Science, Politics and the Pandemic

Suzi Weissman interviews Dr. Irv Weissman

Dr. Irv Weissman, director of Stanford University’s Institute of Stem Cell Biology and Regenerative Medicine.

DR. IRV WEISSMAN is director of Stanford University’s Institute of Stem Cell Biology and Regenerative Medicine, and previously head of the Immunology Program and the Cancer Center. A cancer and stem cell biologist/immunologist, he is widely recognized as a stem cell pioneer — the first scientist to purify blood-forming stem cells in both mice and humans.

Suzi Weissman interviewed her brother Irv Weissman April 19, 2020 for her “Beneath the Surface” program on KPFK radio in Los Angeles. Many thanks to Meleiza Figueroa for transcribing the recording. It is abridged here for space reasons.

Suzi Weissman: I’m very pleased to have my brother Dr. Irv Weissman with us today. Today we’re going to talk about COVID-19 or the coronavirus pandemic. Maybe we can just begin with you explaining to our audience just what it is about this virus that is so devastating to us. Just walk us through it.

Irv Weissman: This is one of those viruses that came from infecting both people and infecting animals — so that eventually the genetic alterations that could happen in an animal, say a bat, could make it more and more dangerous not necessarily for the bat, but for humans. The transmission to humans follows essentially the path of many other very dangerous viruses, going all the way back to AIDS and HIV, or Ebola, or Zika, or Bolivian hemorrhagic fever.

 A whole bunch of these are viruses that affect us. And to get right to the immunology of it and why it affects us, and why it affects mainly older people, is that our immune systems have evolved — that is, in all of the animal species — before trains, planes and cars.

When you get a vaccination, or you have measles, or mumps, you have cells called lymphocytes — two categories, T and B cells — which not only respond to get rid of the infection, the microbe, bacteria, viral, fungal and so on, but they divide a thousandfold. They live as long as you do, as memory cells. And each of them is specific for the particular infection that drove them from the beginning.

That’s how you get immunity to the microbes you encounter. By the time you reach puberty, whether you were a mouse or a human or a monkey, you’d encountered most of them. So you now were prepared, if you didn’t migrate, to have immune cells that immediately and effectively respond to get rid of the infection.

It turns out that the blood-forming stem cells that you have when you are young have to make lots of new lymphocytes to cover the new infections you’re going to have. And we and others have found over the last 15 years that in mice — and we showed, also in humans — the blood-forming stem cells that take over well after puberty make more of the kinds of immune cells that are fast responders.

Trains, Planes and Cars

They can get rid of the infection, not by knowing that it was this or that virus, or this or that bacteria; they have general mechanisms to eat and kill. The body’s stem cells when you age, that take over the blood-forming system, mainly make those cells. Before trains, planes and cars you didn’t have to make a bunch of new lymphocytes for newly emerging infections.

You’re not making a bunch of new lymphocytes that one in 100 or one in 1000 could encounter a new virus. We haven’t worked out the mechanism for that, because as I said, it’s well after puberty that this other system takes place.

If you believe in evolution and not divine intervention, then you’d have to say, “well, why would you be selected to live long lives if you’re no longer reproductively competent and competitive?” Because what gets passed on as traits to the next generation is through reproduction only. I’ll just leave that as a puzzle for the audience.

SW: Without being too technical, can you talk about what might make the coronavirus so much more devastating to deal with than the other groups of viruses we’ve had? Is the study of this virus going to open up new pathways (as happened with AIDS)?

IW: Of course an epidemic, and a funding agency response to the epidemic, and the desire of scientists to do relevant things, has led to a whole group of new people into the science of virology and virus infections.

Every university I know was doing it. So you can thank people like Tony Fauci for saying, “we need to have more science for this infection.”

The virus itself appears to first inhabit mainly the nasal passages in the back of what’s called the pharynx: the throat and then going down. It then really becomes lethal when it spreads to the substance of the lungs.

It goes not only through the tubes that lead to the lungs, but also to the air passages — tiny places where oxygen gets exchanged and CO2 gets out. It hits those cells with a vengeance, and it starts the infection.

The immune response that comes to it is massive because you have so many different parts of the lungs immediately infected. The lymphocytes that come through, back and forth in the body, stop in the lungs and start their immune response. They’re trying each on their own to wall off the infection — that’s called inflammation — and make killer cells that would either kill the infected cells (T lymphocytes) or eat the infected cells; that’s the scavenger macrophages in the body.

With this infection, for some reason, not everybody makes a rapid immune response. But this virus spreads so fast, and infects cells so fast, that you can get overwhelmed. And when you’re overwhelmed, the main place that you’re infected — I mean almost exclusively — is where you breathe. And we know that you can die if you can’t breathe.

SW: You’re saying that it’s the human immune response that exacerbates the bad work of the virus?

IW: It does, but in the absence of the immune response, I’ll bet you the virus would still be bad. It would be bad in a different way. But it is safe to say that if you’re young and you have lots of new lymphocytes being made, you’ll make an immune response that is effective. 

