it, like oral rehydration therapy, first of all, it has to be founded on absolutely confirmed, meticulous science. For instance, one issue which came up at the recent Prince Mahidol Annual Conference in Bangkok was the current focus, as Tom has elucidated in his recent book, where in the developing world, due to oral rehydration therapy, and vaccination programs, and other improvements, the mortality of the under-fives and five-to-tens has dropped. More people are surviving into young adulthood and later on. So having survived the infectious diseases, they’re moving into an age group where they’re beginning to show up with hypertension, diabetes, cardiovascular diseases, et cetera, and cancer.
Now, if we look at that array of diseases, it’s quite complex. It’s multifactorial. In some cases, we don’t know the cause. But it’s critical not to lump them all together. For example, more and more we’re discovering that cancer is, in fact, a communicable disease, because many cancers are caused by viruses or bacteria that produce cancer-causing substances or genetic changes within our system. So we have the papillomavirus, which has a vaccine, that causes six human cancers, and maybe more. More studies are underway. We have Hepatitis B, which causes liver cancer, and C, which causes liver cancer. We have Epstein Barr virus. And I could go on. There are another ten or so linked coarsely to cancer. Helicobacter pylori in the stomach cancer.
So having that in mind, for cancer we shouldn’t really lump it together with accidents and alcoholism—although alcoholism can be a causative factor. But for control, if we take that point of view, we’ll overlook the most likely avenues of control, vaccines against the underlying infectious organism. So for each of these, we have to really look at the scientific basis of causality, what is the paradigm, and the therapeutic or prophylactic paradigm has to be appropriate to that.
CASH: Though there’s—I think David’s point about science being a basis for interventions and change is really critical. We should practice evidence-based public health, not faith-based public health. By faith, I don’t mean, you know, belief in some deity, but rather it must be so because I believe it to be so. That’s—we shouldn’t be practicing that. Now, I think, although there’s a lot of—it’s not necessarily simple, but immunizations I think are probably one of the most powerful tools that we have. And look what’s happened in recent days. We have measles epidemics. And so not only does the technology need to be straightforward and so on, but we have to look at people’s behavior. Behavior is really, really, really critical. It’s not just the—it’s not just simply: Here it is. Do it. Take it. We’ve got to understand this.
I would also say that we do need to keep our interventions as simple as possible. If you don’t keep it simple, and you add layer, upon layer, upon layer, it becomes extremely difficult to decide what to do, and so on. So we should be stripping away things that aren’t important and adding the things that are really important. Again, that Mercedes to Volkswagen model. But there are, I’m sure, many others that we could use. So I think that there are some incredibly powerful interventions that we have. But we haven’t always been able to connect those with the people who need them.
And this problem, by the way, will continue. Vaccines, as you know, we got to keep going until we eradicate a disease. And the fact is that smallpox was the low-hanging fruit. And it’s quite likely we won’t be able to do this again even with polio—even with polio. Even though we’re that close. It’s sort of the myth of Sisyphus, you know? He gets up to the top there, and just before he gets there, it kind of rolls down the hill again, the rock? But so that means you got to have strong systems, systems that will persist, even when the incidents of disease goes down.
NALIN: And that—following up on that, probably one of the greatest threats to public health in the United States and elsewhere now is so-called vaccine hesitancy. The anti-vaccine movement spreading propaganda through social media and through books and pamphlets, purporting to show that vaccines are harmful. They keep playing the now-debunked autism theory, along with a lot of others. And as we see with the spreading measles epidemic in the U.S. now, and in Europe even worse, this poses a major threat to public health. And this may be true in the future if the answer to many cancers is vaccination against an underlying organism. So I would urge that the government authorities take this on more seriously than has been undertaken to date.
BOLLYKY: Great. I am now going to turn it over to you. I’m pleased to see there’s already a list of people who have questions. I have Alyssa, then Paul, then Elizabeth, Holly, then Katherine, then Daniel, and then Charles here.
If you can state your name and affiliation when you ask your question. Please make your question sound like a question. And I’ll try to get to everybody. (Laughter.) Please.
Q: Well, since I work at the Council on Foreign Relations, I’m well trained on asking the question and not making a statement. I’m Tom’s colleague here at CFR. I work on India, Pakistan, and South Asia. So wonderful to be able to hear the story of ORS from the perspective of your experiences in Dhaka.
