Thank you.
I'm a developmental biologist. I'm a scientist, not a clinician. I've been studying how thalidomide acts on the embryo for the last 15 years.
The drug itself is quite complicated. It exists as enantiomer, which means it can exist in two different forms in the body. One form is believed to be positive. That's what gives us its good benefits, its anti-inflammatory actions. The other side is supposed to be its teratogenic side effects, and that's damage to the embryo.
I've been interested in how the drug works. I got interested in this some time ago. Janet McCredie's work from the 1970s suggested that the nerves were targeted by the drug to cause the various birth defects. I've always been interested in that work and interested in how a drug like thalidomide could cause such massive damage. This drug, in just a short time period, affects almost every tissue in the body apart from the brain and the central nervous system. How it can do that is just amazing.
As Dr. Johnson just alluded, in the report from Smithells and Newman in 1992, they talk about just one tablet being enough to cause damage to an embryo. If you took more than one tablet, you would get lots more damage.
We took apart the drug. We made different versions of it, broke it down, and asked the question, what does the drug do in an embryo? We used chicken embryos and zebra fish embryos because they develop in very similar ways to early humans. They have similar genetic and molecular makeups to us. They're simple to use. You can put drops on them and see what they do. We found that, if you make versions of the drug, you can change the molecular structure. You can find versions of the drug that affect blood vessels. You can find versions of the drug that affect the inflammatory system and the immune system.
This is what the drug does normally. If you take a tablet of the drug, it's useful to treat cancers because it destroys blood vessels. It's useful to treat conditions like leprosy and multiple myeloma because it's anti-inflammatory.
We found that the drug's anti-angiogenic actions are what causes its effects on the embryo, and the anti-inflammatory actions don't seem to do much to it. We're now looking at molecular targets of that action, and if we can understand molecular targets, you could perhaps, possibly, identify or have a tool to identify who might be at risk.
We're also now looking at drug safety. Dr. Johnson also mentioned that there is a new generation of thalidomide babies in Brazil, and I would strongly recommend that you contact Lavinia Schuler-Faccini in Brazil because she is leading all the diagnostics there. In Brazil they have a leprosy problem, and thalidomide is very useful to treat leprosy. It's very effective, but the side effect is that they have a new population of babies with thalidomide-like damage.
We've been trying to make forms of thalidomide that don't cause birth defects. We're looking for versions that are not anti-angiogenic—that is, don't affect the blood vessels—and that are purely anti-inflammatory. We have identified some of those, and we're now trying to use those in other inflammatory conditions to see if we can use them as an alternative to thalidomide.
That's my expertise. I'm not a clinician, but I would say that, from the animal evidence from the 1960s through to recent years, if you look at particularly the primate studies—that's the studies in monkeys—this drug causes an amazing range of damage. If you look at monkeys, you have four or five embryos per litter, and each embryo is different. Each embryo is affected differently by the drug. You can have some that have phocomelia, as Dr. Johnson mentioned, where they have the digits sticking out of the top of the shoulders, and some that have almost no damage at all.
How the drug can do that, how the drug can affect one pregnancy and affect each embryo in such a different way, we still don't understand, but the fact is that in animal evidence the drug affects each embryo differently.
I think Dr. Johnson can confirm this or disagree, but I think each individual thalidomide survivor has a different range of damage as well. This is one of the reasons it's been so difficult to understand how the drug acts and how it causes its problems, because each person seems to have a different amount of damage. This is one of the problems we have in science, trying to understand how the drug acts.
Thank you for your time. I hope that was helpful.