Safety, Testing and Vaccines

Here’s two points: one, you want to know everybody who’s infected, because before they get the symptoms, and some never get symptoms, they’ll pass it on with high efficiency. And you’ve heard that you’ve got to wash your hands, you have to wash surfaces, you have to wear a mask. That’s critical.

If you stay by yourself, like each of us are now, you won’t get infected. The only way you could get infected is if you do something stupid, like go meet somebody at the door who was infected and has not protected.

Second, you have to be able to test for the genetic material of the virus. Luckily, all of molecular biology has made very, very fast and reproducible ways to make tests. 

SW: The testing problem has been right at the core of what’s made this so awful, the U.S. response in particular. Why is it such a huge problem?

IW: I’m told that the CDC chose to develop a test that didn’t work well. They depended on it for a long time, and for some reason the federal government said, “All testing has to go through the CDC.”

That’s like saying all steaks in the world have to come from Great Falls, Montana. It’s hard not to see the problem — the federal government did not take charge, like the Obama administration took charge of the Ebola epidemic. It did not anticipate what you need to do.

The first thing you need to do, on a global scale, or at least within the whole country, is to make sure that you can get testing fast, and that it’s accurate. Not only that it gets out fast, but that you get the results fast.

Anything you are going to do — isolation or freeing people up from isolation — means you have to be able to take a sample from their nose, and know in an hour or two if they are infected. Then you track their contacts and their contacts’ contacts. Yet even today — despite the promises — we don’t have enough testing. 

But we also need to know whether this is like other infections: If you recover, and you make antibodies as well as activated killer T cells, can you consider yourself safe from a reinfection? And while in 99% of the time you could assume that to be so, we do have the experience of HIV, whose target is those T cells that control developing an immune response.

That’s why we don’t have an HIV/AIDS vaccine now, thirty-some years after the epidemic began. We still don’t have a vaccine. But we’re lucky that we have good responses to it.

SW: Do you think that it’s going to be that difficult to get a vaccine for this one too?

IW: The science in making vaccines — to influenza or coronaviruses — is well established. There’s no evidence yet that this coronavirus destroys the T cells, like HIV destroys some of the T cells. And so the waiting time depends on two things.

First, when the epidemic became known and the agent became known, and you could get the agent to make vaccines, that was the moment that not one company, not one agency, but many, should have been developing vaccines and been richly subsidized to do it. You need to anticipate that vaccines will work.

Second, which we’re finding out anecdotally, is: If you have recovered from the infection — you had a bad infection, but you’ve recovered — do you make antibodies and immunity T cells that will prevent you from being reinfected? You can do that through case studies, but you’d better be organized to do that. From the very beginning, tracking people — not only who got the infection and by testing had the virus that caused the infection, but also seeing if they were making antibodies — an immune response.

Then you would ask, “What’s the likelihood as they interact with people who are freshly infected, that they get reinfected?” You can also test to make sure the virus is all gone. Those are the key factors. 

Back before antibiotics, the way we could treat people with these kinds of bacterial or viral infections was to isolate the antibodies from the serum or the plasma of those who’d had them.

There’s a quick way to purify the antibodies so any other virus or infection the person had doesn’t get passed on. You collect them all together, you make what’s called an IVIG, a convalescent immunoglobin of the type that can neutralize the virus on contact and/or help neutralize or get rid of the infected cells. So you want that.

They may be an immediate therapeutic, which is being tested. It used to work before; people used to immunize horses and then collect lots of antibody. Then they found out that when you put horse serum in people, people would make an immune response against horse serum, because horses are genetically different. The response could be as bad as the disease.

But working with people, and the variation in our immunoglobins, our antibodies, is such that probably you could safely transfer them, and that will be critical to know. Those people who are immune — if you know that through testing — can go back to work.

Herd Immunity

SW: We’ve seen different responses around the world, and in some cases, they said that distancing or isolating in place isn’t necessary because herd immunity will take care of that. Can you explain what “herd immunity” is?

IW: It’s easy for anybody to understand. If only 10% of the people get infected, 90% are infectable. At 50%, it’s still too many infectable. If 80% or 90% of the people are infected and have a sufficient immune response, you’re getting to where the herd, all of us, don’t have enough susceptible people that you would have the chain of infection to uninfected, to uninfected, to uninfected. That’s herd immunity.

We’re not going to get to herd immunity with this infection because too many people die. And our social isolation is good. So that means we need a vaccine. We need convalescent antibodies for those who got infected without the vaccine. Those should have been going full force from the beginning.

Suppose you make a vaccine. You think you’re making it just like you always made vaccines, and now you put into somebody of a certain age and you find out there was a mistake in producing the vaccine. Another virus crept along that causes a disease. Or you made a vaccine and part of it mimics your own body structure so that you might make an antibody or a T cell against the virus, but you also destroy your own organ that has a mimic of that.

Therefore we have developed for every drug, every antibody, every vaccine, FDA pre-clinical proof of principle, pre-clinical testing in animals as close to humans as you can, and then test in a cohort or a first group of healthy volunteers.

Can you vaccinate them? Can you show an immune response? Can you follow them long enough to know that the immune response won’t kill them eventually, that you haven’t introduced something that you didn’t think, or couldn’t think, of ahead of time?