I wonder if you can speak a little bit more about what it sounds to me may have been Bangladeshi health systems already in place that helped to bring about the confirmation or the effectiveness of ORS, so early on. What led the country and what led BRAC to have such deep grassroots outreach already? Do you have some insights into that?
CASH: Well, actually, the Bangladesh, or East Pakistan health system, which we were a part of, was really not very vibrant. (Laughter.) We worked an international laboratory. And I think that that was very important. It was a laboratory that was sponsored by a number of—it was a SEATO laboratory. Then Pakistan got out of SEATO and so on. But I think the presence of that lab has done a huge amount for Bangladesh because it brought science to a lot of decisions. BRAC was a very large NGO. And they had—they were doing all sorts of work, including microcredit and so on. This was their first national approach. And I think the vibrancy of the NGO community, of large NGOs, so BRAC, Grameen Bank and so on, were very important. The role of civil society is an important element in the—in the Bangladesh story. But it wasn’t a strong ministry, no. It’s gotten better, but at the time.
BOLLYKY: Yeah. Paul.
Q: (Coughs.) Excuse me. Thanks. I’m Paul Isenman. I’m now an independent consultant on health, nutrition, and education.
And I was in Dhaka from ’65 to ’67, just before Richard and David came. I’m absolutely ever since been, you know, thrilled and amazed by what you’ve been able to accomplish. So bravo for that.
The question is the following: Josh Ruxin, in his history of this, emphasizes much more the obstacles and the missed opportunities, starting from when, I think, it was Phillips, you know. So he’s saying—he’s sort of laying out, well, this could have been done, this could have been done, and it didn’t happen. On the other hand, the fact that the spread has been remarkable. And I wonder if you could please comment on how you see the dissemination of this science-based idea as compared to others in health? And do you think it could—you know, there were lots of missed opportunities that, in reality, could have been overcome, or, in fact, in your view, was this extremely fast? And let me add, I think, that the way you two took up the idea of oral rehydration and not only tested it but did the sort of things that you’ve done to get it disseminated, that’s absolutely remarkable. But still, there’s a question: Could it have been done faster? Was this—was this an A in speed or a B in speed?
NALIN: If I could address that. Oral therapy is not just a magic bullet, although Josh’s article is entitled The Magic Bullet. It is not just a solution. It was necessary to have an absorbable solution in diarrhea patients. But it’s also a method. Phillips (sp) was a great scientist and was the first person—he said accidentally, not on—not having read basic science at the time although he was versed in basic science. It was a time when the active transport science was just beginning. And he was in Taipei. It took months for the ships to bring him the journals. He says he never saw those. He picked glucose off as shelf when he was testing infusion of saline into the intestine of a cholera patient and added it to increase the concentration. Low and behold, they started to absorb. But he didn’t have the appropriate methods. So the first trial was a total failure.
Phillips wrote in his journal article in 1967 that we tried to stop the diarrhea using a concentrated solution of glucose and salts. His idea, his concept, was wrong. You couldn’t stop it. But if you gave it in matching volumes to the losses, you could prevent death from dehydration. That was the idea we developed. Due to the fiasco in the Philippines, when a number of patients died using this hyper-concentrated solution, Phillips actually banned all further studies. He said it would never be practical. And yes, we had to overcome that, along with our colleagues Bert Hirschhorn and David Sachar (sp) who proceeded us to rebuild the steps of the physiologic studies, and ultimately lead to a practical method to go with the absorbable solution.
CASH: And we were very young and didn’t know any better. (Laughter.)
NALIN: That’s actually—we freely admit. We were totally green. Cholera, at the Montefiore Hospital? Never heard of it. So we, in a sense, our minds were tabula rasa. And we went out there and we looked at everything very skeptical. We didn’t know what we were doing. (Laughs.) And we thought, yeah, this should work. You know.
BOLLYKY: All right—a testament to the power of youth. We have sixteen minutes and about five questions. So I’m going to start taking them in twos. So I have next Elizabeth and then after that it will be Holly.
Q: OK. Quick question. Elizabeth Fox, USAID. And thank you for the plug and partnership in rolling out ORS over the years. It’s been huge.
Five hundred thousand deaths of under-fives from diarrhea is still a lot. And what we’re seeing as we track deaths—preventable deaths in priority countries, where the highest mortality is—is that the use of ORS has pretty much flatlined. And these are the hardest to reach. What are your suggestions and thoughts on breaking that flatline and getting some more traction in those hardest to reach under-fives that are dying of very preventable—
CASH: Such as?
Q: In refugee camps, the most isolated parts of countries, ethnic differences, conflict, you name it.
BOLLYKY: Great. Holly, your question.
Q: I’m Holly Wise from Georgetown University. And I’m the proud daughter-in-law of Bob Phillips, that you’ve just been talking about.
The—I just wanted to follow on that sort of how did it happen, how could it happen differently? I love the story that you paint about the evidence-based and the science behind this being proven, disproven, and then proven again, and then being able to come forward to market. But the idea that it was, like other kind of innovations or public health discoveries, it disrupts systems in a way that there are many obstacles to its uptake because it is low tech, because it is—has different service providers, because the financial incentives are different. And so I guess it’s sort of re-asking a question, like Alyssa might have asked, if there’s a similar type of—or, if you had to do it over again, could you see different ways of partnering or different ways of bringing it forward to get from bench to baby in a more fulsome way?
BOLLYKY: That’s a nice pairing of questions.
CASH: I think that there are always many actors to this. You know, I don’t want this to sound like we rode out from the gates of the city and slew all the dragons. Obviously that was not the case. There were many actors—BRAC, and so on. But let me give you an example—and I wasn’t there. So if there were people at the Ebola outbreak, I apologize if I’ve given misinformation. But as part of the treatment of diarrhea, there’s something called the cholera cot. What is that? It’s like an Army cot, costs, you know, fifty bucks to make, made out of jute. And there’s a hole in the middle of it. And a plastic sleeve fits over this bed. And that plastic sleeve goes into a bucket. And somebody who diarrhea, they go—
NALIN: A calibrated bucket.
CASH: A calibrated bucket, so you know how much is going into it. And somebody lies on this bed, doesn’t sound very aesthetic, you know, and defecates through the hole. And you go by, and you measure, and you decide what to do. I remember, in the midst of the Ebola outbreak, they were importing beds from the United States to treat these patients. Now, if you’ve ever taken care of somebody with diarrhea and they’re defecating in the bed, you have absolutely no idea what’s going on there. You just know the sheets are wet and so on. Why weren’t they using this piece of appropriate technology? Now, this is fifty years after the first paper has come out.
NALIN: More money for the bed company.
CASH: Well, that’s possible, one reason. Maybe there was millions of dollars and how can you say, well, we want millions, but actually these beds only cost fifty bucks or a hundred bucks, and we’re going to do the—or, was it that people who went out there, well-meaning, good clinicians, but didn’t know about this. How would they know about it? How would somebody at Children’s Hospital or San Francisco Hospital, or anybody else know what this—unless they had been involved in it? So it’s a continual process of getting people up to date on things that they may not have thought about. So I would say these things, what was the movie, Back to the Future. It’s a bit of back to the future. That you go back, and you look at other things that have worked. And I still remember the story. I said, why are they importing beds to West Africa to treat this epidemic? It makes zero sense to me. It still makes zero sense.
NALIN: With cholera—watch the next round of cholera on BBC or PBS. They show the patients. Mostly they’re getting IV where they have IV. But they don’t show any cholera cots. Now, the cholera patients are losing a liter—adult cholera patient—a liter to a liter and a half per hour. And one of our worst cases lost a total of 250 liters. So you can imagine that going into a standard bed, versus a cholera cot where you can keep up with the losses by matching it with ORS or with IV if you have it.
CASH: And also, if you’ve got diarrhea and you’re running to the bathroom, you’re going to infect people as you go, as opposed to lying in his bed and simply defecating through the hole—which goes against our aesthetic sense of, what, being the Mass General Hospital. I mean, God, I’m paying $1500 a day to sit on a cot and defecate through a hole? Yeah, actually. That’s what we’re doing. We’ll give you a fancy sheet. (Laughter.)