That’s why you have to start with pre-clinical testing and toxicity tests. You have to know if the vaccine is safe for everybody. If that works out then there are phase I, II, and III clinical trials, which can be accelerated.

So, when Tony Fauci says a year to a year and a half, he’s saying that even with the number of companies or agencies that are starting out, that’s the minimum.

Politics Costs Lives

SW: I wanted to go into the political side of it, because one thing that this virus has done is to show just how fragile our public health infrastructure is — or what’s left of it is — combined with misinformation, disinformation and concentration on only “opening up the economy” at any cost. Some right-wing congresspeople are saying that it’s worth it restarting the economy even if that means old people die. Are we capable in this country of effectively, first of all, testing and tracing, and then devising what needs to be done next?

IW: In addition to masks, gloves, washing, ventilators: for those already sick or preventing them from getting sick, you dare not open up social interactions, for business or any other reason, if you have 50% or more still infectable.

If you’re going to say, “I’m going to try to save as many lives as possible,” then you would say “social isolation will flatten the curve.” And we’ll save many lives with social isolation and what people need to get through it. But you’ll never reach herd immunity with infection alone. You can flatten the curve and keep people who aren’t infected from being infected.

That means you’re now dependent on a vaccine to do what herd immunity would do: stimulate your lymphocytes, get immune memory that lasts your life, and then you should be safe. That’s what the game is, and any other business or economic or personal financial interest has to take a back seat to it. Unfortunately, as you know, it’s not taking a back seat.

I am afraid we are going to be in a situation where lives are lost that don’t need to be lost, for reasons that are not medical or scientific or public health. It’s just money.

If you enact a policy that puts everybody at risk who hasn’t been infected or vaccinated, that’s just stupid.

We understand the reasons. There are people in our country, as we know throughout our history, who have valued economic rights over individual human rights. And we have people of particular religions who want to impose their religions on everybody.

Today, we know that a human fetal lung, put into an immunodeficient mouse, can be infected with this virus. We need a way to test and understand the disease. But Trump, Pence, Mulvaney, and Grogan — against the advice of HHS, the Deputy Director of HHS, the head of NIH, and Tony Fauci — imposed a ban on any research using human fetal tissue using federal funds.

You could appeal it, because experiments are in progress — but they said in addition to that ban, no trainee who receives federal funds under any circumstance can work with human fetal tissue. But in our labs in academia we don’t have workers. We have graduate students and post-docs and medical students and undergraduates who work.

This was the most effective way for them to enforce their own personal, political, moral, religious beliefs on the rest of the country. As you know, Texas can’t receive money related to the epidemic to fund abortions. Politics places their own personal beliefs above the lives of others. I find that objectionable. I wrote a USA Today op-ed on it, and a much longer article in a scientific journal.

A couple of weeks ago Amy Goldstein at the Washington Post wrote a really powerful article on just this issue. Fifteen state attorney generals have gone to the federal government to try to stop the ban, to see if the use of the human fetal tissues can accelerate our development of vaccines, of drugs, and of ways to slow down or halt this epidemic.

SW: Does that mean that if you can’t use federal funds, once again, as with AIDS research, private venture capital could be used? Or is there some sort of ban on that too?

IW: Private venture capital is money to make money. Don’t blame them, that’s how business goes. But we in the state of California had an initiative in 2004 called Proposition 71, because of the federal bans for fetal or embryonic tissue. It was for state-funded research where those tissues could be used.

If you follow many of the discoveries we made — even though I told you how long it takes to develop a drug — many of them are now in late-phase clinical trials. And the state of California has done more clinical trials with its small budget in Proposition 71 than the federal government has done in the same field.

The funding for research and therapy development that has been underway since the voters approved Prop 71 in 2004 is coming to an end, so there is an initiative — the California Stem Cell Research, Treatments and Cures Initiative of 2020 on the ballot in November — to renew the funding. Luckily, you can vote for the re-do, so if there’s any other reason to mail in your ballot safely, it’s to renew Proposition 71. Even if the country stays on a course that values things like money or religion or political advantage over the lives of people, at least in California we can continue along the road that we began in order to try to save lives for that small window of opportunity they have for therapy.

Every time a bureaucratic process slows down — because they want to have a committee do this or a committee do that, let’s meet next month — there are people who will die because their window of opportunity to be saved by those drugs and those therapies are not available.

I was at a meeting of the Vatican Science Council in 2006, where I said, “Your ban on fetal tissue and embryonic tissue to do biomedical research, your ban on telling people about condoms and safe use sex, has clearly slowed down the advancement of medicine.” And from my point of view — just mine, because I know some people will be pissed off when I say this — you’re responsible for the lives lost because you imposed a ban, or a slow-down, or a delay.

We want to have an efficient, people-oriented way of doing research, and we accept, even in the so-called Communist countries, businesses springing up one way or another to deliver it. I’m not saying anything that we throw away everything, I’m saying that we do things we don’t need to do to slow them down from getting to whatever mechanism you have eventually to distribute.

July-August 2020, ATC 207