NALIN: In fact, when I was at the Boston City Hospital in the Harvard service in 1971, a patient—an American patient was admitted with what’s called the salmonella cholera syndrome. It’s a typhoid-like infection which—in which the organism produced a cholera toxin, basically. And he had clinical cholera. So they called myself and a colleague who had also been at Dhaka and asked our advice. And we told them: You’d better pump that IV up to a liter every fifteen minutes. They said, are you crazy? They’d never heard of that. That patient went into shock four times—fortunately they survived—because they didn’t listen to me. So that’s what would happen if we had an epidemic now.
One thing I’ll say is, to answer your question, in the face of protracted war and political conflict, everything dissolves. You cannot have rational medical care being given when the objective is to kill children and young adults of the other party. And the other very insidious effect of prolonged conflicts is illustrated by the fact that when I was invited to join the National Institutes of Health Office of International Research in ’65, I was offered nineteen laboratories around the world—nineteen laboratories focused on different disease problems. And I could choose one of them. Today, the only one that survives is the Cholera Research—actually, now the International Center for Diarrheal Disease in Bangladesh. One out of nineteen. Again, illustrating the devastating effect on scientific research and progress of political upheaval, funding vicissitudes, terrorism, and other factors that have wiped out all these institutions.
BOLLYKY: Great. So I have a colleague, Gina Suh, who’s an infectious disease doctor who did part of her residency at that international center. She has these great series of photos of those cholera bed covers cleaned and hanging outside of that center. And they look like prayer flags glistening in the sun. They’re all different colors and it’s really quite something.
I wanted to ask, did either of you want to say anything as to the question of whether, looking back now, there is anything you would have done differently? Do you want to make a comment on that?
CASH: Not really. I mean, I think—I think the fact, actually, that we were U.S. government employees with the NIH, and there was no possibility—at least in our mind—that we were going to benefit from this financially. People—one of the questions they always ask was, well, how much did you make out of this? We didn’t make anything. I don’t—I’m not a big fan of the Bayh-Dole amendment—is it still called the Bayh-Dole amendment—where you get a certain amount of money if you discover something. I don’t think that’s what really drives young scientists. I don’t think they’re being driven by that. I think that this is something that we just did, and we got enthusiastic about it. And we were lucky. Luck is a big thing here in scientific discovery. Luck is something that we don’t like to talk about because—but luck is there. We were at the right place, at the right time, in the right situation. And that was important.
Now, chance—as Louis Pasteur said—chance does favor the prepared mind. So we had come into the situation with that kind of thing. But I don’t know whether I would have done anything differently. I would have bought real estate in those days. (Laughter.) And, you know, bought some of the brownstones around here. (Laughter.) But other than that? No.
BOLLYKY: You and me both. Fair enough. (Laughter.)
Next I have Katherine and then Daniel.
Q: Thank you so much. And I’m Katherine Hagen, working with the group that is known as the Scaling Up Nutrition Movement in Geneva—based in Geneva, but working worldwide.
And your presentation on the ORT dissemination challenges and solutions I think is very relevant to the Scaling Up Nutrition effort, which is intended to be multi-stakeholder. The groups that are involved in it are NGOs, private sector governments, and multisectoral agencies. But very little of the health professionals involved in it, because it is much oriented to prevention of malnutrition for young children rather than dealing with malnutrition. And I’m just wondering if one could think about looking at how the ORT dissemination and other kinds of principles that are for simple good health can be oriented to a prevention strategy that would involve other groups than health professionals, and whether there is a challenge in terms of reaching out to these different kinds of groups.
BOLLYKY: Great. Daniel.
NALIN: I think our approach—
BOLLYKY: Oh, we’re just going to two so that we can get to everyone. Please.
Q: Briefly. My name is Dan Lucey. I’m an infectious disease physician, and teach at Georgetown, and go to outbreaks each year, including Ebola.
So my question was really, I think, probably answered by you already, a follow-up about Ebola. Whether anybody consulted with you or asked you for your advice, either in 2014 or any time since then, about the treatment of diarrhea with oral rehydration solution—diarrhea due to Ebola virus disease.
CASH: Well, just the second one first and then I’ll respond to you. That—it was interesting early on in Nigeria they had I think maybe only one death or two. And they said—early on said, look, the reason that these people survived is because we used—we treated diarrhea with ORS. They actually said that. Now, how did that spread? Did it go beyond that? As I say, I’m not a student of this. But I do feel like there were missed opportunities in the Ebola situation, in the West Africa thing.
In terms of your own question, I think that a lot of undernutrition is because kids are getting infections that they shouldn’t get. And that involves doctors. Making sure that kids are immunized against measles, that are immunized against certain things. That’s a preventive thing that every physician, every provider of care should be aware of. It’s not simply changing the diet and this or that. I believe in fact the measles vaccine has probably done more than any single intervention to reduce a lot of the severe malnutrition that we used to see a lot of. And Bangladesh is way down. So involving the physicians in the preventive aspects I think is very much a part of the process.
NALIN: Yes. As far as malnutrition, of course, now we’re faced with undernutrition—marasmus, kwashiorkor—and overnutrition, leading to diabetes. Two different problems. But with regard to undernutrition, as Leonardo Mata showed years ago in his Children of Cauqué in Guatemala, it was the repeated episodes of diarrheal disease treated with starvation therapy that led to most of the undernutrition. And I believe that’s still the case in many countries. One thing I’ve been struck with, when you see the news reports about the starving children, where they’re saying it’s due to no food, striking thing is that the mother holding the child is not only well nourished, but she has gold ornaments and a very nice dress. And I’m sure that child is a victim of probably poorly mixed formula leading to infection after infection, nothing by mouth. So that has to be looked at carefully, to see how much of that is not due to the fact that there was no milk. Why didn’t she sell her gold ornament to get the milk? But there’s something else at a play here.
And as far as Ebola goes, I’ve been disappointed from the beginning of the epidemic—as soon as it was made clear that diarrhea plays an important part—I wrote several letters, including to the Lancet and other journals—all were rejected—recommending the most important thing in diarrheal disease. The first thing you have to do is analyze the diarrheal flow to find out what the patient is losing—how much salt, how much bicarbonate, how much potassium. Finally, one journal of tropical medicine accepted that recommendation, just—but there still hasn’t been a single analysis. So we’re starting in an area of blindness. And I think what’s happened is it’s gotten to be a free-for-all out there with aid agencies, and bed exporting companies, and a whole bunch of things. And they’re not interested in looking at scientific expertise that’s relevant.
BOLLYKY: Great. We have two questions and three minutes. So I’m going to ask you to be very, very brief, and hopefully we’ll have two answers to those questions. So Charles and then Roger.
Q: Well, the long argument about public health people, vertical versus horizontal is important to get disease or to have a well-engaged health system. The way you’ve described it, health professionals can be part of the problem and part of the solution in a country. You’ve been now spreading this excellent technology all over the world. You mentioned your Bangladesh experience. What’s the best system in a country?
BOLLYKY: Roger, briefly.
Q: I was just going—thank you, Tom, for this. This is such an important innovation. It was young people, going to where the problems where. They never would have discovered this in NIH. It’s a reverse technology, so we use it at home. And then Office of International Health was—director was Milo Levitt (sp), and that became the Fogarty International Center. So these two guys are the first Fogarty fellows. And I just want to celebrate what they’ve done.
What they haven’t done is in fifty years we’re still using the same solution. And there are drugs and other opportunities to stop diarrhea, because oral therapy really allows the diarrhea to continue. So I don’t know if you have any ideas of how to stop the diarrhea.
BOLLYKY: All right, so you’ll have to give them in a single minute, so.
NALIN: I do. OK. I just completed a study at the laboratory in Bangladesh that is looking at something we accidentally discovered in ’76 but never published because my co-investigator died. We weren’t sure about the analyses. The new study has confirmed something unknown previously, that the cholera stool contains enormous quantities of a hormone called VIP, which is the cause of the disease pancreatic cholera, caused by a cancer of the pancreas that produces VIP, leading to cholera-like symptoms. So we’re preparing that for publication. And I’m not going to at this point say that it will lead to a cure, but there are, in fact, compounds available now which can stop VIP right away. So I’m going to recommend studies in dogs and other animal models.
CASH: And, Charles, to your comment, I think that you can initiate programs through vertical, but ultimately if you want things to continue over time you have to have a primary health care system that addressed all of this. So that you can drill down, and you can get great success. But that does not obviate the need to make it part of a package.
BOLLYKY: Great. I hope you will join me in celebrating and thanking these two gentlemen. (Applause.)
This is a corrected transcript.